Liver flukes: Clonorchis, Opisthorchis, and Metorchis
- Karin Leder, MBBS, FRACP, PhD, MPH, DTMH
Karin Leder, MBBS, FRACP, PhD, MPH, DTMH
- Section Editor — Travel Medicine
- Head of Infectious Diseases Unit
- Monash University, Australia
- Peter F Weller, MD, FACP
Peter F Weller, MD, FACP
- Editor-in-Chief — Infectious Diseases
- Section Editor — Tropical Medicine
- William Bosworth Castle Professor of Medicine
- Harvard Medical School
- Professor of Immunology and Infectious Diseases
- Harvard School of Public Health
The three major liver trematodes (flukes) that infect humans are Clonorchis sinensis, Opisthorchis species, and Fasciola hepatica. Clonorchiasis, opisthorchiasis, and the North American liver fluke, Metorchis conjunctus, will be reviewed here. Fascioliasis is discussed separately. (See "Liver flukes: Fascioliasis".)
CLONORCHIS SINENSIS AND OPISTHORCHIS SPECIES
Epidemiology — C. sinensis (or Opisthorchis sinensis), also known as the Chinese liver fluke, is endemic in the Far East, particularly in China, Japan, Taiwan, Vietnam, and Korea; it is also endemic in far eastern Russia [1,2]. Clonorchis is a parasite of fish-eating mammals; dogs and cats are the most common reservoirs. It is estimated that more than 35 million people are infected worldwide, with 600 million at risk . Prevalence rates in endemic areas vary widely; in different provinces of China, for example, the prevalence ranges from <1 to 57 percent . One study in Korea noted a prevalence of 16 percent .
Opisthorchiasis is generally caused by Opisthorchis felineus or O. viverrini. These are liver flukes of cats, dogs, and other fish-eating mammals, which serve as reservoir hosts. O. felineus occurs in Southeast Asia and in Central and Eastern Europe, particularly in Siberia and other parts of the former Soviet Union. Prevalence rates are 40 to 95 percent in some areas, and it is estimated that more than 16 million people are infected . O. viverrini is endemic in Thailand, Vietnam and Cambodia, and Laos. Prevalence rates of over 24 to 90 percent in villages in Thailand and 40 to 80 percent in Laos have been reported, and it is estimated that worldwide over 23 million people are infected, including 15 million in China [6-9].
Adult flukes can remain in the bile ducts for 26 years . Protective immunity does not develop and repeat infection can occur, so the cumulative worm burden can increase with age among infected individuals in endemic areas. As a result, symptomatic infection is most common in older adults and may be delayed for many years following initial infection . In endemic areas, the incidence of cholangiocarcinoma is very high. (See 'Chronic symptoms and complications' below.)
Travelers to or immigrants from endemic areas may harbor the infection and import it to nonendemic areas. Surveys in the United States have suggested that up to 26 percent of Southeast Asian immigrants have an active liver fluke infection [12,13]. In addition, frozen, dried, or pickled fish that contain surviving metacercariae can be exported to nonendemic areas, so occasionally infection occurs in individuals who have never traveled to endemic areas [14-16].
- Rim HJ. Clonorchiasis: an update. J Helminthol 2005; 79:269.
- Wang KX, Zhang RB, Cui YB, et al. Clinical and epidemiological features of patients with clonorchiasis. World J Gastroenterol 2004; 10:446.
- Keiser J, Utzinger J. Emerging foodborne trematodiasis. Emerg Infect Dis 2005; 11:1507.
- Maclean JD, Cross J, Mahanty S. Liver, lung, and intestinal fluke infections. In: Tropical Infectious Diseases: Principles, Pathogens and Practice, 2nd ed, Guerrant RL, Waker DH, Weller PF (Eds), Churchill Livingstone, Philadelphia 2006. p.1349.
- Kim BJ, Ock MS, Kim IS, Yeo UB. Infection status of Clonorchis sinensis in residents of Hamyang-gun, Gyeongsangnam-do, Korea. Korean J Parasitol 2002; 40:191.
- Control of foodborne trematode infections. Report of a WHO Study Group. World Health Organ Tech Rep Ser 1995; 849:1.
- Ramasoota T. Current status of food-borne parasitic zoonoses in Thailand. Southeast Asian J Trop Med Public Health 1991; 22 Suppl:23.
- Harinasuta T, Pungpak S, Keystone JS. Trematode infections. Opisthorchiasis, clonorchiasis, fascioliasis, and paragonimiasis. Infect Dis Clin North Am 1993; 7:699.
- Andrews RH, Sithithaworn P, Petney TN. Opisthorchis viverrini: an underestimated parasite in world health. Trends Parasitol 2008; 24:497.
- Tan WB, Shelat VG, Diddapur RK. Oriental liver fluke infestation presenting more than 50 years after immigration. Ann Acad Med Singapore 2009; 38:735.
- Liu LX, Harinasuta KT. Liver and intestinal flukes. Gastroenterol Clin North Am 1996; 25:627.
- Schwartz DA. Cholangiocarcinoma associated with liver fluke infection: a preventable source of morbidity in Asian immigrants. Am J Gastroenterol 1986; 81:76.
- Yossepowitch O, Gotesman T, Assous M, et al. Opisthorchiasis from imported raw fish. Emerg Infect Dis 2004; 10:2122.
- Morsy AT, Al-Mathal EM. Clonorchis sinensis a new report in Egyptian employees returning back from Saudi Arabia. J Egypt Soc Parasitol 2011; 41:221.
- Lewin MR, Weinert MF. An eighty-four-year-old man with fever and painless jaundice: a case report and brief review of Clonorchis sinensis infection. J Travel Med 1999; 6:207.
- Chan CW, Lam SK. Diseases caused by liver flukes and cholangiocarcinoma. Baillieres Clin Gastroenterol 1987; 1:297.
- Upatham ES, Viyanant V, Kurathong S, et al. Relationship between prevalence and intensity of Opisthorchis viverrini infection, and clinical symptoms and signs in a rural community in north-east Thailand. Bull World Health Organ 1984; 62:451.
- Upatham ES, Viyanant V, Kurathong S, et al. Morbidity in relation to intensity of infection in Opisthorchiasis viverrini: study of a community in Khon Kaen, Thailand. Am J Trop Med Hyg 1982; 31:1156.
- Mairiang E, Haswell-Elkins MR, Mairiang P, et al. Reversal of biliary tract abnormalities associated with Opisthorchis viverrini infection following praziquantel treatment. Trans R Soc Trop Med Hyg 1993; 87:194.
- Pungpak S, Harinasuta T, Bunnag D, et al. Fecal egg output in relation to worm burden and clinical features in human opisthorchiasis. Southeast Asian J Trop Med Public Health 1990; 21:275.
- Marcos LA, Terashima A, Gotuzzo E. Update on hepatobiliary flukes: fascioliasis, opisthorchiasis and clonorchiasis. Curr Opin Infect Dis 2008; 21:523.
- Keiser J, Utzinger J. Food-borne trematodiases. Clin Microbiol Rev 2009; 22:466.
- Sithithaworn P, Haswell-Elkins MR, Mairiang P, et al. Parasite-associated morbidity: liver fluke infection and bile duct cancer in northeast Thailand. Int J Parasitol 1994; 24:833.
- Pungpak S, Chalermrut K, Harinasuta T, et al. Opisthorchis viverrini infection in Thailand: symptoms and signs of infection--a population-based study. Trans R Soc Trop Med Hyg 1994; 88:561.
- Watanapa P, Watanapa WB. Liver fluke-associated cholangiocarcinoma. Br J Surg 2002; 89:962.
- Okuda K, Kubo Y, Okazaki N, et al. Clinical aspects of intrahepatic bile duct carcinoma including hilar carcinoma: a study of 57 autopsy-proven cases. Cancer 1977; 39:232.
- Pungpak S, Radomyos P, Radomyos BE, et al. Treatment of Opisthorchis viverrini and intestinal fluke infections with Praziquantel. Southeast Asian J Trop Med Public Health 1998; 29:246.
- Sakolvaree Y, Ybanez L, Chaicumpa W. Parasites elicited cross-reacting antibodies to Opisthorchis viverrini. Asian Pac J Allergy Immunol 1997; 15:115.
- Akai PS, Pungpak S, Chaicumpa W, et al. Serum antibody responses in opisthorchiasis. Int J Parasitol 1995; 25:971.
- Sirisinha S, Chawengkirttikul R, Haswell-Elkins MR, et al. Evaluation of a monoclonal antibody-based enzyme linked immunosorbent assay for the diagnosis of Opisthorchis viverrini infection in an endemic area. Am J Trop Med Hyg 1995; 52:521.
- Wongsaroj T, Sakolvaree Y, Chaicumpa W, et al. Affinity purified oval antigen for diagnosis of Opisthorchiasis viverrini. Asian Pac J Allergy Immunol 2001; 19:245.
- Lin YL, Chen ER, Yen CM. Antibodies in serum of patients with clonorchiasis before and after treatment. Southeast Asian J Trop Med Public Health 1995; 26:114.
- Watwiengkam N, Sithithaworn J, Duenngai K, et al. Improved performance and quantitative detection of copro-antigens by a monoclonal antibody based ELISA to diagnose human opisthorchiasis. Acta Trop 2013; 128:659.
- Kim SI. A Clonorchis sinensis-specific antigen that detects active human clonorchiasis. Korean J Parasitol 1998; 36:37.
- Li S, Shin JG, Cho PY, et al. Multiple recombinant antigens of Clonorchis sinensis for serodiagnosis of human clonorchiasis. Parasitol Res 2011; 108:1295.
- Wongratanacheewin S, Pumidonming W, Sermswan RW, et al. Detection of Opisthorchis viverrini in human stool specimens by PCR. J Clin Microbiol 2002; 40:3879.
- Kim EM, Verweij JJ, Jalili A, et al. Detection of Clonorchis sinensis in stool samples using real-time PCR. Ann Trop Med Parasitol 2009; 103:513.
- Umesha KR, Kumar S, Parvathi A, et al. Opisthorchis viverrini: detection by polymerase chain reaction (PCR) in human stool samples. Exp Parasitol 2008; 120:353.
- Arimatsu Y, Kaewkes S, Laha T, et al. Rapid detection of Opisthorchis viverrini copro-DNA using loop-mediated isothermal amplification (LAMP). Parasitol Int 2012; 61:178.
- Hong ST, Yoon K, Lee M, et al. Control of clonorchiasis by repeated praziquantel treatment and low diagnostic efficacy of sonography. Korean J Parasitol 1998; 36:249.
- Elkins DB, Mairiang E, Sithithaworn P, et al. Cross-sectional patterns of hepatobiliary abnormalities and possible precursor conditions of cholangiocarcinoma associated with Opisthorchis viverrini infection in humans. Am J Trop Med Hyg 1996; 55:295.
- Choi D, Hong ST, Lim JH, et al. Sonographic findings of active Clonorchis sinensis infection. J Clin Ultrasound 2004; 32:17.
- Choi D, Jeon YH, Lee GC, et al. Changes in sonographic findings after treatment of patients with clonorchiasis in a heavy endemic area. Korean J Parasitol 2009; 47:19.
- Lim JH. Radiologic findings of clonorchiasis. AJR Am J Roentgenol 1990; 155:1001.
- Jeong YY, Kang HK, Kim JW, et al. MR imaging findings of clonorchiasis. Korean J Radiol 2004; 5:25.
- Drugs for Parasitic Infections, The Medical Letter, 2010.
- Jong EC, Wasserheit JN, Johnson RJ, et al. Praziquantel for the treatment of Clonorchis/Opisthorchis infections: report of a double-blind, placebo-controlled trial. J Infect Dis 1985; 152:637.
- Tinga N, De N, Vien HV, et al. Little effect of praziquantel or artemisinin on clonorchiasis in Northern Vietnam. A pilot study. Trop Med Int Health 1999; 4:814.
- Bunnag D, Harinasuta T. Studies on the chemotherapy of human opisthorchiasis: III. Minimum effective dose of praziquantel. Southeast Asian J Trop Med Public Health 1981; 12:413.
- Pungpak S, Bunnag D, Harinasuta T. Clinical and laboratory evaluation of praziquantel in opisthorchiasis. Southeast Asian J Trop Med Public Health 1983; 14:363.
- Pungpark S, Bunnag D, Harinasuta T. Albendazole in the treatment of opisthorchiasis and concomitant intestinal helminthic infections. Southeast Asian J Trop Med Public Health 1984; 15:44.
- Liu YH, Wang XG, Gao P, Qian MX. Experimental and clinical trial of albendazole in the treatment of Clonorchiasis sinensis. Chin Med J (Engl) 1991; 104:27.
- Jaroonvesama N, Charoenlarp K, Cross JH. Treatment of Opisthorchis viverrini with mebendazole. Southeast Asian J Trop Med Public Health 1981; 12:595.
- Soukhathammavong P, Odermatt P, Sayasone S, et al. Efficacy and safety of mefloquine, artesunate, mefloquine-artesunate, tribendimidine, and praziquantel in patients with Opisthorchis viverrini: a randomised, exploratory, open-label, phase 2 trial. Lancet Infect Dis 2011; 11:110.
- Qian MB, Yap P, Yang YC, et al. Efficacy and safety of tribendimidine against Clonorchis sinensis. Clin Infect Dis 2013; 56:e76.
- Viravan C, Bunnag D, Harinasuta T, et al. Clinical field trial of praziquantel in opisthorchiasis in Nong Rangya Village, Khon Kaen Province, Thailand. Southeast Asian J Trop Med Public Health 1986; 17:63.
- Vivatanasesth P, Sornmani S, Schelp FP, et al. Mass treatment of opisthorchiasis in Northeast Thailand. Southeast Asian J Trop Med Public Health 1982; 13:609.
- Jongsuksuntigul P, Imsomboon T. Epidemiology of opisthorchiasis and national control program in Thailand. Southeast Asian J Trop Med Public Health 1998; 29:327.
- Jongsuksuntigul P, Imsomboon T. The impact of a decade long opisthorchiasis control program in northeastern Thailand. Southeast Asian J Trop Med Public Health 1997; 28:551.
- Mordvinov VA, Yurlova NI, Ogorodova LM, Katokhin AV. Opisthorchis felineus and Metorchis bilis are the main agents of liver fluke infection of humans in Russia. Parasitol Int 2012; 61:25.
- Brassard P, Hoey J, Ismail J, Gosselin F. The prevalence of intestinal parasites and enteropathogenic bacteria in James Bay Cree Indians, Quebec. Can J Public Health 1985; 76:322.
- Behr MA, Gyorkos TW, Kokoskin E, et al. North American liver fluke (Metorchis conjunctus) in a Canadian aboriginal population: a submerging human pathogen? Can J Public Health 1998; 89:258.
- MacLean JD, Arthur JR, Ward BJ, et al. Common-source outbreak of acute infection due to the North American liver fluke Metorchis conjunctus. Lancet 1996; 347:154.
- CLONORCHIS SINENSIS AND OPISTHORCHIS SPECIES
- Life cycle
- Clinical manifestations
- - Acute symptoms
- - Chronic symptoms and complications
- - Microscopy
- - Laboratory assays
- - Imaging
- Differential diagnosis
- - Anthelminthic therapy
- - Other interventions
- METORCHIS CONJUNCTUS
- SUMMARY AND RECOMMENDATIONS