| Opisthorchiasis | |
|---|---|
| Specialty | Infectious diseases, helminthologist  |
Opisthorchiasis is aparasitic disease caused by certain species of genusOpisthorchis (specifically,Opisthorchis viverrini andOpisthorchis felineus). Chronic infection may lead tocholangiocarcinoma, acancer of thebile ducts.
Medical care and loss of wages caused byOpisthorchis viverrini in Laos and in Thailand costs about $120 million annually.[1] In Asia, infection byOpisthorchis viverrini and otherliver flukes affects the poorest people.[2] Along with other foodbornetrematode infections such asclonorchiasis,fascioliasis andparagonimiasis,[3] opisthorchiasis is listed among theWorld Health Organization's list ofneglected tropical diseases.[2]
Symptoms of opisthorchiasis are indistinguishable fromclonorchiasis.[4] About 80% of infected people have no symptoms, though they can haveeosinophilia.[1] Asymptomatic infection can occur when there are less than 1000 eggs in one gram of feces.[1] Infection is considered heavy when there are 10,000-30,000 eggs in one gram of feces.[1] Symptoms of heavier infections may includediarrhea,epigastric and right upper quadrant pain,lack of appetite,fatigue,yellowing of the eyes and skin and mildfever.[1]
These parasites are long-lived and cause heavy chronic infections that may lead to accumulation of fluid in the legs (edema) and in theperitoneal cavity (ascites),[1] enlarged non-functionalgallbladder[1] and alsoascending cholangitis, which can lead to periductalfibrosis,cholecystitis andcholelithiasis, obstructivejaundice,hepatomegaly and/orportal hypertension.[citation needed]
Both experimental and epidemiological evidence strongly implicatesOpisthorchis viverrini infections in the etiology of a malignant cancer of the bile ducts (cholangiocarcinoma) in humans which has a very poor prognosis.[5]Clonorchis sinensis andOpisthorchis viverrini are both categorized by theInternational Agency for Research on Cancer (IARC) asGroup 1 carcinogens.[6]
In humans, the onset of cholangiocarcinoma occurs with chronic opisthorchiasis, associated with hepatobiliary damage, inflammation, periductal fibrosis and/or cellular responses to antigens from the infecting fluke.[5] These conditions predispose to cholangiocarcinoma, possibly through an enhanced susceptibility ofDNA to damage bycarcinogens. Chronic hepatobiliary damage is reported to be multi-factorial and considered to arise from a continued mechanical irritation of theepithelium by the flukes present, particularly via their suckers, metabolites and excreted/secretedantigens as well as immunopathological processes.In silico analyses using techniques ofgenomics andbioinformatics is unraveling information on molecular mechanisms that may be relevant to the development of cholangiocarcinoma.[7]
In regions whereOpisthorchis viverrini is highlyendemic, the incidence of cholangiocarcinoma is unprecedented.[5] For instance, cholangiocarcinoma represents 15% of primary liver cancer worldwide, but in Thailand'sKhon Kaen province, this figure escalates to 90%, the highest recorded incidence of this cancer in the world. Of all cancers recorded worldwide in 2002, 0.02% were cholangiocarcinoma caused byOpisthorchis viverrini.[5] Cancer of the bile ducts caused by opisthorchiasis occurs in the ages 25–44 years in Thailand.[8] A few cases have appeared in later life among U.S. veterans of theVietnam War, who consumed poorly cooked fish from streams in endemic areas near the border of Laos and Vietnam.[9]
Themedical diagnosis is usually established by finding eggs ofOpisthorchis viverrini in feces[1] using theKato technique.[8]Alternatively, an antigen ofOpisthorchis viverrini can be detected byELISA test.[1] Apolymerase chain reaction test that can be performed on faeces has been developed and evaluated in a rural community in central Thailand.[10]
Cholangiocarcinoma is typically incurable at diagnosis.[11][12] Because of this, intervention strategies are focused on theprevention or treatment of liver fluke infection. Prevention can be accomplished through education (by persuading people not to consume raw or undercooked fish), but the ancient cultural custom to consume raw, undercooked or freshly pickled fish persists in endemic areas. One community health program, known as theIntegrated Opisthorchiasis Control Program, has achieved success in the Lawa Lakes region south ofKhon Kaen.[13]
Cooking or deep-freezing (-20 °C for 7 days)[14] of food made of fish is an effective method of prevention.[1] Methods for prevention ofOpisthorchis viverrini inaquaculture fish ponds have also been proposed.[15]
Treatment of opisthorchiasis is usually accomplished withpraziquantel. A single dose of praziquantel of 40 mg/kg is effective against opisthorchiasis (and also againstschistosomiasis).[8] Despite the efficacy of this compound, the lack of acquired immunity to infection predisposes humans to reinfection in endemic regions. In addition, under experimental conditions, the treatment ofOpisthorchis viverrini-infectedhamsters with praziquantel induced a dispersion of parasite antigens, resulting in adverse immunopathological changes following re-infection withOpisthorchis viverrini, a process which has been proposed to initiate and/or promote the development of cholangiocarcinoma in humans.[7]Albendazole can be used as an alternative.[16]
Arandomized controlled trial published in 2011 showed thattribendimidine, a broad-spectrumanthelmintic, appears to be at least as efficacious as praziquantel.[17]Artemisinin was also found to have anthelmintic activity againstOpisthorchis viverrini.[18]
Opisthorchiasis is prevalent where rawcyprinid fishes are a staple of the diet.[19] Prevalence rises with age; children under the age of 5 years are rarely infected byOpisthorchis viverrini. Males may be affected more than females.[20][21] The WHO estimates that foodborne trematodiases (infection by worms or "flukes", mainlyClonorchis,Opisthorchis,Fasciola andParagonimus species) affect 56 million people worldwide and 750 million are at risk of infection.[22][23] 80 million people are at risk of opisthorchiasis (67 million from infection withOpisthorchis viverrini in Southeast Asia and 13 million fromOpisthorchis felineus in Kazakhstan, Russia, and Ukraine).[24][25] In the lowerMekong River basin, the disease is highly endemic, and more so in lowlands,[19] with a prevalence up to 60% in some areas of northeast Thailand. However, estimates using polymerase chain reaction-based diagnostic techniques indicate that prevalence is probably grossly underestimated.[26] In one study from the 1980s, a prevalence of over 90% was found in persons greater than 10 years old in a small village near Khon Kaen in northeast Thailand in the region known asIsan.[27] Sporadic cases have been reported from Malaysia, Singapore, and the Philippines.[23] Although the overall prevalence has declined since initial surveys performed in the 1950s, an increase has occurred since the 1990s in some areas, possibly related to large increases inaquaculture.[25]
UsingCRISPR gene editing technology in animal models, researchers have been able to eliminate the genes responsible for symptoms of opisthorchiasis, which may lead to further research toward novel treatment and control of this disease and its sequelae.[28]
