Plasmodium and Babesia

Sporozoa - class of parasites that have no obvious structures II. Once inside the human body, the
for the purpose of motility Mature schizont sporozoites are carried through the
Phylum - Apicomplexa Merozoites - fully developed stage of the asexual sporozoa peripheral blood to the parenchymal cells
Class - Aconoidasida trophozoites (liver)
Order - Haemosporida - The number and arrangement of these merozoites III. It is here that schizogony (asexual
Blood species/ Most clinically relevant organisms: vary and are described in detail under each malarial multiplication) occurs
● Plasmodium vivax species - Infective stage – sporozoites
● Plasmodium ovale - Chromatin bodies w/c are the nucleus of the
● Plasmodium malariae plasmodium Erythrocytic cycle (asexual) - happens in the circulation
● Plasmodium falciparum - 8 to 36 (ave. 25) arranged in clusters I. Infected liver cells rapture and introduce merozoites
● Plasmodium knowlesi !! Except for Plasmodium vivax, cytoplasmic material is not into the circulating blood
6 Morphologic Forms: visible and is presumed to be absent. II. Migrating merozoites targets age- and size- specific
● Ring form (early trophozoites) RBCs to invade and initiate the phase of reproduction
● Developing trophozoite Microgametocyte - large diffuse chromatin mass that stains pink involving RBCs
● Immature schizont to purple and is surrounded by a colorless to pale hale !! In this asexual phase that the plasmodia feed on hemoglobin
● Mature schizont - Pigment is usually visible; its distribution and color and pass through the numerous stages of growth (6)
● Microgametocyte vary by species Merozoites - chromatin bodies responsible for production
● Macrogametocyte - Typical microgametocyte is roundish in shape asexually
!! Except for P. falciparum, w/c is crescent shaped
Ring form - ringlike appearance of malarial parasite following Sporogonic cycle (sexual) - inside the mosquito occurs in the
invasion into a previously healthy RBC Macrogametocyte - range in shape from round to oval stomach of the mosquito and form sporozoites
- Usu. seen in infected RBC - The compact chromatin mass is partially to I. Transmission of the parasite bach into the vector
● Giemsa stain - consist of a blue cytoplasmic circle completely surrounded by cytoplasmic material occurs when the mosquito ingested mature male
connected with or to (depending on the species) a red - Pigment is also present, and its color and distribution (micro) and female (amcro) sex cells called
chromatin dot (nucleus) in this morphologic form vary by indiv. Plasmodium gametocytes during a blood meal, thus initiating the
● Vacuole - space inside the ring species sexual cycle of growth.
!! Except for P. falciparum, w/c is crescent shaped II. Male and female gametocytes unite in the mosquito’s
Developing trophozoite - remnants of the cytoplasmic circle and Micro - male stomach and form a fertilized cell called a zygote
chromatin dot, which are in some cases both still intact until late Macro - female (ookinete)
in development Gametocyte - sex cells III. The zygote becomes encysted and matures into an
- Hemozoin (brown pigment) is often visible; it is the oocyst
remnants of parasites that fed in RBC hemoglobin Plasmodium Life Cycle IV. On complete maturation, the oocyst ruptures and
● Exoerythrocytic cycle (asexual) releases numerous sporozoites, which migrate into
Immature schizont - active chromatin replication ● Erythrocytic cycle (asexual) the salivary gland of the mosquito and are ready to
- Visible cytoplasmic material surrounds the growing ● Sporogonic cycle (sexual) infect another unsuspecting human. Thus, the cycle
chromatin repeats itself.
- Pigment granules, often brown in color, are also Exoerythrocytic cycle - reproduction outside the RBCs (human Vector - anopheles mosquito
commonly seen liver cells) Sporozoites infective stage from the vector to the human
Chromatin body - nucleus - Growth and reproduction lasts from 8 to 25 days **life cycle would differ based on vactor and the species
Nucleus - contain the genetic components (DNA and RNA) I. The vector (anopheles) transfer the
- Responsible for the replication infective stage (sporozoites) via blood meal Hypnozoïtes - dormant Plasmodium- infected liver cells ;
Merozoite - chromatin bodies erythrocytic
 - May form during infection with P. vivax or P. ovale
- Also known as sleeping forms may be dormant for
months to years after the initial infection
- Once stimulated, it rupture and introduce merozoites
into the circulating blood, thus initiating the
erythrocytic cycle and a relapse infection, or
recrudescence
Dormant - temporarily inactive
Recrudescence - recurring of plasmodium infection
Other Mode of Transmission:
● Transfusion malaria - occurs when uninfected patients
receive blood tainted with malaria collected from an
infected donor
● Mainline malaria - spread through the sharing of
needles and syringes, common practice among IV
drug users
● Congenital malaria - the passing of the parasite from
mother to child
Malaria testing - part of the screening during blood donation
Laboratory Diagnosis
● The timing of blood collection for the study of malaria
is crucial to success in retrieving the malarial
parasites
● The greatest number of parasites is present in the
blood in between characteristic bouts of fever and
chills (rigor) resulting from the release of merozoites
and toxic waste products from infected RBCs, known
as paroxysms
- This is the optimal time to collect peripheral
blood samples to determine the presence
of Plasmodium spp. parasites
Paroxysms - last for about a number of hours
P. vivax - every 48 hours (timing of cyclic paroxysms)
P. ovale - every 48 hours
P. malariae - every 72 hours
P. falciparum - every 36 to 48 hours
● Giemsa stained peripheral blood films - specimen of
choice
● Wright’s stain - may also be used and will result in an
accurate diagnosis
○ Both thick and thin blood films should be
made and examined
○ Thick blood smears serves as screening
slides, whereas thin blood smears are used
in differentiating the Plasmodium species
*** thick blood smear is for screening of Plasmodium whereas
thin blood smear is for the differentiation of morphologic forms
○ All blood films should be studied under oil
immersion
!! It is important to note that mixed Plasmodium infections may
occur, with the most frequently encountered being P. vivax and
P. falciparum.
● Serologic test and polymerase chain reaction (PCR)
techniques for malaria are available
**It is recommended that blood should be collected every 6 to
12 hours for up to 48 hours before considering a patient to be
free of Plasmodium spp, parasites
!! It is important to note that multiple sets of blood films, which,
as noted, consist of thick and thin smears, are necessary to rule
out malarial infections.
Pathogenesis and Clinical Symptoms:
● The typical patient remains asymptomatic following
the initial mosquito bite and exoerythrocytic cycle of
malarial infection
● Once the erythrocytic phase is initiated and large
numbers of rupturing RBCs simultaneously occur, the
resulting merozoites and toxic waste byproducts in
the blood symptom produce the first clinical symptom
● Patients may experience clinical symptoms as a
result of having a recrudescence (recurrence)
** patient symptoms in erythrocytic phase - fever and chills
accompany paroxysms
** hypnozoites - responsible for the recurrence of P. vivax
● There is an allergic response of the body to the
development of schizonts and to the circulating
parasitic antigens following the release of merozoites,
a paroxysm is characterized by chills (rigor), typically
lasting for 10 to 15 minutes or longer, followed by 2 to
6 hours or more of a fever. As the fever subsides and
returns to normal, the patient experiences profuse
sweating and extreme fatigue.
● Additional malarial symptoms may include:
headache,lethargy, anorexia, ischemia (insufficient
blood supply in other body tissues caused by
blockage of the capillaries and blood sinuses),
nausea, vomiting and diarrhea.
** plasmodium - systemic infection
● Anemia, central nervous system (CNS) involvement
and nephrotic syndrome may occur in all Plasmodium
infections.
● Malaria may mimic a number of other diseases,
including meningitis, pneumonia, gastroenteritis,
encephalitis or hepatitis.
Persons exhibiting erythrocyte structural abnormalities tend to
have a greater resistance to malarial infections than those who
do not possess the abnormalities:
● Heterozygous glucose-6-phosphate dehydrogenase
(G6PD) deficiency
● Hemoglobinopathies (S,C,E, and thalassemia)
● Duffy blood group-negative also tend to show a
greater resistance than those who are positive for the
antigens on their red blood cells.
 Species Associated Disease Morphologic Forms

Ring Form Developing Immature schizont Mature schizont Microgametocyte Macrogametocyte

Plasmodium vivax Benign tertian Trophozoite
malaria, vivax malaria
● Delicate ● Irregular ameboid ● Multiple chromatin ● 12 to 24 merozoites ● Large to pink ● Round to oval
cytoplasmic ring appearance bodies occy most of purple chromatin cytoplasm
measuring ⅓ of ● Ring remnants ● Often contains infected RBC mass surrounded ● Eccentric chromatin
RBC diameter common clumps of brown ● MErozoites by colorless to pale mass
● Single chromatin ● Brown pigment pigment surrounded by halo ● Delicate light-brown
dot becomes apparent, cytoplasmic ● Brown pigment is pigment - may be
● Ring surrounds a increases in material common visible throughout a
vacuole number and ● Brown pigment cell
● Accole forms visibility as may be present ** light brown pigment
possible parasites mature **mature schizont is - due to consumption
**cytoplasmic ring specific to P. vivax of hemoglobin
measuring ⅓ of the ** Schuffner;s dot -
RBC diameter fine, round, uniform
dots or eosinophilic
stippling
** The more they
consume hemoglobin,
the more the brown
pigment is seen

Plasmodium ovale Benign tertian ● Resemble that of P. ● Ring appearance ● Progressive ● Parasites occupy Similar to P. vivax, only smaller in size
malaria, ovale malaria vivax usu. maintained dividing chromatin 75% of RBCs
● Ring longer in size until late in surrounded by ● Rosette
than P. vivax development cytoplasmic arrangement of
● Ring thich and ● Ameboid material - often merozoites (ave. of
often somewhat tendencies not as maintains circular 8 merozoites)
ameboid in evident as in P. shape early in
appearance vivax development
** irregular ring ** chromatin body -
appearance active production of
cytoplasmic material

Plasmodium malariae Quartan malaria, ● Smaller than P. ● Nonameboid solid ● Similar to that of P. ● Typically contains 6 SImilar to P. vivax, only smaller in size; pigment
malarial malaria vivax cytoplasm that may vivax, only smaller; to 12 merozoites usually darker and coarser. Older forms
● Occupies one sixth assume roundish, may contain large arranged in assume an oval shape
of the RBC oval, band, or bar and dark peripheral rosettes or irregular
● Heavy chromatin shape. or central clusters !! The cytoplasms of heavily stained P. malariae
dot ● Cytoplasm ● Central may contain Ziemann’s dots.
● Vacuole may contains coarse arrangement of
appear filled in dark brown brown-green
● Pigment pigment; may mask pigment may be
 characteristically chromatin material visible
forms early. ● Vacuoles absent in ● Infected RBC may
mature stages not be seen
because
developing
parasites often fill
the cell completely

Plasmodium Black water fever, ● Circle configuration ● Heavy rings ● Multiple chromatin ● Typically contains ● Sausage-or ● Sausage-or
falciparum malignant tertian ( 1 chromatin dot) common bodies surrounded 8-36 merozoites crescent- shaped crescent- shaped
malaria, aestivo or headphone ● Fine pigment by cytoplasm (average 24) in ● Dispersed central ● Compact chromatin
autumnal malaria, configuration (2 granules ● Only detected in cluster chromatin with ● black pigment
subtertian malaria, chromatin dots) ● Mature forms only severe infections arrangement nearby black surrounding
falciparum malaria ● Scanty cytoplasm seen in severe ● Only detected in pigment usually chromatin may be
● Small vacuole infection severe infections visible visible
**tertian - paroxysm usually visible !! The cytoplasm of
occur every 2 days ● Multiple rings RBC infected with P.
malignant - bec of the common falciparum may
symptoms ● Accole forms contain Maurer’s dot.
benign - not severe possible

Plasmodium knowlesi Infection proved to be Depending on the morphologic forms present, P. knowlesis may resembles P. falciparum
- Parasite of the old fatal
world monkeys

Babesia ● Two most commonly encountered forms in human specimens will be: trophozoites and merozoites
● Other morphologic forms are responsible for invading RBCS but are generally never seen at the point of laboratory diagnosis
Trophozoites:
● Appearance - resembles a ring form; does not contain Schuffner’s, Ziemann’s or Maurer’s dots
● Ring characteristics when stained with Giemsa - blue cytoplasmic circle connected with or to red chromatin dot; vacuole usu. present
Merozoite
● Appearance - resembles 4 trophozoite attached by their respective chromatin dot in the shape of a Maltese cross
● Undergo binary fission in the human host to produce more sporozoites

Species Lab Diagnosis Life Cycle and Epidemiology Clinical Symptoms Treatment Prevention and Control

Plasmodium vivax
● All morphological stages of
P. ovale may be seen in
blood film preparations.
● Thick and thin blood smears
are generally examined.
● The mature schizont may
ultimately be the
morphologic form of choice
for examination
Life Cycle: There are numerous ● Personal protection such
● Relative age of infected antimalarial drugs on the as netting, screening,
RBCs - only young and market including: protective clothing and
immature cells Quinine, Quinidine, repellents for persons
● Appearance of infected Chloroquine, Amodiaquine, entering known endemic
RBCs - enlarged, distorted Primaquine, Pyrimethamine, areas.
Epidemiology: Sulfadoxine, Dapsone, ● Prophylactic treatment
● P. vivax is most widely Mefloquine, Tetracycline, may be used based on the
distributed malarial Doxycycline, Halofantrin, geographic location and
organism Atovaquone, Proguanil, length of exposure.

Plasmodium ovale ● All developmental stages of
P. ovale may be seen in
blood film preparations.
● Thick and thin blood smears
are generally examined.
● The mature schizont may
ultimately be the
morphologic form of choice
for examination.
Plasmodium malariae ● The most frequently
encountered growth stages
of P. malariae seen are the
developing trophozoite and
the immature and mature
schizonts.
● Thick and thin
Giemsa-stained peripheral
blood films will reveal these
morphologic forms in
patients infected with P.
malariae.
● Infections occur worldwide
in both the tropics and
subtropics
Life Cycle
● Relative age of infected
RBCs - only young and
immature cells
● Appearance of infected
RBCS - Oval and enlarged,
distorted with ragged cell
walls.
Epidemiology
● P. ovale is primarily found in
tropical Africa, where it
apparently has surpassed P.
vivax in frequency of
occurrence, as well as in
Asia and South Africa
Life Cycle:
● Relative age of infected
RBCs - only mature cells
● Appearance of infected
RBCS - normal size, no
distortion
Epidemiology
● P. malariae is found in
subtropic and temperate
regions of the world.
● These infections appear to
occur less frequently than
those with both P. vivax and
Benign Tertian Malaria and
Ovale Malaria
● The clinical scenario of P.
ovale, including initial
infection symptoms, time
of typical paroxysm cycle
(every 48 hours), and
relapses caused by the
reactivation of
hypnozoites, resembles
that of P. vivax
● A notable difference
between the two species is
that untreated patients with
P. ovale typically
experience infections that
last approx. 1 year,
whereas similar patient
with P. vivax may remain
infected for several years
Quartan or Malarial Malaria
● Infections caused by the
presence of P. malariae
typically experience an
incubation period of 18 to
40 days followed by an
onset of flu like symptoms
● Cyclic paroxysms occur
every 72 hours (quartan
malaria)
● There are no known
relapses because dormant
hypnozoites are not
Qinghaosu, Artemisinin,
Artemether, Artesunate,
Pyronaridine, Fenozan B07,
Trioxanes, Nonane
endoperoxides, Azithromycin,
WRZ3
!! It is important to know that
these available malarial
medications affect the parasite
in diff. ways, depending on the
specific morphologic life cycle
stages present at the time of
administration.
Same as P. vivax
Same as P. vivax
● Mosquito control or total
eradication of breeding
sites.
● Avoidance of sharing
intravenous needles, as
well as thorough
eliminating the risk of non-
mosquito Plasmodium spp.
Transmission.
● adequate personal
protection
● prophylactic therapy
when indicated
● prompt treatment of
infected persons
● mosquito control
● screening donor blood
● avoidance of sharing
intravenous drug needles
● Prophylactic therapy, when
appropriate, proper clothing,
netting, and screening, as
well as the use of insect
repellents, offer protection
to humans entering known
endemic areas.
● The control of mosquito
breeding areas and
thorough screening of donor
blood units and the
avoidance of sharing
intravenous drug needles

Plasmodium falciparum Peripheral blood smears:
● Mild to Moderate infection -
reveal only the ring forms
and gametocyte forms.
● Severe infection- reveal
only the trophozoites and
schizonts.
Hypnozoites are NOT
produced in the liver of the
patients with P. falciparum
infections and relapses are
NOT known to occur.
Recrudescence may occur,
and these attacks may
ultimately prove fatal. (May
occur but not in the liver, and
when it happens it is the most
fatal type)
Plasmodium falciparum P.knowlesi morphologically
resembles P.malariae to the
extent that there is
documented evidence that
misdiagnosis by microscopic
methods has occurred.
Babesia
Phylum - Apicomplexa
Class - Aconoidasida
Order - Piroplasmida
P. falciparum
** P. falciparum is more
common than P. malariae
Life Cycle
● Relative age of infected
RBCs - May infect cells of
all ages
● Appearance of infected
RBCS - normal size, no
distortion
● P. falciparum invades red
blood cells of any age and
may infect up to 50 % of the
red blood cell population at
any one time throughout the
course of the infection.
● Schizogony generally
occurs in the capillaries and
blood sinuses of internal
organs during infection with
this parasite.
Epidemiology
● Limited to the tropical and
subtropical regions of the
world
Epidemiology
P.knowlesi has recently been
identified in humans suffering
from malaria in Malaysia and
other parts of Southeast Asia.
Blood species/ Most Clinically Relevant Organisms::
● Babesia microti
● Babesia divergens
History
associated with P.
malariae infections
**chills then fever from 2 to 6
hour or more, and after
paroxysm is fatigue and
sweating
Black Water Fever and Same for P. vivax Because of the potential
Malignant Tertian Malaria severity of infections with P.
● Short incubation period of 7 falciparum, prompt
to 10 days, patients infected treatment of known infected
with P. falciparum exhibit individuals is crucial to halt
early flulike symptoms the spread of the disease
● Daily episodes of chills and
fever, as well as severe
diarrhea, nausea, and
vomiting, rapidly develop
followed by cyclic
paroxysms, w/c occur every
36 to 48 hrs.
● P. falciparum typically
produces the most deadly
form of malaria in untreated
patients
● P. falciparum may enter the
kidney, brain, and/or liver.
Kidney involvement known
as black water fever, usus.
results in marked
hemoglobinuria (the
presence of hemoglobin in
the urine) caused by P.
falciparum-induced red cell
destruction
● Babesial organisms were first described in the 1880s
as being responsible for Texas cattle fever or red
water fever.
 ● Several species have demonstrated an ability to
cause illness in humans, who are usually considered
as an accidental host.
● The two babesial organisms most commonly isolated
from clinical specimens are B. microti (Theileria
microti) and B. divergens; other species have
demonstrated an ability to cause disease but are a
rare occurrence.
Life Cycle:
Babesiosis has a sexual and asexual phase in its life cycle:
● Sexual phase vector (tick)
● Asexual phase - host ( eg. mice, deer, cattle, dogs,
humans)
I. The uninfected host must be in contact with the
tick's saliva for 12 hours or longer before this
parasite can be transmitted.
II. The infected tick transmits sporozoites into the
uninfected host.
III. The sporozoites invade the red blood cells and
develop into trophozoites.
IV. Multiple sporozoites can infect an RBC, so multiple
trophozoites can be seen within the infected RBC.
V. The trophozoites continue to develop into
merozoites.
VI. The merozoites mature and develop into
gametocytes inside their normal animal host but
are not generally seen in the accidental human
host.
VII. In the human host, the merozoites undergo binary
fission to produce more sporozoites; when the
number of sporozoites exceeds the red blood cell's
capacity, it ruptures, releasing sporozoites to infect
more red blood cells.
VIII. An ixodid tick bites an infected host and the
gametocytes travel to the gut, where they unite to
form an ookinete.
IX. The ookinete travels to the salivary glands where
sporogony-the process of spore and sporozoite
production via sexual reproduction - takes place,
resulting in numerous sporozoites that can be
transmitted to a new host.
Epidemiology
● B. microti is commonly found in areas of southern
New England, such as Nantucket, Martha's
Vineyard, Shelter Island, Long Island, and
Connecticut.
● B. divergens is commonly found in European
countries, particularly those in the former
yugoslavia, Russia, Ireland, and
● Babesiosis has also been demonstrated to be a
transfusion-transmissible disease and has the
potential to be transmitted congenitally and by the
sharing of intravenous drug needle
Babesia microti
● Vector - deer tick (ixodes dammini)
● Principal reservoir host - white-footed mouse
(Peromyscus leucopus)
Babesia divergens
● Vector - tick (ixodes ricinus)
● Principal reservoir hosts - cattle and rabbits
Laboratory Diagnosis
● Giemsa-stained peripheral blood films are the
specimens of choice for the laboratory diagnosis of
babesiosis.
● Wright's stain may also be used and will result in
an accurate diagnosis.
● Thick and thin blood films should be made and
examined. All blood films should be studied under
oil immersion.
● The timing of blood collection for the study of
Babesia is NOT crucial to success in retrieving the
Babesia parasites; they have not shown periodicity
● Serologic tests and PCR techniques for babesiosis
are available
Pathogenesis and Clinical Symptoms
● The typical patient presenting with babesiosis was
exposed 1 to 4 weeks prior to the onset of
symptoms.
● Babesiosis is generally a self-limiting infection.
● Its onset is usually gradual and characterized by
prodrome like symptoms - fever, headache, chills,
sweating, arthralgias, myalgias, fatigue and
weakness.
● The fever shows no periodicity.
● Hepatosplenomegaly and mild to severe hemolytic
anemia have been recorded.
● Possible confection with Lyme disease and/ or
human granulocytic ehrlichiosis.
● B. divergens tends to be the more severe and is
frequently fatal if left untreated.
● B. microti tends to be rather benign and
selflImiting.
● Disease with either of these organisms is often
more severe with: older adult , immunosuppressed
and splenectomized patients
Treatment
● The treatment of babesiosis often involves a
combination of drugs.
● The most common combination are:
○ Clindamycin and Quinine
○ Atovaquone and Azithromy
Prevention and Control
● Avoid tick infested areas
● Examining the body for ticks immediately after
leaving such an area and rapid removal of the tick
are crucial.
- The tick must feed for at least 12 hours before
it is able to transmit the parasite.
● Using insect repellents