INFECTIOUS DISEASE

 

PARASITOLOGY - CHAPTER SIX  

TREMATODES (FLUKES)  

Dr Abdul Ghaffar
Professor Emeritus
University of South Carolina School of Medicine

SHQIP - ALBANIAN

All life cycle diagrams in this section are courtesy of the DPDx Parasite Image Library 
Centers for Disease Control (CDC)

TEACHING OBJECTIVES
Epidemiology, morbidity and mortality
Morphology of the organism
Life cycle, hosts and vectors
Disease, symptoms, pathogenesis and site
Diagnosis
Treatment, prevention and control

Schistosomiasis (Bilharziasis)

The three species of Schistosoma have different geographic distributions. S. hematobium is prevalent in Africa, S. mansoni is found in Africa and America and S. japonicum is common in the far east.

Epidemiology
Approximately 250 million people are infected with schistosomes and 600 million are at risk.

Morphology
Adult worms are 10 to 20 mm long; the male has an unusual lamelliform shape with marginal folds forming a canal in which the slender female worm resides. Unlike other trematodes, schistosomes have separate sexes (figure 1).

Life cycle
Man is infected by cercaria in fresh water by skin penetration. The cercaria travel through the venous circulation to the heart, lungs and portal circulation. In about 3 weeks, they mature and reach the mesenteric (S. japonicum and S. mansoni) or the bladder (S. hematobium) vessels where they live and ovulate for the duration of the host's life. Eggs germinate as they pass through the vessel wall into  the intestine or bladder and are excreted in feces (S. japonicum and S. mansoni) or urine (S. hematobium). In fresh water, the larval miracidium hatches out of the egg and swims about until it finds an appropriate snail. After two generations of multiplication in the snail, the fork-tailed cercariae emerge into the water and infect another human (figure 2).

Symptoms
Penetration of cercariae causes transient dermatitis (swimmers' itch). The symptoms of schistosomiasis are primarily due to a reaction against the eggs and include splenomegaly, lymphadenopathy and diarrhea. In the bladder, they produce granulomatous lesions, hematuria and sometimes urethral occlusion. Most bladder cancers in endemic areas are associated with chronic infection. In the intestine, they cause polyp formation which, in severe cases, may result in life threatening dysentery. In the liver, the eggs cause periportal fibrosis and portal hypertension resulting in hepatomegaly, splenomegaly and ascites. A gross enlargement of the esophageal and gastric veins may result in their rupture. S. japonicum eggs are sometimes carried to the central nervous system and cause headache, disorientation, amnesia and coma. Eggs carried to the heart produce arteriolitis and fibrosis resulting in enlargement and failure of the right ventricle (figure 2a).

Pathology and Immunology
The 'swimmers' itch is due to physical damage to the skin by proteases and other toxic substances secreted by the cercaria. The host develops both type I and type IV hypersensitivity reactions to schistomal secretions and egg constituents. Embryonated eggs cause collagenase-mediated damage to the vascular endothelium. Host immune responses, both humoral and cell mediated, have been shown to be of some protective value. IgE and eosinophil mediated cytotoxicity has been suggested as a mechanism of killing the adult worm.

Diagnosis
Diagnosis is based on a history of residence in an endemic area, swimmers' itch and other symptoms. The eggs are very characteristic and confirm diagnosis. S. hematobium eggs in urine (55 to 65 by 110 to 170 micrometers) have an apical spine or knob. S. mansoni eggs in feces (45 to 70 by 115-175 micrometers)  have a spine on the side. S. japonicum eggs (55 to 65 by 70 to 100 micrometers) are more round with a vague spine on the side.

Treatment and control
Praziquantel is effective against all species. Contaminated water should be avoided. Control measures include sanitary disposal of sewage and destruction of snails. No vaccine is available.

 Figure 1B
Male and female schistosomes. (Drawn by Sylvia Treadgold)  WHO

Figure 1D
Schistosoma haematobium egg   © Dr Peter Darben, Queensland University of Technology clinical parasitology collection. Used with permission

Figure 1F
Schistosoma haematobium adult male   © Dr Peter Darben, Queensland University of Technology clinical parasitology collection. Used with permission

  Figure 1H
Schistosoma japonicum adult male and female, in copula © Dr Peter Darben, Queensland University of Technology clinical parasitology collection. Used with permission

Figure 1J
Schistosoma japonicum egg   © Dr Peter Darben, Queensland University of Technology clinical parasitology collection. Used with permission

  Figure 1L
Schistosoma japonicum eggs in tissue section (H&E) © Dr Peter Darben, Queensland University of Technology clinical parasitology collection. Used with permission

  Figure 1N
Schistosoma mansoni adult male and female   © Dr Peter Darben, Queensland University of Technology clinical parasitology collection. Used with permission

Figure 1P
Schistosoma mansoni egg, whole and in section (H&E)   © Dr Peter Darben, Queensland University of Technology clinical parasitology collection. Used with permission

Figure 1R
Schistosoma mansoni in section of snail tissue (H&E)   © Dr Peter Darben, Queensland University of Technology clinical parasitology collection. Used with permission

Eggs are eliminated with feces or urine .  Under optimal conditions the eggs hatch and release miracidia , which swim and penetrate specific snail intermediate hosts .  The stages in the snail include 2 generations of sporocysts and the production of cercariae .  Upon release from the snail, the infective cercariae swim, penetrate the skin of the human host , and shed their forked tail, becoming schistosomulae .  The schistosomulae migrate through several tissues and stages to their residence in the veins (, ).  Adult worms in humans reside in the mesenteric venules in various locations, which at times seem to be specific for each species .  For instance, S. japonicum is more frequently found in the superior mesenteric veins draining the small intestine , and S. mansoni occurs more often in the superior mesenteric veins draining the large intestine .  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 most often occurs in the venous plexus of bladder , 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, presinusoidal 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.

Human contact with water is thus necessary for infection by schistosomes.  Various animals, such as dogs, cats, rodents, pigs, hourse and goats, serve as reservoirs for S. japonicum, and dogs for S. mekongi.
 

Figure 2B
Two boys, victims of schistosomiasis showing typical distension of the abdomen. WHO

Fasciolopsis buski (Giant intestinal fluke)

Epidemiology
This is a parasite of central and southeast Asia.

Morphology
The elongate oval fluke is 2 to 7 cm long and lives in the small intestine of man (figure 3).

Life cycle
Man is infected by ingesting water chestnuts contaminated with metacercaria which find access to the small intestine, attach themselves to the mucosa and mature in 25 to 30 days. The fluke eggs are passed in the feces and hatch in fresh water producing miracidia which must penetrate a suitable snail within hours. The miracidia in the snail develop into cercaria and enter fresh water where they attach themselves to water plants (water chestnut) and encyst to become metacercaria (figure 4).

Symptoms
Epigastric pain, nausea and diarrhea are experienced, especially in the morning. In heavier infections, generalized edema and ascites occur.

Pathology
The fluke attaches itself to the intestinal mucosa where inflammation, ulceration and abscesses occur.

Diagnosis
Diagnosis is based on clinical symptoms in endemic areas. Eggs in feces (75 to 100 by 130 to 150 micrometers) provide the final diagnosis.

Treatment and control
Praziquantel has proven effective.  Water chestnuts from contaminated waters should be avoided. Sewage should be treated before disposal.

Figure 3B
Fasciolopsis buski adult, carmine stain  © Dr Peter Darben, Queensland University of Technology clinical parasitology collection. Used with permission

Immature eggs are discharged into the intestine and stool .  Eggs become embryonated in water , eggs release miracidia , which invade a suitable snail intermediate host .  In the snail the parasites undergo several developmental stages (sporocysts , rediae , and cercariae ).  The cercariae are released from the snail and encyst as metacercariae on aquatic plants .  The mammalian hosts become infected by ingesting metacercariae on the aquatic plants.  After ingestion, the metacercariae excyst in the duodenum and attach to the intestinal wall.  There they develop into adult flukes (20 to 75 mm by 8 to 20 mm) in approximately 3 months, attached to the intestinal wall of the mammalian hosts (humans and pigs) .  The  adults have a life span of about one year.
 

Liver Flukes

Epidemiology

Fasciola hepatica, Opisthorchis (previously named Chlonorchis) sinensis, O. felineus and O. viverini affect humans in various parts of the world. F. hepatica is distributed worldwide and is a parasite of grazing animals (sheep and cattle) and man. O. sinensis is a widespread parasite of man, dogs and cats in southeast Asia. It is extraordinarily common in China and is also found in Korea and Japan. Related Opisthorchis species parasitizing European cats (Opisthorchis felinus) and SE Asian dogs (O. viverini) infect humans in the endemic areas. Liver fluke cases are rare in the United States, although snails harboring F. hepatica are present in the western and southern parts of the US.

Fasciola hepatica

Morphology
F hepatica is leaf shaped and measures approximately 1 x 3 cm. The eggs measure 80 x 150 µm.

Life cycle
Humans are infected by the consumption of improperly cooked watercress that harbors encysted larval metacercariae. The larval fluke penetrates the duodenal wall and migrates to the peritoneal cavity, penetrates the liver capsule and migrates into the bile duct where it matures. The adult fluke passes its eggs in stool that hatch in water to produce miracidia. The miracidium must find an appropriate snail to continue the life cycle. In the snail, the miracidium divides and gives rise to cercariae which exit the snail and encyst as metacercariae attached to watercress leaves.

Symptoms
Passage of the larva through the liver produces tenderness and hepatomegaly. The infection results in upper quadrant pain, chills and fever accompanied with eosinophilia. The toxic secretions cause hepatitis. The presence of the worm in the bile duct causes irritation resulting in hyperplasia of the epithelium and bile obstruction. Adult worms may invade the liver and cause necrotic foci (liver rot).

Diagnosis
Diagnosis is based on symptoms and history. The eggs in the stool are indistinguishable from those of F. buski.

Treatment
In contrast with F. buski, F. hepatica is not responsive to praziquantel. However, Triclabendazole is effective.
 

Opisthorchis sinensis, O. felineus and O. viverini

Morphology
These are spindloid flukes measuring about 16x4 mm. The eggs measure 29 x 16 µm.

Life cycle
Man is infected by eating raw or improperly cooked fish that carries the infective metacercaria in a cyst. The cyst is digested and the larval worm migrates up the bile duct to liver where it matures into an adult. The eggs deposited in the biliary duct pass in the feces and find their way to fresh water. Upon ingestion by a suitable fresh water operculate snail, the egg hatches to produce a miracidium. The miracidium in the snail develops into cercaria that break out in water to penetrate under scales of fish. In fish, the cercaria encysts in the muscle and forms the metacercaria that are infectious to man.

Symptoms
The worm causes irritation of the bile ducts that become dilated and deviated. The liver may become enlarged (hepatomegaly), necrotic and tender and liver function may be impaired. Modest infections result in indigestion, epigastric discomfort, weakness and loss of weight. Heavier infections produce anemia, hepatomegaly, slight jaundice, edema, ascites and diarrhea.

Diagnosis
Diagnosis is based on symptoms and presence of endemic infection in the area. Definitive diagnosis is dependent on finding the characteristic eggs in the feces or biliary drainage.

Treatment and control
Praziquantel has proven to be of value. Fish should be cooked well before consumption. Sewage must be treated before disposal.

Figure 5A
Clonorchis sinensis egg 

Figure 5B
Clonorchis sinensis adult, carmine and haematoxylin stain © Dr Peter Darben, Queensland University of Technology clinical parasitology collection. Used with permission

Figure 5C
Clonorchis sinensis adults in section of liver (H&E)

Paragonimus westermani (Lung Fluke)

Epidemiology
Lung fluke is most commonly encountered in parts of Asia, Africa and South America.

Morphology
It is a plump reddish brown oval worm measuring 10 by 4 mm. The ovum measures 85 by 55 micrometers (figure 7).

Life cycle
Lung fluke infects man (and domestic carnivores) when crabmeat infested with encysted metacercaria is consumed. The metacercaria reach the small intestine, exit their shell and bore their way, as young flukes, through the intestinal wall, through the thoracic diaphragm and penetrate the lung. There, they become enclosed in 1 to 2 cm cysts and reach maturity. The eggs are found in the sputum or, if swallowed, in the feces, 2 to 3 months after infection. The eggs, when introduced in fresh water produce a miracidia which penetrates the suitable snail. In the snail they develop into cercaria which break out in water and penetrate gills, muscle or viscera of fresh water crabs and become encysted in flesh as metacercaria (figure 8).

Symptoms
The fluke provokes the development of a fibrous tissue capsule with bloody purulent material containing eggs. There is inflammatory infiltrate around the capsule. The symptoms include a dry cough, followed by production of blood stained rusty brown sputum. Pulmonary pain and pleurisy may develop. Worms may migrate to the brain where they lay eggs and cause a granulomatous abscess resulting in symptoms similar to epilepsy.

Diagnosis
Diagnosis is based on history and symptoms. Eggs are found in rust colored sputum, often being examined for tuberculosis.

Treatment and control
Praziquantel taken orally is quite effective. Adequate cooking of crustaceans is a preventive measure. Improved sanitary conditions have lowered the infection rate in endemic areas.

Figure 7B
Paragonimus westermani adult, carmine stain  © Dr Peter Darben, Queensland University of Technology clinical parasitology collection. Used with permission

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