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11 Trematodes – Flukes

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11.1 Trematodes: introduction

The trematodes are flatworms which are of great importance in tropical pathology. They may affect various organs. They have at least two suckers, one oral and one ventral (Heterophyes has three). The oral sucker surrounds the mouth. The intestinal system has a blind ending. They have no blood circulation. Oxygen is absorbed by diffusion. The diffusion of oxygen is highly dependent on the distance to be covered and plays a part in determining the maximum thickness of the parasite. Most trematodes are hermaphrodites and thus possess both male and female genitalia. They have a cirrus (penis). The function of the Laurer canal is unclear, but it is probably a vestigial vagina. Cross-fertilisation and self-insemination are both possible. There are exceptions, e.g. schistosomes have separate sexes. After leaving the ovary, the eggs are fertilized and subsequently surrounded by yolk in the ootype (an extension of the vitelline duct). Secretions from the Mehlis gland are added to the egg. Several concentric eggshells are formed. The eggshells then undergo a chemical reaction, a kind of tanning process, which makes them tough and harder. In this way the egg acquires its typical form, and becomes more resistant to conditions in the outside world, which are often unfavourable.

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11.2 Trematodes: general morphology

1. oral sucker 

2. ventral sucker 

3. pharynx 

4. oesophagus 

5. intestine 

6. small excretory tubulus 

7. collection tube 

8. excretion bladder 

9. excretory pore 

10. testis 

11. and 12. vas deferens 

13. seminal vesicle 

14. prostate 

15. cirrus (ejaculation duct) 

16. cirrus sac 

17. genital pore 

18. ovary 

19. seminal receptacle 

20. Laurer canal 

21. ootype 

22. Mehlis’ gland 

23. uterus 

24. yolk gland 

25. common yolk channel 

Blue  

digestive system 

Yellow 

excretory system 

Green  

male genital system 

Red  

female genital system 

Black  

yolk (vitellin) system 

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11.3 Trematodes: general life cycle

The trematodes which are of importance in human pathology belong to the Digenea (Gr. di = two, generis = generation). This name refers to the obligatory change of host during the life cycle of the parasite. Details differ depending on the species of parasite. Eggs are produced by the adult parasite and arrive in the outside world via faeces or urine of the host. The eggs hatch, miracidia emerge and penetrate snails. There they change into sporocysts, rediae, possibly daughter rediae and cercariae (in schistosomes there are no rediae). Cercariae emerge from the snail, swim around and then penetrate the next intermediate host to form metacercariae. Cercariae from the Fasciolidae encyst on water plants. Cercariae from schistosomes penetrate the final host directly. Secondary intermediate hosts include fish, crabs, snails and insects. After they have been eaten by the final host the metacercariae grow into adult parasites.

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11.4 Trematodes: localisation

intestinal lumen 

Large intestinal fluke (Fasciolopsis buski) 

Small intestinal flukes (Metagonimus and Heterophyes) 

lungs  

Lung fluke (Paragonimus) 

bile ducts  

Large liver flukes (Fasciola hepatica and F. gigantica) 

Small liver flukes (Opisthorchis, Clonorchis, Dicrocoelium) 

blood vessels  

Blood flukes (Schistosoma sp.) 

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11.5 Trematodes: intestinal flukes

Various trematodes are found as adult worms in human intestines. Examples are Fasciolopsis buski, Metagonimus yokogawai, Heterophyes heterophyes, Echinostoma sp., Gastrodiscoides sp. Most infections are asymptomatic or provoke vague abdominal symptoms. Only in severe infestations (high worm load) are there likely to be signs of malabsorption. Eosinophilia is common. Diagnosis can only be made by examining the faeces for parasites. As a general rule most of these infections can easily be treated with praziquantel.

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11.6 Trematodes: lung flukes – Paragonimus sp.

11.6.1 Trematodes: Paragonimus sp., summary

11.6.2 Trematodes: Paragonimus sp., general

The parasite occurs in Southeast Asia and the Far East, in Central and West Africa. In America its distribution is limited to Central America and the north of South America. Usually P. westermani is reported, but there are a number of other species which can cause infection in humans (Paragonimus africanus, P. bangkokensis, P. heterotremus, P. hueitungensis, P. kellicotti, P. mexicanus, P. miyazakii, P. ohirae, P. philippinensis, P. sadoensis, P. skrjabini, P. uterobilateralis).

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11.6.3 Trematodes: Paragonimus sp., life cycle

Adult worms live in the lungs. Eggs pass to the outside with the sputum. If sputum is swallowed, eggs may also be found in faeces. Once in the outside world and in water, miracidia (first-stage larvae) emerge from the eggs. They penetrate snails, where they undergo a transformation. After 3 to 5 months cercariae (second-stage larvae) leave the snail and penetrate crabs. Here the cercariae develop into metacercariae (third-stage larvae). It is this form which is infectious for the definitive host. Paragonomiasis is a zoonosis of carnivorous animals. Humans are only an exceptional host. They become infected by eating raw fresh-water crabs and river crayfish which contain infectious metacercariae. Excystation occurs in the duodenum. The larvae bore through the intestinal wall and migrate via the abdominal cavity to the lungs. There they develop into adult worms. The worms form a cavity 1 to 4 cm in diameter. Egg-laying begins 8 to 10 weeks after infection. The worms rarely migrate to ectopic sites.

11.6.4 Trematodes: Paragonimus sp., symptoms

Mild infections are asymptomatic. In the acute stage (invasion and migration of the larvae) there may be diarrhoea, abdominal pain, urticaria and eosinophilia. This is followed by fever, thoracic pain, cough, dyspnoea and malaise. The chronic illness resembles chronic bronchitis and TB. There is spasmodic cough (especially after exertion) with expectoration of blood stained sputum, as well as dyspnoea sometimes with wheezing and pleural pain. When the parasite is located in an ectopic site (brain, subcutis, etc.) the symptoms depend on the place where the worms are.

11.6.5 Trematodes: Paragonimus sp., diagnosis

Diagnosis is by detecting the eggs. The eggs often need to be concentrated (e.g. mix sputum + water + potassium hydroxide, then centrifuge and examine the sediment). Differential diagnosis includes tuberculosis of the lungs, pulmonary abscess, chronic bronchitis, melioidosis, lung carcinoma and lung metastases. If sputum is swallowed, eggs may also be found in the faeces.

11.6.6 Trematodes: Paragonimus sp., treatment

Praziquantel 75 mg/day for 3 days is very effective. In cases of cerebral localisation higher doses must be given but only under the protection of steroids due to the risk of epileptic fits secondary to perilesional oedema.

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11.7 Trematodes: liver flukes (biliary tract flukes)

11.7.1 Trematodes: liver flukes: summary

11.7.2 Trematodes: liver flukes, Clonorchis, Opisthorchis and Metorchis

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Opisthorchis viverrini and Clonorchis sinensis (= Opisthorchis sinensis) occur in Asia. Eggs eliminated with the bile and faeces are taken up by snails. After further development in these animals, they leave the mollusc and penetrate freshwater fish. Humans become infected by eating raw fish such as carp. After the larvae are released in the duodenum, they migrate directly via the main bile duct to the intrahepatic bile ducts. Thus there is no tissue passage. The parasites are approximately 1 to 2 cm long and can live for 20 years. Dogs and cats form a reservoir.

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Another parasite which is found in North America is Metorchis conjunctus. The eggs are very similar to those of Opisthorchis. Transmission of Metorchis conjunctus is via eating raw, infected fish (often Catastomus commersoni). It is an important disorder in animals, for example among sleigh dogs in Canada and Alaska.

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There may or may not be symptoms, depending on the worm load and location of the worms. Intermittent pain may occur around the liver which is sometimes enlarged. If bacterial superinfection occurs, febrile suppurating cholangitis results. If impaction with obstruction of the main bile duct occurs, there will be progressive icterus. In long-existing cases of infestation with Clonorchis sinensis, secondary biliary cirrhosis and carcinoma of the bile duct (cholangiocarcinoma) may develop. This is much rarer, however, than primary liver carcinoma (hepatoma) due to chronic hepatitis B or C infection. The diagnosis is made by detecting eggs in the faeces. A concentration technique is necessary. However, if bile duct is obstructed, no eggs can be detected. Sometimes duodenal intubation is necessary (aspiration of bile containing eggs). Serology may be helpful. The treatment consists of praziquantel.

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11.8 Trematodes: liver flukes: Fasciola hepatica and F. gigantica

11.8.1 Fasciola hepatica and F. gigantica, general

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Infection with these large liver flukes is quite wide-spread among animals. For example, Fasciola hepatica causes liver rot in sheep. The encapsulated larvae (metacercariae) are found on all kinds of plants such as water cress (Nasturtium officinale), Lamb’s lettuce, dandelions (Taraxacum officinale), chinese water spinach (Ipomaea aquatica, Pak Boong in Thai cookery). After infected plants have been consumed the larvae are released in the small intestine, migrate within the hour through the intestinal wall to the peritoneal cavity and then bore through the liver capsule about 5 days later. After further migration in the liver, they reach the bile duct after approximately 7 weeks and remain there, laying their eggs. These are transferred via the bile to the intestine, and then excreted with the faeces. A single liver fluke can lay up to 20,000 eggs a day but usually produces smaller numbers. It should be noted that fertilised eggs can be produced by a single liver fluke (they are hermaphroditic). Fasciola indica is a rare cause of fasciolasis. Infection also takes place due to ingestion of water plants infected with metacercariae.

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Various environmental factors such as temperature, humidity, light intensity, oxygen pressure and local pH are important for the further development of the parasite in the outside world. If the eggs remain in the faeces, they cannot undergo embryonation. They may, however, be released from faeces, for example by heavy rain, if faeces land directly in water or if they are trampled by animals. Eggs often remain viable for months and can overwinter. Survival for more than 2 years has been demonstrated at a temperature of 2°C. Fierce heat and drying out kills the eggs. At a temperature of approximately 25° C (the optimum temperature) eggs develop in about three weeks. There is much variation, however, in the rate at which eggs are released, which is an advantage to the parasite, since a particular habitat will remain infectious over longer periods. Under the influence of specific stimuli a 130 µm long larva (miracidium) emerges from the egg. This is covered with cilia and is immediately mobile in water. It can easily swim for hours. The larva has eye spots and is highly phototropic (it swims towards the light). This prevents the larva from wasting time and energy exploring the bottom of the pond, where the intermediate host (usually Lymnaea trunculata) is not to be found. This is unlike F. gigantica where the miracidium actively swims away from light to find L. natalensis, which lives deeper down. If the larva does not find the correct snail within 24 hours its glycogen reserves are exhausted and the larva dies. If a miracidium arrives some 15 cm from a snail, there is pronounced chemotaxis and the larva swims directly to the host and penetrates it. The next development takes place within the snail. These snails can survive long periods of drought (via aestivation) and long-term cold (via hibernation). Inside the snail, the miracidium develops into a sporocyst and then into rediae, a stage named after the Italian physician Francesco Redi (1688). The rediae measure approximately 1-3 mm, are mobile and may cause significant damage in the snail (if the infection is severe the snail dies). After 4-7 weeks the first cercariae emerge from the rediae; they measure 250-350 µm and leave the snail. The cercariae swim around in the water, to encyst within 2 hours on particular plants. Each cercaria then changes into a metacercaria (plural metacercariae). Due to the amplification phase in the snail, a single egg can produce 4000 metacercariae. Metacercariae can survive for more than a year on pasture. They are destroyed by heat and drought (the effect of long hot summers).

11.8.2 Fasciola hepatica and F. gigantica, symptoms

Symptoms are present mainly during the migration period: fever, pain in the liver region, hepatomegaly, eosinophilia. After this period symptoms are generally mild or absent. Sometimes there is cholangitis. If raw goat’s or sheep’s liver is eaten, adult worms can sometimes attach to the throat, resulting in local irritation (halzoun).

11.8.3 Fasciola hepatica and F. gigantica, diagnosis

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The diagnosis is made by detecting the eggs in faeces or duodenal aspirate (eggs appear approximately 12 weeks after infection). Repeated specimens are often necessary in view of the small number of eggs which are produced daily. If an individual has eaten infected sheep’s liver, he/she can have eggs in the faeces, although no real infection occurs (spurious infection). Ultrasound or CT scan of the liver may show a clustering of hyporeflective or hypodense tunnels in the liver parenchyma (these are inflamed bile ducts). Sometimes it is possible to actually visualise the moving worms. Via laparoscopy, one can sometimes find slowly migrating worm tracts. The specificity of serology is lowered by cross-reactivity with other helminths.

11.8.4 Fasciola hepatica and F. gigantica, differential diagnosis

In the differential diagnosis other disorders will be included which cause eosinophilia and hepatic lesions: other biliary tract flukes (Clonorchis, Opisthorchis, Dicrocoelium, Metorchus), schistosomiasis, Ascaris with ectopic migration into the bile duct, echinococcosis (with a leaking cyst), Strongyloides stercoralis hyperinfection, Capillaria hepatica, toxocariasis (visceral larva migrans). Sometimes, certain tumors may mimick fascioliasis.

11.8.5 Fasciola hepatica and F. gigantica, treatment

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The therapy is problematical at present. Praziquantel is not sufficiently active. Triclabendazole (Fasinex®, Egaten®) 10 mg/kg taken in one dose together with a fatty meal is still experimental, but is becoming the treatment of choice. Triclabendazole-resistant F. hepatica strains are already known in cattle. Bithionol, 30-50 mg/kg every 48 hours to a total of 10-15 doses, is an old product which can be used as an alternative. Emetine and metronidazole have also been used as therapy. Nitazoxanide is a new drug. The dose is 500 mg BD for 1 week. Other drugs used in veterinary medicine include oxyclozanide (Zanil®), nitroxinil (Dovenix®) and rafoxanide.

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