2.

2 Trematodes (Flukes)
I. Blood Flukes - Schistosoma japonicum
- Schistosoma mansoni
- Schistosoma haematobium
II. Lung Fluke - Paragonimus westermanni
III. Intestinal Flukes - Fasciolopsis buski
- Echinostoma ilocanum/
Artyfechinostomum malayanum
- Heterophyid Flukes
IV. Liver Flukes - Fasciola hepatica
- Clonorchis sinensis
- Opistorchis felineus
- Opistorchis viverrini
Schistosoma mansoni
Schistosoma mansoni
▪ Schistosoma mansoni is a water-borne parasite of humans, and belongs to the group
of blood flukes (Schistosoma).
▪ The adult lives in the blood vessels (mesenteric veins) near the human intestine.
▪ It causes intestinal schistosomiasis (similar to S. japonicum, S. mekongi, S. guineensis, and S.
intercalatum).
Morphology
▪ The male S. mansoni is approximately 1 cm long (0.6–1.1 cm) and is 0.1 cm wide. It is white, and it has a funnel-
shaped oral sucker at its anterior end followed by a second pediculated ventral sucker.
▪ The external part of the worm is composed of a double bilayer, which is continuously renewed as the outer
layer, known as the membranocalyx, and is shed continuously. The tegument bears a large number of
small tubercules.
▪ The suckers have small thorns in their inner part as well as in the buttons around them.
▪ The male genital apparatus is composed of 6 to 9 testicular masses, situated dorsally.
▪ The female has a cylindrical body, longer and thinner than the male's (1.2 to 1.6 cm long by 0.016 cm wide). It
has the general appearance of a roundworm, rather than a flatworm.
▪ The female parasite is darker, and it looks gray. The darker color is due to the presence of a pigment
(hemozoin) in its digestive tube. This pigment is derived from the digestion of blood.
▪ The ovary is elongated and slightly lobulated and is located on the anterior half of the body. The male
schistosome then continuously fertilizes the female eggs in the gynecophoric canal. The genital pore opens
ventrally.
▪ The digestive tube begins at the anterior extremity of the worm, at the bottom of the oral sucker. The digestive
tube is composed of an esophagus, which divides in two branches (right and left) and that reunite in a
single cecum. The intestines end blindly, meaning that there is no anus.
Egg
▪ Eggs are oval-shaped, about 115–175 µm long and 45–47 µm wide, and ~150 µm diameter on average.
▪ Have pointed spines towards the broader base on one side, i.e. lateral spines. *
▪ When released into the water, a lot of the eggs are immature and unfertilized, they do not hatch. When larger than 160 µm
in diameter, they also fail to hatch.
▪ S. mansoni eggs are capable of damaging the wall of the distal colon (inferior mesenteric venules) by digesting the tissue
with proteolytic enzymes.
Larvae
▪ The miracidium (from the Greek word meirakion, meaning youth) is pear-shaped, gradually elongates as it ages. Measures
about 136 μm long and 55 μm wide.
▪ The body is covered by anucleate epidermal plates separated by epidermal ridges. The epidermal cells give off numerous
hair-like cilia on the body surface. There are 17–22 epidermal cells.
▪ Epidermal plate is absent only at the extreme anterior called apical papilla, or terebratorium, which contains numerous
sensory organelles.
▪ Its internal body is almost fully filled with glycogen particles and vesicles.
▪ The cercariae has a characteristic bifurcated tail, classically called furcae (Latin for fork).
▪ The body is pear-shaped and measures 0.24 mm in length and 0.1 mm in width. Its tegument is fully covered with spine.
▪ A conspicuous oral sucker is at the apex. As a non-feeding larva, there are no elaborate digestive organs, only esophagus is
distinct. There are three pairs of mucin glands connected laterally to the oral sucker at the region of the ventral sucker.
▪ The tail is highly flexible and its beating propels the cercaria in water. It is about 0.2 mm long and 47 μm wide, somewhat
loosely attached to the main body.
Physiology
▪ Developing Schistosoma mansoni worms that infect their definitive hosts, prior to the sexual pairing of males
and females, require a nutrient source in order to properly develop from cercariae to adults.
✓ Developing parasites lyse host red blood cells to gain access to nutrients; the hemoglobin and amino
acids the blood cells contain can be used by the worm to form proteins.
✓ While hemoglobin is digested intracellularly, initiated by salivary gland enzymes, iron waste products
cannot be used by the worms, and are typically discarded via regurgitation.
✓ Kasschau et al. (1995) tested the effect of temperature and pH on the ability of developing S.
mansoni to lyse red blood cells. The parasites were best able to destroy red blood cells for their
nutrients at a pH of 5.1 and a temperature of 37 °C.
▪ Schistosoma mansoni is locomotive in primarily two stages of its life cycle: as cercariae swimming freely
through a body of freshwater to locate the epidermis of their human hosts, and as developing and fully-
fledged adults, migrating throughout their primary host upon infection.
▪ Cercariae are attracted to the presence of fatty acids on the skin of their definitive host, and the parasite
responds to changes in light and temperature in their freshwater medium to navigate towards the skin.
▪ Glandular secretion that deteriorates the host epidermis, and allows the parasite to burrow into
its host is produced by the parasite.
Life cycle:
Intermediate Host: Snail of the Genus Biomphalaria (Biomphalaria glabrata, Biomphalaria straminea,
Biomphalaria tenagophila or Biomphalaria sudanica)
▪ The life cycle of Schistosoma takes about 12 to 14 weeks to complete.
Life cycle of Schistosoma spp. --
1 Eggs are eliminated with feces or urine.

2 Under optimal conditions the eggs hatch and release miracidia

3 which swim and penetrate specific snail intermediate hosts

4 The stages in the snail include 2 generations of sporocysts

5 and the production of cercariae

6 Upon release from the snail, the infective cercariae swim, penetrate the skin of the
human host
7 and shed their forked tail, becoming schistosomulae

8/9 The schistosomulae migrate through several tissues and stages to their residence in the
veins
10 Adult worms in humans reside in the mesenteric venules in various locations, which at
times seem to be specific for each species
A For instance, S. japonicum is more frequently found in the superior mesenteric veins
draining the small intestine
B and S. mansoni occurs more often in the superior mesenteric veins draining the large
intestine
C However, both species can occupy either location, and they are capable of moving
between sites, so it is not possible to state unequivocally that one species only occurs in
one location. S. haematobium however, most often occurs in the venous plexus of the
urinary bladder.
1 but it can also be found in the rectal venules. The females (size 7 to 20 mm; males
slightly smaller) deposit eggs in the small venules of the portal and perivesical systems.
The eggs are moved progressively toward the lumen of the intestine (S. mansoni and S.
japonicum) and of the bladder and ureters (S. haematobium), and are eliminated with
feces or urine, respectively
Pathology of S. mansoni and S. japonicum schistosomiasis includes: Katayama fever, hepatic
perisinusoidal egg granulomas, Symmers’ pipe stem periportal fibrosis, portal hypertension, and
occasional embolic egg granulomas in brain or spinal cord. Pathology of S. haematobium
schistosomiasis includes: hematuria, scarring, calcification, squamous cell carcinoma, and
occasional embolic egg granulomas in brain or spinal cord.
Pathogenesis
▪ Symptoms of S. mansoni infection occur as a result of the passage of the eggs through the mucosa. Affects the
gastrointestinal tract directly & the urogenital tract indirectly by causing immune complex-mediated
Glomerulonephritis.
▪ The parts of the gut damaged by schistosoma mansoni include the large bowel, the liver, colon and rectum.
Stages of Schistosoma mansoni infection (Intestinal Schistosomiasis Stages and associated Clinical features)
1 Stage 1 (stage of Invasion):
Shows the first clinical signs and symptoms of acute infection, usually the symptoms appear within 24 to 48
hours after exposure. This stage is characterized by itching at the sites of entry of the cercariae, the itch is
commonly known as Swimmers itch.
2 Stage 2 ( Toxemia stage/ Katayama syndrome)
Presents with an early allergic manifestation from egg deposition. Symptoms and signs: Katayama Syndrome or
Katayama Fever, which include fever, headache, chills, muscle pains, malaise, diarrhea & vomiting. There may
be generalized lymphadenopathy, hepatosplenomegaly, urticaria and leukocytosis with marked eosinophilia.
3 Stages 3 and 4 (Chronic stage)
occurs about 3 months to several years after infection and is due to deposition of eggs in the tissues. There may
be lethargy, recurrent bloody diarrhea and in some cases, intestinal polyps (bilharziomas) and progressive
fibrosis of the intestinal wall leading to formation of strictures; intestinal obstruction is very rare.
▪ Other manifestations include granulomatous hepatitis followed by progressive peri-portal fibrosis (also called pipe
stem fibrosis) resulting in portal hypertension with associated splenomegaly, ascites and esophageal varices that
occasionally may bleed.
Symptoms
▪ Gastrointestinal hemorrhage ▪ There is Leukocytosis with marked eosinophilia.
▪ Hepatomegaly ▪ Malaise
▪ Massive splenomegaly ▪ Profuse diarrhea
▪ Fever ▪ Nausea and vomiting
▪ Headache ▪ There may be generalized lymphadenopathy
▪ Chills ▪ Urticaria
▪ Myalgias (Muscle pains)
Complications
1. Liver cirrhosis 4. Ascites
2. Portal hypertension 5. Polyposis
3. Hepatosplenomegaly 6. Intestinal Stricture (in rare cases)
Diagnosis
▪ Microscopy - by identifying the characteristic ova in feces which can easily be identified by the
large lateral spine.
▪ Sigmoidoscopy and rectal snip helps to identify lesions and ova of the parasite.
▪ Ultrasound of liver and spleen can demonstrate peri-portal fibrosis and spleen enlargement
▪ Serological Test

Treatment
▪ The drug of choice in the treatment of Schistosoma mansoni infection is Praziquantel and it is
usually given orally as 40mg/kg single dose
▪ Oxaminoquine is also an alternative drug that is effective against Schistosoma mansoni but not
used for other types of Schistosoma species; the drug dosage is 15mg/kg orally and given once
for sensitive strains.

Prevention
1. Proper disposal of human waste to avoid washing of eggs into bodies of water.
2. Destroying snail populations, if possible.
3. Avoid Swimming in endemic areas of schistosoma mansoni infection.
END
 Schistosoma
haematobium
Schistosoma haematobium (urinary blood fluke)
▪ a digenetic trematode species, belonging to a genus of blood flukes (Schistosoma), found in Africa & the Middle East.
History
▪ Bloody urine (haematurea), recorded by Ancient Egyptians in papyri 5,000 years ago, called it Aaa.
▪ In 1910 by Marc Armand Ruffer, a British physician in Egypt, discovered parasite eggs from two mummies, dated
around 1250–1000 BC.
▪ In 1851, Theodor Maximillian Bilharz, a German physician in Cairo recovered adult fluke from a dead soldier, named
it Distomum haematobium, for its apparent two mouths (now called ventral and oral suckers) and blood vessel as
habitat.
▪ Genus Distomum (literally "two-mouthed"), created by Carl Linnaeus in 1758 for all flukes.
▪ A German physician Heinrich Meckel von Hemsbach introduced a new name Bilharzia haematobium in 1856 to
honor the discoverer. Also introduced the medical term bilharzia or bilharziasis to describe the infection.
▪ Unknown to von Hemsbach, a German zoologist David Friedrich Weinland established a new genus Schistosoma in
1858. After a century of taxonomic dispute, Schistosoma was validated in 1954, hence the name Schistosoma
haematobium.
▪ In 1915 a British physician Robert Thomson Leiper discovered the infectious nature, successfully infected mice, rats,
guinea pigs, and monkey using cercariae from four species of snails, belonging to Bullinus (now Bulinus) & Planorbis,
collected from El Marg canal near Cairo; proving that snails are the intermediate hosts.
▪ Its role in cancer was first noted in 1889 by a British Surgeon Reginald Harrison. He recorded that four out of five
cancer victims had bilharzia.
 Schistosoma haematobium (urinary blood fluke) (Cont’d.)
▪ A German physician Carl Goebel confirmed in 1903 that bladder tumor occurred in most bilharzia patients. By 1905,
he was convinced that carcinoma of the bladder was due to bilharzia.
▪ In 2009 WHO International Agency for Research on Cancer (IARC) declared that S. haematobium is a Group 1
carcinogen.
Biology
▪ Adult Schistosoma haematobium has male and female, permanently paired (a condition called in copula) as what
looks like an individual. (Slide # 18)
✓ The male forms the flatworm part, measuring 10–18 mm in length and 1 mm in width. It bears oral and
ventral suckers towards its anterior end.
✓ Its leaf-like flat body is curled up from both sides to form a channel or groove called gynaecophoric canal in
which the female is wrapped up. Thus, it gives the general appearance of a cylindrical roundworm body.
✓ The female gives the general appearance of a cylindrical roundworm body in contrast to the male. It is
cylindrical and elongated, measuring about 20 mm in length and 0.25 mm in width. Only the extreme
anterior and posterior ends of the female are exposed.
▪ Epidermal plate is absent only at the extreme anterior called apical papilla, or terebratorium, which contains
numerous sensory organelles. Its internal body is almost fully filled with glycogen particles and vesicles.
▪ The body of the cercaria is pear-shaped and measures 0.24 mm in length and 0.1 mm in width. Its tegument is fully
covered with spine. A conspicuous oral sucker is at the tip of the body.
 Adult Male & Female Schistosoma haematobium
adult pair collected at the mesenteric vein of an experimentally-infected mouse.
The female appears thin and stringy with its posterior part still in the gynecophoric canal (GC) of the male.
Female organs are easily distinguished, such as the uterus with one egg in the ootype, the vitelline glands throughout the body on each side of the
common caecum.
Each worm has an oral sucker(OS) which also serves as mouth & ventral sucker (VS) or acetabulum which serves as fixation organ.
 Biology (Cont’d.)

▪ The eggs, its pathogenic armament, are oval-shaped, about 144 × 58 µm in diameter,
with characteristic terminal spine. An important diagnostic tool because co-infection
with S. mansoni (having lateral-spined eggs) is common.
▪ The miracidium measures about 136 μm long and 55 μm wide. The body is covered by
anucleate epidermal plates separated by epidermal ridges. The epidermal cells give off
numerous hair-like cilia on the body surface. *
▪ The cercaria has a characteristic bifurcated tail, classically called furcae (Latin for fork);
hence, the name (derived from a Greek word κέρκος, kerkos, meaning tail)
Life Cycle (Slide # 21)
▪ S. haematobium completes it life cycle in humans, as definitive hosts, and freshwater snails, as intermediate hosts,
just like other schistosomes. But unlike other schistosomes that release eggs in the intestine, it releases its eggs in
the urinary tract and excreted along with the urine.
▪ In stagnant freshwater, the eggs hatch within 15 minutes into the larvae called miracidia. Each miracidium is either
male or female. Miracidia are covered with hair-like cilia with which actively swims in search for snails. Unless they
infect a snail within 24–28 hours, they run out of energy (glycogen) reserves and die.
▪ Species of snail belonging to the genus Bulinus, including B. globosus , B. forskalii , B. nasutus , B. nyassanus ,
and B. truncatus , can harbor the miracidia, which simply pierce through the soft skin of the snail and move to the
liver.
▪ Inside the snail, their cilia is cast off and extra-epithelial covering forms within 24 hours. Then they transform into
sporocysts and undergo active cell division after two weeks.
▪ The mother sporocyst produces many daughter sporocysts. Each daughter sporocyst forms new larvae called
cercariae. One mother sporocyst produces half a million cercariae.
▪ After a month, the sporocysts rupture and cercariae are liberated. Free cercariae penetrate the liver and move out
of the snail into water.
▪ Each cercaria has a biforked tail with which it swims to find a human host. Again the cercariae are short lived and can
survive in water for 4–6 days unless they find a human host.
Same life cycle as with S. japonicum
except for the following differences:
1) The snail intermediate host of S.
haematobium is Bulinus.
2) The habitat of the worm in man is
in the venous plexus of the
bladder.
 S. haematobium Life Cycle (Cont’d.)
▪ Humans in contact with infested water, the cercariae using their sucker attach themselves on the skin, pierce the skin
by secreting proteolytic enzymes that widen the skin pores (hair follicles). This process takes about 3–5 minutes and
produces itching, by then, it shall have penetrated the skin.
▪ The tails are removed on penetration, only the head parts enter the blood vessels, now known as schisotomulae.
▪ They enter the systemic system, reach the heart, then the liver, and on the way many are killed by the immune cells.
Survivors enter the liver within 24 hours.
▪ From the liver they enter the portal vein to reach other parts of the body. Unlike other species, the schistosomulae
of S. haematobium reach the vesical vessels through anastomotic channels between radicles of the inferior
mesenteric vein and pelvic veins.
▪ After living inside small venules in the submucosa and wall of the bladder, they migrate to the perivesical venous
plexus (a group of veins at the lower portion of the bladder) to attain full maturation.
▪ To evade detection by the host's immune system, the adults have the ability to coat themselves with host antigen.
▪ The female body is enveloped within the rolled-up gynaecophoric canal of the male; becoming partners for life.
▪ Attains sexual maturation after 4–6 weeks of infection. A female generally lays 500–1,000 eggs in a day.
▪ The female only leaves the male briefly for laying eggs. It has to because only it can enter the small and narrow
peripheral venule in the submucosa so the eggs can be released into the bladder.
▪ The embryonated eggs penetrate the bladder mucosa using proteolytic enzymes, aided by their terminal spines
and by the contraction of the bladder. The enzyme is a toxin specifically for damaging (necrosis) the tissue.
 S. haematobium Life Cycle (Cont’d.)
▪ In normal situation, the eggs released into
the bladder do not cause pathological
symptoms. But eggs often fail to penetrate
the bladder mucosa and remain trapped
in the bladder wall; it is these which
produce the lesions by releasing their
antigens and provoking granuloma
formation.
▪ Granulomata in turn coalesce to form
tubercles, nodules or masses that
often ulcerate. This is the condition
behind the pathological lesions found in
the bladder wall, ureter and renal; and
also tumor, both benign and malignant.
▪ The fluke continuously lays eggs
throughout their life. An average lifespan
is 3–4 years.
Pathology
▪ Normal infection of adults does not produce symptoms. But, when eggs are released, sometimes they become
permanently stuck in the bladder and cause pathological symptoms.
▪ The eggs are initially deposited in the muscularis propria which leads to ulceration of the overlaying tissue.
▪ Infections are characterized by pronounced acute inflammation, squamous metaplasia, blood and reactive epithelial
changes. Granulomas and multinucleated giant cells may be seen. *
▪ The eggs induce a granulomatous host immune response which is indicated by lymphocytes (which mainly produce
T-helper-2 cytokines such as interleukins 4, 5, and 13), eosinophils, and, also activated macrophages. This
granuloma formation induces chronic inflammation.
▪ In response to infection, the hosts' antibodies bind to the tegument of the schistosome. But are quickly removed
because the tegument itself is shed every few hours.
▪ The schistosome can also take on host proteins.
Schistosomiasis can be divided into three phases:
(1) the migratory phase lasting from penetration to maturity
(2) the acute phase which occurs when the schistosomes begin producing eggs, and
(3) the chronic phase which occurs mainly in endemic areas
▪ In late stage, the infection may lead to extra-urinary complication named Bilharzial cor
pulmonale. *
▪ The distinct symptom for urogenital schistosomiasis is blood in the urine (haematuria), which
is often associated with frequent urination, painful micturition, and discomfort in the groin.
▪ In endemic regions, haematuria is so widespread that it is thought a natural sign of puberty for
boys, and is confused with menses in girls.
▪ Under serious infection, urinary tract can be blocked leading to obstructive uropathy
(hydroureter and hydronephrosis), which can be further complicated by bacterial infection
and kidney failure. *
▪ In the most severe condition, chronic bladder ulcers and bladder carcinoma develop.
Diagnosis
▪ Traditionally, diagnoses has been made by examination of the urine for eggs.
▪ In chronic infections, or if eggs are difficult to find, an intradermal injection of schistosome
antigen to form a wheal is effective in determining infection. (Intradermal test)
▪ Alternatively diagnosis can be made by complement fixation tests. *
▪ As of 2012, commercial blood tests included ELISA and an Indirect immunofluorescence test, but
these have low sensitivity ranging from 21% to 71%. *
Treatment
▪ The drug of choice is praziquantel, a quinolone derivative. But it has low cure rate (only 82-88%).
Prevention --
▪ The main cause of schistomiasis is the dumping of human waste into water supplies. Hygienic
disposal of waste would be sufficient to eliminate the disease.
▪ Water for drinking and bathing should be boiled in endemic regions. Infested water should be
avoided.
▪ However, agricultural activities such as fishing and rice cultivation involve long contact with
water, making avoidance impractical.
▪ Systematic eradication of snails is an effective method. *

Epidemiology
▪ S. hematobium is found in Africa and the Middle East, where infants and young children are
most infected.
▪ Infection is most prevalent in both the Nile Delta and the Nile Valley South of Cairo. The first
epidemiological survey in 1937 indicated that infection rate was as high as 85% among people
in the Northern and Eastern parts of the Delta.
▪ Following construction of the Aswan Dam, basin irrigation is converted to perennial irrigation
system, and this has significantly reduced the infection.
END
 The Lung Fluke

Paragonimus westemanni
Paragonimus westemanni -
▪ Paragonimiasis is an infection of humans and other mammals by trematodes of the genus
Paragonimus.
▪ There are 40 known species of Paragonimus, and six are reported to cause infections in
humans.
▪ P. westermani or the Oriental lung fluke causes 90% of paragonimiasis in Asia. In the
Philippines, it is also the major species that causes paragonimiasis in humans; the only other
species is P. siamensis, has only been identified in cats.
▪ In 1879, Ringer observed the first case of pulmonary paragonimiasis in humans in an autopsy
in Formosa.
▪ A year later, Baelz (1880) in Japan & Manson (1880) in Formosa identified Paragonimus ova
in human sputum.
▪ Musgrave (1907) described the first case of human paragonimiasis in the Philippines.
▪ In 1915, Nakagawa discovered that crabs act as a second intermediate host. Two years later,
Nakagawa succeeded in infecting the snail Melania libertine with Paragonimus miracidia.
Parasite Biology
▪ The adult lung fluke is reddish-brown, is 7 to 12 mm in length, 4 to 6 mm in width, 3.5 to 5 mm in thickness, and
resembles a coffee bean. (Slide # 32)
▪ It is rounded anteriorly and slightly tapered posteriorly. The tegument is covered with single-spaced spines.
▪ The two testes are deeply lobed, situated opposite each other, almost midway between the ventral sucker and the
posterior border of the body.
▪ The ovary is located anterior to the testes, posterior to the ventral sucker, and has six long unbranched lobes. The
vitellaria are branched extensively.
▪ The cercaria is covered with spines, has an ellipsoidal body, and a small tail. A stylet is present at the dorsal side of
the oral sucker. (Slide # 32)
▪ The metacercaria is round and measures from 381 to 457 µm. (Slide # 33)
▪ The oval, yellowish-brown, thick-shelled egg measures 80 to 118 µm (Slide # 76)by 48 to 60 µm, and has a flattened
but prominent operculum. Opposite the operculum is a thickened abopercular portion. It is unembryonated at
oviposition. The immature egg embryonates in water, moist soil, or leached feces. (Slide # 33)
▪ A miracidium develops in 2 to 7 weeks, then pushes open the operculum and swims freely in search of its snail host.
Intermediate hosts: (Slide #34)
1) 1st intermediate host a snail, Antemelania asperata and Antemelania dactylus (the former previously known as
Brotia asperata)
2) 2nd intermediate host the mountain crab Sundathelphusa philippina, then known as Parathelphusa grapsoides.
Intermediate Hosts
Paragonimus westemanni Life Cycle (Slide # 37)
▪ Inside the snail, the miracidium passes through one sporocyst and two redial stages of development.
▪ Cercariae subsequently emerge from the snail, seek and infect the second intermediate host, the
mountain crab Sundathelphusa philippina.
▪ The cercaria penetrates the soft parts of the crustacean (crab) and encysts as a metacercaria in the
gills, body muscles, viscera or legs. The crab may also be infected by eating infected snails.
▪ The human definitive host is infected by ingesting raw or insufficiently cooked crabs harboring
metacercariae.
▪ Following ingestion of infected crustacean tissue by the host, the metacercariae of Paragonimus excyst
in the duodenum of the host.
▪ The immature worm then traverses through the intestinal wall into the peritoneal cavity, where it
wanders about for several days, then embeds itself in the abdominal wall.
▪ The parasite then returns to the coelom and migrates through the diaphragm into the pleural cavity. A
juvenile diploid worm wanders in the pleural spaces until it finds one or several diploid worms.
▪ The pair or group then migrates into the lung parenchyma, develop into adults in about 6 weeks,
where they mate and lay eggs.
 P. Westermani Life Cycle
1 The eggs are excreted unembryonated in the sputum, or alternately are
swallowed and passed with stool
2 In the external environment, the eggs become embryonated
3 miracidia hatch, seek first intermediate host, a snail, penetrate its soft tissues
4 Miracidia go through several developmental stages inside the snail:

4a Sporocysts,
4b rediae,
4c the latter giving rise to many cercariae which emerge from the snail.
The cercariae invade second intermediate host, a crustacean, e.g. a crab or
crayfish, where they encyst and become metacercariae.
5 This is the infective stage for the mammalian host
6 Human infection with P. westermani occurs by eating inadequately cooked or
pickled crab or crayfish that harbor metacercariae of the parasite
7 The metacercariae excyst in the duodenum
penetrate through the intestinal wall into the peritoneal cavity, then through the
abdominal wall and diaphragm into the lungs, where they become encapsulated and
develop into adults (7.5 to 12 mm by 4 to 6 mm).
The worms can also reach other organs and tissues, such as the brain and striated
muscles. However, when this takes place completion of the life cycles is not
achieved, because the eggs laid cannot exit these sites. From infection to oviposition
is 65 to 90 days.
Infections may persist for 20 years in humans. Animals such as pigs, dogs, and a
variety of feline species can also harbor P. westermani.
 Paragonimus westemanni Life Cycle (Cont’d.)
▪ 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 the alimentary canal to be passed out
with the feces.
▪ The completion of development in 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. *
Pathogenesis and Clinical Manifestations
▪ In the lungs, Paragonimus worms provoke a granulomatous reaction that gradually gives rise to the development of
a fibrotic cyst containing blood-tinged purulent material, adult worms, and eggs. (Slide # 39/40)
▪ The most common symptoms of paragonimiasis are chronic cough and hemoptysis. Chest pain, dyspnea, low-grade
fever, fatigue, and generalized myalgia may also occur.
▪ Clinical symptoms are less severe after 5 to 6 years.
▪ Occasionally, the disease can have serious sequelae, such as chronic bronchiectasis and pleural fibrosis, secondary
to severe parenchymal and pleural damage.
▪ The circuitous route of migration allows the worms to lodge and mature in different ectopic locations. These
aberrant worms may localize in the lung, pleura, pericardium, myocardium, abdominal wall, omentum, liver,
mesenteric lymph nodes, adrenals, urogenital organs, and eyes. (Localization in lungs - Slide # 39/40)
▪ Heavy intensity infections can cause both pulmonary and ectopic paragonimiasis. Worms that fail to find a mate in
low intensity infections may end up in ectopic locations as well. Cutaneous and cerebral paragonimiasis are the
classic known forms of ectopic infection.
▪ In cases of cutaneous paragonimiasis, a slow-moving, nodular lesion in the subcutaneous tissue on the abdomen
or chest is the characteristic symptom.
 Cross section of lung from patient
Encapsulated cyst in lungs infected with P. westermani
Paragonimus westermanni in lungs
 Pathogenesis and Clinical Manifestations (Cont’d.)
▪ Cerebral involvement is the most serious complication of human paragonimiasis. A juvenile P. westermani may
migrate from the pleural cavity into the cranial cavity through the soft tissues along the internal jugular vein.
(Slide # 42, 43)
▪ The migration worm can cause congestion, vasculitis, and capillary rupture, which may result in exudative
aseptic inflammation, infarction, hemorrhage, and necrosis in the subcortical areas.
▪ After invasion, multiple, conglomerated, and interconnected granulomas form around the parasite, containing
abscess material and eggs.
▪ In the chronic stage, liquefaction necrosis and fibrinous gliosis occur, and these may lead to cortical or subcortical
atrophy, and secondary ventricular dilatation.
▪ Cerebral paragonimiasis may present with headache, meningismus, seizures, hemiparesis, blurring of vision,
diplopia, homonymous hemianopsia, and aphasia.
Cerebral human paragonimiasis
The cerebral form is one of the
typical examples of extrapulmonary
forms due to erratic migrations.
In this form, the worms enter the
cranial cavity through the jugular or
carotid foramen and commonly
invade the temporal and occipital
lobes

CT scan of the brain showing an isodense area surrounded by edema

(arrow) in the left parietal lobe
Brain images of the patient at initial presentation (June 2011).
A A pre-contrast CT scan reveals an acute intracerebral hemorrhage with surrounding edema in the left frontal lobe.

B Left frontal lesion shows hypointensity with surrounding hyperintensity on a T2-weighted MR image.

C On a T1-weighted MR image, the lesion shows hypointensity with curvilinear hyperintensity. These findings suggest
an acute to early subacute hematoma.
D A contrast-enhanced T1-weighted MR image demonstrates a faint, encircling ring enhancement (arrows).
Diagnosis
1) Microscopy - the most basic and most readily available diagnostic tool for paragonimiasis.
o Definitive diagnosis is based on the detection of the characteristic eggs in sputum, stool, or,
less frequently, in aspirated material from abscesses or pleural effusions.
o However, the sensitivity of microscopy is suboptimal, with ova detection in sputum ranging
from 37 to 88%.
o If initial findings are negative, repeat examinations may be helpful.
2) Sputum concentration - with 3% sodium hydroxide, with repeated sputum examinations up to 3X
on different days, provides the best sensitivity for microscopic diagnosis.
3) Chest radiographs may aid in the diagnosis of pulmonary paragonimiasis when combined with a
high index of suspicion.
o usually presents as lung parenchyma lesions which may be infiltrative, nodular, cavitating, or a
combination of these.
o Pleural effusions occur in almost half of patients.
o These radiographic findings are not specific, and may also be seen in other diseases, particularly
pulmonary tuberculosis (PTB), lung cancer, and fungal infections. *
 Diagnosis (Cont’d.)
4) Peripheral blood count for paragonimiasis frequently reveals eosinophilia and elevated levels of
IgE, which is typical for parasitic infections. The total white blood cell count may be in the normal
to elevated range. Eosinophilia is more common in the acute stage of paragonimiasis, whereas IgE
levels have no correlation with the stage of the disease.
5) Immunological methods - Classic methods include:
o Complement fixation (CF) test - has high sensitivity for both diagnosis and assessment of cure
after therapy.
o Intradermal test - simple, rapid, cheap and highly sensitive, although it may still yield positive
results several years after successful treatment.
o Double diffusion in agarose gel, and
o Immunoelectrophoresis
 Diagnosis (Cont’d.)
In lieu of classic serodiagnosis methods for paragonimiasis, more sensitive and specific tests, like:
1 Immunoblotting (IB) - has a sensitivity of up to 99%, and has been used since 1988.
2 Enzyme-linked immunosorbent assay (ELISA)
o has a sensitivity ranging from 96% to 99%, been employed widely in parasitic and non-parasitic infections.
o most ELISA systems are to detect Paragonimus-specific IgG antibody. Attempts are also made to detect
specific IgE, IgM, and circulating antigens. The multiple-dot ELISA was developed for field use in developing
countries.
3 Loop - mediated isothermal amplification (LAMP)
o test is simple, rapid, & cost-effective, developed for field use in epidemiologic surveys in developing countries.
o allows rapid amplification of deoxyribonucleic acid (DNA) with high specificity under isothermal conditions,
using DNA polymerase with strand-displacement activity.
o Magnesium pyrophosphate, the reaction by-product, is visible to the naked eye. Only warm water is required
to perform the assay.
4 Cranial Computer Tomography (CT) scan or Magnetic Resonance Imaging (MRI)
o In cerebral paragonimiasis, the most characteristic finding are conglomerated, multiple, ring-enhancing lesions
(“grape-cluster” appearance) with surrounding edema, typically in one cerebral hemisphere, most commonly
in the posterior part of the brain.
5 Skull radiographs - patients with chronic disease may present with specific soap-bubble calcifications.
Treatment
▪ Praziquantel: drug of choice, highly effective in treating trematode infections, particularly lung fluke infections.
o Induces rapid contraction of trematodes and alters the tegmental surface (e.g., vacuolization).
o Is suitable for treatment of adults and children over 4 years of age. Usual dose is 25 mg/kg, 3X a day, for 2 to 3
days. A higher dose may be required in cases of ectopic paragonimiasis.
o Praziquantel is currently not recommended for paragonimiasis during pregnancy and lactation, although is yet
to prove the drug to have mutagenic, teratogenic, or embryotoxic effects. Treatment preferably be given after
delivery unless immediate intervention is deemed essential.
o Breastfeeding be avoided during and 72 hours after treatment.
o Adverse effects of praziquantel are generally mild: abdominal discomfort, nausea, headache, dizziness, and
rarely, fever, urticaria, drowsiness, and tachycardia.
▪ Triclabendazole is a benzimidazole originally used to treat Fasciola hepatica infections. Recently, triclabendazole has
been demonstrated to be an effective drug against human paragonimiasis.
o binds to B-tubulins of trematodes, leading to depolymerization and disruption of microtubule-based processes.
These result in damage to the external plasma membrane and nuclear membrane, with dissolution of some
heterochromatin, mitochondria, and Golgi complex.
o The cure rate with triclabendazole is comparable with that of praziquantel, and may result in better patient
compliance since the treatment regimen consists only of a single dose.
▪ Bithionol can be used as an alternative drug. It is given orally at a dose of 15 to 25 mg/kg, twice daily on alternate
days, for 10 to 15 days.
Epidemiology
▪ Paragonimiasis - in limited parts of Asia, Latin America (Peru and Ecuador), and Africa (Nigeria and Cameroon).
▪ In recent estimates, 20.7 million people worldwide are infected, and 292.8 million are at risk.
▪ In the Philippines, paragonimiasis is endemic in Mindoro, Camarines, Sorsogon, Leyte, Samar, Zamboanga del
Norte, Davao Oriental, Basilan, and Cotabato. Prevalence rates vary among the endemic provinces.
▪ Infection rates in Sorsogon ranged from 16 to 25% in 1997. In more recent epidemiologic studies done in the
municipality of Pres. Manuel Roxas in Zamboanga del Norte, the prevalence was 14.8% in 2005. *
▪ Paragonimiasis has a focal distribution, largely determined by local patterns of consumption of inadequately
cooked crustaceans and paratenic hosts --
o Examples of dishes that can transmit disease include:
• kinagang (crab in coconut milk), sinugba (grilled crab), and kinilaw (raw crabs in vinegar) in the
Philippines;
• nam prik poo (crab and chilli paste) in Thailand;
• crabs in brine, soy sauce or alcohol (drunken crabs) in China;
• kejang (raw crabs in soy sauce) in Korea, ceviche (raw crabs in lemon sauce) in Peru; and
• sashimi of wild boar and bear meat in Japan.
o Unhygienic food preparation also contributes to the transmission of the disease.
▪ Cultural beliefs and traditions influence the age and sex distribution of paragonimiasis--
Example:
o In Japan, during the 1950s and 1960s, the majority of those infected were children because of
the practice of using raw crayfish juice as a treatment for various cutaneous ailments.
Currently, middle-age Japanese men have the highest prevalence due to their conservative
affinity for traditional dishes.
o Similar practices also existed in Korea during the same period.
o In adolescent girls in Cameroon, a popular belief existed once among the Bakossi people that
crabs aid in fertility, leading to disproportionately high infection rates in this group.
▪ PTB overlaps with paragonimiasis in paragonimiasis endemic areas in the Philippines and other
developing countries. *
▪ Further studies are needed to elucidate the impact of misdiagnosis of pulmonary paragonimiasis and
PTB.
Prevention and Control
▪ The most practical way to prevent infection of human paragonimiasis is to avoid ingestion of raw
or insufficiently cooked crabs and other crustaceans, as well as meat from paratenic hosts like
wild pigs. *
▪ Safe food preparation helps reduce the transmission of the parasite.
▪ Changing the risky dietary habits of the population, through health education and promotion, can
control this parasitic infection.
▪ Capacity building of local health staff on the diagnosis and treatment of this disease is important
for early case detection and treatment.
❖ Elimination of reservoir and intermediate hosts of Paragonimus may not be feasible.
Thank you!!!