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Medical Parasitology in The Philippines. Belizario & de Leon PDF
Medical Parasitology in The Philippines. Belizario & de Leon PDF
in the Philippines
Medical Parasitology
in the Philippines
© 2013 by University of the Philippines Manila ???? (Vicente Y. Belizario, Jr., Winifreda U. de Leon ???????)
All rights reserved.
No copies can be made in part or in whole without prior written permission from the author and the publisher.
The data in this book have been verified with reliable sources, and treatment modalities suggested have been
utilized in clinical practice. However, new researches and changes in the medical sciences should be considered.
Readers are advised to consult other sources such as drug information sheets and dosage, contraindications to
administration, and other relevant data.
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ISBN 978-971-542-________
Foreword.....................................................................................................................................x
Foreword to the Second Edition..............................................................................................x
Foreword to the First Edition..................................................................................................x
Preface.........................................................................................................................................x
Acknowledgments.......................................................................................................................x
List of Figures.............................................................................................................................x
List of Plates...............................................................................................................................x
List of Tables...............................................................................................................................x
Chapter 1: Introduction to Medical Parasitology..................................................................x
General Considerations.......................................................................................................x
Host-Parasite Relationships.................................................................................................x
Immunology of Parasitic Infections.....................................................................................x
Groups of Parasites with Medical and Public Health Importance........................................x
Chapter 2: Protozoan Infections...............................................................................................x
Intestinal Amebae...............................................................................................................x
Commensal Amebae...........................................................................................................x
Free-living Pathogenic Amebae...........................................................................................x
Ciliates and Flagellates........................................................................................................x
Coccidians..........................................................................................................................x
Other Intestinal Protozoans................................................................................................x
Plasmodium spp..................................................................................................................x
Babesia spp..........................................................................................................................x
Blood and Tissue Flagellates................................................................................................x
Chapter 3: Nematode Infections................................................................................................x
Intestinal Nematodes..........................................................................................................x
Tissue Nematodes...............................................................................................................x
vii
viii Medical Parasitology in the Philippines
ix
x Medical Parasitology in the Philippines
Figure 8.11 School teachers administering deworming tablets to students in a public elementary
school in Biñan, Laguna
Figure 8.12 Cumulative STH prevalence and heavy intensity infections in school-age children
in Aklan, Antique, and Capiz, 2007-2009
Figure 8.13 Process, performance, and impact indicators for helminth control
Figure 8.14 Checking for tongue discoloration after administration of deworming tablets to
school children to ensure compliance
Figure 8.15 Former DOH Secretary Francisco Duque III and former Antique Governor
Salvacion Perez administering anthelminthics to school children in Pandan Central
Elementary School, Antique during the launch of the War on Worms—Western
Visayas
Figure 8.16 Parade of school children and teachers during the launch of War on Worms—Biñan,
Laguna
List of Plates
xiii
xiv Medical Parasitology in the Philippines
Plate 3.7 Rectal prolapse in a 9-year old female seen at the Philippine General Hospital with
heavy Trichuris infection
Plate 3.8 Buccal capsules of hookworms
Plate 3.9 Hookworm filariform larvae
Plate 3.10 Hookworm egg
Plate 3.11 Cutaneous larva migrans
Plate 3.12 Strongyloides stercoralis rhabditiform larva
Plate 3.13 Enterobius cephalic alae
Plate 3.14 D-shaped eggs of Enterobius vermicularis
Plate 3.15 Male Capillaria philippinensis
Plate 3.16 Female Capillaria philippinensis
Plate 3.17 Capillaria philippinensis egg
Plate 3.18 Capillaria philippinensis second stage larva from the feces of a person with intestinal
capillariasis
Plate 3.19 31-year old female with intestinal capillariasis before treatment and 1 year after
treatment
Plate 3.20 Proper excreta disposal is important for prevention and control of intestinal
helminthiases including capillariasis
Plate 3.21 Brugia malayi microfilaria
Plate 3.22 Wuchereria bancrofti microfilaria
Plate 3.23 Dermatolymphangioadenitis (acute lymphatic filariasis)
Plate 3.24 Elephantiasis
Plate 3.25 Hydrocele
Plate 3.26 Small and big hydroceles in 2 patients suffering from filariasis
Plate 3.27 Farmer in abaca plantation
Plate 3.28 An axil of abaca: a breeding site of Aedes poecilus
Plate 3.29 Parastrongylus adults
Plate 3.30 Achatina fulica, the intermediate host of Parastrongylus cantonensis
Plate 3.31 Trichinella spiralis larvae in muscle
Plate 4.1 Taenia saginata scolex
Plate 4.2 Taenia saginata gravid segment
Plate 4.3 Taenia egg
Plate 4.4 Taenia solium scolex
Plate 4.5 Cysticercus cellulosae from pork
Plate 4.6 Hymenolepis spp. scolex
Plate 4.7 Hymenolepis spp. gravid segment
List of Plates xv
Plate 7.13 Howell-Jolly bodies in a thin blood smear stained with Giemsa may look like
malaria parasites
Plate 7.14 A nucleated red blood cell may look like a schizont of Plasmodium spp.
Plate 7.15 Fungal spores of Helicosprorium may be mistaken as microfilariae in stained blood
smears
Plate 8.1 Balantidium coli from pig
Plate 8.2 Sarcocyst in sectioned esophageal muscle of water buffalo
Plate 8.3 Cysticercus cellulosae freed from muscle of pig
Plate 8.4 Strobilocercus fasciolaris freed from liver of field rat
Plate 8.5 Anisakis larva from fish
Plate 8.6 Fasciola gigantica and F. hepatica from water buffalo
Plate 8.7 Fasciola metacercariae
Plate 8.8 Schistosoma cercariae
Plate 8.9 Dipylidium caninum from dog
Plate 8.10 Dirofilaria immitis from dog
Plate 8.11 Macracanthorhynchus hirudinaceus from pig
Plate 8.12 Echinostoma lindoense from field rat
Plate 8.13 Eurytrema pancreaticum from cattle
Plate 8.14 Philophthalmus gralli from duck
Plate 8.15 Plagiorchis philippinensis from rat
Plate 8.16 Sparganum of Spirometra from muscle of frog
Plate 8.17 Gnathostoma doloresi from pig
Plate 8.18 Gnathostoma larva from frog muscle
Plate 8.19 Toxacara canis from dog
Plate 8.20 Toxocara canis embryonated egg (infective)
Plate 8.21 Mammomonogamus laryngeus in copula from water buffalo
xviii Medical Parasitology in the Philippines
List of Tables
xix
xx Medical Parasitology in the Philippines
xxi
xxii Medical Parasitology in the Philippines
Foreword to the Second Edition
xxiii
xxiv Medical Parasitology in the Philippines
Foreword to the First Edition
xxv
xxvi Medical Parasitology in the Philippines
Preface
xxvii
xxviii Medical Parasitology in the Philippines
Acknowledgments
xxix
Chapter 1
General Considerations
Vicente Y. Belizario, Jr.
1
2 Medical Parasitology in the Philippines
infection with the parasite. An alteration in of infection. Autoinfection where the infected
the normal life cycle of Strongyloides results in person himself is the source of infection is seen
a large increase in worm burden, which may in the life cycles of Capillaria philippinensis,
lead to severe debilitation or even death due to Enterobius vermicularis, Hymenolepis nana, and
an increase in the proportion of rhabditiform Strongyloides stercoralis.
larvae that transform into filariform larvae while
Modes of Transmission
in the gut.
Since the most common source of parasitic
Sources of Infection
infection is contaminated food and water,
There are various sources of parasitic the most likely portal of entry is the mouth.
infections. The most common sources are Majority of infections with cestodes, trematodes,
contaminated soil and water. Lack of sanitary and intestinal protozoans are foodborne: Taenia
toilets and the use of night soil or human solium, Taenia saginata, and Diphyllobothrium
excreta as fertilizer allow the eggs to come in latum from eating food harboring the infective
contact with the soil and favor the development larval stages; Entamoeba histolytica and Giardia
of Ascaris lumbricoides, Trichuris trichiura, lamblia from drinking water contaminated with
Strongyloides stercoralis, and hookworm. Water cysts; and Clonorchis, Opistorchis, and Haplorchis
may be contaminated with cysts of amebae or through ingesting raw or improperly cooked
flagellates, as well as cercariae of Schistosoma. freshwater fish containing infective larvae.
Another possible source of infection is food, Skin penetration is another route of
which may contain the infective stage of transmission. Hookworms and Strongyloides
the parasite, as exemplified by a number of enter via exposure of skin to soil, while
trematode and cestode infections. Consumption Schistosoma species enter skin via water.
of undercooked or raw freshwater fish can Arthropods also serve as vectors and
result in several intestinal and liver fluke transmit parasites through their bites. Examples
infections. Raw crabs are considered a delicacy are agents of malaria, filariasis, leishmaniasis,
in areas where paragonimiasis is endemic, trypanosomiasis, and babesiosis.
while raw Bullastra snails are associated with Another way of acquiring infection is
Artyfechinostomum malayanum infection. through congenital transmission. Toxoplasma
Arthropods can also transmit infection. gondii trophozoites can cross the placental
Mosquitoes are vectors of malaria and filarial barrier during pregnancy. In transmammary
parasites. Triatoma bugs are carriers of infection with Ancylostoma and Strongyloides,
Trypanosoma cruzi causing Chagas disease. the parasites may be transmitted through
Sand flies (e.g., Phlebotomus spp.) are the mother’s milk.
natural vectors of all types of Leishmania. Other Other ways of acquiring the infection
animals, whether wild or domesticated, may include inhalation of airborne eggs of Enterobius
also harbor parasites. Cats are direct sources of and sexual intercourse as in the case of
Toxoplasma infection, while rats may be infected Trichomonas vaginalis.
with Hymenolepis nana.
Nomenclature
Other sources of infection include another
person, his beddings and clothing, as well as the Animal parasites are classified according
immediate environment he has contaminated, to the International Code of Zoological
or even one’s self. Asymptomatic carriers of Nomenclature. Each phylum is divided into
Entamoeba histolytica working as food handlers classes, which are further subdivided into orders,
in food establishments may be important sources families, genera, and species. At times, the
4 Medical Parasitology in the Philippines
further divisions of suborder, superfamily, and number of worms per infected person. This may
subspecies are employed. Scientific names are be measured directly or indirectly and is also
latinized; family names are formed by adding referred to as the worm burden. In the case of
-idae to the stem of the genus type; generic soil-transmitted helminths, it can be measured
names consist of a single word written in initial directly by counting expelled worms during
capital letter; the specific name always begins treatment, or indirectly by counting helminth
with a small letter. The names of the genera eggs excreted in feces. The latter is expressed as
and species are italicized or underlined when the number of eggs per gram (epg).
written. Clinical consequences of infections or
diseases that affect an individual’s well-being
Life Cycle
refer to morbidity.
Through adaptation to their hosts and the
Treatment
external environment, parasites have developed
life cycles, which may be simple or complicated. Deworming is the use of anthelminthic
Most parasitic organisms attain sexual maturity drugs in an individual or a public health
in their definitive hosts. Some spend their program. Cure rate refers to the number
entire lives within the host with one generation (usually expressed as a percentage) of previously
after another, while others are exposed to the positive subjects found to be egg negative
external environment before being taken up on examination of a stool or urine sample
by an appropriate host. The larval stage of the using a standard procedure at a set time after
parasite may pass through different stages in an deworming. Egg reduction rate (ERR) is the
intermediate host before it reaches a final host. percentage fall in egg counts after deworming
As the life cycle becomes more complicated, the based on examination of a stool or urine sample
lesser the chances are for the individual parasite using a standard procedure at a set time after
to survive. the treatment.
The perpetuation of a species of parasite Selective treatment involves individual-level
depends upon its ability to ensure transmission deworming with selection for treatment based
from one host to the next. The parasite must, on a diagnosis of infection or an assessment of the
therefore, adapt to protect itself from the host’s intensity of infection, or based on presumptive
defenses and the external environment, and it grounds. This strategy can be used in whole
must overcome the attrition in the species by populations, or in defined risk groups. Targeted
producing numerous progeny. treatment is group-level deworming where
the (risk) group to be treated (without prior
Epidemiologic Measures
diagnosis) may be defined by age, sex, or other
Epidemiology is the study of patterns, social characteristics irrespective of infection
distribution, and occurrence of disease. status. Universal treatment is population-level
Incidence is the number of new cases of deworming in which the community is treated
infection appearing in a population in a given irrespective of age, sex, infection status, or other
period of time. Prevalence is the number social characteristics. Preventive Chemotherapy is
(usually expressed as percentage) of individuals the regular, systematic, large-scale intervention
in a population estimated to be infected with involving the administration of one or more
a particular parasite species at a given time. drugs to selected population groups with the
Cumulative prevalence is the percentage of aim of reducing morbidity and transmission of
individuals in a population infected with at selected helminth infections.
least one parasite. Intensity of infection refers Coverage refers to the proportion of the
to burden of infection which is related to the target population reached by an intervention. It
Chapter 1: Introduction to Medical Parasitology 5
could be the percentage of school-age children reservoirs of disease. It also covers the provision
treated during a treatment day. of safe drinking water and food safety; housing
Efficacy is the effect of a drug against an that is adequate in terms of location, quality of
infective agent in ideal experimental conditions shelter, and indoor living conditions; facilities
and isolated from any context. Effectiveness for personal and domestic hygiene; as well as
is a measure of the effect of a drug against safe and healthy working conditions.
an infective agent in a particular host, living Sanitation is the provision of access to
in a particular environment with specific adequate facilities for the safe disposal of human
ecological, immunological, and epidemiological excreta, usually combined with access to safe
determinants. Effectiveness is usually measured drinking water.
by means of qualitative and quantitative
Eradication versus Elimination
diagnostic tests which detect eggs or larvae in
feces or urine after an optimal time interval, Disease eradication is defined as a permanent
which is variable for each parasite. Cure rate reduction to zero of the worldwide incidence of
and egg reduction rate are indicators that are infection caused by a specific agent, as a result
commonly used to measure the reduction of deliberate efforts. Once this is achieved,
in prevalence and reduction in intensity of continued measures are no longer needed. On
infection, respectively. the other hand, disease elimination is a reduction
Drug resistance is a genetically transmitted to zero of the incidence of a specified disease in a
loss of susceptibility to a drug in a parasite defined geographic area as a result of deliberate
population that was previously sensitive to the efforts. Continued intervention or surveillance
appropriate therapeutic dose. measures are still required.
Prevention and Control References
Morbidity control is the avoidance of illness Beaver PC, Jung RC, Cupp EW. Clinical
caused by infections. It may be achieved by parasitology. 9th ed. Philadelphia: Lea and
periodically deworming individuals or groups, Febiger; 1984.
known to be at risk of morbidity. Markell EK, John DT. Medical parasitology.
Information-education-communication 8th ed. Philadelphia: W. B. Saunders
(IEC) is a health education strategy that aims Company; 1999.
to encourage people to adapt and maintain Markell EK, Voge M, John DT. Medical
healthy life practices. parasitology. 7th ed. Philadelphia: W. B.
Environmental management is the planning, Saunders Company; 1992.
organization, performance, and monitoring Muller R. Worms and disease: a manual of
of activities for the modification and/or medical helminthology. London: William
manipulation of environmental factors or their Heinemann Medical Books Limited; 1975.
interaction with human beings with a view to Neva FA, Brown HW. Basic clinical parasitology.
preventing or minimizing vector or intermediate 6th ed. Connecticut: Appleton and Lange;
host propagation and reducing contact between 1994.
humans and the infective agent. Walter-Beck J, Davies J. Medical parasitology.
Environmental sanitation involves 3rd ed. Missouri: The C. V. Mosby
interventions to reduce environmental health Company; 1981.
risks including the safe disposal and hygienic World Health Organization. Prevention and
management of human and animal excreta, control of schistosomiasis and intestinal
refuse, and waste water. It also involves the nematodes. Geneva: World Health
control of vectors, intermediate hosts, and Organization; 2002.
6 Medical Parasitology in the Philippines
Host-Parasite Relationships
Vicente Y. Belizario, Jr.
is by interference with the vital processes of blood factor increases the susceptibility of an
the host through parasitic enzymes. Secretory individual to Plasmodium vivax infection.
and excretory products elaborated by many Another important aspect is the nutritional
parasites allow them to metabolize nutrients status of the host. A diet rich in protein is
obtained from the host and store these for not suitable for the development of intestinal
energy production. This is best exemplified by protozoans, while a low-protein diet favors
Entamoeba histolytica trophozoites that secrete the appearance of symptoms of amebiasis
cysteine proteinases, which do not only digest and complications of the disease. A high
cellular materials but also degrade epithelial carbohydrate diet favors the development of
basement membrane facilitating tissue invasion. some tapeworms.
Another mechanism is through invasion Immune processes play an important role in
and destruction of host tissue. One example host-parasite relationships. Absolute immunity
is Plasmodium, which invades red blood cells. to reinfection occurs rarely following protozoan
After multiplication, the host’s red blood cells infections, and probably never happens with
rupture resulting in the release of merozoites. helminth infections in humans. Acquired
In Schistosoma japonicum infection, cumulative immunity may be very important in modifying
deposition of eggs in the liver stimulates an the severity of disease in endemic areas.
immune response mechanism resulting in
References
granuloma formation and then fibrosis which
leads to portal hypertension and massive Beaver PC, Jung RC, Cupp, EW. Clinical
hemorrhage in the venules. Hookworms have parasitology. 9th ed. Philadelphia: Lea and
cutting plates, which can attach to the intestinal Febiger; 1984.
mucosa and destroy the villi. Large numbers of Crompton DW, Savioli L. Intestinal parasitic
worms such as Ascaris form tangled masses that infections and urbanization. Bull World
can lead to intestinal obstruction. An Ascaris Health Organ. 1993;71(1):1–7.
worm in the intestine may invade other organs Markell EK, John DT. Medical parasitology.
like the appendix and bile ducts and may cause 8th ed. Philadelphia: W. B. Saunders
a surgical emergency. Company; 1999.
Parasites can also deprive the host of essential Markell EK, Voge M, John DT. Medical
nutrients and substances. Heavy hookworm parasitology. 7th ed. Philadelphia: W. B.
infection causes massive intestinal bleeding which Saunders Company; 1992.
results in chronic blood loss and iron deficiency Muller R. Worms and diseases: a manual of
anemia. Diphyllobothrium latum competes with medical helminthology. London: William
its host for the available supply of Vitamin B12, Heinemann Medical Books Limited; 1975.
thus resulting in megaloblastic anemia. Neva FA, Brown HW. Basic clinical parasitology.
6th ed. Connecticut: Appleton and Lange;
Effects of the Host on the Parasite
1994.
There are several factors which determine Que X, Reed SL. The role of extracellular
the outcome of an infection. The genetic make- cysteine proteinases in pathogenesis of
up of the host may influence the interaction Entamoeba histolytica invasion. Parasitol
between host and parasite. In falciparum Today. 1997;13(5):190–3.
malaria, possession of sickle-cell trait confers Walter-Beck J, Davies J. Parasitology. 3rd ed.
some protection, while the presence of Duffy Missouri: The C. V. Mosby Company;
1981.
8 Medical Parasitology in the Philippines
as well. Tight junctions between epithelial cells defenses rely on humoral and cell-mediated
serve to prevent passage of all but the smallest mechanisms of action.
molecules. The low pH of vaginal secretions The innate response happens when the
and gastric juices present a hostile environment body detects and eliminates pathogens through
to many microorganisms. For instance, the non-specific mechanisms that use mechanical,
trophozoites of Trichomonas vaginalis are unable chemical, and cytokine-mediated methods to
to survive the acidic environment of the vagina, destroy or disrupt invading organisms with
and once intestinal secretions envelope Giardia little or no delay from the time of invasion. One
lamblia, its motility is greatly diminished method is through phagocytosis by macrophages
reducing injury to the host. To evade this type and dendritic cells with subsequent pathogen
of host defense, the infective stages of helminths elimination through oxidative killing and use of
that are ingested, like embryonated eggs of toxic peptides. Some intracellular pathogens are
Ascaris, Trichuris, and Taenia spp. are protected able to invade and multiply inside macrophages,
from the acidic environment by thick egg shells. like Leishmania spp., Toxoplasma gondii, and
The cystic wall of intestinal protozoa like the Trypanosoma cruzi, in which case cell-mediated
Entamoeba and Giardia are also resistant to immune mechanisms (whether non-specific
acidic pH. such as natural killer cells, or acquire cell-
Chemical components of body fluids play mediated immunity through T-lymphocytes)
a major role in the protection of the host. The are required to identify and destroy them.
lipase content of breast milk, for example, has Toll-like receptors (TLRs) recognize
been found to be toxic to Giardia lamblia in specific molecules that are non-native to the
vitro. Lysozyme found in tears and saliva is able body and so represent some of the earliest
to destroy microorganisms, along with secreted recognition mechanisms for pathogens. To
IgA immunoglobulins in these fluids. date, ten TLRs have been identified and each
Physiologic functions of the body also is activated by a bacterial components [e.g.,
inhibit parasite invasion. Peristalsis, motion LPS (TLR4), diacylated lipoprotein (TLR2
of cilia, and human reflexes all serve to expel and 6) and triacylated lipoprotein (TLR 1
parasites. Coughing enables expectoration of and 2), flagellin (TLR5)], viral RNA (TLR3),
aberrantly situated adult Ascaris lumbricoides and other unfamiliar components. Binding of
and eggs of Paragonimus westermani, and the a specific ligand to a TLR causes a cascade of
flushing action of urine decreases the numbers reactions down a common signaling pathway
of Trichomonas vaginalis. which produces cytokines such as interferon
In the event that the parasite is able to gamma and interleukin-1. These cytokines
overcome physical barriers, a second host activate natural killer cells and macrophages,
defense comes into play. The penetration of stimulation of which leads to further production
the body’s barriers results in a series of events of inflammatory cytokines, and co-stimulatory
that facilitate sensing of the invading parasite molecules. TLRs are therefore largely responsible
via pathogen-associated molecular patterns, or for triggering the initial inflammatory response.
through pattern recognition responses which They function as pyrogens and synthesize
enable the body to mount an immune response inflammatory response proteins, which then
that acts towards eliminating or limiting the increase the number and function of phagocytic
infection. cells.
The host, once infected, is exposed to the
Host-Immune Response
parasite antigens, which in turn can stimulate
The host possesses both innate and the host to mount an acquired specific response
acquired immune defenses. Both kinds of against the antigen. The expression of acquired
10 Medical Parasitology in the Philippines
ADCC. Among these are eosinophil activating parasite life cycles, location within body sites
factor (EAF), interleukin-5, and granulocyte- that are relatively protected from the immune
monocyte colony stimulating factor (GM-CSF). response, and antigenic complexity.
Destruction of microfilariae among patients In addition, natural selection and
with tropical pulmonary eosinophilia has been adaptation have resulted in deployment by
attributed to ADCC mediated by IgE and the parasite of various mechanisms to avoid
eosinophils. Cells like neutrophils and platelets the destructive effect of the host response.
have been found to participate in ADCC as well. These major mechanisms include induction of
With homocytotrophic IgG1, IgE can immune suppression, antigenic variation, host
act on mast cells and basophils, which can mimicry, and sequestration among others.
lead to degranulation and eventual release
A. Resistance to Immune Response
of pharmacologically active substances.
Unregulated activation can result in an Protozoa and helminthic parasites that
anaphylactic Type 1 hypersensitivity reaction enter the blood stream or tissue are often
as seen during the rupture of Echinococcus able to survive and replicate because they are
granulosus hydatid cysts. The same immediate resistant to the host innate immune response.
hypersensitivity reaction has been observed at Parasites in humans are usually resistant to
the site of the bite of several arthropods like complement. Macrophages can phagocytose
mites and ticks. protozoa, but the cuticle and integument of
The combined activity of IgG and IgM helminthic parasites make them resistant to
can prevent penetration of erythrocytes by the cytotoxic effects of both neutrophils and
Plasmodium spp. and Babesia spp., but are macrophages. This may be due to the loss of
generally ineffective against gastrointestinal surface molecules that bind complement or
helminths. In the presence of complement acquisition of host regulatory proteins such as
activity, these antibodies can mediate lysis of decay accelerating factor. Trypanolytic factors
trypomastigotes of Trypanosoma cruzi and, even such as apolipoprotein L-1 (APOL1) destroy
in the absence of the complement, are involved non-human trypanosomes except Trypanosoma
in the rapid phagocytosis of the same parasites. brucei which has evolved resistance through
Secretory IgA in the intestines protect against expression of serum resistance-associated
metacestode and gastrointestinal infections. IgM protein. A frameshift mutation in the APOL1
with secretory IgA mediate ADCC in Giardia gene enables a non-human trypanosome (T.
lamblia infection. Among immunocompetent evansi) to infect a human, and addition of
individuals, Cryptosporidium infection is self- recombinant APOL1 restored trypanolytic
limited due to the combined action of IgA and activity.
lgG with cell-medicated immunity, which helps
B. Immune Suppression
cleave the parasite from the enterocytes.
In many infections, be it microbial or There are parasites that can reduce
parasitic, the host can activate its non-specific, the immune function of macrophages that
specific, humoral, and cell-mediated defenses result in lower capacity of phagocytosis and
all at the same time. defective processing of antigen, as in the case
of Plasmodium spp. infection. In Trypanosoma
Parasite Evasion Mechanisms
brucei infection, the trypomastigotes can
Parasites have several characteristics that produce large amounts of surface glycoproteins.
make it difficult for the host to detect and This affects the processing of the proteins
eliminate them: parasite size, complicated due to antigenic competition and at the
12 Medical Parasitology in the Philippines
same time impairs the B- and T-lymphocyte Malarial parasites, especially Plasmodium
activities resulting in diminished production of falciparum, exhibit antigenic diversity. The
lymphokines and immunoglobulins. mechanism is through repeat variation of the
Entamoeba histolytica suppresses macrophage encoded polypeptides, which contain tandem
respiratory burst and consequent nitric oxide sequences of amino acids, as observed in
production, produces a suppressor factor that merozoite surface antigen (MSA) and ring-
can inhibit movement of monocytes to the site infected erythrocyte surface antigen (RESA).
of invasion (monocyte locomotion inhibitory These repeat sequences are antigenic epitopes,
factor), and inhibits complement assembly. In which stimulate antibody production. With
Fasciola infection, there is down regulation of variation, therefore, antibodies fail to recognize
Th1 lymphocytes. In filarial infections with the antigen.
Wuchereria bancrofti and Brugia malayi, there
D. Host Mimicry
is polyclonal hypergammaglobulinemia where
antibodies lack specificity against these parasites. The larval stage of Echinococcus granulosus
This has also been observed in Plasmodium spp. in the hydatid cyst has been found to carry
infection. P blood group antigen, and the tegument of
Blocking antibodies produced by several Schistosoma spp. adult can acquire antigenic
parasites like Wuchereria bancrofti can also molecules from the host. Antibodies produced
dampen the effect of immune responses. In against the parasite then fail to recognize non-
Necator americanus infection, the immune self from self-antigens.
response is directed against the deeper layers
E. Intracellular Sequestration
of its cuticle but the immune response is
diverted to the rapidly changing surface of its Amastigotes of Trypanosoma cruzi and
integument. Leishmania spp. proliferate in macrophages
Immune complexes produced in cysticercus in various organs. Toxoplasma gondii multiply
cellulosae infection suppress inflammatory inside macrophages as well as in other nucleated
response through inhibition of complement cells. Once intracellular, they are able to evade
activity. Infection with Plasmodium spp. the host immune response.
and Trypanosoma cruzi can also lead to The late intracellular stages of Plasmodium
immunosuppression through the production falciparum are sequestered from the circulation
of immune complexes. In Schistosoma spp. in deep vasculature beds. This is mediated by
infection, complement cannot participate in the the presence of knobs on infected erythrocytes
destruction of the parasite; it has been found that enable them to attach to endothelial cells of
that the complement is consumed by the soluble capillaries. This sequestration process excludes
antigens of the Schistosoma spp. the parasitized red blood cells from splenic
filtration and the action of antibodies.
C. Antigenic Variation
Adverse Effects of the Immune Response
In Trypanosoma brucei infection, the initial in the Host
host response against the surface glycoproteins
of the trypomastigotes is very effective. But in Under normal circumstances, orderly
the subsequent releases of trypomastigotes, the progression of host defenses through the
immune response is no longer effective since different phases results in a well-controlled
the parasites have changed the antigenic profile immune and inflammatory response that
of their surface coat through variant surface protects the host from the offending antigen.
glycoproteins (VSG). Surface protein variation However, dysfunction of any of the host defense
has also been observed in Giardia lamblia. systems can result in damage to host tissue and
Chapter 1: Introduction to Medical Parasitology 13
produce clinical disease. The normal immune The main clinical manifestations of
response itself might contribute substantially to Schistosoma spp. infection are related to the
tissue damage as one of four types of reactions: host immune response to eggs that are trapped
Type 1 (Immediate type hypersensitivity), in various organs of the host. This usually
Type 2 (Immune complex formation), Type 3 results in hepatosplenomegaly, fibrosis, portal
(Cytotoxic reactions of antibody), and Type 4 hypertension, and esophageal varices. High
(Delayed-type hypersensitivity). levels of Schistosoma spp. circulating antigen in
In acute infection with Trypanosoma cruzi, immune complexes can produce a condition
the intense immune response to the parasite is very similar to serum sickness. T-cell mediated
accompanied by massive damage not only to the delayed-type of hypersensitivity lymphocytes,
infected cells but also to the surrounding cells when stimulated such as in Schistosoma spp.
including nerve cells and myocytes. It is believed infection, can produce attractants and activators
that this is partially responsible for heart failure of other cells that form destructive granulomas
and meningoencephalitis. Moreover, it has around Schistosoma spp. eggs. In Leishmania
been postulated that antibodies to T. cruzi may spp. infections, more macrophages are damaged,
activate adrenergic and muscarinic receptors be it the cutaneous, mucocutaneous, or visceral
because of similarities between these and parasite type of infection.
antigens, leading to autonomic dysfunction and
Practical Applications
predisposition to arrhythmias. In Wuchereria
bancrofti, there is an overproduction of IgM Understanding the host immune response to
(polyclonal hypergamma-globulinemia) due parasitic invasion is useful in immunodiagnosis,
to the functional T-suppressor cell (T8) defect, and predicting the resulting pathology.
which explains the formation of a large amount Current concepts on immunoregulation and
of immune complexes in Tropical Pulmonary immunomodulation are products of intense
Eosinophilia (TPE). and meticulous studies on these immune
In recurrent Plasmodium spp. infection, mechanisms. These insights may hold the key
immune complexes are associated with for potential control through vaccination and
a condition called hyperactive malarious development of novel anti-parasitic drugs.
splenomegaly (HMS). There is a disturbance
References
in the ability of T-lymphocytes to control the
humoral response resulting in polyclonal IgM Blum JA, Zellweger MJ, Burri C, Hatz C.
antibodies. Patients suffer from persistent Cardiac involvement in African and
splenomegaly and anemia. In patients with American trypanosomiasis. Lancet Infect
Plasmodium malariae infection, these immune Dis. 2008;8(10):631–41.
complexes may be deposited in the basement Garcia LS, editor. Diagnostic medical
membrane of the glomeruli leading to parasitology. 5th ed. Washington DC:
kidney failure and nephrotic syndrome. This ASM Press; 2006.
phenomenon may also occur in schistosomiasis. Kasper DL, Braunwald E, Fauci AS, Hauser SL,
While the sequestration of late Longo DL, Jameson JL, editors. Harrison’s
intraerythrocytic Plasmodium falciparum principles of internal medicine. 16th ed.
from the circulation and their attachment to New York: McGraw-Hill; 2005.
endothelial cells is protective to the parasite, MacDonald AS, Araujo MI, Pearce EJ.
this is also believed to be the main cause of Immunology of parasitic helminth
manifestations of cerebral malaria. infections. Infect Immun. 2002;70(2):427–
33.
14 Medical Parasitology in the Philippines
Maizels RM. Parasite immunomodulation and Ndam NT, Deloron P. Molecular aspects
polymorphisms of the immune system. J of Plasmodium falciparum infection
Biol. 2009;8(7):62. during pregnancy. J Biomed Biotechnol.
Mandell GL, Bennett JE, Dolin R, editors. 2007;2(5):43785.
Mandell, Douglas, and Bennett’s principles Rasmussen SB, Reinert LS, Paludan SR. Innate
and practice of infectious diseases. 7th ed. recognition of intracellular pathogens:
Philadelphia, PA: Churchill Livingstone detection and activation of the first line of
Elsevier; 2010. defense. APMIS. 2009; 117(5–6):323-37.
Moncada DM, Kammanadiminiti SJ, Chadee Sacks D, Sher A. Evasion of innate immunity
K. Mucin and toll-like receptors in host by parasitic protozoa. Nat Immunol. 2002;
defence against intestinal parasites. Trends 3(11):1041–7.
Parasitol. 2003;19(7):305–11. Takeda K, Akira S. TLR signaling pathways.
Moreau E, Chauvin A. Immunity against Semin Immunol. 2004;16(1):3–9.
helminths: interactions with the host Vanhollebeke B, Truc P, Poelvoorde P, Pays
and the intercurrent infections. J Biomed A, Joshi PP, Katti R, et al. Human
Biotechnol. 2010;428593. Trypanosoma evansi infection linked to a
lack of apolipoprotein L-I. N Engl J Med.
2006;355(26): 2752–6.
Chapter 1: Introduction to Medical Parasitology 15
infections in man belong to three groups, Larvae of Trichinella are encysted in the host
namely, annelids, nematodes, and flatworms. muscles.
Under the annelids, only the leeches are There are various ways by which
considered to be of medical importance. humans acquire these helminths. Ingestion
The nematodes are also known as of embryonated eggs is the mode of infection
roundworms because they are elongated and of Ascaris, Trichuris, and Enterobius. Skin
cylindrical in shape, with bilateral symmetry. penetration by filariform larvae is the mode
Generally, they have a complete digestive tract of infection of hookworms and Strongyloides,
and a muscular pharynx that is characteristically while the bite of mosquito vectors is the
triradiate. They are provided with separate mode of transmission of Wuchereria and
sexes, although some may be parthenogenetic. Brugia. Ingestion of infective larvae is the
There are sensory organs in the anterior and mode of infection for Capillaria from fish,
posterior ends of the worm called amphids Trichinella from pork, and Parastrongylus from
and phasmids, respectively. The latter are very snails. Autoinfection occurs in Capillaria,
useful in the grouping of the nematodes. Those Strongyloides, and Enterobius. Transmission
roundworms with phasmids are described as through inhalation of embryonated eggs is
phasmid nematodes, while those without them possible for Enterobius and Ascaris.
are described as aphasmid worms. Among
Cestodes
the nematodes of medical and public health
importance, only three are aphasmid worms The two other groups of worms are
(Adenophorea). These are Trichuris, Trichinella, tapeworms or cestodes, and flukes or trematodes.
and Capillaria. The rest of the nematodes are, These belong to Platyhelminthes or the
therefore, phasmid nematodes (Secernentia). flatworms. Members of Platyhelminthes, in
The phasmid worms belong to several general, are dorso-ventrally flattened with
orders in the scientific taxonomic classification bilateral symmetry. The cestodes are segmented,
of the worms. Ascaris belongs to Ascaridida, with a ribbon-like appearance, while the
Parastrong ylus and the hookworms to trematodes are leaf-like and unsegmented.
Strongylida, Strongyloides to Rhabditida, Cestodes do not have a digestive tract, while
Enterobius to Oxyurida, and the filarial worms trematodes have an incomplete one. Both
to Spirurida. A more extensive discussion of cestodes and trematodes do not have a
the taxonomic groupings of these worms can circulatory system.
be found in other references. Adult tapeworms are hermaphroditic. They
These nematodes can be grouped on the are found in the intestines of the definitive
basis of the habitat of the adult worms. Most host, and the larval stage is encysted in the
of these nematodes are found in the small and tissues of the intermediate host. They have an
large intestines, while some are found outside anterior structure called the scolex, which is
the intestines. the main organ of attachment of the worm to
Those typically found in the small the definitive host. After the scolex is the neck,
intestines are Ascaris, hookworms, Strongyloides, which is then followed by the strobila. The neck
and Capillaria, while those usually located is considered the region of growth, because
in the colon are Trichuris and Enterobius. segmentation or strobilization originates from
Extraintestinal nematodes like Wuchereria and it. Segments or proglottids that are nearest to
Brugia have been recovered from the lymph the neck are the most immature, followed by
nodes and lymph vessels, whereas Parastrongylus increasingly mature segments, and the most
has been reported from the eyes and meninges. distal are gravid segments.
18 Medical Parasitology in the Philippines
The cestodes are grouped together into various species of Taenia produce the cysticercus
different orders, just like the nematodes. type, while Hymenolepis, Dipylidium, and
However, there are only two orders of tapeworms Raillietina produce the cysticercoid type. A
with medical and public health significance, third type called the hydatid is produced by
namely, Order Pseudophyllidea and Order Echinococcus spp.
Cyclophyllidea. These two orders differ in terms Infection with adult tapeworms is generally
of the morphology of the scolex, segments, and acquired through the consumption of infected
eggs, as well as in the number of intermediate intermediate hosts. There are cases, however,
hosts and the type of encysted larvae that where humans are infected with the larval stage
develop in the intermediate hosts. of Taenia solium, called cysticercosis, and of
Pseudophyllidean tapeworms have a Echinococcus spp., called hydatid cyst.
spatulate scolex with sucking grooves, called
Trematodes
bothria, while the Cyclophyllidean scolex
is globular with four muscular suckers. The other group of flatworms is composed
Segments of both orders have genital pores of the flukes or trematodes. Adult trematodes
but Pseudophyllidean segments, in addition, are equipped with an oral sucker, and a
have a uterine pore which allows release of eggs ventral sucker called an acetabulum. A third
from the gravid uterus. Since Cyclophyllidean sucker called a genital sucker or gonotyl is
segments do not have the uterine pore, they observed only among the heterophyids. They
undergo the process of apolysis whereby gravid are all hermaphroditic. All trematodes require
segments are detached from the main body two intermediate hosts in their life cycle.
of the worm and eggs are eventually released. All trematodes have operculated eggs, and
For diagnostic purposes, in Cyclophyllidean the infective stage for all these trematodes
infections, both eggs and segments are recovered is the encysted larva, the metacercaria, that
from the patients, while in Pseudophyllidean develops in the second intermediate host. These
infections, segments may not be found. characteristics are observed in all medically
Non-operculated Cyclophyllidean eggs are important trematodes, with the exception of
passed out readily, containing the hexacanth the schistosomes in which the infective stage is
embryo. On the other hand, Pseudophyllidean the cercaria. While the first intermediate host
eggs, which are operculated and immature, is always a snail, the second intermediate host
require aquatic development of the embryo, may be a fish, crustacean, another snail, or fresh
called the coracidium. water plants.
Pseudophyllidean worms generally require Trematodes are generally grouped together
two intermediate hosts in their life cycle. based on their habitat. Adult schistosomes are
In the first intermediate host, eggs encyst found in the mesenteric veins; hence they are
as procercoid larvae, then into plerocercoid called blood flukes. Adult Paragonimus worms
larvae in the second intermediate host. This are found in the lung parenchyma. There is
group of tapeworms is best represented by a group of flukes that inhabits the liver and
Diphyllobothrium, which utilizes humans as bile passages. This group includes Fasciola,
definitive hosts, and Spirometra, which employs Clonorchis, and Opisthorchis. Another group
humans as an intermediate host. composed of Fasciolopsis, Echinostoma, and
Cyclophyllidean worms require only one heterophyids inhabits the intestines.
intermediate host, but different species of Mature eggs contain an embryo called the
Cyclophyllideans produce different types of miracidium. Eggs passed out by an infected host
encysted larvae in the intermediate hosts. The may be mature, as in the case of Schistosoma,
Chapter 1: Introduction to Medical Parasitology 19
Protozoan Infections
Intestinal Amebae
Pilarita T. Rivera, Windell L. Rivera, Juan Antonio A. Solon
20
Chapter 2: Protozoan Infections 21
although natural infection of primates has been Infection with E. histolytica occurs when cysts
reported. The quadrinucleate cyst is resistant to are ingested from fecally-contaminated material
gastric acidity and desiccation, and can survive (Figure 2.1). Other modes of transmission
in a moist environment for several weeks. include venereal transmission through fecal-oral
and cytophagocytosis. In vitro, amebic killing study involving 206 patients with probable
of target cultivated mammalian cells involve ALA as diagnosed by ultrasound, the two
receptor-mediated adherence of ameba to most frequent manifestations were fever in
target cells, amebic cytolysis of target cells, 77% and RUQ pain in 83%. Pain is either
and amebic phagocytosis of killed or viable localized in or referred to the right shoulder.
target cells. E. histolytica trophozoites adhere The liver is tender, especially in acute cases,
to the colonic mucosa through a galactose- and hepatomegaly is present in 50% of cases.
inhibitable adherence lectin (Gal lectin). Then, Chronic disease (>2 weeks duration) is found
the amebae kill mucosal cells by activation of in older patients and it involves wasting with
their caspase-3, leading to their apoptotic death significant weight loss rather than fever. Only
engulfment. 30% of ALA cases have concurrent diarrhea.
Recent studies have shown that susceptibility However, daily stool cultures revealed that 72%
of humans to E. histolytica infection is associated harbored trophozoites even in asymptomatic
with specific alleles of the HLA complex. infections. Mortality in uncomplicated ALA is
Majority of cases present as asymptomatic less than 1%.
infections with cysts being passed out in The onset of amebic colitis may be sudden
the stools (cyst carrier state). The recent after an incubation period of 8 to 10 days, or
differentiation of E. dispar and E. histolytica after a long period of asymptomatic cyst carrier
by PCR has confirmed the high prevalence state. ALA may have all acute presentation of
of non-pathogenic E. dispar compared to the less than 2 weeks duration or a chronic one of
pathogenic E. histolytica. However, studies also more than 2 weeks duration. The recurrence
revealed that most E. histolytica infections in rate was found to be 0.29% in a five-year study
endemic communities are asymptomatic. of ALA in Mexico.
Amebic colitis clinically presents as gradual The most serious complication of amebic
onset of abdominal pain and diarrhea with or colitis is perforation and secondary bacterial
without blood and mucus in the stools. Fever peritonitis. Colonic perforation occurs in 60%
is not common and it occurs only in one third of fulminant colitis cases.
of patients. Although some patients may only In ALA, the most serious complications are
have intermittent diarrhea alternating with rupture into the pericardium with a mortality
constipation, children may develop fulminant rate of 70%, rupture into the pleura with
colitis with severe bloody diarrhea, fever, and mortality of 15 to 30%, and super infection.
abdominal pain. Intraperitoneal rupture, which occurs in 2 to
Ameboma occurs in less than 1% of 7.5% of cases, is the second most common
intestinal infections. It clinically presents as complication. However, it is not as serious as
a mass-like lesion with abdominal pain and colonic perforation because ALA is sterile.
a history of dysentery. It can be mistaken for Secondary amebic meningoencephalitis
carcinoma. Asymptomatic ameboma may also occurs in 1 to 2%, and it should be considered
occur. in cases of amebiasis with abnormal mental
Amebic liver abscess (ALA) is the most status. Renal involvement caused by extension
common extra-intestinal form of amebiasis. of ALA or retroperitoneal colonic perforation is
The cardinal manifestations of ALA are fever rare. Genital involvement is caused by fistulae
and right upper quadrant (RUQ) pain. Several from ALA and colitis or primary infection
studies have shown these two as the most through sexual transmission.
frequent complaints, particularly in acute Natural or innate immunity to E. histolytica
cases (<2 weeks duration). In a Philippine in the intestines involves mucin inhibition of
24 Medical Parasitology in the Philippines
amebic attachment to the underlying mucosal Acute amebic colitis should be differentiated
cells. In the systemic circulation, the mechanism from bacillary dysentery of the following
is that of complement-mediated killing of etiology: Shigella, Salmonella, Campylobacter,
trophozoites. Acquired immunity primarily Yersinia, and enteroinvasive Escherichia coli
involves cell-mediated responses, although (Table 2.1). Although stools may be grossly
humoral responses may also contribute to bloody or heme-positive in both conditions,
anti-amebic immunity. Activated T-cells kill fever and significantly elevated leukocyte count
E. histolytica by: a) directly lysing trophozoites are less common in amebic colitis. Another
in a contact-dependent process; b) producing differential is inflammatory bowel disease.
cytokines which activate macrophages and other Amebic colitis should be ruled out before
effector cells (neutrophils and eosinophils); and steroid therapy for inflammatory bowel disease
c) providing helper effect for B-cell antibody is started because of the risk of developing toxic
production. In vitro studies using activated megacolon.
murine and human T-cells demonstrated The differential diagnoses of ALA include
significant killing of trophozoites in a contact- pyogenic liver abscess, tuberculosis of the liver,
dependent and antibody independent manner. and hepatic carcinoma. On the other hand,
Cytokine studies revealed that interferon (IFN) genital amebiasis should be differentiated
and interleukin (IL-2) may have a role in from carcinoma, tuberculosis, chancroid, and
activating macrophages for amebicidal activity. lymphogranuloma venereum.
More recent studies demonstrated that activated
macrophages produce nitric oxide (NO) which Table 2.1. Comparison of bacillary and amebic
was lethal to trophozoites. Tumor necrosis factor dysentery
(TNF) was shown to stimulate NO production.
Bacillary Dysentery Amebic Dysentery
Although it is known that antibodies are
May be epidemic Seldom epidemic
produced against amebic antigens, there has
Acute onset Gradual onset
been no direct evidence of T-cell help for
Prodromal fever and No prodromal features
B-cells. Studies have revealed that the principal malaise common
antibody-dependent cell cytotoxicity (ADCC) Vomiting common No vomiting
did not work against amebae. Antibodies which Patient prostrate Patient usually ambulant
were detected by seroepidemiologic studies and
Watery, bloody diarrhea Bloody diarrhea
secretory IgA isolated in the gut may merely
Odorless stool Fishy odor stool
be an indicator of current or recent invasive
Stool microscopy:
amebiasis. numerous bacilli, pus
Amebic modulation of host immune cells,
responses exists. For instance, infected human macrophages, red cells, Stool microscopy: few
no Charcot-Leyden bacilli, red cells,
subjects and animals have been shown to be in crystals trophozoites with
a state of immunosuppression during the acute ingested red blood
cells, Charcot-Leyden
stage of amebiasis. This state, characterized crystals
by T-cell hyporesponsiveness, suppressed Abdominal cramps Mild abdominal cramps
proliferation and cytokine production, depressed common and severe
delayed-type hypersensitivity (DTH), and Tenesmus common Tenesmus uncommon
macrophage suppression, is favorable for amebic Natural history: Natural history: lasts for
survival. It is the reversal of these modulatory spontaneous recovery weeks; dysentery
in a few days, weeks or returns after remission;
effects, which is the key in controlling amebiasis. more; no relapse infection persists for
years
Chapter 2: Protozoan Infections 25
countries, prevalence depends on the level of cases should be done. Food handlers should be
sanitation, crowding, socio-economic status, screened for cyst carriage, and asymptomatic
cultural habits, and age. In developed countries, cyst carriers should be treated.
infection is usually caused by E. dispar, and Vaccines can be a cost-effective and
is prevalent in certain groups: immigrants, potent strategy for amebiasis prevention
travelers from endemic countries, homosexual and eradication. Unlike in other protozoan
males (men having sex with men), HIV patients, infections, amebic vaccine development has
and institutionalized people. fewer problems. The ameba life cycle is simple,
A microscopic study of diarrheic stools in and no intermediate hosts are involved. Amebae
Australia (n=5,921) revealed 177 (3%) positive are extracellularly located, and do not undergo
samples. PCR detected 5 E. histolytica, 63 E. antigenic variation. All these characteristics are
dispar, and 55 E. moshkovskii infections. The supportive of an achievable amebic vaccine.
latter two species, which are both commensals, Studies have also demonstrated the
are 10 times more prevalent than E. histolytica. acquisition of protective immunity to amebae,
A stool survey done in Iran (n=16,592) showed particularly that of mucosal immune response.
226 positive samples. Only 101 isolates were Trials with recombinant amebic antigens as
successfully cultured in Robinson’s medium. vaccines have proven to be more advantageous
Of these isolates, 93 (92.1%) were E. dispar, than inactivated/attenuated amebae. The
and only 8 (7.9%) were E. histolytica or mixed candidate vaccine molecules which have been
infections by PCR- RFLP. most intensely studied are the serine-rich E.
A field study in Northern Philippines histolytica protein (SREHP), the adherence
(n=1,872) showed 137 (7.3%) E. dispar, and lectin (Gal/GalNAc lectin), and the 29 kDa
18 (0.96%) E. histolytica by PCR. A study in a cysteine-rich amebic antigen. However, most
mental institution (n=113) showed E. histolytica of these studies have utilized animal models
or E. dispar in 43 subjects (38.1%), while PCR and artificial infection during challenge.
detected 74 (65.5%) E. histolytica-positive Testing these candidate vaccines in humans
samples, and 6 (5.3%) E. dispar/E. histolytica and developing them as food-based vaccines
mixed samples. will be in the forefront of future directions of
amebiasis control.
Prevention and Control
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Chapter 2: Protozoan Infections 29
Commensal Amebae
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E. histolytica, E. hartmanni does not ingest red by the following features: 1) a more vacuolated
blood cells. or granular endoplasm with bacteria and
debris, but no red blood cells; 2) a narrower,
Entamoeba coli
less-differentiated ectoplasm; 3) broader and
Entamoeba coli is cosmopolitan in blunter pseudopodia used more for feeding
distribution, and is considerably more common than locomotion; 4) more sluggish, undirected
than other human amebae. Trophozoites of E. movements; and 5) thicker, irregular peripheral
coli measure 15 to 50 μm in diameter. It can chromatin with a large, eccentric karyosome in
be differentiated from E. histolytica trophozoite the nucleus (Plate 2.7).
Chapter 2: Protozoan Infections 31
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34 Medical Parasitology in the Philippines
Acanthamoeba spp.
Parasite Biology
increased susceptibility to infection, and may fluorescence microscopy. GAE usually occurs
lead to disseminated disease in the lungs and in immunocompromised hosts including
brain (GAE). the chronically ill and debilitated, and
Symptoms of AK include severe ocular those on immunosuppressive agents such as
pain and blurring of vision. Corneal ulceration chemotherapy and anti-rejection medications.
with progressive corneal infiltration may occur. The acquired immune deficiency syndrome
Primary amebic infection or secondary bacterial (AIDS) epidemic in the 1980’s dramatically
infection may lead to hypopyon formation. increased the numbers of person with GAE,
Progression of infection may cause scleritis and but these numbers have since fallen with the
iritis, and may ultimately lead to vision loss. advent of highly effective antiretroviral therapy.
Major differentials which need to be ruled out Signs and symptoms of GAE are generally
include fungal and herpetic keratitis. related to destruction of brain tissue and the
associated meningeal irritation. Systemic
B. Granulomatous Amebic Encephalitis
manifestations early in the course include fever,
Acanthamoeba was documented as the malaise, and anorexia. Neurologic symptoms
causative agent of human GAE by Stamm in may include increased sleeping time, severe
1972. Amebae were demonstrated in brain headache, mental status changes, epilepsy, and
sections of a GAE patient using indirect coma. Neurologic findings depending on the
36 Medical Parasitology in the Philippines
location of the lesions include hemiparesis, Diagnosis of GAE is usually made post-
blurring of vision, diplopia, cranial nerve mortem in most cases. The rarity of the
deficits, ataxia, and increased intracranial disease and unfamiliarity of most physicians
pressure. with the pathogen contribute to frequently
Entry of Acanthamoeba into the central missed diagnosis. Signs and symptoms of
nervous system is still incompletely understood. disease are usually attributed to more common
From a primary site of infection in the differentials. Moreover, recovery of ameba from
skin or lungs, the likely route of invasion is cerebrospinal fluid is exceedingly rare, and
hematogenous. Direct infection through the imaging results are generally nonspecific.
olfactory valves has also been proposed, but Immunocompromised patients such
not conclusively demonstrated. Recent reviews as those with AIDS are at the highest risk
have focused on blood-borne invasion, with for acquiring GAE. While opportunistic
a combination of host factors, elucidation of infections of the central nervous system such
serine proteases, and parasite adhesion using as Cryptococcus meningitis and toxoplasmosis
a mannose-binding protein all contributing to are much more common than GAE, the lack of
brain endothelial cell damage and subsequent response despite appropriate treatment should
breakdown of the blood-brain barrier. prompt a more thorough evaluation for more
Gross examination of neural tissue post- esoteric organisms.
mortem reveals cerebral hemispheres that are Specific diagnosis depends on demonstrating
edematous and soft, with areas of hemorrhage the trophozoites or cysts in tissues using
and focal abscesses. The most affected areas histopathologic stains and microscopy. The
of the brain are the posterior fossa structures, organisms can rarely be demonstrated in the
thalamus, and the brainstem. In the affected cerebrospinal fluid and can be cultured for
areas, the leptomeninges are opaque and exhibit further studies.
purulent exudates and vascular congestion.
Treatment
The incubation period from initial
inoculation is approximately 10 days, with a Medical treatment of AK has been met
subacute and chronic clinical course of infection with increasing success in recent years. While
that lasts for several weeks to several months. historically, only surgical excision of the infected
The clinical manifestations of disease include cornea with subsequent corneal transplantation
decreased sensorium, altered mental status, was curative, early recognition of AK coupled
meningitis, and neurologic deficits. The natural with aggressive combination anti-amebic
course of the disease eventually results in coma agents can preclude the need for extensive
and death. surgery. D’Aversa and his colleagues have
achieved acceptable results with clotrimazole
Diagnosis
combined with pentamidine, isethionate,
Acanthamoeba keratitis is diagnosed by and neosporin. Other agents that have been
epithelial biopsy or corneal scrapings for used include polyhexamethylene biguanide,
recoverable ameba with characteristic staining propamidine, dibromopropamidine isethionate,
patterns on histologic analysis. Amebae have neomycin, paromomycin, polymyxin B,
also been isolated from the contact lens and lens ketoconazole, miconazole, and itraconazole.
solution of patients. Species-specific identification Topical corticosteroids should be avoided, as
can be made from culture and molecular analysis this retards the immune response. Advanced
through PCR. Known species that have caused AK usually requires debridement, but complete
AK include A. castellani, A. culbertsoni, A. excision of the cornea can be avoided if the
hutchetti, A. polyphaga, and A. rhysoides. infection is confined to more superficial areas.
Chapter 2: Protozoan Infections 37
Deep lamellar keratectomy is the procedure of of the risk of infection, and physicians treating
choice. these patients should maintain a high index
Clinically apparent neurologic disease in of suspicion in the presence of compatible
GAE usually heralds a fatal outcome within signs and symptoms of infection which do not
3 to 40 days. A few patients have shown good respond to conventional antimicrobial therapy.
responses to combinations of amphotericin
References
B, pentamidine isethionate, sulfadiazine,
flucytosine, fluconazole or itraconazole. D’Aversa G, Stern GA, Driebe WT Jr. Diagnosis
One liver transplant patient survived after and successful medical treatment of
decompressive frontal lobectomy and treatment Acanthamoeba keratitis. Arch Ophthalmol.
with amphotericin, cotrimoxazole, and 1995;113(9):1120–3.
rifampin. Poor prognostic factors include severe De Jonckheere JF. Ecology of Acanthamoeba.
immunosuppression and advanced disease. Rev Infect Dis. 1991;13(Suppl 5):S3857.
Enriquez GL, Lagmay J, Natividad FF, Matias
Epidemiology
GA. Pathogenicity of two human isolates of
Acanthamoeba spp. have a protean Acanthamoeba keratitis in mice. Proc. IXth
distribution, having been isolated from a International Congress of Protozoology;
multitude of natural and artificial aquatic 1993. Berlin, Germany.
environments including fresh and salt water, Fung KT, Dhillon AP, McLaughlin JE, Lucas
sewage, hospital equipment, and contact lenses SB, Davidson B, Rolles K, et al. Cure of
and lens solution. Acanthamoeba cerebral abscess in a liver
De Jonckheere first diagnosed Acanthamoeba transplant patient. Liver Transpl. 2008;
GAE in a living patient in 1991. Previously, 14(3):308–12.
diagnosis of GAE was post-mortem. AK was Khan NA. Acanthamoeba and the blood-
recognized earlier in the 1970s and has been brain barrier: the breakthrough. J Med
reported in the United States, Europe, South Microbiol. 2008;57:1051–7.
America, and Asia. The first case of AK was Matias R, Schottelius J, Raddatz CF, Michel R.
recognized in the Philippines in the 1990s Species identification and characterization
from a patient from the Philippine General of an Acanthamoeba strain from human
Hospital, and samples obtained from the patient cornea. Parasitol Res. 1991;77(6):469–74.
was shown to cause GAE in mice. Multiple Salvana EM, Matias RR. Histopathology of
environmental isolates have likewise been well- mouse brain infected with Acanthamoeba
characterized from all over the Philippines, isolate IB-17 [undergraduate thesis].
including a few containing endosymbionts. Quezon City, Philippines: University of
the Philippines Diliman; 1996.
Prevention and Control
Visvesvara GS, Moura H, Schuster FL.
The ubiquitious nature of Acanthamoeba Pathogenic and opportunistic free-living
spp. makes exposure unavoidable. A robust amoebae: Acanthamoeba spp., Balamuthia
immune system is able to prevent infection, mandrillaris, Naegleria fowleri, and Sappinia
except in relatively immunocompromised diploidea. FEMS Immunol Med Microbiol.
sites such as the cornea. Meticulous contact 2007;50:1–26.
lens hygiene is essential in avoiding infection, Yagita K, Matias RR, Yasuda T, Natividad FF,
and rinsing contact lenses in tap water should Enriquez GL, Endo T. Acanthamoeba sp.
be avoided. Prolonged heating and boiling from the Philippines: electron microscopy
kill amebic trophozoites and cyst forms. studies on naturally occurring bacterial
Immunocompromised persons should be aware symbionts. Parasitol Res. 1995;81(2):98–102.
38 Medical Parasitology in the Philippines
Naegleria spp.
Plate 2.10. Naegleria fowleri trophozoites in ameboid (left) and ameboflagellate (right) forms
(Accessed from www.dpd.cdc.gov/dpdx)
Naegleria fowleri has three stages, cysts, by penetrating the nasal mucosa and migrating
trophozoites, and flagellated forms, in its life to the brain via the olfactory nerves. N. fowleri
cycle. The trophozoites replicate by promitosis trophozoites are found in cerebrospinal fluid
(nuclear membrane remains intact) and can turn (CSF) and tissue, while flagellated forms are
into temporary non-feeding flagellated forms, occasionally found in CSF. Cysts are not seen
which usually revert back to the trophozoite in brain tissue (Figure 2.4).
stage. Trophozoites infect humans or animals
Chapter 2: Protozoan Infections 39
are the major host of balantidiasis, although Dodd LG. Balantidium coli infestation as a
primates have been reported to harbor infection. cause of acute appendicitis. J Infect Dis.
Prevalence studies in the United States and in 1991; 163:13–92.
Europe have reported infection rates ranging Goldberg JE, Parasitic colitides. Clin Colon
from 5% to as high as 100% in some areas. In Rectal Surg. 2007;20:38–46.
a study done in two (northern and southern) Karanis P, Kourenti C, Smith H. Waterborne
sites in the Philippines, an examination of pigs transmission of protozoan parasites: a
revealed 66.1% prevalence of B. coli infection. worldwide review of outbreaks and lessons
There has been a single report of an outbreak learnt. J Wat Health. 2007;5:1–38.
of balantidiasis that occurred in the Truk island Koopowitz A, Smith P, van Rensburg N,
in Micronesia in 1971. Rudman A. Balantidium coli-induced
pulmonary haemorrhage with iron
Prevention and Control
deficiency. S Afr Med J. 2010;100:534–6.
Control measures for balantidiasis include Ladas SD, Savva S, Frydas A, Kaloviduris
proper sanitation, safe water supply, good A, Hatzioannou J, Raptis S. Invasive
personal hygiene, and protection of food from balantidiasis presented as chronic colitis
contamination. Measures to limit contact of and lung involvement. Dig Dis Sci.
pigs with water sources and food crops may 1989;34(10):1621–3.
also contribute to reducing transmission La Via MV. Parasitic gastroenteritis. Pediatr
and infection. Use of pig feces as fertilizer Ann. 1994;23(70):556–60.
should also be avoided. Though cysts may Lee JL, Lanada EB, More SJ, Cotiw-an
be resistant to environmental conditions and BS, Taveros AA. A longitudinal study
may survive for long periods of time, they are of growing pigs raised by smallholder
easily inactivated by heat and by 1% sodium farmers in the Philippines. Prev Vet Med.
hypochlorite. Ordinary chlorination of water 2005;70:75-93.
is not effective against B. coli cysts. Nakauchi K. The prevalence of Balantidium coli
infection in fifty-six mammalian species. J
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1984. coli isolated in the Philippines. Parasitol
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Farthing MJ. Treatment options for the Skotarczak B. Cytochemical identification of
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46 Medical Parasitology in the Philippines
Giardia duodenalis
Juan Antonio A. Solon
body temperature and stable at a pH of 7.8 be asymptomatic. For acute cases, patients
to 8.2. The parasite may also produce a lectin experience abdominal pain, described as
which, when activated by duodenal secretions, cramping, associated with diarrhea. There is
is able to facilitate attachment. Once attached, also excessive flatus with an odor of “rotten
the organism is able to avoid peristalsis by eggs” due to hydrogen sulfide. Other clinical
trapping itself in between the villi or within the features include abdominal bloating, nausea,
intestinal mucus. and anorexia. Diarrhea is the most common
Upon attachment to the intestinal cells, symptom, occurring in 89% of cases. It is
G. duodenalis is able to cause alterations in followed by malaise and flatulence. Spontaneous
the villi such as villous flattening and crypt recovery occurs within 6 weeks in mild to
hypertrophy. These alterations lead to decreased moderate cases. In untreated cases, patients may
electrolyte, glucose, and fluid absorption, and experience diarrhea with varying intensities, for
cause deficiencies in disaccharidases. Studies on weeks or months.
Giardia muris-infected mice showed diffuse loss Chronic infection is characterized by
of microvillous surface area which investigators steatorrhea, or the passage of greasy, frothy
also correlated to decreased maltase and stools. In some cases, periods of diarrhea have
sucrase activities. The physiologic disturbances been observed to alternate with normal or even
subsequently result in malabsorption and constipated bowel periods. There may be weight
maldigestion, which in turn cause the signs and loss, profound malaise, and low-grade fever. In
symptoms experienced by the patient. Bacterial developing countries, it has been described as a
colonization of the area may further worsen the cause of the failure-to-thrive syndrome.
damage already caused by the parasite.
Diagnosis
In other studies, G. duodenalis was shown
to rearrange the cytoskeleton in human colonic Diagnosis is made by demonstration of G.
and duodenal monolayers. Cytoskeleton is duodenalis trophozoites (Plate 2.11) and/or cysts
essential for proper cell attachment to the (Plate 2.12) in stool specimens. Trophozoites
extracellular matrix and the other neighboring in direct fecal smears may be characterized as
cells. Changes observed in apoptotic cells having a floating leaf-like motility. To detect
include disruption of the cytoskeleton that leads
to structural disintegration and detachment
from the substrate. Hence, the parasite has
been suggested to cause enterocyte apoptosis.
This finding was strengthened by another study,
which showed the ability of the parasite not
only to disrupt cellular tight junctions but also
to increase epithelial permeability, thus, leading
to the loss of epithelial barrier function. With
this loss of barrier function, luminal contents
may penetrate the submucosal layers causing
more damage in the intestinal tissue.
From ingestion of the cysts, it takes about Plate 2.11. Giardia duodenalis trophozoite
1 to 4 weeks (average of 9 days) for the disease (Courtesy of the Department of Parasitology,
to manifest. Half of the infected patients may UP-CPH)
Chapter 2: Protozoan Infections 49
The first published study on Giardia or by infected food handlers. Normal water
genotypes in the Philippines showed that the chlorination will not affect cysts, but usual
majority (86%) of the isolated genotypes belong water treatment modalities should be adequate.
to assemblage B.
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Avila MS, Garcia MR, Narcelles MV, Serra
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Baldo ET, Belizario VY, de Leon WU, Kong Esparar DG, Belizario VY, Jr., Relos JR.
HH, Chung DI. Infection status of Prevalence of intestinal parasitic infections
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2000;31(3):478–81. status of inhabitants in the Roxas City,
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Dib HH, Lu SQ, Wen SF. Prevalence of Giardia Natividad FF, Buerano CC, Lago CB,
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Chapter 2: Protozoan Infections 53
Trichomonas vaginalis
Juan Antonio A. Solon
acridine orange stains. Trichomonas can also be detection tests and polymerase chain reaction
cultured using Diamond’s modified medium, (PCR) assays are commercially available, but
and Feinberg and Whittington culture medium. not widely used locally. PCR among females
The Pap smear may also show trichomonads does not seem to offer an added diagnostic
(sensitivity 60%; specificity 95%). Antigen advantage. Among males, however, diagnosis is
Chapter 2: Protozoan Infections 55
characterized molecularly showing low genetic Gumbo FZ, Duri K, Kandawasvika GQ,
polymorphism. Kurewa NE, Mapingure MP, Munjoma
It is relevant to discuss trichomoniasis in the MW, et al. Risk factors of HIV vertical
context of HIV. In Zimbabwe and South Africa, transmission in a cohort of women
trial participants diagnosed with trichomoniasis under a PMTCT program at three peri-
were more likely to test positive for HIV in their urban clinics in a resource-poor setting. J
next visit. Perinatal transmission of HIV was Perinatol. 2010;30(11):717–23.
likewise more likely if the mother had vaginal Ju e c o N L , A r a n e t a C A , Ta d i n a E G .
infections. Epidemiology of Trichomonas vaginitis
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Prevention and Control
Acta Med Philipp. 1988;24(3):85–6.
Prevention is best achieved by reducing Mavedzenge SN, Pol BV, Cheng H, Montgomery
the risk of exposure. Limiting the number of ET, Blanchard K, de Bruyn G, et al.
sexual partners, and proper use of protective Epidemiological synergy of Trichomonas
devices such as condoms and spermicidal foams vaginalis and HIV in Zimbabwean and
may help prevent infection. To prevent “ping- South African women. Sex Transm Dis.
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be simultaneous treatment of sexual partners. Monzon OT, Santana RT, Paladin FJ, Bautista
Prompt follow-up of patients and their contacts, A, Fajutagana L, Eugenio S. The Prevalence
as well as health and sex education about of sexually transmitted diseases (STDs) and
venereal disease are also important. human immunodeficiency virus (HIV)
infection among Filipino sex workers. Phil
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Chapter 2: Protozoan Infections 59
Coccidians
Winifreda U. de Leon
A study done in San Lazaro Hospital attempted gametes. The microgametes fertilize the
to describe Cryptosporidium among diarrheic macrogametes to produce oocysts, which are
patients and reported a prevalence of 8.5%, passed out with feces when the host cells are
while a study done in the Philippine General sloughed off from the intestinal wall. The
Hospital on diarrheic patients had a much lower oocysts undergo complete sporulation within
prevalence at 1.7%. 7 to 12 days in a warm environment.
It is assumed that the oocyst is the infective
Prevention and Control
stage and when ingested, the sporozoites are
Water-borne transmission is the most released and enter intestinal cells to go through
common source of cr yptosporidiosis. schizogony and gametogony. The different
Chlorination does not affect the parasite. The developmental stages of the parasite may be
synergistic effect of multiple disinfectants and found in the intestinal tissue (Figure 2.9).
combined water treatment processes may reduce
Pathogenesis and Clinical Manifestations
C. hominis oocysts in drinking water. Natural
water and swimming pool water should not be Initial symptoms include malaise and low
swallowed. Contamination of drinking water by grade fever, which may occur 12 to 24 hours
human and animal feces should be prevented. after exposure. Chronic and intermittent watery
diarrhea occurs early in the infection and may
Cyclospora cayetanensis alternate with constipation. The diarrhea
may continue for 6 to 7 weeks with six or
When first associated with diarrhea,
more stools per day. Other symptoms such as
this organism was thought to be a
fatigue, anorexia, weight loss, nausea, vomiting,
me m ber o f cyan ob a c t e r i a b e c a use i t
abdominal pain, flatulence, bloating, and
showed photosynthesizing organelles and
dyspnea may develop. D-xylose malabsorption
autofluorescing particles characteristic of the
has been found to develop in some of the
blue green algae.
patients. Infections are usually self-limiting
Parasite Biology and immunity may result with repeated
infections. No death has been associated with
Cyclospora cayetanensis was originally cyclosporidiosis.
called a cyanobacterium-like body (CLB)
but upon careful study, it was found to be Diagnosis
a coccidian parasite. Similar to the other
Direct microscopic examination of fecal
intestinal coccidians, the life cycle begins with
smears under high magnification (400x)
the ingestion of sporulated oocyst, which
is recommended. Various concentration
contains two sporocysts with two sporozoites
techniques and acid-fast staining (Kinyoun’s
each. The released sporozoites invade the
stain) are also useful. Oocysts are auto-
epithelial cells of the small intestines, although
fluorescent and under fluorescent microscopy,
the site of predilection was found to be the
they appear as blue or green circles depending
jejunum. Multiple fissions of these sporozoites
on the filter (365-450 DM). This technique
take place inside the cells to produce meronts,
is useful for screening. Safranin staining
which contain 8 to 12 merozoites during the
and microwave heating are also helpful. A
first generation, and only four merozoites in
polymerase chain reaction (PCR) technique has
the second generation. Some of the merozoites
been developed to differentiate Cyclospora from
develop into male (micro) and female (macro)
closely related Eimeria species.
Chapter 2: Protozoan Infections 63
Pathogenesis and Clinical Manifestations Other concentration techniques that can also
be used include zinc sulfate and sugar flotation.
Among the immunocompetent, infection is
Oocysts are thin walled, transparent, and ovoid
generally asymptomatic or may present as a self-
in shape. They appear as translucent, oval
limiting gastroenteritis. However, in more severe
structures measuring 20 to 33 μm by 10 to
infections, severe diarrhea and fat malabsorption
19 μm. Alternatively, oocysts can be seen in a
can occur. Symptoms include low-grade fever,
fecal smear stained by a modified Ziehl-Neelsen
anorexia, vomiting, general body malaise,
method, where they stain granular red color
anorexia, weight loss, and flatulence. Stools
against a green background. Phenol-auramine,
usually contain undigested food, mucus, and
as well as iodine staining of the specimen
Charcot-Leyden crystals.
can help visualize the organism. Acid-fast
Infection in immunocompromised
stain, such as Kinyoun’s stain or an auramine-
individuals ranges from a self-limiting enteritis
rhodamine stain, is also useful. A considerable
to severe diarrheal illness resembling that of
amount of stool may have to be examined
cryptosporidiosis, giardiasis or cyclosporiasis.
because oocysts in the samples are often few in
Mucosal bowel biopsy may reveal flattened
number. Charcot-Leyden crystals may be seen
mucosa and damaged villi. Infiltration of the
in the stool specimen. In blood examination,
lamina propria with lymphocytes, plasma cells,
peripheral eosinophilia is common. String
and eosinophils has been reported. However,
capsule (Enterotest®) and duodenal aspirate
the mechanism by which the parasite produces
examinations may be of value. Molecular based
these lesions is still not clear.
techniques may prove useful as an additional
Diagnosis diagnostic tool.
The oocysts of C. belli may be detected Treatment
in the feces by direct microscopy or formalin-
Asymptomatic infections may be
ether/ethyl acetate concentration (Plate 2.13).
managed with bed rest and a bland diet,
while symptomatic infections, such as those
occurring in AIDS patients, can be treated with
trimethoprim-sulfamethoxazole 160/800 mg
four times per day for 10 days, then two times
per day for 3 weeks. Combination therapy with
pyrimethamine and sulfadiazine for 7 weeks has
also been used successfully.
Epidemiology
of those with AIDS were infected; in South Microsporidia, Isospora and Cyclospora. Ann
America, 10%, and in Haiti and Africa, a range Intern Med. 1996;124:429–441.
of 7 to 20% was observed. The disease has also He y w o r t h M F. Pa r a s i t i c d i s e a s e s i n
been reported among those with lymphoma, immunocompromised hosts,
leukemia, and organ transplants. Considered cr yptosporidiosis, isosporiasis and
endemic are the following: Africa, Australia, strongyloidiasis. Gastroenterol Clin North
the Caribbean Islands, Latin America, and Am. 1996;25:691–707.
Southeast Asia. Cystoisosporiasis has been Hoepelman IM. Human cryptosporidiosis. Int
reported in both adults and children, but severe J STD AIDS. 1996;7(suppl)l:28–33.
diarrhea is common among infants. Both sexes Jueco NL, Belizario VY, Jr., de Leon WU,
were found susceptible to infection. Tan-Liu N, Bravo LC, Gregorio GV.
Cryptosporidiosis among selected patients
Prevention and Control
in the Philippine General Hospital. Acta
Cystoisosporiasis can be prevented by Med Philipp. 1991;27:244–247.
following good sanitary practices, thorough Lindsay DS, Dubey JP, Blagburn BL. Biology
washing and cooking food, and drinking safe of Isospora spp. from humans, non human
water. primates and domestic animals. Clin
Microbiol Rev. 1997;10:19–34.
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A c k e r s J P. G u t C o c c i d i a — I s o s p o ra , Gradus MS, Blair KA, Peterson DE, et
Cryptosporidium, Cyclospora and Sarcocystis. al. A massive outbreak in Milwaukee of
Semin Gastrointest Dis. 1997;8(1):33–44. Cryptosporidium infection transmitted
Brennan MK, MacPherson DW, Palmer J, through the Public water supply. N Engl J
Keystone JS. Cyclosporiasis: a new cause of Med. 1994;331:161.
diarrhea. CMAJ. 1996;155(9):1293–1296. Marshall MM, Naumovitz D, Ortega, Sterling
Cross JH, Serchand JB, Sharma P, Escheverria CR. Waterborne protozoan pathogens.
P. Cyclosporiasis at the Kanti Children’s Clin Microbiol Rev. 1997;10:67–85.
hospital in Kathmandu, Nepal: a cursory Millard PS, Gensheimer KF, Addis DG, Sosin
survey. J Trop Med Parasitol. 1997;20:30– DM, Beckett GA, Houck-Jankoski A,
32. et al. An outbreak of cryptosporidiosis
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of the world 1995, a compilation of the 1994;272:1592.
national science foundation a database Orenstein JM. Isosporiasis. In: Connor D.
of known species of coccidian [Internet]. et al, editors. Pathology of Infectious
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1995 [cited 2009 Mar 1]. Available from Ortega YR. Cyclospora species a new protozoan
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Florida: CRR Press, Boca Raton; 1997. cayetanensis- a food and water-borne parasite.
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Goodgame RW. Understanding intestinal Ro s e J B . E n v i r o n m e n t a l e c o l o g y o f
spore forming protozoa: Cryptosporidia, Cryptosporidium and Public Health
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I m p l i c a t i o n s . A n n u R e v Pu b l i c S m i t h H V, R o s e J B . Wa t e r b o r n e
Health.1997;18:135–161. cryptosporidiosis: current status. Parasitol
Serchand JB, Cross JH, Jimba M, Serchand M, Today. 1998; 14:14–22.
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in healthcare facilities, sewage water 1996;23:429–437.
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Chapter 2: Protozoan Infections 69
Toxoplasma gondii
into bradyzoites that are protected by a cyst antibodies against T. gondii. A seroconversion
wall and proliferate at a slower rate. Cysts to a positive titer or a four-fold increase in titers
can be found in the brain, skeletal and heart is indicative of an infection. The Sabin-Feldman
muscles, and retina. Clinical manifestations methylene blue dye test is very sensitive and
become apparent when the immune system specific but it requires the maintenance of
is suppressed as in old age, drug-induced live organisms in the laboratory. High titers
immunosuppression after organ transplantation, (>1,024), although usually indicating an acute
or in the case of AIDS. More often, symptoms infection, may also be seen in chronic cases,
appear when there is relapse of chronic hence the need for IgM antibody detection
infections as a result of a suppressed immune through either the IgM indirect fluorescent
system rather than as a response to an acute antibody technique or through a double
infection. Among the immunocompromised sandwich IgM enzyme immunoassay. Handling
patients, the most common manifestation is of live trophozoites may result in accidental
encephalitis. Myocarditis and focal pneumonia infection of the laboratory personnel. Other tests
have also been reported. It is also possible are the indirect hemagglutination test, indirect
that the immunosuppressed patient acquires fluorescent antibody test, and enzyme-linked
the infection from blood transfusion or immunosorbent assay. Latex agglutination test
organ transplantation. Clinical manifestations is also available. Differentiating pre-existing
include retinochoroiditis, lymphoreticular antibody from passively transferred antibody
hyperplasia with enlargement of the posterior from the mother or antibody related to illness
cervical lymph node, hepatitis, splenomegaly, is important in the assessment of serological
pneumonia, extramedullary hematopoiesis, and test results.
failure to gain weight. Better diagnostic assays are being developed
Stillbirth and abortion may result when because toxoplasmosis has been recognized
mothers acquire the infection during the first as an important disease associated with
trimester of pregnancy. Babies may exhibit AIDS. Polymerase chain reaction (PCR) has
clinical manifestations like chorioretinitis, been successfully used in the diagnosis of
epileptic seizures, jaundice, hydrocephaly, and toxoplasmosis using samples taken from the
microcephaly. Death of the infected newborn patient, which include serum, amniotic fluid,
babies is usually due to anemia with pneumonia. cerebrospinal fluid, and broncheoalveolar
There are cases when clinical manifestations lavage, especially in cases where there is very
may not be apparent during the neonatal little amount of specimen available.
period, but will appear later in childhood. Most
Treatment
babies will harbor the infection and grow up
without any clinical manifestation until such Treatment consists of pyrimethamine
time later in life when their immune system is (25-100 mg daily) and sulfadiazine (1-1.5 g
suppressed and there is reactivation of chronic four times daily) used in combination for one
toxoplasmosis. month. These drugs keep the Toxoplasma under
control but do not kill it. Since pyrimethamine
Diagnosis
can lower blood counts in most people, it
Identification of the parasite can be done should be given together with leucovorin (folic
through examination of tissue imprints stained acid). Sulfadiazine may cause serious allergic
with Giemsa. Tissue sections can be processed reactions like fever and rash, but it can be
and stained with hematoxylin and eosin. substituted with clindamycin. Spiramycin,
Serodiagnostic methods are used to detect azithromycin, clarithromycin, dapsone, and
72 Medical Parasitology in the Philippines
Sarcocystis spp.
Alice Alma C. Bungay, Raezelle Nadine T. Ciro
diagnosis. Currently, 24 wall types have been America, China, India, Tibet, and Southeast
identified in 62 species. S. hominis and S. Asia.
suihominis both have walls of type 10. The wall Of fecal specimens examined from children
of S. hominis is up to 6 µm thick and appears in Poland and Germany, 10.4% and 7.3% were
radially striated from villar protrusions that are found positive, respectively. In Tibet, Sarcocystis
up to 7 µm long. The wall of S. suihominis is was detected in 42.9% of beef specimens
4 to 9 µm thick, with villar protrusions up to examined from the marketplace, and S. hominis
13 µm long. and S. suihominis were found in stool samples
Recently, polymerase chain reaction of 21.8% and 7% of 926 persons, respectively.
(PCR) amplification of the 18S rRNA was Stool examination among Thai laborers showed
demonstrated to be useful in distinguishing S. that Sarcocystis infection had a prevalence of
hominis, S. fusiformis, and S. cruzi sarcocysts about 23%; all cases were asymptomatic which
and oocysts. The technique makes possible probably explained the lack of recognition. A
amplification and identification of species- study of 100 human tongues obtained post
specific gene sequences based on DNA extracted mortem in Malaysia revealed an infection rate
from as few as seven excreted sporocysts (the of 21%. There was no sex difference and the age
equivalent of 3 ½ oocysts) from freshly prepared range was 16 to 57 years (mean 37.7 years). A
material, or as few as 50 sporocysts from fecal seroepidemiological survey in West Malaysia
samples that had been stored in potassium found that 19.7% of 243 persons had antibodies
dichromate (K2Cr2O7) for as long as 6 years. for Sarcocystis.
In the Philippines, studies involving
Treatment
the examination of muscle tissues obtained
Because infection is often asymptomatic, from water buffaloes, cattle, pigs, and goats
treatment is rarely required. There have been revealed the presence of S. cruzi in backyard
no published trials so treatment remains cattle (Bos taurus) possessing a type 7 sarcocyst
empirical. Agents that have been used include wall, S. levinei in water buffaloes (Bubalus
albendazole, metronidazole, and co-trimoxazole bubalis) possessing a type 7 sarcocyst wall
for myositis. Corticosteroids have also been used with similarities to S. cruzi, S. miescheriana in
for symptomatic relief. domestic pigs (Sus scrofa domestica) with a type
10 sarcocyst wall, and S. capracanis in domestic
Epidemiology
goats (Capra hircus) with a type 14 sarcocyst
There are very few large-scale population wall. There is a lack of local studies on human
surveys that have been conducted for Sarcocystis sarcocystosis.
in humans. Prevalence data for Sarcocystis Prevention and Control
infections often come from case reports and
findings of physicians, public health workers, Intestinal sarcocystosis can be prevented
and scientists with specific interests. by thoroughly cooking or freezing meat to kill
Human infection is considered rare with bradyzoites in the sarcocysts. Alternatively,
less than 100 published cases of invasive freezing the meat at –5°C for several days
disease (approximately 46 cases reported by will kill the sporocysts. Where contaminated
1990). These figures may represent a gross drinking water is suspected, boiling should be
underestimate of the human burden of disease. considered to ensure disinfection.
Sarcocystosis has been reported in Africa, The administration of anticoccidial
Europe (Germany, Spain, and Poland), the drugs, amprolium and salinomycin, as
United States (California), Central and South chemoprophylactic agents was effective
Chapter 2: Protozoan Infections 77
the vacuolar form and the precystic form, as flatulence, mild to moderate diarrhea without
this stage allows the parasite to ingest bacteria fecal leukocytes or blood, nausea, vomiting, low
in order to enhance encystment. Studies grade fever, and malaise. Symptoms usually last
of Tan and Suresh have revealed that the about 3 to 10 days, but may sometimes persist
ameboid forms predominated in isolates from for weeks or months.
symptomatic cases. It has been found that in subjects suffering
Granular forms are multinucleated and from immunosuppression, Blastocystis showed
are mainly observed from old cultures. The a significant association with gastrointestinal
diameter of the cell varies from 10 to 60 μm. symptoms. Other studies have also provided
The granular contents develop into daughter evidence of changes in the cellular immune
cells of the ameba-form when the cell ruptures. function of infected individuals.
Multiple fission forms arise from vacuolated
Diagnosis
forms. It is believed that these multiple fission
forms produce many vacuolated forms. Specific diagnosis based on clinical
The size of the resistant cystic form is presentation alone may prove difficult, because
about 3 to 10 μm in diameter, and has one or the spectrum of symptoms is seen in other
two nuclei. It has a very prominent and thick, intestinal infections. Laboratory detection of
osmophilic, electron dense wall. It appears the organism from stool is needed to confirm
as a sharply demarcated polymorphic, but the diagnosis. Multiple stool samples should
mostly oval or circular, dense body surrounded be collected from patients showing clinical
by a loose outer membranous layer. This signs and symptoms. Microscopic examination
membranous layer seen in phase contrast using direct fecal smear is useful, but sensitivity
microscopy corresponds to the fibrillar layer is increased when concentration techniques
described around the cyst at the ultrastructural are used. Hematoxylin or trichrome staining
level, and is the easiest diagnostic feature to offers a very convenient and easy method to
identify. differentiate the various stages of Blastocystis.
It is postulated that the thick-walled cyst Leukocytes are usually seen in fecal smears and
may be responsible for external transmission, stool eosinophilia may also be observed. The
while those cysts with thin walls may be the organism can be cultured using the Boeck and
cause of reinfection within a host’s intestinal Drbohlav’s or the Nelson and Jones media.
tract.
Treatment
Pathogenesis and Clinical Manifestations
Blastocystis is difficult to eradicate. It hides
Infection with B. hominis is called in the intestinal mucus, as well as sticks and
blastocystosis. B. hominis as a cause of holds on to intestinal membranes. The drug of
gastrointestinal pathology is controversial. choice is metronidazole given orally, 750 mg
Several studies have shown that the presence three times daily for 10 days (Pediatric dose:
of the parasite in a majority of patients was not 35-50 mg/kg/day in three doses for 5 days)
associated with symptoms; or, it was found or iodoquinol given at 650 mg three times
with other organisms that were more likely to daily for 20 days. However, there have been
be the cause of the symptoms. However, other reported cases of resistance. Trimethroprim-
studies have concluded that the presence of sulfamethoxazole (TMP-SMX) has also been
Blastocystis in large numbers produces a wide found to be highly effective against Blastocystis.
variety of intestinal disorders, such as abdominal Nitazoxanide has been clinically tested on
cramps, irritable bowel syndrome, bloating, patients with blastocystosis, and was found to
80 Medical Parasitology in the Philippines
resolve symptoms in 86% of patients after 3 Blastocystis similar to those found in humans.
days of administration. Evidence has also shown that Blastocystis is
present in house lizards and cockroaches,
Epidemiology
raising the possibility that food and water
Blastocystis hominis has been reported contaminated by fecal droppings of these “home
virtually worldwide, with infections occurring visitors” may transmit Blastocystis.
most commonly in tropical, subtropical, and In the Philippines, studies of 32
developing countries. Studies from developed morphologically similar isolates from different
countries have reported approximately 1.5 to hosts: 12 from humans, 12 from pigs, and 8
17.9% overall prevalence of B. hominis. All from chickens, using the restriction fragment
ages are affected, but symptomatic cases are length polymorphism (RFLP) analysis of small
more often found in children and in those with subunit rDNA (SSUrDNA), have shown
weakened immune systems. A prevalence of up extensive genomic polymorphism.
to 11.6% was reported from Stanford University
Prevention and Control
Hospital. Prevalence rates of 32.6 % and as high
as 52.3% had been reported from China and Available data on B. hominis indicate that
Malaysia, respectively. the disease can be prevented by consuming safe
Occurrence of the parasite in temperate drinking water. While food has not been fully
countries is generally associated with recent implicated, provisions for sanitary preparation
travel to the tropics and consumption of may be of value in efforts to prevent and
untreated drinking water. This indicates that control this infection. The cysts of B. hominis
infection is possibly through the oral route, can survive up to 19 days in water at normal
and it is more likely to occur in crowded and temperature, and have shown resistance to
unsanitary conditions. Outbreaks of B. hominis chlorine at the standard concentrations.
in day-care centers have been reported in Spain
References
(5.3-10.3%), Brazil (34.7%), and Canada
(13.4%). Avila MS, Garcia MR, Narcelles MV, Serra
In the Philippines, examination of FB, Tejida GM. Prevalence of intestinal
772 stools from consecutive patients at the helminth and protozoan infections among
Department of Parasitology, College of Public food handlers in selected school canteens
Health, University of the Philippines Manila, in Manila [undergraduate special study].
showed a prevalence of 20.7%, sometimes with 2003. Located at: College of Public Health
concomitant infection with other intestinal Library, University of the Philippines
parasites. Studies have also shown prevalence Manila.
rates of 40.6% among food service workers Department of Parasitology. Diagnostic
in a tertiary hospital, and 23.6% among Laboratory Records. 1997. Located at:
food handlers in selected school canteens College of Public Health Library, University
in Manila. Stool surveys conducted by the of the Philippines Manila.
Field Epidemiology Training Program of the Department of Parasitology. Diagnostic
Department of Health in Tapel, Gonzaga, Laboratory Records. 1998. Located at:
Cagayan Valley, and Talavera, Nueva Ecija College of Public Health Library, University
showed prevalence rates of 20% and 44%, of the Philippines Manila.
respectively. Doyle PW, Helgason MM. Epidemiology and
Some animals, like pig-tailed macaques, pathogenicify of Blastocystis hominis. J Clin
chickens, dogs, and ostriches may harbor Microbiol. 1990;28:116–21.
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Diaczok BJ, Rival J. Diarrhea due to Blastocystis Mclure HM, Strobeft EA, Healy GR.
hominis: an old organism revisited. South 1980 Blastocystis hominis in a pigtailed
Med J. 1987;80(7):931–2. macaque: a potential enteric pathogens
Esparar, DG, Belizario VY. Prevalence of for non-humans primates. Lab Anim Sci.
parasitic infection among food-handlers 1980;30(5):890–4.
in a dietary service of a tertiary hospital Rivera W, Tan MA. Molecular characterization
in Manila. 2003. Located at: College of of Blastocystis isolates in the Philippines
Public Health Library, University of the b y r i b o p r i n t i n g . Pa r a s i t o l R e s .
Philippines Manila. 2005;96(4):253–7.
Garcia LS, Brucknel DA, Clancey MN. Clinical Rivera WL. Phylogenetic analysis of Blastocystis
relevance of Blastocystis hominis. Lancet. isolates from animal and human hosts in the
1984;1:1233–4. Philippines. Vet Parasitol. 2008;156:178–
Guirges SY, Al Waili NS. Blastocystis hominis: 82.
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effectiveness of metronidazole therapy. Clin Younis AM. Effect of nitazoxanide in
Exp Pharmacol Physiol. 1986;4:333–335. persistent diarrhea and enteritis associated
Haresh H, Suresh K, Khairul A, Saminathan with Blastocystis hominis. Clin Gastroenterol
S. Isolate resistance of Blastocystis hominis Hepatol. 2005;3(10):987–91.
to metronidazole. Trop Med Int Health. Silberman JD, Sogin ML, Leipe DD, Clark CG.
1999;4:274–7. Human parasite finds taxonomic home.
Jiang JB, He, JG. Taxonomic status Blastocystis Nature.1996;380(6573):398.
hominis. Parasitol Today. 1993;9(10):2–3. Tan KS. New insights on classification,
Kain KC, Noble MA, Freeman HJ, Barteluk identification, and clinical relevance
RL. Epidemiology and clinical features of Blastocystis spp. Clin Microbiol Rev.
associated with Blastocystis hominis infection. 2008;21(4):639–65.
Microbiol Infect Dis. 1987;8(4):235–44. Tan TC, Suresh KG. Predominance of Ameboid
Koutsavlis AT, Valiquette L, Allard R, Soto J. forms of Blastocystis hominis in isolates
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Long HY, Handschack A, Konig W. Blastocystis Blastocystis hominis in simplified soft agar
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cytokine release in colonic epithelial cells. 7.
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Markell EK, Udkow MP. Blastocystis hominis: Yamanari K, Iwatani S, Kimata I. Fecal-
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Matsamuto Y, Yamada M, Yoshida Y. Light 2004; 94(6):391–6.
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82 Medical Parasitology in the Philippines
Dientamoeba fragilis
Vicente Y. Belizario, Jr., Timothy M. Ting
Plasmodium spp.
Vicente Y. Belizario, Jr., Carlos Miguel P. Perez
positive for P. knowlesi. The life cycle of P. in humans consists of schizogony, which leads to
knowlesi is microscopically indistinguishable the formation of merozoites, and gametogony,
from P. malariae, and differentiation is only which leads to the formation of gametocytes.
achieved through polymerase chain reaction The sexual cycle in the mosquito involves
(PCR) assay and molecular characterization. sporogony, which leads to the formation
These protozoans are pigment producers of sporozoites. The life cycles of all human
and are ameboid in shape, with some being species of malaria are similar. The infected
more ameboid than the others. Their asexual female Anopheles mosquito bites and sucks
cycle occurs in humans, the vertebrate and blood from the human host. In the process,
intermediate host, while the sexual cycle occurs salivary fluids containing sporozoites are also
in the Anopheles mosquito, the invertebrate and injected. These sporozoites, the infective stage
definitive host. of the parasite, are immediately carried to the
liver and enter the parenchymal cells. The
Parasite Biology
parasites then commence exo-erythrocytic
Various processes comprise the life cycle schizogony, which produces the merozoites
(Figure 2.14) of the parasite. The asexual cycle in varying duration and amounts, depending
on the species. Merozoites proceed to the gut as an ookinete, which then develops into
peripheral blood to enter the erythrocytes. Some an oocyst. The oocyst grows and produces
merozoites of P. vivax and P. ovale re-invade the sporozoites, which escape from the oocyst and
liver cells forming hypnozoites, while the other enter the salivary glands of the mosquito. These
species do not. These dormant exo-erythrocytic sporozoites may be injected into another human
forms may remain quiet for years. Within host when the mosquito takes a blood meal.
the red blood cell, the merozoite grows as a The entire developmental cycle in the mosquito
ring form developing into a trophozoite. The takes 8 to 35 days, depending to some extent
trophozoite has an extended cytoplasm and on ambient temperature.
a large chromatin mass which further divides Morphologically, the early trophozoite
to form more merozoites within schizonts. form is ring-shaped with a red chromatin dot
The merozoites of P. falciparum develop in the and a scant amount of blue cytoplasm when
parasitophorous vacuolar membrane (PVM) stained with Giemsa or Wright’s stain. The
within the mature red cells and modify the trophozoite form has a large chromatin mass
structural and antigenic properties of these and a prominent ameboid cytoplasm, which
cells. The parasites feed on the hemoglobin is spread through the erythrocyte. The parasite
resulting in the production of pigment known develops into a schizont when the chromatin has
as hematin. Soon after, the erythrocytes rupture divided into two or more masses of chromatin
and the merozoites are released into the blood, with small amounts of cytoplasm, the so-called
ready to enter new erythrocytes. This asexual merozoites. The number of merozoites is species
cycle is synchronous, periodic, and species- dependent. Clumps of pigment accumulate in
determined. the middle of a mature schizont.
Some merozoites develop into The gametocyte stage fills the entire
microgametocytes (male) or macrogametocytes red blood cell and is characterized by a large
(female) which are picked up by feeding female chromatin mass and a blue cytoplasm with
mosquitoes for completion of the life cycle. In pigment. It is round to banana-shaped. The
the gut of the mosquito, the male gametocytes microgametocyte has a lighter blue cytoplasm,
exflagellate and produce eight sperm-like while the cytoplasm of the macrogametocyte
microgametes which may fertilize the female is a darker blue. Species identification depends
macrogamete to form a zygote. The zygote on various characteristics of these stages of
becomes motile and penetrates the mosquito’s development as described in Table 2.5.
Plasmodium species
Parameter P. falciparum P. vivax P. ovale P. malariae
(malignant tertian) (benign tertian) (benign tertian) (quartan)
Infected red blood Normal: multiple Larger than normal, Somewhat larger than Larger than normal,
cells (RBC) infection of RBC pale, often bizzare; normal, often with pale, often bizzare;
very common Schüffner's dots fringed or irregular Schüffner's dots
are often present; edge, and oval in are often present;
multiple infection shape; Schüffner's multiple infection
of RBC not dots appear even of RBC not
uncommon with younger uncommon
stages; stains more
readily and deeply
than in P. vivax
88 Medical Parasitology in the Philippines
Plasmodium species
Parameter P. falciparum P. vivax P. ovale P. malariae
(malignant tertian) (benign tertian) (benign tertian) (quartan)
Small trophozoite Same as P. vivax Signet-ring form with Small, darker in Same as P. vivax
but with small heavy red dot and color, and but with blue
threadlike blue blue cytoplasmic generally more cytoplasmic circle,
cytoplasmic ring solid than those smaller, thicker and
circle with one of P. falciparum; heavier
or two small red Schüffner's dots
chromatin dots; regularly present
double chromatin in almost 100% of
common; infected cells
marginal forms
common
Growing trophozoite Remains in ring Like small trophozoite, Resembles closely Chromatin rounded
form but grows as above, same stage of or elongated;
resembling small with increased P. malariae but cytoplasm
trophozoite of P. cytoplasm is considerably compact or in
vivax in size; usually and ameboid larger; pigment narrow band
the oldest asexual activity; small- is lighter and less across cell:
stage seen in yellowish brown conspicuous dark brown
peripheral blood pigment granules granules may
in cytoplasm, have peripheral
increasing with arrangement
age of parasite
Large trophozoite Seldom present Large mass of Seldom present Chromatin often
chromatin; elongate,
loose, irregular, or indefinite in outline;
close compact cytoplasm dense,
cytoplasm with compact, in
increasing amount rounded oblong
of fine brown or band forms;
pigment; parasite pigment granules
fills cell in 30 to 40 larger, darker than
hours P. vivax parasite fills
cells frequently
Schizont Not present Chromatin divided; About 25% of Same as P. vivax
(presegmenting) cytoplasm shows infected cells are except parasite
varying degrees definitely oval is smaller, shows
of separation shaped: usual less chromatin
into strands and picture is that of a division, more
particles; pigment round parasite in delayed clumping
collects in parts of the center of an of pigment
the parasite oval cell; many
cells with indefinite
fringed outline;
pigment lighter
and less coarse
than in P. malariae
Schizont Rarely present; 8-24 12-24 merozoites; Usually eight 6-12 (average of
(mature) merozoites; smaller pigment in one merozoites 8-10) merozoites
than other species to two clumps; arranged around in rosette form;
parasite almost fills a central block of parasite almost
enlarged cells pigment fills cell
Pathogenesis and Clinical Manifestations species involved, this may range from 11 days
to 4 weeks. The average pre-patent period for
The interval from sporozoite injection to
P. falciparum is 11 to 14 days, for P. vivax, 11
detection of parasites in the blood is referred
to 15 days, for P. ovale, 14 to 26 days, and 3
to as the pre-patent period. Depending on the
to 4 weeks for P. malariae. The incubation
Chapter 2: Protozoan Infections 89
Plasmodium species
Parameter P. falciparum P. vivax P. ovale P. malariae
(malignant tertian) (benign tertian) (benign tertian) (quartan)
Gametocyte Present in peripheral Microgametocyte: Distinguished from P. Same as P. vivax
blood stream, light red to pink malariae by size except smaller; fills
similar to P. vivax; chromatin, of infected cells or almost fills cells
crescent or diffuse, central; and by Schüffner’s
sausage shape gives tint to light dots; less easy to
blue cytoplasm; differentiate from
yellowish P. vivax
brown pigment
throughout
cytoplasm; usually
round and about
the size of normal
RBC
Macrogametocyte:
small, compact,
dark red eccentric
chromatin;
cytoplasm dark
blue, no vacuoles;
abundant dark
brown pigment
scattered
throughout the
cytoplasm
Stages in peripheral Ring forms and All stages present All stages present All stages present
blood gametocytes;
other stages rare
Length of asexual 48 hours or less 48 hours 48 hours 72 hours
cycle
Note: P. knowlesi is microscopically indistinguishable from P. malariae.
period, the time between sporozoite injection with the associated asymptomatic intervals.
and the appearance of clinical symptoms, is Prodromal symptoms may include: a feeling
typically 8 to 40 days, depending again on of weakness and exhaustion, a desire to stretch
the involved species. For P. falciparum, it lasts and yawn, aching bones, limbs, and back, loss
an average of 8 to 15 days, for P. vivax, 12 to of appetite, nausea and vomiting, and a sense of
20 days, for P. ovale, 11 to 16 days, and for P. chilling. At the onset, symptoms may include
malariae, 18 to 40 days. The incubation period malaise, backache, diarrhea, and epigastric
may range from 9 days to 3 years, depending discomfort. The classical malaria paroxysms
on the parasite strain, the dose of sporozoites have three stages: the cold stage, the hot stage,
inoculated, the immune status of the host, and and the sweating stage. The cold stage starts
the host’s malaria chemoprophylaxis history. with a sudden inappropriate feeling of coldness
Partial or incomplete prophylaxis may prolong and apprehension. Mild shivering quickly turns
the incubation period several weeks after to violent teeth chattering and shaking of the
termination of medication. Any person who entire body. Although the core temperature is
has traveled to a malaria-endemic area must be high or may be rising quickly, there is intense
considered at risk of developing malaria up to peripheral vasoconstriction. The patient may
2 years and even longer upon leaving the area. vomit and febrile convulsions may ensue at
There are no absolute clinical features of this stage in young children. These rigors last
malaria except for the regular paroxysms of fever for 15 to 60 minutes after which the shivering
90 Medical Parasitology in the Philippines
ceases, and the hot stage or flush phase begins. distribution. They also depend on the age,
The patient becomes hot and manifests with genetic constitution, state of immunity, general
headache, palpitations, tachypnea, epigastric health and nutritional status of the host, and
discomfort, thirst, nausea, and vomiting. The on any chemoprophylaxis or chemotherapy
temperature may reach a peak of 41°C or even previously used.
more. The patient may become confused or There may be a tendency to recrudesce or
delirious, and the skin may be notably flushed relapse over a period of months to several years.
and hot. This phase lasts from 2 to 6 hours. In Recrudescence is the renewal of parasitemia
the sweating stage, defervescence or diaphoresis or clinical features arising from persistent
ensues with the patient manifesting with undetectable asexual parasitemia in the absence
profuse sweating. The temperature lowers over of an exo-erythrocytic cycle. Relapse is renewed
the next 2 to 4 hours, and symptoms diminish asexual parasitemia following a period in which
accordingly. The total duration of a typical the blood contains no detectable parasites
attack is 8 to 12 hours. The classic periodicity (Figure 2.15). Relapses, which occur with vivax
of attacks develops only if the patient is left and ovale malaria, result from the reactivation
untreated until the time when the life cycle of hypnozoite forms of the parasite in the liver.
phases become synchronized and sufficient Cold, fatigue, trauma, pregnancy, and infections
numbers of red blood cells containing schizonts including intercurrent falciparum malaria may
rupture at about the same time. The interval precipitate reactivation.
between attacks is determined by the length of The pathological processes in malaria
the erythrocytic cycle. For P. falciparum, it is are the result of the erythrocytic cycle. Once
48 hours. For P. vivax and P. ovale, paroxysms the merozoites of P. falciparum invade the
occur on alternate days. For P. malariae, they erythrocytes, the cells reduce their deformability,
occur every 72 hours, causing paroxysms on the degree of which is directly proportional
days 1 and 4, hence the term, quartan malaria. to parasite maturity. This reduction in
Due to the lack of an exoerythrocytic stage in deformability is due to changes in the red
P. knowlesi, fever follows a quotidian pattern, or blood cell cytoskeleton and the increase in
is noted to be non-relapsing. membrane stiffness and cytoplasmic viscosity.
The five species also differ in the age of In the course of invasion, electron-dense sub-
infected erythrocytes. The non-falciparum membranous structures appear and enlarge.
species infect erythrocytes only of a certain These become the so-called “knobs” which are
age: P. vivax and P. ovale infect only young red important in cytoadhesion. They contain several
blood cells, while P. malariae infects only aging proteins such as rosettins, riffins, histidine-
cells. This limits the number of red blood cells rich proteins (HRP), and the Plasmodium
that can be parasitized to less than 3% of all falciparum erythrocyte membrane protein 1
erythrocytes. P. falciparum, as well as P. knowlesi, (PfEMP-1), which is the most adhesive protein
may infect erythrocytes of all ages. As the among the knobs. PfEMP-1 is encoded by a
infected erythrocytes rupture, more falciparum multi-gene family termed var and is clonally
malaria parasites are released to infect more red variant enabling it to evade specific immune
blood cells. The severity of complications and responses. Rosettins and PfEMP-1 are the
mortality increase as the level of parasitemia ligands for rosette formation. They adhere to
increases. The course and severity of the attack parasitized and non-parasitized cells as well
of malaria depend on the species and the strain as blood platelets. In more recent studies, it
of the infecting parasite; therefore, geographical has been suggested that febrile temperatures
origin of infection plays a major role in disease induce the cytoadherence of the ring-staged
Chapter 2: Protozoan Infections 91
Figure 2.15. Diagram of the course of malaria infections showing the primary attack, relapses,
and recrudescence (From World Health Organization. Chemotherapy of malaria and resistance to
antimalarials: report of a WHO scientific group. Technical report series no. 529.
Geneva: World Health Organization; 1973.)
P. falciparum erythrocytes, and that the factor cytokines at the time of schizont rupture.
responsible for this heat-induced cytoadherence The combination of altered red cell surface
is PfEMP-1. HRP, on the other hand, localize to membranes and the host’s immunological
the cytoadherence ligands making the adhesion response to the parasite antigens bring about the
more effective. pathologic changes such as alteration in regional
Infected erythrocytes also undergo blood flow in the vascular endothelium, altered
altered membrane transport mechanisms. biochemistry, anemia, and tissue and organ
The hemoglobin is digested forming the hypoxia. Other destructive tissue processes
pigment hematin, and variant strain-specific include increased capillary permeability which
neoantigens are expressed. The soluble antigens allows fluid to leak into surrounding tissues, and
of P. falciparum are potent inducers of pro- congestion in blood vessels resulting in tissue
inflammatory as well as anti-inflammatory infarction and necrosis.
cytokines from monocytes and macrophages. In severe forms of malaria, impairment
Glycosylphosphatidyl inositol (GPI) moieties of consciousness and other signs of cerebral
that are seen covalently linked to the surface dysfunction, such as delirium and generalized
antigens of these protozoans act like the convulsions, are commonly observed. Other
endotoxin of gram-negative bacteria, manifestations are severe hemolytic anemia
lipopolysaccharide (LPS). They stimulate the with a hematocrit less than 20%, hemoglobin
monocytes to release tumor necrosis factor levels less than 7 g/dL and hyperbilirubinemia
(TNF) or cachexin, which is implicated as with levels more than 50 mmol/L (Table 2.6).
the cause of malarial fever. The fever, febrile Cerebral malaria generally manifests with
paroxysms, headache, various aches and pains, diffuse symmetric encephalopathy. Other signs
and prostration, which are the more familiar and symptoms include retinal hemorrhage,
symptoms of an acute malarial attack, are bruxism (fixed jaw closure and teeth grinding),
probably the result of the release of these and mild neck stiffness. Pouting may occur or
92 Medical Parasitology in the Philippines
Table 2.6. Clinical features and laboratory findings in severe malaria infection
Source: World Health Organization. Management of severe malaria: a practical handbook. Geneva: World Health Organization; 2000.
a pout reflex may be elicited by stroking the affected. Malaria ARF is defined as having a
sides of the mouth. Lumbar tap usually reveals serum creatinine of more than 265 mmol/L
a normal to elevated opening pressure, clear (3 mg/dL) and a 24-hour urine output of
cerebrospinal fluid (CSF) with fewer than 10 less than 1 ml/kg/hr, despite rehydration, in
leukocytes/mL, and slightly elevated protein and patients with asexual forms of the parasite
CSF lactic acid concentration. If left untreated, present in their peripheral blood smear. The
symptoms progress to persistent coma and patient may also present with hyperkalemia
death. The neurological complications, once and hyperuricemia earlier in the course.
promptly and adequately treated, are reversible The cytoadherence, rosette formation, and
and a majority of the patients make a complete sequestration of parasitized erythrocytes lead
recovery. to a decrease in tissue perfusion resulting in
Respiratory findings are also a major decreased renal blood flow. The increase of TNF
feature of severe malaria. Altered pulmonary in tubular epithelial cells leads to inflammatory
function is common, and it includes air flow cell infiltration in the interstitium and altered
obstruction, impaired ventilation and gas tubular transport, which result in tubular
transfer, and increased pulmonary phagocytic damage and dysfunction. The presence of GPI
activity. In African children, pneumonitis from and other falciparum malaria antigens lead to
sequestered, parasitized RBC and inflammatory release of cytokines and mediators that decrease
cells are seen in postmortem pulmonary the systemic vascular resistance and increase
vasculature, while in adults, non-cardiogenic renal vascular resistance. All these changes
pulmonary edema and acute pulmonary distress eventually lead to acute tubular necrosis causing
syndrome (ARDS) may be observed. There is a acute renal failure.
high mortality rate (over 80%) when pulmonary Malaria in pregnancy increases the risk of
edema develops in a patient with severe malaria. maternal death, maternal anemia, intrauterine
Factors which predispose to pulmonary edema growth retardation, spontaneous abortion,
include hyperparasitemia, renal failure, and stillbirth, and low birth weight associated with
pregnancy. risk for neonatal death. Non-immune pregnant
The incidence of acute renal failure (ARF) women are susceptible to all complications
reaches up to 60% of patients with severe associated with severe malaria such as cerebral
falciparum malaria, with more males being malaria, hypoglycemia, and pulmonary edema.
Chapter 2: Protozoan Infections 93
For partially immune pregnant women, Not everyone infected with the malaria
especially primigravid, severe anemia may parasite becomes seriously ill or dies. In areas
develop but the other complications of severe where endemicity is stable, repeated exposures
malaria are unlikely to occur. Falciparum to the parasite lead to specific immunity.
malaria may induce uterine contractions, thus This restricts occurrence of serious problems
may push the patient to premature labor. In in young children, while older patients have
severe malaria, the prognosis of the fetus is poor. relatively mild febrile illness. In people who are
Falciparum malaria in a young child is exposed to malaria for the first time, possible
considered a medical emergency for it can be outcomes may range from apparent resistance to
rapidly fatal. The initial symptoms may be death. Any resistance, therefore, is nonspecific.
atypical and difficult to recognize, but within It also does not necessarily depend on prior
hours, life-threatening complications may start exposure to malaria and may be either acquired
to occur. The most common complications or innate. Poor prognostic factors in falciparum
of severe malaria in children are cerebral malaria include hyperparasitemia defined as
malaria, severe anemia, respiratory distress, and a peripheral count more than 250,000/µL or
hypoglycemia. Children with severe malaria more than 5% of the RBCs infected, and the
most commonly present with seizures. These presence of mature or immature schizonts in
convulsions are common before or after the a peripheral blood smear. It has been shown
onset of coma and are significantly associated that a peripheral count of 10% or more of
with neurologic sequelae. Opisthotonos may red blood cells infected has a mortality rate
also be observed in some children. As much as of 50%, particularly in non-immune cases,
10% of children who survive cerebral malaria despite treatment. The clinical indicators of
will develop sequelae such as hemiparesis, poor prognosis include deep coma, absence
cerebellar ataxia, speech disorders, generalized of corneal light reflex, respiratory distress
spasticity, or some behavioral disturbances (acidosis), circulatory collapse, decerebrate
(Table 2.7). or decorticate rigidity, opisthotonos, and age
Table 2.7. Comparison of sign and symptoms of sever malaria in adults and children
These tests can be performed in 15 to 30 differentiate between current and past infections
minutes without the use of electricity, special and are therefore most helpful in epidemiologic
equipment, or any training in microscopy, and studies. Current studies are using PCR to
most kits have more than 90% specificity. More significantly enhance microscopic diagnosis of
recent studies have shown that test kits based malaria especially in cases of low parasitemia
on HRP II have a sensitivity and specificity of and in cases of mixed infection.
92.5% and 98.3% respectively, while kits based
Treatment
on the pLDH antigen have a lower sensitivity
(88.5%) albeit a higher specificity at 99.4%. Antimalarial drugs have selected actions
The use of RDTs can be easily taught to village on the different phases of the life cycle of the
health workers and the results can likewise be malaria parasite. These drugs may be classified
easily interpreted. The main disadvantages into causal prophylactic drugs, which prevent
of RDTs compared to microscopy are: the the establishment of the parasite in the liver,
lack of sensitivity at low levels of parasitemia; and blood schizonticidal drugs, which attack
the inability to quantify parasite density; the the parasite in the red blood cell, preventing
inability to distinguish among P. vivax, P. ovale, or terminating the clinical attack. Tissue
and P. malariae, as well as sexual and asexual schizonticides act on pre-erythrocytic forrns
stages; the persistently positive tests (for some in the liver. Gametocytocidal drugs destroy
antigens) despite parasite clearance following the sexual forms of the parasite in the blood.
chemotherapy; and the relatively higher cost Some drugs are hypnozoitocidal or antirelapse
per test. drugs, which kill the dormant forms in the liver.
In recent studies conducted in various areas Sporonticidal drugs inhibit the development
of the Philippines to describe the validity of a of the oocysts on the gut wall of the mosquito,
few specific malaria RDT kits, results showed which has fed on a gametocyte carrier so that
sensitivity and specificity levels below the the mosquito cannot transmit the infection.
WHO recommended ideal of 95% and 90%, The main uses of antimalarial drugs are:
respectively. Reasons for these findings could be (a) protective (prophylactic), (b) curative
manufacturer-related problems, the instability (therapeutic), and (c) preventive. Drugs for
of the substances used in the diagnostic prophylaxis are used before the infection occurs
technique to varying environmental conditions or before it becomes evident, with the aim of
such as extremes of temperature and humidity, preventing either the occurrence of the infection
and user-related problems. Quality assurance of or any of its symptoms. A blood schizonticidal
these malaria RDT kits is, therefore, necessary drug may have minimal effects on parasites
before they are deployed on a larger scale in growing in the liver, but if it is still present in
remote and rural areas. More recent studies are the blood when the merozoites leave the liver
now concentrating on quality assurance of these and invade the blood cells for the first time, it
tests and on identifying the factors which may will effectively prevent symptomatic malaria.
affect RDT performance in the field. Curative or therapeutic use refers to action on
Malaria can also be diagnosed serologically the established infection, which involves the use
but presently available methods are not of blood schizonticidal drugs for the treatment
capable of making a definitive diagnosis of of the acute attack and in the case of relapsing
acute malaria. Available serologic tests like malaria, radical treatment of the dormant liver
indirect hemagglutination (IHA), indirect forms. Prevention of transmission means the
fluorescent antibody test (IFAT), and enzyme- deterrence of infection of mosquitoes with
linked immunosorbent assay (ELISA) cannot the use of gametocytocidal drugs to attack the
96 Medical Parasitology in the Philippines
gametocytes in the blood of the human host. It be given in pregnancy and in children less than
also means the interruption of the development 4 years of age.
of the sporogonic phase in the mosquito when In contrast with falciparum malaria, vivax
it feeds on the blood of an infected person who malaria remains sensitive to chloroquine. Clinical
has been given the appropriate sporonticidal studies and extensive in vitro observations have
compound. shown that P. vivax is still generally sensitive to
Chloroquine was the mainstay of chloroquine, although resistance is prevalent
antimalarial treatment for the last 50 years. and increasing in Indonesia, Peru, and Oceania.
Because of emergence of multidrug-resistant Moreover, vivax malaria is sensitive to all other
(MDR) strains, subsequent chloroquine use antimalarial drugs albeit slightly less sensitive to
has been rendered ineffective against falciparum artesunate plus sulfadoxine-pyrimethamine. The
malaria, and the current DOH Malaria asexual stage of P. vivax remains susceptible to
Control Program (MCP) recommends the use primaquine; therefore, combination treatment
of artemisinin-based combination therapies with chloroquine and primaquine affords blood
(ACTs) for severe and uncomplicated falciparum stage and liver stage treatment, respectively.
malaria, replacing the chloroquine plus Often referred to as radical treatment, the use of
sulfadoxine-pyrimethamine combination. The primaquine, together with chloroquine, allows
following drug combinations are recommended: for the prevention of relapse in vivax malaria. In
artemether plus lumefantrine, artesunate plus comparison with no primaquine treatment, the
amodiaquine, artesunate plus mefloquine, risk of relapse decreases for every additional mg/
and artesunate together with sulfadoxine- kg of primaquine given. Repeated vivax malaria
pyrimethamine. For severe malaria, parenteral relapses are debilitating at any age, hence they
antimalarial treatment should be started must be prevented. At least a 14-day course of
without delay after rapid clinical assessment and primaquine is needed for the radical treatment
confirmation of the diagnosis. The following of P. vivax.
antimalarial drugs are recommended: artesunate Resistance of P. malariae and P. ovale
intravenous (IV) injection or intramuscular to antimalarials is not well characterized,
(IM) injection, quinine IV or IM, or artemether and infections with these species are still
IM. In a placebo-controlled trial, patients with considered sensitive to chloroquine. The
severe malaria who could not be treated orally treatment for relapsing fever caused by P.
and where access to IM and IV treatment was ovale is similar to that of vivax malaria (i.e.,
unavailable, a single artesunate suppository at chloroquine and primaquine). In the case of
the time of referral reduced the risk of death or mixed malarial infections, ACTs remain the
permanent disability. mainstay treatment. Moreover, the use of
Current guidelines also recommend artemisinin-based compounds and a partner
the use of gametocytocidal drugs to reduce drug with a long half-life (i.e., artesunate
transmission. Seen in the context of malaria plus amodiaquine and dihydroartemisinin
elimination, the use of primaquine 0.75 plus piperaquine) has been effective against
mg base/ kg body weight single oral dose in chloroquine-resitant vivax malaria. Radical
demonstrates an added benefit to artemisinins treatment with primaquine should also be
in eliminating gametocytes. The addition of a considered in cases of confirmed P. vivax and
single dose of primaquine to current ACTs is P. ovale infections.
therefore recommended provided that the risk Artemisinin and its derivatives (Qinghaosu
for hemolysis in G6PD deficient patients is derivatives), artesunate, and artemether produce
considered. Moreover, primaquine should not rapid clearance of parasitemia and rapid
Chapter 2: Protozoan Infections 97
shows an initial reduction in parasitemia after without previously meeting any of the criteria
treatment but there is failure to clear the blood of ETF; and (b) presence of parasitemia and
of asexual parasites and soon after an increase an axillary temperature of 37.5°C (or history
of parasitemia follows. RIII is the severest form of fever) on any day from Day 4 to Day 28,
of resistance in which parasitemia will either without previously meeting any of the criteria
show no significant change with treatment or for ETF. Late parasitological failure for intense
will eventually increase. transmission areas is defined as presence of
MDR malaria is considered when treatment parasitemia on Day 14 and axillary temperature
failure occurs with three or rnore antimalarial of 37.5°C without previously meeting any of the
agents. In this case, a combination of artesunate criteria for ETF or late clinical failure.
has been combined with mefloquine and is now For low to moderate transmission areas,
the first-line regimen for MDR malaria in some late parasitological failure is defined as presence
Southeast Asian countries. of parasitemia on any day from Day 7 to Day
Classification of response to malaria 28 and axillary temperature of 37.5°C without
treatment can be divided into early treatment previously meeting any of the criteria for ETF
failure, late treatment failure, and adequate or late clinical feature. Adequate clinical and
clinical and parasitological response. Early parasitologic response for intense transmission
treatment failure (ETF) is present when there areas is defined as absence of parasitemia on Day
is: (a) development of danger signs or severe 14 (Day 28 for low to moderate transmission
malaria on Day 1, 2, or 3 in the presence of areas) irrespective of axillary temperature
parasitemia; (b) parasitemia on Day 2 higher without previously meeting any of the criteria of
than the Day 0 count irrespective of axillary ETF, late clinical failure, or late parasitological
temperature; (c) parasitemia on Day 3 with failure.
axillary ternperature of 37.5°C; and (d) In cases of renal failure in severe malaria,
parasitemia on Day 3 which is 25% of count dopamine may be given at 3 to 5 μg/kg/
on Day 0. This classification of ETF holds for minute. If the patient remains unresponsive
both intense transmission and low to moderate despite adequate rehydration and other forms
transmission areas. Late treatment failure (LTF) of therapeutic management, and blood urea
is further divided into late clinical failure and and creatinine are rising progressively, dialysis
late parasitological failure. The definitions for is indicated.
these two would differ depending on whether For control of seizures, diazepam may be
the area is an intense transmission area or a given at 10 mg intravenous (pediatric dose at
low to moderate one. Late clinical failure for 0.3 mg/kg IV up to 10 mg) or in cases of status
intense transmission areas is defined as: (a) epilepticus, phenytoin at a loading dose of 13
development of danger signs or severe malaria to 18 mg/kg and a maintenance dose of 3 to 5
after Day 3 in the presence of parasitemia, mg/kg per day (pediatric dose: loading dose of
without previously meeting any of the criteria 15-20 mg/kg slow IV push and maintenance
of ETF; and (b) presence of parasitemia and dose of 5 mg/kg in two divided doses). The
axillary temperature equal to or greater than following are now not considered useful and are
37.5°C on any day from Day 4 to Day 14, therefore not recommended in the management
without previously meeting any of the criteria of cerebral malaria: corticosteroids, other anti-
for ETF. For low to moderate transmission inflammatory agents, low molecular weight
areas, late clinical failure is defined as: (a) dextran, epinephrine, and heparin.
development of danger signs or severe malaria Proper management of malaria also
after Day 3 in the presence of parasitemia, includes general and supportive measures
Chapter 2: Protozoan Infections 99
especially in P. falciparum infections. If fluid malaria have shrunk considerably over the past
replacement or blood transfusion is necessary, 50 years, but control is becoming more difficult,
it must be administered with care to avoid and past gains have been threatened. The spread
pulmonary edema. Antipyretics and sponging of the disease is linked to activities like road
for high fever are important especially in building, mining, logging, and new agricultural
children to prevent convulsions. Blood sugar and irrigation projects, particularly in “frontier”
should be monitored regularly especially in areas (e.g., forest fringe, mountain valleys and
severe malaria. If hypoglycemia develops, 50 reclaimed areas). Elsewhere, disintegration
mL of 50% dextrose (1.0 mL/kg for children) of health services, armed conflict, and mass
diluted in an equal volume of infusion fluid movements of refugees have worsened the
should be infused over a 5-minute period, malaria situation.
followed by a continuous intravenous infusion Malaria remains a public health problem
of 5 to 10% dextrose. today in more than 90 countries inhabited by
a total of some 3.3 billion people (Figures 2.17
Epidemiology
to 2.19). Of these, 2.1 billion are at low risk
Malaria is the world’s most important (<1 case per 1,000 population), 94% of whom
tropical parasitic disease. The disease kills live in areas outside the WHO African region.
more people than any other communicable The 1.2 billion at high risk (>1 case per 1,000
disease except tuberculosis. In many developing population) live in the WHO African (47%)
countries, especially in Africa, malaria has an and Southeast Asian Regions (37%).
enormous toll on lives, medical costs, and days In 2010, the WHO reported an estimated
of labor lost. The geographical areas affected by 216 million cases of malaria, of which 81% or
Figure 2.17. Global distribution of malaria: malaria-free and malaria-endemic countries in phases of
control, elimination and prevention of reintroduction (From World Health Organization. World Malaria
Report 2009. Geneva: World Health Organization; 2009.)
100 Medical Parasitology in the Philippines
Figure 2.18. Distribution of malaria in the WHO Southeast Asia Region: areas in red indicate malaria-
endemic countries (Accessed from http://www.map.ox.ac.uk)
Figure 2.20. Malaria cases per 100,000 population in the Philippines from 2000 to 2009
(From Department of Health-National Center of Disease Prevention and Control. Malaria medium term
development plan 2011-2016. Manila (Philippines): Department of Health; 2011.)
morbidity since 2006. Cases have been notably reported in 2009 (Figure 2.21). Similarly, the
decreasing as reported in 2009 (Figure 2.20). malaria morbidity rate has decreased by 58.3%,
However, disease prevalence, seen in the 2010 with 18,781 malaria cases reported in 2009.
DOH-Malaria Control Program (MCP) Among blood smears examined from 2005 to
report, remains markedly high in Regions 2009, 69.4 to 80% of patients were diagnosed
IV-B, Caraga, III, XII, and II. There remains with P. falciparum, 17.0 to 23.4% with P. vivax,
an estimated 10.8 million people still at risk approximately 1% with P. malariae, and a small
for the disease, consisting mostly of farmers, number of cases (0.5%) were diagnosed to have
indigenous cultural groups, miners, forest mixed malaria infection, falciparum and vivax
product gatherers, and soldiers. Fifty nine out of malaria being the usual mixed infection.
the 80 provinces in country are endemic for the Macrostratification of malaria endemic
disease, with 60.4% of the endemic provinces areas serves to classify the different provinces
located in Luzon, 39.5% in Mindanao, and based on annual incidence of the disease
0.1% in Visayas. As of 2009, the provinces of in each respective province (Table 2.8).
Cagayan, Isabela, Palawan, Sulu, and Tawi-Tawi Macrostratification provides an opportunity
comprise the five provinces having the highest for planning, policy making, and resource
number of malaria cases reported. allocation of the provincial MCP. The number
It appears that in areas of low malaria of provinces in Category A has been reduced
endemicity, there is a clustering of cases, from 26 in 2000, to nine in 2005 and finally to
resulting in pockets of high endemicity. five in 2008. The values reported for Category
Mortality rate for malaria has markedly B provinces have changed from 22 in 2000 to
decreased by 88.2% from 2005 figures to values 31 in 2005, and to 27 in 2008. Malaria-free
102 Medical Parasitology in the Philippines
Figure 2.21. Malaria-related deaths per 100,000 population in the Philippines from 2005 to 2009
(From Department of Health-National Center of Disease Prevention and Control. Malaria medium term
development plan 2011-2016. Manila (Philippines): Department of Health; 2011.)
by contaminated needles and syringes. Blood breeding sites, and estimation of mosquito
from semi-immune donors without clinical density.
symptoms may contain malaria parasites. In
Prevention and Control
congenital malaria, infected mothers transmit
parasites to their child before or during birth. Early diagnosis and prompt treatment
The evaluation of the amount and of malaria are essential for malaria control.
conditions of transmission of malaria in a Breeding sites of Anopheles flavirostris should
given locality is called the malaria survey. be detected early and contained. Personal
Disease control efforts must always take into protection measures against mosquito bites
consideration the findings of the malaria are also helpful and cost-effective. The use
survey. The survey involves looking into of insecticide- (permethrin or deltamethrin)
epidemiologic data regarding the disease, such as treated nets (ITNs) and long lasting insecticide-
malaria mortality and morbidity, investigations treated nets (LLIN) remains the major vector
relating to the human host, and investigations control strategy coupled with indoor residual
relating to the insect vector. Investigations spraying (IRS), with the latter used in epidemic
relating to the human host include blood and situations, areas with stable transmission but
spleen examinations. Investigations relating without reduction of malaria incidence, and
to the vector, on the other hand, may include areas of displaced populations. Wearing of
identification of mosquito vectors and their light colored clothing, which cover most of the
104 Medical Parasitology in the Philippines
body (since dark colors attract mosquitoes), and rice fields and bacterial insecticide (PG-14
using insect repellants containing DEET Bacillus thuringiensis), and chemical control
(N,N-diethyl-m-toluamide, optimally as a 35% such as the use of mosquito repellants and
concentration lotion) on exposed parts of the insecticide treated mosquito nets.
body, using a insect spray containing pyrethrum In the field of molecular entomology,
in living areas, and use of permethrin insecticide stable germline transformation of the Anopheles
as a repellant spray for clothing have known to mosquito is being investigated. This research
be effective personal protection measures as well. involves inserting genes (e.g., immune response
Chemoprophylaxis may be protective to genes) that will inhibit the development of
travelers who have no immunity to malaria, the parasite in the mosquito. With the recent
although no chemoprophylactic regimen sequencing of the genomes of Plasmodium
ensures 100% protection. Because of this, falciparum and of the Anopheles mosquito,
precautions to avoid mosquito bites are new areas of research for malaria treatment and
needed even if antimalarials have been taken. prevention are now being explored.
Prophylactic drugs should be taken with good
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Chapter 2: Protozoan Infections 107
Babesia spp.
Florencia G. Claveria
fission, and eventually forms sporokinetes. Once the organs of the larva, nymphs, and adult
the sporokinetes are released, they continue to ticks. With the stage-to-stage (transstadial)
infect and multiply in various organs, including transmission, each of the developmental stages
the ovaries of the replete tick, until death ensues. is generally capable of parasite transmission to
The transovarian route represents one pattern mammals. The complicated phase of Babesia
of parasite transmission in the vector, which life cycle in the tick vector ends with the
terminates with the death of the vector. formation of the infective sporozoites in various
With the passage of sporokinetes to eggs organs or in the salivary glands, for subsequent
(transovarian), similar cycles of multiple fissions transmission to the mammalian hosts during
continue to take place in the embryo and in blood feeding (Figure 2.23).
Pathogenesis and Clinical Manifestations bigemina (4-5 µm by 2-3 µm) and B. caballi (3
µm by 2 µm) are less virulent. Several factors can
Smaller forms like Babesia bovis (2.4 µm
influence the susceptibility of hosts to infection,
by 1.5 µm) and B. equi (2 µm by 1 µm) are
like the age and breed of farm animals, and the
more pathogenic, while larger forms such as B.
health and immune state of humans.
Chapter 2: Protozoan Infections 109
blood or NOD/sch-scid mice with the patient’s The drug combination azithromycin and
blood can be useful in parasite detection and atovaquone is as effective as clindamycin-
identification. quinine, with less adverse effects. Both drug
The polymerase chain reaction (PCR) is combinations are ineffective in suppressing
highly specific and is generally considered to disease progression in immunosuppressed
be the gold standard for Babesia detection. It is, patients. Very recently, there have been reports
however, unrealistic for epidemiologic surveys of immunocompromised patients who,
because it is time consuming and expensive. during 28 days of uninterrupted treatment
The current practice is the use of PCR in the with azithromycin-atovaquone, manifested
isolation of the SSU rDNA from asymptomatic recurrence of marked parasitemia, suggesting
patients, followed by gene sequencing and its the development of drug-resistant B. microti.
comparison with known SSU rDNA gene Ar temisinin, pyrimethamine, and
sequences from pathogenic strains. pamaquine can strongly inhibit the growth of
The continued work on the isolation of B. equi and B. caballi in vitro. Pyrimethamine
specific and highly immunogenic antigens can indirectly interrupt the parasite life cycle
of Babesia species and isolates, and their through its inhibitory effect on dihydrofolate
intended utilization in the development reductase, essential in folate metabolism, while
of immunochromatographic test (ICT) is pamaquine can interfere in the recycling of
practicable for epidemiologic surveys in the endosomal proteins into the plasma membrane
field. ICT is simple, quick, reliable, sensitive, by direct interaction with the endosomes.
and inexpensive, and has gained acceptability in
Epidemiology
the diagnosis of both acute and latent infections.
Currently, there are ICT strips or dipsticks Babesiosis is essentially a zoonotic infection,
employed in the detection of infected livestock. regarded of major economic importance
to livestock, particularly in the cattle and
Treatment
horse industry. Its documentation in humans
The standard treatment of human babesiosis worldwide has increased its recognition as
utilizes a drug combination of clindamycin and a disease of public health concern. The first
quinine, or azithromycin and atovaquone. The human case attributed to the cattle form was
clindamycin and oral quinine combination reported in 1956, in Europe, and followed
was first used in 1982 in a newborn infant with reports of more cases in Europe and in
suffering from babesiosis, and since then, this North America, including the discovery of
combination has become the drug of choice. the transmission of a B. microti-like species to
Clindamycin is given 1.2 g intravenously twice humans in 1970. A review of the 136 human
a day or 600 mg orally three times a day, and cases examined in New York (1982-1991)
combined with oral quinine at a dose of 650 revealed almost all cases were among those
mg three times a day. Clindamycin-atovaquone living in Suffolk, Long Island. Of the 103
combination is efficacious in clearing the (76%) who were hospitalized, seven patients
parasites in normal individuals and prevents previously underwent splenectomy, 31 patients
recurrence of infection, but produces adverse had symptoms of babesiosis and Lyme disease,
effects like vertigo, tinnitus, and gastrointestinal and seven died. The Asian cases reported have
symptoms. Supportive and symptomatic been few and sporadic with the first records in
management is important. In severe cases where 1984, in Yunnan, China, and a recent report
there is progressive exacerbation of hemolytic in Japan attributed to B. microti (Table 2.10).
anemia, total blood exchange may be indicated.
Chapter 2: Protozoan Infections 111
Table 2.10. Summary of human cases of babesiosis reported in some Asian countries
The Centers for Disease Control and habitation with livestock and wild animals,
Prevention, USA has confirmed more than and where ticks were abundant. The parasites
40 human cases that contracted the disease detected were pyriform-shaped, suggestive of
from transfusion of packed RBC and tested Babesia. One case recorded in the rural area
positive for anti-B. microti antibodies. In Asia, in Southwestern Taiwan was serologically and
the two cases have been associated with renal morphologically diagnosed with a chronic and
transplantation and blood transfusion. Thus, subclinical infection of a geographic isolate
subclinical or asymptomatic cases cannot simply of Babesia named Taiwan isolate (TW1). The
be ignored, considering their potential role in detection of anti-Babesia antibodies in 83%
the spread of human babesiosis. Rattus coxinga endemic in the locality where the
Phylogenetic analyses of the gene sequences Taiwanese patient lived, suggested the rodents
of the SSU rDNA of Babesia spp. obtained as the highly likely source of infection. The SSU
from human cases helped clarify three patterns rDNA isolated from the Japanese patient and
or groupings, worldwide, namely: (a) human from the NOD/sch-scid mice inoculated with
babesiosis attributed to the B. divergens-related the patient’s blood revealed 99.2% sequence
parasites in Europe; (b) human babesiosis caused homology with the US B. microti SSU rDNA
by B. microti principally in the Northeastern (Genbank/EMBL/DDBJ: U09833).
USA; and (c) human babesiosis caused by newly In Japan the wild rodents, Apodemus
emerging species, the WA1-type in the Western speciosus and A. argenteus, are infected with B.
USA, tentatively grouped with B. microti or microti-like forms. In Taiwan, the bandicoot
alternatively with Theileria spp. Recently in rats, Bandicola indica, and the spiny rat, R.
Italy and Austria, parasites obtained from coxinga, carry morphologically similar B.
splenic cases revealed SSU rDNA sequences microti-like forms. The TW1 isolated from
more closely related to B. odocoileus, a species the first human case in Taiwan is serologically
that bears morphological, molecular, and related to the US B. microti SSU rDNA.
immunological similarities with B. divergens. In the Philippines, studies on animal
The B. divergens-related species now has been babesiosis have been limited and mainly
expanded to include B. odocoileus and possibly concentrated on hematological parameters and
B. bovis. In Asia, the etiologic agent of human clinical manifestations in cattle B. bigemina and
babesiosis has been identified as B. microti or B. argentina (syn. B. bovis), and B. canis. Using
B. microti-like isolate or strain. the ICT, 13 (28%) stray dogs in an impounding
Human cases recorded in China were facility in Dasmarinas, Cavite tested positive for
generally among farmers living in close anti-p50 truncated B. gibsoni antigen. The dogs
112 Medical Parasitology in the Philippines
had infestation mainly with Rhipicephalus ticks, In Europe and the USA, the Ixodes ricinus
suggestive of their putative role in the spread of and Ixodes triangulicep, and the Ixodes scapularis
canine babesiosis in the country. and Ixodes pacificus are the principal vectors,
Slaughtered and race horses in the respectively. In Asia, the tick vectors are poorly
Philippines tested seropositive for B. caballi established. The predominance of Ixodes
and/or B. equi infection, using ICT containing a granulatus in Southeast Asian countries makes
recombinant B. caballi 48-kDa rhoptry protein it a favorable vector, though this warrants
(rBc48) and a recombinant truncated B. equi confirmation (Plate 2.17). In Japan, Ixodes
merozoite antigen 2 (rEMA-2t). Serological ovatus has been suggested as a highly likely
data correlated well with the detection of the tick vector of human babesiosis for its human
morphologies of the specific etiologic agent(s) biting activity.
in blood smears.
Plate 2.17. Ixodes sp. A. Non-engorged female. B. Engorged female. C. Mouthparts showing
the hypostome (H), pedipalp (P), and scutum (S). (Courtesy of Ms. Mary Jane Cruz-Flores
and Dr. Florencia Claveria)
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Chapter 2: Protozoan Infections 115
into the body through broken skin, or through result in cardiomegaly, congestive heart failure,
mucous membranes that are rubbed with fingers thromboembolism, and even arrhythmias. Less
contaminated with the bug’s feces. severe signs and symptoms associated with
the chronic phase of the disease include chest
Pathogenesis and Clinical Manifestations
pain, palpitations, dizziness, syncopal episodes,
Chagas disease can be divided into an abnormal electrocardiogram findings, achalasia
acute and a chronic phase. The acute phase is associated with megaesophagus, and chronic
characterized by a focal or diffuse inflammation constipation associated with megacolon. About
mainly affecting the myocardium. Non- one-third of patients in the latent stage develop
specific signs and symptoms, such as fever, some manifestation of chronic Chagas disease
malaise, nausea, vomiting, and generalized after several years or decades. The majority of
lymphadenopathy often accompany the acute symptomatic, chronic patients manifest with
phase. Cutaneous manifestations of the disease the cardiac form, while the rest develop the
can sometimes appear during this phase, gastrointestinal form.
usually associated with a localized inflammatory
Diagnosis
reaction at or near the site of inoculation.
Chagomas are furuncle-like lesions associated A complete patient history is the primary
with induration, central edema, and regional tool for diagnosing Chagas disease. Possible
lymphadenopathy. These lesions represent exposure to T. cruzi should be established, and
the site of entry of the parasite. If the parasite risk factors such as place of residence or work,
penetrates through the conjunctiva, eyelid recent blood transfusion in an endemic area,
swelling called Romaña’s sign may form. This and contact or exposure to T. cruzi intermediate
lesion is characterized by unilateral painless host should be evaluated.
bipalpebral edema and conjunctivitis, and may The definitive diagnosis of Chagas
involve the lacrimal gland and surrounding disease during its acute phase relies on direct
lymph nodes. After 1 or 2 months, symptoms visualization of the parasites in thick and thin
resolve, and the patient goes into a latent or blood smears using Giemsa stain. Cerebrospinal
indeterminate, but usually asymptomatic phase. fluid (CSF), tissue samples, or lymph can also be
During this phase, patients infected with T. used for parasite visualization. However, only in
cruzi are still capable of transmitting it to others the first two months of acute disease can T. cruzi
through insect vectors, blood transfusion, or trypomastigotes be seen by direct examination.
organ transplantation. Other diagnostic techniques include
The pathophysiology of the chronic concentration methods (microhematocrit),
phase of the disease was initially thought to blood culture, and polymerase chain reaction
be autoimmune in nature; however, this is (PCR). Xenodiagnosis, wherein laboratory-
controversial. Newer evidence shows that reared triatomine bugs are allowed to feed on
chronic Chagas disease is multifactorial, suspected patients and are later examined for the
and dependent on the interaction between presence of T. cruzi metacyclic trypomastigotes,
parasite and host. Nonetheless, the chronic may also be utilized as a diagnostic modality.
phase is manifested by fibrotic reactions that During the chronic phase, a variety of
cause injury to the myocardium, cardiac serologic tests may be used, such as enzyme-
conduction network, and enteric nervous linked immunosorbent assay (ELISA), indirect
system (decrease in nerve ganglia leading to hemaglutination, indirect immunofluorescence,
megasyndromes). The heart is the primary and PCR. The WHO recommends using at
organ affected during this phase, which may least two techniques with concurrent positive
Chapter 2: Protozoan Infections 119
Chagas disease is estimated to have infected There have been major breakthroughs
more than 10 million people worldwide. Most in the control and prevention of American
cases are reported in the Latin Americas, where trypanosomiasis, particularly by Brazil, Chile,
more than 25 million people are at risk for the and Uruguay. Vector control and blood
disease. Serologic techniques have identified that transfusion regulations have delivered positive
up to 13% of populations in certain endemic outcomes, in terms of disease prevention in
regions are positive for T. cruzi antibodies. An these countries. Spraying of insecticides, use
estimated 10,000 to 12,000 people die of the of insecticide-treated bed nets, and house
disease annually. improvements to prevent vector infestation
120 Medical Parasitology in the Philippines
have been proven cost-effective. International highly fatal disease caused by two subspecies of
organizations such as the WHO and the Trypanosoma brucei: T. brucei gambiense and T.
manufacturers of the antiparasitic drugs are brucei rhodesiense. A third subspecies, T. brucei
working in tandem to ensure the availability of brucei, primarily affects wild and domestic
drugs for the treatment of the disease. animals; collectively, the three subspecies
In Mexico and non-endemic countries represent the Trypanosoma brucei complex. The
near endemic countries, the coverage, quality earliest reports of sleeping sickness in Africa
and safety of blood transfusion screening date back to 1734, while the formal correlations
is being evaluated as avenues for disease between the symptoms, the parasite in blood
prevention. Vaccine development has not and CSF, and the relationship between the
yet been successful, but the advent of newer parasite and its insect vector were established
technologies and characterization of the T. cruzi during the early 1900s.
genome may aid in future vaccine research.
Parasite Biology
Trypanosoma brucei gambiense Members of the T. brucei complex belong to
Trypanosoma brucei rhodesiense the trypanosome family Salivaria. The parasite
is usually transmitted via the bite of the blood-
Human African trypanosomiasis (HAT), sucking tsetse fly (Glossina spp.) feeding from an
also known as African sleeping sickness, is a infected mammalian host (Figure 2.25). Since
the disease relies heavily on the tsetse fly for its through mechanical methods (accidental needle
transmission, HAT cases are localized in regions pricks, other blood sucking insects), as well as
of sub-Saharan Africa, primarily in remote rural vertically, via mother-to-child infection through
areas where tsetse fly habitats are located. the placenta.
T. brucei gambiense is localized mostly in
Pathogenesis and Clinical Manifestations
the western and central regions of sub-Saharan
Africa. It primarily affects humans, but utilizes Human African trypanosomiasis has two
dogs, pigs, and sheep as reservoir hosts. It is types, acute and chronic, depending on the
responsible for the chronic type of sleeping subspecies causing the disease. Trypanosoma
sickness, and accounts for 95% of all HAT cases. brucei gambiense sleeping sickness manifests
T. brucei rhodesiense is found in east Africa months or years after initial infection, while
and is primarily a zoonosis of cattle and wild symptoms of T. brucei rhodesiense sleeping
animals, with humans being accidental hosts. sickness may appear just weeks after infection.
It causes the more acute and rapidly fatal form The initial lesion of African trypanosomiasis
of sleeping sickness, and accounts for the begins as a local, painful, pruritic, erythematous
remaining 5% of HAT cases. chancre located at the bite site, progressing
Only the epimastigote and trypomastigote into a central eschar, and resolving after 2 to
forms are exhibited by the T. brucei complex. 3 weeks. This trypanosomal chancre is more
The trypomastigotes are polymorphic: there common in Gambian sleeping sickness. Several
are typical slender forms, and short, stumpy days after the development of the chancre,
forms. They are flattened and fusiform in usually within 3 to 10 days, the next stages of
shape, 14 to 33 µm in length and 1.5 to 3.5 the disease manifest.
µm in width. The body tapers anteriorly and is Both types of HAT undergo two stages:
blunt posteriorly. The centrally located nucleus early and late. During the early phase of HAT,
contains a large central karyosome. There is an called the hemolymphatic stage, the parasites
undulating membrane, and a single flagellum proliferate in the bloodstream and lymphatics.
that runs along the edge of the undulating The patient may manifest with irregular bouts
membrane and becomes free anteriorly. of fever, headache, joint and muscle pain, and
Once ingested by the intermediate malaise. Anemia, myocardial inflammation,
host, Trypanosoma brucei trypomastigotes disseminated intravascular coagulation, and
undergo several developmental changes from renal insufficiency may occur. Frequently,
trypomastigote into procyclic forms in the in Gambian trypanosomiasis, the posterior
insect’s midgut. After multiplying for 15 to 20 cervical lymph nodes are enlarged, non-tender,
days, the epimastigotes migrate to the foregut and rubbery in consistency (Winterbottom’s
into the insect’s salivary glands, where they sign). Other lymph nodes, such as axillary
mature into metacylic trypomastigotes. When and supraclavicular lymph nodes, may also be
the infected fly bites another mammalian host, involved in both types of sleeping sickness. The
these infective trypomastigotes are injected into signs and symptoms manifested within this
the new host where they multiply and mature phase are due to tissue damage, either from
in blood and connective tissue. In humans, parasitic toxins or immune complex reactions
T. brucei lives in the blood, in the reticular that target organs and RBCs. The early systemic
tissue of lymph and spleen, and the CSF. The phase lasts from 1 to 6 months.
long, slender trypomastigotes multiply by The late phase of the disease, known as
longitudinal binary fission. the meningoencephalitic stage, marks the
Though mostly transmitted through its involvement of the central nervous system.
insect vector, the disease can also be transmitted The brain and meninges become involved
122 Medical Parasitology in the Philippines
as the parasites find their way into the CNS due the relative higher levels of parasitemia.
through the bloodstream. This usually occurs Serial examinations may be necessary due
3 to 10 months after initial infection in to varying levels of parasitemia. Other
Gambian infections, but can manifest after diagnostic techniques include enzyme-linked
just a few weeks in Rhodesian trypanosomiasis. immunosorbent assay, immunofluorescence,
Neurologic symptoms become evident, such indirect hemagglutination test, mini-anion
as apathy, behavioral changes, headache, and exchange centrifugation technique, and PCR.
sleep pattern changes. These may be followed CSF examination is mandatory in patients
by more severe symptoms, such as convulsions, with suspected HAT to detect CNS involvement.
tremors, speech defects, disturbances in speech Abnormal CSF findings include increase in cell
and reflexes, and even paralysis. Kerandel’s sign count, opening pressure, protein concentration,
may manifest as a deep, delayed hyperesthesia and IgM levels. The latter is considered
(delayed bilateral pain out of proportion to pathognomonic for the meningoencaphalitic
the extent of tissue injury). In the later stages, stage of the disease.
somnolence manifests, followed by a deep coma. Card agglutination test for trypanosomiasis
Death eventually follows either from the disease (CATT) detecting circulating antigens in
itself, or from intercurrent infection due to persons infected with T. brucei complex is
immunosuppression. available commercially and can be used in the
Areas of the CNS usually involved in the field setting to screen at-risk populations. This
meningoencaphalitic phase include the frontal technique provides a rapid and highly specific
lobes, pons, medulla, and perivascular areas. method of screening for HAT cases; however,
Parasites may also be seen in the CSF. Autopsy the method has low sensitivity for certain strains
of HAT patients reveals edema and numerous, of T. brucei gambiense in certain areas of West
small, and confluent hemorrhages. Africa.
Trypanosomes are able to evade the immune
Treatment
response of the host through a process called
antigenic variation. This refers to the ability Treatment of African sleeping sickness
of the trypomastigote to continuously change depends on the stage of the disease. For the first
its surface coat, composed of variant surface stage, intravenous suramin sodium for both T.
glycoproteins, so that the host’s antibodies brucei gambiense and T. brucei rhodesiense, and
cannot recognize the parasite in subsequent intramuscular pentamidine for the Gambian
recurrent waves of parasitemia. form can be used. These drugs have side effects,
which include fever, rash, renal insufficiency,
Diagnosis
muscle pain, and paresthesia for suramin; and
Diagnosis of human African trypanosomiasis tachycardia, hypotension, and hypoglycemia
depends upon the demonstration of highly for pentamidine. These drugs do not cross the
motile trypomastigotes in expressed fluid from blood-brain barrier, and so, they cannot be used
a chancre, lymph node aspirate, and CSF. for the CNS stage of the disease.
Thick and thin blood films can be stained Once CNS involvement occurs, intravenous
with Giemsa. Buffy coat concentration method melarsoprol is the drug of choice for both types
is recommended to detect parasites when of sleeping sickness. This arsenic-containing
they occur in low numbers. Examination for drug can cause fatal arsenic encephalopathy
trypomastigotes is usually done during the (usually prevented by co-administration of
hemolymphatic stage of the disease, and is more corticosteroids), and resistance to the drug
useful for the diagnosis of T. brucei rhodesiense has also been observed. A febrile episode
Chapter 2: Protozoan Infections 123
arises from the kinetoplast and extends to the incubation period ranges from two weeks to
anterior tip. several months. An erythematous papule or
Promastigotes have a single free flagellum nodule, called an “oriental button,” is produced
arising from the kinetoplast at the anterior end. at the inoculation site. The lesion has raised
They measure 15 to 20 µm in length and 1.5 to edges and a central crater. During the course
3.5 µm in width. The infective promastigotes in of several weeks, the papule forms a violaceous
the proboscis of the sandfly are injected into the ulcer as it enlarges in size. The lesion may heal
host’s skin during feeding (Figure 2.26). They spontaneously after a few months, leading to
then invade the cells of the reticuloendothelial a disfiguring scar; in the case of New World
system, transform into amastogotes, and leishmaniasis, CL may progress to other forms
multiply via binary fission. When the parasitized of leishmaniasis.
cell ruptures, the amastigotes that are released
B. Diffuse Cutaneous Leishmaniasis
either invade new cells, or are taken up by
sandflies during feeding, where they transform The manifestation of DCL, also called
into promastigotes in the gut, multiply by anergic or lepromatous leishmaniasis, is
binary fission, and migrate to the foregut. characterized by a localized, non-ulcerating
Leishmania spp. may also be transmitted papule, eventually developing numerous
congenitally, through blood transfusion, by diffuse satellite lesions that affect the face and
contamination of bite wounds, and by direct extremities. This type of leishmaniasis may be
contact with contaminated specimens. initially diagnosed as lepromatous leprosy.
Pathogenesis and Clinical Manifestations C. Mucocutaneous Leishmaniasis
cost-effective drug formulation for cutaneous mostly poor and malnourished children below
and visceral leishmaniasis. 15 years old.
In India, where sodium pentavalent Leishmaniasis is primarily a disease of
antimony resistance is high, the antineoplastic poverty. It affects people living in squalid
drug miltefosine was introduced in 2002 to treat conditions, and is associated with poor housing,
VL. Miltefosine is the only oral drug currently malnutrition, a weak immune system, and
given to VL patients. lack of resources. Environmental changes such
Pentamidine is another second-line drug as deforestation, new irrigation schemes, and
for cutaneous as well as the visceral form of the urbanization are also linked to changes in the
disease. However, due to side-effects and the epidemiology of the disease. In urban areas
development of drug resistance, pentamidine where leishmaniasis occurs, there is a greater
use has been limited. For the cutaneous form of epidemic threat.
leishmaniasis, topical paromomycin has shown Visceral leishmaniasis is an important
efficacy in certain areas. opportunistic infection in AIDS patients. VL/
Combination therapy using two or more of HIV co-infection is currently a major threat in
the anti-leishmanial drugs is being studied. The the control and prevention of either disease.
presence of drug resistance especially towards Immunosuppression from HIV predisposes
the pentavalent antimonials, poor treatment to VL, while VL infection accelerates HIV
outcomes of complicated cases (such as HIV replication and progression to AIDS. VL/
coinfection), the potential for greater efficacy, HIV co-infection has been documented in
better compliance, and fewer side effects are 35 countries, with most cases coming in from
reasons why combination therapy for VL Ethiopia, southern Europe (Spain, Italy, France,
is the current consensus. Among the drug and Portugal), and Brazil.
combinations currently being used or under In the Philippines, there have been
clinical trials are: sodium stibogluconate plus imported cases of cutaneous lesions referred
paromomycin, and liposomal amphotericin B to the University of the Philippines—College
plus either miltefosine, or sodium stibogluconate. of Public Health, where amastigotes were
identified from the patients.
Epidemiology
Prevention and Control
Leishmaniasis is a global disease distributed
across 88 countries in four continents. It affects Preventive measures against leishmaniasis
more than 12 million people worldwide, and include usage of insect repellants containing
more than 350 million are at risk for the DEET and permethrin, insecticide-treated
disease. New cases of cutaneous leishmaniasis clothing, and fine-mesh bed nets. Use of fine
number between 1 to 1.5 million per year, the mesh screens and spraying of houses and
majority of which occur in Afghanistan, Brazil, buildings are also being done in certain areas.
Iran, Peru, Saudi Arabia, and Syria. American However, interval spraying predisposes to
soldiers deployed in Afghanistan and Iraq have resistance of sandflies to the insecticides, not
also demonstrated cases of CL. Mucocutaneous to mention the impact of insecticides on the
leishmaniasis occurs in Bolivia, Brazil, and environment.
Peru, while half a million new cases annually Regulation of reservoir hosts is another
of visceral leishmaniasis occur primarily in important aspect in the control and prevention
Bangladesh, Brazil, India, Nepal, and Sudan. of leishmaniasis. Insecticide-treated dog collars,
In 2009, there was a noted upsurge in VL cases mass testing of domestic dogs, and even
in Sudan compared to previous years, affecting extermination of infected dogs are current
128 Medical Parasitology in the Philippines
strategies that address zoonotic transmission Markell EK, Voge M, John DT. Medical
of the disease. parasitology. 9th ed. Philadelphia: W. B.
At present, there is no commercially Saunders Company; 1992.
available form of either active or passive Nantulya VM. TrypTect CIATT a card indirect
chemoprophylaxis against leishmaniasis. agglutination trypanosomiasis test for
However, in immunocompetent individuals, diagnosis of Trypanosoma gambiense and
a form of immunity persists after resolution T. rhodesiense infections. Trans R Soc Trop
of active lesions. Certain countries, such as Med Hyg. 1997;9(1):551–3.
endemic areas in the Middle East, have been Neva FA, Brown HW. Basic clinical parasitology.
using live parasites either from infected insect 6th ed. Connecticut: Appleton & Lange;
vectors, or in recent years, from cultures, to 1994.
inoculate inconspicuous areas (such as the Roberts LS, Janovy J. Foundations of
buttocks) so as to protect themselves from parasitology. 5th ed. Dubuque: Wm. C.
disfiguring facial lesions from future infections. Brown Publishers; 1996.
Commercial vaccines are currently under Wilson WR, Sande MA. Current diagnosis
development. and treatment in infectious diseases. USA:
Lange Medical Books, McGraw-Hill; 2001.
References
p. 842–53.
Beaver PC, Jung RC, Cupp E.W. Clinical World Health Organization. WHO Fact
parasitology. 9th ed. Philadelphia: Lea & Sheet no. 116. Geneva: World Health
Febiger; 1984. Organization; 1999.
Leyritana, KT, Saniel MC, Carpo BG, Murray World Health Organization. Chagas disease:
HW. New world cutaneous leishmaniasis interruption of transmission. Wkly
in a traveler: the first documented case in Epidemiol Rec. 1998;73(1-2):1–4.
the Philippines. Acta Med Philipp. 2011; World Health Organization. Leishmaniasis:
45(3):73–6. second generation vaccines. TDR news.
Mahmoud AA. Tropical and geographical 2001;65:13.
medicine companion handbook. 2nd ed. World Health Organization. Miltefosine—1,200
Singapore: McGraw-Hill Book Co.; 1993. patients in Phase IV trial in Inidia. TDR
news. 2002;69:12.
Chapter 3
Nematode Infections
Intestinal Nematodes
Vicente Y. Belizario, Jr., Francis Isidore G. Totañes
129
130 Medical Parasitology in the Philippines
Plate 3.1. Ascaris unfertilized egg (a), fertilized egg (b), and embryonated egg (c)
(Courtesy of the Department of Parasitology, UP-CPH)
to the cecum or proximal colon where they of the infection. Ascariasis was estimated to have
penetrate the intestinal wall. These larvae enter contributed to a total of 1.85 million disability-
the venules to go to the liver through the portal adjusted life years (DALYs) in 2004.
vein, on to the heart and pulmonary vessels The varied pathology of ascariasis includes
where they break out of capillaries to enter the the reaction of tissues to invading larvae,
air sacs. In the lungs, larvae undergo molting irritation of the intestine by the mechanical
before migrating to the larynx and oropharynx and toxic action of the adult, and complications
to be swallowed into the digestive tract. This arising from the parasite’s extraintestinal
hepato-tracheal migration phase takes about migration (Plates 3.2–3.4). The usual infection
14 days, while the development of egg-laying of 10 to 20 worms may not show symptoms,
adult worms takes about 9 to 11 weeks after hence, may go unnoticed by the host unless
egg ingestion. The life span of an adult worm it is discovered by stool examination or the
is about 1 year. spontaneous passing of worms in the stool.
A female Ascaris produces about 200,000 During lung migration, the larvae may
eggs per day, but this number decreases with cause host sensitization resulting in allergic
increasing worm load. The eggs are deposited manifestations such as lung infiltration,
in the soil when a person with Ascaris infection asthmatic attacks, and edema of the lips.
defecates indiscriminately. In the soil, it takes Symptoms of difficulty of breathing and fever
about 2 to 3 weeks for eggs to develop into the similar to pneumonia may occur as a result
infective stage (embryonation) under favorable of penetration by several larvae through the
conditions with suitable temperature, moisture, lung capillaries as they enter the air sacs.
and humidity. The larvae undergo two molts to The most frequent complaint of patients is
reach their 3rd stage within the egg and become vague abdominal pain. Eosinophilia is present
embryonated. Only when this infective egg is during larval migration. Moderate infections
swallowed can humans become infected with may produce lactose intolerance and vitamin
Ascaris (Figure 3.1). The embryonated eggs can A malabsorption. Heavy infections are likely
survive in moist shaded soil for a few months to cause bowel obstruction (due to bolus
to about two years in tropical and sub-tropical formation), intussusception, or volvulus that
areas, but for much longer in temperate regions. may result in bowel infarction and intestinal
perforation.
Pathogenesis and Clinical Manifestations
Serious, and at times, fatal effects of
A majority of Ascaris infections are ascariasis are due to erratic migration of adult
asymptomatic, although an estimated 120 to worms. They may be regurgitated and vomited,
220 million cases exhibit morbidity as a result may escape through the nostrils or rarely, inhaled
Chapter 3: Nematode Infections 131
into the trachea. The worms may invade bile abscesses. Penetration of the worms through
ducts through the ampulla of Vater and enter the intestinal wall into the peritoneal cavity
the gallbladder or liver. Patients with biliary may occur and result in either acute peritonitis
ascariasis experience severe colicky abdominal or chronic granulomatous peritonitis.
pain, which is brought about by the movement Complications brought about by the larvae
of the worms inside the biliary tract. Worms and adult worms are a cause for concern. The
may also lodge in the appendix or occlude the continuous biting or pricking of the intestinal
pancreatic duct and cause acute appendicitis or mucosa for food by a few Ascaris adults may
pancreatitis, respectively. Intestinal bacteria may irritate nerve endings in the mucosa and
be carried to these migration sites producing result in intestinal spasm leading to intestinal
132 Medical Parasitology in the Philippines
Plate 3.2. Ascaris in the liver Plate 3.3. Intestinal obstruction with Ascaris
(Courtesy of Dr. Benjamin Cabrera) (Courtesy of Dr. Benjamin Cabrera)
Figure 3.2. Global distribution of soil-transmitted helminth (STH) infections and proportion of children
requiring preventive chemotherapy for STH infections in each country
(From World Health Organization. Helminth control in school-age children: a guide for managers of
control programmes. 2nd ed. Geneva: World Health Organization; 2011.)
are estimated to have ascariasis, and about 2,000 reported an overall prevalence of 27.7%
die annually. The disease remains endemic in among school-age children and 30.9% among
many countries of Southeast Asia, Africa, and preschool children. Prevalence rates are parallel
Central and South America. Children ages with those of trichuriasis due to similar modes
5 to 15 years have the highest intensities of of infection and risk factors.
infection with Ascaris compared with the other The level of transmission of Ascaris and
age groups. Children are particularly vulnerable other STH from soil to humans depends on
since they are at risk of ingesting embryonated socio-economic factors more than on physical
Ascaris eggs while playing in soil contaminated factors. The main factors appear to be a high
with human feces. density of human population, involvement
Worldwide estimates reveal that the in agriculture (including use of night-soil as
highest number of cases of ascariasis is found fertilizer), illiteracy, and poor sanitation. Poor
in East Asia and the Pacific Islands, although health education on personal, family, and
A. lumbricoides is also known to be able to community hygiene are also important factors
survive colder temperatures compared with contributing to the transmission of Ascaris.
Trichuris and hookworm. In many low and
Prevention and Control
middle income countries like the Philippines,
the prevalence may reach 80 to 90% in certain Surveillance and monitoring are important
high risk groups like public elementary school components of an STH Control Program.
children. Recent local sentinel surveys have Baseline cumulative prevalence and prevalence
Chapter 3: Nematode Infections 135
Table 3.1. Core indicators of mass drug administration for soil-transmitted helminth infections
deworming. Nutritional status and school framework (Table 3.2) for the control of STH
performance may also be monitored alongside infections. When mass treatment is being
parasitologic parameters. undertaken, submission to the said intervention
Prevention and control measures for Ascaris should be a goal of health education.
and other STH infections involve provision of War on Worms (WOW) approach in
safe water, environmental sanitation, hygiene Biñan, Laguna is a school-based, school teacher-
education, and regular deworming, which assisted mass drug administration led by the
are the components of the WASHED (water, Local Government Unit (LGU) which started in
sanitation, hygiene, education, deworming) 1999. The approach was initially supported by
Table 3.2. The WASHED framework for a comprehensive control of soil-transmitted helminth infections
Johnson & Johnson, Inc. (J&J) and eventually do not reach the point of eradication due to
taken over by LGU and the Department of implementation challenges and the limited
Education (DepEd) District of Biñan. Part of practice of the WASHED strategies in the
the WOW experience was that STH infections communities (Figure 3.4).
Figure 3.4. Comparison of cumulative prevalence in San Vicente Elementary School (SVES) and sentinel
schools in Biñan, Laguna from 1999 to 2010 (Courtesy of Dr. Vicente Belizario, Jr.)
Trichuris trichiura
Vicente Y. Belizario, Jr., Francis Isidore G. Totañes
Pathogenesis and Clinical Manifestations is common. The lumen of the appendix may be
filled with worms, and consequent irritation
The anterior portions of the worms,
and inflammation may lead to appendicitis or
which are embedded in the mucosa, cause
granuloma formation.
petechial hemorrhages, which may predispose
The intensity of infection is important in
to amebic dysentery, presumably because the
understanding the clinical picture. Infections
ulcers provide a suitable site for tissue invasion
with over 5,000 T. trichiura eggs per gram of
by E. histolytica. The mucosa is hyperemic and
feces are usually symptomatic. In patients with
edematous; enterorrhagia or intestinal bleeding
heavy intensity infection, the worms may be
142 Medical Parasitology in the Philippines
found throughout the colon and rectum, and patient suffers from frequent blood-streaked
may result in Trichuris dysentery syndrome diarrhea, abdominal pain and tenderness, and
manifested by chronic dysentery and rectal rectal prolapse where adult worms attached to
prolapse (Plate 3.7). Such cases of heavy chronic the rectal mucosa can be seen. In light infections
trichuriasis are often marked by frequent blood- where symptoms are absent, laboratory diagnosis
streaked diarrheal stools, abdominal pain and is essential.
tenderness, nausea and vomiting, and weight Laboratory diagnosis may be done by
loss. Anemia is strongly correlated to heavy direct fecal smear (DFS) with a drop of saline.
intensity trichuriasis, and blood loss from such An alternative diagnostic technique is the Kato
infections can range from 0.8 to 8.6 ml per day. thick smear method that uses about 20 to 60
Furthermore, infection with over 800 worms mg of stool sample. This method is highly
can result in anemia in children. On the other recommended in the diagnosis of trichuriasis.
hand, light infections are moderately associated The Kato-Katz technique is a quantitative
with anemia, although these infections are method that employs egg counting to determine
usually asymptomatic and the presence of the the intensity of helminth infection. This
parasite may be discovered only in routine stool technique can be used to assess the efficacy of
examinations. Trichuriasis has also been shown anthelminthic drugs in terms of cure rate (CR)
to result in poor appetite, wasting, stunting, and egg reduction rate (ERR). This technique
as well as reduced intellectual and cognitive can also be used for epidemiological surveys for
development in children. the monitoring of a helminth control program.
Both Kato thick and Kato-Katz techniques are
simple and low-cost methods that have high
sensitivity and specificity for the detection of
Trichuris eggs, as well as eggs of other soil-
transmitted helminths. A single Kato-Katz
examination has a sensitivity and specificity for
the detection of Trichuris of 91.4% and 94.4%,
respectively.
The acid-ether and the formalin-ether/
ethyl acetate concentration techniques can also
be used for the diagnosis of trichuriasis. The
FLOTAC technique has also been shown to be
more sensitive in the diagnosis of trichuriasis
Plate 3.7. Rectal prolapse in a 9-year old female compared with Kato-Katz and ether/ethyl
seen at the Philippine General Hospital with
heavy Trichuris infection
acetate concentration techniques.
(Courtesy of Dr. Benjamin Cabrera) Treatment
The prognosis of trichuriasis is very good. The drug of choice in the treatment of
Because there is no larval migration through the trichuriasis is mebendazole given 100 mg twice
lungs as in Ascaris and hookworm infections, no a day for 3 days. Albendazole may be used as
lung pathology occurs. an alternative drug. Both are benzimidazole
derivatives and are available as chewable tablets.
Diagnosis
Administration of mebendazole 500 mg once a
Clinical diagnosis is possible only in very day for 3 days has been shown to have the highest
heavy chronic Trichuris infection where the cure rate (71%) compared with albendazole 400
Chapter 3: Nematode Infections 143
mg given once a day for 3 days (56%). For the Prevention and Control
purposes of preventive chemotherapy through
Strategies for the prevention and control
mass drug administration, mebendazole is given
of Trichuris infection are similar to those for
as a 500 mg single dose, while albendazole is
Ascaris infections. The WHO recommends
given as a 400 mg single dose. In recent local
biannual mass drug administration with
studies, it has been shown that albendazole in
mebendazole 500 mg or albendazole 400 mg
combination with ivermectin, a drug that is
among school-age children in communities
also used to treat filariasis, exhibited better cure
where the prevalence of STH infections is
and egg reduction rates than albendazole alone.
≥50%. Treatment of other high-risk groups such
A contraindication for mebendazole
as preschool children, women of childbearing
and albendazole is hypersensitivity and early
age, including pregnant women in the 2nd
pregnancy (within the 1st trimester). Adverse
and 3rd trimesters as well as lactating women,
effects of these two drugs are usually mild and
adults in certain high-risk occupations should
transient and may present as headache, nausea,
also be considered. On the other hand, once a
vomiting, gastrointestinal discomfort, and
year treatment is recommended in communities
itchiness.
with STH prevalence <50%. Other strategies
Deworming of children has been
such as provision of safe water, environmental
shown to contribute to improved motor and
sanitation, and hygiene education are also
language development, as well as to reduced
important in STH control.
malnutrition. Nutritional status and intellectual
development have also been shown to improve References
after deworming.
Bates I, McKew S, Sarkinfada F. Anaemia: a
Epidemiology useful indicator of neglected disease burden
and control. PLoS Med. 2007;4(8):e231.
Trichuriasis occurs in both temperate
Belizario VY, Amarillo ML, de Leon WU,
and tropical countries but is more widely
de los Reyes AE, Bugayong MG,
distributed in warm, moist areas of the world.
Macatangay BJ. A comparison of the
Approximately 604 to 795 million are infected
efficacy of single doses of albendazole,
globally. In tropical and subtropical regions,
ivermectin, and diethylcarbamazine alone
Trichuris is most prevalent in East Asia and
or in combinations against Ascaris and
Pacific Island regions, and least prevalent in the
Trichuris spp. Bull World Health Organ.
Middle East and North African regions. Among
2003;81:35–42.
the different age groups, children 5 to 15 years
Bethony J, Brooker S, Albonico M, Geiger
of age are most frequently infected, and have
SM, Loukas A, Diemert D, et al. Soil-
the highest intensities of infection. In a recent
transmitted helminth infections: ascariasis,
sentinel survey in the Philippines, the prevalence
trichuriasis, and hookworm. Lancet.
of Trichuris ranged from 4.5 to 55.1% in
2006;367:1521–32.
preschool children, and from 8.1 to 57.9% in
Cabrera BD, Cruz AC. A comparative study
school-age children. Distribution of trichuriasis
on the effect of mass treatment of the
is similar to that of A. lumbricoides. Prevalence of
entire community and selective treatment
co-infections with the two helminths is 19.1%
of children alone in the total prevalence
in a recent sentinel survey.
of soil-transmitted helminthiases in two
144 Medical Parasitology in the Philippines
Hookworms
Vicente Y. Belizario, Jr., Francis Isidore G. Totañes, John Robert C. Medina
Plate 3.8. Buccal capsules of hookworms: N. americanus (a) and A. duodenale (b)
(Courtesy of Dr. Benjamin Cabrera)
146 Medical Parasitology in the Philippines
these manifestations seem to be rare in the lymph, and protein. Other symptoms are
tropics. In the stage of maturation of the exertional dyspnea, weakness, dizziness, and
worm in the intestine, there is abdominal pain, lassitude, while signs include rapid pulse,
steatorrhea, or sometimes diarrhea with blood edema, and albuminuria. Unlike in ascariasis,
and mucus, as well as eosinophilia. the complications in hookworm infection are
Hookworm infection is usually chronic, quite mild, and remedial measures are readily
hence patients often show no acute symptoms. applied. In general, the prognosis of hookworm
Studies have shown greater blood loss per worm infection is good.
per day in A. duodenale infection compared with During the migration of the larva in the
N. americanus infection. Chronic moderate human body, the parasite continuously presents
or heavy hookworm infection results in a diverse immunogenic challenges to the host.
progressive, secondary, microcytic, hypochromic Extensive humoral responses are produced
anemia of the iron-deficient type, due primarily against the larva and the adult hookworm,
to continuous loss of blood. which share many antigens. Cellular immune
Hypoalbuminemia is another manifestation response is primarily mediated by eosinophils,
of hookworm infection. There is low level mast cells, and Th2 cells. Despite all of these,
of albumin due to combined loss of blood, there has been no clear evidence that the
148 Medical Parasitology in the Philippines
host develops perpetual immunity against one end immersed in water. Culture
hookworm infection; however, polyvalent IgE methods are recommended for species
antibodies have been suggested to provide some identification.
protective roles.
Molecular approaches, which include
Diagnosis PCR-based detection of hookworm DNA in
feces and enzyme-linked immunosorbent assay
The clinical picture, though characteristic,
(ELISA) for the detection of secretory/excretory
is not pathognomonic to permit differentiation
coproantigens, have also been developed.
from other helminth infections. Final diagnosis
depends on the identification of parasite Treatment
ova in the feces. The following techniques
All diagnosed cases of hookworm infections
are inexpensive and can be applied to both
should be treated; however, where the risk
individual and mass screening:
of reinfection is high, mass screening before
1. Direct fecal smear is of value only when treatment may be impractical. As with other
the infection is quite heavy. It may not soil-transmitted helminth infection control, the
detect the parasite in light infections WHO recommends mass drug administration
(i.e., egg count of <400 eggs per gram among school-age children at least once a
feces). year for communities with cumulative STH
2. The Kato thick or Kato-Katz method prevalence greater than or equal to 20%.
may increase detection rates since Treatment of other high-risk groups such as
more stools are examined using these preschool children, women of childbearing age,
techniques. The latter technique may including pregnant women in the second and
also provide quantitative diagnosis by third trimesters and lactating women, should
determining the intensity of infection also be considered.
in terms of number of helminth eggs Albendazole, the drug of choice, is
per gram of feces. The disadvantage of larvicidal and ovicidal against N. americanus
these methods is the rapid clearance of and A. duodenale. It is given as a 400 mg single
hookworm eggs after 30 to 60 minutes dose for adults and children over 2 years old.
with the use of glycerine as a clearing Chewable tablets or suspension preparations are
agent. available. Mebendazole for children and adults
3. Concentration methods like zinc is given as a 500 mg single dose. These drugs are
sulfate centrifugal flotation and both benzimidazole derivatives that block the
the formalin-ether/ethyl acetate uptake of glucose by most intestinal and tissue
concentration method use greater nematodes. Adverse effects for both drugs are
quantity of stool that may contribute rare, and are usually mild and transient. These
to the increase in sensitivity. FLOTAC, include epigastric pain, diarrhea, headache, and
which is also a centrifugal flotation dizziness, among others.
method, has been shown to have a Anemia and hypoproteinemia should also
higher sensitivity for the diagnosis of be addressed by giving iron supplementation
soil-transmitted helminths compared and adequate diet.
with multiple examinations of Kato- In recent years, tolerance and resistance of
Katz smears. human hookworms to these drugs had been
4. Culture methods like the Harada- reported in countries where regular deworming
Mori allow hatching of larvae from is the main control strategy. Studies had shown
eggs on strips of filter paper with that the use of the recommended single dose
Chapter 3: Nematode Infections 149
of the drugs led to low cure rate. Monitoring high. Among pregnant women and adolescent
the efficacy of and drug resistance to these females, the prevalence rates are 5.5% and
benzimidazole derivatives has not yet been done 2.8%, respectively. A study among military
in the local setting. Baseline data are necessary and para-military personnel showed that
for the evaluation and adjustment of the 46.9% had the infection. In indigenous people
treatment regimen. Cure rates, egg reduction communities in Davao del Norte, 13.6% of
rates, and reinfection rates are important the school children were found to be infected.
parameters in drug monitoring. Among food handlers, 22.7% in Metro Manila
and 14.8% in Cebu had hookworm infection.
Epidemiology
Factors that contribute to the distribution
About 576 to 740 million people in and transmission of hookworms are: (a)
tropical and subtropical countries are estimated suitability of the environment for eggs or
to be infected with either A. duodenale or N. larvae: damp, sandy or friable soil with decaying
americanus. Associated anemia causes at least vegetation, and temperature of 24 to 32°C, (b)
50,000 deaths annually. mode and extent of fecal pollution of the soil
Geographical distribution of the two (through open defecation or the use of night soil
human hookworms used to be relatively as fertilizer), and (c) mode and extent of contact
distinct. A. duodenale was prevalent in Europe between infected soil and skin or mouth.
and Southwestern Asia, while N. americanus Whereas the method of human infection
was prevalent in tropical Africa and the in necatoriasis is purely percutaneous, in
Americas. But now, both species have become ancylostomiasis, it is both percutaneous and
widely distributed throughout the tropics and through the oral route. The latter occurs upon
subtropics, and rigid demarcations are no longer eating raw vegetables contaminated with
present. infective larvae and probably also through
In the Philippines, local studies on ingestion of raw or insufficiently cooked infected
speciation of human hookworms revealed that meat, although it is not clear whether infection
out of 1,958 samples positive for hookworm in through eating raw meat occurs in humans. A.
cultures, 97% were identified as N. americanus, duodenale may remain dormant in the intestines
1% as A. duodenale, and 2% were mixed or in the muscles, resulting in a prolonged
infections. incubation period and creating problems in
The local distribution of human hookworm treatment. Transmammary transmission has
infection is greater in agricultural areas. Farmers also been reported.
are prone to the infection because they work In the Philippines, the first human case of
in rice fields and vegetable gardens, and they Ancylostoma ceylanicum was reported in 1968
are not properly protected from contact from a 53-year old woman from Ilocos Norte
with infective soil. In agricultural areas of where 23 adult worms were collected. There
Compostela Valley province, infection rates are also animal hookworms like Ancylostoma
have been shown to be more than 50% in the braziliense (cat hookworm) and Ancylostoma
late 1990s. Recent surveillance in sentinel sites caninum (dog hookworm) that can infect
in the Philippines revealed an overall prevalence humans causing “creeping eruption,” also
of hookworm infection at 1.1% and 1.9% known as cutaneous larva migrans (CLM)
for preschool children and school children, (Plate 3.11).
respectively. Much of the necessary information about
In other high-risk groups, the prevalence hookworm infection and the disease, i.e,
of hookworm infection remains relatively morbidity and mortality rates, are still lacking
150 Medical Parasitology in the Philippines
Strongyloides stercoralis
Vicente Y. Belizario, Jr., Percy G. Balderia
hatch into rhabditiform larvae, migrate into the intestinal mucosa by adult females may occur
lumen, and pass out in the feces. simultaneously, particularly in hyperinfection.
Autoinfection occurs when rhabditiform In the first phase of acute infection,
larvae pass down the large intestine and develop larval invasion of the skin produces erythema,
into filariform larvae. Being the infective stage, and pruritic elevated hemorrhagic papules.
these filariform larvae may invade the mucosa During the larval migration phase, the lungs
and enter the circulation to start another are destroyed causing lobar pneumonia with
parasitic cycle without leaving the body of the hemorrhage. Cough and tracheal irritation may
host (Figure 3.7). also occur, mimicking bronchitis. In the third
phase, adult female worms may be found in
Pathogenesis and Clinical Manifestations
the intestinal mucosa from the pylorus to the
There are three phases of acute infection rectum, but the greatest numbers are found in
in strongyloidiasis: (a) invasion of the skin by the duodenal and upper jejunal regions.
filariform larvae, (b) migration of larvae through Light infection does not cause intestinal
the body, and (c) penetration of the intestinal symptoms. Moderate infection causes diarrhea
mucosa by adult female worms. The migration alternating with constipation. Heavy infection
of larvae through the body and penetration of produces intractable, painless, intermittent
154 Medical Parasitology in the Philippines
diarrhea (Cochin China diarrhea) characterized The culture technique is practical, low-
by numerous episodes of watery and bloody cost, and suited for mass screening as well as
stools. Hyperinfection is a syndrome of individual diagnosis. The modified Harada-
accelerated autoinfection which usually, but not Mori culture method makes use of polyethylene
invariably, occurs in the immunocompromised. plastic bags or tubes instead of glass tubes.
It manifests with exacerbation of gastrointestinal Plastic bags and tubes are unbreakable, lighter
and pulmonary symptoms and increased to transport, and do not occupy much space.
numbers of larvae in the stool and/or sputum. These are therefore recommended for use in the
Chronic strongyloidiasis is often field. On the other hand, the main advantage
asymptomatic. However, intermittent vomiting, of serologic testing is the rapidity and ease of
diarrhea, constipation, and borborygmi may performance of the procedure.
be observed. Anal pruritus, urticaria, and larva
Treatment
currens rashes are also common. Recurrent
asthma and nephritic syndrome have also been All infected individuals should be treated.
reported in cases of chronic infection with S. Treatment was previously based on albendazole
stercoralis. or thiabendazole. However, recent studies show
Complications include edema, emaciation, that ivermectin also provides the best results in
loss of appetite, anemia, lobar pneumonia, ileus, chronic uncomplicated strongyloidiasis with
intestinal obstruction, gastrointestinal bleeding, regard to efficacy and tolerability. Higher doses
and malabsorption leading to cachexia. given for longer periods may be necessary.
Prognosis is good in light infections, Strongyloides stercoralis is quite sensitive to the
but moderate and heavy infections have high ovicidal and larvicidal actions of the drugs.
mortality rates due to the massive invasion Albendazole, thiabendazole, and ivermectin
of tissues by adults and larvae. Disseminated have been used to treat hyperinfection or
infection occurs among patients with cancer, disseminated disease singly or in combination,
malnutrition, HIV/AIDS, HTLV-1, or those but data are limited to case reports or case series.
using immunosuppressive drugs after organ Albendazole and thiabendazole are
transplantation. contraindicated in pregnant women and in
those with known hypersensitivity to the
Diagnosis
drugs. Thiabendazole may give rise to dizziness,
The finding of unexplained eosinophilia gastrointestinal irritation, drowsiness, pruritus,
in a patient may be a clue pointing to and headache lasting for several hours. Adverse
strongyloidiasis. The application of repeated reactions with albendazole are transient
concentration techniques, like the Baermann gastrointestinal discomfort and headache.
funnel gauze method, usually leads to detection Egg reduction rate cannot be determined
of the infection. Harada-Mori culture is because eggs are not passed out in the feces
considered one of the most successful methods but are oviposited in the intestine and other
in parasite identification. At present, using the tissues of the host. Reinfection rate is difficult
nutrient agar plates is also recommended. Other to calculate because of autoinfection.
laboratory methods that can be done are Beale’s
Epidemiology
string test, duodenal aspiration, and small bowel
biopsy. In disseminated strongyloidiasis, larvae Strongyloides stercoralis is found throughout
may be found in sputum or urine. Serology may the world and follows a distribution pattern
not be useful in filariasis endemic areas since similar to hookworm in the tropics and
there are cross-reactions between Strongyloides subtropics, as well as in Europe and the USA.
and filarial worm antigens. Some 50 to 100 million people are estimated
Chapter 3: Nematode Infections 155
to be infected with this parasite. Strongyloides and mortality. People with cancer, debilitating
is a soil-transmitted helminth. diseases like pulmonary tuberculosis, and
In the Philippines, strongyloidiasis is malnutrition, and those about to undergo
relatively rare. Local data on the prevalence of organ transplantation should be cleared of
Strongyloides stercoralis reveal that out of 4,208 Strongyloides infection. This important step is
stools examined using Harada-Mori culture, taken to prevent the occurrence of disseminated
only 50 samples or 1.2% were found positive strongyloidiasis, which is almost always fatal
for the worm. If all studies on prevalence were because larvae invade vital organs.
included, out of 294,176 stools examined, only
References
148 or 0.05% were found positive. Prevalence
rates have been described to fluctuate between Bon B, Houze S, Talabani H, Magne D, Belkadi
0 to 2.3%, depending on the area selected. This G, develoux M, et al. Evaluation of a rapid
infection is more frequent in male children 7 to enzyme-linked immunosorbent assay
14 years old, than among females and adults. for diagnosis of strongyloidiasis. J Clin
Infection and disease rates as well as Microbiol. 2010;48(5):1716–9.
morbidity and mortality figures are not Cabrera BD. Prevalence of Strong yloides
well documented. The factors that affect stercoralis infection in selected areas in the
transmission include poor sanitation and Philippines using a modified Harada-Mori
indiscriminate disposal of human feces that culture technique. Acta Med Philipp.
may contain Strongyloides larvae. Autoinfection 1981;17(3):19–26.
explains how some people remain infected Gann PH, Neva FA, Gam AA. A randomized
for more than 30 years even after leaving the trial of single- and two-dose ivermectin
endemic area. This phenomenon has been seen versus thiabendazole for treatment
in American veterans who returned from the of strongyloidiasis. J Infect Dis.
Korean and Vietnam wars. 1994;169(5):1076–9.
Igual-Adell R, Oltra-Alcaraz C, Soler-Company
Prevention and Control
E , Sánchez-Sánchez P, Matogo-Oyana J,
Prevention and control measures for this Rodríguez-Calabuig D. Efficacy and safety
disease are similar to those for hookworm of ivermectin and thiabendazole in the
infection. Both worms use the soil for further treatment of strongyloidiasis. Expert Opin
development and maintain their endemicity in Pharmacother. 2004;5(12):2615–9.
areas where environmental sanitation is poor and Keiser P, Nutman T. Strongyloides stercoralis
human feces is deposited indiscriminately in the in the immunocompromised population.
soil by infected people. Infection is acquired by Clin Microbiol Rev. 2004;17(1):208–17.
individuals who usually walk barefoot. There is Segarra-Newnham M. Manifestations,
a need to provide health education on personal, diagnosis, and treatment of Strongyloides
family and community hygiene to change stercoralis infection. Ann Pharmacother.
behavior and practices. Infected individuals 2007;41(12):1992–2001.
should be treated in order to prevent morbidity
156 Medical Parasitology in the Philippines
Enterobius vermicularis
Vicente Y. Belizario, Jr., Percy G. Balderia
Plate 3.13. Enterobius cephalic alae Plate 3.14. D-shaped eggs of Enterobius
(Courtesy of the Department of Parasitology, vermicularis (Courtesy of the Department of
UP-CPH) Parasitology, UP-CPH)
Chapter 3: Nematode Infections 157
intestines. Gravid female worms migrate down usually dies. Eggs on the perianal region become
the intestinal tract and exit through the anus to fully embryonated within 6 hours. When
deposit eggs on the perianal skin. Adult female ingested, eggs containing the 3rd stage larvae
worms migrate to the perianal area, usually in hatch in the duodenum, pass down the small
the evening hours. A single female lays from intestines to the cecum, and develop into adults
4,672 to 16,888 eggs per day with an average (Figure 3.8). Eggs are resistant to disinfectants
of 11,105 eggs. After egg deposition, the female but succumb to dehydration in dry air within
a day. However, in moist conditions, these eggs relieved only by vigorous scratching. Diagnosis
can remain viable for up to 13 days. The eggs is confirmed by finding adult worms or eggs on
remain viable longest under conditions of fairly microscopic examinations. Adult worms may
high humidity and moderate temperature. The be seen in the feces or in the perianal region.
eggs may survive for some days in dry dust, and Eggs are found in the feces in only about 5%
airborne eggs can infect persons at a distance of infected persons. The method of laboratory
via inhalation. diagnosis is the Graham’s scotch adhesive tape
swab (perianal cellulose tape swab), which gives
Pathogenesis and Clinical Manifestations
the highest percentage of positive results, and
Enterobius vermicularis is a relatively the greatest number of eggs seen. This low-cost
innocuous parasite and rarely produces any diagnostic method is easy to perform and is very
serious lesions. Mild catarrhal inflammation sensitive and specific.
of the intestinal mucosa may result from
Treatment
the attachment of the worms. Mechanical
irritation and secondary bacterial invasion The drugs of choice are mebendazole 100
may lead to inflammation of the deeper layers mg PO single dose or albendazole 400 mg PO
of the intestines. Invasion of the appendix is single dose. Pyrantel pamoate 11 mg/kg base
not unusual, but whether this invasion is a PO single dose (max. of 1 g) is considered a
significant cause of appendicitis is not known. secondary drug of choice. E. vermicularis is
Migration of egg-laying females to the anus quite susceptible to these drugs, with reported
causes irritation of the perineal region. Intense cure rates of over 90%. Moreover, since family
itching leads to scratching, and may give rise to members are usually infected, treatment of
secondary bacterial infection. Children infected the entire household is recommended. Cure
with this parasite may suffer from insomnia due can only be considered after seven perianal
to the pruritus. Other signs of infection are smears, on consecutive days using scotch-tape
poor appetite, weight loss, irritability, grinding swab method, are all found to be negative.
of teeth, and abdominal pain. The egg reduction rate is difficult to determine
Complications such as appendicitis, because eggs are collected from the perianal
vaginitis, endometritis, salpingitis, and area instead of from the feces using Kato-Katz.
peritonitis are all due to aberrant adult worm Mebendazole, albendazole, and pyrantel are
migration. Entry into the peritoneal cavity via contraindicated in individuals with known
the female reproductive system may result in the hypersensitivity. Adverse effects of these
formation of granuloma around eggs or worms. drugs include mild, transient gastrointestinal
Pinworms or their eggs have occasionally been disturbance, and headache.
reported from other ectopic sites such as the
Epidemiology
liver and lung.
The prognosis of enterobiasis or oxyuriasis Enterobiasis occurs in both temperate and
is good. This parasitic disease is extremely tropical regions of the world, and has a high
contagious and can easily spread among prevalence in both developed and developing
members of a family or in institutions. Hence, countries. It is the only intestinal nematode
it has been described as a familial or a group infection that cannot be controlled through
disease. sanitary disposal of human feces, because
the eggs are deposited in the perianal region
Diagnosis
instead of the intestinal lumen. Eggs usually
Enterobiasis should be suspected in contaminate underwear and beddings. The
children and adults who show perianal itching route of infection is through the mouth, the
Chapter 3: Nematode Infections 159
respiratory system (by inhalation of dust opportunities for health education of teachers
containing Enterobius eggs), and through the and school children regarding measures on
anus (wherein the hatched larvae enter the anus control and prevention of intestinal helminth
and cause retroinfection when they go back into infections, including pinworm infections.
the large intestine). Risk factors for infection
References
include overcrowding, thumb-sucking, nail-
biting, and lack of parental knowledge on Cabrera BD, Garcia EG, Cruz TA, Salazar NP,
pinworms. Jueco NL. Studies on enterobiasis in the
There are around 208.8 million infected Philippines. I: Frequency of enterobiasis
persons in the world, with 18 million in among schoolchildren in the city of Manila.
Canada and the United States of America. J Philipp Med Assoc. 1961;37(12):1032–
Prevalence is 12 to 41% in Washington, D.C. 45.
In the Philippines, prevalence levels have been Cabrera BD, Garcia EG, Cruz TA, Salazar
found to be 29% among schoolchildren from NP, Jueco NL. Studies on enterobiasis
exclusive private schools, and 56% among in the Philippines. II: The occurrence
those from public schools. Locally, prevalence is of Enterobius ova in the fingertips and
consistently higher in females (16%) compared fingernails of infected schoolchildren. J
to males (9%). Eggs were found in nail clippings Philipp Med Assoc. 1961;37(12):1032–45.
of school children. Crompton DW, Montresor A, Neishem MC,
Local data on infection and disease rates, Savioli L. Controlling disease due to
as well as morbidity and mortality figures are helminth infections. Geneva: World Health
inadequate. Organization; 2003.
Djakovic A, Tappe D, Dietl J. Diagnosis of
Prevention and Control
and anthelminthic therapy for Enterobius
Personal cleanliness and personal hygiene vermicularis infections during pregnancy:
are essential. Fingernails should be cut short review of the literature and case report. Z
and hand washing should be done after using Geburtshilfe Neonatol. 2006;210(4):147–
the toilet, as well as before and after meals. 52.
The use of showers rather than bathtubs is Jong EC, Sanford C, editors. The travel and
suggested, and infected persons should sleep tropical medicine manual. Philadelphia:
alone until adequately treated. Underwear, Saunders Elsevier; 2008.
night clothes, blankets, and bed sheets should Kim DH, Son H, Kim JY, Cho MK, Park
be handled with care and washed in hot soapy MK, Kang SY. Parents’ knowledge about
water. Vacuum cleaning around beds and enterobiasis might be one of the most
contaminated areas will be useful. Being a important risk factors for enterobiasis
familial disease, chemotherapy of the entire i n c h i l d re n . Ko re a n J Pa r a s i t o l .
family is recommended, and will help in the 2010;48(2):121–6.
control of the disease. Markell EK, John DT, Krotoski WA. Medical
The implementation of mass drug Parasitology. 8th ed. Philadelphia: W. B.
administration targeting soil-transmitted Saunders Company; 1999.
helminthiases is expected to have an impact St. Georgiev V. Chemotherapy of enterobiasis
on the prevalence of enterobiasis as well. (oxyuriasis). Expert Opin Pharmacother.
Control efforts in elementary schools provide 2001;2(2):267–75.
160 Medical Parasitology in the Philippines
Capillaria philippinensis
Vicente Y. Belizario, Jr., Francis Isidore G. Totañes
the soil or water. They must reach the water The eggs hatch in the intestines of the fish and
in order to be ingested by small species of grow into the infective larvae. When the fish
freshwater or brackish water fish (Figure 3.9). is eaten uncooked, the larvae escape from the
fish intestines and develop into adult worms in Endoscopic finding may reveal non-specific
human intestines. segmental erythematous inflammation in the
The first generation of female worms small bowel with superficial erosions with
produces larvae to build up the population. exudation.
Subsequent generations predominantly produce Histologically, the intestines also show
eggs, although there are always a few female flattened and denuded villi, and dilated mucosal
worms that produce both larvae and eggs, or glands. The lamina propria is infiltrated with
larvae only. Some of these larvae are retained plasma cells, lymphocytes, macrophages, and
in the gut lumen and develop into adults. This neutrophils.
leads to hyperinfection and autoinfection,
Diagnosis
which result in the production of very large
numbers of worms. In one autopsy, as many as Diagnosis is based on finding characteristic
200,000 worms were recovered from one liter eggs in the feces by direct smear or wet mount,
of bowel fluid. as well as by stool concentration methods. There
Fish-eating birds are believed to be the may also be various larval stages of the parasites,
natural hosts of C. philippinensis, and humans as well as adult worms in the feces. The uterus
are considered incidental hosts. of the female worms may contain developing
eggs and sometimes larvae (Plate 3.18). The
Pathogenesis and Clinical Manifestations
parasites can also be recovered from the small
Persons with C. philippinensis usually have intestines by duodenal aspiration.
abdominal pain and borborygmi. Patients
initially experience intermittent diarrhea, which
progresses to passing out 8 to 10 voluminous
stools per day. After a few weeks, there is
noticeable weight loss, malaise, anorexia,
vomiting, and edema. Laboratory findings
show severe protein-losing enteropathy and
hypoalbuminemia; malabsorption of fats and
sugars; decreased excretion of xylose; low serum
potassium, sodium and calcium; and high levels
of immunoglobulin E. If the disease is not
treated soon after the symptoms occur, severe Plate 3.18. Capillaria philippinensis second stage
larva from the feces of a person with intestinal
manifestations of the disease develop with a capillariasis (Courtesy of Dr. John Cross)
potentially fatal outcome.
The large number of worms that A study done in Egypt demonstrated
develop in humans is responsible for the high specificity of sandwich enzyme-linked
severe pathology. The parasites do not invade immunosorbent assay (ELISA) in the detection
intestinal tissue, but they are responsible of coproantigen prepared from stool samples of
for micro-ulcers in the epithelium, and the patients with capillariasis. This technique did
compressive degeneration and mechanical not show cross-reaction with coproantigen from
compression of cells. Homogeneous material is patients with Fasciola gigantica and Schistosoma
seen at the anterior end of the worm by electron mansoni. Another study demonstrated cross-
microscopy. The ulcerative and degenerative reaction of capillariasis patient antibodies with
lesions in the intestinal mucosa may account for Trichinella spiralis antigen in immunoblot
malabsorption of fluid, protein, and electrolytes. assay, suggesting the prospective use of T.
164 Medical Parasitology in the Philippines
spiralis antigen for the immunodiagnosis of towns and resulted in more than 1,000 cases
capillariasis. ELISA using T. spiralis antigen and 77 deaths. Cases of human capillariasis have
has been tested and shown to have a sensitivity been subsequently reported in Thailand, Iran,
of 100% in the diagnosis of capillariasis (43 Japan, Indonesia, United Arab Emirates, South
positive cases) and a specificity of 100% (57 Korea, India, Taiwan, Egypt, and Lao People’s
negative cases). Democratic Republic. A review of data from
local hospitals throughout Taiwan from 1983
Treatment
to 2003 revealed a total of 30 capillariasis cases,
In severe cases with electrolyte and protein 21 of whom were from two major Taiwanese
loss, patients should be given electrolyte aboriginal tribes.
replacement and a high protein diet (Plate In the Philippines, nearly 2,000 cases have
3.19). Anthelminthic drugs should also be been documented from the Northern Luzon
given. The drug of choice for the treatment provinces from 1967 to 1990. Cases have also
of intestinal capillariasis is mebendazole, 200 been documented in Zambales and Southern
mg twice a day for 20 days. Alternatively, Leyte. Infections are acquired by eating
albendazole 400 mg may be given once daily uncooked small freshwater/brackish water
for 10 days. Relapses may occur if the treatment fish. Ilocano people enjoy eating bagsit and
regimen is not followed and completed. other fishes found in the lagoons. In Monkayo,
Compostela Valley Province, an outbreak
described as a “mystery disease” in 1998 resulted
in the death of villagers due to misdiagnosis.
Intestinal capillariasis was diagnosed in 17%
of the cases presenting with chronic diarrhea.
A more recently described endemic area in the
Philippines involved Zamboanga del Norte,
where more than 70 deaths were recorded and
4.9% of those examined in a parasitologic survey
were confirmed to have capillariasis. A few cases
have also been confirmed in Zamboanga del
Sur, Agusan del Sur, and Misamis Occidental.
Prevention and Control
Tissue Nematodes
Vicente Y. Belizario, Jr., Timothy M. Ting
be seen enclosed in a sheath, and having angular damage, and migrate towards the mosquito’s
curvatures with secondary kinks, and two nuclei head and proboscis. During a blood meal, larvae
at the tip of the tail. The column of indistinct emerge from the proboscis onto the skin of the
and confluent nuclei is composed of two rows. susceptible host and actively penetrate the skin
Adult male and female W. bancrofti worms through the bite wound to reach the lymphatic
are found tightly coiled in nodular dilated vessels and nodes where they develop into adult
nests (lymphangiectasia) in lymph vessels and worms. They are usually localized in the lymph
in sinuses of lymph glands. Adult females vessels of the lower extremities, inguinal lymph
produce microfilariae, which gain entrance to nodes, epididymis of males, and labia of females.
the peripheral blood circulation where they are Microfilariae migrate from the parent worm,
picked up by the appropriate mosquito vector through the walls of the lymphatics, and into
during a blood meal (Plate 3.22). Mosquitoes the neighboring blood vessels.
belonging to the genera Aedes, Culex, and The life cycle of B. malayi generally follows
Anopheles have been shown to be biologic the same pattern as that of W. bancrofti with a
vectors of Wuchereria. Microfilariae ingested few exceptions (Figure 3.10). Mosquito vectors
by the mosquito migrate to its muscles where of B. malayi belong to the genus Mansonia.
they develop into first (L1), second (L2), and Development of the microfilariae to the
third (L3) stage larvae. After 6 to 20 days infective stage in the mosquito takes about 2
of development, 3rd stage larvae force their weeks. Maturation time for the 3rd stage larvae
way out of the muscles, causing considerable to become adults takes about 3 to 9 months.
Thereafter, microfilariae are produced and may
be seen in the circulation.
Pathogenesis and Clinical Manifestations
and lymphangitis, individuals with this lymphatic endothelial cell proliferation and
syndrome also present with allergic reactions differentiation leading to collateralization.
such as hives, rashes, and blood eosinophilia. These lymphatic dysfunctions have been shown
Lymphatic localization is important to predispose infected individuals to secondary
in parasite survival because lymph is a less bacterial infections and trigger inflammatory
aggressive medium than blood: no platelets, no reactions in the skin and subcutaneous tissue,
complement system, incomplete coagulation leading to lymphedema and elephantiasis.
system, and no granulocytes; in addition, its A characteristic feature of chronic LF
flow is much less violent. Filarial adult worms infection is fibrosis and cellular hyperplasia
cause parasite-induced lymphatic dilatation in and around the lymphatic walls; these
(lymphangiectasia); this is a common feature changes are postulated to render lymphatic
of patent infection, though clinically apparent endothelial cells less effective at transporting
lymphedema is rarely seen. Another cardinal interstitial fluid, thereby contributing to the
feature of LF is lymphangiogenesis, where edema and collagen accumulation. Dead
live filarial parasites or filarial antigens induce and decalcifying adult worms elicit immune
Chapter 3: Nematode Infections 169
The drug’s mechanism of action is not well ivermectin alone. There is probably no added
understood, but it is clear that host components effect against adult worms in LF. DEC or
are necessary, such as the arachidonic acid ivermectin in combination with albendazole
pathway and the 5-lipoxygenase pathway. used in LF elimination programs has the added
Recent trials show that DEC has no role in the benefit of clearing soil-transmitted helminth
treatment and prevention of ADLA attacks in (STH) infections.
lymphedema. DEC is the treatment of choice Doxycycline and related antibiotics kill the
for the treatment of TPE and is given for 3 to endosymbiont Wolbachia, which is essential
4 weeks. for growth, development, embryogenesis, and
Adverse events (AEs) include fever, myalgia, survival of filarial worms. Treatment of LF with
headache, and sore throat or cough lasting 24 a course of doxycycline at 200 mg daily for 4 to 6
to 48 hours. These are mild and self-limiting, weeks results in long-term sterility and eventual
and may be treated symptomatically. These death of adult worms. Anti-Wolbachia therapy
AEs represent an immune response that is showed significant improvements in lymphatic
mainly due to the destruction of microfilaria pathology and a decrease in the severity of
that is similar to the Mazzotti reaction seen lymphedema and hydroceles. Studies have also
in onchocerciasis. There may also be AEs shown that prior treatment with doxycycline
associated with rapid killing of adult worms reduces the frequency and severity of AEs to
(AFL), which can lead to scrotal pain in men, DEC-albendazole. This relatively good safety
and systemic inflammation due to the release profile is due to the avoidance of parasite-
of Wolbachia. Direct adverse events due to the mediated or Wolbachia-mediated inflammatory
drug are rare. adverse reactions. Although anti-Wolbachia
Ivermectin is a drug primarily used in chemotherapy has many benefits especially in
the treatment of onchocerciasis, loiasis, and the treatment of individual patients, its use
strongyloidiasis. It is also effective against in community-based control and elimination
ectoparasites such as lice and scabies. Used in programs is hindered by the logistics of the
LF, it is highly effective and well tolerated at length of treatment and contraindications in
doses of 100 to 200 µg/kg for the reduction children and pregnant women.
of microfilaremia for up to 1 year. Ivermectin The treatment recommendations for
leads to hyperpolarization of glutamate-sensitive ADLA include bed rest, cooling the affected area
channels and immobilization of microfilaria. to relieve the pain, analgesics and antipyretics
AEs are similar to DEC but milder due to its for pain and fever, topical antibiotics and
relatively slower parasite clearance. It has no antifungals for superficial bacterial and fungal
proven action against adult worms and TPE. infections, systemic antibiotics (e.g., penicillin)
Albendazole is a broad-spectr um for moderate to severe cases, and elevation of
anthelminthic given orally that is effective the involved extremity. Enrollment in a hygiene
against nematodes, cestodes, and flatworms. education program dramatically reduces the
Its mechanism of action is via inhibition of incidence of ADLA and the progression of
polymerization of -tubulin and microtubule lymphedema to elephantiasis. A proper “foot
formation. A low dose of 400 mg used for care program” includes: (a) washing the affected
the treatment of most intestinal helminth limb twice a day with soap and water especially
infections decreases W. bancrofti microfilaremia the webs of toes and skin folds, and drying
progressively for 6 to 12 months. Based on with a clean cloth to remove moisture; (b)
current studies, combination with DEC or clipping nails often and keeping them clean; (c)
ivermectin reduces microfilarial loads in the preventing and promptly treating local injuries
periphery longer than treatment with DEC or and infections with topical agents; (d) regular
174 Medical Parasitology in the Philippines
use of properly fitting footwear; and (e) raising effects, and have not been adequately evaluated
the affected limb at night to reduce the swelling. in filariasis-endemic areas. Current WHO
In the setting of severe lymphedema and guidelines call for the complete surgical removal
elephantiasis, the hygiene education program of the tunica vaginalis to minimize or prevent
stated above may be supplemented with the recurrence.
use of compressive bandages, stockings, manual
Epidemiology
lymphatic drainage (massage), heat therapy,
and, in refractory cases, surgical procedures. About 120 million people worldwide
An estimated 27 million males suffer are affected by the disease, and more than
from hydroceles, and the prevalence is strongly 1 billion people are at risk (one-fifth of the
associated with the intensity of parasite world’s population), mostly in the poorest
transmission (microfilaremia prevalence). areas. Bancroftian filariasis accounts for 90%
Recent observations from Brazil, Egypt, and of cases in 83 endemic countries while the
Haiti indicate that many acute hydroceles Malayan filarial worm (and B. timori) causes
resolve spontaneously, and about 24% persist to the remainder. W. bancrofti affects more than
become chronic. Surgery is the recommended l00 million people in the tropical areas of India,
treatment for hydrocele, and if done properly, Southeast Asia, the Pacific Islands, Africa, and
is deemed curative. Other methods such as South and Central America. India has the largest
aspiration of fluid and injection of sclerosing number of cases. B. malayi and B. timori affect
substances are less effective, are associated with 12.5 million people in Southeast Asia (Figure
hydrocele recurrence, have unacceptable side 3.11). The prevalence of infection continues to
Figure 3.11. Distribution and status of preventive chemotherapy for lymphatic filariasis, worldwide, 2010
(Accessed from gamapserver.who.int)
Chapter 3: Nematode Infections 175
Dreyer G, Addiss D, Dreyer P, Noroes L. Basic compression for filarial lymphoedema. Nat
lymphedema management: treatment and Med J India. 2002;15(4):192–4.
prevention of problems associated with Taylor M, Hoerauf A, Bockarie M. Lymphatic
lymphatic filariasis. New Hampshire: filariasis and onchocerciasis. Lancet.
Hollis Publishing Company; 2002. 2010;376:1175–85.
Galvez Tan, J. The elimination of lymphatic The Global Alliance to Eliminate Lymphatic
filariasis: a strategy for poverty alleviation Filariasis. Lymphatic filariasis [Internet].
and sustainable development—perspectives 2010 [cited 2012 Mar 3]. Available from
from the Philippines. Filaria J. 2003; 2:12. http ://www.filariasis. org/index.pl
Hernandez L. Current status of filariasis in the World Health Organization. Control of
Philippines. Southeast Asian J Trop Med lymphatic filariasis: a manual for health
Pub Health. 1993;24:8-9. personnel. Geneva: World Health
Hoerauf A. Filariasis: new drugs and new Organization; 1987.
opportunities for lymphatic filariasis and World Health Organization. WHO technical
onchocerciasis. Curr Opin Infect Dis. report series 821, lymphatic filariasis: the
2008;21:673–81. disease and its control, fifth report of the
Houston R. Salt fortified with diethylcarbamazine WHO expert committee on filariasis.
(DEC) as an effective intervention for Geneva: World Health Organization; 1992.
lymphatic filariasis, with lessons learned World Health Organization. Tropical disease
from salt iodization programmes. Parasitol. research progress 1975–94, Highlights
2000;121(suppl):S161–73. 1993–1994, Twelfth programme report of
Jenson J, O’Connor R, Osborne J, Devaney the UNDP/World Bank. WHO Special
E. Infection with Brugia microfilariae Programme for Research and Training in
induces the apoptosis of CD4+ T Tropical Diseases (TDR). Geneva: World
lymphocytes: a mechanism of immune Health Organization; 1995.
unresponsiveness in filariasis. Euro J World Health Organization. WHO fact sheet
Immunol. 2002;32(3):858–67. on lymphatic filariasis. Geneva: World
Kron M, Walker J, Hernandez L, Torres E, Health Organization; 2000.
Libranda-Ramirez B. Lymphatic filariasis World Health Organization. The global
in the Philippines. Parasitol Today. elimination of lymphatic filariasis: the
2000;16(8):329–33. story of Egypt. global elimination of
Manjula Y, Kate V, Ananthakrisnan N. Evaluation lymphatic filariasis. Geneva: World Health
of sequential intermittent pneumatic Organization; 2003.
Chapter 3: Nematode Infections 179
Parastrongylus cantonensis
Vicente Y. Belizario, Jr., Francis Isidore G. Totañes
include the following slugs and snails: Achatina Although the mechanism by which humans
fulica (Plate 3.30) or giant African snail, get infected is not yet entirely clear, transmission
Hemiplecta sagittifera, Helicostyla macrostoma, is usually attributed to: (a) ingestion of the raw
Vaginilus plebeius, and Veronicella altae. Its mode mollusk intermediate host infected with the
of infection is by ingestion or active penetration. third stage larva; (b) ingestion of leafy vegetables
In the mollusk, larva eventually develops into contaminated with mucus secretions of the
the 3rd larval stage in about 12 days. mollusk carrying the infective stage (3rd larval
Chapter 3: Nematode Infections 181
Meningeal lesions may be appreciated Further studies showed that its prevalence
with the use of computed tomography (CT) in rats is less than 7%. The presence of P.
scan. CT scans may also reveal non-specific cantonensis as a parasite of rats and/or snails
cerebral edema and ventricular dilatation. has been reported in the following provinces
Magnetic resonance imaging (MRI) may show of Luzon: Batangas, Bulacan, Cavite, Ilocos
lesions with hyperintense T2 signal. Although Norte, Laguna, Mountain Province, Nueva
enzyme-linked immunosorbent assay (ELISA) Ecija, Pampanga, Pangasinan, Quezon, Rizal,
for the diagnosis of parastrongyliasis is still not Sorsogon, Tarlac, and Metro Manila. Two cases
commercially available, a dot-blot ELISA that of ocular parastrongyliasis have been reported
tests blood has been demonstrated to be 100% from the East Avenue Medical Center. The
sensitive and specific for use in epidemiological patients were blood relatives coming from
surveys. In addition, serum antigens from P. Isabela who have eating history of improperly
cantonensis can also be detected by immuno- cooked snails. The worms were identified at
polymerase chain reaction (PCR). the College of Public Health, University of the
Philippines Manila.
Treatment
Prevention and Control
No a n t h e l m i n t h i c t r e a t m e n t i s
recommended at present, although mebendazole The main preventive strategy against
and albendazole have been demonstrated to parastrongyliasis is through awareness and
effectively treat parastrongyliasis in China, education on proper eating habits and safe
Taiwan, and Thailand. Anthelminthic therapy food preparation. The public should be
has been shown to relieve symptoms and discouraged from eating raw or poorly cooked
reduce the duration of the disease. Ocular mollusks or unwashed vegetables. Hand
parastrongyliasis may require surgical removal washing after gardening should also be advised.
of worms from the eyes. Symptomatic treatment Farmers occasionally use molluscicides, such
with the use of analgesics and lumbar puncture as metaldehyde or iron phosphate food bait
can relieve the headaches experienced by the pellets to control intermediate hosts. Copper
patient with eosinophilic meningitis. Prednisone barriers against snails and slugs are also
30 mg daily is recommended, particularly in utilized by farmers to prevent contamination
severe cases with cranial nerve involvement. of vegetable and fruit crops. Health workers in
The anti-inflammatory and immunosuppressive endemic areas should also be educated on the
effects of steroids are helpful in mitigating the diagnosis, treatment, control, and prevention
disease process. of parastrongyliasis.
Epidemiology References
Human infection with P. cantonensis was Chen ER. Angiostrongyliasis and eosinophilic
first reported in 1945 by Nomura and Lin in meningitis in Taiwan: a review.. In: Cross
Taiwan. As a human parasite, P. cantonensis has JH, editor. Studies on angiostrongyliasis
also been documented in approximately 30 in East Asia and Australia. Taipei, Taiwan:
countries including Thailand, China, Tahiti, U.S. Naval Medical Research Unit No. 2,;
French Polynesia, USA, Cuba, New Caledonia, 1979. p. 57–73.
Japan, Australia, Vanuatu, India, and the Cross JH. Public health importance of
Philippines. Angiostrongylus cantonensis and its relations.
In the Philippines, Nishimura and Yogore Parasitol Today. 1987;367–9.
reported the presence of Parastrongylus in rats.
Chapter 3: Nematode Infections 183
Trichinella spiralis
Vicente Y. Belizario, Jr., Francis Isidore G. Totañes
The infective encysted larvae enter the After a few days, the female worm deposits
host through ingestion of raw or insufficiently larvae in the mucosa. The larvae penetrate the
cooked meat. The cysts are digested in the mucosa, pass through the lymphatic system into
stomach, and the larvae excyst either in the the circulation, and finally into striated muscles
stomach or in the small intestine. The larvae (Figure 3.14). In the muscles, the larvae grow
then burrow into the subepithelium of the villi and develop. After about 3 weeks, they start
where they undergo four molts. Maturation to coil into individual cysts. Encapsulation is
takes about 2 days, and adult worms begin to completed 4 to 5 weeks after infection. The larva
mate 5 to 7 days post infection. The female in the cyst remains viable for many years. The
produces eggs that grow into larvae in its uterus. average lifespan of the encysted larva is about 5
to 10 years, and can survive for up to 40 years in dyspnea, dysphagia, and difficulty in chewing.
humans. In humans, calcification of the collagen Occasionally, there is paralysis of the extremities
capsule in the infected muscle cell and the larva and splenomegaly. In severe cases, there may be
may occur. This process may be observed 6 to gastric and intestinal hemorrhages.
12 months after infection and may lead to the Larval migration into the heart muscle
destruction or death of the larva. can result in pericardial pain, tachycardia, and
electrocardiogram abnormalities. Pericardial
Pathogenesis and Clinical Manifestations
effusion, congestive heart failure, and other
The severity of symptoms depends on chronic heart abnormalities have also been
the intensity of infection. Patients with light observed. Neurological complications, which
infection, i.e., harboring up to 10 larvae, are are caused by small subacute cortical infarcts,
usually asymptomatic, while patients with may occur in chronic infections. Meningitis
moderate infection (50-500 larvae) show and meningoencephalitis may also develop.
symptoms. Infection with a few hundred In heavy infections, ocular disturbances,
larvae can result in gastroenteritis, diarrhea, diplegia, deafness, epileptiform attacks, and
and abdominal pain approximately two days coma may occur. In the convalescent phase,
post infection. Infection with 100 to 300 larvae fever, weakness, pain, and other symptoms
may lead to symptomatic trichinellosis, while start to abate. Full recovery is expected since
more than 1,000 to 3,000 larvae can result in trichinellosis is a self-limiting disease. However,
severe disease. protean neurologic signs arising from brain
Clinical manifestations vary depending on damage may persist.
the stage of the parasite. The clinical conditions Prognosis is good, especially in mild
are divided into three phases, namely: enteric infections. Death is uncommon except in
phase, invasion phase, and convalescent phase. cases of heart failure, encephalitis, or other
These correspond to the stages of: (a) incubation complications such as pneumonia or septicemia.
and intestinal invasion, (b) larval migration Low-grade or absent peripheral blood
and muscle invasion, and (c) encystment and eosinophilia is indicative of poor prognosis.
encapsulation.
Diagnosis
Symptoms in the enteric phase may
resemble those of an attack of acute food The most definitive diagnostic examination
poisoning, including diarrhea or constipation, is the demonstration of the larva through
vomiting, abdominal cramps, malaise, and muscle biopsy. Muscle biopsy is done through
nausea. During the invasion phase, the histological examination of 0.2 to 0.5 g of
migrating larvae and resulting metabolites lead muscle tissue. Digestion of muscle samples with
to immunological, pathological, and metabolic pepsin and hydrochloric acid can also be done
reactions. Inflammatory reaction to the infection to determine the number of larvae per gram
results in eosinophilia, which results in the of muscle, or to isolate larvae for molecular
release of histamines. Histamines, serotonins, characterization. The digestion technique,
bradykinins, and prostaglandins contribute to however, is limited to muscle larvae that are
an increase in vascular permeability, resulting about 10 to 12 days old (about 2-3 weeks post
in tissue edema. The cardinal signs and infection) since younger larvae may be destroyed
symptoms of trichinellosis include severe by the digestion fluid.
myalgia, periorbital edema, and eosinophilia. Non-specific laboratory tests to detect
Other typical signs and symptoms include eosinophilia, muscle enzymes (creatine
high remittent fever and chills, headache, phosphokinase, lactate dehydrogenase, and
Chapter 3: Nematode Infections 187
myokinase), and total IgE in serum may be children 2 years and older, albendazole should
useful in diagnosis. An algorithm for the be given at 10 mg/kg body weight. A treatment
diagnosis of individual cases is shown in Table cycle may be repeated five days after the initial
3.4. cycle in case of severe infection. Thiabendazole
is no longer used due to its associated adverse
Table 3.4. Algorithm for the diagnosis of the drug reactions.
probability of acute trichinellosis in humans Supportive treatment through analgesics
and antipyretics is commonly used to control
Group Symptom symptoms. Corticosteroids may be given with
A Fever, eyelid and/or facial edema, myalgia anthelminthics to control hypersensitivity
B Diarrhea, neurological signs, cardiac signs, reactions to the larvae, and may also be given
conjunctivitis, subungual hemorrhages,
cutaneous rash to treat acute vasculitis and myositis.
C Eosinophilia (>1,000 eosinophils/ml) and/ Epidemiology
or increased total IgE levels, increased
levels of muscular enzymes
Trichinella infections in humans have
D Positive serology (with a highly specific test),
seroconversion, positive muscular biopsy already been documented in 55 countries
worldwide. There are about 10,000 cases
reported each year, 0.2% resulting in mortality.
The diagnosis of trichinellosis is very Human trichinellosis occurs wherever meat
unlikely in the occurrence of only one symptom is a part of the diet. Outbreaks have been
from group A, B or C. Trichinellosis may be reported in Argentina, Bosnia-Herzegovina,
suspected in the presence of one symptom China, France, Laos, Romania, Spain, Sweden,
from group A or two from group B, and one Thailand, Turkey, Ukraine, Uzbekistan, and
from group C, while a diagnosis is probable Vietnam. Trichinella infection has never been
when there are three group A and one group documented in a small number of island
C symptoms. Diagnosis is highly probable in countries, including the Philippines.
the presence of three group A and two group Trichinellosis is primarily a zoonosis.
C symptoms. A diagnosis is confirmed in case Humans get infected after ingestion of raw
of three group A, two group C, and one group or insufficiently cooked meat from infected
D symptoms; or any of symptom from group animals. The infection is usually maintained in
A or B, and one from group C and one from a pig-to-pig or pig-to-rat-to-pig cycle.
group D.
Prevention and Control
Currently, enzyme-linked immunosorbent
assay (ELISA) is recommended for the diagnosis Health education is an important
of trichinellosis. Confirmation of ELISA- component of prevention and control
positive samples may be done through Western measures against this parasitic infection. It
blot technique. Latex agglutination technique is recommended that meat be cooked at a
may be utilized for rapid (<1 hour) confirmation minimum of 77°C (170°F). Freezing is another
of trichinellosis. way to kill larvae. Storage at –15°C for 20 days
Treatment
or –30°C for six days is suggested. Smoking,
salting, or drying meat is not effective. Other
The treatment of choice for trichinellosis control measures include regular animal
is mebendazole 5 mg/kg body weight daily, or monitoring (meat inspection or detection of
albendazole 15 mg/kg body weight per day circulating antibodies), keeping pigs in rat-free
in two divided doses, for 10 to 15 days. For pens, and proper disposal of suspected carcasses.
188 Medical Parasitology in the Philippines
Anisakis spp.
Winifreda U. de Leon
Outside of these more common locations, When the oropharynx is involved, the
the larvae have been found invading the presentation is commonly known as “tingling
oropharynx, esophagus, and colon. This throat syndrome.”
condition is referred to as ectopic anisakidosis.
Chapter 3: Nematode Infections 191
Acute allergic reactions have been reported There have been reported cases from Egypt as
in anisakidosis, when biochemical substances well. The condition is more common in the
are released by the parasites into the flesh of the coastal population of these countries due to the
host fish. Urticaria, asthma, conjunctivitis, and consumption of raw and inadequately cooked
contact dermatitis have been observed among fish. In the Philippines, anisakidosis has not yet
workers in fish and marine products processing been documented.
factories and are forms of occupational Considered to be high risk for anisakidosis
hypersensitivity. are fish dishes such as Japanese sushi and
sashimi, pickled anchovies, gravlax, salted and
Diagnosis
smoked herring, and possibly fish bagoong as
Anisakidosis should be highly suspected well as fish kinilaw in the Philippines. Salting,
if there is a recent history of eating raw marinating, pickling, smoking, and other curing
or improperly cooked fish or squid prior techniques are effective against some foodborne
to the acute onset of symptoms. Through pathogens, but not for anisakid larvae.
gastroscopic/endoscopic examination, the larvae Several species of marine fish and
can be visualized and removed for identification. cephalophods (squid) have been found to be
Intestinal anisakidosis is more difficult to infected with anisakid larvae. Mostly involved
establish, and may be diagnosed only after are the Pacific/Atlantic cod, Pacific halibut, red
surgery. Serological procedures to detect specific snapper, mackerel, eels, salmon, and anchovies.
antibodies have been employed with good In the Philippines, anisakid larvae have been
results, such as enzyme-linked immunosorbent found in blue mackerel scad (galunggong), but
assay (ELISA), and radioallergosorbent test the prevalence and density of the larvae seems
(RAST). to be seasonal. Infected eels (palos) have been
found in Cebu, Mactan, and Leyte.
Treatment
The increasing number of cases is believed
The main approach is to mechanically to be due to multi-factorial causes. Deep
remove the larva using endoscopic forceps. sea marine mammals are currently being
It is strongly recommended that endoscopic protected. Therefore, there has been an
removal be done early to avoid invasion of increase in the population of the definitive
the gastric submucosa. Corticosteroids have hosts. The worldwide distribution of the
been used in cases of allergic anisakidosis but anisakid nematodes may result in widespread
clinical trials have not been performed. A contamination of marine fish and squid. The
possible therapeutic benefit from albendazole increasing popularity of the consumption of
for intestinal anisakidosis has been reported sushi and sashimi globally may also contribute
in Spain. to the increase in cases.
Epidemiology Control and Prevention
Human anisakidosis is not a very common In order to best control and prevent
infection, but it has been reported from all anisakidosis, marine fish, squid, and
over the world. In Asia, the majority of reports shellfish must be thoroughly cooked prior
have come from Japan and Korea, while in to consumption. For raw or undercooked
Europe, human cases have been identified preparations, fish and shellfish must undergo
in the Netherlands, France, Germany, Italy, blast freezing at –35°C for at least 15 hours.
Spain, and the United Kingdom. It has also Freezing at –20°C for 7 days has also been
been reported in North and South America. found to be effective. Furthermore, raising the
192 Medical Parasitology in the Philippines
awareness of both producers and consumers of Kliks MM. Anisakiasis in the western United
potentially infectious products through health States: four new case reports in Calufornia.
education may be helpful. Am J Trop Med Hyg. 1983;32:526.
Oshima T. Anisakiasis—is sushi bar guilty?
References
Parasitol Today. 1987;3:44.
Amato Neto V, Amato JG, Amato VS. Probable Pacios E, Arias-Diaz J, Zuloaga J, Gonzalez-
recognition of human anisakiasis in Armengol J, Villarroel P, Balibrea JL.
Brazil. Rev Inst Med Trop Sao Paulo. Albendazole for the treatment of anisakiasis
2007;49(4):261–2. ileus. Clin Infect Dis. 2005;41(12):1825–
Audicana TM, Kennedy MW. Anisakis simplex 6.
from obscure infectious worm to inducer Petersen F, Palm H, Cuzi MA. Flesh parasites
of immune hypersensitivity. Clin Microbiol of fish in Central Philippine Waters. Dis
Rev. 2008;21(2):360–79. Aquat Org. 1993;15:81–6.
Jueco NL, Bobis TA , Ramirez LM. Seasonal Sakanari JA, Mckerrow JH. Anisakiasis. Clin
prevalence and density of Anisakis larvae Micro Rev. 1989;2:278.
in fish (galunggong) sold in public Velasquez CC. Resume of findings on Anisakis
markets in Manila. J Philipp Med Assoc. larvae. Philipp Zool Soc. 1976;4:17.
1971;47:467–76.
Chapter 3: Nematode Infections 193
Toxocara canis
Toxocara cati
Ernesto C. Balolong, Jr., Winifreda U. de Leon
asymptomatic and eosinophilia is less frequent. In addition to the blood test, diagnosis of
Usual symptoms may include: coughing, toxocariasis includes identifying the presence
wheezing, chronic or recurrent abdominal pain, of typical clinical signs of OLM or VLM and a
hepatomegaly, sleep disturbances, headache, history of exposure to cats and dogs.
malaise, and anorexia. Manifestations such Medical imaging techniques can be used
as polyarthralgias, monoarthritis, migratory to detect and localize granulomatous lesions
cutaneous lesions, and small-vessel vasculitis due to Toxocara larvae. Abdominal ultrasound
may coincide with VLM. had shown multiple hypoechoic areas in
A n o t h e r re c o g n i z e d s y n d r o m e i s livers of patients who initially presented with
neurological toxocariasis, which is also one of hepatomegaly, eosinophilia, and a positive
the causes of encephalitis. Larvae may migrate Toxocara serology. Using computed tomography
to the brain, meninges, and may be found (CT), hepatic lesions appear as low-density
present in the cerebrospinal fluid (CSF). Solitary areas. In the CNS, more sensitive magnetic
mass lesions may be observed in the brain resonance imaging (MRI) may reveal granulomas
tissue causing seizures, static encephalopathy, appearing as hyper-intense areas.
arachnoiditis, spinal cord lesions, optic neuritis,
Treatment
and eosinophilic meningitis, a form of aseptic
meningitis in which the WBCs in the CSF Visceral toxocariasis can be treated with
mainly consist of eosinophils. antiparasitic drugs such as albendazole or
mebendazole, usually in combination with
Diagnosis
anti-inflammatory medications. Although
Toxocariasis in human is difficult to most patients with toxocariasis recover without
diagnose because the symptoms of toxocariasis therapy, for those patients with neurological
are similar to the symptoms of other infections. toxocariasis or lung or cardiac complications,
Fecalysis cannot be utilized in the evaluation of anthelminthic treatment is mandatory. Patients
human toxocariasis as eggs are not produced or presenting with inflammatory reaction due to
excreted. Definitive diagnosis of toxocariasis is higher doses of praziquantel or albendazole
based on the detection of larvae from biopsy were found to respond very well to steroids.
tissues, but this test is time-consuming and Treatment of ocular toxocariasis is more difficult
difficult to perform. Currently, diagnosis is and usually consists of measures to prevent
commonly based on clinical and serologic progressive damage to the eye.
tests. Commercial immunoglobulin G (IgG)
Epidemiology
enzyme-linked immunosorbent assay (ELISA)
kits are available wherein Toxocara excretory- Human toxocariasis is primarily a soil-
secretory (TES) antigens are used to detect transmitted zoonosis with the infection
IgG antibodies against the larvae. In general, more commonly found in children than
however, these assays do not have adequate adults. Children are more at risk because
specificity for use in countries where other soil- of their tendency to play in soil and exhibit
transmitted helminths are endemic. Western geophagia or soil eating, thus increasing the
blot is more specific but is unable to differentiate risk of toxocariasis. Cases are more frequently
between new and old infections. Polymerase seen in children living in homes and in
chain reaction (PCR) has good results in the neighborhoods where dogs and puppies are not
identification of Toxocara species in tissues using dewormed. Poor personal hygiene as well as
animal models. consumption of inadequately washed vegetables
196 Medical Parasitology in the Philippines
antigens (TES-26, TES-30USM, and TES- Vidal J, Sztajnbok, Seguroa AC. Eosinophilic
120). J Clin Microbiol. 2009;47(6):1712– meningoencephalitis due to Toxocara canis:
17. a case report and review of literature. Am J
Rai SK, Uga S, Kataoka N, Matsumura T. Trop Med Hyg. 2003;69(3):341–43.
Atlas of medical parasitology. 1st ed. Kobe
(Japan): Kyokuseisya Co., Ltd.; 1996.
Chapter 4
Cestode Infections
Intestinal Cestodes
Winifreda U. de Leon
Taenia spp.
Taenia saginata
198
Chapter 4: Cestode Infections 199
may result in intestinal obstruction. Individual Gravid proglottids are pressed or flattened in
T. saginata proglottids are actively motile between two glass slides and are examined
and they have been documented to cause against the light. This will allow one to have
obstruction in the bile and pancreatic ducts, a rough count of the lateral branches from the
as well as the appendix. The sight of actively main uterus. Injection of India ink through
motile proglottids in the perianal area and in the genital pore will help one make an accurate
the undergarments may result in anxiety and count of the lateral branches of the uterus
distress. (15-20 for T. saginata and 7-13 for T. solium).
Mature segments can be stained to demonstrate
Diagnosis
the vaginal sphincter for T. saginata and the
Specific diagnosis rests on identifying the accessory ovarian lobe for T. solium.
characteristic proglottids, eggs or scolex. The Examination of the stool can be done for
first specimen usually brought in by patients are the presence of eggs, but eggs are irregularly
the gravid proglottids, either single or in chains. passed out with the stools. Concentration
They are passed out with the feces or may techniques like the formalin-ether/ethyl
be recovered in the patient’s undergarments. acetate concentration technique will be useful
Chapter 4: Cestode Infections 201
drinking alcohol is a delicacy. Neurocysticercosis Eom KS, Rim HJ. Morphologic description of
has been reported in local literature. There has Taenia asiatica. Korean J Parasitol. 1993;
been one report of ocular cysticercosis. 31:1.
Flisser A. Neurocysticercosis in Mexico.
Prevention and Control
Parasitol Today. 1988;4:13l.
Prevention and control of taeniasis may G a r g R K . Me d i c a l m a n a g e m e n t o f
appear simple but may be difficult to implement. n e u r o c y s t i c e r c o s i s . Ne u r o In d i a .
Thorough cooking of meat is a primary 2001;49:329–337.
measure. Freezing at –20°C for 10 days kills the Mahmoud AA. Tropical and geographical
cysticerci. Sanitary inspection of all slaughtered medicine companion handbook. 2nd ed.
pigs, cows, and cattle should be done. Meat Singapore: McGraw Hill Book Co.; 1993.
inspection should include examination of the McManus DP, Bowles J. Asian (Taiwan)
liver as well. Taenia species or strain? Parasitol Today.
1994;10(7):273–275.
References
Jubelt B, Miller JR. Parasitic infections. In:
Arambulo PV, Cabrera BD, Cabrera MG. The Rowland LP, editor. Merritt’s Neurology.
use of mebendazole in the treatment of 10th ed. Philadelphia: Lippincott Williams
Taenia saginata taeniasis in an endemic and Wilkins; 2000.
area in the Philippines. Acta Trop. Pawlowski ZS. Perspectives on the control of
1978;35(3):281–286. Taenia solium. Parasitol Today. 1990;6(12):
Arambulo PV, Cabrera BD. Studies on the 311–313.
zoonotic cycle of Taenia saginata taeniasis Quimosing EM, Conde BJ, Ranoa CP, Cross
and cysticercosis in the Philippines. Int J JH. A case of subcutaneous and cerebral
Zoonosis. 1976;3:77–108. cysticercosis treated with praziquantel. Phil
Beaver PC, Jung RC, Cupp EW. Clinical J Microbiol Infect Dis. 1984;13(l):25–35.
parasitology. 9th ed. Philadelphia: Lea & Roberts LS, Janovy J. Foundations of
Febiger; 1984. parasitology. 5th ed. Dubuque: Wm. C.
Belding DL. Textbook of parasitology. 3rd Brown Publishers; 1996.
ed. New York: Appleton-Century Crofts; Strickland GT. Hunter’s tropical medicine
1965. and emerging infectious diseases. 8th ed.
Bengzon AR, Perlas AP, Reyes VA. Cysticercosis Philadelphia: W. B. Saunders; 2000.
cerebri in the Philippines. Acta Med Tsang VC, Brand JA, Boyer AE. An enzyme
Philipp. 1965;27(l–4):1. linked immunoelectrotransfer blot assay
Cabrera BD. Case report: Multiple infection and glycoprotein antigens for diagnosing
with adult Taenia solium. Acta Med Philipp. human cysticercosis (T. solium). J Infect
1965;1(3):147–150. Dis. 1989;159:50.
Corona T, Lugo R, Medina R, Sotelo J. Single-day Urbina EC. Ocular cysticercosis. Phil J
praziquantel therapy for neurocysticercosis. Ophthamology. 1988;17(4):153–155.
N Engl J Med. 1996;334:125. White AC Jr. Neurocysticercosis: a major cause
of neurological disease worldwide. Clin
Infect Dis. 1997;24:101–113.
Chapter 4: Cestode Infections 207
Hymenolepis nana
Plate 4.6. Hymenolepis spp. scolex Plate 4.7. Hymenolepis spp. gravid segment
(Courtesy of the Department of Parasitology, (Courtesy of the Department of Parasitology,
UP-CPH) UP-CPH)
208 Medical Parasitology in the Philippines
Hymenolepis diminuta
Human infection occurs worldwide but Prevention and control measures include
is more common among children than adults rodent control, elimination of the insect
in poor communities with rat infestation. It intermediate hosts, protection of food, especially
probably occurs by accidental ingestion of grain the precooked cereals from such insects, sanitary
beetles infesting dried grains, dried fruits, flour, disposal of human waste, and treatment of
and cereals. In a nationwide survey of rats in human cases.
the Philippines, prevalence of H. diminuta was
found to be about 8%.
212 Medical Parasitology in the Philippines
Dipylidium caninum
Pathogenesis and Clinical Manifestations of the egg capsules is not recommended, since
the gravid proglottids do not disintegrate in the
Infection is rarely heavy and symptoms
intestines but in the environment. Egg capsules
are minimal. Slight intestinal discomfort,
are rarely recovered from the stool.
epigastric pain, diarrhea, anal pruritus, and
allergic reactions have been reported. While Treatment
most patients are asymptomatic, moderate
Treatment consists of praziquantel 5 to 10
eosinophilia has been reported.
mg/kg given as a single dose.
Diagnosis
Epidemiology
Diagnosis is established upon recovery
Human infection is rare but has been
of the characteristic gravid proglottids passed
reported in European countries, USA, Argentina,
out singly or in chain. Gravid proglottids may
Rhodesia, China, and the Philippines. Infants
crawl out of the anus, and may be passed out
and very young children are usually infected
involuntarily. Proglottids should be pressed
because of their close contact with their pet
or flattened between two glass slides for
cats and dogs. Likely, transmission could have
examination. Stool examination for the presence
214 Medical Parasitology in the Philippines
occurred through hand to mouth contamination city of Manila showed a prevalence of 5.19 to
or accidentally swallowing the arthropod hosts 36.0%, while dissection of dog and cat fleas for
when hugging and kissing the animal. Parents cysticercoids showed only a prevalence of 2.4%.
usually observe the presence of actively motile
Prevention and Control
proglottids in children feces or underwear.
Adults are not commonly infected possibly Periodic deworming of pet cats and dogs is
because of age tolerance against the parasite. recommended. Insecticide dusting of dogs and
In the Philippines, the first human infection cats are effective against fleas. The potential
was reported as early as 1912 by M.P. Mendoza- danger of playing with pets must be included
Guanzon in a child. Surveys of dogs in the in the health education of children.
Chapter 4: Cestode Infections 215
Raillietina garrisoni
Diphyllobotrium latum
Plate 4.14. Diphyllobothrium latum scolex Plate 4.15. Diphyllobothrium latum egg
(Courtesy of the Department of Parasitology, (Courtesy of the Department of Parasitology,
UP-CPH) UP-CPH)
218 Medical Parasitology in the Philippines
(Figure 4.6), a ciliated embryo, which is ingested intestinal wall and reaches maturity in about
by freshwater copepods of the genera Cyclops and 3 weeks.
Diaptomus. A procercoid larva develops in the
Pathogenesis and Clinical Manifestations
copepod. The procercoid measures 550 μm and
still retains the three hooklets in the cercomer, Infections are usually limited to one worm,
a caudal attachment organ. The copepod is although there have been reports of mechanical
in turn ingested by fish. The procercoid larva obstruction due to a large number of worms.
migrates through fish tissues and develops into Infected individuals may show no signs of
a plerocercoid larva in the muscles and viscera. disease. Some, however, may experience nervous
The plerocercoid larva or sparganum measures disturbances, digestive disorders, abdominal
20 mm or more and appears glistening, opaque discomfort, weight loss, weakness, and anemia.
white, and unsegmented. Fish with the infective Symptoms may be due to absorbed toxins or
plerocercoid larva is ingested raw by a definitive by-products of degenerating proglottids, or due
host like man, dog, cat, and other mammals. to mucosal irritation.
Carnivorous fish may serve as paratenic or D. latum infection results in
transport hosts as well. Among fish intermediate hyperchromic, megaloblastic anemia with
hosts are perch, trout, salmon, and pike. In the thrombocytopenia and leukopenia. Anemia
definitive host, the plerocercoid attaches to the seen in diphyllobothriasis is typically similar to
Chapter 4: Cestode Infections 219
that seen in Vitamin B12 deficiency and could be for the propagation of the infection in the
mistaken for pernicious anemia. Worms located endemic areas.
high up in the jejunum compete effectively with D. latum is prevalent in the temperate zones
the host for the Vitamin B12 in the diet. If worms where the population has a habit of eating raw
are pushed further down the intestines, with or improperly cooked fish. It is present in the
treatment, anemia is relieved. The vitamin B12 Baltic countries, Switzerland, Romania, and
content of D. latum is approximately 50 times the Danube Basin. In Asia, it can be found in
that of T. saginata. Russia, Turkistan, Israel, Northern Manchuria,
and Japan. In the Americas, it can be found in
Diagnosis
Chile, Argentina, and in some North American
Residence in or travel to an endemic area, states and Canada. Seven human infections have
a raw-fish diet, and a pernicious type of anemia been documented in the Philippines.
may be suggestive of diphyllobothriasis. Definite
Prevention and Control
diagnosis is made on finding the characteristic
operculated eggs or on occasion, proglottids in All freshwater fishes should be thoroughly
stools. Sometimes, proglottids may be vomited. cooked. Freezing for 24 to 48 hours at a
Since eggs are usually numerous, direct fecal temperature of –18°C kills all plerocercoids.
smears usually suffice. The Kato technique is In endemic areas, prevention should center
also useful in demonstrating eggs. on controlling the source of infection, proper
To d i f f e r e n t i a t e a n e m i a d u e t o disposal of sewage and marketing of fish.
diphyllobothriasis from pernicious anemia,
References
examination of the gastric juice for the presence
of free hydrochloric acid is useful. Pernicious Beaver PC, Jung RC, Cupp EW. Clinical
anemia is associated with achlorhydria. parasitology. 9th ed. Philadelphia: Lea &
Febiger; 1984.
Treatment
Belding DL. Textbook of parasitology. 3rd
The drug of choice is praziquantel as 5 to ed. New York: Appleton-Century Crofts;
10 mg/kg single dose. The criterion for cure is 1965.
recovery of the scolex in feces after treatment. Garcia EY, Africa CM. Diphyllobothrium latum
If the scolex is not recovered, a repeat stool (Linnaeus, 1758) Luhe, 1910 in a native
examination is done after 3 months to be certain Filipino. Phil J Sci. 1935;57:451–7.
that the patient is no longer infected. Hinz E. Human helminthiases in the Philippines.
Berlin: Springer-Verlag; 1984.
Epidemiology
Mahmoud AA. Tropical and geographical
Human infection is dependent on the medicine companion handbook. 2nd ed.
presence of human or animal definitive hosts, Singapore: McGraw-Hill Book Co.; 1993.
the presence of suitable intermediate hosts, Neva FA, Brown HW. Basic clinical parasitology.
dietary habits, and amount of pollution of fresh 6th ed. Connecticut: Appleton & Lange;
waters. The preference for eating raw fish and 1994.
the lack of sanitary toilet facilities contribute Roberts LS, Janovy J. Foundations of
to the transmission of the parasite. Although parasitology. 5th ed. Dubuque: Wm. C.
other mammalian hosts like dogs, cats, and Brown Publishers; 1996.
bears exist as reservoir hosts, man is responsible
220 Medical Parasitology in the Philippines
Extraintestinal Cestodes
Vicente Y. Belizario, Jr., Francis Isidore G. Totañes
organs such as the lungs and the brain, the worldwide. Cystic echinococcosis is most
serodiagnostic reactivity is lowered, decreasing prevalent in countries in the temperate
the reliability of this adjunctive diagnostic test. zones, such as southern South America, the
Detection of IgG antibodies to hydatid cyst Mediterranean, southern and central parts of
fluid-derived native or recombinant antigen B Russia, Central Asia, China, Australia, and
subunit, through ELISA or immunoblot, is the parts of Africa. Reemergence of cases have
current gold standard serology for human cystic been reported in Bulgaria, where the incidence
echinococcosis. of echinococcosis in children increased from
0.7 to 5.4/100,000 between the 1970s and the
Treatment
mid-1990s. Similarly, prevalence of infected
Surgical resection is still considered canines in Wales doubled between 1993 (3.4%)
the preferred treatment for echinococcosis and 2002 (8.1%).
presenting with a large (>10 cm in diameter) Filipinos who have traveled to or worked
liver cyst, secondary infection, or cysts in in endemic areas may get infected. A 35-year
extrahepatic sites. Small (<7 mm in diameter), old Filipino overseas contract worker in the
isolated cysts, uncomplicated cysts, and Middle East presented with a right hilar mass
patients with negative serology respond best to on routine chest x-ray. Thoracotomy showed a
chemotherapy with benzimidazole compounds. 10 cm by 6 cm cystic mass containing hydatid
Treatment with albendazole (10-15 mg/kg/ sand. Another Filipino overseas contract worker
day) or mebendazole (40-50 mg/kg/day) from Iraq presented with a growing mass in
for a minimum of three months has been the hip area. Biopsy results showed presence of
demonstrated to be effective. Percutaneous hydatid sand. More recently, a Filipino female,
aspiration, injection, re-aspiration (PAIR) with no apparent history of travel to an endemic
technique may be indicated for patients with area, consulted her physician for neurologic
single or multiple cysts in the liver, abdominal symptoms. Histopathologic findings of tissue
cavity, spleen, kidney, or bones, who cannot obtained during neurosurgery also showed the
undergo surgery. This technique involves: (a) presence of hydatid sand.
ultrasound-guided percutaneous puncture, (b)
Prevention and Control
aspiration of substantial amounts of cystic fluid,
(c) injection of a protoscolicidal agent (e.g., Prevention is achieved by reducing the
95% ethanol or hypertonic saline) for at least 15 infected populations and by minimizing
minutes, and (d) re-aspiration. Treatment with opportunities for transmission. Regular testing
PAIR plus albendazole or mebendazole has been and quarantine, and treatment of dogs with
shown to have greater efficacy and lower rates praziquantel in endemic areas are important
of morbidity, mortality, and disease recurrence. control strategies that have resulted in the
reduction of echinococcosis cases. To minimize
Epidemiology
transmission, dogs should not be allowed in
Cystic echinococcosis is the most common slaughterhouses, and refuse from these facilities
presentation of echinococcal infection in should be sterilized or properly disposed. Health
humans, accounting for >95% of global cases, education should include knowledge on the
with a burden of disease of about one million mode of transmission, and should emphasize
disability-adjusted life years (DALYs). There the danger of intimate contact with dogs.
are approximately 2 to 3 million cases of New strategies for the control and prevention
human cystic echinococcosis, and 0.3 to 0.5 of echinococcosis include vaccination of
million cases of human alveolar echinococcosis livestock, which has been proven to provide
224 Medical Parasitology in the Philippines
>95% protection against E. granulosus, as well Ito A, Sako Y, Ishikawa Y, Nakao M, Nakaya
as the development of more sensitive diagnostic K. Differential serodiagnosis of cystic
techniques for definitive and human hosts. and alveolar echinococcosis using ntrtive
and recombinant antigens in Japan.
References
Southeast Asian J Trop Med Public Health.
Ahluwalia BK, Khurana AK, Gupta NC, 2001;32(Suppl2):111–5.
Mehtani VG. Hydatid cyst of the orbit. Lightowlers MW, Flisser A, Gauci CG, Heath
Philipp J Ophthalmol. 1989;18(4):145–6. DD, Jensen O, Rolf R. Vaccination against
Akkiz H, Akinoglu A. Colakoglu S, Demirytirek cysticercosis and hydatid disease. Parasitol
H, Yagnrur O. Endoscopic management Today. 2000;16(5):191–5.
of biliary hydatid disease. Can J Surgery. Mondragon-dela Pena C, Ramos-Solis S,
1996;39:287–92. Barbosa-Cisneros O, Rodriguez-Padilla
Budke CM. Global socioeconomic impact of C, Tavizon- Garcia P, Herrera-Esparza R.
cystic echinococcosis. Emerg Infect Dis. Echinococcus granulosus down regulates
2006; 12:296–303. the hepatic expression of inflammatory
Canete R, Escobedo AA, Almirall P, Gonzalez cytokines IL- 6 and TNF alpha in BALB/c
ME, Brito K, Cimerman S. Mebendazole in mice. Parasite. 2002;9(4):351–16.
parasitic infections other than those caused Moro PL, Schantz PM. Echinococcosis:
by soil-transmitted helminths. Trans R Soc historical landmarks and progress in
Trop Med Hyg. 2009;103:437–42. research and control. Ann Trop Med
Center for Disease Control and Prevention— Parasitol. 2006;100:703–14.
Division of Parasitic Diseases. Echinococcosis Moro PL, Schantz PM. Echinococcosis: a
[Internet]. 2011 [cited 2012 Mar 3]. review. Int J Infect Dis. 2009;13:125–33.
Available from http://www.dpd.cdc.gov/ Romig T, Dinkel A, Mackenstedt U. The
dpdx/html/Echinococcosis.htm present situation of echinococcosis in
Craig PS, McManus DP, Lightowlers MW, Europe. Parasitol Int. 2006;55:S187–91.
Chabalgoity JA, Garcia HH, Gavidia Schantz PM, Gottstein B, Ammann R, Lanier
Cm, et al. Prevention and control of A. Hydatid and the Arctic. Parasitol Today.
cystic echinococcosis. Lancet Infect Dis. 1991;7:35–6.
2007;7:385–94. Wang Y, Bradshaw I, Rogan MT, Craig PS.
Dalisay JS. Pulmonary echinococcosis (a case Rapid dot-ELISA for the detection of
report). Chest Dis. 1985;14(4):148–51. specific antigens in the cyst fluid from
Ito A, Wandra T, Sato MO, Mamuti W, Xiao human cases of cystic echinococcosis. Ann
N, Sako Y, et al. Towards the international Trop Med Parasitol. 2002;96(7):691–4.
collaboration for detection, surveillance World Health Organization. International
and control of taeniasis, cysticercosis and classification of ultrasound images in cystic
echinococcosis in Asia and the Pacific. echinococcosis for application in clinical
Southeast Asian J Trop Med Public Health. and field epidemiological settings. Acta
2006;37(suppl 3):82–90. Trop. 2003;85:253–61.
Chapter 4: Cestode Infections 225
Spirometra spp.
Winifreda U. de Leon
released, infects Cyclops and develops into the cm in length. When the larvae are flattened, a
procercoid larva. Once the infected Cyclops spatulate scolex can be appreciated, together
are ingested by the secondary intermediate with pseudosegmentation, and a slit like
hosts such as frogs, snakes, and chickens, the invagination at the anterior end. Species
procercoid larva develops into the plerocercoid identification, however, can only be done
larva which is also known as sparganum (pl. through experimental animal infection.
spargana). If the infected tissues of the second
Treatment
intermediate host are ingested by the definitive
host (cats and dogs), the plerocercoid larva The main form of treatment is surgical
develops into an adult worm. These adults are removal of the larvae from the infected tissues.
usually mistaken for adult Diphyllobothrium Praziquantel has been recommended, but its
latum, although Spirometra sp. adults are efficacy in humans has not been proven.
shorter.
Epidemiology
Pathogenesis and Clinical Manifestations
Cases of sparganosis have been reported
Humans may be infected through: (a) worldwide: in Africa, India, Holland, Australia,
drinking water containing Cyclops or copepods and South America. In Asia, the majority
infected with procercoid larvae; (b) eating of cases came from Japan, Korea, Thailand,
infected second intermediate hosts like frogs, Malaysia, and Indonesia.
toads, or snakes containing the plerocercoid The first case reported in the Philippines
larvae; (c) applying plerocercoid infected flesh was in 1935, when a sparganum was recovered
of frogs and snakes as poultices on sores on the from the abdominal wall of a seminarian
eye, vagina, and skin resulting in subsequent originally from Pulilan, Bulacan. The second
penetration into cutaneous tissues; and (d) case, reported in 1950, was that of a fisherman
consumption of infected flesh of paratenic hosts from Libon, Albay, presenting with a 4 cm lower
like wild pigs. The resulting condition is called chest lump. The third case, reported in 1953,
sparganosis. was that of a 50-year old nun, also from Pulilan,
The larvae may be found in any part of Bulacan, complaining of an erythematous,
the body. Most commonly, they are found in slightly painful, pruritic mass in the inner aspect
and about the eyes, in the subcutaneous and of the thigh. Although two of the cases were
muscular tissues of the thorax, abdomen, thighs, from the same place, it was possible that the
inguinal region, and in the viscera. Patients may nun got infected during her stay as a missionary
complain of painful edema due to migrating in Mindanao. A fourth case, reported in 1962,
larvae, hence, the condition is also known as was that of a 46-year old female with a slightly
migrating tumor. Local indurations, periodic painful, subcutaneous nodule at the base of the
giant urticaria, edema, and erythema with neck. In the late 1970’s, and the early 1980’s,
chills, fever, and high eosinophilia may be seen two more cases of human sparganosis were
in patients. confirmed at the Department of Parasitology,
College of Public Health, University of the
Diagnosis
Philippines Manila.
Sparganosis is diagnosed through the In all six cases, the spargana were motile
recovery of the plerocercoid larvae from upon excision of the mass. With the last two
infected tissues. The larvae that are opaque cases, the spargana showed the typical solid
and glistening white usually measure about 3.5 body with worm-like appearance. There
Chapter 4: Cestode Infections 227
Trematode Infections
Blood Flukes
Edsel Maurice T. Salvaña, Vicente Y. Belizario, Jr.
228
Chapter 5: Trematode Infections 229
host when the host comes into contact with to 2,000 immature eggs/day in the branches
infested fresh water. Cercariae then lose their of the portal vein. These require 10 to 12 days
tails and transform into schistosomula and enter to mature and embryonate. Eggs deposited
superficial lymphatic vessels or subcutaneous
veins and reach the lungs. Most authors believe
that from the pulmonary circulation, the
schistosomules migrate intravascularly to reach
the portal vein where they mature. However,
there is some evidence that schistosomules can
escape from the lungs into the pleural cavity and
pass through the diaphragm into the liver to
reach the portal vein. In the portal circulation,
schistosomules differentiate into male and
female forms and pair up, with the larger female Plate 5.1. Schistosoma japonicum male (left)
occupying the gynecophoric canal on the adult and female (right) (Courtesy of the Department
male (Plate 5.1). Each female fluke deposits 500 of Parasitology, UP-CPH)
230 Medical Parasitology in the Philippines
The mechanism by which snail intermediate shed cercariae. Mortality among infected snails
hosts are located and infected by miracidia, as is increased in comparison with uninfected
well as what may divert them from infecting snails. Infected Oncomelania have decreased
snails has not been well-elucidated. Although egg-laying capacity.
it is postulated that secretions or excretions Mature cercariae emerge from daughter
of O. h. quadrasi attract the miracidia, but sporocysts and escape from the snail into fresh
these chemotactic molecules have not yet been water. The cercaria has a body and a forked tail.
identified. In early experiments performed The main body measures from 100 to 500 µm
in Leyte, initial contact between a single in length and 40 to 60 µm transversely. The
miracidium placed equidistant from O. h. tail trunk is 140 to 150 µm by 20 to 35 µm;
quadrasi and other snails was purely random. and the fork is 50 to 70 µm long. The cercaria
After contact with soft parts of the snail, has an oral sucker, which occupies the anterior
miracidial penetration is effected by movement end of the body, and a small ventral sucker.
and the lytic action of cephalic gland secretions. Cercarial penetration is mediated by lytic
Factors that influence the infection of snails by enzymes secreted by cephalic glands and aided
miracidia include the age of the snails and the by muscular activity.
miracidia, the number of miracidia per snail, There are several ways by which cercariae
the length of contact time, water flow, and emerge from snails infected by miracidia. Singly
turbulence. infected snails may shed cercariae as early as the
The ciliated surface of a miracidium 42nd day after miracidial penetration, although
disappears once penetration is completed. the average time is 62 days. Multiply infected
Within several days, the miracidium develops snails take somewhat longer, but shed more
into a first generation or mother sporocyst near cercariae and have a longer shedding period.
the point of entry. At 96 hours after penetration, The total number of cercariae shed during the
it transforms into an elongated sac filled with whole length of infection is about 230 for singly
germinal cells. On the 8th day, germ cells bud off infected snails and 280 for snails with multiple
the epithelial lining and develop into daughter infections. On the average, a snail sheds only
sporocysts. These migrate through loose about two cercariae per day. Snails may climb
connective tissue to the liver. In the connective vegetation above the water line or get stranded
tissues of the liver, further development of germ on the dryer portion of the snail habitat for
balls into daughter sporocysts takes place. Free several days. Because O. h. quadrasi can easily
swimming cercariae are ultimately produced. withstand drying for 7 to 10 days because of
Thus, from a single miracidium, through its operculum, it may shed scores of cercariae
the process of asexual multiplication within upon re-entry into water. This phenomenon
the mother and daughter sporocysts, scores is exploited in the laboratory to recover more
of cercariae of a single sex are produced. The cercariae. Snails are taken out of the aquaterraria
limiting factor for the number of cercariae that for 2 to 4 days before these are crushed or made
develop from one miracidium is the size of the to shed the parasites.
snail host. In S. mansoni and S. haematobium, Studies done in Leyte indicate that cercariae
thousands of cercariae are produced since their are most abundant in the field during the early
snail hosts are much larger. evening hours. These observations parallel those
Only a relatively small proportion of the of Bauman et al. who also found that the natural
miracidia that enter snails eventually produce release of cercariae is nocturnal, occurring from
cercariae. Only 6 to 10% of exposed O. h. early evening to midnight. Two factors have
quadrasi found in a study done in Mindoro been proposed to explain this occurrence: the
232 Medical Parasitology in the Philippines
negative effects of exposure to sunlight, and intrahepatic portions of the portal vein. This is
the fact that O. h. quadrasi is more active and likely the more common path of migration to
mobile at night, allowing it to reach water the portal circulation, while the vascular route
sources more often in the evening. Cercariae via the arterial circulation may be a secondary
can survive for up to 24 hours after release, and pathway.
so infested water can be infectious at any time Unlike other trematodes, schistosomes are
during the day. dioecious. Adults have a large sucker capping the
Cercariae swim on the surface of the water, anterior end, a ventral sucker, and a gonophore,
which facilitates contact and attachment to located slightly posterior to the ventral sucker.
the skin of the host. Host identification by S. The suckers aid in movement and enable the
japonicum seems to be non-specific, although flukes to maintain their position inside veins.
in thermal gradients they show a preference to The male is the shorter but sturdier sex and
a temperature of 35°C ± 3°C. Penetration is measures 12 to 20 mm in length by 0.4 to 0.5
stimulated by skin lipids. Some chemicals like mm in diameter. It has a gynecophoral canal
dimethylate and niclosamide repel cercariae where the longer and more slender female is
when applied to the skin. However, routine held (Plate 5.3). Females measure 15 to 26 mm
use is impractical due to the need for frequent by about 0.3 mm. They can live for up to 30
reapplication. years but the mean life span is much shorter
After skin penetration, the cercaria loses (3-8 years). In the male, the testes are arranged
its tail and transforms into a schistosomule. in one row above the ventral sucker, while in
Schistosomules have adapted to survive in serum the female, a single pyramidal ovary is located
or physiologic saline at 37°C. The cercarial in the midline.
tegument is replaced by a five to seven-layered Schistosomes have an incomplete digestive
membrane. In the laboratory, a cercaria can be system and an excretory system made up
transformed into a schistosomule by repeated of flame cells. These internal structures are
passage through small bore syringe needles surrounded by circular and longitudinal
resulting in shearing off of the tail, by passage muscles. The worms ingest red blood cells
through isolated skin, and by application to a and possess a protease (hemoglobinase) that
surface with skin lipids or crude egg lecithin. breaks down globulin and hemoglobin. They
One study showed that schistosomules can be
found in the pleural cavity on the 2nd day of
infection, in the parenchyma of the diaphragm
on the 4th day, in the liver parenchyma on the
6th day, and in the intrahepatic branches of the
portal vein afterwards. There was a very close
correlation between the number of superficial
lung petechiae on the 4th to 6th day after
cercarial penetration, and the number of flukes
recovered at day 30 from the portal system by
perfusion. These observations seem to indicate
that schistosomules break out of the pulmonary
microvasculature and traverse the lungs to
escape into the pleural cavity. They later go Plate 5.3. Schistosoma japonicum adults
through the diaphragm, enter the peritoneal in copula (Courtesy of the Department of
space and penetrate the liver to reach the Parasitology, UP-CPH)
Chapter 5: Trematode Infections 233
utilize glucose at a rapid rate and likely absorb the host and mature to lay eggs determine the
nutrients through the body wall. More research severity of infection, with repeated infection
is needed to elucidate the mechanisms for from continuing exposure causing the most
nutrient uptake and metabolism including severe burden of disease. Correlations between
enzyme systems. excretal egg-output, number of resident flukes,
and egg counts in the liver have been shown in
Pathogenesis and Clinical Manifestations
experimentally infected monkeys.
Cercarial penetration of skin is usually Egg deposition can occur in any organ, but
accompanied by dermatitis with pruritus and those most commonly involved are the liver,
localized reaction known as “swimmer’s itch.” intestines, lungs, and much less frequently,
This is similar to that seen from non-japonicum the central nervous system. In whatever organ
and non-schistosome cercariae that do not lead the eggs are entrapped, the primary lesion is a
to chronic disease in humans. The manifestation granulomatous hypersensitivity reaction around
is self-limited and repeated cercarial exposure a single egg or egg cluster. Since S. japonicum
causes these acute reactions to wane over time. typically deposits eggs in clusters, very large and
Non-endemic travelers to endemic areas are the destructive granulomas are formed. After initial
most likely to experience this phenomenon. egg deposition, there is an accelerated formation
Typically after 2 to 12 weeks following of larger and more destructive granulomas.
cercarial penetration, schistosomule migration However, as the infection becomes chronic,
can give rise to a syndrome characterized by easy granulomas become smaller or modulated.
fatigability, respiratory symptoms, arthralgias, Appreciation of the immunologic basis of this
myalgias, malaise, eosinophilia, fever, and phenomenon raises the question of vaccination
abdominal pain, which has been termed against the disease. Immunization to promote
“snail fever,” Katayama fever, or Katayama a modulated granuloma response could lead
syndrome. The latter term is currently preferred to a reduced likelihood of developing severe
since not all patients may present with fever. hepatosplenic disease.
Hepatosplenomegaly is not uncommon and In view of the collateral circulation
can be quite debilitating during this period of established, eggs are shunted into the systemic
infection, and in rare cases may lead to severe circulation and filtered in the pulmonary
hepatic dysfunction and death. Migration microvasculature, eventually causing pulmonary
through the pulmonary circulation can cause hypertension.
wheezing and coughing. Aberrant migration The clinical course of infection is arbitrarily
of maturing schistosomules may occlude the divided into three stages, namely: (a) incubation
circulation of the brain and the spinal cord (corresponding to the period from cercarial
precipitating seizures, paresthesias, transient penetration and schistosomular migration to
ischemic attacks, and strokes. While most the time the flukes mature); (b) period of early
patients will get better without medication, egg deposition and extrusion; and (c) period of
treatment with anthelminthics usually leads to tissue proliferation. Since there is a significant
faster resolution of symptoms. overlap of the second and third stages of the
The main pathology and chronic disease disease due to repeated infection, it is usually
manifestations of schistosomiasis japonica are more useful to refer to organ involvement as the
due to the host granulomatous reaction to eggs basis for clinical classification or description.
deposited in the liver and other organs. Since American soldiers who landed in Leyte
S. japonicum does not multiply in the definitive in 1944 and acquired schistosomiasis became
host, the initial quantum of cercariae that infect subjects for the study of early manifestations.
234 Medical Parasitology in the Philippines
Early neurologic involvement is brought about kept indefinitely. Processing can therefore be
by the parasite’s transition from the portal resumed in the laboratory or at some later
vein via mesenteric and pelvic veins to the convenient time. Protozoans are also preserved
spinal veins. Acute cases usually present with and stained in the preparation allowing
fulminating meningoencephalitis with fever, diagnosis of polyparasitism.
headache, confusion, lethargy, and coma, while The Kato-Katz technique is the preferred
chronic cases give a clinical picture of a tumor egg-counting technique and is considered the
with localizing signs and increased intracranial most suitable for quantification of eggs. It is
pressure. the most commonly used stool examination
technique for evaluating epidemiology, effect
Diagnosis
of control measures, and drug trials. The
Because S. japonicum is primarily a parasite Kato-Katz preparation can be kept for at least
of the portal vein and its branches, eggs are 2 weeks for later examination depending on the
not immediately demonstrable in the feces workload. There is practically no loss of eggs
unless they are deposited in the terminal during storage and processing which makes
vein or capillaries of the intestinal mucosa or the technique satisfactory for determining
submucosa, and subsequently escape to the fecal egg density. Specimens with less than 20
intestinal lumen. In infections where there eggs per gram of feces require examination of
is scarring or fibrosis of sites of ulcerations, at least three Kato-Katz preparations to have
passage of eggs into the intestinal lumen can 92% sensitivity.
be impeded. In these cases, stool examinations Rectal snips and imprints require specialized
can give negative results even in active infection. equipment and personnel, but are among the
Schistosome eggs can also be recovered by rectal most sensitive techniques. It is also the most
or liver biopsy. However, these procedures invasive since biopsy specimens are required.
require specialized equipment and are not Another drawback is the inability to distinguish
practical for mass screening or field surveys. between untreated and treated infection since
Moreover, tissue diagnosis cannot reliably eggs can persist in rectal tissue long after active
distinguish active from treated infection. infection has been eradicated. Some techniques
Microscopic examination techniques are such as vital staining and egg morphology
the most specific since these directly visualize and embryo motility have been proposed to
the parasite egg. Microscopic techniques distinguish viable from nonviable eggs, but none
include stool examination and rectal imprint. of these are consistently reliable.
S. japonicum eggs tend to clump together, so a The intimate tissue contact between
small stool sample may turn out falsely negative. parasite and host during cercarial penetration,
This may also occur in cases of light infection. schistosomular migration, intravascular growth
To establishing a diagnosis, the merthiolate- and development of adults, and deposition of
iodine-formalin concentration technique eggs in the tissues stimulate and provoke specific
(MIFC) has sufficient sensitivity for moderate immune responses which can be demonstrated
and heavy infections, but it is not adequate as evidence of infection.
for very light infections (<10 eggs per gram of Locally evaluated immunodiagnostic
feces). This technique has certain advantages tests include the following: (a) intradermal
over other stool concentration techniques test for immediate cutaneous hypersensitivity
making it suitable for field surveys. Fecal using adult worm extracts; (b) indirect
samples mixed with merthiolate-formalin hemagglutination using adult worm and egg
(MF) solution in screw-capped vials can be antigens; (c) circumoval precipitin test (COPT);
236 Medical Parasitology in the Philippines
and (d) the enzyme-linked immunosorbent 55 to 91% (n=14). Urine and serum tests on
assay or ELISA using soluble antigens of other schistosome species in Africa and Brazil
adults and eggs. A multicenter evaluation of S. have so far shown disappointing sensitivity and
japonicum diagnostics conducted by the World specificity for antigen based tests. A variety of
Health Organization, in which the Philippines the currently available antibody and antigen
participated, showed that crude egg antigens tests should be compared using sera collected
were most specific. In view of this, only the from low endemic areas. This will determine
COPT, ELISA, and indirect hemagglutination which assays are practicable for field use in
using egg antigens are recommended for use. endemic areas. The method of choice will
There are inherent problems with depend on cost, simplicity, and sensitivity.
parasitological diagnosis especially in low The COPT demonstrates the formation
endemic areas. Thus, there may be a role for of bleb-like or septate precipitates attached to
antibody or antigen detection that may have one or more points on the egg surface after
advantages over parasitological diagnosis. In the incubation of schistosome eggs in a patient’s
Philippines, a proportion of COPT positive but serum. It is currently regarded as the method of
single Kato-Katz negatives were shown to have choice for definitive diagnosis of this infection
eggs on repeated sampling. in the Philippines. The sensitivity of COPT is
The intradermal test is highly sensitive due to the fact that it is a microprecipitation
but nonspecific for infection. It cannot reliably reaction visualized under the microscope with
distinguish active from old infection. It is no sensitivity comparable to passive or indirect
longer used routinely as other immunodiagnostic hemagglutination.
tests have replaced it. The COPT may take more than two
Indirect hemagglutination has been shown years to become negative. The time spent
to be highly sensitive. However, it does require in examining is very much reduced with
specialized reagents and training but can be standardized egg preparation obtained from
performed with minimal equipment in the field. 50 to 60-day old S. japonicum infections of
ELISA formats are among the most sensitive rabbits. During this period of infection, there
tests but the need for laboratory equipment is a maximum proportion of mature eggs from
and trained personnel limits its use to banked the liver, which can be used as antigens for the
specimens and cannot be a point of care test. test. At least 25% of the eggs can be visualized
New lateral flow assays, which use card tests with precipitates after incubation with a positive
with visually apparent results, harness ELISA serum, so examination of the slide requires a
technology for point of care and field use minimum amount of time.
and have been validated extensively in China. Epidemiological studies in Barrio San
Lateral flow assays are likely the best suited for Antonio in the town of Basey, Samar, where the
elimination programs. However, the biggest whole population was examined using MIFC
drawback for antibody detection tests remains and COPT, indicated that many infections,
the persistence of antibodies long after active particularly of the population above 10 years old
infection has been treated. were not detected by a single stool examination.
Antigen detection reflects active infection. Seventy percent of the population tested positive
In more recent studies, adult worm antigens by COPT, while only 40% tested positive with
were found to be better than egg antigens for a single stool examination.
detecting low level infections (<100 eggs/g). Because COPT is technically demanding
Egg antigens detected only 65 to 85% of cases and requires specialized equipment, it is not
(n=7), while adult worm antigens detected routinely used for field testing. Moreover, it
Chapter 5: Trematode Infections 237
cannot distinguish active from past infection. intervals of several hours. Even if the patient
Currently, COPT is used as an adjunct tool for is not fully cured, the passage of eggs becomes
diagnosis in patients who are stool negative but significantly reduced. Improvement after
remain highly suspicious for schistosomiasis. It treatment is clinically apparent. There is a
is not recommended for use as a screening tool reduction in the degree of portal hypertension,
in the Philippines. hepatosplenomegaly, and cerebrospinal
manifestations. In local studies, egg reduction
Treatment
rates have ranged from 80 to 96% in patients
Praziquantel, a heterocyclic who received treatment with praziquantel 60
prazinoisoquinoline compound, represents mg/kg in two divided doses.
a major breakthrough in the treatment of The frequency of side effects varies in the
schistosomiasis. It is safe and highly effective different treated groups but these are generally
in single or divided doses against all the major mild and transitory. In a retrospective study
species of schistosomes. The active substance of 25,693 S. japonicum patients treated with
is a hygroscopic, colorless, almost odorless, praziquantel in China, only 0.4% of patients
crystalline powder with a bitter taste, which were reported to have serious adverse effects.
is stable under normal conditions but melts In local studies involving more than 6,000
and decomposes at 136 to 140°C. It is very patients, praziquantel given at 60 mg/kg in
soluble in chloroform and dimethyl-sulfoxide, two divided doses resulted in mild to moderate
sparingly soluble in ethanol and very slightly side effects in 68% while severe reactions were
soluble in water. Praziquantel is active against recorded in 1.2%. The most frequent adverse
adult schistosomes both in vitro and in vivo. In effects are epigastric or diffuse abdominal pain
vitro experiments have shown that schistosomes or discomfort, nausea, anorexia, dizziness,
instantly become immobile and undergo headache, and fever. Most of these were noted
contraction on contact with the drug. to be mild and transient.
Acute toxicity studies conducted in Artemisinins including artemether have
rats, mice, and rabbits have shown that in recently been shown to be effective in decreasing
comparison with other anti-schistosomal drugs, S. japonicum infections when used as pre-
praziquantel has a very low acute toxicity profile. exposure prophylaxis during the planting season
Rats tolerated daily doses of up to 1 mg/kg for 4 in China. Artemether is effective against
weeks, and dogs tolerated daily dosages of up to the juvenile stages of the worm and so this
180 mg/kg for 13 weeks without organ damage. drug is ideal for the non-endemic traveler.
No effects were seen on the whole reproductive However, routine use for endemic natives may
process in rats. Teratogenic effects were not be problematic in areas where malaria is co-
observed in mice, rats or rabbits. endemic since this may give rise to resistance.
A single dose of 40 to 50 mg/kg, or 25 mg/ Combination therapy with praziquantel has
kg in two doses or three doses of 20 mg/kg given shown high cure rates in laboratory animals
every 4 hours or even a dose as low as 10 mg/kg and may be an option in areas with high worm
given three times a day for 2 days provide high burden or emerging drug resistance.
cure rates. A dosage of 30 mg/kg given after
Epidemiology
breakfast and repeated after lunch has been used
in trials involving more than 6,000 patients with Transmission dynamics vary considerably
light to moderate S. japonicum infections with in the different endemic areas due to the
a cure rate of almost 90%. many factors that influence the common
Generally, a single large dose has the environment, the behavioral patterns of the
same efficacy as several smaller doses at definitive host, and the bionomics of the
238 Medical Parasitology in the Philippines
chemotherapy against schistosomiasis since the to improve knowledge, attitudes, and perception
WHO Expert Committee on Bilharziasis first with respect to transmission, diagnosis, and
met in 1953. Treatment in this age group has control of schistosomiasis. Since behavior
been shown to reduce significant morbidity is influenced by local culture, knowledge,
in the short-term and prevent the long- attitudes, and practices (KAP) of the target
term sequelae in adulthood associated with area should be taken into consideration. This
chronic infection. Continued transmission of will permit the design of a more applicable and
schistosomiasis will depend on how rigorously relevant educational program. Health education
chemotherapy can be applied, as well as on programs should not only be concerned with
epidemiological factors. In order to achieve a modifying KAP but should also encourage
sustainable reduction in transmission, health and promote community participation in
education, attention to the water supply and contributing to schistosomiasis control.
sanitation, environmental management, and O. h. quadrasi is an operculated fresh water
where appropriate, snail control need to be amphibious snail (Plate 5.6) with separate male
part of an overall strategy from the very start. and female sexes. These attain sexual maturity
The primary objective of chemotherapy using by the time the snails measure 3.5 mm. A single
praziquantel is the reduction and prevention of copulation will allow the fertilized female to lay
morbidity. Since it is inevitable that prevalence two eggs every 5 days for 1 month. The usual
will decrease following treatment, it is important snail habitats are small clear water streams,
to measure the effect of chemotherapy on water-logged rice fields, swamps, and water
incidence, worm burden, and morbidity of new seepage areas along mountains or foothills.
cases. The use of an effective chemotherapeutic In a stream or small swamp, snails are found
agent like praziquantel requires efficient case both in the water and on the banks. Snails are
detection systems and diagnostic tests in order most numerous in areas where the soil is moist.
to optimize priorities for treatment where Those in the water are found in shallower areas,
resources will not permit treatment of all on protruding rocks, or on floating leaves and
infected individuals. branches.
Chemotherapy using praziquantel to Two general strategies for snail control are
reduce morbidity is the principal thrust of in use: focal and area-wide. The focal approach
the Philippine program for schistosomiasis
control. However, it should be stressed that
equal emphasis should be placed on control
of transmission and eventual elimination of S.
japonicum, O. h. quadrasi, or both, as has been
achieved in Japan and in extensive portions of
China.
While effective and safe chemotherapy,
improved environmental management, and
snail control all contribute to the control of
schistosomiasis, the long term solution to this
problem requires sustained and appropriate
health education and strong community
Plate 5.6. Oncomelania h. quadrasi,
participation. Consequently, health education intermediate host of Schistosoma japonicum
must be recognized as an integral part of the (Courtesy of the Department of Parasitology,
control program. Strong effort should be made UP-CPH)
Chapter 5: Trematode Infections 241
may be more feasible where transmission sites implement the necessary environmental changes
and resources are limited, but area-wide control without resorting to large capital expenditure.
is more pragmatic if transmission is spread over a In the Philippines where there is a perennial
watershed or an irrigation system. Focal control shortage of funds, increased community
requires water contact studies to identify the participation is needed to ensure the success
most common transmission sites. To control an of snail control programs. The advantages of
entire area or watershed unit, all snail habitats snail control by environmental methods include
should be identified and treated. Area-wide the following: (a) it can be incorporated or
control is more difficult and expensive, but it integrated into regional agricultural and other
is also likely to be longer lasting and ultimately rural development projects; (b) the results can
more cost-effective than focal measures. be made permanent or persistent provided
Environmental control methods involve adequate maintenance is done regularly; (c) it
alteration of the snail habitat to reduce survival results in increased agricultural productivity; (d)
and prevent or deter snail reproduction. in the absence of adequate funding, the control
Control of breeding has a more lasting effect measures can be done on a focal basis by the
than killing snails. The more radical the people themselves; (e) it results in increased land
intervention, the more profound the effect of value; and (f ) it does not require foreign aid and
the control measure on the snail population. technology, unlike chemical control.
Methods of control are based on removal of the No outstanding novel molluscicide or
environmental requirements of Oncomelania. chemical for killing snails has been developed
These include: (a) drainage of breeding sites in the past decade. Interest in such research
and proper management of irrigation systems; by industry has diminished because of high
(b) removal of shade or shelter from the sun research and development cost and the lack
by clearing vegetation around bodies of water; of an assured market. Most countries that
(c) prevention of breeding on the banks of have schistosomiasis cannot afford the cost
streams or irrigation canals by lining these with of deploying molluscicides, and there is
concrete or making them more perpendicular; increasing concern about the consequent
(d) acceleration of flow of water by proper environmental pollution with pesticides that are
grading and cleaning of the stream bed and not biodegradable or have long half-lives. The
removal of debris; (e) construction of ponds future role of molluscicides may be determined
if the area cannot be drained; and (f ) covering by economic considerations and the priority
snail habitats with landfills. afforded schistosomiasis in relation to other
The effectiveness of these alterations public health problems.
is lasting if there is proper maintenance. The objective of sanitary disposal of
Although snail control is usually done on a human feces is to prevent contamination of
focal basis, when possible, it should include watercourses inhabited by snails. However, this
entire watershed. All of these methods have has limited value in S. japonicum transmission
been found to be effective experimentally as if animal reservoir hosts represent a significant
early as 1958 in the Philippines. One of the rate source of miracidia for infecting snails.
limiting factors of environmental modification The use of properly constructed and
of habitat is the cost involved. Japan was able hygienic latrines should be encouraged as this
to afford the large capital expenditure needed contributes to the control of water and fecal-
for cementing canals, reclaiming swampy areas, borne viral, bacterial, and parasitic infections.
and sustaining the control program. In China, Latrines for use in rural areas have been regarded
the socio-political structure made it possible to as unsatisfactory because of flies, mosquitoes,
242 Medical Parasitology in the Philippines
and maintenance problems. These issues should operational efficiency so that evaluation of the
be resolved to increase toilet utilization. effects of control operations will be valid and
The simplicity of diagnostic techniques, will truly reflect the epidemiologic profile of
the safety of praziquantel, the relative facility the disease.
of focal control of snails, and the availability of A transmission blocking vaccine has been
epidemiologic information for some endemic developed for water buffaloes in China and
areas permit adoption and integration of represents a major breakthrough in controlling
schistosomiasis control into primary health animal reservoirs. However, domesticated
care. This stimulates active involvement of animals seem to be the minority reservoir
the community and facilitates the entry into in the Philippines in comparison to sylvan
endemic communities of support services and reservoirs and human sources of infection.
schistosomiasis teams of the Department of Development of a human vaccine has proven
Health. difficult since Schistosoma is well-adapted to
Primary health care workers in endemic evading the immune system in its niche as an
areas should have some basic knowledge of intravascular parasite. Several parasite antigens
schistosomiasis, including major clinical are promising vaccine candidates, including
manifestations, method of diagnosis, treatment, paramyosin, which has generated immunity
transmission, and control. They should be to repeated infection in pilot studies. The
involved in stool collection, surveys, and mapping of the schistosome genome will enable
treatment of patients. They should also the identification of more vaccine candidate
be utilized as health educators, and asked molecules and other possible novel mechanisms
to encourage community participation, for the treatment and control of this parasite.
particularly in sanitation and snail control.
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Chapter 5: Trematode Infections 245
Lung Flukes
Vicente Y. Belizario, Jr., Alexander H. Tuliao
Paragonimus westermani
Plate 5.8. Paragonimus westermani egg; note Plate 5.9. Antemelania asperata, first
the flattened operculum and the abopercular intermediate host of Paragonimus westermani
portion (Courtesy of the Department of (Courtesy of the Department of Parasitology,
Parasitology, UP-CPH) UP-CPH)
subsequently emerge from the snail to seek Following the ingestion of infected
and infect the second intermediate host, the crustacean tissue by the host, the metacercariae
mountain crab Sundathelphusa philippina of Paragonimus excyst in the duodenum of
(Plate 5.10), formerly known as Parathelphusa the host. The immature worm then traverses
grapsoides. The cercaria penetrates the soft parts through the intestinal wall into the peritoneal
of the crustacean and encysts as a metacercaria cavity, where it wanders about for several days
in the gills, body muscles, viscera or legs (Plate and embeds itself in the abdominal wall. The
5.11). The crab may also be infected by eating parasite then returns to the coelom and migrates
infected snails. The definitive host acquires through the diaphragm into the pleural cavity.
the infection by ingesting raw or insufficiently A juvenile diploid worm wanders in the pleural
cooked crabs harboring metacercariae. spaces until it finds one or several diploid
worms. The pair or group then migrates into
the lung parenchyma to develop into adults in
about 6 weeks, where they mate and lay eggs.
Juvenile triploid worms in Japan, Korea, and
Taiwan can establish themselves in the lung
parenchyma without a mate. Groups of diploid
and triploid parasites have also been observed.
In the lung parenchyma, a fibrotic capsule
forms around the parasite or their group. The
fibrotic capsule has openings that allow the eggs
to escape into the respiratory tract where they
are moved up and out by the ciliary epithelium
along with lung exudates. In the pharynx,
they are either coughed out or swallowed into
Plate 5.10. Sundathelphusa philippina, the
the alimentary canal to be passed out with
second intermediate host of Paragonimus
westermani (Courtesy of the Department of the feces. The completion of development in
Parasitology, UP-CPH) the definitive host takes 65 to 90 days. Adult
worms are known to persist in humans for 20
years or longer.
Cysteine proteases have been found to
play an important role in the development of
young parasites because of their involvement in
the metacercarial excystment, tissue invasion,
and immune modulation of the host. Cysteine
proteases with masses of 27 and 28 kD are
released from the excretory bladder of the
metacercariae during excystment. The proteases
are most abundant in the tegmentum of
newly excysted worms, facilitating migration
through the tissues of the host. The 27 and 28
kD cysteine proteases are also found to cleave
Plate 5.11. Paragonimus westermani
metacercaria in crab heart muscle human immunoglobulin G, thereby creating
(Courtesy of the Department of Parasitology, a zone of immune privilege around the worm.
UP-CPH) As the juvenile parasite moves actively towards
248 Medical Parasitology in the Philippines
the lungs, additional proteases of 15, 17, and result in exudative aseptic inflammation,
53 kD are expressed. Protease activity decreases infarction, hemorrhage, and necrosis in the
as worm matures. subcortical areas. After invasion, multiple,
conglomerated, and interconnected granulomas
Pathogenesis and Clinical Manifestations
form around the parasite, containing abscess
In the lungs, Paragonimus worms provoke material and eggs. In the chronic stage,
a granulomatous reaction that gradually gives liquefaction necrosis and fibrinous gliosis occur,
rise to the development of a fibrotic cyst and these may lead to cortical or subcortical
containing blood-tinged purulent material, atrophy, and secondary ventricular dilatation.
adult worms, and eggs. The most common Cerebral paragonimiasis may present with
symptoms of paragonimiasis are chronic cough headache, meningismus, seizures, hemiparesis,
and hemoptysis. Chest pain, dyspnea, low-grade blurring of vision, diplopia, homonymous
fever, fatigue, and generalized myalgia may also hemianopsia, and aphasia.
occur.
Diagnosis
Since it takes several weeks for the parasite
to migrate and mature, the early stages of the Microscopy is the most basic and
infection are usually asymptomatic. Clinical most readily available diagnostic tool for
symptoms are less severe after 5 to 6 years. paragonimiasis. Definitive diagnosis is based
Occasionally, the disease can have serious on the detection of the characteristic eggs in
sequelae, such as chronic bronchiectasis and sputum, stool, or, less frequently, in aspirated
pleural fibrosis, secondary to severe parenchymal material from abscesses or pleural effusions.
and pleural damage. However, the sensitivity of microscopy is
The circuitous route of migration allows the suboptimal, with ova detection in sputum
worms to lodge and mature in different ectopic ranging from 37 to 88%. If initial findings are
locations. These aberrant worms may localize negative, repeat examinations may be helpful.
in the lung pleura, pericardium, myocardium, Sputum concentration with 3% sodium
abdominal wall, omentum, liver, mesenteric hydroxide, with repeated sputum examinations
lymph nodes, adrenals, urogenital organs, and up to three times on different days, provides the
eyes. Heavy intensity infections can cause both best sensitivity for microscopic diagnosis.
pulmonary and ectopic paragonimiasis. Worms Chest radiographs may aid in the diagnosis
that fail to find a mate in low intensity infections of pulmonary paragonimiasis when combined
may end up in ectopic locations as well. with a high index of suspicion. Pulmonary
Cutaneous and cerebral paragonimiasis are paragonomiasis usually presents as lung
the classic known forms of ectopic infection. parenchyma lesions which may be infiltrative,
In cases of cutaneous paragonimiasis, a slow- nodular, cavitating, or a combination of
moving, nodular lesion in the subcutaneous these. Pleural effusions occur in almost half of
tissue on the abdomen or chest is the patients. These radiographic findings are not
characteristic symptom. specific, and may also be seen in other diseases,
Cerebral involvement is the most serious particularly pulmonary tuberculosis (PTB),
complication of human paragonimiasis. A lung cancer, and fungal infections. Since PTB
juvenile P. westermani may migrate from the and paragonimiasis are usually co-endemic,
pleural cavity into the cranial cavity through PTB should always be ruled out.
the soft tissues along the internal jugular vein. The peripheral blood count for
The migration worm can cause congestion, paragonimiasis frequently reveals eosinophilia
vasculitis, and capillary rupture, which may and elevated levels of IgE, which is typical for
Chapter 5: Trematode Infections 249
parasitic infections. The total white blood cell In cerebral paragonimiasis, the most
count may be in the normal to elevated range. characteristic finding in either cranial Computer
Eosinophilia is more common in the acute stage Tomography (CT) scan or Magnetic Resonance
of paragonimiasis, whereas IgE levels have no Imaging (MRI) are conglomerated, multiple,
correlation with the stage of the disease. ring-enhancing lesions (“grape-cluster”
Va r i o u s i m m u n o l o g i c a l m e t h o d s appearance) with surrounding edema, typically
have been developed for the diagnosis of in one cerebral hemisphere, most commonly
paragonimiasis. Classic methods include the in the posterior part of the brain. On skull
complement fixation (CF) test, intradermal radiographs, patients with chronic disease may
test, double diffusion in agarose gel, and present with specific soap-bubble calcifications.
immunoelectrophoresis. CF has high sensitivity
Treatment
for both diagnosis and assessment of cure after
therapy. The intradermal test is simple, rapid, Praziquantel is the drug of choice. It is
cheap and highly sensitive, although it may still highly effective in the treatment of trematode
yield positive results several years after successful infections, particularly lung fluke infection. It
treatment. induces rapid contraction of trematodes and
The classic methods for serodiagnosis of alters the tegmental surface (e.g., vacuolization).
paragonimiasis have been gradually replaced These changes are thought to be linked to
by more sensitive and specific tests, like the drug-dependent disruption of calcium
immunoblotting (IB) and enzyme-linked homeostasis. Praziquantel is suitable for
immunosorbent assay (ELISA). IB has a treatment of adults and children over 4 years of
sensitivity of up to 99%, and has been used age. Usual dose for treatment is 25 mg/kg, three
since 1988. ELISA has a sensitivity ranging times a day, for 2 to 3 days. A higher dose may
from 96% to 99%, and has been employed be required in cases of ectopic paragonimiasis.
widely in various parasitic and non-parasitic Praziquantel is currently not recommended
infections. For paragonimiasis, most ELISA for the treatment of paragonimiasis during
systems were developed to detect Paragonimus- pregnancy and lactation, although current
specific IgG antibody. Attempts have also literature has not proven the drug to have
been made to detect specific IgE, IgM, and mutagenic, teratogenic, or embryotoxic effects.
circulating antigens. The multiple-dot ELISA Treatment should preferably be given after
was developed for field use in developing delivery unless immediate intervention is
countries. deemed essential. Breastfeeding should be
The loop-mediated isothermal avoided during and 72 hours after treatment.
amplification (LAMP) test is a simple, rapid, Adverse effects of praziquantel are generally
and cost-effective method currently being mild, and these include abdominal discomfort,
developed for field use in epidemiologic surveys nausea, headache, dizziness, and rarely, fever,
in developing countries. LAMP allows the urticaria, drowsiness, and tachycardia.
rapid amplification of deoxyribonucleic acid Triclabendazole is a benzimidazole that was
(DNA) with high specificity under isothermal originally used for the treatment for Fasciola
conditions, using DNA polymerase with hepatica infections. Recently, triclabendazole
strand-displacement activity. Magnesium has been demonstrated to be an effective drug
pyrophosphate, the reaction by-product, is against human paragonimiasis. Triclabendazole
visible to the naked eye. Only warm water is probably binds to B-tubulins of trematodes,
required to perform the assay. leading to depolymerization and disruption of
250 Medical Parasitology in the Philippines
microtubule-based processes. These result in meat in Japan. Unhygienic food preparation also
damage to the external plasma membrane and contributes to the transmission of the disease.
nuclear membrane, with dissolution of some Cultural beliefs and traditions influence the
heterochromatin, mitochondria, and Golgi age and sex distribution of paragonimiasis. In
complex. The cure rate with triclabendazole is Japan, during the 1950s and 1960s, the majority
comparable with that of praziquantel, and may of those infected were children because of the
result in better patient compliance since the practice of using raw crayfish juice as a treatment
treatment regimen consists only of a single dose. for various cutaneous ailments. Similar practices
Bithionol can be used as an alternative also existed in Korea during the same period.
drug. It is given orally at a dose of 15 to 25 Currently, middle-age Japanese men have the
mg/kg, twice daily on alternate days, for 10 to highest prevalence due to their conservative
15 days. affinity for traditional dishes. In adolescent
girls in Cameroon, a popular belief existed
Epidemiology
once among the Bakossi people that crabs aid
Paragonimiasis has a focal distribution in in fertility, leading to disproportionately high
limited parts of Asia, Latin America (Peru and infection rates in this group.
Ecuador), and Africa (Nigeria and Cameroon). PTB overlaps with paragonimiasis in
According to recent estimates, 20.7 million paragonimiasis endemic areas in the Philippines
people worldwide are infected, and 292.8 and other developing countries. Since PTB
million are at risk. and pulmonary paragonimiasis share the same
In the Philippines, paragonimiasis is symptoms, misdiagnosis and mismanagement
endemic in Mindoro, Camarines, Sorsogon, are not uncommon. Further studies are needed
Leyte, Samar, Zamboanga del Norte, Davao to elucidate the impact of misdiagnosis of
Oriental, Basilan, and Cotabato. Prevalence pulmonary paragonimiasis and PTB.
rates vary among the endemic provinces.
Prevention and Control
Infection rates in Sorsogon ranged from 16 to
25% in 1997. In more recent epidemiologic The most practical way to prevent
studies done in the municipality of Pres. Manuel acquisition of human paragonimiasis is to
Roxas in Zamboanga del Norte, the prevalence avoid ingestion of raw or insufficiently cooked
was 14.8% in 2005. crabs and other crustaceans, as well as meat
Paragonimiasis has a focal distribution, from paratenic hosts like wild pigs. Safe food
largely determined by local patterns preparation helps reduce the infectivity of food.
of consumption of inadequately cooked Furthermore, it is believed that changing the
crustaceans and paratenic hosts. Examples risky dietary habits of the population, through
of dishes that can transmit disease include health education and promotion, can control
kinagang (crab in coconut milk), sinugba (grilled this parasitic infection. Elimination of reservoir
crab), and kinilaw (raw crabs in vinegar) in the and intermediate hosts of Paragonimus may not
Philippines, nam prik poo (crab and chilli paste) be feasible. Capacity building of local health
in Thailand, crabs in brine, soy sauce or alcohol staff on the diagnosis and treatment of this
(drunken crabs) in China, kejang (raw crabs in disease is important for early case detection
soy sauce) in Korea, ceviche (raw crabs in lemon and treatment.
sauce) in Peru, and sashimi of wild boar and bear
Chapter 5: Trematode Infections 251
Intestinal Flukes
Vicente Y. Belizario, Jr., Percy G. Balderia
Inside the snail, the miracidium transforms The egg is large, operculated, unembryonated
into a sporocyst, which subsequently produces when first passed, and indistinguishable from
mother rediae, daughter rediae, and finally, eggs of F. hepatica and F. gigantica. It measures
cercariae. Cercariae leave the daughter rediae 130 to 140 μm by 80 to 85 μm.
and undergo further development in the snail
Pathogenesis and Clinical Manifestations
tissues. Seven weeks after infection, cercariae
emerge from the snails into water. Cercariae Pathological changes caused by the
attach themselves and encyst as metacercariae on worms are traumatic, obstructive, and toxic.
the surfaces of seed pods, bulbs, stems, or roots Inflammation and ulceration occur at the site
of various aquatic plants such as Trapa bicornis of worm attachment, producing an increase
(water caltrop) (Plate 5.12), Eliocharis tuberosa in mucus secretion, and minimal bleeding.
(water chestnut), Ipomea obscura (morning glory Gland abscesses are occasionally formed in the
or kangkong), and Nymphaea lotus (lotus). These mucosa. In heavy infections, the worms may
plants serve as the second intermediate hosts of cause intestinal obstruction. Intoxication results
the parasite. Pigs and humans are the important from the absorption of worm metabolites by the
definitive hosts. host. The patient experiences generalized toxic
and allergic symptoms, such as edema of the
face, abdominal wall, and lower limbs. Profound
intoxication can result in death of the host.
Diagnosis
Echinostoma ilocanum
Artyfechinostomum malayanum
Heterophyid Flukes
to consider intestinal fluke infection when Haplorchis taichui. Infection rates were high in
dealing with bowel disturbance and a history of both males and females, and in all age groups,
consumption of raw fish. Definitive diagnosis especially the working age group. Children
is by detection of eggs in the stool using the and the elderly were not spared of infection.
modified Kato thick method, which has a higher Intestinal heterophyidiasis has since then
sensitivity compared to formalin-ether/ethyl been recognized as an emerging public health
acetate concentration technique (31.0% vs. concern in the southern part of the Philippines.
13.6%). The eggs of the different heterophyid Altogether, eight provinces in two regions of
species are difficult to distinguish. Care must Mindanao have reported thousands of cases to
be taken to distinguish them from Clonorchis date. High prevalence levels were detected in
and Opisthorchis eggs. Heterophyid eggs have areas where investigations for an outbreak of
also been referred to as Opisthorchid-like eggs intestinal capillariasis were being conducted.
where the liver fluke is endemic.
Prevention and Control
Polymerase chain reaction (PCR) may be
useful as a sensitive diagnostic tool, particularly Preventive measures include avoiding
for low-intensity heterophyid infections. ingestion of raw or improperly cooked fish.
It may be difficult to change eating habits.
Treatment
Capacity building of laboratory staff will help
Praziquantel is the drug of choice, given at in early diagnosis when doing routine stool
25 mg/kg per dose, three doses in 1 day. examination. This will facilitate provision of
appropriate treatment. Surveillance in other
Epidemiology
regions where raw fish (kinilaw) is eaten should
The parasite has been reported in Egypt, be considered.
Greece, Israel, Western India, Central and
References
South China, Japan, Korea, Taiwan, and the
Philippines. Its worldwide distribution may be Africa CM. Evidence of intramucosal
due to the fact that heterophyids have adapted invasion in the life cycle of Haplorchis
to snails belonging to various families, and are yokogawai (Katsuta, 1932) Chen, 1936
not very specific with respect to their second (Heterophyidae). J Philipp Med Assoc
intermediate hosts. Both intermediate hosts 1937;17:737–43.
may be found in different habitats (fresh, Africa CM, Garcia EY. Intestinal heterophyidiasis
brackish, and salt waters), and in different with cardiac involvement. Phil J Public
climates. Reservoir hosts include dogs, cats, Health. 1935;2:1–22.
and birds. Belizario VY Jr, Geronilla GG, Anastacio MB,
In the Philippines, the prevalence was de Leon WU, Suba-an AP, Sebastian AC,
previously considered low, and its distribution et al. Echinostoma malayanum infection,
spotty, as shown by previous parasitologic the Philippines. Emerg Infect Dis.
surveys. In the 1980s, less than 1% of 30,000 2007;13(7):1130–1.
stools examined in surveys done nationwide Belizario VY Jr, Bersabe MJ, de Leon WU,
were found positive for heterophyid ova. A more Hilomen VV, Paller GV, de Guzman AD
recent parasitologic survey done in 1998 in Jr, et al. Intestinal heterophyidiasis: an
Monkayo, Compostela Valley, however, revealed emerging food-borne parasitic zoonosis in
31% prevalence with a majority of those Southern Philippines. Southeast Asian J
infected having moderate to heavy intensities Trop Med Public Health. 2001;32(Suppl
of infection. The species was identified as 2):36–42.
262 Medical Parasitology in the Philippines
Liver Flukes
Vicente Y. Belizario, Jr., Raezelle Nadine T. Ciro
metacercariae will remain alive for many weeks, to the whole lateral field of the hind body. The
depending on the temperature. They survive intestinal ceca are long and highly branched,
longer at a temperature below 20°C; higher extending to the posterior end of the body.
temperatures and desiccation will destroy the Compared to F. hepatica, the F.gigantica
metacercariae in a short time. adult worm is longer (25-75 mm), with about
F. hepatica has a large, broad, and flat body the same width (3-12 mm), with less developed
which measures 18 to 51 mm in length and 4 shoulders, and a shorter cephalic cone. The
to 13 mm in width (near the mid-body). A ceca are more branched especially towards the
distinguishing feature is the cephalic cone which midline of the body and the branches of the
has a marked widening at the base of the cone ovary are longer and more numerous. The
(“shoulder”). The suckers are comparatively average distance between the posterior testes
small and are located close to each other in the and the posterior border of the body is longer.
conical projection. The two testes are highly The F. hepatica egg (Plate 5.18) is large,
branched occupying the second and third ovoidal, operculated, and yellowish to brownish
quarters of the body. The ovary is dendritic and in color. It measures 140 to 180 µm by 63 to 90
situated in front of the anterior testis. The uterus µm in size and is released from the worm still
is coiled and relatively short. Vitellaria extend immature, containing a large unsegmented mass
Chapter 5: Trematode Infections 265
phase of infection when applied to the acute nodules and tunnel-like branching hypodense
or chronic stages, respectively. tracts. Hepatic sonographic findings have been
Differentials for human fascioliasis described as small clustered hypoechoic lesions
include diseases which may present with with poorly defined contours and hypoechoic
similar symptoms such as acute viral hepatitis, nodular lesions. The biliary phase of the disease
schistosomiasis, visceral toxocariasis, biliary occurs in the presence of parasites in the biliary
tract diseases, and hepatic amebiasis. system. Sonography is the useful method in the
Parasitological diagnosis may be made detection of biliary lesions. The oval shaped,
through the identification of eggs in stool, leaf-like, or snail-like echogenic structures
duodenal contents, or bile, or the recovery of with no acoustic shadowing in the gall bladder
adult worms during surgical exploration, after or common bile duct have been described
treatment, or at autopsy. However, the eggs may as characteristics of fascioliasis. Endoscopic
be present in very small numbers at irregular retrograde cholangiopancreatography (ERCP)
intervals and thus may be difficult to find. Eggs can also be used in diagnosing fascioliasis in the
may also be transiently present in the stool after biliary phase, since it can demonstrate biliary
ingestion of poorly cooked liver from infected obstruction or filling defects.
animals (spurious or false fascioliasis). This
Treatment
situation, with its potential for misdiagnosis,
can be avoided by having the patient follow a Triclabendazole is the drug of choice
liver-free diet several days before a repeat stool for treating fascioliasis because of its efficacy,
examination. safety, and ease of use. The first report of
Although techniques for showing the successful treatment of human fascioliasis
presence of eggs in stools have long been used with triclabendazole dates back to 1986. The
to confirm the diagnosis, these methods have recommended treatment is a single 10 mg/
limitations in determining human fascioliasis kg oral dose of triclabendazole following food
because parasite eggs are not found in feces until intake. For individuals with heavy infections,
three to four months after infection, and due the recommended treatment is two doses
to low sensitivity in low-intensity infections. of 10 mg/kg spaced by 12 hours. Mild and
Because the release of Fasciola coproantigens transient abdominal pain, biliary colic, fever,
takes place before egg shedding, immunologic nausea, pruritus, vomiting, weakness, liver
methods are preferable to egg examination for the enlargement, and mild, limited disturbances
detection of acute infections. Immunodiagnosis in liver function have been observed as adverse
including enzyme-linked immunosorbent assay events associated with the drug. Liver flukes
(ELISA) and Western blot are now widely resistant to triclabendazole have been found
applied as alternative methods of confirming in livestock, probably due to the widespread
early and extrabiliary human fascioliasis. use of the drug. Resistant F. hepatica have been
Radiological examinations may also help reported in Australia, Ireland, the Netherlands,
in the diagnosis of fascioliasis. Radiological Scotland, and recently, in Spain. No resistance
findings of fascioliasis, mainly on sonography in Fasciola infecting humans has been reported
and computed tomography (CT), have been so far.
described in several reports. In the hepatic Bithionol may also be used to treat
phase of the disease, parenchymal lesions are fascioliasis. The fasciolicidal activity of bithionol
due to migration of the parasites through the was first described in the early 1960s. Cure
liver. The characteristic features on CT are rates ranging from 58 to 100% have been
described as multiple confluent, hypodense reported. Although bithionol is no longer
Chapter 5: Trematode Infections 267
commercially available for human use in many patients are estimated to require treatment each
countries, it is still used for the treatment of year. There has been an increase in the number
fascioliasis (e.g., in the United States by the of cases reported, in response to the availability
Centers for Disease Control and Prevention) of treatment. Transmission to humans is highly
because the drug is often more readily available linked to eating raw water-grown vegetables
than triclabendazole. Adverse events including that harbor F. gigantic metacercariae. Washing
anorexia, nausea, vomiting, and abdominal vegetables with water, vinegar, or lemon
pain are mild and transient. A key drawback juice is not sufficient to remove the encysted
of bithionol is that long treatment duration is metacercariae. Use of contaminated kitchen
necessary. Bithionol is given at 30 to 50 mg/kg tools in preparing other foods can also cause
body weight on alternate days to complete 10 the metacercariae to be transmitted.
to 15 doses. In Asia, most human cases have been
Peroxidic compounds, such as semi- reported in Iran, especially in Gilan Province,
synthetic artemisinins and synthetic trioxolanes, on the Caspian Sea. In parts of eastern Asia,
which are known for their antimalarial and human fascioliasis appears to be sporadic. Few
antischistosomal properties, have been reported cases have been documented in Japan, Korean
to show trematocidal activities. Single 200 peninsula, and Thailand. In the Philippines, no
to 400 mg/kg oral doses of artesunate and case of human fascioliasis has been documented.
artemether completely cured chronic F. hepatica In Europe, human fascioliasis mainly occurs
infections in rats. in France, Spain, Portugal, and the former
USSR. France is considered an important
Epidemiology
human endemic area. A total of 5,863 cases
Fascioliasis has a worldwide distribution have been recorded from nine French hospitals
and is of great economic importance in from 1970 to 1982.
livestock-raising countries. The prevalence in
Prevention and Control
animals in Central and Latin America is about
25% but may reach 70% in cattle, goats, and Preventive measures include thorough
sheep in other countries. In the Philippines, washing or cooking of vegetables, and boiling
the dominant species affecting cattle and of water in areas where the infection is endemic.
water buffaloes is F. gigantica. Examination of Cilla et al. in 2001 reported the decrease in
cows, carabaos, and horses in South Cotabato infection over the years in Gipuzkoa, Spain
in 2007 showed a fascoliasis prevalence of which is probably related to a change in dietary
89.5%. Human fascioliasis is typically sporadic. habits. Control measures include elimination
However, clinical cases and some outbreaks have of the snail intermediate host through the
recently occurred. The estimated number of application of copper sulfate, and killing the
people with fascioliasis is 360,000 in Bolivia, parasite in the reservoir host by chemotherapy.
830,000 in Ecuador, 10,000 in Islamic Republic Spitfill and Dalton in 1998 demonstrated
of lran, 742,000 in Peru, and 37,000 in Yemen. that animals can be significantly protected
The total estimated number of people infected against infection by vaccination with defined
is 2.4 to 17 million, in 51 countries, from five Fasciola antigens. These include a fatty-
continents. The number of persons at risk is acid binding protein (FABP) termed Fh12,
more than 180 million worldwide. glutathione-S-transferase (GST), cathepsin
Fascioliasis due to F. gigantica is typical of L (CatL) proteinase, and hemoglobin (Hb).
rural areas of Vietnam, but is not infrequent in Apart from reducing fluke burden, some
areas around urban centers as well. About 5,000 vaccines have elicited concurrent reductions
268 Medical Parasitology in the Philippines
in parasite egg production. It was also noted Haridy FM, Morsy TA, Gawish NI, Antonios
that in those vaccinated with cathepsin L2-Hb, TN, Abdel Gawad A. The potential reservoir
>98% of the eggs recovered did not embryonate role of donkeys and horses in zoonotic
to miracidia. A juvenile protease known as F. fascioliasis in Gharbia Governorate, Egypt.
hepatica cathepsin B2 (FhCB2) was also recently J Egypt Soc Parasitol. 2002;32(2):561–70.
validated as a vaccine for fascioliasis using the Ishii Y, Nakamura-Uchiyama F, Nawa Y. A
rat model. The FhCB2 vaccine was shown to be praziquantel-ineffective fascioliasis case
highly immunogenic, induced a 60% reduction successfully treated with triclabendazole.
in fluke burden, and a 63% reduction in the size Parasitol Int. 2002;51(2):205–9.
of the recovered flukes. Vaccination with FhCB2 Kabaalioglu A, Ceken K, Alimoglu E, Saba R,
also led to significantly reduced liver damage Cubuk M, Arslan G, et al. Hepatobiliary
(61%), suggesting a killing effect on young fascioliasis: sonographic and CT findings
parasites before extensive damage occurs in the in 87 patients during the initial phase and
liver. A commercially feasible vaccine that might long-term follow-up. Am J Roentgenol.
also reduce parasite transmission and reduce the 2007;189:824–8.
chances of liver damage in the field is a realistic K a b a a l i o l u A , Cu b u k M , Se n o l U ,
goal. Alternative adjuvants, routes of delivery, as Cevikol C, Karaali K, Apaydin A, et al.
well as the production of a recombinant protein Fascioliasis: US, CT, and MRI findings
that mimics the protection of the native protein with new observations. Abdom Imaging.
are among the latest developments. 2000;25:400–4.
Keiser J, Utzinger J. Emerging foodborne
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Alvarez-Sánchez MA, Mainar-Jaime RC, Pérez- 2005;11:1507–14.
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2006;59(13):424–5. Trends Parasitol. 2007;23(11):555–62.
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A, Fernandez J. Sonographic findings of Fascioliasis and other plant-borne
hepatic lesions in human fascioliasis. J Clin trematode zoonoses. Int J Parasitol.
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Dreyfuss G, Vignoles P, Abous M, Rondelaud Mezo M, Gonzalez-Warleta M, Carro C,
D. Unusual snail species involved in the Ubeira FM. An ultrasensitive capture
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Esteban JG, González C, Bargues MD, Angles Parasitol. 2004;90:845–52.
R, Sánchez C, Náquira C, et al. High Richter J, Freise S, Mull R, Millan JC.
fascioliasis infection in children linked to Fascioliasis: sonographic abnormalities
a man-made irrigation in Peru. Trop Med of the biliary tract and evolution after
Int Health. 2002;7(4):339–48. treatment with triclabendazole. Trop Med
Graham CS, Brodie SB, Wellea PF. Imported Int Health. 1999;4:774–81.
Fasciola hepatica infection in the United Rondelaud D, Vignoles P, Abrous M, Dreyfuss
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Clin Infect Dis. 2001;1(1):331–5. of Fasciola hepatica in natural watercress
Chapter 5: Trematode Infections 269
Clonorchis sinensis
The metacercaria excysts in the duodenum, the feces. The miracidium hatches only after the
and the young fluke moves through the ampulla egg is ingested by the first intermediate host.
of Vater to the common bile duct, and then to The first snail intermediate host of C. sinensis
the distal biliary capillaries where it matures belongs to the following genera: Parafossarulus
into an adult worm. The adult fluke attaches (P. manchouricus, P. anomalospiralis, and P.
itself to the mucosa of the bile duct by using stratulus), Bulinus (B. striatulus), Semisulcospira,
its suckers, and by embedding itself in sticky Alocinma (A. longicornis), Thiara (T. granifera),
mucus without causing permanent ulceration and Melanoides (M. tuberculatus). On the other
of the epithelial lining. The flukes may also be hand, O. felineus and O. viverrini require snails
found in the pancreatic duct and the gallbladder. belonging to the genus Bithynia.
The worm feeds on tissue fluids, red blood cells, Upon entry into the snail host, the
and mucus. miracidium transforms into a sporocyst, which
The egg is fully mature when it is released subsequently produces rediae. Each redia, in
from the worm. It passes with the bile to the turn, produces cercariae that are released into
intestine, and escapes into the environment with the surrounding water. Upon contact with the
272 Medical Parasitology in the Philippines
non-specific clinical signs, such as diarrhea and upper quadrant abdominal pain, nausea, and
abdominal pain. Infections with a moderate emesis have been reported. Chronic symptoms
parasite load (101-1,000 flukes) may cause fever, include biliary tract obstruction, inflammation,
diarrhea, loss of appetite, rash, edema, night and fibrosis, as well as liver abscess formation,
blindness, swollen abdomen, and enlargement of pancreatitis, and suppurative cholangitis.
the liver. Patients with a very high worm burden
A. Correlation of Opisthorchiasis and
(up to 25,000 flukes) may also present with Clonorchiasis with Cholangiocarcinoma
acute pain in the right upper quadrant. Often,
the acute symptoms subside after a few weeks, Opisthorchis and Clonorchis parasitize the
and are followed by chronic complications. In bile ducts of millions of individuals in the Far
the chronic stages, liver malfunction can occur. East. The most important aspect of infection
Calculi, acute suppurative cholangitis, recurrent with these flukes is their role in carcinogenesis.
pyogenic cholangitis, cholecystitis, hepatitis, Numerous studies have shown that these flukes
and pancreatitis are among the more severe late are closely associated with the development
complications. of cholangiocarcinoma. The link between C.
An increased risk of developing hepatocellular sinensis and cholangiocarcinoma is supported
carcinoma and cholangiocarcinoma are among by epidemiological data. In 1956, it was
the most significant sequelae. C. sinensis has estimated that 15% of primary liver cancers
been classified by the International Agency in Hong Kong were cholangiocarcinomas
for Research on Cancer (IARC) as a probable associated with C. sinensis. A study of 2,635
carcinogen (group 2A). necropsy cases in Thailand showed that
Infections with O. viverrini are often 78% of cholangiocarcinomas were associated
asymptomatic, particularly those of light with liver fluke infection. In certain areas
intensity. Flatulence, fatigue, dyspepsia, right of Korea with an extremely high prevalence
upper quadrant abdominal pain, anorexia, and of Clonorchis, fluke infection increased the
mild hepatomegaly occur in approximately 5 relative risk of cholangiocarcinoma six-fold.
to 10% of infections. Severe infections, which Experimental studies in animals have confirmed
are rare, might cause obstructive jaundice, the carcinogenic potential of these parasites.
cirrhosis, cholangitis, acalculous cholecystitis, Studies carried out in the northeastern
or bile peritonitis. part of Thailand found a positive correlation
Cholangiocarcinoma is the most serious between the endemicity of opisthorchiasis
complication of infection with O. viverrini. and the frequency of cholangiocarcinoma.
Studies carried out in the northeastern part The highest incidence of cholangiocarcinoma
of Thailand found a positive correlation has been reported for areas where O. viverrini
between the endemicity of opisthorchiasis is highly endemic. Sakol Nakhon (upper
and the frequency of cholangiocarcinoma. Northeast Thailand) has the highest national
Although the pathophysiology is not entirely mortality rate of liver and bile duct cancer, at
understood, many factors are likely involved 61.4 attributed deaths per 100,000 people. A
in carcinogenesis, including mechanical and similar association between opisthorchiasis and
chemical irritation of the tissue by the flukes, bile duct cancer has been observed in Lao PDR,
and host immune responses. where the prevalence of O. viverrini is high.
In contrast to infections with C. sinensis The pathogenesis of Clonorchis and
and O. viverrini, many patients infected with Opisthorchis-associated cholangiocarcinoma
O. felineus suffer from fever and hepatitis-like involves several mechanisms. Chronic irritation
symptoms in the acute stage of infection. Right and inflammation caused by the fluke can result
274 Medical Parasitology in the Philippines
Agents and biologically active fractions Korea, Japan, Vietnam, and India; and O.
derived from medicinal plants grown in viverrini in Thailand, Laos, Malaysia, and
Siberia have been tested in vitro and in vivo. in immigrants to North America. A case of
The extract from the aspen bark displayed the a Chinese immigrant with clonorchiasis in
highest activity against Opisthorchis. The results Australia has been reported. The patient was
of chemical and chromatographic studies have said to have harbored the parasite for 26
indicated that active fractions contain salicin years without developing neoplasia. A case
and its derivatives. The aspen bark produces of opisthorchiasis has been reported from the
no substantial toxic effect in laboratory animals Davao Medical Center in the Philippines.
and belongs to the class “low toxic substances.” The parasite was recovered during a surgical
The artemisinins and synthetic peroxides operation of the bile ducts.
(i.e., OZ78) also possess trematocidal properties O. viverrini infections remain a major public
against schistosomes, C. sinensis, and Fasciola health problem in Northeast Thailand, where
hepatica in vivo. Tribendimidine also shows approximately one-third of the population
activity against the intestinal trematode is infected. The northeast region is largely
Echinostoma caproni, C. sinensis, and O. populated by Thais and people of Laotian
viverrini. A single 150 mg/kg of body weight descent who eat raw fish, which harbor the
oral dose of either artemether, artesunate, infective stage of the fluke.
or tribendimidine resulted in worm burden The distribution of liver fluke disease
reductions of 99 to 100% in rats harboring is related, in part, to the distribution of
adult C. sinensis. OZ78, at a single 300 mg/kg intermediate hosts and animal reservoir hosts.
oral dose, achieved a worm burden reduction of Traditional consumption of improperly cooked
98.5% against adult C. sinensis in rats. fish, and indiscriminate defecation habits
among rural inhabitants are significant factors
Epidemiology
that determine the high prevalence of liver fluke
Transmission of clonorchiasis and infection in an area.
opisthorchiasis is by consumption of raw,
Prevention and Control
undercooked, salted, dried, or pickled freshwater
fish that harbor encysted metacercariae. The main strategies for liver fluke control
Reservoir hosts are fish-eating mammals such consist of three interrelated approaches, namely:
as dogs, cats, and rats. (a) stool examination and treatment of positive
Current global estimates for C. sinensis cases with praziquantel in order to eliminate
infection is 35 million, with 601 million people human host reservoir, (b) health education for
at-risk of acquiring the infection. The estimated the promotion of cooked fish consumption
number of persons infected with O. viverrini is in order to prevent infection, and (c) proper
9 million, with 68 million people at-risk, while human waste disposal in order to interrupt
about 1.2 million are estimated to be infected transmission.
with O. felineus, and 12.5 million at-risk. An alternative approach to control
O. viverrini and C. sinensis chronically transmission is by making the fish intermediate
infect over 30 million people in Southeast host safe for consumption. A study suggested
Asia, resulting in significant morbidity and that irradiating fish at a dose of 0.15 kGy
predisposition to cholangiocarcinoma. C. could control the infectivity of C. sinensis
sinensis is endemic in China, Korea, Japan, metacercariae. Freezing or storing infected
and Vietnam; O. felineus has been reported in freshwater fish in heavy salt may not be effective
Europe, Turkey, the former USSR countries, in the prevention of clonorchiasis. Acetic acid
276 Medical Parasitology in the Philippines
(3-6%) pretreatment for four hours increases Khandelwal N, Shaw J, Jain MK. Biliary parasites:
the salt penetration rate into the muscles of diagnostic and therapeutic strategies. Curr
fish, which accelerates the death of O. felineus Treat Options Gastroenterol. 2008;11:85–
metacercariae. 95.
In the Philippines, only two cases of Kuznetsova VG. Pathogenesis of chronic and
clonorchiasis, both in foreigners and likely residual opisthorchiasis. Med Parazitol
imported, had been diagnosed at the College (Mosk). 2001;21–3.
of Public Health, University of the Philippines Le TH, De NV, Blair D, Sithithaworn P,
Manila. McManus DP. Clonorchis sinensis and
Opisthorchis viverrini: Development of a
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a n d c h o l a n g i o g r a p h i c p i c t u re o f Li BZ. Discovery of Parafossarulus anomalospiralis
hepatic clonorchiasis. Gastroenterol. as the first intermediate host of Clonorchis
2002;34(2):183–6. sinensis. Zhonghua Liu Xing Bing Xtte Za
Eduardo SL. Food-borne parasitic zoonoses in Zhi. 1985;6(4):199.
the Philippines. Southeast Asian J Trop Lim JH. Radiologic findings in clonorchiasis.
Med Public Health. 1991;(22):16–22. Am J Roentgenol. 1990;155(5):1001–8.
Fan PC. Viability of metacercariae of Clonorchis Sayasone S, Odermatt P, Phoumindr N,
sinensis in frozen or salted freshwater fish. Vo n g s a r a v a n e X , Se n s o m b a t h V,
Int J Parasitol. 1998;28(4):603–5. Phetsouvanh R, et al. Epidemiology of
Keiser J, Utzinger J. Emerging foodborne Opisthorchis viverrini in a rural district of
trematodosis. Emerg. Infect. Dis. southern Lao PDR. Trans R Soc Trop Med
2005;11:1507–14. Hyg. 2007;101:40–7.
Keiser J, Utzinger J. Food-borne trematodiasis. Siththarvorn P, Pipitgool V, Srisawangwong T,
Clin Microbiol Rev. 2009; 22(3): 466–83. Elkins DB, Haswell Elkins MR. Seasonal
Keiser J, Xiao SH, Chollet J, Tanner M, Utzinger variation of Opisthorchiasis viverrini
J. Evaluation of the in vivo activity of infection in cyprinoid fish in northeast
tribendimidine against Schistosoma mansoni, Thailand: implications for parasite control
Fasciola hepatica, Clonorchis sinensis, and and food safety. Bull World Health Organ.
Opisthorchis viverrini. Antimicrob Agents 1997;75(2):125–31.
Chemother. 2007;51:1096–8. Sithiathaworn P, Yongvanit P, Tesana S,
Keiser J, Xiao SH, Dong Y, Utzinger J, Pairojkul C. Liver flukes. In: Murrell KD,
Vennerstrom JL. Clonorchicidal properties Fried B, editors. Food-borne parasitic
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P, Tesana S, et al. Effect of artesunate and Sripa B, Pairojkul C. Cholangiocarcinoma:
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Chapter 5: Trematode Infections 277
278
Chapter 6: Arthropods and Mollusks of Medical Importance 279
Classification of Arthropods
kidney-shaped. The outer face of the compound soluble foods. The mandibles are absent, and
eye is composed of many small six-sided lenses the maxillae are represented only by the palps.
called facets. In general, the active flying insects The labrum and labium fuse to form a proboscis
have large eyes with many facets, while the with a spongy tip called the labellum. The insect
walking types have fewer facets. Some parasitic regurgitates saliva to dissolve the food. Then,
insects have poorly developed eyes, as in some the capillary grooves at the base of the labellum
fleas. carry the liquefied food to the food canal inside
Insects have an upper lip or labrum, a lower the proboscis (Figure 6.4).
lip or labium, a pair of maxillae or upper jaw,
and a pair of mandibles or lower jaw. The shapes
and sizes of these structures vary according
to the insects’ feeding habits. There are four
principal types of mouthparts:
1. Chewing mouthparts
3. Piercing-sucking mouthparts
B. Thorax
B. Respiratory System
They are milky white to opaque in appearance Because of the chitinized cuticle, the
due to deposition of waste products within insect’s skin is not sensitive to contact. The
their cells. sense of touch is made possible by sensory
hairs connected to a nerve (sensory nerve cell),
F. Reproductive System
which is stimulated if hairs are disturbed.
Insects are dioecious; the male and female Nerve endings are usually concentrated in the
must mate before eggs are produced. Insects mouthparts, antennae, and tarsi.
which lay eggs are called oviparous, while those Taste is usually perceived by the mouth and
which deposit larvae are called viviparous. mouthparts, by the palpi or even by the protarsi.
The reproductive organs of the female Palps also bear olfactory organs. The sense of
(Figure 6.14A) consist of a pair of ovaries which smell is highly developed in insects and is used
produce eggs and pass them into the oviduct, for locating food, finding a mate, and locating
where they may be fertilized by sperm cells a suitable oviposition site.
stored in the spermatheca. Some species have Insects generally respond only to specific
accessory glands which secrete an adhesive noises, such as the sound made by the wings of
coating for the eggs. a female mosquito. Sound waves may be picked
The male reproductive organs (Figure up by fine sensory hairs or by an auditory drum
6.14B) consist of a pair of testes in which sperm located on the lower part of the insects’ front
cells are developed. The seminal vesicle serves legs. Only some insects, like grasshoppers,
as storage for spermatozoa until mating occurs. cicadas, crickets, and other species of moths
The accessory glands secrete a liquid substance have “ears” or tympanic membrane. Flies and
to serve as a vehicle for the sperm cells, which mosquitoes are believed to hear by means of a
are then passed into the vas deferens and into cup-like organ on the second antennal segment,
the penis or ejaculatory organ. which responds to sound waves picked up by
the rest of the antennae.
The principal organs of sight are the
compound eyes and ocelli. Insects cannot move
nor focus their eyes. It is not possible for insects
to see a sharp clear image, and they are only able
to see blurred images. These eyes are provided
with nerves, which transmit stimuli to the brain.
Because of these different senses, insects
are able to react to their environment. Their
responses arise from simple stimuli, such as
Figure 6.14. Reproductive systems of an insect
light, heat, gravity, hunger, and smell. Their
(From Baltazar CR, Salazar NP. Philippine insects:
an introduction. Quezon City: University of the reactions consist of more or less fixed behavioral
Philippines Press; 1979.) patterns and they react similarly to the same
stimulus. This is called automatic behavior,
G. The Senses
which does not involve reasoning. With insects,
behavioral reactions are usually immediate.
Insects also possess the senses of touch, Although the brain is located in its head, each
taste, smell, hearing, and sight. They also of the body regions act independently, or in
possess other auxiliary senses such as the sense a semi-autonomous manner, because pairs of
of balance, and possibly orientation. nerve centers called ganglia are located along
Chapter 6: Arthropods and Mollusks of Medical Importance 285
the bottom side of the insect’s body and are D. Class Chilopoda (centipedes or hundred-
connected to the brain by a nerve cord. legged worms)
Arthropods can cause direct and indirect These arthropods are terrestrial, elongated,
injuries to humans. Below is the list of medically and have many segments. The body is
important classes and orders under Phylum dorsoventrally flattened with a pair of legs on
Arthropoda. Discussion of their important each body segment. The appendages of the first
features and roles in human disease are given body segment are modified to serve as poison
in the next two sections. claws.
A. Class Insecta
E. Class Diplopoda (millipedes or thousand-
Order Diptera (mosquitoes and flies) legged worms)
Order Siphonaptera (fleas) These are terrestrial, elongated and have
Order Hymenoptera (bees, wasps, and ants) many segments. The body is cylindrical with
Order Lepidoptera (moths and butterflies) two pairs of legs per body segment. There are
Order Hemiptera (bed bugs and kissing no poison claws. They do not bite humans, but
bugs) secrete substances that are irritants to human
Order Anoplura (sucking lice) skin.
Order Coleoptera (beetles)
F. Class Pentastomida (tongue worms)
B. Class Crustacea
Adults have elongated bodies which are
These arthropods are aquatic in nature. either flattened (e.g., Linguatula in dogs) or
Their bodies are divided into two: cephalothorax cylindrical (e.g., Armillifer in pythons). In
(head and thorax fused together) and abdomen. Armillifer, the body is divided into a series of
Respiration is either by means of true gills or unusually conspicuous rings, which are not true
directly through the body wall. segments. This characteristic raises questions
There are two orders of medical importance: on whether this class should be under Phylum
Order Copepoda (cyclops) Arthropoda. The larval stage, however, is
Order Decapoda (macrocrustaceans, e.g., segmented. The adults usually live in the lungs
crabs, lobsters, and shrimps) or air passages of their hosts, while larvae live
free or encysted in the viscera of some other
C. Class Arachnida hosts.
These arthropods are both aquatic and References
terrestrial in nature. Their bodies are divided
into a cephalothorax and abdomen. The Baltazar CR, Salazar NP. Philippine insects: an
cephalothorax bears six pairs of appendages: introduction. Quezon City: University of
anterior chelicerae, pedipalps, and four pairs the Philippines Press; 1979.
of walking legs. de las Llagas LA. Study guide in medical
There are three orders of arachnids which entomology. 1987. Located at: College of
are of medical importance: Public Health Library, University of the
Philippines Manila.
Order Scorpionida (scorpions) de las Llagas LA, Abong J. Identification and
Order Araneida (spiders) characterization of local house dust mites:
Order Acarina (mites and ticks) potential for native allergen production for
286 Medical Parasitology in the Philippines
Ways by which Arthropods Affect Humans follow repeated exposure to various venomous
arthropods. Arthropods that cause direct injury
T he direct effects of arthropods on humans are
generally classified as: (a) envenomization;
(b) ectoparasitism; (c) ingestant and inhalant
through envenomization are described below.
A. Order Hymenoptera (bees, wasps, and
allergens; (d) food, water, and house pests; (e) ants)
myiasis; and (f ) entomophobia and delusory The name of the order comes from the
parasitoses (Table 6.2). Greek word hymen meaning membrane and
ptery meaning wing. These are, therefore,
Table 6.2. Specific injuries and their causative membranous-winged arthropods. Their
agents mouthparts have strong jaws, which are
adapted for biting. Typically, there are two
Injury Agents
pairs of wings, with the hind pair being smaller
Envenomization Venomous arthropods: bees,
wasps, kissing bugs, ants, than the front pair. The wings are folded back
caterpillar, centipede over the abdomen when at rest. The body is
spider and scorpion
divided into three segments: head, thorax, and
Ectoparasitism Non-venomous arthropods:
mosquito, flea, lice, mite
abdomen. The abdomen is further divided into
and ticks abdominal segments, but usually only six or
Inhalant allergens Dead/decomposing bodies of eight are evident. The last abdominal segment
insects: cockroach feces,
hairs and spines, house dust
is a modified ovipositor, the stinging apparatus
mites (HDM) of a female hymenopteran. This modification
Ingestant allergens Mites, cockroach feces, larval of the egg-laying tube enables it to function as
stages of small beetles a very efficient weapon for both offense and
Contact allergens Urticating caterpillar hair, blister defense. The sting is withdrawn into the body
beetle, millipede
when not in use. The presence of an ovipositor
Food and water pests Moth, beetle, mites,
chironomids, maggots serves to identify the female since the sting is
House pests Mosquitoes, flies, cockroaches absent in the male.
Myiasis Fly maggots feeding on
The stinging hymenopterans are divided
human wounds into two distinct groups: those that kill their
prey by stinging, and those that sting only to
paralyze their prey.
Envenomization
Formic acid, which causes the paralysis,
Venoms are poisonous substances, which can be found at the base of the stinger of
certain animals secrete and introduce by biting some hymenopterans. The apparatus of the
or stinging. Arthropod venoms are usually hymenopteran that kills has an acid gland
poisonous when they are injected through the opening directly into the poison sac, and an
integument, or come in contact with injured alkaline gland, which is comparatively small.
skin. The toxic effect of the injected venom It is the combination of these acid and alkaline
depends upon its chemical composition and fluids that results in the death of the prey or
the amount injected. Allergic reactions may causes extreme pain.
288 Medical Parasitology in the Philippines
The larvae of moths and butterflies are Plate 6.6. Caterpillar head and thorax, lateral
called caterpillars (Plates 6.5–6.6). They usually view (Courtesy of Dr. Lilian de las Llagas)
have a cylindrical, worm-like body which is
divided into 12 segments: the first three make mechanical effect, similar to that of glass fibers.
up the thorax, and the other nine the abdomen. The hairs are of several kinds and many of them
The well-developed head bears a mouth, 12 are barbed, so that they tend to stick to the skin.
tiny eyes and two very short antennae. The Upon contact, the susceptible individual may
mouthparts of the larvae consist of strong biting experience a burning sensation on the affected
jaws and mandibles adapted for biting. This skin, which may show redness or inflammation.
differs from the adults, which have sucking Other areas may show urticarial wheals.
mouthparts. Some larval species have spines If the hairs get into clothing, widespread
or hairs, which may contain toxin. In some dermatitis may occur. Wind-blown hairs in
instances, irritation seems to be largely due to a drinking water can also cause inflammation of
the mucous membrane of the mouth.
D. Class Chilopoda
of their hiding places at night to obtain food, and Loxosceles (brown widow/recluse spider).
consisting mainly of insects and other arachnids. The females of both spiders destroy or kill the
Although scorpions rarely sting humans, males after mating. Thus, they are called “widow
they are considered dangerous since they spiders.”
produce hemolytic and neurotoxic venom.
1. Latrodectus
Investigators have described the venom to be
protein in nature, and its toxicity is dependent The mature female black widow spider is
on sulfhydryl groups. Hemolytic venom causes deep black in color. It has red markings in the
painful swelling at the site of the sting, which form of an hourglass on the underside of its
diminishes within 30 minutes. Neurotoxic abdomen. It is approximately 1.2 to 5.1 cm in
venom may produce numbness at the sting size (Plate 6.10).
site, profuse sweating, salivation, nausea, and
paresthesia of the tongue. Drowsiness may
follow the immediate sharp pain. It has been
observed that if the victim is alive for three hours
after the sting, survival is probable. No other
arthropod produces these symptoms.
A. Order Araneida (spiders)
Plate 6.13. Sandfly (Phlebotomus spp.) Plate 6.14. Horsefly (Tabanus spp.)
(Courtesy of Dr. Lilian de las Llagas) (Courtesy of Dr. Lilian de las Llagas)
Eggs require a moist environment with habitat, where the environment is moist. Most
high humidity, such as holes in the ground and species are aquatic or semi-aquatic.
leaf litters. Because of their mouthparts, these flies
inflict very painful bites, resulting in erythema
2. Suborder Brachycera (e.g., horseflies and
deerflies) and swelling. Their attacks are usually persistent,
producing multiple painful non-pruritic lesions
The antennae are shorter than the head on exposed areas.
and thorax combined, and is composed of
3. Suborder Cy clorrapha/Or thorapha
three segments. The third segment is enlarged
(e.g., houseflies, Stomoxys, “biting housefly,”
and bears a terminal bristle called the style. The and other biting flies)
mouthparts belong to the cutting-sponging
type. The antennae consist of three segments.
The third segment is enlarged and carries
a. Family Tabanidae (Tabanus and Chrysops)
a conspicuous bristle called the arista. The
These flies vary in size depending on the mouthparts are of the sponging and piercing
species. They can be smaller than a housefly, or types.
they can be very large, measuring 5 to 25 mm. This fly resembles the housefly (Musca)
Tabanus (horse fly) is uniformly black but has very closely, but differs from the housefly by
whitish markings on the thorax and abdomen. having a piercing-sucking type of mouthparts.
Its wings are clear (Plate 6.14). Chrysops (deer It has four brown-black longitudinal bands on
fly) is smaller than the horse fly and has a more its thorax, and its antennae are of the aristate
rounded head. The middle part of its wing is type. It breeds in moist, rotting, and fermenting
patterned with a brown coloration. Males of vegetable matter, such as grass, hay, or horse
these flies do not bite. Eggs are deposited on manure. Both males and females suck blood.
the underside of leaves, twigs, stems, stones, They are active at daytime and bite outdoors.
and rocks overhanging or adjacent to their larval They inflict very painful bites.
296 Medical Parasitology in the Philippines
Plate 6.15. Louse (Pediculus humanus capitis) Plate 6.16. Pubic louse (Phthirus pubis)
(Courtesy of Dr. Lilian de las Llagas) (Courtesy of Dr. Lilian de las Llagas)
Chapter 6: Arthropods and Mollusks of Medical Importance 297
Linognathus (cattle louse), Menopon (chicken time. Any change in humidity, temperature, or
louse), and Columbicola (pigeon louse). These vibration stimulates the pupae to escape from
are lice of domestic animals, and they do not their cocoons and enable them to emerge as
attack or infest humans. adults. As fleas suck blood from their hosts, they
All lice have similar life histories. The adult inject saliva to prevent the host’s blood from
lays eggs, which are called nits. These appear as clotting. This secretion contains amino acids,
white or gray oval bodies which are glued to the peptides, ketones, low molecular weight sugars,
hair by the head, or by the gonopod, as seen polyhydric alcohols, phenols, aldehydes, and
in pubic lice. The young resemble the adults, phosphates, all of which are capable of inducing
except in size. They require at least 1 week to sensitivity in the host.
complete development. Bites appear as small punctures, which
represent areas probed by the fleas. Initially, the
C. Order Siphonaptera (fleas)
flea explores the exposed skin area completely,
These are wingless insects measuring less frequently stopping to probe the surface without
than 4 mm, usually l.4 to 2 mm in length. necessarily feeding at each probe site. Once a
The body is laterally compressed and covered suitable site is selected, the flea bites and remains
with spines which enable them to move freely. attached. It then moves along, biting and feeding
The antennae are short, three-segmented, in a grouped but irregular pattern, resulting in
club-shaped, and embedded in a deep groove. multiple lesions. Grouping, therefore, is one
The legs are adapted for jumping, allowing of the most distinct descriptions of the lesions.
them to jump as far as 28 cm vertically or 32 Appearing immediately around the probe
cm horizontally. On smooth surfaces, they site is a wheal with or without accompanying
progress by means of short jumps and running. erythema. Aside from the presence of multiple
Both sexes feed on blood. The mouthparts are zigzag lesions, the diagnosis of flea bites is also
adapted for piercing and sucking. Compound confirmed by previous exposure to animal hosts.
eyes are lacking. Some species, however, possess
D. Order Hemiptera (bed bugs)
degenerate eyes without distinct facets, while
others are completely blind. In some species, Cimex hemipterus is common in tropical
a conspicuous row of spines or a “comb” climates. Bed bugs inflict very irritating and
is present. This is useful in recognizing the itchy bites. On examination, multiple bite
different species of fleas. lesions are found with erythematous wheals
The most common species are Ctenocephalides of uniform size with red punctate centers that
canis (dog flea), C. felis (cat flea), Pulex irritans persist for many days. The skin condition caused
(human flea), and Xenopsylla cheopis (rat flea). by a Cimex bite is called cimicosis. Bed bugs are
Although Ctenocephalides preferably feed on generally nocturnal feeders (Plate 6.17).
dogs and cats, they can also bite humans when The bug uses its beak-like proboscis,
their preferred hosts are not around. with its mandibles and maxillae, to pierce or
Fleas remain on their hosts less constantly puncture the skin of the host. It feeds directly
than lice do. Female fleas, after blood feeding, from the capillaries. The combination of initial
lay their eggs on the fur of the hosts, in dust, skin piercing, and the subsequent probing for
on debris, in floor cracks, and under rugs and blood, results in swelling and irritation. It is
carpets. The larvae feed on organic debris. They reported that the amount of saliva injected
usually avoid light. Pupae emerge after 10 to by the bed bug is around 0.16 µL. This saliva
12 days and may remain inactive for some contains an anticoagulant.
298 Medical Parasitology in the Philippines
1. Mites
a. Chigger infestation
groups, and is very common in crowded stumpy legs, and the abdomen is annulated.
dwellings. The usual transfer of the mite is by Other than Demodex, infestation may also
direct contact. The variety of S. scabiei that be caused by Dermanyssus (red poultry mite),
causes sarcoptic mange in dogs can also burrow Ornithonyssus (tropical rat mite), Pyemotes (grain
in human skin but stays only for a limited itch mite), and Acarus (cheese mite).
duration. The mite causes intense pruritus
• Dermanyssus. This mite is known
that is more severe at night and may persist for
to attack humans, but is actually a
some time.
common parasite of wild birds. It
The female mite is 0.3 to 0.45 mm
feeds on blood, causing irritation
in length. It is whitish, disc-shaped, and
and discomfort. Its common name
flattened ventrally. The mite is covered with
is derived from its ability to thrive in
membranous, small, peg-like protuberances, has
poultry houses. The adult is about 1
a few bristles, both dorsally and ventrally. The
mm long and its red color is due to
mite has a few lines across the body, giving it a
ingested blood. The mouthparts are
striated appearance.
modified for piercing and sucking.
The female mite favors places on the body
• Ornithonyssus. This mite attacks people
where the skin is wrinkled, such as wrists,
living in rat-infested buildings, like
elbows, feet, penis, scrotum, breasts, axillae,
dormitories, restaurants, warehouses,
and in between fingers. Using its short, stout,
and granaries. It is capable of inflicting
sharp pincer-like chelicerae, the mite digs and
a bite that is irritating and painful.
eats its way through the surface of the stratum
Ornithonyssus generally resembles D.
corneum. It buries itself, excavates, and creates
gallinae, and is also red after a blood
a tunnel then feeds on liquids oozing from
meal.
dermal cells. During the mite’s progress along
• Pyemotes. People handling infested
the tunnel, it lays about four to six eggs and
grain, cotton, and hay may develop
sometimes defecates while feeding.
dermatitis due to this mite. The adult
Definitive diagnosis is by demonstration
is about 0.2 to 0.3 mm, and is whitish
of the female mite. Physical examination of the
or yellowish. The female has a pair of
patient reveals mite burrows. In chronic cases,
club-shaped setae between its first and
the skin becomes eczematoid.
second pair of legs. The male is about
c. Demodex folliculorum and Demodex brevis 0.16 mm, has a broader body, and has
no club-shaped setae on its thorax.
Demodex folliculorum (on face) and
• Glycyphagus, Acarus, Tyrophagus.
Demodex brevis (on face and trunk) cause
These stored product mites cause
follicle mite infestation. These mites are found
dermatitis in humans often called
in the hair follicles and sebaceous secretions of
miller’s, grocer’s, copra, or worker’s
humans. They are sometimes present on the skin
rash, depending on the material
and usually cause no severe symptoms. These
being handled. These parasites can
mites, especially D. folliculorum, are associated
also precipitate an attack of bronchial
with “black heads.” On rare occasions, the mites
asthma. These mites are about 0.4 to
produce an erythematous follicular eruption in
0.5 mm long. They are whitish or pale
the beard area of men.
yellow in color and resemble Pyemotes
The adult mite is usually less than 0.5 mm
mites, though their chelicerae are large,
in length, and is worm-like and elongated in
and the setae on their bodies are longer
appearance. The thorax bears eight very short,
and more conspicuous.
300 Medical Parasitology in the Philippines
Two types of ticks bite humans: soft Decomposed and pulverized arthropods,
or Argasid, and hard or Ixodid ticks. Hard cast skin, scales, hairs, spines, cocoons, and webs
ticks, which are difficult to remove, are more permeate the air via upward air streams and
frequently encountered. Ticks are readily convection currents, and are thus considered
distinguished from insects by their strongly inhalant allergens of humans (Plate 6.18). Their
fused thorax and abdomen. The body is ovoidal relationship to inhalant-respiratory allergic
and is capable of great expansion, particularly in disease has been the subject of interest of many
females. There are six legs in the larval stage, and workers in the field of allergology.
eight in the nymphal and adult stages. Ticks are
bigger than mites and are usually more than 1
mm in length. The head bears the mouthparts,
which consist of two small, retractile mandibles
or chelicerae, a pair of short palpi, and a well-
developed hypostome armed with teeth.
Generally, ticks pass through the egg, larval,
nymphal, and adult stages over months or years.
Eggs are usually laid on the ground in batches
of 100 to 18,000. The larvae emerge and climb
up any available object in order to reach passing
hosts. Ticks of some species remain on the same
host until they reach maturity, but others find
two or more hosts for their blood meal. Females
take prolonged blood meals lasting for 8 to 10
days. Males, however, remain attached to the
host only for a few hours in order to mate with
females.
Once the tick comes in contact with a host, Plate 6.18. Butterfly scales
(Courtesy of Dr. Lilian de las Llagas)
the hypostome and chelicerae are inserted into
the skin. Using their recurved teeth, a firm
hold is maintained, reinforced by a cement-like Despite the close association between
secretion. The tick can detach quickly once it arthropods and respiratory allergy, there is
is fully engorged without the host noticing still no direct evidence available to justify this.
it. Forceful removal of the tick may result in Evidence has stemmed from positive skin tests
granuloma formation which may persist for days utilizing arthropod extracts, the inability to find
or even months after the bite. This granuloma other etiological factors to explain respiratory
may be due to either a reaction to mouthparts, symptoms, and the presence or abundance
or to injected salivary secretions. The granuloma of arthropods in the immediate environment
measures 0.5 to 2 cm. coinciding with the patients’ allergic symptoms.
Tick paralysis is an acute disorder of the The work of Agbayani et al. in 1989 showed
central nervous system, and is believed to be this relationship.
caused by a neurotoxin secreted by the salivary House dust mites (Dermatophagoides) have
gland of many species of ticks in the process of also been implicated as a source of allergens
prolonged feeding. by some investigators. A study on house dust
Chapter 6: Arthropods and Mollusks of Medical Importance 301
mites (HDM) by de las Llagas and Abong spp., Cheyletus malaccensis, and Suidasia
(2002) on the association between mites and pontifica (Plates 6.19–6.22).
respiratory allergy showed the presence of six Wi n g e d i n s e c t s s u c h a s m a y f l i e s
species of HDM in dust samples collected from (Order Ephemeroptera), caddisflies (Order
houses of patients with a history of bronchial Trichoptera), moths and butterflies (Order
asthma and allergic rhinitis. These mites Lepidoptera), and aphids (Order Hemiptera),
are Dermatophagoides pteronyssinus, Blomia have been observed to be the most common
tropicalis, Glycyphagus spp., Austroglycyphagus arthropods inducing respiratory allergy.
Plate 6.19. Dust mite (Blomia tropicalis) Plate 6.20. Dust mite (Glycyphagus sp.)
(Courtesy of Dr. Lilian de las Llagas) (Courtesy of Dr. Lilian de las Llagas)
Plate 6.21. Dust mite (Dermatophagoides Plate 6.22. Dust mite (Cheyletus malaccensis)
pteronyssinus) (Courtesy of Dr. Lilian de las Llagas) (Courtesy of Dr. Lilian de las Llagas)
Arthropods as Transmitters of Pathogenic their bodies. Some vectors (e.g., fleas, beetles,
Agents crabs, and copepods) serve as intermediate hosts
to some parasites.
A rthropods which are capable of acquiring
and transmitting pathogens that cause
diseases are called vectors. There are two types
Most of the arthropods which are classified
as vectors of diseases belong to Class Insecta,
subclass Pterygota (winged insects such as
of vectors: biological vectors and mechanical
mosquitoes, flies, and cockroaches) and Order
or passive vectors. Biological vectors, (e.g.,
Acarina (mites and ticks).
mosquitoes and biting flies), acquire pathogenic
Several arthropod-associated diseases in
agents in the act of blood-feeding. These
the Philippines are summarized in Table 6.6.
agents undergo multiplication, propagation,
The diseases listed have varying degrees of
and development inside the arthropod’s body.
importance. Based on morbidity and mortality,
After some time, the pathogens assume their
the most important diseases are the mosquito-
infective form and are then transmitted from
borne diseases. Others do not rank high among
one host to another. Mechanical vectors, on
national health care priorities, but they have
the other hand, transmit pathogens by way of
significant public health implications. Diseases
their oral secretions (vomitus of flies) and the
associated with cockroaches and non-biting flies
contaminated external surfaces of their body
(e.g., diarrhea and amebiasis) are important,
(feet, wings, etc.). Mechanical vectors serve
although evidence linking diseases to the
as mere contaminators; the pathogens do not
filthy behavior of these arthropods is purely
undergo multiplication or development inside
circumstantial.
Table 6.6. List of arthropod-associated diseases and their corresponding agents and vectors
The succeeding topics describe the most organ called the siphon, which extends from
important vectors of tropical diseases in the the eighth abdominal segment. The culicine
Philippines: mosquitoes, flies, and cockroaches. larva therefore hangs down from the surface of
the water by the tip of the siphon in order to
Mosquitoes
breathe. The Culex larva has a long and slender
There are two important divisions or siphon, with many ventral hair tufts. Aedes has
tribes of mosquito vectors. The anopheline a short and stout siphon with only one pair of
mosquitoes, consisting of Genus Anopheles, hair tufts. Mansonia breathes through a siphon
which are vectors of human malaria and human modified for piercing and adhering to stems of
filariasis; and the culicine mosquitoes, vectors aquatic plants.
of dengue, Japanese encephalitis, and human C. Pupa
filariasis, which includes the genera Aedes,
Culex, and Mansonia. Mosquitoes undergo a This is the non-feeding stage, found on the
complete type of metamorphosis. Fertilized surface of the water sources. The pupa is mobile
eggs go through four larval stages, develop into and is able to dive rapidly when disturbed. It
the comma-shaped pupae, and then emerge as breathes through a pair of respiratory trumpets.
adults. The immature stages require an aquatic Culicine pupae have longer trumpets than
environment, while the adult, an aerial and anophelines.
terrestrial one. D. Adult
A. Egg
Generally, the wings of anophelines have
Anophelines lay their boat-shaped eggs dark and pale areas, whereas culicines have
individually over the surface of water, each unpatterned wings. Another visual distinction is
having lateral air floats to keep it buoyant. that, at rest, the body of an anopheline mosquito
Culex lay their eggs in rafts. Each Culex egg is forms an angle nearly vertical with the surface
cigar-shaped, and is provided with a corolla at (i.e., the head, thorax, and abdomen are in a
the end. Mansonia lay their eggs under leaves of straight line). The culicine mosquito, on the
aquatic plants. Aedes eggs are laid individually, other hand, lies almost parallel to the surface,
often in artificial containers, and dry hollows, sometimes appearing as “hump-backed.”
which become flooded after the rain. These The abdominal tip is pointed in the
“dry-laid” eggs are able to retain their viability female Aedes, and blunt in Culex. Mansonia has
for long periods without water. speckled legs with asymmetrical brown, yellow,
and gold scales.
B. Larva
Palpi of female Anopheles are as long as the
Eggs of mosquitoes generally hatch after 2 proboscis. Palpi of its males are club-shaped,
to 3 days of contact with water. They are about each with rounded scutellum. Palpi of female
1 to 1.5 mm long when newly hatched and grow culicines are not as long as the proboscis (usually
to a full length of about 8 mm. The larva casts a quarter of the proboscis); male culicine palpi
its skin four times. The stages between molts are are not clubbed, and the scutellum is trilobed.
known as instars. The mosquito larva breathes E. Mosquito Bionomics
through two openings called spiracles. The
spiracles of the anopheline larvae are situated Bionomics deals with the relationship
on the eighth abdominal segment so that in between a species and its environment. An
order to breathe, the larva rests in a horizontal understanding of mosquito bionomics is
position at the surface of the water. In culicines, important in the epidemiology of mosquito
the spiracles are situated at the end of a tubular borne diseases, and in planning methods of
306 Medical Parasitology in the Philippines
and below, but completed at 20 to 30°C. Also, outside human dwellings. This may indicate
the growth of the filarial parasite Wuchereria that An. flavirostris exhibits certain degrees of
in Culex quinquefasciatus is inhibited at mean exophily and exophagy. These observations
temperatures below 24°C and above 34°C. deserve serious attention, as the current indoor
Temperature and humidity affect the residual spraying of insecticide may no longer
survival of mosquitoes. At extremely high or low be effective.
humidities, mosquitoes are unable to regulate Deviations in the characteristics of this
their water loss. They thrive best at 70 to 80% mosquito have been observed, and this may
relative humidity and at a temperature of 20 disqualify the claim that Anopheles flavirostris
to 30°C. is made up of one or two species.
Major Mosquito-Borne Diseases 2. Anopheles litoralis
(Bontoc), Palawan and Sulu. Mansonia has to golden in color. Its legs have many pale
been found in Agusan del Sur. Eastern Samar, markings, and its wings have white and dark
Palawan, and Sulu. broad scales, many of which are asymmetrical.
Morphological Characteristics, Breeding C. Dengue/Dengue Hemorrhagic Fever
Places, and Habits of Vectors at Filariasis
The vectors of dengue in the Philippines
1. Aedes poecilus include Aedes aegypti, which is associated with
This mosquito is associated with urban dengue, and Aedes albopictus, which
Bancroftian filariasis. It breeds in the axils is associated with rural dengue. There is a
of plants like abaca (Musa textiles), banana widespread distribution of these vectors in the
(Musa sapientum), pandanus, gabi (Colocasia Philippines.
esculentum), and biga (Alocasia macrorrhiza). Morphological Characteristics, Breeding
The adult Aedes poecilus has scutellar scales Places, and Habits of Vectors of Dengue
that are mostly broad and white. The dark scales
1. Aedes aegypti
are found on the mid-lobe and form a distinct
dark central patch. A variable number of white This is primarily known as the “tiger
scales are also present at the base of the first four mosquito.” It is black in color, and small to
tarsal segments. medium in size. It has characteristic lyre-shaped,
This mosquito is a nocturnal feeder. silvery markings on its mesonotum. The fore-
However, it is possible to find it seeking a blood and mid-pairs of legs have white narrow bands
meal during the day. It is highly anthrophilic but at the base of the tarsi. The hind pair of legs has
it may feed on animals like birds, bovids, and five broad white bands, hence the name “tiger
dogs. The highest density of these mosquitoes mosquito” (Plate 6.24).
is observed from 10 p.m. to 12 a.m., which This mosquito breeds in clear water
coincides with W. bancrofti periodicity. The collecting in indoor and outdoor containers
density of these mosquitoes is also related such as old tires, vases, jars, and bottles.
to rainfall patterns in endemic areas. This
mosquito is endophilic and partially exophilic.
2. Mansonia
Plate 6.25. American cockroach (Periplaneta Plate 6.27. Oriental cockroach (Blatta orientalis)
americana) (Courtesy of Dr. Lilian de las Llagas) (Courtesy of Dr. Lilian de las Llagas)
Medical Malacology
Lydia R. Leonardo
d. Family Pilidae – Pila spp. (intermediate in the United States and Mexico)
host of Parastrongylus cantonensis and and Planorbarius metidjensis
Echinostoma ilocanum) (intermediate host of Schistosoma
e. Family Synceridae – Syncera luteola haematobium in Portugal and
(intermediate host of Paragonimus Morocco)
iloktsuenensis in rodents in China) iii. Subfamily Segmentininae –
f. Family Hydrobiidae Segmentina spp. and Hippeutis
spp. (both intermediate hosts of
i. Su b f a m i l y Hy d r o b i i n a e –
Fasciolopsis buski and Echinostoma
Oncomelania spp. (intermediate
ilocanum in the Orient)
host of Schistosoma japonicum)
iv. Subfamily Bulininae – Bulinus spp.
a n d Po m a t i o p s i s l a p i d a r i a
(intermediate host of Schistosoma
(intermediate host of Paragonimus
haematobium in Africa, Near East,
kellicoti)
Middle East) and Indoplanorbis
ii. Subfamily Buliminae (syn.
exustus (intermediate host of
Bythiniinae) – Parafossarulus spp.
Schistosoma spindale, S. nasale in
and Bulimus spp. syn. Bythinia
India, Malaysia, and Sumatra)
and Bithinia (intermediate hosts
c. Family Ancylidae – Ferrissia tenuis
of Opisthorchis felineus, Clonorchis
(intermediate host of Schistosoma
sinensis, Metagonimus yokogawai,
haematobium in India)
and Echinochasmus perfoliatus)
d. Family Physidae – Physa spp.
B. Subclass Pulmonata (intermediate host of Echinostoma
re v o l u t u m i n t h e O r i e n t a n d
1. Order Basommatophora
schistosome cercariae producing
a. Family Lymnaeidae – Lymnaea, dermatitis from freshwater and marine
Fossaria, Pseudosuccinea, Radix, shoreline snails)
Stagnicola (first intermediate hosts of
2. Order Stylommatophora
Fasciola hepatica, Fasciola gigantica,
several species of Echinostoma, a. Family Achatinidae – Achatina fulica,
Plagiorchis, and freshwater dermatitis- also known as giant African land snail
producing schistosome cercariae) (intermediate host of Parastrongylus
cantonensis)
b. Family Planorbidae
b. Family Helicellidae – Helicella
i. Su b f a m i l y P l a n o r b i n a e – candidula (intermediate host of
Biomphalaria spp. (intermediate Dicrocoelium dendriticum in Europe
host of Schistosoma mansoni in and Western Asia)
Africa and Near East and in c. Family Cionellidae – Cionella lubrica
tropical America) and Gyraulus (intermediate host of D. dendriticum
spp. (intermediate host of in the United States)
Echinostoma ilocanum in the d. Family Limacidae – common slugs
Orient) Limax and Deroceras (intermediate
ii. Subfamily Helisomatinae – hosts of lungworms of domestic
Helisoma spp. (intermediate mammals and experimentally of
host of Echinostoma revolutum Parastrongylus cantonensis)
314 Medical Parasitology in the Philippines
Temperature and altitude affect snail protection from increased water velocities and
habitats by changing the rate of photosynthesis predators, such as fish and birds, and maintains
and the rate of decomposition, as well as the a suitable temperature and humidity. Aquatic
rate of reproduction of the resident snails. species die when they get trapped on dry land
Permanence and stability of the habitat are during the dry season. Amphibious species
critical factors affecting the presence of snails. like the oncomelanids can survive dessication
Water levels affect the balance in the ecosystem, by burying themselves in mud while sealing
particularly those involving the producers, their apertures with their operculum. They
consumers, and reducers. Small- or medium- can withstand longer periods of drought
sized habitats are less stable than the bigger ones. in the temperate zone than in the tropics.
Snails naturally prefer to build large populations Oncomelanids are found both in and out of
in permanent habitats where they can reproduce the water in moist areas, such as poorly tilled
and establish more secure colonies. Snails that rice fields, sluggish streams, secondary and
find themselves in non-permanent habitats take tertiary canals of irrigation systems, swamps,
advantage of favorable periods by reproducing and roadside ditches.
rapidly. They also resort to estivation to survive
Snail-Parasite Interaction
adverse conditions of drought.
Aside from physico-chemical factors, there Host specificity is noted to be very high
are biological factors that affect snail distribution in the choice of snail intermediate hosts by the
in a potential habitat. Aquatic vegetation can digenean parasites. Out there in the aquatic snail
serve as anchorage, and microflora provide habitat, a schistosome miracidium can most
food sources. Bacteria and fungi are pathogens likely penetrate other species of snails, but its
that may be detrimental to snails. Predators biochemical adaptation to its compatible snail
such as insects, crabs, crayfishes, other snails, species will determine its fate in the tissues of
fishes, amphibians, birds, and mammals can the snails. In a compatible snail species, the
feed on the snails. Lastly, snails are susceptible miracidium is able to develop with the slightest
to parasites like digenetic trematodes and of problems into the cercariae. There might be
nematodes. Snail distribution is usually patchy; slight or restricted encapsulation, which causes
therefore, habitats should be examined at little damage to the parasite. In other species
different sites. Seasonal variations also affect however, they are walled off and unable to
snail densities. develop further as a result of the strong host
Aquatic snail hosts of schistosomes inhabit reaction brought about by the innate cellular
shallow water near the margins of lakes, ponds, defense mechanisms. These capsules that trap
marshes, streams, and irrigation canals. They are the parasites eventually result in the latter’s
found creeping on water plants and mud that destruction.
is rich in decaying organic matter, or on rocks, While the chemical basis for the death of
stones or hard objects covered with algae, or on the parasites in incompatible snail hosts remains
various types of debris. They abound in waters unclear, encapsulation by leukocytes and/or
where water plants thrive, and where the water fibroblasts resulting in death is the simplest way
is moderately polluted with organic matter, of explaining the most effective form of innate
such as feces and urine, as is often the case near resistance in mollusks against incompatible
human habitations. trematode larvae. This shows that susceptibility
Vegetation is an important component of or resistance of snail to infection is a hereditary
the habitat since this provides not only a food character.
source, but also substrates for oviposition and
316 Medical Parasitology in the Philippines
Cross et al. proposed that the snail- consumed by the parasites. There is an overall
trematode compatibility is a highly specific reduction in proteins and free amino acids,
relationship often at the population or strain level especially the methionine and heme-containing
for both participants. In the course of millions moiety of hemoglobin, which is eaten up by the
of years of selection and adaptation, the authors parasites. Furthermore, there is an increase in
proposed that the vector-parasite compatibility the activities of acid and alkaline phosphatases
has reached its optimum condition, particularly resulting in increased intracellular activities, and
between the local species of Oncomelania and in exchange of polysaccharides between host
the local strain of S. japonicum. and parasite. Significant reduction in glycogen
After the miracidium settles in a compatible reserve weakens the host tolerance to anaerobic
snail host and starts the intramolluscan conditions.
development, the pressure effects manifest as The presence of parasites affects growth,
congestion of the blood sinuses due to migration fecundity, life span, heart rate, respiration, and
and maturation of the sporocysts. Other general thermal tolerance of the snail host. Growth
effects include toxic effects that may lead to rate is reduced among infected snails, especially
destructive changes in organs, particularly the among younger snails. Reduction in size and
digestive glands, starvation as nutrients are degeneration of the albumen gland result
drained by the parasites, and tissue reaction in lowered egg production. Ohmae et al. in
particularly noted as marked generalized 2003 reported that oogenesis was abnormal
proliferative tissue reaction around dead and in infected snails, as shown by fewer eggs laid
trapped cercariae. and poor hatching ability. Declining heart
The most affected organ, the digestive rate and oxygen uptake have an effect on the
gland or the hepatopancreas, shows radical metabolic rate. Other physiological changes
histopathological modifications such as include lowered maximum thermal tolerance
displacement of tubules and loss of branched limit and hemolymph osmolarity. Snails with
nature, erosion of the tubules’ epithelium, heavy infection have been shown to have higher
rise in the number of cytoplasmic vacuoles, mortality. In general, infected snails are less
overall destruction of gland epithelium and mobile and migrate more slowly.
neighboring tissues, and significant reduction
Snail Control
in the size of the glands.
At the cellular level, marked changes Snail control is an integral component
are noted, such as: cristolysis and reduction in the control and prevention of digenean
in size and number of mitochondria; slight parasites, especially schistosomes. Elimination
atrophy of the Golgi apparatus in the secretory of schistosomiasis through chemotherapy
cells of the epithelium and digestive glands; alone is difficult. Japan is credited with having
irregular outline of secretion granules; myelin eliminated schistosomiasis in the absence of a
figures and electron dense material filling up well-accepted drug of choice (i.e., praziquantel),
vacuoles; and connective tissue matrix becoming mainly relying on measures that targeted the
more electron dense and filled, accumulating snail intermediate host with considerable
collagen-like fibers. success.
Marked alterations in the biochemistry Physical control by handpicking may
of the parasitized snails are shown by the be suitable for large terrestrial snails, but in
decreased level of host glycogen and blood the early phase of schistosomiasis control,
proteins, including fluctuations in lipid the Japanese government resorted to massive
content suggesting that food reserves are being collection of O. nosophora by residents in
Chapter 6: Arthropods and Mollusks of Medical Importance 317
endemic areas, providing various incentives to Ecological control focuses on the alteration
promote this campaign. This method may be of snail habitats to reduce survival of the snails
hard to implement in the Philippines because of and to slow down or prevent their breeding.
the extreme difficulty in locating and collecting This includes radical modification of the
the local species of snail intermediate host, environment to destroy snail habitats and their
which are usually found underneath leaf litter residents. It may be as extreme as removal
and mud. of water by drainage, and proper water
Chemical control using molluscicides management in irrigation systems that may
can wipe out huge populations of snails and involve stream channelization, seepage control,
should be done using appropriate strategies. and construction of diversion and intercepting
Chemical molluscicides include potassium channels. This can be very expensive and will
aluminum sulfate, calcium arsenate, NaPCP require participation of the local irrigation
(sodium pentachlorophenate), Yuramin agency.
(3,5-dibromo-4-hydroxy-4-nitroazobenzene), Removal of shade or shelter from the sun
B-2 (sodium 2,5-dicholoro-4-brompophenol), by clearing of vegetation exposes the snails
and niclosamide (2’,5-dichloro-4- with deleterious effects. Although this method
nitrosalicylanilide). Niclosamide has been produces favorable results, sustainability is
proven to be the most versatile and most a major problem since this has to be done
effective of these synthetic molluscicides, and regularly and is labor-intensive. Cementing
has become the molluscicide of choice. In recent linings of irrigation canals or making them
years, however, the use of niclosamide has been more perpendicular prevents snails from
restricted following claims of its deleterious breeding on the banks or margins of streams
effect on the environment and non-target and irrigation canals. This was one of Japan’s
organisms. Plant derivatives have been shown ways of controlling O. nosophora, and to date,
to have molluscicidal properties. Endod fruits this is seen also as evidence of better agricultural
(Phytolacca dodecandra) are used in Africa management.
to kill snail intermediate hosts of S. mansoni Velocity of water can be accelerated to
and S. haematobium. In the Philippines, dislodge snails by proper grading and cleaning
Croton tiglium, Jatropha curcas, and Entada of the stream bed and removal of debris. If the
phaseoloides have been proven to have promising area cannot be drained, the depth of the water
molluscicidal efficacies. may be increased rendering it uninhabitable
When resources are limited and snail to snails. Snail habitats may be simply covered
colonies are confined to limited areas, with landfill.
focal mollusciciding is effective. Area-wide Japan’s success in eliminating snails in
mollusciciding is recommended in endemic Kurume can be attributed to conversion of the
areas where transmission is spread over a marshy lands into extensive golf courses and
watershed or an irrigation system. Repeated orchards. Constant monitoring and surveillance
applications of molluscicides are needed and of the once endemic area has consistently failed
must be accompanied by vegetation clearing to yield O. nosophora.
to make sure that repopulation of snails is Ecological control methods can be
prevented. The use of chemical molluscicide has incorporated into agricultural programs. Results
been banned in the Philippines in compliance can be permanent if adequately maintained, as
with a widespread campaign because of its shown by the experience in Kurume, Japan.
harmful effects on non-target organisms and Increased agricultural productivity is assured.
accumulation in the environment. The activities can be locally initiated and do
318 Medical Parasitology in the Philippines
not require foreign exchange, unlike the use of The successful elimination of schistosomiasis in
chemical molluscicides. Japan emphasizes the fact that there can be snails
Corollary to ecological control is proper rice even without the disease, and that the snails
cultivation, which brings about environmental can be eliminated by radical transformation
changes and increased productivity. With of the environment resulting in widespread
rice fields serving as important snail habitats, destruction of the snail habitats. Molluscicides,
measures such as deep plowing that turns over may result in large scale mortality of snails but
the soil and buries the snails, harrowing that may not be enough to kill them all. Altering
removes the weeds which provide cover, spacing the environment to make it uninhabitable to
that exposes them to sunlight, and weeding snails is effective, but the cost and effect on the
that removes vegetation, are surefire ways of environment are still uncertain.
destroying the snails. Pesticides used by farmers
References
may even be molluscicidal. The stoppage of
flow of irrigation water between harvesting Bao-Zhen Q, Thomas K, Bogh HE. Allozyme
and planting can certainly interrupt breeding. variation among six populations of the
Drainage makes sure that waterlogged areas are freshwater snail Oncomelania hupensis in
prevented from becoming transmission sites. Zhejiang, China. Southeast Asian J Trop
There have been efforts in some endemic areas Med Public Health. 1996;27(2):400-5.
in the Philippines to coordinate snail control Cross JH, Lo CT. Susceptibility of new
with the local agriculture agency, especially Taiwan foci of Oncomelania hupensis to
where farming methods and irrigation are geographic strains of Schistosoma japonicum.
involved. Southeast Asian J Trop Med Public Health.
In evaluating the effectiveness of the snail 1980;11:374-7.
control program, certain parameters should Dewitt WB. Susceptibility of snail vectors to
be measured, such as reduction in size of area geographic strains of Schistosoma japonicum.
inhabited by snail population, reduction in snail J Parasitol. 1954;40:453-6.
density, change in population structure, and Hsu SYL, Hsu HF. Infectivity of the Philippine
mortality or percentage of dead snails as a result strain of Schistosoma japonicum in
of mollusciciding. Monitoring should include Oncomelania hupensis, O. formosana and
regular checks of snail density and population O. nosophora. J Parasitol. 1960;46:793-6.
structure. Ishi A. Successful parasite controls in Japan:
eradication of schistosomiasis. Asian
The Future of Snail Control
Parasitol. 2005;5:184-276.
Experience in many endemic countries Iwanaga Y, Santos MJ, Blas BL. The
shows that snail control is an integral part in determination of the Oncomelania hupensis
any program to eliminate snail-borne parasitic quadrasi population density using the
diseases, foremost of which is schistosomiasis. banana leaf method in four municipalities
Since the discovery of praziquantel, control of Eastern Leyte, Philippines. Hiroshima J
programs have focused mainly on control of Med Sci. 1977;26:19-27.
morbidity by chemotherapy. Japan eliminated Leonardo L, de Lara A, Regadio A, Estores M,
schistosomiasis even before the advent of Vicente IM, Victoria MV. Molluscicidal
praziquantel primarily through snail control. To activities of four botanical extracts against
date, O. nosophora still thrives in rice fields and Oncomelania hupensis quadrasi, snail
other habitats in the Kofu Basin but has been intermediate host of Schistosoma japonicum.
eradicated in Kurume along the Chikugo River. Acta Med Philipp. 2007;41(2):37-44.
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Malek EA. Snail-transmitted parasitic diseases. Sturrock RF. Current concepts of snail control.
New Orleans: University Book Publishing Mem Int Oswaldo Cruz. Rio de Janeiro.
Company; 1980. 1995;90(2):241–8.
Minai M, Hosaka Y, Ohta N. Historical view Takahiro T, Hirai H, Upatham S, Agatsuma
of schistosomiasis japonica in Japan: T. Sex chromosome differences among
implementation and evaluation of disease the three races (alpha, beta, gamma) of
control strategies in Yamanashi prefecture. the snail intermediate host of Schistosoma
Parasitol Int. 2003;52:321–6. mekongi, Neotricula aperta. Parasitol Int.
Nihei N, Kanazawa T, Blas BL, Saitoh Y, 2000;49:267–72.
Itagaki H, Pangilinan R, et al. Soil factors Tanaka H, Santos MJ, Matsuda H, Yasuraoka
influencing the distribution of Oncomelania K, Santos AT Jr. A quantitative sampling
quadrasi, the intermediate host of method for Oncomelania quadrasi by filter
Schistosoma japonicum, on Bohol Island, paper. Jpn J Exp Med. 1975;45:255–62.
Philippines. Ann Trop Med Parasitol. 1998; Woodruff DS, Staub KC, Upatham S,
92(6):699–710. Viyanani V, Yuan HC. Genetic variation
Ohmae H, Iwanaga Y, Nara T, Matsuda H, in Oncomelania hupensis: Schistosoma
Yasuraoka K. Biological characteristics japonicum transmitting snails in China
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of Schistosoma japonicum. Parasitol Int. Malacologia. 1988;29(2):347–61.
2003;52:409–17. Woodruff DS, Carpenter MP, Upatham S,
Sobhon P, Upatham S. Snail hosts, life cycle Viyanant V. Molecular phylogeography
and tegumental structures of Oriental of Oncomelania lindoensis (Gastropoda:
schistosomes. UNDP/World Bank/WHO; Pomatiopsidae), the intermediate host of
1990. Schistosoma japonicum in Sulawesi. J Mol
Studies. 1999;65:21–31.
Chapter 7
Diagnostic Parasitology
320
Chapter 7: Diagnostic Parasitology 321
All of these drugs have been found to leave Appropriate fixation of parasites in the stool
crystalline residues that can interfere with the will preserve protozoan morphological features
identification of parasites. Stool samples should and prevent possible destruction of helminth
be collected a week after the last intake of any eggs and larvae. Several stool preservatives are
of these drugs. available, but only the more common ones will
be discussed here. When selecting a fixative, the
B. Intake of antibiotics usually decreases possibility of preparing a permanently stained
the number of protozoans for several slide should be considered. Stool samples
weeks. must be adequately mixed with the selected
322 Medical Parasitology in the Philippines
preservative in a proportion of one part stool stools can be examined through the
to three parts preservative. Any of the following wet mount, but difficulty in the
stool preservatives can be used: specific identification of protozoans
may be encountered. The Lugol’s
1. Formalin is an all purpose fixative. A
iodine component should always be
5% concentration is recommended
freshly prepared since it is unstable.
for protozoan cysts, while a 10%
Staining of preserved stools in MIF
concentration is recommended
yields unsatisfactory results.
for helminth eggs and larvae. The
5. Sodium acetate-acetic acid formalin
solution may be buffered with
(SAF) has the advantage of not
sodium phosphate to preserve the
containing mercuric chloride. Images
morphological characteristics of the
of organisms fixed in SAF, however, are
organisms. Preserved stool can be
not as sharp after staining compared
concentrated using formalin-ether/
with those fixed in PVA or Schaudinn’s
ethyl acetate concentration technique
solution. It is a liquid fixative with a
(FECT).
long shelf-life.
2. Schaudinn’s solution is used to
preserve fresh stool in preparation for Methods of Examination
staining the stool smears. It contains
Stool samples are submitted to the
mercuric chloride which is highly
laboratory in the fresh state or as preserved
toxic to humans. Problems of mercury
samples. If stools are fresh, the laboratory can
disposal may therefore arise.
classify the consistency of the stools as formed,
3. Polyvinyl alcohol (PVA) is a plastic
semi-formed, soft, loose, or watery. The
resin which serves to adhere a stool
consistency can give an indication of the stage of
sample onto a slide. It is normally
the organism that may be present in the sample.
incorporated into the Schaudinn’s
Protozoan trophozoites are generally observed
solution, therefore the actual fixation
in soft or liquid stool, while the cysts are often
is done by the Schaudinn’s. The main
found in formed or semi-formed samples.
advantage of using PVA is related to
On the other hand, helminth eggs and
the preservation of protozoan cysts and
larvae can be found in any type of consistency. In
trophozoites for permanent staining.
watery samples, there may be a reduction in the
Stools preserved in PVA can be
number of eggs and larvae due to the dilution
concentrated using FECT and can be
factor. Some authorities recommend the use
shipped to any laboratory for further
of purged stools to increase the chances of
examination. One major drawback of
recovering the protozoan trophozoites. Purged
PVA is the use of mercuric chloride.
samples should be examined immediately after
Some laboratory technologists have
collection.
suggested replacing this compound
The color of the stool can be indicative of
with cupric sulfate.
the presence of the parasite. Presence of blood
4. Merthiolate-iodine-formalin (MIF)
should always be reported. Dark-colored blood
contains merthiolate (also called
suggests bleeding high up in the gastrointestinal
thimerosal) and iodine which act as
tract, while bright red blood means bleeding
staining components, while formalin
from a more distal location. Blood and mucus
acts as the preservative. It is useful for
in soft or watery stools may possibly yield the
the fixation of intestinal protozoans,
presence of trophozoites. Ingestion of some
helminth eggs, and larvae. Preserved
Chapter 7: Diagnostic Parasitology 323
slide and covered with cut cellophane paper of Trichuris, Capillaria, and trematode eggs,
soaked in a mixture of glycerine and malachite especially Schistosoma. This is also the choice if
green solution. Glycerine is a clearing solution stool material comes from animals like cats and
and malachite green is used to give color to dogs. Drawbacks in the use of this technique
the cellophane in order to give a pale green include: loss of parasite to the plug of debris and
background to the eggs and to minimize the possible destruction of protozoan cysts.
brightness of the microscopic field. If malachite
b. Formalin-Ether/Ethyl Acetate Concentration
green is not available, green cellophane soaked Technique (FECT)
in glycerine may be used. The preparation is best
examined within 10 to 20 minutes. This procedure makes use of 10% formalin
The technique is simple and economical, which is an all purpose fixative, and ether, which
and is therefore useful in mass stool examinations. can dissolve neutral fats in the stool. This is
It is very good in detecting eggs with thick shells useful in the recovery of both helminth eggs and
(e.g., Ascaris and Trichuris) but not eggs with protozoan cysts. FECT can also be done with
thin shells (e.g., hookworm). In many instances, formalin-preserved and PVA-preserved stools.
if the preparation is kept too long before More parasites can be recovered from formalin-
examination, hookworm eggs become too preserved samples. Parasite morphology is also
transparent or distorted, making identification better preserved in formalin than in PVA.
very difficult. Usefulness is limited if stools are Sediments from FECT can be stored for a long
diarrheic or watery. Likewise, it is not able to period of time.
detect protozoan cysts and trophozoites. The use of ether has been a cause for
concern in the laboratory sector because of
C. Concentration Techniques
problems in storage and handling of this
Concentration techniques can separate explosive and flammable compound. In
protozoan cysts and helminth eggs from a place of ether, ethyl acetate may be used in
larger amount of stool (usually 1 g in amount) sedimentation procedures. Those who have
based on differences in specific gravity. In tried ethyl acetate claim that it is more efficient
cases of light infections, or if there is a need than ether in the recovery of cestode eggs and
to recover more parasites, stool concentration Giardia cysts. However, ethyl acetate is not
procedures are recommended. These procedures as efficient as ether in the extraction of fat or
are based either on sedimentation or flotation. mucoidal material from the stool.
In sedimentation techniques, a parasite that 2. Flotation Procedures
has a higher specific gravity than the reagent
will sink to the bottom of the preparation, a. Zinc Sulfate (ZnSO4) Flotation
while a parasite with a lower specific gravity The main reagent is a 33% zinc sulfate
will float to the surface. Mounts prepared from solution. Before use, the specific gravity should
flotation techniques are cleaner than those from be checked. The ideal specific gravity ranges
sedimentation. from 1.18 to 1.20. If parasites are exposed to
1. Sedimentation Procedures high specific gravity, distortion and shrinkage
of protozoan cysts and thin-walled nematode
a. Acid Ether Concentration Technique (AECT)
eggs may occur.
The main reagents are 40% HCl, which b. Brine Flotation
can dissolve albuminous material, and ether,
which can dissolve neutral fats in the stool. This This makes use of a saturated table salt
technique is recommended for the recovery solution. Stools are directly mixed with the brine
Chapter 7: Diagnostic Parasitology 325
and the reduction of worm burden following constant, there may be a need for a correction
treatment. factor in computing for the egg count taking
into consideration stool consistency.
1. Kato-Katz Method or the Cellophane
Covered Thick Smear F. Staining of Stool Specimen
This procedure uses a measured amount of Staining of stool specimen can also be done
stool which has been sieved through a wire mesh specifically in the examination of the nuclear
and pressed under cellophane paper soaked in characteristics of amebae. These are also useful
glycerine-malachite green solution. A uniform in the identification of the other intestinal
amount of stool is examined through the use protozoans like Balantidium and Giardia.
of a template with a uniform-sized hole in the Techniques available include:
middle. All eggs seen in the whole preparation
are counted. The total egg count is multiplied 1. Iron-Hematoxylin
with a factor depending on the amount of 2. Trichome
stool used. 3. Periodic Acid Schiff (PAS)
The procedure is useful for assessing the 4. Chlorazol Black E
intensity of infection with Schistosoma and The abovementioned techniques are not
common soil-transmitted helminths like Ascaris, very useful for the identification of coccidian
Trichuris, and hookworm. oocysts like Cryptosporidium, Cyclospora, and
Consistency of the stool is the main Cystoisospora. For these parasites, Kinyoun’s
determinant for the sensitivity of this technique, method of acid-fast staining is recommended.
since well-formed stools yield higher egg counts Acid-fast staining of stool specimen
than moist ones. The technique can only be requires spreading a thin layer of stool on a
done on fresh formed stools and not on liquid glass slide. The oocysts of the three coccidian
and preserved samples. parasites stain pink to red with a blue or green
For the identification of Schistosoma ova, background. The background actually depends
1% eosin solution can be layered over the on the counter stain used. For Cryptosporidium
cellophane paper. This method can help in the and Cyclospora, oocysts are spherical, although
visualization of the miracidium. Cryptosporidium has a diameter of 4 to 6 μm,
2. Stoll Egg Count while Cyclospora are 8 to 10 μm in diameter. On
the other hand, Cystoisospora oocysts are more
This technique makes use of 0.1 N NaOH ovoid than spherical.
and a stool displacement flask calibrated at 56 Generally, these organisms are recovered
mL and 60 mL. The sodium hydroxide acts as a better from diarrheic and watery samples.
stool diluent. It saponifies fat and frees eggs from
fecal debris. The amount of diluted stool used Perianal Swab
for egg counting is measured by Stoll pipettes The perianal swab can be used to recover
calibrated at 0.075 mL and 0.15 mL. The eggs of Enterobius vermicularis and Taenia spp.
constant used to multiply the total egg count The Enterobius gravid female migrates out
depends on the amount of stool examined. through the anus at night time, and deposits
Like the Kato-Katz method, sensitivity eggs on the perianal skin. Taenia spp. gravid
is determined by the consistency of the stool segments can crawl out of the anus and in the
since formed stool can displace more sodium process, ova are squeezed out of the segment and
hydroxide than liquid stool. Aside from the are deposited on the perianal skin.
Chapter 7: Diagnostic Parasitology 327
Duodenal aspiration may be done through 20 minutes, while the morphology and motility
intestinal intubation but there is a simple and of Naegleria trophozoites are also affected
convenient procedure now available in the within the same time period. The CSF must
collection of duodenal contents. This is done be centrifuged at 7,000 g for 10 minutes, the
through the “Entero Test,” also known as the supernatant fluid discarded, and the parasites
String test, where a capsulated yarn is swallowed visualized from the sediment.
by the patient. The yarn is expected to reach
Examination of Tissue Biopsy Material
the duodenum. After about 4 hours, the yarn
is retrieved and the mucoidal material clinging A. Muscle Biopsy
to the yarn is examined for the presence of the
This specimen is very useful in the diagnosis
above mentioned parasites.
of Trichinella spiralis infection, where small
B. Cutaneous or Skin Aspirates pieces of muscles are pressed between two glass
slides and the preparation is examined under
In very rare occasions, there may be
the microscope. Encapsulated larvae may be
requests to examine aspirates taken from
appreciated. While Trichinella spiralis is not
cutaneous ulcerations, like in cases of cutaneous
present in the Philippines, larval infection with
leishmaniasis. Like some of the parasites
Taenia solium can result in cysticercosis, or a
mentioned in other sections of this chapter,
larval infection with Spirometra spp. can result
leishmaniasis is not supposedly endemic in the
in sparganosis. In both cases, muscle biopsy
Philippines but due to exposure in endemic
will be useful in the diagnosis of the conditions.
countries, there are reported leishmaniasis cases
locally. B. Rectal Biopsy
One clinical form of leishmaniasis is
A more common biopsy material
cutaneous, otherwise known as an Oriental sore.
submitted for parasitic diagnosis is rectal
The recommended specimen is an aspirate taken
biopsy. Examination of the rectal tissues can
from below the ulcer bed using a sterile needle.
reveal the presence of deposited Schistosoma
Smears are prepared and stained with Giemsa
japonicum eggs.
when dried. Positive samples will show the
presence of amastigotes. In endemic countries, References
part of the needle aspirate can be inoculated
Ash L, Orihel TC. Parasites: a guide to
into a culture medium.
laboratory procedures and identification.
Examination of Cerebrospinal Fluid (CSF) Chicago: SCP Press; 1987.
Garcia LS, Buckner DA. Diagnostic medical
Trypomastigotes of Trypanosoma cruzi,
parasitology. New York: Elsevier; 1989.
Trypanosoma brucei rhodesiense, and Trypanosoma
Goldsmith R, Heyneman D. Tropical medicine
brucei gambiense may be demonstrated in
and parasitology. Connecticut: Appleton
the CSF. Likewise, trophozoites of Naegleria
and Lange; 1989.
may also be found in the CSF. In cases of
Heinz M. Parasitology in focus: facts and trends.
parastrongyliasis, CSF eosinophilia is a common
Germany: Springer-Verlag; 1988.
finding, although there were reports that among
Manson-Bahr PE, Bell DR. Manson’s tropical
infected children, Parastrongylus larvae have
diseases. 19th ed. London: Bailliere Tindall;
been recovered.
1987.
Immediate examination of the CSF is
Parzy D, Raphenon B, Martet G, Nicolas P, Touze
required since trypomastigotes perish within
JE, Baudon D, et al. Quantitative buffy
Chapter 7: Diagnostic Parasitology 331
coat test kit for falciparum comparative Schmidt GD. How to know the tapeworms.
value in the rapid diagnosis of malaria. Med Iowa: Wm. C. Brown Company Publishers;
Tropicale. 1990;50(1):98–101. 1987.
Rickman L, Oberst R, Sangalang R, Chulay Valencia CI, Abear RF. A modification of
J, Long G, Cabanban A, et al. Rapid the quantitative thick smear method for
diagnosis of malaria by acridine orange Schistosoma japonicum. Southeast Asian J
staining of centrifuged parasites. Lancet. Trop Med Public Health. 1981;12:280–3.
1989;8629(1):3–9. World Health Organization. Basic laboratory
methods in medical parasitology. Geneva:
World Health Organization; 1991.
332 Medical Parasitology in the Philippines
Examination of Tissues
Elia G. Paulino-Cabrera
Plate 7.1. Cysticercus in brain Plate 7.2. Ovary with incidental finding of
(Courtesy of Dr. Elia Paulino-Cabrera) Schistosoma japonicum ova
(Courtesy of Dr. Elia Paulino-Cabrera)
Plate 7.3. Fallopian tube with incidental finding of Plate 7.4. Colon with adenocarcinoma and
Schistosoma japonicum ova Schistosoma ova
(Courtesy of Dr. Elia Paulino-Cabrera) (Courtesy of Dr. Elia Paulino-Cabrera)
Chapter 7: Diagnostic Parasitology 333
obtaining other specimens like blood or stool for factor. It is more practical to biopsy a skin mass
detection of parasites, tissues are usually not the than a visceral mass to document cysticercosis.
initial specimens sent for diagnostic purposes. A fourth factor is the possible complications
Biopsies are done when other specimens yield of the procedure. A hepatic puncture is more
repeatedly negative results or when other tests likely to have complications than a lymph node
are equivocal. For example, clinically suspected biopsy in the diagnosis of visceral leishmaniasis.
ameba cases with negative stool examinations Examples of commonly biopsied organs
may be definitely diagnosed by a direct smear and parasites which may be found therein are
or biopsy of the intestine. A biopsy may also be shown in Table 7.2.
needed in the case of chronic schistosomiasis
when the patient no longer excretes ova. Some Table 7.2. Organs and parasites isolated
parasites are found only in tissues, and biopsy
is the best means of diagnosis. The presence of Organ Parasite
Trichinella spiralis larva in muscle, for instance, Skin and Ancylostoma Gongylonema
subcutaneous braziliense Loa loa
provides a definitive diagnosis of trichinellosis. tissue (larva) Onchocerca
Virtually any organ of the body can be Ancylostoma Sparganum
caninum Strongyloides
examined. Ova, larvae, adult forms, cysts, and (larva)
trophozoites may all be seen. Before doing a Cysticercus
cellulosa
biopsy, several factors should be considered. Dracunculus
First is the nationality and travel history of the Gnathostoma
patient. Leishmaniasis, which is not endemic Lymph node Filaria Trypanosoma
Leishmania
in the Philippines, should be a differential
Brain Cysticercus Schistosoma
diagnosis in a patient with hepatosplenomegaly, cellulose
lymphadenopathy, and a history of travel to Hydatid cyst
the Middle East. The second factor is the life Lung Hydatid cyst Paragonimus
cycle and tissue trophism of the parasite. An Liver Entamoeba Leishmania
adult nematode in a lymph node, for instance, Hydatid cyst Schistosoma
is almost certainly a filarial worm (Plate 7.5). Small intestine Cryptosporidium Microsporidia
Plate 7.6. Adult Trichuris identified by ova in Plate 7.7. Cysticercus with calcareous corpuscles
genital tract (Courtesy of Dr. Elia Paulino-Cabrera) (Courtesy of Dr. Elia Paulino-Cabrera)
characteristics: (a) integument, (b) musculature, to them. Grossly, organs may appear normal,
(c) body cavity, (d) digestive system, (e) enlarged, necrotic, or inflamed. Lesions may
reproductive organs and ova present (Plate 7.6), present as tumorous masses such as in an
and (f ) special glands or structures. ameboma of the colon or echinococcosis of the
The integument may be chitinized liver or kidney. Fibrosis may cause hardening of
(arthropods), striated (acanthocephala), spiny the parenchyma, such as pipestem fibrosis in
(platyhelminths), or smooth (nematodes). schistosomiasis. Microscopic findings may be
Muscles are described either as striated or varied as well. In some instances, no pathologic
smooth, and circular or longitudinal. Points of changes are evident. Intestines of patients with
muscle attachment to the body and the number giardiasis and uncomplicated hookworm disease
of cells per circumference are also noted. typically show normal-looking mucosa.
Meromyarian pertains to few cells (four or Acute reactions are present when there is
less), while polymyarian pertains to numerous tissue necrosis. These are exemplified by early
cells per circumference. The body cavity is amebiasis, ulcerated cutaneous leishmaniasis,
described according to content, which may be trichomoniasis, and strongyloidiasis. Chronic
parenchymatous matrix, mesenchyme cells, or inflammation is seen in any long-standing
fluid. Of interest in the digestive tract are the infection. A specific type of chronic infection
pharynx and intestines. The number of branches is characterized by granuloma formation. Dead
of the pharynx and the number of intestinal cells or degenerating parasites form the center of
should be noted. For the reproductive system, the lesion and are surrounded by lymphocytes,
it should be determined whether the sexes are plasma cells, macrophages, multinucleated giant
separate and whether the gonads are paired and cells, and fibroblasts. Hyaline or eosinophilic
tubular or sac-like. Special copulatory structures material may be present. Several parasitic
may be present. Examples of special structures diseases show this reaction. Schistosomiasis
which serve as diagnostic aids are the calcareous and ascariasis lesions exhibit the characteristic
corpuscles (Plate 7.7) seen in cestodes, and Splendore-Hoeppli phenomenon. In filariasis,
reduplication of esophageal glands as seen in granulomas are known as Meyers-Kouvenaar
the group Trichinellina. bodies.
Tissue specimens may show not only the There are findings that are pathognomonic
parasites themselves but also the body’s reaction for some parasitic diseases. Lymph nodes in
Chapter 7: Diagnostic Parasitology 335
toxoplasmosis are characterized by the presence Trichrome stain has been found to be useful in
of epithelioid histiocytes in the perifollicular differentiating the trophozoites of ameba and
zone. Malaria is characterized by the presence Giardia from host tissue. It also emphasizes
of hemozoin pigment in parasitized red blood structures such as flagella. Giemsa is used for
cells. In the brain, the characteristic finding different protozoa. Table 7.3 summarizes the
is Durck’s granuloma, which consists of glial parasites and special stains used for them.
proliferations around capillaries.
Fine needle aspiration biopsy (FNAB) may Table 7.3. Special stains and corresponding
be done prior to or in lieu of a formal biopsy. parasites
Parasite identification and host tissue response
evaluation may be achieved with this method. Stain Parasite
Aspiration may be done on palpable lesions or Acid-fast Cryptosporidium Isospora
Cyclospora
under the guidance of ultrasound or computed
PAS Entamoeba Toxocara
tomography. Giardia Toxoplasma
Biopsy specimens are placed in 10% Microsporidia (bradyzoites)
(polar Trichomonas
buffered formalin for fixation. Many laboratories granule)
have automated tissue processors which allow Giemsa Giardia Toxoplasma
slides to be completed the next day. Processing Malaria
can also be done manually. Tissues are usually GMS Microsporidia Toxoplasma
(cyst wall)
cut 3 µm thick. Examination of serial sections
Gram stain Microsporidia Trichomonas
may be needed before a diagnosis is made.
Sometimes the parasite is simply too big that Luxol Fast Blue Microsporidia
Song SM, Park JH, Kim J, Kim SI, Hong B. Fine needle aspiration of toxoplasmic
YC, Kong HH, et al. Identification and (Piringer-Kuchinka) lymphadenitis:
characterization of Paragonimus. Parasitol acytohistologic correlation study. Acta
Int. 2008;57(3):334–41. Cytol. 2005;49(2):139–43.
Sun T, Ilardi CF, Asnis D, Bresciani AR, Wong MT, Goh L, Chia KH. Intestinal
Goldenberg S, Roberts B, et al. Light and schistosomiasis manifesting as colonic
electron microscopic identification of intussuception arising from a mucocele of
Cyclospora species in the small intestines. the appendix: report of a case. Surg Today.
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Vega-Lopez F. Diagnosis of cutaneous Warton A. Diagnostic ultrasound of human
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338 Medical Parasitology in the Philippines
for diagnosis can pose some risk to the patient. A antigens as they provide a larger repertoire of
positive antibody test can be a useful indicator of antigens recognized by the immune system.
a recent infection if the patient has no previous However, different types of antigen preparation
exposure to the parasite prior to travel in an (such as native protein, purified peptides,
endemic area. In contrast, positive antibodies and recombinant proteins) may also produce
in a resident of an endemic area may reflect variable antibody results. The use of a mixture
either past or current infection with a specific of antigens can increase antibody detection but
parasite under consideration. Therefore, cross reactivity between parasite species cannot
parasite diagnosis based on positive antibodies be ruled out leading to false positive results.
can only be indicative of infection at some Given these limitations, the results of
indeterminate time and not necessarily current antibody tests in the diagnosis of parasitic
or acute infection. In addition, antibody tests infections must be interpreted with caution.
are useful when significant levels of antibodies The greatest utility of antibody tests is in
are produced with parasitic infections. In some investigating etiology of disease outbreaks and
people, parasitic infections may not stimulate in epidemiologic investigations to map foci of
antibody response or seroconversion may be disease transmission essential to institute control
delayed with onset of clinical symptoms. measures.
Antibody detection assays use whole There are a number of antibody tests
parasites from animal models or in vitro cultures available for the diagnosis of parasitic diseases at
or soluble crude extracts as antigens. Better the Centers for Disease Control and Prevention
sensitivity is achieved with the use of these (CDC), USA (Table 7.4). There are only a few
commercially available antibody detection tests available kits range from 93 to 100% when
to diagnose blood-borne parasitic infections used in clinical settings. Some EIA tests come
such as malaria and filariasis, intestinal parasitic in microplate format and are robust enough
diseases such as giardiasis, cryptosporidiosis, to detect Cryptosporidium antigens either
schistosomiasis, and cysticercosis. from fresh, frozen or preserved stool samples
B. Detection of Antigen
in either formalin or sodium acetate-acetic
acid-formalin (SAF). However, concentrated
A more sensitive and specific or polyvinyl alcohol (PVA)-treated samples are
immunodiagnostic test to determine the not suitable for EIA testing. Combined antigen
disease status of patients is the detection of detection of either Cryptosporidium and Giardia
specific parasite antigens. Antigen detection or Cryptosporidium, Giardia and E. histolytica
in serum or whole blood (for blood parasites) are also commercially available as rapid
and in feces, urine, duodenal fluid or biopsy immunochromatographic assays in fresh or
specimens from the small intestine or urine preserved stool specimens. As the name implies,
(for intestinal parasites) is commonly achieved rapid tests have the advantage of quickest
by immunocapture utilizing two antibodies. turnaround time and the least requirement
The first antibody (either monoclonal or for an experienced laboratory personnel. They
polyclonal) is immobilized in a solid phase such also offer the convenience of multiple results
as a microtiter plate or nitrocellulose membrane. in one reaction device without the need for
This will capture the parasite antigen which special equipment. Both EIA and rapid test
is detected by the second antibody, usually a kits show good correlation with DFA, which is
monoclonal antibody labeled with an enzyme. reported to be the most sensitive and specific
A colored reaction is observed after the addition test in the diagnosis of cryptosporidiosis. It uses
of an enzyme substrate. Antigen detection a fluorescein isothiocyanate (FITC)-labeled
tests have quicker turnaround times than monoclonal antibody which detects antigens on
microscopy and do not require experienced the surface of Cryptosporidium oocysts in either
microscopists. To date, much research work concentrated or unconcentrated fecal samples.
has been achieved towards development and Pathogenic E. histolytica and commensal E.
optimization of parasite antigen tests that dispar are morphologically identical. Antigen
resulted in commercially available reagents/kits detection tests that differentiate the two species
for intestinal parasites such as Cryptosporidium eliminate unnecessary treatment of patients.
spp., E. histolytica, Giardia intestinalis, and Commercially available diagnostic kits are
Trichomonas vaginalis (Table 7.5). mostly enzyme-based assays using monoclonal
Several commercially available kits for antibodies that detect galactose adhesins of
the detection of Cryptosporidium antigens the pathogenic E. histolytica. The Techlab E.
come in different formats such as enzyme histolytica II specific for E. histolytica was found
immunoassay (EIA), direct immunofluorescence to be highly sensitive and specific by several
(DFA), or IFA. These kits detect either studies conducted in at least five countries in
Cryptosporidium alone, or combinations the world. A major drawback in using this kit
involving Cryptosporidium and Giardia or in the diagnosis of intestinal amebiasis is the
Cryptosporidium, Giardia, and E. histolytica. The requirement for fresh, unpreserved fecal sample.
choice of test will depend on particular need for Extraintestinal manifestations of amebiasis such
single tests in clinical settings or batch testing as amebic liver abscess (ALA) on the other hand
in epidemiological investigations or research. can be diagnosed by serology. Detection of Gal/
Sensitivities and specificities of commercially GalNac lectin antigen in serum provides early
Chapter 7: Diagnostic Parasitology 341
diagnosis of ALA and can be used as a test of fluorescence resonance energy transfer (FRET),
treatment efficacy. Additionally, the presence of and Scorpion primers.
lectin in saliva can also be used as a predictor The principle of real-time PCR using two
for invasive disease with the advantage of fluorescence chemistries is illustrated below:
noninvasive sample collection. The principle of SYBR Green detection
Commercially available immunodiagnostic in real-time PCR is outlined in Figure 7.1.
tests for diagnosis of giardiasis are in the The fluorescent dye SYBR Green is added to
same format as the diagnostic test kits for the the PCR mixture (1). SYBR Green is a DNA
diagnosis of cryptosporidiosis and amebiasis. binding dye that fluoresces strongly when
The same requirement for unpreserved stool bound to double-stranded DNA. At the start of
specimen applies for enzyme-based assays for the reaction, very little double-stranded DNA is
the diagnosis of giardiasis. Detection of Giardia present, and so the fluorescent signal detected
cysts by DFA assay employs FITC-labeled by the thermocycler is low (3). As the reaction
monoclonal antibody which is highly sensitive proceeds and PCR product accumulate, the
and specific compared to microscopy. amount of double-stranded DNA increases
and with it the fluorescence signal (4-5). The
Molecular Diagnosis
signal is only detectable during annealing and
Nucleic acid-based assays offer greater extension, since the denaturation step contains
sensitivity and specificity than the above predominantly single-stranded DNA (6).
mentioned tests. They allow for direct detection
of parasites in samples including those with
very low parasite load from asymptomatic
patients. The use of gene amplification
technology by polymerase chain reaction (PCR)
detects nucleic acid sequences specific to the
parasite in question. This technique uses two
oligonucleotide primers which flank the parasite
target sequence and Taq polymerase. The process
involves successive cycles of DNA denaturation,
annealing of primers, and extension to generate
an exponential number of copies of the target
sequence using a thermocycler. The amplified
target is then analyzed by gel electrophoresis
or alternatively, by ELISA methods. Several
variations of the traditional PCR have been
developed to increase sensitivity such as nested
PCR where a second round of amplification
is introduced using a set of primers internal
to the target sequence; multiplex PCR using
parasite/species-specific primer sets to detect/
differentiate parasite/species simultaneously
in one reaction tube; and real-time PCR to Figure 7.1. SYBR Green detection in real-time PCR
(From da Silva A, Pieniazek N. Latest advances
quantify original template concentration by and trends in PCR-based diagnostic methods.
using various fluorescence chemistries such as In: Dionisio D, editor. Textbook-Atlas of Intestinal
SYBR Green, sequence-specific TaqMan probes, Infections in AIDS. Springer; 2003. p. 397-412.)
Chapter 7: Diagnostic Parasitology 343
The principle of TaqMan real-time PCR Real-time PCR assays using SYBR Green
is depicted in Figure 7.2. The TaqMan probe are simpler and less expensive than TaqMan
is designed to be complementary to a specific probe assays. However, all fluorescence bound to
sequence spanned by the PCR primers. The double-stranded DNA are detected, including
TaqMan probe has a reporter dye at its 5’ end and primer-dimers and other PCR artifacts. Caution
a quencher dye at its 3’ end. As long as the probe should be exercised when analyzing data
is intact and the reporter and the quencher dyes resulting from this assay. To improve specificity,
are in close proximity, no fluorescence signal a melt/dissociation curve analysis should be
is emitted due to the quenching effect (black included to distinguish real PCR products
arrow in 1, 2, and 3) (1). After the annealing of from artifacts. Probe-based assays on the other
the TaqMan probe (2) and the primers (3), the hand, are highly specific and can detect multiple
primers are extended by the DNA polymerase. targets in one tube.
As the polymerase reaches the TaqMan probe, it Other new molecular approaches in the
uses its exonuclease activity to remove the probe diagnosis of parasitic diseases such as loop-
one nucleotide at the time (4). This releases the mediated isothermal amplification (LAMP) and
reporter from the proximity of the quencher and Luminex-based technologies are also currently
allows for the release of a fluorescence signal available. LAMP reactions are easier to set up
from the reporter (5). as they do not require extraction of parasite
DNA. The specimen of interest is mixed with
diagnostic primers, substrates, and DNA
polymerase capable of strand displacement
in a microcentrifuge tube. Large quantities
of pyrophosphate ions are produced during
the reaction forming white precipitates. The
resulting turbidity is proportional to the
amount of DNA synthesized which can be
measured in real-time or by the naked eye.
Unlike a conventional PCR, LAMP is carried
out at a constant temperature (usually 60-
65°C) therefore eliminating the need for a
thermocycler. LAMP can also be multiplexed
for simultaneous detection and differentiation
of parasite species. Because of its simplicity,
the use of LAMP technology in the diagnosis
of parasitic diseases in peripheral laboratories
shows promise.
The Luminex xMAP Technology is another
new method that allows for high throughput
diagnosis of parasitic diseases in large scale
studies, but is applicable only in central
laboratories. It is a bead-based flow cytometry
assay that allows for simultaneous detection of
Figure 7.2. TaqMan real-time PCR
(From da Silva A, Pieniazek N. Latest advances
different targets (parasite species or genotypes)
and trends in PCR-based diagnostic methods. in the same reaction using very low volumes.
In: Dionisio D, editor. Textbook-Atlas of Intestinal The microsphere beads are covalently bound
Infections in AIDS. Springer; 2003. p. 397-412.) to antigens, antibodies or oligonucleotides and
344 Medical Parasitology in the Philippines
used as probes in the assay. This assay is very primers and TaqMan probes for E. histolytica
useful in parasite genetic diversity and drug and Giardia intestinalis were designed on a
resistant allele studies. small subunit ribosomal RNA gene, while
those of Cryptosporidium spp. were designed on
Molecular Diagnosis of Stool Specimens
Cryptosporidium oocyst wall protein (COWP).
At the CDC, both conventional and real- This assay was found sensitive and specific when
time PCR analysis are currently used to detect validated with clinical specimens.
Cryptosporidium spp., Cyclospora cayetanensis, Another multiplex real-time PCR assay
E. histolytica, and E. dispar, while conventional using primers and probes targeting the
PCR is used to detect Giardia duodenalis and cytochrome C oxidase gene of Schistosoma can
microsporidia. DNA is extracted from fecal detect and quantify two important species (S.
samples and diagnostic primers are used to mansoni and S. haematobium) in fecal samples.
amplify target gene or sequence. Amplification Real-time PCR cycle threshold (CT) values
products of conventional PCR are loaded in representing parasite/species DNA extracted
agarose gels and analysed. Real-time PCR, on from fecal material show good correlation with
the other hand, measures the fluorescence signal egg counts of S. mansoni in stool and egg counts
in the reaction tube per cycle and is proportional of S. haematobium in urine.
to the amount of accumulated amplified Recently, a rapid diagnostic multiplex PCR
product. The concentration of amplified DNA (RD-PCR) to distinguish S. haematobium,
is measured by comparing it to a standard curve. causing human schistosomiasis from S. bovis,
A TaqMan-based real-time PCR has been causing schistosomiasis in cattle was developed.
developed and validated at the CDC which There is a sympatric occurrence of these two
differentiates Cryptosporidium hominis from species in Africa and they have the ability to
Cryptosporidium parvum. The assay combines infect the same intermediate snail host, Bulinus,
a generic TaqMan assay which targets the 18S thus, there is a need for a reliable method to
rRNA to detect Cryptosporidium species and differentiate the larval stages of the parasite.
two other TaqMan assays to identify C. hominis This assay uses a single forward primer and
and C. parvum. The generic TaqMan assay two species-specific reverse primers targeting
can detect one to 10 oocysts in a 300 µL stool the cytochrome oxidase subunit 1 (COX 1)
specimen, and the two species-specific TaqMan mitochondrial DNA (mtDNA) which gives a
assays are ten-fold more sensitive. These are 306 bp PCR product for S. bovis and 543 bp
valuable tools in outbreak investigations of PCR product for S. haematobium.
cryptosporidiosis. Several molecular methods of detection
A single-tube multiprobe real-time PCR and differentiation of Taenia species in stool
assay can simultaneously detect the pathogenic samples have been developed. These include
E. histolytica and the non-pathogenic E. dispar. PCR restriction fragment length polymorphism
The assay uses two species-specific probes (PCR-RFLP), multiplex PCR targeting
encompassing new SSU RNA regions of the mitochondrial DNA, and nested PCR method
ribosomal DNA-containing episome. It is a targeting Tso31 gene encoding the T. solium
highly sensitive assay capable of detecting one oncosphere-specific protein. A simple but highly
Entamoeba per mL of feces and is therefore sensitive and specific LAMP technology, on the
more sensitive than a conventional nested other hand, targets COX 1 and cathepsin L-like
PCR method. A multiplex real-time PCR cysteine peptidase (clp) genes for differential
assay can simultaneously detect E. histolytica, detection of Taenia species. This method utilizes
Giardia intestinalis and Cryptosporidium spp. a Bst DNA polymerase with strand replacement
in one tube using parasite-specific probes. The activity and four primers that recognize six
Chapter 7: Diagnostic Parasitology 345
sequences on the target DNA under isothermal filarial antigens are detected by either ELISA
conditions. DNA prepared from proglottids, or immunochromatographic test (ICT). Several
cysticerci, and fecal samples of taeniasis patients PCR-based assays are available to diagnose
can be used for this assay. malaria or Bancroftian filariasis separately. In
areas where the two parasitic diseases are co-
Molecular Diagnosis of Blood Specimens
endemic, a multiplex PCR assay can be used
A highly sensitive multiplex real-time PCR to simultaneously detect P. falciparum and W.
assay has been shown to detect the five human bancrofti in humans and a real-time multiplex
Plasmodium species (P. falciparum, P. vivax, P. quantitative PCR assay to detect P. falciparum
malariae, P. ovale, and P. knowlesi) in a single and W. bancrofti or P. vivax and W. bancrofti in
reaction tube even in samples with very low mosquitoes. Recently, a multiplex, post-PCR
parasitemia. This method has been optimized oligonucleotide ligation detection reaction-
for the detection of mixed infections with the fluorescent microsphere assay (LDR-FMA)
increased sensitivity of detecting minor species was developed for simultaneous detection of
by using species-specific forward primers in four Plasmodium spp. and W. bancrofti in
combination with a conserved reverse primer. blood samples. This methodology is very useful
It also provides great advantage over standard in the conduct of large scale epidemiologic
microscopy as it allows quick turnaround investigations in areas where malaria and
time and reduces cost per assay in large scale Bancroftian filariasis are co-endemic.
investigations. Multiplex real-time PCR can also PCR-based assays are capable of detecting
be used in differentiating drug-sensitive from very low parasite loads, making them more
drug-resistant strains of Plasmodium, important sensitive methods of diagnosis. Their quick
in instituting malaria treatment. turnaround times offer the benefit of early
LAMP technology was recently used in diagnosis and treatment of patients. Efficacy
the diagnosis of malaria by targeting the 18S of treatment can be monitored as a decrease in
rRNA gene to simultaneously detect the four parasite DNA concentrations by quantitative
human Plasmodium species. When compared to real-time PCR; however, results should be
nested PCR in the diagnosis of malaria, LAMP interpreted with caution as they may not
demonstrated a similar level of sensitivity, necessarily mean non-viability of the parasite in
greater specificity, and a faster turnaround time. question. The chances of false negatives due to
Three LAMP assays based on SAG1, presence of PCR inhibitors that may be present
SAG2, and B1 genes of Toxoplasma gondii are in blood and other clinical specimens and false
highly specific and sensitive, and allow rapid positives due to carry-over contamination
detection of active toxoplasmosis compared should not be overlooked. In this regard, proper
to conventional nested PCR. The lowest standardization procedures are needed for more
limit of detection of these LAMP assays is 0.1 reliable and reproducible results. Without these,
tachyzoite, and they do not cross react with PCR-based assays cannot be routinely used and
DNA of other parasites. may be limited to in-house research use only.
Malaria and lymphatic filariasis are co-
Rapid Diagnostic Tests (RDTs)
endemic in many tropical and sub-tropical
regions such as Southeast Asia, Western Pacific, While molecular-based assays show
Africa, South and Central America. As such, excellent sensitivity, specificity, and rapidity
other diagnostic tests have been developed than other methods of diagnosis of parasitic
to complement microscopic examination of diseases, their use is still uncommon in daily
stained blood smears to detect Plasmodium laboratory practice especially in rural endemic
spp. and Wuchereria bancrofti. Circulating areas where cases of parasitic infections are
346 Medical Parasitology in the Philippines
concentrated. Early diagnosis and treatment of stool, urine or other body fluids. These assays
any parasitic disease are essential components employ immunochromatographic methods in
of control programs, hence the continued lateral flow devices where results are available
development of diagnostic tests that can within 15 minutes. They do not require skilled
be performed on site without the need for microscopists but provide accurate diagnosis
electricity, sophisticated equipment, or extensive in a timely manner important for prompt and
training of laboratory personnel. The use of appropriate treatment.
Rapid Diagnostic Tests (RDTs) therefore has
A. RDTs for malaria
great potential in improving diagnostic accuracy
of parasitic infections in field settings that still A malaria RDT (Figure 7.3) is a lateral flow
rely on the microscope. immunochromatographic device that detects
RDTs use antibodies (monoclonal or protein [antigen (Ag)] derived from the blood
polyclonal) to detect parasite antigens in blood, stage of malaria parasites. Blood is usually
Figure 7.3. Mode of action of antigen-detecting malaria rapid diagnostic tests (RDTs)
(From Bell D, Wongsrichanalai C, Barnwell JW. Ensuring quality and access for malaria diagnosis: how
can it be achieved? Nat Rev Microbiol. 2006 4(9 Suppl):S7-20.)
Chapter 7: Diagnostic Parasitology 347
obtained from a finger prick, in a similar way test kits detect pLDH from all four species of
to that usually used for malaria microscopy. A Plasmodium and can differentiate falciparum
small sample of blood, usually 5 to 20 μL, is from non-falciparum species but not between
placed on the RDT strip, or in a well of the P. malariae, P. vivax, and P. ovale. Newer RDTs
cassette or card test device, and lysed to release developed can detect both PfHRP-2 and pLDH
the Ag from within red blood cells and parasites at the same time.
from within these cells (a variable amount of To date, over 50 brands of malaria RDTs
Ag is also present in the serum). After several are manufactured, and over 150 products are
minutes, the test produces a series of visible commercially available. RDTs for malaria are
lines to signal the presence or absence of Ag in easier to perform than the standard microscopy
the blood sample by the mechanism outlined and have great potential to accurately diagnose
below. (a) Dye-labelled antibody (Ab), specific malaria in endemic areas. Several malaria
for the target Ag, is present on the lower end RDTs have been tested in the field, and good
of the nitrocellulose strip, or in a well provided levels of sensitivity have been achieved with
by a casing covering the strip. Ab, specific for parasitemia levels of >100 parasites/µL blood.
another epitope on the target Ag, is bound to However, sensitivity drops when parasitemia is
the strip in a thin (test) line, and Ab specific for <100 parasites/µL. Failure to detect cases with
the labelled Ab is bound at the control line; (b) very high parasitemias have been reported.
Blood and buffer, which have been placed on Variability in performance of commercially
the strip or in the well, are mixed with labelled available RDTs in the field have been found
Ab and are drawn up the strip across the lines to be influenced by several factors such as kit
of bound Ab; (c) If Ag is present, labelled Ab transport and storage conditions (sensitive to
will be trapped on the test line. Other labelled extreme temperature and humidity), quality of
Ab is trapped on the control line. If sufficient manufacture, and variability in interpretation
labelled Ab accumulates, the dye labels will of results by laboratory personnel. Generally,
become visible to the naked eye as a narrow line. HRP-2 based assays demonstrate comparable
RDTs for malaria detect either P. falciparum sensitivity to good quality microscopy, and
histidine-rich protein 2 (PfHRP-2), a water other factors affecting their performance have
soluble protein specific to P. falciparum, been recently investigated. Genetic diversity
or parasite lactate dehydrogenase (pLDH) of PfHRP-2 gene was determined and it was
produced by all four Plasmodium species. found that the deduced amino acid sequences
PfHRP-2 is synthesized throughout the asexual are highly polymorphic in different isolates. The
life cycle of the parasite and identified as a number and sequence of specific repeats present
surface-exposed protein in infected red blood in PfHRP-2 vary widely; therefore, the epitopes
cells. It is also found circulating in the peripheral recognized by the monoclonal antibodies
blood of infected individuals, hence a good specific to HRP also vary between isolates.
target for the diagnosis of P. falciparum. HRP-2 Additionally, it was found that monoclonal
based kits however, cannot be used to monitor antibodies raised against PfHRP-2 can also
treatment efficacy as HRP-2 stays in circulation bind to PfHRP-3 which raises its potential
for as long as two weeks after parasite clearance. role in the performance of HRP-based RDTs.
While pLDH (an intracellular metabolic Despite extensive global sequence variation in
enzyme produced by both asexual and sexual PfHRP-2, no statistically robust correlation
stages of malaria parasites) does not persist in between gene structure and RDT detection rate
the blood, it may provide a good indication of for P. falciparum parasites at 200 parasites/µL
parasite clearance following treatment. Current blood was identified. However, a more recent
348 Medical Parasitology in the Philippines
Han ET, Watanabe R, Sattabongkot J, Mehlotra RK, Gray LR, Blood-Zikursh MJ,
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H, et al. Detection of four Plasmodium al. Short report: Molecular-based assay for
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Jothikumar N, da Silva AJ, Moura I, species including P. knowlesi by real-time
Qvarnstrom Y, Hill VR. Detection polymerase chain reaction. Eur J Clin
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Lau YL, Meganathan P, Sonaimuthu P, point-of-care tests for improving rapid
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352 Medical Parasitology in the Philippines
cells are sometimes misidentified as malaria 7.8–7.15). These practices lead to inaccurate
parasites. Fungal spores of Helicosporium diagnosis of parasitic infections (false positives)
may also be mistaken as microfilariae (Plates and inappropriate treatment of patients.
Plate 7.8. A fungal spore in a wet mount stool Plate 7.9. A mite egg in a formalin-concentrated
may look like a cyst of Entamoeba spp. stool specimen may look like a hookworm egg.
(Accessed from www.dpd.cdc.gov/dpdx) (Accessed from www.dpd.cdc.gov/dpdx)
Plate 7.10. A plant cell in a concentrated wet Plate 7.11. A pollen grain in a concentrated wet
mount of stool may look like a helminth egg. mount of stool may look like a fertilized egg of
(Accessed from www.dpd.cdc.gov/dpdx) Ascaris lumbricoides.
(Accessed from www.dpd.cdc.gov/dpdx)
358 Medical Parasitology in the Philippines
Plate 7.12. Plant hair in a concentrated wet Plate 7.13. Howell-Jolly bodies in a thin blood
mount of stool may look like a hookworm or smear stained with Giemsa
Strongyloides stercoralis larva. may look like malaria parasites.
(Accessed from www.dpd.cdc.gov/dpdx) (Accessed from www.dpd.cdc.gov/dpdx)
Plate 7.14. A nucleated red blood cell Plate 7.15. Fungal spores of Helicosporium may be
may look like a schizont of Plasmodium spp. mistaken as microfilariae in stained blood smears.
(Accessed from www.dpd.cdc.gov/dpdx) (Accessed from www.dpd.cdc.gov/dpdx)
Quality Assurance in Parasite Microscopy differ in terms of basic training and skills.
A physician, health manager, or a scientific
For many parasitic conditions as in
investigator should be assured of the quality
helminth infections and malaria, microscopic
of the microscopic examination. On some
examination is still considered to be the “gold
occasions, the requesting party may also be
standard” procedure. Microscopists, however,
interested to know the burden of infection
Chapter 7: Diagnostic Parasitology 359
World Health Organization Regional Office for New Delhi: World Health Organization;
South-East Asia. Guidelines on standard 2003.
operating procedures for microbiology World Health Organization. Malaria microscopy
and parasitology. Geneva: World Health quality assurance manual. Geneva: World
Organization; 2000. Health Organization; 2008.
World Health Organization Regional Office World Health Organization. Laboratory quality
for South-East Asia. Quality assurance in management system (handbook). Geneva:
health laboratory services: a status report. World Health Organization; 2011.
Chapter 8
Parasitic Zoonoses
Salcedo L. Eduardo
362
Chapter 8: Special Topics in Parasitology 363
2. Cryptosporidiosis
and in animals in close confinement aggravated (one definitive and the other intermediate hosts)
by coprophagy. Humans become infected and no invertebrate hosts in the completion of
by ingesting cysts directly through fecal-oral the life cycle. Humans may be obligatory or
transmission or contaminated food or water. non-obligatory hosts. There are two subtypes.
5. Scabies (human) and mange (animals) Subtype 1: Human as an obligatory definitive
host (Figure 8.2)
Aside from Sarcoptes scabiei, Sarcoptes spp.,
and Demodex spp. from other animals, as well
as Notoedres cati of cats affect humans. These
mites are the cause of mange in animals. Lesions
are usually found on the hands and forearms
of pet owners. Sarcoptes spp. from cattle, water Man
buffaloes, horses, pigs, and S. scabiei of human (definitive host)
and Notoedres cati of cats have been recorded in
the Philippines.
6. Trombiculidosis
T h e m i t e f a m i l y Tr o m b i c u l i d a e
(chigger mites) is an assemblage of several
genera whose adults and nymphal stages
are free living but whose larvae normally
attack rodents, insectivores, and ground
dwelling birds causing dermatoses. Given Vertebrate
the opportunity, they will feed on human, Animal
(intermediate host)
livestock, and poultry. In the Philippines,
the following trombiculid genera have been
recorded: Eutrombicula, Leptotrombidium,
Neoschoengastia, Schoengastiella, Trombicula,
Toritrombicula, and Walchiella. Figure 8.2. Cyclozoonoses subtype 1:
human as an obligatory (definitive) host
Eutrombicula wichni is the cause of
human trombiculidosis. Leptotrombidium 1. Sarcocystosis
akamushi is a known vector of scrub typhus
or tsutsugamushi disease in humans caused by Members of the genus, Sarcocystis, which
Orientia tsutsugamushi. Scrub typhus has been has an obligatory prey-predator two-host cycle,
reported in China, Japan, Southwest Pacific cause this condition. Asexual and sexual stages
to Siberia, and Pakistan. Cases of human develop in the intermediate and definitive hosts,
infestation in the Philippines have occurred respectively. Intermediate host becomes infected
especially among soldiers during World War II through ingestion of oocysts in food and water
and cases of infestation in the navel and scrotum contaminated with feces of the definitive host.
among children playing on areas where rat nests Definitive host becomes infected through
abound. ingestion of mature sarcocysts (Plate 8.2) from
tissues of infected intermediate host.
B. Cyclozoonoses
Humans serve as definitive hosts for
To this group belong those infections whose two species, namely, Sarcocystis hominis and
causative agents require only vertebrate hosts S. suihominis. Cattle and swine serve as the
Chapter 8: Special Topics in Parasitology 365
rats (Rattus tanezumi) examined in Bay, Laguna contaminated food and water. Transplacental
revealed 37.4% infection with S. fasciolaris infection occurs when previously non-infected
(unpublished). Cats become infected through hosts become infected during pregnancy. The
ingestion of infected rat liver where the larva is organism multiplies in the placenta and spreads
released in the intestine, attaches to the mucosa to the fetal tissues. Cats play an important role
to grow to maturity. Similarly, infection in in the transmission of T. gondii. The disease is
human can result from ingestion of raw or a major public health concern because of the
improperly cooked liver of infected rodents. risk of transplacental transmission when cats (as
Although human infections with this species the source of infective oocysts) are in the same
have been reported in other parts of the world, households with pregnant women. Oocysts are
none has been recorded in the Philippines. resistant to most disinfectants and can survive
up to two and a half years even in unfavorable
Subtype 2: Human as a non-obligatory (optional)
host (Figure 8.3) environmental conditions. In the Philippines,
serological surveys revealed prevalence rates to
be as high as 52.7% in cats, and 19.0%, 8.1%,
1.9%, and 2.4%, in pigs, rats, water buffaloes,
and humans, respectively.
Vertebrate Man 2. Echinococcosis/Hydatidosis
Animal
(definitive host) The species involved is Echinococcus
granulosus. The dog and wild canids are the
definitive hosts where the adults occur in the
intestine. Mammals, including humans, serve
as the intermediate host where the metacestode
(Echinococcus or hydatid cyst) develops.
Humans become infected by ingestion of the
egg from infected definitive hosts.
Vertebrate While the disease is common in other
Man parts of Asia, there are only very few reports in
Animal
(intermediate the Philippines. There is only one record of E.
host) granulosus in a dog, one report of Echinococcus
cyst in water buffalo, and a few cases of human
hydatidosis.
Figure 8.3. Cyclozoonoses subtype 2: human as
a non-obligatory (optional) host 3. Anisakiasis
Table 8.1. Philippine fishes found harboring anisakine larvae (from various authors)
levels of transmission
between humans and
dogs. Infection is
through penetration of
the skin by the cercaria
(Plate 8.8) when the
host comes in contact
with infected water.
3. Dipylidiasis
Dipylidium
caninum (Plate 8.9)
infection is common in
dogs and cats worldwide.
In the Philippines, the
Plate 8.7. Fasciola metacercaria prevalence rate especially Plate 8.8.
(Courtesy of Dr. Salcedo Eduardo) among stray dogs may Schistosoma
range from 5 to 81%. cercaria
(Courtesy of
The cat (Ctenocephalides Dr. Salcedo
countries. It has been estimated that 2.4 felis) and dog flea Eduardo)
million people are infected with this trematode
and another 180 million are at risk. In the
Philippines, only two cases of human infection
with Fasciola have been recorded. The exact
origin of the infection could not be traced but
it probably resulted from the partly cooked
edible water plant, Ipomea (kangkong) or the
accidental ingestion of other water plants
harboring metacercariae of the fluke. The high
prevalence in animals in endemic areas puts the
local human population at risk to infection.
2. Schistosomiasis
(Ctenocephalides canis), and the dog louse In the Philippines, land snails (Achatina fulica,
(Heterodoxus longitarsus) serve as intermediate Hemiplecta sagittifera, Helicostyla macrostoma,
hosts that harbor the cysticercoid stage. Chlorea fibula, and Cyclophorus spp.), garden
Humans, especially children, become infected slugs (Imerina plebeia, Laevicaulus alte) serve
when fleas and lice containing cysticercoid are as primary intermediate hosts of the parasite.
accidentally ingested. In the rice field, A. fulica and other snails have
been observed to be important sources of food
4. Hymenolepiasis
of rodents and especially when grains become
Two species with cosmopolitan distribution, scarce. This snail and infected rats contributed
Hymenolepis nana (previously known as to the spread and its introduction to many
Vampirolepis nana and also known as the dwarf regions of the world.
tapeworm) and H. diminuta are involved in Humans are accidental hosts. Infection
this infection. The adult form occurs in rats results from ingestion of infective larvae
and humans. Completion of their life cycle frequently through the paratenic hosts (e.g.,
requires intermediate hosts, but for H. nana, fresh water prawns) which are eaten raw
this is optional. Intermediate hosts include and whose juices are used in the preparation
flour beetles, and other arthropods where of local dishes, or ingestion of vegetables
the metacestode (cysticercoid) is formed. H. contaminated with larvae from infected obligate
diminuta is widely distributed among rats with intermediate hosts. Parastrongylosis in humans
a prevalence rate of 10.8%. In humans, the affects the central nervous system where the
prevalence is 1%. Human infection results from migrating larvae cause a condition called
ingestion of uncooked food contaminated with tropical eosinophilic meningitis. Human cases,
infected intermediate hosts or their accidental including cases of ocular parastrongylosis, which
ingestion. The infection is prevalent among are all non-fatal and presumably due to larvae of
children. P. cantonensis, have been reported locally.
5. Raillietiniasis 7. Dirofilariasis/Human Pulmonary Dirofilariasis
The genus Raillietina is well represented in Dirofilaria immitis (Plate 8.10), the
domestic and wild birds in the Philippines with heartworm of dogs, is common and widely
at least 19 species reported. Only one species, distributed in dogs in the Philippines and
R. madagascariensis, also known as R. garrisoni, transmitted by mosquitoes. Latest data showed
has been involved in human infection, and its an incidence rate of 20% among client owned
prevalence rate among rodents may range from dogs from the Greater Metropolitan Manila.
22% to as high as 86%. It has been shown that The dog therefore is an important source for
beetles and ants serve as intermediate hosts. human infection through the bites of infected
Human infection results from ingestion of the mosquitoes.
intermediate host infected with cysticercoid. Human infection with this species usually
involves the lungs, thus the term pulmonary
6. P a r a s t r o n g y l o s i s o r E o s i n o p h i l i c
Meningoencephalitis dirofilariasis. However, the involvement of other
organs such as the eye, posterior vena cava,
Parastrongylus cantonensis is the cause abdominal cavity, spermatic cord, and possibly
of the condition and the only species of the the meninges has been reported. Although no
genus reported in the Philippines. This species human case so far has been reported in the
occurs as adults in the lungs of rats (Rattus Philippines, several cases have been recorded in
spp.) with prevalence ranging from 3 to 10%. Australia, Japan, Spain, and the United States.
Chapter 8: Special Topics in Parasitology 371
Subtype 2: More than one invertebrate hosts conica. Filipinos eat the
(first and second intermediate hosts) and one latter species, which is
vertebrate host (Figure 8.5) considered the primary
source of infection. The
Ilocanos of Northern
Luzon are known to
Vertebrate consume partly cooked
Man Pila conica (locally called
Animal
(definitive host) bisukol), hence human
infection is highest in
this region.
Echinostoma
lindoense (Plate 8.12)
Invertebrate Invertebrate is another cause of
Animal Animal human intestinal
(2nd Intermediate (1st Intermediate
Host) Host) echinostomiasis. It has
been first described
and reported as a
Figure 8.5. Metazoonoses subtype 2: more
human infection in
than one invertebrate host (first and second
intermediate hosts) and one vertebrate host Indonesia and later in
other Southeast Asian
countries (Indonesia, Plate 8.12.
1. Echinostomiasis Echinostoma
Malaysia, and Thailand) lindoense from field
Human echinostomiasis in the Philippines and Brazil in both rat (Courtesy of Dr.
is caused by Echinostoma ilocanum. The adult animals and humans. Salcedo Eduardo)
fluke is found in the small intestines, thus It has recently been
the disease condition is also called intestinal recorded in rice field rats
echinostomiasis. It is widespread with a in the Philippines, although no human case has
prevalence of 3%, but it is more commonly been reported locally. The life cycle of this species
found in Northern Luzon where prevalence follows the same pattern as that of Echinostoma
reached as high as 44%. ilocanum and Artyfechinostomum malayanum,
Rattus spp. are important animal hosts but in addition, daughter sporocyst is produced.
but dogs and cats may equally be important. The first intermediate hosts are freshwater snails:
However, no data are available on the prevalence Gyraulus convexiusculus and G. sarasinorum.
of natural infection especially on the last two The second intermediate hosts are snails
hosts. A variety of laboratory animals especially (Gyraulus convexiusculus, Lymnaea rubiginosa,
rats, mice, and hamsters are the most susceptible L. exustus, and Biomphalaria glabrata), mussels
experimental hosts. (Corbicula lindoensis, C. subplanata), and
E. ilocanum requires fresh water snails as tadpoles (Rhacophorus leucomystax). The
intermediate host to complete its life cycle. intermediate hosts in the Philippines are not
Locally, the freshwater planorbid snail, Gyraulus yet known but Gyraulus and Lymnaea abound
phrasadi serves as the first intermediate host. The in the country. Human infection results from
second intermediate hosts include a variety of ingestion of viable metacercaria contained in
freshwater snails including G. phrasadi and Pila the second intermediate hosts.
Chapter 8: Special Topics in Parasitology 373
2. Artyfechinostomosis
Carneophallus brevicaeca is the etiologic buffaloes, sheep). The prevalence of the first
agent for this condition. In the Philippines, it has three species in cattle and water buffaloes
been reported in birds (Sterna albifrons sinensis), locally is 11.4%, 2.6%, 4%, and 5.3%, 0.66%,
fish (Glossogobius giuris), and in humans where it 1.33%, respectively. The first three species
is particularly associated with lesions in the heart occur in the pancreas, while the last species in
and spinal cord. Snails serve as first intermediate the perirectal fat in sheep. This group requires
hosts, while shrimps (Macrobrachium sp.) have two intermediate hosts: land snails (first),
been found to harbor metacercariae thus serving and grasshoppers and crickets (second). The
as second intermediate hosts for the parasite. second intermediate hosts contain the infective
Infection occurs through ingestion of raw or metacercarial stage.
partly cooked shrimps. Other invertebrate Grasshoppers and crickets are among
intermediate and vertebrate definitive hosts still the many insects eaten in many parts of the
remain to be known. world. This is especially true in Africa and Asia
where these are prepared in a variety of ways
4. Eurytremiasis
as good sources of protein. Human infection
Members of the genus Eurytrema are the results from ingestion of grasshoppers and
etiologic agents of this condition which are crickets containing live metacercariae of the
parasites of ruminants. Four species namely Eurytrema. Two cases of human infection with
E. pancreaticum (Plate 8.13), E. coelomaticum, E. pancreaticum have been recorded in Japan.
E. escuderoi, and E. ovis have been recorded No human infection with Eurytrema so far has
in Philippine ruminants (cattle, goats, water been reported in the Philippines.
374 Medical Parasitology in the Philippines
5. Paragonimiasis
1. Heterophyidiasis
Invertebrate 2. Opisthorchiasis
Vertebrate
Animal Animal
(Intermediate
Opisthorchis (Clonorchis) sinensis, the
(intermediate
host) host) etiologic agent of this condition, has been
reported in humans in the Philippines during
routine stool examination. In a survey of 30,000
Filipinos, ova similar to that of Opisthorchis
Figure 8.6. Metazoonoses subtype 3: one
invertebrate host (intermediate) and two sinensis were detected in 135 stool samples.
invertebrate hosts (one definitive and one This parasite requires snails and a variety of
intermediate) freshwater fishes as intermediate hosts, but for
376 Medical Parasitology in the Philippines
Heterophyid Heterophyid
Scientific name (local name) Scientific name (local name)
species* species*
Acentrogobius janthinopterus PC Liza subviridis (banak) HT, HY, PC, SF
(biyang sapa) Mugil dussumieri (talilong)
Ambassls buruensis (lañgaray) HY, PC Mugil sp. (banak) HY, PC, SF
Anabas testudineus (martiniko) PC, SF Oreochromis niloticus (tilapia) HT
Arius manillensis (Manila kanduli) HY Pelates quadrilineatus (agaak) HY, PC, SF
Atherina balabacensis (guno) PC Platycephalus indicus (sunog) PC
Butis amboinensis (biyang sunog) PC Poecilia latipinna (bubuntis) PC
Channa striata (dalag) HT, HY, PC Puntius binotatus (pait) HT
Chanos chanos (bangus) PC Rhynchorhamphus georgii (buging) HY, PC
Clarias batrachus (hito) HY Scatophagus argus (kitang) PC
Eleutheronema tetradactylum (mamali) PC Siganus canaliculatus (barangan) HY, PC
Epinephelus corallicola (lapu-lapu) HT, PC Siganus gutatus (barangan) HT, HY
Gerres filamentosus (malakapas) PC Siganus javus (barangan) HY, PC
Gerres kappas (malakapas) HY Spratellicypis palata (manobud) HT
Glossogobius giuris (biya) PC Terapon jarbua (bagaong) HT, HY, SF
*Legend: HT-Haplorchis taichui; HY-Haplorchis yokogawai; PC-Procerovum calderoni; SF-Stellantchasmus falcatus
Plate 8.17. Gnathostoma doloresi from pig Plate 8.18. Gnathostoma larva from frog muscle
(Courtesy of Dr. Salcedo Eduardo) (Courtesy of Dr. Salcedo Eduardo)
378 Medical Parasitology in the Philippines
frogs and Ophicephalus striatus (dalag) from A number of animal hookworms (Ancylostoma
Laguna Lake, suggesting that this fish serves as braziliense, A. caninum, and Bunostomum
the intermediate host. spp.) and threadworms (Strongyloides spp.)
Human infection may result from are involved in cutaneous larva migrans. The
consumption of improperly cooked infected first two species occur in dogs and cats, while
fish or paratenic host, or through drinking water the third occurs in ruminants. Threadworms
contaminated with infected copepods. The larva are common intestinal parasites of mammals
migrates to the subcutaneous tissues, central including humans, and many of the nonhuman
nervous system, and other tissues. species can cause larva migrans in humans. A.
braziliense is the cause of creeping eruption.
D. Zaprozoonoses
Human acquires the infection through contact
In this group, the causative agent of the with soil containing infective larvae. Normally
infection develops from a non-infective to an larvae are restricted to and die in the skin but
infective stage in an environment containing may also migrate to the lungs.
organic matter including food, soil, or plant, or Toxocara canis (Plate 8.19), a common dog
a reservoir before transmission to the vertebrate Ascaris is the main causative agent of visceral,
host (Figure 8.7). ocular, and even covert larva migrans in human.
Other ascarids like T. cati of cats and other
felids, and T. vitulorum of cattle and water
buffaloes may also be involved, but their role
is limited due to the infrequency of human
Vertebrate contact with their eggs. Puppies are infected
Animal Man with T. canis as early as the fetal stage or at
(definitive host) birth due to transplacental and transmammary
transmission from the infected bitch, and
infective non-infective
stage stage
1. Larva migrans
detested due to its slimy texture. Even the local Some maintain that cooking not only destroys
term, susong linta, meaning “leech-like” snail, the flavor they relish, but also the nutritive
sounds unpleasant to the ear. value of the food. Nevertheless, with a more
Kilawen is also popular among folks in aggressive health education campaign, together
Leyte. Pig liver is cut into thin slices, soaked with programs directed to the improvement of
in vinegar with salt and condiments and eaten the living condition of the inhabitants in these
raw. Pig meat, partly cooked and prepared as areas, preventive measures against many of these
above, is also eaten. Cysticercus (larva) of Taenia zoonotic diseases can be achieved successfully.
solium and T. saginata asiatica are found in the
Zoonotic Parasites as Indicators of Fecal
muscle and liver respectively of pigs, which serve Pollution of the Environment
as intermediate hosts. Human infection occurs
through consumption of raw or partly cooked Many of the protozoa and helminth
infected organs. agents causing zoonoses described in this
Pila conica (kuhol, bisukol) and Sundathelpusa section are associated with fecal pollution of
philippina (talangka), the second intermediate the environment, whether land or aquatic.
hosts of E ilocanum and P. westermani filipinus, Many protozoan and helminth parasites shed
respectively, are eaten practically all over cysts (Balantidium coli, Cryptosporidium spp.,
the country. However, echinostomiasis and Entamoeba histolytica, Giardia duodenalis,
paragonimiasis are prevalent or endemic Toxoplasma gondii, Sarcocystis spp.) and eggs/
only in certain areas. In Northern Luzon, larvae (Toxocara canis, Ancylostoma spp.,
echinostomiasis has the highest prevalence as Strong yloides spp.), respectively, that are
the snail host is eaten sometimes raw or partly disseminated to the environment through the
cooked in this area. Similarly, paragonimiasis is feces. Furthermore, many helminth parasites
endemic in areas where inhabitants are known require intermediate hosts to complete their
to consume the crab host raw. A preparation cycle (cyclozoonoses and metazoonoses). The
with fresh crab juice locally known as kinagang is eggs/larvae of the parasites are passed out
considered a local delicacy. Males in these areas with the feces of the definitive host to the
were observed to eat raw crabs during drinking environment before they develop and gain
sessions with the local wine (basi), especially access to the intermediate host.
during festivities. The same is true for intestinal Echinostoma spp., Artyfechinostomum
capillariasis in Northern Luzon. The fish host, malayanum, Fasciola spp., heterophyids,
Hypseleotris bipartite, is especially desired when Ca r n e o p h a l l u s b re v i c a e c a , Pl a g i o rc h i s
gravid (filled with eggs), and the entire fish is spp., Schistosoma japonicum, Paragonimus
eaten raw. Another fish host, Ambassis miops, in westermani, and Capillaria philippinensis
the raw form, is bitten at the belly by some to reach their intermediate hosts through fecal
suck out the juice. Residents of endemic areas contamination of the water environment.
in Northeastern Mindanao were also noted to Sarcocystis spp. Eurytrema spp., Taenia spp., and
consume fish raw. Macracanthorhynchus hirudinaceous reach their
Simply giving up the habit of eating raw intermediate hosts through fecal contamination
food of animal origin may prevent human of the pasture or direct access of the intermediate
infection with a number of these zoonoses. host (pig and cattle) to fecal matter of infected
However, as the saying goes, old habits may not definitive host (humans) in case of human
easily be given up. Furthermore, some people taeniasis. Proper disposal of fecal material,
in these areas, though properly informed about whether of humans or animals, therefore, is
this transmission, still value their food habits. everyone’s concern.
Chapter 8: Special Topics in Parasitology 381
The presence of reservoir hosts in depends on agriculture, fishery, and forestry for
combination with the presence of suitable livelihood. One-third of all goods and services
invertebrate intermediate hosts also maintains produced by the economy is accounted for by
the infection in a particular area. Field rats are the agricultural/rural sector, which also employs
maintaining the cycle of zoonotic parasites such half of the country’s workers, and earns 36%
as Echinostoma spp., A. malayanum, Schistosoma of the country’s export income. An unhealthy
japonicum, Plagiorchis spp., and Paragonimus working population can only mean low or
westermani. Because of the intermediate hosts, reduced productivity, while infected animals
the potential risk of human infection is ever mean unwholesome meat such as in cases of
present. The snail, Bullastra cummingiana, fascioliasis and cysticercosis. This, in turn, can
had high prevalence of infection with A. only lead to further reduction of supplies due
malayanum in Sampaloc Lake in San Pablo to carcass condemnation of what is already an
City. It should be noted that piggeries are insufficient meat supply. In a country like the
concentrated around Sampaloc Lake, and their Philippines where poverty is widespread in rural
excreta pollute the lake. Pigs, apart from rats, are areas, these diseases can only worsen what is
known as a definitive host of the parasite and already a bad situation.
are maintaining the cycle in that area. While
Medical-Veterinary Cooperation in the
there are no human cases of infection as yet, the Control of Parasitic Zoonoses
presence of the parasite in the area still poses a
threat to human health. Animals, both invertebrates and vertebrates,
domesticated and wild, are hosts to a number
Economic Losses Resulting from Parasitic
of parasitic zoonoses as already shown in the
Zoonoses
above discussions. Their role as definitive,
The Philippines has a fast growing human intermediate, and reservoir hosts make them
population and currently has already reached essential in maintaining the zoonotic agents
94 million. It is even projected that at a growth in nature. As paratenic or transport hosts, they
rate of 2% annually, the population may reach prolong the availability of the agent as potential
113 million by the year 2020. However, food sources of human infection, as well as increase
animal production has not increased to keep the potential of disease dissemination.
pace with the demand of the increasing human Studies to better understand the processes
population. Recent statistics revealed a slow involved in the maintenance, transmission,
growth for food animal production. A large and epidemiology of these diseases should
proportion of the human population live in involve the participation of those concerned,
the rural areas, and a much larger proportion especially physicians, veterinarians, and public
of the food animal population are raised in the health workers. In most countries including
backyard. This food animal population remains the Philippines, parasitic zoonoses are the
large compared to the number raised in large most underdiagnosed diseases in human. Some
commercial farms. This ecological profile of human infections with these diseases may
human and animal population distribution have passed unnoticed or may have been
makes a large proportion of both populations misdiagnosed, as some are difficult to detect or
at risk of infection. many simply are not aware of them.
Although it is difficult to assess exactly The control of zoonoses involves:
economic losses from zoonoses, it is evident control in animals, the veterinarian’s concern;
in the Philippine setting that these diseases are prevention and treatment in humans, the
prevalent in rural areas where the population physician’s responsibility; and the control
382 Medical Parasitology in the Philippines
new records of species. Philipp J Vet Med. Monzon RB, Kitikoon V. Radix quadrasi
2006;43(1):33–45. and Physastra hungerfordiana: additional
Eduardo SL, Manalo VC, Tayag-Kaw MC. New natural second intermediate hosts of
records of and previously known helminth Echinostoma malayanum in the Philippines.
parasites of the catfish and mudfish in Southeast Asian J Trop Med Public Health.
Laguna Lake, Philippines. Philipp J Vet 1992;23:159–61.
Med. 2001;38:110–111. Natividad FF, Buerano CC, Lago CB,
Fernandez TJ Jr, Tarafder MR, Balolong E Jr, Mapua CA, de Guzman BB, Seraspe
Joseph L, Willingham AL 3rd, Bélisle P, EB, et al. Prevalence rates of Giardia and
et al. Prevalence of Schistosoma japonicum Cryptosporidium among diarrheic patients
infection among animals in fifty villages in the Philippines. Southeast Asian J Trop
of Samar province, the Philippines. Vector Med Public Health. 2008;39:991–9.
Borne Zoonotic Dis. 2007;7:147–55. Nawa Y, Imai J, Ogata K, Otsuka K. The
Hong SJ, Woo HC, Chan JY. A human first record of a confirmed human case
case of Plagiorchis muris (Tanabe, 1922: of Gnathostoma doloresi. J Parasitol.
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of infection. J Parasitol. 1996;32:647–9. report of and description of parasite in
Ishii Y, Koga M, Fugino T. Human infection with Mammomonogamus laryngeus (human
pancreatic fluke, Eurytrema pancreaticum. syngamosis) infection. J Clin Microbiol.
Am J Trop Med Hyg. 1983;32:1019–22. 1995;33:998-1000.
Fan PC Chung WC. Taenia saginata asiatica: Ogata K, Imai J, Nawa Y. Three confirmed and
epidemiology, infection, immunological five suspected human cases of Gnathostoma
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Konnai S, Mingala CN, Sato M, Abes NS, 1988;37:358–64.
Venturina FA, Gutierrez CA, et al. A Palmer SR, Soulsby EJ, Simpson IH, editors.
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in livestock in Luzon, the Philippines, Public Health Control. England: Oxford
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2007;103:269–73. of a piglet with ova of a tapeworm
Laxer MA, Alcantara AK, Javato-Laxer M, (Taenia saginata-like) from a human in
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Cryptosporidium from Palawan, Republic 2000;37:109–10.
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384 Medical Parasitology in the Philippines
Table 8.3. Protozoans and helminthic organisms between protozoans or helminths and cellular
of special importance to immunocompromised immunity. Uncontrolled enteric parasite
patients
infection contributes to increasing malnutrition
Protozoans Helminths from malabsorption and direct damage, which
Toxoplasma gondii Strongyloides stercoralis
in turn further taxes the immune system.
Cryptosporidium spp. Filaria spp.
Metabolic derangements from HIV infection
Cystoisospora belli
itself further contribute detrimental effects to
the host.
Microsporidia
A study by Chaisson et al. on the impact
Cyclospora spp.
of opportunistic diseases in the United States
Giardia duodenalis
among a cohort of 2,081 patients with HIV
Blastocystis hominis
infection between 1989 and 1995 revealed a
Entamoeba histolytica
total of 1,499 (49%) opportunistic diseases
Babesia spp. during follow-ups. The predominance of enteric
Leishmania spp. protozoans, especially Cryptosporidium, as causes
Trypanosoma spp. of chronic diarrhea has been reported to occur
Plasmodium spp. in 30 to 60% of AIDS patients in Haiti, Africa,
and other developing countries. Infections with
cases of life-threatening opportunistic infections microsporidia, Cystoisospora, Giardia, and other
due to bacteria, fungi, viruses, and parasites. rarer organisms have also been reported. Enteric
protozoans are among the important etiologic
A. HIV and Parasitic Infection
agents of diarrhea in AIDS in Thailand. Of 288
HIV depletes the helper (CD4+) subset patients screened over a 10 month period in
of T-lymphocytes with drastic consequences 1999 to 2000, 55 (19.2%) had Cryptosporidium
on cell-mediated immunity. Unmodulated spp., 13 (4.5%) had Cystoisospora oocysts,
inflammation and immune activation increase 11(3.8%) had G. lamblia, 3 (0.9%) had
susceptibility to a host of illnesses and Entamoeba histolytica, and 1 (0.3%) had
malignancies, and may allow previously latent Iodamoeba butschlii infection. The prevalence
infections to become active. These latent of microsporidia was 11% in this study. Studies
infections include tuberculosis, herpes viruses, in Dakar, Senegal by Gassama, et al. among
Leishmania, and Toxoplasma. Low pathogenicity HlV-infected and non-infected patients with
organisms in immunocompetent hosts such as diarrhea revealed Microsporidium (9.4%),
Pneumocystis jirovecii and intestinal sporozoans Cryptosporidium sp. (8.2%), E. histolytica
may develop into life-threatening infections. (5.1%), and Cystoisospora belli (4.4%) to be
Finally, pathogens which may be mild or the more frequent parasites seen among the
less severe such as Babesia and Plasmodium immunocompromised individuals and were
may become more virulent as a result of the often identified in patients with low CD4+
permissive environment. count. Blastocystis hominis was identified only
The pattern and types of HIV-related among HIV-infected individuals. Additionally,
opportunistic infections throughout the world high levels of asymptomatic carriage of A.
is affected by endemic infections, general lumbricoides and T. trichiura were observed.
health, nutrition, and access to health care A follow-up study on the progression
and medical services. The dramatic frequency of HIV infection performed by Manaloto et
of parasitic infections in AIDS presents an al., in a cohort of 54 HIV-infected Filipino
important lesson about the interrelationship commercial sex workers from May 1985 to
388 Medical Parasitology in the Philippines
July 1992 revealed Mycobacterium tuberculosis formation of pseudocysts and cysts that contain
and Pneumocystis carinii pneumonia as a more slowly replicating stage (bradyazoites).
the initial indicators of immunodeficiency The cysts are distributed throughout the body.
following a CD4+ cell count of <200 cells/ In the central nervous system, they appear to
mm. Cryptosporidiosis and brain toxoplasmosis persist in latent form for the entire lifespan of
were also seen in two patients. Among the 145 the host, provoking little if any inflammatory
patients with HIV infection seen at the Research response. These dormant organisms can be
Institute for Tropical Medicine (RITM) from reactivated in immunosuppressed persons. In
1985 to 1996, cryptosporidiosis was diagnosed recent years, the importance of toxoplasmosis
in 31% of cases. G. lamblia was detected in in immunocompromised host has been
13%, Ascaris lumbricoides in 11%, E. histolytica increasingly recognized. Patients with a variety
in 9%, E. nana in 7%. B. hominis, H. nana, and of neoplastic diseases, including Hodgkin’s
T. trichiura each in 2% of the cases. Follow-up lymphoma, as well as patients receiving
of 103 symptomatic cases through 1998 did not immunosuppressive therapy are at risk of
reveal significant differences in the prevalence reactivation of this infection. The incidence
of the parasitic infections seen previously. of toxoplasmosis has raised dramatically with
Additionally, 2% of the cases revealed CNS the increasing population of AIDS patients.
toxoplasmosis and 3% had B. hominis. T. gondii is now the leading cause of space-
occupying cranial lesions in persons with AIDS.
B. Toxoplasma gondii
Infection of immunologically normal
Toxoplasma gondii is a sporozoan in persons with Toxoplasma usually results in a
parasite that infects up to a third of the persistent but asymptomatic infection in 80 to
world’s population. It infects all orders of 90% of patients. Primary disease is also usually
mammals and some birds. The domestic cat is subclinical but in some patients may present as
a definitive host and produces infective oocysts. a mononucleosis-like syndrome with cervical
Handling of cat feces is a strong risk factor lymphadenopathy and rarely with ocular
for contracting primary disease. Ingestion of manifestations.
food or water contaminated with oocysts, and Toxoplasmosis in AIDS patients usually
eating of undercooked meat is the usual means develops at CD4 counts of less than 100
of infection. Toxoplasma gondii can be passed cells/mm3. While virtually any organ may be
transplacentally to the fetus when a pregnant involved, the most common manifestations are
woman has a primary infection, leading to fetal in the central nervous system and may involve
infection leading to severe congenital anomalies. the eyes. Virtually all toxoplasmosis in AIDS
The prevalence of Toxoplasma antibodies varies patients is reactivation, and so only Toxoplasma
considerably among different populations and IgG positive patients are considered at risk.
ranges from 3 to 70% in the United States to Other underlying conditions that may give
as high as 80% in Western Europe. rise to reactivation of toxoplasmosis include
Toxoplasma is an intracellular parasite various malignancies (such as Hodgkin’s disease,
capable of invading and replicating within non-Hodgkin’s lymphomas, leukemias, and
nucleated cells. Ingested oocysts enter host solid tumor collagen vascular disease, organ
cells either by rupturing the membrane or transplantation, and prolonged steroid use).
by invaginating them. After multiplication More than 50% of these patients show altered
by repeated endodyogeny, the macrophage mental status, motor impairment, seizures,
finally ruptures, liberating the replicating stage abnormal reflexes, and other neurologic
(tachyzoites) of the parasite and giving rise to the sequelae. The most common presenting
Chapter 8: Special Topics in Parasitology 389
symptom is still seizure, followed by focal rise in antibody titer with serial specimens.
neurologic deficits including ocular symptoms. Since the interpretation of serological tests
Diagnosis of acute disease is through for toxoplasmosis is not uniform, it must be
detection of IgM antibodies or a four-fold rise correlated with other diagnostic techniques
in antibody titer. The presence of high titers including radiographic and other laboratory
(>1:1024) by the Sabin-Feldman dye test, direct abnormalities as well as the clinical situation.
agglutination tests, or conventional indirect The detection of Toxoplasma antigen in
immunofluorescent antibody (IFA) technique serum or other body fluids (e.g., CSF, ocular
is suggestive of acute infection. However, fluid, urine) may be particularly important in
high antibody titers may persist for years after immunocompromised patients in whom active
infection. Therefore, in patients with stable disease is not always associated with rises in
high titer and detection of IgM antibody by antibody titers. The gold standard for diagnosis
the IgM-IFA double sandwich IgM enzyme remains demonstration of the organism in
immunoassay (EIA), or immunoblot tests may tissue.
be useful. Other assays include complement- Toxoplasma gondii has been identified
fixation test and conventional IgA-EIA. A in biopsy specimens of the bone marrow,
negative IgM test essentially excludes recent myocardium, skeletal muscle, lung, and brain
infection, but a positive IgM test is difficult using both hematoxylin and eosin (H&E) stain
to interpret because Toxoplasma-specific IgM and immunospecific stains for Toxoplasma.
antibodies may be detected by EIA for as long Biopsy samples can also be inoculated into mice
as 18 months after acute acquired infection. or sensitive cell lines to isolate the organism.
Detection of IgG antibodies indicates However, because many individuals have
prior infection and the possible presence of been exposed to Toxoplasma and may have
tissue cysts. In the immunocompromised cysts within tissues, recovery of the organism
hosts, interpretation of serological test is from cell culture or animal inoculation maybe
dependent on understanding of the degree of misleading. Recently, the use of molecular
underlying immunosuppression, the serological technology techniques (such as PCR, DNA
status of the patient prior to the development hybridization using ABGTg7 probe) have
of symptoms indicating acute Toxoplasma been found to be sensitive, specific, and rapid
infection, and knowledge of the pathogenesis of methods for the detection of T. gondii DNA
Toxoplasma infection in the risk group to which in amniotic fluid, blood, BAL fluid, tissue
the patient belongs (e.g., transplant recipients). samples, and CSF. These are currently research
Serologic tests may reveal changes in antibody tools and are considered ancillary diagnostics
titers without necessarily being indicative of especially when only very small amount of
active infection. Therefore, serological rises in specimen is available, when the condition is
antibody titers in immunocompromised patient dubious, when the result is required urgently or
cannot be used as the sole diagnostic criterion if serological tests are inconclusive. Radiologic
of active infection with Toxoplasma, especially examinations such as computerized axial
if the clinical manifestations are non-specific. tomography (CAT) scan and nuclear magnetic
In contrast to rises in antibody titers in some resonance imaging (MRI) have been found to
immunocompromised patients without any be extremely useful in the demonstration of
definite signs or symptoms of active toxoplasmic abnormalities associated with TE in patients
infection, other immunocompromised patients with no underlying immunosuppression as
with fulminant toxoplasmosis may have low well as in immunocompromised hosts. In
or negative dye test or IFA titers and show no AIDS patients, the most significant differential
390 Medical Parasitology in the Philippines
diagnosis is central nervous lymphoma, and cysts or by food contaminated with oocysts,
differentiation can be quite difficult. If the susceptible patients should not eat raw or
mass is small and there are no life-threatening undercooked meat and should thoroughly wash,
complications, empiric treatment followed by peel or blanch fresh produce. Careful hand
serial MRI’s to document improvement can washing after handling potentially contaminated
be done. However, in cases where diagnosis material including cat litter, raw meat, and fresh
is urgent and delay can lead to serious clinical produce is essential. The presence of a cat at
consequences, brain biopsy must be pursued. home is a risk for infection, and steps should
Treatment for Toxoplasma infections be taken to minimize contact between the cat
is indicated for patients who develop and the patient, and if unavoidable, the patient
acute infection during pregnancy, and for should follow strict hand washing.
immunocompromised patients with evidence
C. Cryptosporidium
of reactivation disease. The combination of
pyrimethamine and sulfadiazine is the most Cryptosporidium was initially described in
effective regimen. Empiric therapy should be mice in 1907, but it was not until 1976 that
instituted in seropositive immunocompromised it was first reported in humans. The advent
patients who present with compatible of the AIDS epidemic substantially increased
neurologic symptoms and characteristic the number of cases. Cryptosporidium is an
imaging. Asymptomatic patients may become intestinal spore forming protozoa which mainly
symptomatic and symptomatic patients may causes diarrheal illness. In otherwise healthy
briefly worsen when initiating antiretroviral individuals, Cryptosporidium sp. typically causes
therapy for HIV due to immune reconstitution. watery or mucoid diarrhea with abdominal pain
Trimethoprim-sulfamethoxazole (TMP- lasting for several days or occasionally weeks
SMZ) when used as prophylaxis for Pneumocystis that is self-limited even without treatment.
jiroveci is effective prophylaxis for toxoplasmosis. Cryptosporidium causes far more serious disease
If TMP-SMZ cannot be tolerated, there are in immunocompromised individuals, with no
alternative prophylactic regimens which include effective treatment for those with AIDS.
clindamycin and dapsone plus pyrimethamine. The most commonly identified species
Atovaquone with or without pyrimethamine considered pathogenic for man is C. parvum.
may also be considered. Patients with a history Two genotypes of C. parvum are responsible
of central nervous system toxoplasmosis should for most human infections. These include the
be administered suppressive therapy with drugs human anthroponotic genotype 1 found almost
active against Toxoplasma to prevent relapse, exclusively in humans and the bovine or zoonotic
until the CD4 count is above 100 for over a genotype 2 found in both ruminants and
year, or the initial immunosuppresing condition human. However, studies revealing molecular
has resolved. diversity among human Cryptosporidium isolates
Immunocompromised patients should suggest that multiple subgenotypes or more
be tested for IgG antibody to Toxoplasma to than one species may be implicated in human
detect latent infection and offered prophylaxis disease.
as appropriate. Seronegative patients should Experimental-infection studies with mice
be counseled about the various sources of and calves show that immunity is dependent
toxoplasmic infections and advised appropriate on the number of CD4 T-cells generating
methods of preventing exposure especially. gamma interferon. No difference was found
Because infection is usually transmitted by between cryptosporidiosis in normal and
ingestion of undercooked meat with viable B-cell-depleted neonatal mice, suggesting that
Chapter 8: Special Topics in Parasitology 391
antibody production may play a less important post outbreak period compared with four deaths
role in recovery from infection. Interleukin-12 overall in the two years before the outbreak. This
also plays a role by inducing gamma interferon represented a more than a 13-fold increase in
production. cryptosporidiosis-associated mortality.
All species of Cryptosporidium that Zoonotic and person-to-person
have been studied are obligate intracellular transmission may occur through direct or
parasites, however, unlike other coccidians, indirect contact with stool material in the
their developmental stages do not occur deep environment, day-care centers, and the hospital
within the host cells but are confined to an setting. Direct transmission may occur sexually
extracytoplasmic location. Each stage is within a during oral-anal contact. Indirect contact may
parasitophorous vacuole within the microvillous occur through exposure to positive specimens
region of the mucosal epithelium of several in the laboratory setting or from contaminated
organs including the respiratory tract and the surfaces or food or water. Studies have shown
biliary tract, but most commonly that of the that calves and other animals, including
gastrointestinal tract. Cryptosporidium differs kittens, rodents, puppies, and birds may serve
from other coccidians in its ability to undergo as potential sources of human infections.
complete development within a single host. The Cryptosporidium oocyts, are resistant to most
sporozoites, after being released from the host disinfectants, and are difficult to filter due to
cell, can penetrate the microvillous region of their small size, thus enabling them to persist
other cells and reinitiate the life cycle. Oocysts and spread in the environment.
excreted in stool are immediately infective to Cryptosporidiosis is a substantial threat to
the same host and to others. This auto-infective HIV infected individuals, who have a lifetime
capability contributes to the refractory nature risk of infection of around 10%. The most
of cryptosporidial infection in patients with common clinical feature of cryptosporidiosis
impaired immunity. is diarrhea. Among adult HIV patients,
Cryptosporidium is ubiquitous around the cryptosporidiosis is the reported cause of
world, with the highest prevalence observed in diarrhea in 15 to 40%.
less developed countries. It is transmitted via C. parvum infections are not always
contaminated food or water. Cryptosporidium confined to the gastrointestinal tract; additional
contamination of surface water is quite common. symptoms (respiratory problems, cholecystitis,
The number of ingested Cryptosporidium hepatitis, and pancreatitis) have been associated
oocysts required to cause illness is quite low, with extraintestinal infections. Chronic
with median human infective dose of 132 cough, dyspnea, and fever have been reported
oocysts. to be the major symptoms in pulmonary
Cryptosporidiosis is the most common cryptosporidiosis, with diarrhea only as an
cause of waterborne disease in the United associated symptom.
Kingdom. In the United States, the Milwaukee Diagnostic techniques include stool
cryptosporidiosis outbreak in 1993 was examination, histologic examination of intestinal
the largest outbreak of waterborne disease biopsy, and examination of duodenal aspirates.
ever reported in the United States due to Cryptosporidium oocysts in the stool range
Lake Michigan water contaminated with from 4 to 6 µm in diameter and can be very
Cryptosporidium oocysts. An estimated 403,000 difficult to identify. Stools and other body fluid
residents and visitors of Milwaukee experienced specimens (e.g., sputum) should be submitted
watery diarrhea and 54 cryptosporidiosis- as fresh material or in 5 or 10% formalin,
associated deaths occurred during the two-year sodium acetate-acetic acid-formalin (SAF),
392 Medical Parasitology in the Philippines
or polyvinyl alcohol (PVA) with zinc sulfate- Cryptosporidium-infected HIV patients in India,
based Schaudinn’s fixative. Fixed specimens are the efficacy of short-term azithromycin in the
recommended because of potential biohazard management of cryptosporidiosis was studied.
considerations. Some techniques have included Short-term azithromycin (500 mg once daily for
sugar flotation, formalin sedimentation, 5 days) treatment for cryptosporidial diarrhea in
Giemsa stain, trichrome, periodic acid-Schiff AIDS patients was associated with good clinical
(PAS), silver methenamine, acridine orange, improvement but parasitological benefit was
auramine-rhodamine, iodine, modified acid- doubtful. All 13 patients, who had symptoms
fast, Kinyoun and Ziehl-Neelsen acid-fast, of cryptosporidiosis, symptomatically improved
immunofluorescence assay and immunoassay with 5 days of treatment with azithromycin and
methods. Immunoassay procedures for the became asymptomatic after 7 days of antibiotic,
direct detection of Cryptosporidium antigen but the stool sample remained positive for
or oocysts in fecal specimens have proven Cryptosporidium even after 7 days of therapy.
to be much more sensitive than the routine After 14 days of treatment with azithromycin
acid-fast stains. Enzyme immunoassays, in 13 patients, stool samples from five patient
solid-phase immunochromatographic assays, were free of cryptosporidial oocyst. The
and immunofluorescence assays, which use drug was well tolerated in all the patients.
monoclonal antibodies against the oocyst This small study suggests that short-term
wall, are currently available. A flow-cytometric azithromycin can be used as a safe and effective
method for the quantitation of Cryptosporidium treatment for symptomatic cryptosporidiosis
oocysts in stool specimens have been developed but is not effective in eradicating cryptosporidial
as an alternative method, however, the approach infection. Supportive measures are important in
appears to be somewhat impractical. PCR the management of cryptosporidial diarrhea.
technology also offers alternatives to conventional Nutritional supplements and anti-diarrheal
diagnosis and allows the differentiation of agents may be necessary for symptomatic
Cryptosporidium genotypes. Antibody assays treatment of severe disease. In the absence of
using crude extracts of disrupted oocysts or effective therapy, prevention of infection is
recombinant antigens of Cryptosporidium in paramount. Immunocompromised patients,
an ELISA format and specific Cryptosporidium especially HIV-infected persons, should be
antigens by immunoblot method have been educated and counseled about Cryptosporidium
used for the diagnosis and monitoring of acquisition and transmission. They should
Cryptosporidium infections. be advised to avoid contact with feces and to
Although many therapeutic regimens have wash their hands after handling pets or contact
been tried, there is no completely satisfactory with soil. Patients should avoid sexual practices
therapy for cryptosporidiosis in humans. A that might result in oral exposure to feces (e.g.
recent meta-analysis of trials of antiparasitic oral-anal contact). Cryptosporidiosis may
drugs in cryptosporidiosis noted significant be acquired by drinking contaminated water
improvement of non-AIDS patients with or contact with contaminated water during
nitazoxanide, but no clear evidence of efficacy recreational activities. Water from suspect
for other antiparasitic drugs in cryptosporidiosis sources should be boiled or filtered, and at risk
or for nitazoxanide in AIDS patients. Drugs patients should refrain from swimming in fresh
that have been tried in different regimens water. Since patients with cryptosporidiosis
include paromomycin plus azithromycin, eliminate large amounts of oocysts in their feces,
clarithromycin, and hyperimmune bovine they can easily contaminate the environment
colostrums. In a randomized controlled trial of and persons in contact with them. Because
Chapter 8: Special Topics in Parasitology 393
of this, some experts recommend that HlV- and duodenal and colonic mucosal biopsies,
infected persons or other immunocompromised numerous Cystoisospora oocysts were detected.
patients should not share a room with a patient Extraintestinal infections, including biliary
with known cryptosporidiosis. tract, respiratory tract, lymphatic channel, and
spleen involvement, have been reported. Relapse
D. Cystoisospora belli
tends to be common and may be associated with
Cystoisospora belli is another sporozoan extraintestinal stages. Charcot-Leyden crystals
that causes diarrhea in immunocompromised derived from eosinophils have also been found
hosts. These organisms can infect both adult in stools of patients with C. belli infection.
and children, and intestinal involvement Diagnosis is made by examination of a fecal
and symptoms are generally transient unless specimen for oocysts. Wet mount examination
the patient is immunocompromised. C. either by direct smear or concentrated material
belli is thought to be the only species of allows the demonstration of very pale and
Cystoisospora that infects humans, and no other transparent oocysts. They appear long and
reservoir hosts are recognized for this infection. oval measuring 20 to 33 µm by 10 to 19 µm
Transmission is through ingestion of food or in size. One or, less commonly, two immature
water contaminated with mature, sporulated sporonts may be present as well. Similar to other
oocysts. Sexual transmission by direct oral- coccidians, acid-fast and auramine-rhodamine
anal contact has been postulated. The oocysts staining can be used to demonstrate organisms
are very resistant to environmental conditions in stool.
and may remain viable for months if kept cool Effective treatment is with TMP-SMZ,
and moist. pyrimethamine-sulfadiazine, primaquine
Schizogenic and sporogenic stages have phosphate-nitrofurantoin, or primaquine
been found in the epithelial cells of the distal chloroquine phosphate. TMP- SMZ is the
duodenum and proximal jejunum of the drug of choice. Therapy must be continued
intestines. Eventually, oocysts are passed in indefinitely for immunosuppressed or
the stool. Oocysts continue to mature within immunocompromised patients with recurrent or
48 hours after stool evacuation and are then persistent cystoisosporiasis. Since transmission
infectious. Chronic infections develop in some is via infective oocysts, meticulous hygiene and
patients and oocysts can be shed for several sanitation are essential for preventing spread of
months to years. the disease.
Patients who are immunocompromised,
E. Cyclospora cayetanensis
particularly those with AIDS, often present
with profuse diarrhea associated with weakness, Cyclospora cayetanesis is an acid-fast
anorexia, and weight loss. Bowel movements variable enteric coccidian that can infect
are watery, soft, foamy, and offensive smelling, travelers in developing countries as well as
suggestive of a malabsorption process. immunosuppressed hosts including AIDS
Aside from AIDS patients, C. belli has patients. Spherical unsporulated oocysts, 8 to
been reported to cause opportunistic diarrhea 10 μm in size (twice the size of Cryptosporidium)
in patients with Hodgkin’s disease, non- or ovoid sporocysts, 4 by 6.3 µm in size, are
Hodgkin’s, human T-cell leukemia, and passed in the stools, and sporulation occurs
acute lymphoblastic leukemia. A case report within approximately 7 to 13 days. Complete
in Iran described a patient with mediastinal sporulation produces two sporocysts that
thymoma with an eight-month history of rupture to reveal two crescent-shaped sporozoites
recurrent diarrhea. On direct fecal smear measuring 1.2 by 9.0 µm. The transmission of
394 Medical Parasitology in the Philippines
disposal of animal feces possibly containing in HIV-infected patients and appears to have
infective sporocysts can minimize risk of an ever expanding clinicopathologic spectrum
infection. among immunocompromised hosts. Severely
immunocompromised patients may have
G. Microsporidia
concurrent infections causing diarrhea on top
The microsporidia are obligate intracellular of microsporidia, and so reponse to empiric
parasites that have been recognized in a therapy may be blunted and misleading. To
variety of animals. The organisms found in date, nine genera have been recognized in
humans tend to be smaller, ranging from humans (Table 8.4). These are Enterocytozoon,
1.5 to 2 μm long. They are characterized Encephalitozoon, Pleistophora, Trachipleistophora,
by having spores containing a polar tubule Brachiola, Nosema, Vittaforma, Microsporidium,
which serves as the extrusion mechanism for and Septata. Enterocytozoon bieneusi and the
injecting the spore content into the host cell. three species of Encephalitozoon are the primary
Human microsporidiosis remained rare until microsporidia species associated with human
the AIDS epidemic. Microsporidiosis is an infections. Intestinal microsporidiosis due to
important emerging opportunistic infection Enterocytozoon bieneusi causes chronic diarrhea,
malabsorption, and wasting in AIDS patients. The life cycle includes repeated divisions
Infections with the other species are rare and by binary fission (merogony) or multiple
sporadic. fissions (schizogony) and spore production
The spore is the only life cycle stage able (sporogony). Both merogony and sporogony
to survive outside the host cell (Figure 8.8). can occur in the same cell at the same time.
Acquisition of infection is through ingestion of During sporogony, a thick spore wall is formed.
the spores, and once inside the body, single cells The spores are released into the intestinal
are infected by injection of infective sporoplasm lumen and are passed out with the stool.
through the polar tubule. The microsporidia Spores are environmentally resistant and can
multiply extensively within a parasitophorous then be ingested by prospective hosts. In the
vacuole (genus Encephalitozoon) or directly immunocompromised, microsporidial infection
in the host cell cytoplasm (e.g., E. bieneusi). can lead to overwhelming disease and death.
396 Medical Parasitology in the Philippines
with detection of increased numbers of larvae and 99% specific, however infections with
in stool and/or sputum is the hallmark of filariae or Ascaris can lead to false-positives
hyperinfection. Among the conditions that may results and does not distinguish active from
trigger hyperinfection are AIDS, glucocorticoid past infections.
treatment, and Human T-lymphotropic virus In disseminated strongyloidiasis, filariform
type 1 (HTLV-1) infection. larvae can be found in stool samples as well as
Glucocorticoids are strongly associated sputum, bronchoalveolar lavage fluid, pleural
with transforming chronic strongyloidiasis to fluid, peritoneal fluid; and surgical drainage
hyperinfection. Aside from the decrease in cell- fluid. The typical rhabditiform larvae of S.
mediated immunity, corticosteroids increase stercoralis are characterized by short buccal
the production, mainly in the intestinal wall, capsule with an open mouth and the presence
of ecdysteroid-like substances which may act of a conspicuous genital primodial packet
as molting signals and increase production of of cells. Extreme care should be taken when
auto-infective larvae. working with materials from a patient suspected
Patients who have developed severe systemic of having strongyloidiasis because of possible
S. stercoralis infections include those with filariform larvae in the specimen. Gloves should
hematologic malignancies, connective tissue be worn to prevent skin penetration by these
disease such as systemic lupus erythematosus, larval forms.
solid organ transplant recipients, and other Thiabendazole is the drug of choice in both
underlying immunosuppresive conditions. uncomplicated and disseminated infections, but
When migrating larvae increase in numbers, due to potentially severe side effects, alternative
abdominal complaints and repeated episodes chemotherapy with ivermectin and albendazole
of unexplained bacteremia or meningitis with can be attempted. In a prospective, randomized,
enteric bacteria may occur. This is likely due open-labelled study comparing a seven-day
to larval penetration of the bowel leading to course of oral albendazole 800 mg day versus
translocation of bowel flora into the bloodstream a single oral dose of ivermectin 200 µg, cure
either from the sites of microperforation, rates were 38.1% and 76.2%, respectively. In
attached to the larva, or excreted by the larvae a different randomized trial in rural Zanzibar,
in circulation. a single dose of 200 µg/kg of ivermectin and
Diagnosis of Strongyloides infection is 400 mg/day for 3 days of albendazole in 301
best made by detecting rhabditiform larvae in children with Strongyloides stercoralis resulted
concentrates of multiple stools. Single stool in cure rates of 83% and 45%, respectively. In
exam may miss up to 70% of cases; while three another open randomized study of 60 patients
stool samples increases diagnostic sensitivity with Strongyloides stercoralis infection treated
to 50% and seven serial stool samples raises with albendazole 400 mg/day for 3 days or
sensitivity to more than 90%. ivermectin 150 to 200 µg/kg single dose,
S. stercoralis resides in the duodenum, parasitological cure with the former was 38%
making recovery of the larvae in the stool and 83% for the latter.
difficult in patients with low worm burden. The efficacy of therapy should be monitored
Ancillary techniques like the Entero-Test string with serial examinations until a negative stool or
capsule and the duodenojejunal aspiration may upper small bowel fluid is obtained. Treatment
increase yield. Other techniques for recovering failure and relapse are not infrequent. In patients
Strongyloides larvae include the Harada-Mori with the hyperinfection syndrome, case fatality
and petridish culture techniques. ELISA to rates are high (up to 87%) despite appropriate
detect Strongyloides antibody is 88% sensitive anthelminthic therapy due to the concomitant
Chapter 8: Special Topics in Parasitology 399
elderly. Inadequate sanitation is a major risk million cases of malaria occur every year, at least
factor for acquisition of giardiasis, and drinking a million of which cause deaths. An estimated
of contaminated water is the usual mode of 30 to 36 million people are living with HIV in
infection to travelers in developing countries. Africa, resulting in more than 3 million deaths
AIDS patients presenting with diarrhea should every year. Malaria is more common and severe
be screened for giardiasis. Trophozoites can in adults with HIV, pregnant women, and
be seen on wet mounts and are better seen children.
with Giemsa staining. Lateral flow assays Guidelines for treatments of the two
that detect antigen in stool are commercially infections are often conflicting. There are also
available and are usually combined with issues around drug resistance and cross-reactions
Cryptosporidium. While treatment of giardiasis between drugs, as well as concerns that some
in healthy hosts is straighttforward with medications used to treat HIV-positive persons
metronidazole or tinidazole, those who are could be harmful for malaria treatment in
severely immunocompromised may require certain settings.
longer duration of treatment and may have HIV not only increases the incidence and
more frequent relapse. severity of malaria, it also compromises malaria
Epidemiological studies also suggest that treatment. HIV infection can decrease the
malaria is a deadly co-factor for AIDS. The response to standard antimalarial treatment. For
results of Ugandan study by Whitworth, et al. HIV-positive adults with a weakened immune
involving 484 participants making 7,220 clinic system (a low CD4 count), antimalarial drugs
visits between 1990 and 1998 did show an are less likely to be effective. Malaria contributes
increased frequency of clinical malaria (2.0%) to an increase in viral load among HIV-positive
and parasitemia (11.8%) associated with HIV- people which can potentially accelerate the
1 infection as opposed to their HIV-negative progression from HIV to AIDS.
counterparts, 0.7% and 6.3%, respectively. In a prospective, cross-sectional study, in
Lower CD4 cell counts were associated with the Central Hospital of Maputo, Mozambique
increased parasite densities and increased risk last October 2006, risk factors for fatal outcome
of clinical malaria. In addition, infants born to were determined and impact of HIV on the
mothers co-infected with HIV and malaria had accuracy of malaria diagnosis was assessed.
a four-fold higher mortality rate than infants Among 333 included patients, 15% (51/333)
born to mothers infected with either HIV or had “presumptive malaria,” 10% (28 of 285
malaria alone. tested persons) had positive malaria blood slides,
There is considerable geographical overlap while 69.1% (188/272) were HIV positive.
between malaria and HIV and increasing Seven percent (n=23) had confirmed malaria,
evidence on a direct link with one disease after the diagnosis was rejected in patients with
making the other worse and more difficult to neck stiffness or symptom duration longer than
treat. two weeks (n=5) and persons with negative
Malaria and HIV/AIDS are two of the (n=19) or unknown malaria blood slide (n=4).
most important infectious diseases worldwide, Clinical stage of HIV infection, hypotension,
accounting for almost 9% of the total burden and hypoglycemia were associated with fatal
of disease in sub-Saharan Africa (Figure outcome. The study suggests that the fraction
8.9). Malaria and HIV cause more than four of febrile illness attributable to malaria is lower
million deaths a year combined, and are both in HIV positive adults. HIV testing should be
concentrated primarily in sub-Saharan Africa, considered early in evaluation of patients with
Asia, and South America. More than 500 suspected malaria.
Chapter 8: Special Topics in Parasitology 401
Superimposed endemic parasitic infections parasitic infections among HIV infected and
in tropical countries present a major health uninfected children with diarrhea in Thailand,
problem among HIV-infected individuals intestinal parasites were identified in the
and malnourished hosts. Non-opportunistic stool specimens of 27 out of 82 (33%) HIV
intestinal parasites such as hookworms, infected children and were significantly higher
Opisthorchis viverrini, and A. lumbricoides than the uninfected children [12 out of 80
are common regardless of HIV status. In a (15%)]. In Africa faster progression to AIDS
prospective observational study on intestinal and increased HIV viral load occurred in areas
402 Medical Parasitology in the Philippines
highly endemic for helminths. These long- Bangkok, Thailand. Southeast Asian J Trop
lasting parasitic infections cause widespread Med Public Health. 2001;32(4):770–775.
activation and dysregulation, inducing a DuPont HL, Chapelli CL, Sterling CR,
dominant Th2 cytokine immune profile and Okhuysen PC, Rose JB, Jakubowski W.
an immune hyporesponsive state. Helminths The infectivity of Cryptosporidium parvum
induce a predominantly Th2 response, and this in healthy volunteers. N Engl J Med.
has been associated with progression of HIV. 1995;332(13):855–9.
Endemic tropical non-opportunistic parasitic Farthing MJ. Clinical aspects of human
infections present a special and significant cryptosporidiosis. Contrib Microbiol.
risk in immunocompromised individuals. It 2000;6:50–74.
is important for the clinicians and laboratory Foreman EB, Abraham PJ, Garland JL. Not
personnel to be aware of the problems these your typical Strongyloides infection: a
organisms can cause and recognize their clinical literature review and case study. South Med
relevance. J. 2006;99(8):847–52.
Gassama A, Sow PS, Fall F, Camara P, Gueye-
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Berg A, Patel S, Langeland N, Blomberg Husni RN, Gordon SM, Longworth DL, Adal
B. Falcipar um malaria and HIV- KA. Disseminated Strongyloides stercoralis
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Chaisson RE, Gallant JE, Keruly JC, Moore for cryptosporidiosis in human
RD. Impact of opportunistic disease on immunodeficiency virus disease. J Postgrad
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Chokephaibulkit K, Wanachiwanawin D, immunocompromised population. Clin
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Chapter 8: Special Topics in Parasitology 403
Figure 8.10. Global distribution of neglected tropical diseases (NTDs) by number of NTDs per country
(Accessed from http://ffctn.com/a/ghs-ntd)
a majority of foodborne trematode infections schistosomiasis are also in this region. Table 8.5
can be found in Southeast Asia and China. enumerates the NTDs targeted by the World
Approximately one-half of the active trachoma Health Organization (WHO) for control, with
infections, and a significant proportion of the a focus on those endemic to the Philippines.
number of cases of lymphatic filariasis (LF) and
Chapter 8: Special Topics in Parasitology 405
Table 8.5. Neglected tropical diseases targeted year is attributable to schistosomiasis in the
by the WHO Philippines.
The concept of disability-adjusted life years
Endemic
Disease in the (DALYs) was developed to quantitatively assess
Philippines the burden of individual diseases. DALYs take
Buruli ulcer into account both premature mortality (years
Chagas disease* of life lost) and disability (years of life lived
Cysticercosis* with a disability weighted by the severity of the
Dengue disability). DALYs assigned to a specific disease
Dracunculiasis (guinea-worm disease)* at a particular time gives the estimated sum of
Echinococcosis*
years of potential life lost due to premature
Fascioliasis*
mortality and years of productive life lost. For
Human African trypanosomiasis
example, it is estimated that 5,941,000 years of
potential life are lost globally due to lymphatic
Leishmaniasis*
filariasis. The use of DALYs, however, is
Leprosy
somewhat controversial since its design contains
Lymphatic filariasis*
inherent systematic flaws that result in under
Onchocerciasis*
evaluation of the importance of chronic diseases
Rabies
such as NTDs. Because DALYs focus more on
Schistosomiasis* individual risk rather than the ecology of the
Soil-transmitted helminthiasis* disease, the weight of disability for chronic
Trachoma diseases in the context of poverty tend to be
Yaws underestimated.
*Diseases caused by parasites The concept of a quality-adjusted life years
(QALYs) is an alternative means to quantify
losses attributable to disease. The QALYs system
Burden of Neglect
uses estimates from preference-based health
NTDs disproportionately affect the poorest related quality-of-life interviews administered to
and most marginalized, including the rural groups of patients or to members of the general
poor, residents of urban slums, out of school population in an endemic community. QALYs
youth, women, and indigenous people whose are better able to assess the societal context
access to formal health services are limited for of disease impact that may not be accurately
cultural, social, or geographic reasons. It is captured by DALYs. Improvement of DALYs
difficult to quantify the social burden associated calculations and development of new metrics
with crippling disabilities and reductions in such as QALYs are ongoing. Such efforts are an
productivity of individuals and communities important aspect of assessment of the burden of
caused by NTDs. Nevertheless, efforts to NTDs because they provide a mechanism for
measure the social and economic impact of determining health priorities.
NTDs can provide an understanding of the Polyparasitism
extent of disease burden, and are important in
order to guide policies and prioritize disease The burden of NTDs is further compounded
control programs. Calculations of disability by the fact that infection with multiple parasite
rate, for example, estimate that a total of species, known as polyparasitism, is more often
45.4 days off-work lost per infected person/ the norm rather than the exception. Community
406 Medical Parasitology in the Philippines
surveys in Cote d’Ivoire demonstrated infection (15-24 years old), and are more common in
with at least two intestinal parasites (Schistosoma males. A community parasitologic survey in
mansoni, soil-transmitted helminths and/or Cote d’Ivoire observed the highest frequency
intestinal protozoans) in 90.2% of the sampled of polyparasitism among adolescents and young
population. In Brazil, co-infection with Necator adults (15-24 years old).
americanus and S. mansoni was observed Geographic distribution, in relation to
in 41.0% of the community participants the overlapping of areas of endemicity, also
examined. In a community survey in China, contributes to the occurrence of polyparasitism.
27.8% of those surveyed were infected with at In addition, behavioral factors may also be
least two parasite species (Ascaris, Trichuris, and/ attributed to polyparasitism. Behavior related
or S. japonicum). to personal hygiene can greatly contribute to
Local sentinel parasitologic surveys on infection of parasites with similar modes of
school-age children revealed multiple infections transmission. Socioeconomic status, living
with at least two helminths (soil-transmitted conditions and access to health and sanitary
helminths, Schistosoma japonicum and/or facilities also influence the distribution of
heterophyids) in 20.4% of those examined. polyparasitism and parasitic infections in
Similarly, co-infections between different general. Individuals of lower socioeconomic
STH species and S. japonicum were observed status are less likely to have adequate water
in 13.1% of school-age children in indigenous and sanitation, and are less likely to invest in
peoples in Davao del Norte. bed nets for protection against mosquito-borne
Although there are existing data diseases. Similarly, low education levels have
on the global prevalence and burden of been associated with limited access to effective
individual parasitic diseases, there are still no treatment, and less compliance with preventive
accurate estimations on the global burden of measures.
polyparasitism. Estimates of populations at A study by Ellis et al. that looked into
risk of multiple parasitic infections have been environmental and genetic predispositions to
described by looking into co-distribution rather polyparasitism revealed that the risk of Ascaris
than co-infection. Currently, there are limited and Trichuris co-infection, and S. japonicum
studies on the epidemiology and impact of and Trichuris co-infection were significantly
polyparasitism. Research looking into the use influenced by environmental or household
of polyparasitism as a parameter for effective conditions. Data from this study also revealed
disease control needs to be explored. that there is a significant genetic component
attributed to the risk of multiple parasitic
Risk Factors for Polyparasitism
infections. This suggests that polyparasitism
The risk for polyparasitism, as with may aggregate in a familial pattern.
individual infections, is influenced by the
Combined Impact of Polyparasitism
combined effects of several factors. Intrinsic
factors are attributed to host resistance that Infection with multiple parasites intuitively
is influenced by age and sex; and linked to results in higher morbidity than the impact of
frequency of exposure to infection, as well as a single infection. Malnutrition, as exemplified
development of immunity, or a combination by wasting and stunting, arises as a result
of both. Ascaris and Trichuris infections, for of co-infections with malaria, STH, and/or
example, are most prevalent among the 5 to15 Schistosoma. Intestinal helminth infections
years old age group. Hookworm infections are cause intestinal inflammation and reduced
most prevalent among middle-aged individuals food intake, while malaria and schistosomiasis
Chapter 8: Special Topics in Parasitology 407
may trigger inflammatory cytokines that cause A synergistic effect has also been demonstrated
anorexia and induce a catabolic response. between Ascaris and Trichuris infections, while
Anemia in malaria infection is from protective effects against malaria have been
hemolysis and phagocytosis, while anemia from reported as a result of Ascaris or S. haematobium
STH infections arises from chronic intestinal infections.
blood loss. A local study has demonstrated a
Strategic Approaches
significant association between anemia and
S. japonicum infection. Given the different A. Disease Surveillance
mechanisms by which these infections bring
Successful control of NTDs requires
about malnutrition and anemia, it is possible
active surveillance programs at the local level
that the effects of co-infection on malnutrition
in order to understand prevalence and disease
and anemia are additive. Studies in Kenya
distribution. Information on the burden of
revealed significantly lower hemoglobin among
NTDs is important to determine specific disease
preschool and school age children with malaria-
control and prevention strategies. On the other
hookworm co-infections, compared to those
hand, data on the geographical distribution of
with single infection. Another study done in
NTDs can help direct resources to priority areas,
Nigeria has shown lower mean hemoglobin
especially in low-income countries where NTDs
among pregnant women with co-infections with
are prevalent and resources are limited.
malaria and STH, although the difference was
Strengthening the capacity of health
not statistically significant.
professionals is important for early diagnosis
An increasing number of studies have
and treatment of cases. The local medical
demonstrated significant associations between
technologist plays a major role in the
co-infections with different helminth species.
performance of appropriate and accurate
Helminth infection has been shown to elicit
laboratory examinations. Accurate and timely
an immune response that either results in
diagnosis will not only contribute to the proper
the production of non-cytophilic antibodies
treatment and early prevention of morbidity,
allowing increased susceptibility to further
but also limit under- or over-reporting of cases.
infection, or results in effective inflammatory
This will also result in reporting of reliable data
factors that offers protection against other
for proper disease monitoring and surveillance.
parasitic infections.
A notable increase in hookworm intensity B. Preventive Chemotherapy
has been described with an increasing number of
The WHO defines preventive chemotherapy
co-infecting helminths (Ascaris and S. mansoni).
as a major strategy for the control of a number
With regard to Ascaris infection, there was a
of parasitic diseases through morbidity and
significant increase in intensity of infection in
transmission control. Preventive chemotherapy
the presence of hookworm co-infection, and a
through mass drug administration is
significant decrease in the presence of S. mansoni
recommended for the control of lymphatic
co-infection. The synergistic effect of hookworm
filariasis, onchocerciasis, schistosomiasis, and
infection with other helminth infections may be
soil-transmitted helminthiasis. Given the
attributed to immunomodulation resulting in
overlapping distribution of many NTDs, the
reduced cellular reactivity. T-regulatory cells
WHO recommends combined control strategies
(Tr1) that secrete cytokines may play a role
in a drug-based rather than a disease-based
in the down-regulation of the host’s immune
approach. The drug-based approach looks into
response to subsequent helminth infections,
combined control of diseases that are targeted
thus resulting in greater intensities of infection.
by the same drugs.
408 Medical Parasitology in the Philippines
Ellis MK, Raso G, Li YS, Rong Z, Chen HG, Lazdins J. Assessment of pharmacokinetic
McManus DP. Familial aggregation of drug interactions and tolerability of
human susceptibility to co- and multiple albendazole, praziquantel and ivermectin
helminth infections in a population from combinations. Trans R Soc Trop Med Hyg.
the Poyang Lake region, China. Int J 2006;100:335–45.
Parasitol. 2007;37(10-3):1153–61. Pullan RL, Bethony JM, Geiger SM, Cundill
Egwunyenga AO, Ajayi JA, Nmorsi OPG, B, Correa-Oliveira R, Quillen RJ, et al.
Duhlinska-Popova DD. Plasmodium/ Human helminth co-infection: analysis
intestinal helminth co-infections among of spatial patterns and risk factors in a
pregnant Nigerian women. Mem Inst Brazilian community. PLoS Negl Trop Dis.
Oswaldo Cruz. 2001;96(8):1055–9. 2008;2(12):e352.
Ezeamama AE, Friedman JF, Acosta LP, Pullan R, Brooker S. The health impact
Bellinger DC, Langdon GC, Manalo DL, of polyparasitism in humans: are we
et al. Helminth infection and cognitive underestimating the burden of parasitic
impairment among Filipino children. Am diseases? Parasitology. 2008;135:783–94.
J Trop Med Hyg. 2005;72(5):540–8. Raso G, Luginbühl A, Adjoua CA, Tian-Bi
Feasey N, Wansbrough-Jones M, Mabey DC, NT, Silué KD, Matthys B, et al. Multiple
Solomon AW. Neglected tropical diseases. parasite infections and their relationship
Br Med Bull. 2009;93(1):179–200. to self-reported morbidity in a community
Hotez PJ, Ehrenberg JP. Escalating the global of rural Côte d’Ivoire. Int J Epidemiol.
fight against neglected tropical diseases 2004;33:1092–102.
through interventions in the Asia Pacific Department for International Development.
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Polyparasitism with Schistosoma mansoni, World Health Organization. Preventive
geohelminths, and intestinal protozoa Chemotherapy in Human Helminthiasis.
in rural Cote d’Ivoire. J Parasitol. Geneva: World Health Organization; 2006.
2002;88(3):461–6. World Health Organization. Global plan
King CH, Bertino A-M. Asymmetries of to combat neglected tropical diseases
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Mwangi TW, Bethony JM, Brooker S. Malaria World Health Organization. Working to
and helminth interactions in humans: an overcome the global impact of neglected
epidemiological viewpoint. Ann Trop Med tropical diseases. Geneva: World Health
Parasitol. 2006;100(7):551–70. Organization; 2010.
Na-Bangchang K, Kietinunb S, Pawab KK,
Hanpitakponga W, Na-Bangchangc C,
410 Medical Parasitology in the Philippines
Preventive Chemotherapy
Vicente Y. Belizario, Jr., Francis Isidore G. Totañes, Paul Lester C. Chua
specialized personnel on individuals reporting complete their life cycle. Consequently, direct
to health facilities. human-to-human spread is unfeasible and
Lastly, PCT is implemented at regular disease transmission becomes a slow process.
intervals based on the parasitologic status These facts suggest that the rate of increase in
as determined by the population-based number of worms within a human host that
surveillance. The intervention is repeated contributes to the intensity of infection is slow
without the need for further diagnostic depending on subsequent re-infection episodes.
interventions, although implementation of a The risk of developing morbidity and the
monitoring system is important. likelihood of disease transmission are dependent
on the individual’s intensity of infection. As
Modalities of Implementation
the intensity of infection increases slowly, the
There are three modalities by which PCT individual’s risk of developing morbidity also
interventions can be implemented. increases slowly, explaining why early-stage
manifestations associated with the targeted
• Un i ve r s a l t re a t m e n t i s t h e helminth infections are frequently overlooked.
administration of anthelminthics to Second, community diagnostic procedures are
the entire population of an area (e.g., available for each of the four diseases. Third,
state, region, province, district, sub- drug delivery strategies relying on resource
district, village) at regular intervals, persons based in schools or within communities
irrespective of the individual infection have been developed; and lastly, recommended
status. anthelminthics are low cost or given by
• Ta r g e t e d t r e a t m e n t i s t h e pharmaceutical companies as donations. All
administration of anthelminthics at these factors contribute to contain costs and
regular intervals to specific high-risk make the PCT interventions feasible for
groups in the population, defined by implementation against the four target diseases.
age, sex, or other social characteristics In addition, all anthelminthics currently
(e.g., school-age children, farmers), used in PCT interventions [albendazole (ALB),
irrespective of the individual infection diethylcarbamazine (DEC), ivermectin (IVM),
status. mebendazole (MBD), and praziquantel (PZQ)]
• Selective treatment is the are safe (i.e., adverse events are rare, mild, and
administration of anthelminthics to transient), and therefore appropriate for use
all infected individuals (confirmed or in interventions targeting infected, as well as
suspected) who are identified after a non-infected individuals. Temporary minor
regular parasitologic screening of a reactions following treatment occur mainly
population group living in an endemic as a result of the body’s response to the dying
area. worms. Thus, heavily infected individuals are
Currently Targeted Diseases expected to experience the most reactions. In
general, the number of individuals reporting
PCT targets four NTDs (LF, onchocerciasis, for adverse reactions is highest during the first
schistosomiasis, and STH) because of a number round of treatment and tends to decrease during
of reasons. First, helminths responsible for the succeeding rounds.
four diseases are unable to replicate in humans Such effective anthelminthics are also simple
and require one or more obligate passages to administer allowing the drug distribution by
outside the host (e.g., in an intermediate host, non-medical personnel possible. In the War on
in a vector, or in the environment) in order to Worms—Western Visayas approach, a local
412 Medical Parasitology in the Philippines
government unit (LGU) led, school-based, in the prevalence and intensities of infection
school teacher-assisted mass drug administration among the school children after two years of
(MDA) has resulted in significant reductions implementation (Figure 8.12).
Figure 8.12. Cumulative STH prevalence and heavy intensity infections in school-age children in Aklan,
Antique, and Capiz, 2007-2009
(Courtesy of Dr. Vicente Belizario, Jr.)
same area. This is to minimize the risk In the Philippines, three helminth
of targeted individuals suffering from infections are targeted for control or elimination
adverse reactions due to interactions by the Department of Health through national
between drugs distributed by different programs that utilize MDA as a major strategy
programs. (Table 8.6).
Table 8.6. Target population, drug recommended, and mass drug administration frequency of health
programs in the Philippines
Figure 8.13. Process, performance, and impact indicators for helminth control
(From World Health Organization. Helminth control in school-age children: a guide for managers of
control programmes. 2nd ed. Geneva: World Health Organization; 2011.)
Chapter 8: Special Topics in Parasitology 415
Table 8.7. Categories, usage, and frequency of policy formulation for NTD control
collection of indicators and elimination.
• Difficulties encountered during
Frequency of
Category Use rounds of MDA can be revealed such
collection
Process Determine whether At every drug as the identification of areas where
organizational administration fewer individuals receive drugs than
elements of the round
control program intended.
are in place and • Providers of drugs and funds to
are functioning
properly support drug delivery, including the
Performance Assess whether At every drug
governments of disease-endemic
coverage of the administration countries, can be assured that the
control program round
has reached its
provided support is cost-effective.
objective • Workers and volunteers involved in
Impact Assess whether the At baseline drug delivery can be informed about
health impact of and every
the program has 2-3 years
their efforts, which can contribute to
been achieved thereafter maintaining staff morale.
Source: World Health Organization. Helminth control in school-age • Advocacy for more support for NTD
children: a guide for managers of control programmes. 2nd
ed. Geneva: World Health Organization; 2011. control is strengthened by knowledge
that many people in need are getting
Every effort should be made to ensure direct treatment.
observation of MDA (i.e., administration of the • Forecasting for drug supplies for future
appropriate dose in the presence of the drug treatment rounds is supported.
provider) (Figure 8.14). If actual swallowing Role of Social Mobilization
of tablets by targeted individuals cannot be
observed directly, random cluster surveys can These neglected diseases, especially
be undertaken to estimate the actual coverage. helminth diseases, do not rapidly cause death
Monitoring drug coverage has several and are more insidious in nature than many
important outcomes. diseases of acute onset. Health care providers
therefore consider NTDs a low priority.
• Reliable drug coverage rates contribute The objective of PCT interventions is to
to accurate information necessary for ensure that all eligible individuals in affected
communities swallow the recommended
drugs. This behavioral change is dependent
on the acceptance of targeted individuals for
treatment, as well as on the health care providers’
capacity to adequately inform and motivate the
community. Social mobilization is a complex
process that involves program implementation,
health care delivery services, health care
providers, and strategies for mobilization
and communication interacting to influence
behavioral change in people. Experiences with
Figure 8.14. Checking for tongue discoloration
existing health care programs have shown that
after administration of deworming tablets to
school children to ensure compliance this aspect of social mobilization is not given
(Courtesy of Dr. Vicente Belizario, Jr.) adequate priority during the planning of PCT
416 Medical Parasitology in the Philippines
Spiegel JM, Dharamsi S, Wasan KM, Yassi Geneva: World Health Organization;
A, Singer B, Hotez PJ, et al. Which 2010. p. 1–7.
new approaches to tackling neglected World Health Organization. Working to
tropical diseases show promise. PLoS Med. overcome the global impact of neglected
2010;7(5):1–5. tropical diseases: first WHO report on
War on worms goes to Western Visayas. neglected tropical diseases. Geneva: World
Philippine Star. 2007 Nov 27;Health & Health Organization; 2010. p. 1–5.
Family:E-2. World Health Organization. Assuring safety
World Health Organization. Report on active of preventive chemotherapy interventions
surveillance for adverse events following for control of neglected tropical diseases.
the use of drug coadministrations in Geneva: World Health Organization;
the Global Programme to Eliminate 2011. p. 4–9.
Lymphatic Filariasis. Wkly Epidemiol Rec. World Health Organization. Helminth control
2003;78:315–-7. in school-age children: a guide for managers
World Health Organization. Preventive of control programmes. 2nd ed. Geneva:
chemotherapy in human helminthiasis: World Health Organization; 2011.
coordinated use of anthelminthic drugs in World Health Organization. Integrated
control interventions: a manual for health preventive chemotherapy for neglected
professionals and programme managers. tropical diseases: estimation of the number
Geneva: World Health Organization; 2006. of interventions required and delivered,
p. 1–62. 2009-2010. Wkly Epidemiol Rec.
World Health Organization. Monitoring drug 2012;87:17–26.
coverage for preventive chemotherapy.
418 Medical Parasitology in the Philippines
The Pre-Travel Medical Consultation new vaccines. Allergies to food and drugs are
elicited, as well as any reactions to previous
In order to minimize the possibility of
vaccinations. Some vaccines may cause allergic
travel related illness, the traveler must gather
reactions in those who are hypersensitive to
as much information about the travel
poultry products because these may be produced
destination(s) and possible activities that
in chicken or duck eggs. Influenza vaccines in
he will engage in. A traveler should ideally
particular may give a reaction in those allergic
consult a medical practitioner with experience
to poultry. A list of current medications is also
in travel medicine at least four weeks prior to
useful to determine whether drug interactions
departure. A longer preparation period may be
may occur with those that may be prescribed for
needed if long-term travel or overseas work is
prophylaxis or treatment. An adequate supply
expected, while consults as late as the day before
of medication should be brought with the
travel may still be of benefit.
traveler since obtaining medication abroad may
Itinerary be difficult, along with the risk of counterfeit
medication.
A detailed itinerary should be made
Physiologic states such as pregnancy,
available to the travel medicine provider prior
or breastfeeding status may present special
to the consultation so that the practitioner
problems during travel. For instance, access
can adequately determine possible medical,
to birthing facilities abroad may need to
environmental, and physical risks to the
be determined when traveling during late
traveler. This includes dates of departure and
pregnancy. Certain airlines place restrictions
return, countries and cities which will be visited
on travel of pregnant women who are near
including accommodations, and whether the
term. Breastfeeding mothers may have to stop
traveler will stay within urban limits or sojourn
breastfeeding if certain prophylactic medicines
into rural and sylvan areas. Transit cities should
are used, such as doxycycline and ciprofloxacin.
also be included, as some countries have specific
vaccination requirements for visas going to and Interventions
from origin countries and entry may be denied
Patient education on avoiding food- and
on this basis.
water-borne diseases, as well as use of insect
An excellent reference that is used for risk
repellents such as N,N-diethyl-meta-toluamide
assessment is the Centers for Disease Control
(DEET)-containing preparations to avoid
and Prevention (CDC) Yellow Book, which has
arthropod and other vector-borne diseases should
detailed descriptions of destinations and risks
be done. Instructions for self-medication for
therein. Commercial travel medicine websites
travel-related diarrhea (including antimicrobial
such as www.travax.com can be used to generate
use and oral rehydration solutions), as well as
useful information, including patient handouts
avoidance of contaminated water and ice should
to help guide the traveler during his or her trip.
be emphasized. Use of sunblock and protective
Clinic Visit clothing should be mentioned, especially
since some prophylactic medications such as
Basic demographic data along with specific
doxycycline can cause photosensitivity. Special
health data is needed by the travel physician to
instructions regarding avoidance of specific
make a complete risk assessment for the traveler.
illnesses (e.g., avoid wading in fresh water in
Aside from age, sex, and past medical history,
schistosomiasis- and leptospirosis-endemic
a good vaccination history is also imperative in
areas) should be given on a case-by-case basis.
order to determine the need for boosters and
Risks of sexually transmitted diseases (STDs),
420 Medical Parasitology in the Philippines
including HIV and AIDS, should be assessed Table 8.8. Vaccines for travelers
and appropriate measures taken. Finally,
Category Vaccine
arrangements should be made regarding access
1. Routine vaccination Diphtheria, pertussis, and
to medical treatment in emergent situations. tetanus
The need for any vaccinations and Hepatitis B
Haemophilus influenzae
prophylaxis will depend on multiple factors. type b
Most travel medicine authorities will make Human papillomavirus
Seasonal influenza*
recommendations on the use of these Measles, mumps and
interventions depending on risk of exposure, rubella
Meningococcal disease**
clinical impact, potential adverse reaction to Pneumococcal disease
the medication, and quarantine and infection Poliomyelitis
Tuberculosis (BCG)
risk to others. The only consistently required Varicella
vaccine for travel purposes is yellow fever (for 2. Selective use for Cholera
travel to endemic areas), while all others are travelers Hepatitis A**
recommended in varying degrees and depend Japanese encephalitis
Rabies
on the type of exposures anticipated. Tick-borne encephalitis
Typhoid fever
Vaccine-Preventable Diseases 3. Mandatory vaccination Yellow fever**
Meningococcal disease
Local recommendations for the and polio (required
immunization of adult Filipinos have been by Saudi Arabia for
pilgrims; updates are
developed by the Philippine Society for available from www.
Microbiology and Infectious Diseases with the who.int/wer)
* Routine for certain age groups and risk factors, selective for
Philippine Foundation for Vaccination in 2009 general travelers
and are available online at www.pcp.org.ph. **Included in the routine immunization program in several
countries
Indications for age, exposure, risk, and specific (Adapted from WHO International Travel and Health 2010)
Disease/
Etiologic Transmission Nature of disease Occurrence Risk for travelers Preventive measures
agent
Hepatitis A Fecal-oral route • Abrupt onset of fever, • Worldwide, levels of • Risk varies with living • Two vaccine doses at 0 and
malaise, anorexia, nausea, endemicity are related conditions, length of stay, 6-12 months (HAVRIX, VAQTA)
and abdominal discomfort, to hygienic and sanitary and the incidence of • Accelerated schedule of
followed within a few days by conditions in the geographic Hepatitis A infection in the the combined Hepatitis A+B
jaundice areas area visited vaccine (TWINRIX) – days 0, 7,
• Frequently acquired during • Intermediate to high • Risk increases with visit to and 21 PLUS a booster dose
early childhood and is usually endemicity throughout the rural areas, trekking in back- at 1 year
asymptomatic or mild developing world country areas, or frequent • One dose administered at
eating or drinking in settings any time before departure
of poor sanitation can provide protection
for most healthy persons,
as early as 2 weeks after
administration
• Indication for Hepatitis A
Immunoglobulin (passive
vaccination) 0.02 mL/kg:
<1yr old, allergy to a vaccine
component; single dose
provides protection up to 3
months
Hepatitis B Transmission • During acute infection: • Low prevalence (<2%) in • Generally low, except for • Vaccine given in a 3-dose
through blood nausea, vomiting, abdominal Northern and Western Europe, travelers to countries with high series on a 0-, 1-, and
or blood- pain, and jaundice; rashes, North America, Australia, New prevalence 6-month schedule
derived fluids joint pain, and arthritis may Zealand, Mexico, and South • Adventure travelers, • Accelerated schedule for
occur America Peace Corps volunteers, ENGERIX and TWINRIX as
• Intermediate (2-7%) in South, missionaries, and military described above
Central, and Southwest Asia, personnel, may be at • Initiate vaccine, if indicated,
Israel, Japan, Eastern and increased risk for infection even if it cannot be
Southern Europe, Russia, completed before departure
most areas surrounding
the Amazon River basin,
Honduras, and Guatemala
• High (≥8%) in Africa;
Southeast Asia, China, Korea;
the Middle East, except Israel;
South and Western Pacific
islands; the interior Amazon
River basin; and certain parts
of the Caribbean (Haiti and
Chapter 8: Special Topics in Parasitology 421
in this section. Malaria is found in over plains. Plasmodium falciparum accounts for 70
100 countries, and greater than 125 million to 80% of cases, while P. vivax accounts for 20 to
international travelers are at risk every year. It 30%. P. falciparum resistant to chloroquine and
remains the most common cause of fever in sulfadoxine-pyrimethamine has been reported,
returning travelers. Many travelers continue to and so chloroquine should not be taken to
acquire malaria, and more than 10,000 reported prevent malaria when traveling to endemic
cases likely represent only the tip of the iceberg. areas (Table 8.10).
Malaria, especially falciparum malaria can be a Anophelene mosquitoes that transmit
life-threatening disease, but is quite amenable malaria are known to be night biters. Preventing
to treatment when recognized early. In the mosquito bites can be done through: wearing
Philippines, malaria risk exists throughout the long-sleeved clothing and trousers, especially at
year in areas below 600 m, except in the 22 night; use of insect repellents including DEET-
provinces declared as malaria-free: Aklan, Albay, containing and citronella-based preparations
Benguet, Bilaran, Bohol, Camiguin, Capiz, with periodic reapplication; and mosquito nets
Catanduanes, Cavite, Cebu, Guimaras, Iloilo, which should ideally be treated with insecticide.
Northern Leyte, Southern Leyte, Marinduque, Garlic, vitamin B, and ultrasound devices do
Masbate, Eastern Samar, Northern Samar, not prevent bites. Travelers should be wary
Western Samar, Siquijor, Sorsogon, Surigao of the symptoms of malaria especially fever
Del Norte, and Metropolitan Manila. No risk occurring 1 week after the possible exposure
is considered to exist in urban areas or in the and up to 2 years after the return.
Geographic
Disease Cause Transmission Nature of disease Risk for travelers Prevention
distribution
Amebiasis Previously discussed
Avian influenza Highly pathogenic • Contact with avian • Influenza-like illness, • Only sporadic human • Contact with • Avoid consumption of
avian influenza fecal material diarrhea, and other infections have environments such as undercooked eggs,
A (H5N1) virus or • Bird-to-human, GI complaints occurred to date live animal markets poultry or poultry
other non-human possibly environment- • Pneumonia with • Between November and poultry farms, products
influenza subtypes to-human and, very radiographic infiltrates 2003 and July 2008, any free-ranging or • Hand hygiene
(e.g., H7, H9) rarely, limited, non- of varying patterns nearly 400 human caged poultry, or • Avoid contact with
sustained human-to- • Hemoptysis frequent cases of H5N1 were surfaces that might animals and dead
human transmission • Multi-organ failure, reported to WHO be contaminated migratory birds
• No evidence that sepsis-like syndromes from 15 countries in by poultry droppings • Treatment and post-
properly cooked • Fatality rate among Africa, South-East and increase risk exposure prophylaxis:
poultry or poultry hospitalized patients Central Asia, Europe, oseltamivir, zanamivir
products can be a with H5N1 high and the Middle East • Although the
source of infection (~60%) vaccines are
• Severe illness also immunogenic,
for H7N7 but mild for unknown effectiveness in
other avian influenza preventing the H5N1
subtypes (e.g., H9N2) infection or reducing
disease severity
Anthrax Bacillus anthracis • Contact with products • Acute skin infection • Sporadic cases occur • Very low for most • No prophylaxis
from infected animals (most common form) in animals worldwide travelers vaccine available
(mainly cattle, goats, • Untreated infections • Occasional outbreaks for people at
sheep), such as may spread to in Africa and Central high risk because
leather or woolen regional lymph Asia. of occupational
goods, or souvenirs nodes and to the exposure to B.
made from animal bloodstream, and anthracis not
skins may be fatal. commercially
• Contact with soil available in most
containing anthrax countries
spores • Avoid direct contact
with soil and with
products of animal
origin.
Brucellosis Several species of • Direct contact with • Generalized infection • Worldwide, in animals • Low • No prophylaxis
Brucella bacteria infected cattle with insidious onset, • Most common in • Visit to rural and • Avoid consumption
(Brucella abortus), causing continuous or developing countries, agricultural areas, of unpasteurized milk
dogs (B. canis), pigs intermittent fever and South America, intake of raw, and milk products
(B. suis), or sheep and malaise, which may Central Asia, the unpasteurized milk • Avoid direct contact
Goats (B. melitensis) last for months if not Mediterranean, and increase the risk with animals,
• Consumption of treated adequately the Middle East particularly cattle,
unpasteurized (raw) • Relapse common goats and sheep.
milk or cheese after treatment
Chapter 8: Special Topics in Parasitology 427
Geographic
Disease Cause Transmission Nature of disease Risk for travelers Prevention 428
distribution
Chikungunya Chikungunya virus— • Bites of Aedes aegypti • Acute febrile illness • Chikungunya occurs • Risk for travelers • No antivirals
an alphavirus from and Aedes albopictus with joint pains, in sub-Saharan Africa, in areas where • No vaccine
the Togaviridae mosquitoes bite particularly affecting South-East Asia and Chikungunya is • Treatment is
family during daylight with the hands, wrists, tropical areas of the endemic supportive.
peak activity in the ankles, and feet Indian subcontinent, • Mosquito bite
early morning and • Recovery after a few as well as islands in precaution during
late afternoon days but joint pains the South-Western both day and night
• No direct person-to- may persist Indian Ocean
person transmission • Muscle pain,
headache, rash,
leukopenia, GI,
ocular, heart
and neurologic
complaints reported
Coccidiomycosis Coccidioides spp., a • Inhalation of fungal • Diseases range from • Mainly in the • Low • No vaccine.
fungus conidia from dust asymptomatic to Americas • Risk increases • Reduce exposure,
influenza-like illness to with activities that wear well-fitted mask
disseminated disease result in exposure
to dust, e.g., dirt
biking, excavation,
construction
Dengue Dengue virus—a • Bite of Aedes aegypti • Occurs in 3 forms: (1) • Widespread in • Significant risk for • No vaccine
flavivirus with mosquito during acute febrile illness tropical and travelers in areas • No antiviral
serotypes 1 to 4 daytime followed by severe subtropical regions where dengue is • Avoid mosquito bites.
• No person-to-person musculoskeletal of Central and South endemic
transmission pain and rash, (2) America, South and
• Monkey acts as fever followed by South-East Asia,
reservoir host in west thrombocytopenia Africa, and Oceania
Africa and South-east and hemorrhagic • The risk is lower at
Asia complications, and altitudes above 1,000
(3) acute febrile m
illness followed by
hypotension and
Medical Parasitology in the Philippines
shock
Disease Cause Transmission Nature of disease
Geographic
Risk for travelers Prevention
distribution
Giardiasis Previously discussed
Hemorrhagic Fevers: Ebola and Marburg • Transmitted by • Severe acute viral • Ebola and Marburg • Low • No prophylaxis
Ebola and Marburg belong to the mosquitoes (RVF), infections, usually hemorrhagic fevers • Travelers visiting rural • Avoid mosquito bites.
hemorrhagic fevers, Filoviridae family; ticks (CCHF), rodents with sudden onset and Lassa fever or forest areas may • Avoid unpasteurized
Crimean-Congo CCHF and RVF (Lassa) or bats (Ebola, of fever, malaise, occur in parts of sub- be exposed. milk.
hemorrhagic fever belong to the Marburg) headache, and Saharan Africa.
(CCHF), Rift Valley Bunyaviridae • For Ebola or Marburg myalgia followed by • CCHF occurs in the
fever (RVF), family; Lassa fever viruses, infection pharyngitis, vomiting, steppe regions of
Lassa fever belongs to the from direct contact diarrhea, skin rash, Central Asia and in
Arenaviridae family with the body fluids and bleeding Central Europe, as
or secretions of • Outcome is fatal in well as in tropical and
infected patients, a high proportion of Southern Africa.
and less commonly, cases (more than • RVF occurs in Africa
contact with tissues 50%). and has recently
of diseased primates spread to Saudi
and other mammals Arabia.
• Lassa fever virus • Other viral
transmitted through hemorrhagic fevers
rodent excreta (via occur in Central and
aerosols or direct South America.
contact)
• Blood/body fluid
transmission for other
hemorrhagic fevers
• Consumption of
unpasteurized milk
Hantavirus diseases Hantaviruses belong • Specific viruses • Acute viral diseases • Worldwide, in rodents • Low • No prophylaxis
viral infections; to the Bunyaviridae carried by particular damaging vascular • May increase in • Avoid rodent
important examples family rodent hosts endothelium environment with exposure.
are haemorrhagic • Direct contact with increased vascular many rodents
fever with renal infected rodent feces, permeability and for adventure
syndrome saliva or inhalation of hypotension, travelers, back-
(HFRS) and hantavirus virus via the excreta hemorrhagic packers,campers
pulmonary syndrome manifestations, and
(HPS shock
• Oliguria with HFRS;
Respiratory failure
caused by acute
non-cardiogenic
pulmonary edema
occurs in HPS
• The outcome is fatal
in up to 15% of HFRS
cases and up to 50%
of HPS cases.
Chapter 8: Special Topics in Parasitology 429
Geographic
Disease Cause Transmission Nature of disease Risk for travelers Prevention 430
distribution
Hepatitis C Hepatitis C virus, a • Parenteral • Gradual anorexia, • Worldwide, with • Risk with unsafe • No prophylaxis
hepacivirus transmission abdominal regional differences in behavior involving the • Safe sexual practices
discomfort, nausea levels of prevalence use of contaminated • Blood and body-fluid
and vomiting, needles for injection, precautions
followed by jaundice acupuncture,
in some cases piercing or tattooing,
• Most patients will blood transfusion if
develop a chronic the blood has not
infection, which may been screened for
lead to cirrhosis and/ HCV
or liver cancer. • Travelers engaged in
humanitarian relief
activities may be
exposed to infected
blood or other body
fluids.
Hepatitis E Hepatitis E virus—not • Fecal-oral • Similar to Hepatitis A • Worldwide • Risk when exposed • No prophylaxis.
yet classified transmission but more severe in • Most cases, both to poor conditions • Avoid potentially
• Domestic animals as pregnant women in sporadic and of sanitation and contaminated food
reservoir hosts, e.g., their 3rd trimester epidemic occur in drinking-water control and drinking-water.
pigs countries with poor
standards of hygiene
and sanitation.
Histoplasmosis Histoplasma • Inhalation of • Most cases • Worldwide • Generally low • Avoid bat-inhabited
capsulatum, a spores from soil asymptomatic • Persons who visit caves.
dimorphic fungus contaminated with • May cause endemic areas • No vaccine available
bat guano or bird acute pulmonary and are exposed
droppings histoplasmosis (high to bird droppings
fever, headache, and bat guano are
non-productive at increased risk of
cough, chills, infection.
weakness, pleuritic • High-risk activities
chest pain and include spelunking,
Medical Parasitology in the Philippines
Plague Yersinia pestis • Transmitted by fleas • Three clinical forms: • Wild rodent plague • Generally low; • A vaccine effective
from rodents to (1) Bubonic plague present in Central, travelers in rural areas for high occupational
other animals and to – from the bite Eastern and Southern of plague-endemic exposure not
humans of infected fleas Africa, South America, regions may be at commercially
• No direct person-to- lymphadenitis, the Western part of risk, particularly if available in most
person transmission “buboes” North America, and in camping or hunting countries
does not occur (2) Septicemia large areas of Asia. or if contact with • Treatment:
except in the case of plague – rodents takes place tetracycline and
pneumonic plague dissemination in fluoroquinolones.
respiratory droplets the blood results • Avoid any contact
in meningitis, with live or dead
endotoxic shock rodents.
and DIC fatal
(3) Pneumonic
plague – severe
pneumonia
without prompt
and effective
treatment, 50-60%
of cases fatal
Rabies Rabies virus, a • Bite, penetrating • Acute viral • Rabies is present in • The risk to travelers in • No treatment
rhabdovirus of the scratch, licking of encephalomyelitis, mammals in many areas endemic for • Pre- and post-
genus Lyssavirus broken skin and which is fatal countries worldwide rabies is proportional exposure prophylaxis
mucosa of an • Initial signs • Most rapid deaths to the probability available
infected animal include a sense occur in Africa and of contact with • Modern cell-culture
• Person-to-person of apprehension, Asia. potentially rabid or embryonated egg
transmission other headache, fever, mammals. vaccine given at
than via organ malaise and sensory Days 0, 3, 7 and 28
transplant has not changes around the (post-exposure)
been laboratory- site of the animal bite. • Immunoglobulin for
confirmed. • Excitability, high-risk dog-bites
hallucinations, available
Medical Parasitology in the Philippines
Typhus fever Rickettsia prowazekii • Transmitted by the • Headache, chills, • Louse-borne typhus • Very low for most • No prophylaxis
human body louse, high fever, prostration, fever is the only travelers • Cleanliness important
infected by feeding coughing, and rickettsial disease that • Humanitarian relief in preventing
on the blood of severe muscular pain can cause explosive workers may be infestation by body
patients with acute followed epidemics. exposed in prisons, lice
typhus fever • After 5-6 days: dark • Occurs in colder refugee camps, • Insecticidal powders
• Infected lice excrete spots on the trunk and (i.e., mountainous) and other settings available for body-
rickettsia onto the to the rest of the body regions of Central characterized by louse control and
skin while feeding on but usually NOT on the and Eastern Africa, crowding and poor treatment of clothing
a second host, who face, palms of the Central and South hygiene. for those at high risk of
becomes infected by hands or soles of the America, and Asia, exposure
rubbing louse fecal feet Burundi, Ethiopia, and
matter or crushed lice • Case-fatality rate is Rwanda.
into the bite wound. up to 40% without
treatment.
Chapter 8: Special Topics in Parasitology 435
436 Medical Parasitology in the Philippines
incubation period. According to the CDC, in the likelihood of infection vis-a-vis an infection
terms of clinical severity, most travel-related with a bacterial etiology increases with the
illnesses are mild. Approximately 1 to 5% of duration of symptoms. Parasites may also be the
travelers become sick enough to seek medical likely etiologic agent for diarrhea unresponsive
care either during or after travel. A careful travel to antibacterials. Examples of intestinal parasites
history, therefore, should be part of the routine that may cause persistent symptoms include
medical history for every ill patient, especially Cryptosporidium parvum, Cystoisospora belli,
those with a febrile illness. Of particular concern Entamoeba histolytica, microsporidia, and
are adventure travelers and persons visiting Dientamoeba fragilis, as well as Cyclospora
friends and relatives overseas, since they are at cayetanensis. Other tests that may be requested
greater risk for becoming ill due to increased in the evaluation of patients with persistent TD
exposure to pathogens. includes stool microscopy with at least three ova
The most frequent health problems and parasite stool examinations, Clostridium
encountered by returned travelers are broken difficile toxin assay, D-xylose test, duodenal
down as follows: aspirate, or empiric treatment for Giardia.
1. Persistent gastrointestinal illness (10%) References
– diarrhea was more common for
Centers for Disease Control and Prevention.
travelers returning from South Central
CDC health information for international
Asia
travel 2010. Atlanta: U.S. Department of
2. Skin lesions or rashes (8%) – insect
Health and Human Services, Public Health
bites, pyoderma, scabies, allergic rash,
Service; 2009.
and cutaneous larva migrans; most
Philippine Department of Tourism. Industry
frequent diagnoses among travelers
performance statistics article: tourist
returning from the Caribbean, Central
volume in top destinations grew by
or South America
6.64% in the first quarter of 2010
3. Respiratory infections (5-13%),
[Internet]. 2010 [cited 2010 Nov 15].
depending on the season of travel
Available from www.tourism.gov.ph/Pages/
4. Fever (up to 3%) – associated with the
IndustryPerformance.aspx.
most serious complaints since certain
Philippine Society for Microbiology and
conditions may be life-threatening
Infectious Diseases with the Philippine
(malaria) or may pose public health
Foundation for Vaccination. Handbook
hazard (measles, tuberculosis); malaria,
on adult immunization for Filipinos
typhoid, and dengue were identified as
[Internet]. 2009 [cited 2010 Nov
the most frequent causes of systemic
1 5 ] . Ava i l a b l e f ro m h t t p : / / w w w.
febrile illness among travelers from
psmid.org.ph/contents/Handbook_
any region
on_Adult_Immunization_2009_%28con
While bacteria accounts for most TD tents%29.pdf
cases, persistent symptoms suggest protozoan World Health Organization. International travel
parasites as the etiology. In fact, in chronic and health 2010. Geneva: World Health
diarrhea, parasites are commonly isolated, and Organization; 2010.
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