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Clonorchiasis

[Clonorchis sinensis]

Causal Agents

The trematode Clonorchis sinensis (Chinese or oriental liver fluke).


Life Cycle

Life cycle of Clonorchis sinensis

Embryonated eggs are discharged in the biliary ducts and in the stool The number 1. Eggs are ingested by a suitable snail intermediate host The number 2. Each egg releases a miracidia The number 2a, which go through several developmental stages (sporocysts The number 2b, rediae The number 2c, and cercariae The number 2d. The cercariae are released from the snail and after a short period of free-swimming time in water, they come in contact and penetrate the flesh of freshwater fish, where they encyst as metacercariae The number 3 Infection of humans occurs by ingestion of undercooked, salted, pickled, or smoked freshwater fish The number 4. After ingestion, the metacercariae excyst in the duodenum The number 5 and ascend the biliary tract through the ampulla of Vater The number 6 Maturation takes approximately 1 month. The adult flukes (measuring 10 to 25 mm by 3 to 5 mm) reside in small and medium sized biliary ducts. In addition to humans, carnivorous animals can serve as reservoir hosts.

Geographic Distribution

Endemic areas are in Asia including Korea, China, Taiwan, and Vietnam. Clonorchiasis has been reported in non endemic areas (including the United States). In such cases, the infection is found in Asian immigrants, or following ingestion of imported, undercooked or pickled freshwater fish containing metacercariae.

Clinical Presentation

Most pathologic manifestations result from inflammation and intermittent obstruction of the biliary ducts. In the acute phase, abdominal pain, nausea, diarrhea, and eosinophilia can occur. In long-standing infections, cholangitis, cholelithiasis, pancreatitis, and cholangiocarcinoma can develop, which may be fatal.

Clonorchis sinensis eggs.

 

Clonorchis sinensis eggs are small, ranging in size from 27 to 35 µm by 11 to 20 µm. The eggs are oval shaped with a convex operculum, that rests on visible "shoulders" at the smaller end of the egg. At the opposite (larger, abopercular) end, a small knob or hooklike protrusion is often visible. The miracidium is visible inside the egg.
	Figure A

Figure A: C. sinensis egg: the small knob at the abopercular end is visible in this image.

	Figure B

Figure B: C. sinensis egg. Note the operculum resting on "shoulders;" image taken at 400× magnification.

	Figure C

Figure C: C. sinensis egg; images taken at 400× magnification.

	Figure D

Figure D: C. sinensis egg; images taken at 400× magnification.

C. sinensis adults.

 

Clonorchi sinensis adults are flattened and measure approximately 10-25 mm long by 3-5 mm wide. Like other flukes, they are hermaphroditic, with a single ovary situated anterior to two branches testes. Adults reside in the biliary passages of the liver of the definitive host.
	Figure A

Figure A: Adult of C. sinensis.

	Figure B

Figure B: Adult of C. sinensis stained with carmine. Clearly visible in this image are the oral sucker (OS), pharynx (PH), ceca (CE), acetabulum, or ventral sucker (AC), uterus (UT), vitellaria (VT) and testes (TE).

Snail intermediate hosts of C. sinensis.

 

Clonorchis sinensis requires two intermediate hosts for completion of its life cycle. The first is a snail and the second is cyprinoid fish (although at least eight families of fish may serve as intermediate hosts for C. sinensis). Among the snails, over 100 species in several general may serve as the primary intermediate host. In China, Japan, Korea, Taiwan and other endemic areas, Parafossarulus manchouricus is the most common snail host. Other genera include Bithynia, Tarebia, Alocinma and Bulimus.
	Figure A

Figure A: Shells of Parafossarulus manchouricus, the most common snail host of C. sinensis in endemic areas in southeast Asia. Image courtesy of the Web Atlas of Medical Parasitology and the Korean Society for Parasitology.

	Figure B

Figure B: Bithynia sp., another common intermediate host of C. sinensis. Image courtesy of Michal Maňas.

Laboratory Diagnosis

Microscopic demonstration of eggs in the stool or in duodenal aspirate is the most practical diagnostic method. The adult fluke can also be recovered at surgery.

Serologic testing is currently not available for clonorchiasis in the United States.

More on: Morphologic comparison with other intestinal parasites.

Treatment Information

Praziquantel, adults, 75mg/kg/day orally, three doses per day for 2 days; the pediatric dosage is the same. Praziquantel should be taken with liquids during meals.

Alternative:

Albendazole* is an alternative drug; the dosage for adults is 10mg/kg/day for 7 days. The pediatric dosage is the same. Albendazole should be taken with food; a fatty meal increases the bioavailablility.

Praziquantel

Oral praziquantel is available for human use in the United States.

Praziquantel is pregnancy category B. There are no adequate and well-controlled studies in pregnant women. However, the available evidence suggests no difference in adverse birth outcomes in the children of women who were accidentally treated with praziquantel during mass prevention campaigns compared with those who were not. In mass prevention campaigns for which the World Health Organization (WHO) has determined that the benefit of treatment outweighs the risk, WHO encourages the use of praziquantel in any stage of pregnancy. For individual patients in clinical settings, the risk of treatment in pregnant women who are known to have an infection needs to be balanced with the risk of disease progression in the absence of treatment.

Pregnancy Category B: Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters).

Praziquantel is excreted in low concentrations in human milk. According to WHO guidelines for mass prevention campaigns, the use of praziquantel during lactation is encouraged. For individual patients in clinical settings, praziquantel should be used in breast-feeding women only when the risk to the infant is outweighed by the risk of disease progress in the mother in the absence of treatment.

The safety of praziquantel in children aged less than 4 years has not been established. Many children younger than 4 years old have been treated without reported adverse effects in mass prevention campaigns and in studies of schistosomiasis. For individual patients in clinical settings, the risk of treatment of children younger than 4 years old who are known to have an infection needs to be balanced with the risk of disease progression in the absence of treatment.

Albendazole

Oral albendazole is available for human use in the United States.

Albendazole is pregnancy category C. Data on the use of albendazole in pregnant women are limited, though the available evidence suggests no difference in congenital abnormalities in the children of women who were accidentally treated with albendazole during mass prevention campaigns compared with those who were not. In mass prevention campaigns for which the World Health Organization (WHO) has determined that the benefit of treatment outweighs the risk, WHO allows use of albendazole in the 2nd and 3rd trimesters of pregnancy. However, the risk of treatment in pregnant women who are known to have an infection needs to be balanced with the risk of disease progression in the absence of treatment.

Pregnancy Category C: Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal, or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

It is not known whether albendazole is excreted in human milk. Albendazole should be used with caution in breastfeeding women.

 

The safety of albendazole in children less than 6 years old is not certain. Studies of the use of albendazole in children as young as one year old suggest that its use is safe. According to WHO guidelines for mass prevention campaigns, albendazole can be used in children as young as 1 year old. Many children less than 6 years old have been treated in these campaigns with albendazole, albeit at a reduced dose.

*Not FDA-approved for this indication

References
  • Keiser J, Utzinger J. The drugs we have and the drugs we need against major helminth infections. Adv Parasitol 2010;73:197-230.
  • Keiser J, Utzinger J. Food-borne tremadodiases. Clin Microbiol Rev 2009;22:466-83.
  • Keiser J, Utzinger J. Food-borne trematodiasis: current chemotherapy and advances with artemisinins and synthetic trioxolanes. Trends Parasitol 2007;23:605-12.
  • Liu YH, Wang XG, Gao P, Ming-xin Q. Experimental and clinical trial of albendazole in the treatment of clonorchiasis (Clonorchis) sinensis. Chin Med J (Engl) 1991;104:27-31.
  • Yangco BG, De Lerma C, Lyman GH, Price DL. Clinical study evaluating efficacy of praziquantel in clonorchiasis. Antimicrob Agents Chemother 1987;31:135-8.
  • Jong EC, Wasserheit JN, Johnson RJ, Carberry WL, Agosti J, Dunning S, Clark H. Praziquantel for the treatment of Clonorchis/Opisthorchis infections: report of a double-blind, placebo-controlled trial. J Infect Dis 1985;152:637-40.

DPDx is an education resource designed for health professionals and laboratory scientists. For an overview including prevention and control visit www.cdc.gov/parasites/.

  • Page last reviewed: May 3, 2016
  • Page last updated: May 3, 2016
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