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{{Opisthorchiasis}}
{{Opisthorchiasis}}


==Overview==
==[[Opisthorchiasis overview|Overview]]==
'''Opisthorchiasis''' is a parasitic disease caused by species in the genus [[Opisthorchis]] (specifically, ''[[Opisthorchis viverrini]]'' and ''[[Opisthorchis felineus]]'').


[[Medical care]] and loss of [[wage]]s caused by ''Opisthorchis viverrini'' in Laos and in Thailand costs about $120 million annually<ref name="Muller 2002">Muller R. & Wakelin D. (2002). ''Worms and human disease''. CABI. [http://books.google.com/books?id=bWtCMIGF_FMC&lpg=PA43&ots=XqJMTRaVuJ&dq=Opisthorchis%20viverrini%20Stiles%20%26%20Hassal%2C%201896&hl=cs&pg=PA43#v=onepage&q&f=false page 43]-44.</ref> or $120 million per year can cost Northeast Thailand only.<ref name="Kingl 2001">{{cite doi|10.3347/kjp.2001.39.3.209}}</ref>
==[[Opisthorchiasis historical perspective|Historical Perspective]]==


Infection of ''Opisthorchis viverrini'' and of other liver flukes in Asia affect the [[Poverty|poor and poorest people]].<ref name="Sripa 2008"/> Opisthorchiasis have received less attention in comparison of other diseases and it is a neglected disease in Asia.<ref name="Sripa 2008">{{Cite doi|10.1371/journal.pntd.0000232}}.</ref>
==[[Opisthorchiasis pathophysiology|Pathophysiology]]==


==Prevalence==
==[[Opisthorchiasis causes|Causes]]==
O. viverrini is found mainly in northeast Thailand, Laos, and Kampuchea.  O. felineus is found mainly in Europe and Asia, including the former Soviet Union.


[[File:Incidence of CCA and O. viverrini in Thailand from 1990–2001.jpg|thumb|Prevalence of ''Opisthorchis viverrini'' in Thailand in 1990–2001 correlates with a higher [[cholangiocarcinoma]]:<br/>
==[[Opisthorchiasis differential diagnosis|Differentiating Opisthorchiasis from other Diseases]]==
19.3% in North Thailand,<br/>
15.7% in North East Thailand,<br/>
3.8% in Central Thailand,<br/>
0% in Southern Thailand.<ref name="Stripa 2007">{{Cite doi|10.1371/journal.pmed.0040201}}.</ref>]]


Opisthorchiasis is prevalent in geographical regions where raw [[cyprinid]] fishes are a staple of the diet of humans.<ref name="Young 2010"/> The [[prevalence]] of human infection can be as high as 70% in some regions, for example in [[Khon Kaen Province]] in Thailand.<ref name="Young 2010"/> The parasite establishes in the [[bile duct]]s of the liver as well as [[extrahepatic duct]]s and the [[gall bladder]] of the mammalian (definitive) host.<ref name="Young 2010">{{Cite doi|10.1371/journal.pntd.0000719}}.</ref>
==[[Opisthorchiasis epidemiology and demographics|Epidemiology and Demographics]]==


Children under the age of 5 are rarely infected by ''Opisthorchis viverrini''.<ref name="Muller 2002"/>
==[[Opisthorchiasis risk factors|Risk Factors]]==


In the [[Lao People's Democratic Republic]], the prevalence of opisthorchiasis was:
==[[Opisthorchiasis natural history, complications and prognosis|Natural History, Complications and Prognosis]]==
* 40% in 1992 causing about 1 744 000 people infected<ref name="WHO 1995">[[World Health Organization]] (1995). ''Control of Foodborne Trematode Infection''. WHO Technical Report Series. 849. [http://whqlibdoc.who.int/trs/WHO_TRS_849_(part1).pdf PDF part 1], [http://whqlibdoc.who.int/trs/WHO_TRS_849_(part2).pdf PDF part 2]. page 89-91.</ref>


In Thailand, the prevalence of opisthorchiasis was:
==Diagnosis==
* scaterred reports by Verdun & Bruyant (1908), Leiper (1911), Prommas (1927), Bedier & Chesneau (1929)<ref name="Wykoff 1965"/>
* The national control programme have started in Thailand in 1950.<ref name="WHO 2004"/>
* 25% in 1953 causing about 2 million infected people.<ref name="WHO 1995"/> The first widespread report of opisthorchiasis in Thailand was in 1953.<ref name="WHO 1995"/>
* 1965: over 3.5 millions infected people<ref name="Wykoff 1965">{{cite PMID|14275209}}, [http://www.jstor.org/stable/3276083 JSTOR].</ref>
* 14% in 1980-1981 causing about 7 million infected people.<ref name="Harinasuta 1984"/>
* 63.6% in 1984-1987,<ref name="WHO 2004"/><ref name="Jongsuksuntigul 2003"/> but another [[WHO]] report mention prevalence 35% in Nort-east Thailand for 1984.<ref name="WHO 1995"/>
* 35.6% in 1988<ref name="Jongsuksuntigul 2003"/>
* 30% in 1989<ref name="WHO 2004"/>
* The decline of opisthorchiasis was caused by opisthorchiasis control programme, that includes health education including [[mass distribution]] of [[cooking pot]]s<ref name="WHO 1995"/> and using [[praziquantel]], that was available since 1984.<ref name="WHO 1995"/>
* 15.2% in 1991 causing 7 million infected people.<ref name="WHO 1995"/> About 45 million people were at risk of infection.<ref name="WHO 1995"/> There was prevalence 22.8% in North Thailand, 24.0% in North East Thailand, 7.3% in Central Thailand and 0.3% in Southern Thailand.<ref name="WHO 1995"/>
* 12% in 1996<ref name="WHO 2004"/>
* In 1992-1996 the [[National Public Health Development Plan]] used the strategy by the Faculty of Tropical Medicine, [[Mahidol University]] against opisthorchiasis.<ref name="WHO 1995"/>
* 7% in 2000<ref name="WHO 2004"/>
* 9.4% in 2001<ref name="Jongsuksuntigul 2003"/> In Thailand, the prevalence of opisthorchiasis is 9.4% in 2001,<ref name="Jongsuksuntigul 2003">{{cite doi|10.1016/j.actatropica.2003.01.002}}.</ref> causing about 6 million people are infected with ''Opisthorchis viverrini''.<ref name="Stripa 2007"/><ref name="Laha 2007">{{cite doi|10.1186/1471-2164-8-189}}.</ref>


''Opisthorchis viverrini'' was thought to be the only species of [[liver fluke]] in Thailand,<ref name="Harinasuta 1984">{{cite PMID|6542383}}</ref> but [[PCR]] techniques have revealed also ''[[Clonorchis sinensis]]'' in (central) Thailand in 2008.<ref name="Traub 2009">{{cite doi|10.1371/journal.pntd.0000367}}.</ref>
[[Opisthorchiasis history and symptoms|History and Symptoms]] | [[Opisthorchiasis physical examination|Physical Examination]] | [[Opisthorchiasis laboratory findings|Laboratory Findings]] | [[Opisthorchiasis imaging findings|Imaging Findings]] | [[Opisthorchiasis other diagnostic studies|Other Diagnostic Studies]]
 
Another reference from 2002 lists worldwide number of cases about 9 million (without year of estimation).<ref name="Muller 2002"/> In Thailand, about 7.3 million.<ref name="Muller 2002"/> About 50 million people are at risk of infection.<ref name="Muller 2002"/>
 
In 2005, 67.3 million of people worldwide are at risk of infection.<ref name="Keiser 2005">Keiser J. & Utzinger J. (2005). "Emerging foodborne trematodiasis". ''[[Emerging Infectious Diseases]]'' [serial on the Internet]. 2005 Oct. Available from http://www.cdc.gov/ncidod/EID/vol11no10/05-0614.htm</ref>
 
Keiser & Utzinger (2005)<ref name="Keiser 2005"/> have speculated that [[aquaculture]] development is the key risk factor for foodborne trematodiases including opisthorchiasis caused by ''Opisthorchis viverrini''.<ref name="Keiser 2005"/>
 
'''Etiologic agent:'''
 
Trematodes (flukes) Opisthorchis viverrini (Southeast Asian liver fluke) and O. felineus (cat liver fluke).
 
 
'''Life cycle:'''
 
[[Image:Opisthorchis LifeCycle.gif|left|Life cycle of Opisthorchis]]
 
The adult flukes deposit fully developed eggs that are passed in the feces '''1'''. 
 
After ingestion by a suitable snail (first intermediate host) '''2''', the eggs release miracidia '''2a''', which undergo in the snail several developmental stages (sporocysts '''2b''', rediae '''2c''', cercariae '''2d'''). 
 
Cercariae are released from the snail '''3''' and penetrate freshwater fish (second intermediate host), encysting as metacercariae in the muscles or under the scales '''4'''. 
 
The mammalian definitive host (cats, dogs, and various fish-eating mammals including humans) become infected by ingesting undercooked fish containing metacercariae. 
 
After ingestion, the metacercariae excyst in the duodenum '''5''' and ascend through the ampulla of Vater into the biliary ducts, where they attach and develop into adults, which lay eggs after 3 to 4 weeks '''6'''. 
 
The adult flukes (O. viverrini: 5 mm to 10 mm by 1 mm to 2 mm; O. felineus: 7 mm to 12 mm by 2 mm to 3 mm) reside in the biliary and pancreatic ducts of the mammalian host, where they attach to the mucosa.
<br clear="left"/>
 
== Diagnosis ==
Diagnosis is based on microscopic identification of eggs in stool specimens.  However, the eggs of Opisthorchis are practically indistinguishable from those of Clonorchis.
 
=== History and Symptoms ===
Most infections are asymptomatic.  In mild cases, manifestations include [[dyspepsia]], abdominal pain, [[diarrhea]] or [[constipation]].  With infections of longer duration, the symptoms can be more severe, and hepatomegaly and malnutrition may be present.  In rare cases, cholangitis, cholecystitis, and chlolangiocarcinoma may develop.  In addition, infections due to O. felineus may present an acute phase resembling Katayama [[fever]] ([[schistosomiasis]]), with fever, facial edema, [[lymphadenopathy]], arthralgias, rash, and [[eosinophilia]].  Chronic forms of O. felineus infections present the same manifestations as O. viverrini, with in addition involvement of the pancreatic ducts.
 
[[File:Symptoms of Raw fish infection.svg.png|thumb|Symptoms of opisthorchiasis/[[clonorchiasis]].]]
{{main|clonorchiasis}}
Symptoms of opisthorchiasis (caused by ''Opisthorchis'' spp.) are indistinguishable from [[clonorchiasis]] (caused by ''[[Clonorchis sinensis]]''),<ref name="Kingl 2001"/> so the disease should be referred as clonorchiasis.<ref name="Kingl 2001"/>
 
About 80% of infected people have no symptoms, though they can have [[eosinophilia]].<ref name="Muller 2002"/> This is when the infection is weak and there are less than 1000 eggs in one gram in feces.<ref name="Muller 2002"/>
 
When there are 10.000-30.000 eggs in one gram of feces, then the infection is heavy.<ref name="Muller 2002"/> Symptoms of heavier infections with ''Opisthorchis viverrini'' may include: [[diarrhoea]], pain in [[epigastric]] and pain in the upper right quadrant, lack of appetite ([[Anorexia (symptom)|anorexia]]), [[Fatigue (medical)|fatigue]], yellowing of the eyes and skin ([[jaundice]]) and mild [[fever]].<ref name="Muller 2002"/>
 
These parasites are long-lived and cause heavy chronic infections may led to accumulation of fluid in legs ([[edema]]) and in the [[peritoneal cavity]] ([[ascites]]),<ref name="Muller 2002"/> enlarged non-functional [[gall-bladder]]<ref name="Muller 2002"/> and also [[cholangitis]],<ref name="Young 2010"/> which can lead to periductal [[fibrosis]], [[cholecystitis]] and [[cholelithiasis]], obstructive [[jaundice]], [[hepatomegaly]] and/or fibrosis of the periportal system.<ref name="Young 2010"/>
 
Importantly, both experimental and epidemiological evidence strongly implicates ''Opisthorchis viverrini'' infections in the etiology of a malignant cancer of the bile ducts ([[cholangiocarcinoma]]) in humans which has a very poor prognosis.<ref name="Young 2010"/> Indeed, ''Clonorchis sinensis'' and ''Opisthorchis viverrini'' are both categorized by the [[International Agency for Research on Cancer]] (IARC) as [[List of IARC Group 1 carcinogens|Group 1 carcinogens]].<ref name="Young 2010"/>
 
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.<ref name="Young 2010"/> These conditions predispose to cholangiocarcinoma, possibly through an enhanced susceptibility of [[DNA]] to damage by [[carcinogen]]s.<ref name="Young 2010"/> Chronic hepatobiliary damage is reported to be multi-factorial and considered to arise from a continued mechanical irritation of the [[epithelium]] by the flukes present, particularly via their suckers, metabolites and excreted/secreted [[antigen]]s as well as immunopathological processes.<ref name="Young 2010"/> In regions where ''Opisthorchis viverrini'' is highly endemic, the incidence of cholangiocarcinoma is unprecedented.<ref name="Young 2010"/> For instance, cholangiocarcinomas represent 15% of primary liver cancer worldwide, but in Thailand's Khon Kaen region, this figure escalates to 90%, the highest recorded incidence of this cancer in the world.<ref name="Young 2010"/> Of all cancers worldwide from 2002, 0.02% were cholangiocarcinoma caused by ''Opisthorchis viverrini''.<ref name="Stripa 2007"/>
 
The cancer of the bile ducts caused by opisthorchiasis occur in the ages 25–44 years in Thailand.<ref name="WHO 1995"/>
 
===Laboratory Findings===
For [[medical diagnosis]] there is need to find eggs of ''Opisthorchis viverrini'' in feces<ref name="Muller 2002"/> using [[Kato technique]].<ref name="WHO 1995"/>
 
An [[antigen]] 89 kDa of ''Opisthorchis viverrini'' can be detected by [[ELISA]] test.<ref name="Muller 2002"/>
 
A [[PCR]] test capable of amplifying a segment of the internal transcribed spacer region of [[ribosomal DNA]] for the opisthorchiid and [[heterophyid]] flukes eggs taken directly from faeces was developed and evaluated in a rural community in central Thailand.<ref name="Traub 2009"/> The lowest quantity of DNA that could be amplified from individual adults of ''Opisthorchis viverrini'' was estimated to 0.6 pg.<ref name="Traub 2009"/>
 
==Prevention==
Currently, there is no effective chemotherapy to combat cholangiocarcinoma, such that intervention strategies need to rely on the [[Preventive medicine|prevention]] or treatment of liver fluke infection/disease.<ref name="Young 2010"/> Although effective prevention could be readily achieved by persuading people to consume cooked fish (via [[education program]]s), the ancient cultural custom to consume raw, undercooked or freshly pickled fish persists in endemic areas.<ref name="Young 2010"/> Cooking or deep-freezing (-20 °C for 7 days)<ref name="WHO 2004">[[World Health Organization]] (2004). ''REPORT JOINT WHO/FAO WORKSHOP ON FOOD-BORNE TREMATODE INFECTIONS IN ASIA''. Report series number: RS/2002/GE/40(VTN). 55 pp. [http://whqlibdoc.who.int/wpro/2004/RS_2002_GE_40(VTN).pdf PDF]. pages 15-17.</ref> of food made of fish is sure method of prevention.<ref name="Muller 2002"/> Methods for prevention of ''Opisthorchis viverrini'' in [[aquaculture]] fish ponds were proposed by Khamboonruang et al. (1997).<ref>{{Cite PMID|9656352}}.</ref>


==Treatment==
==Treatment==
There was unsuccessful use of [[chloroquine]] for opisthorchiasis treatment in 1951-1968.<ref name="WHO 1995"/>
Thus, currently, the control of opisthorchiasis relies predominantly on [[anthelmintic]] treatment with [[praziquantel]].<ref name="Young 2010"/> The single dose of praziquantel of 40&nbsp;mg/kg is effective against opisthorchiasis and also against [[schistosomiasis]].<ref name="WHO 1995"/> A randomised-controlled trial published in 2011 showed that the broad-spectrum anti-helminthic, tribendimidine, appears to be at least as efficacious as praziquantel.<ref>{{cite doi| 10.1016/S1473-3099(10)70250-4}}</ref>
[[Artemisinin]] was also found to have [[anthelmintic]] activity against ''Opisthorchis viverrini''.<ref>{{Cite PMID|17975411}}.</ref>


Despite the efficacy of this compound, the lack of an acquired immunity to infection predisposes humans to reinfections in endemic regions.<ref name="Young 2010"/> In addition, under experimental conditions, the short-term treatment of ''Opisthorchis viverrini''-infected [[hamster]]s with praziquantel (400&nbsp;mg per kg of live weight) has been shown to induce a dispersion of parasite antigens, resulting in adverse immunopathological changes as a result of oxidative and nitrative stresses following re-infection with ''Opisthorchis viverrini'', a process which has been proposed to initiate and/or promote the development of cholangiocarcinoma in humans.<ref name="Young 2010"/>
[[Opisthorchiasis medical therapy|Medical Therapy]] | [[Opisthorchiasis prevention|Prevention]] | [[Opisthorchiasis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Opisthorchiasis future or investigational therapies|Future or Investigational Therapies]]


Given the current reliance on a single trematocidal drug against ''Opisthorchis viverrini'', there is substantial merit in searching for new intervention methods, built on a detailed understanding of the interplay between the parasites and their hosts as well as the biology of the parasites themselves at the molecular level.<ref name="Young 2010"/> Furthermore, the characterization of the genes expressed in these parasites should assist in elucidating the molecular mechanisms by which opisthorchiasis initiate and enhance the development of cholangiocarcinoma.<ref name="Young 2010"/>
==Case Studies==


==References==
[[Opisthorchiasis case study one|Case #1]]
{{Reflist|2}}


{{Helminthiases}}
{{Helminthiases}}

Revision as of 19:54, 26 November 2012

Opisthorchiasis
Classification and external resources
ICD-10 B66.0
ICD-9 121.0
DiseasesDB 29303
MeSH D009889

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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