opisthorchiasis

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Opisthorchiasis is a parasitic disease caused by certain species of genus Opisthorchis (specifically, Opisthorchis viverrini and Opisthorchis felineus). Chronic infection may lead to cholangiocarcinoma, a cancer of the bile ducts.

Medical care and loss of wages caused by Opisthorchis viverrini in Laos and in Thailand costs about $120 million annually.Muller R. & Wakelin D. (2002). Worms and human disease. CABI. [https://books.google.com/books?id=bWtCMIGF_FMC&dq=Opisthorchis%20viverrini%20Stiles%20%26%20Hassal%2C%201896&pg=PA43 page 43]-44. In Asia, infection by Opisthorchis viverrini and other liver flukes affects the poorest people. Along with other foodborne trematode infections such as clonorchiasis, fascioliasis and paragonimiasis,{{cite web |title=Foodborne trematode infections |url=https://www.who.int/foodborne_trematode_infections/en/ |publisher=WHO |access-date=5 September 2018}} opisthorchiasis is listed among the World Health Organization's list of neglected tropical diseases.{{Cite journal | last1 = Sripa | first1 = B. | editor1-last = Loukas | editor1-first = Alex | title = Concerted Action is Needed to Tackle Liver Fluke Infections in Asia | doi = 10.1371/journal.pntd.0000232 | journal = PLOS Neglected Tropical Diseases | volume = 2 | issue = 5 | pages = e232 | year = 2008 | pmid = 18509525| pmc =2386259 | doi-access = free }}.

Signs and symptoms

File:Symptoms of Raw fish infection.svg]]

Symptoms of opisthorchiasis are indistinguishable from clonorchiasis.{{Cite journal | last1 = King | first1 = S. | last2 = Scholz | first2 = T. Š. | doi = 10.3347/kjp.2001.39.3.209 | title = Trematodes of the family Opisthorchiidae: A minireview | journal = The Korean Journal of Parasitology | volume = 39 | issue = 3 | pages = 209–221 | year = 2001 | pmid = 11590910| pmc =2721069 }} About 80% of infected people have no symptoms, though they can have eosinophilia. Asymptomatic infection can occur when there are less than 1000 eggs in one gram of feces. Infection is considered heavy when there are 10,000-30,000 eggs in one gram of feces. Symptoms of heavier infections may include diarrhea, epigastric and right upper quadrant pain, lack of appetite, fatigue, yellowing of the eyes and skin and mild fever.

These parasites are long-lived and cause heavy chronic infections that may lead to accumulation of fluid in the legs (edema) and in the peritoneal cavity (ascites), enlarged non-functional gallbladder and also ascending cholangitis, which can lead to periductal fibrosis, cholecystitis and cholelithiasis, obstructive jaundice, hepatomegaly and/or portal hypertension.{{citation needed|date=July 2020}}

=Chronic opisthorchiasis and cholangiocarcinoma=

File:Incidence of CCA and O. viverrini in Thailand from 1990–2001-french.svgBoth 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.{{cite journal|last1=Sripa|first1=B|last2=Kaewkes|first2=S|last3=Sithithaworn|first3=P|last4=Mairiang|first4=E|last5=Laha|first5=T|last6=Smout|first6=M|last7=Pairojkul|first7=C|last8=Bhudhisawasdi|first8=V|last9=Tesana|first9=S|last10=Thinkamrop|first10=B|last11=Bethony|first11=JM|last12=Loukas|first12=A|last13=Brindley|first13=PJ|title=Liver fluke induces cholangiocarcinoma.|journal=PLOS Medicine|date=July 2007|volume=4|issue=7|pages=e201|pmid=17622191|doi=10.1371/journal.pmed.0040201|pmc=1913093|doi-access=free}} {{open access}} Clonorchis sinensis and Opisthorchis viverrini are both categorized by the International Agency for Research on Cancer (IARC) as Group 1 carcinogens.{{cite web|title=IARC Monographs on the Evaluation of Carcinogenic Risks to Humans|url=http://monographs.iarc.fr/index.php|website=monographs.iarc.fr|access-date=17 July 2017}}

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. These conditions predispose to cholangiocarcinoma, possibly through an enhanced susceptibility of DNA to damage by carcinogens. 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 antigens as well as immunopathological processes. In silico analyses using techniques of genomics and bioinformatics is unraveling information on molecular mechanisms that may be relevant to the development of cholangiocarcinoma.

In regions where Opisthorchis viverrini is highly endemic, the incidence of cholangiocarcinoma is unprecedented. For instance, cholangiocarcinoma represents 15% of primary liver cancer worldwide, but in Thailand's Khon 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 by Opisthorchis viverrini. Cancer of the bile ducts caused by opisthorchiasis occurs in the ages 25–44 years in Thailand. A few cases have appeared in later life among U.S. veterans of the Vietnam War, who consumed poorly cooked fish from streams in endemic areas near the border of Laos and Vietnam.{{cite news|title=Still Fighting: Vietnam Vets Seek Help for Rare Cancer|url=https://www.nytimes.com/aponline/2016/11/11/us/ap-us-vietnam-vets-liver-flukes-abridged.html?_r=0|access-date=19 November 2016|work=The New York Times|date=11 November 2016}}

Diagnosis

The medical diagnosis is usually established by finding eggs of Opisthorchis viverrini in feces using the Kato technique.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.

Alternatively, an antigen of Opisthorchis viverrini can be detected by ELISA test. A polymerase chain reaction test that can be performed on faeces has been developed and evaluated in a rural community in central Thailand.{{Cite journal | last1 = Traub | first1 = R. J. | last2 = MacAranas | first2 = J. | last3 = Mungthin | first3 = M. | last4 = Leelayoova | first4 = S. | last5 = Cribb | first5 = T. | last6 = Murrell | first6 = K. D. | last7 = Thompson | first7 = R. C. A. | editor1-last = Sripa | editor1-first = Banchob | title = A New PCR-Based Approach Indicates the Range of Clonorchis sinensis Now Extends to Central Thailand | doi = 10.1371/journal.pntd.0000367 | journal = PLOS Neglected Tropical Diseases | volume = 3 | issue = 1 | pages = e367 | year = 2009 | pmid = 19156191| pmc =2614470 | doi-access = free }}.

Prevention

Cholangiocarcinoma is typically incurable at diagnosis.{{Cite journal |last1=Zhang |first1=Tan |last2=Zhang |first2=Sina |last3=Jin |first3=Chen |last4=Lin |first4=Zixia |last5=Deng |first5=Tuo |last6=Xie |first6=Xiaozai |last7=Deng |first7=Liming |last8=Li |first8=Xueyan |last9=Ma |first9=Jun |last10=Ding |first10=Xiwei |last11=Liu |first11=Yaming |last12=Shan |first12=Yunfeng |last13=Yu |first13=Zhengping |last14=Wang |first14=Yi |last15=Chen |first15=Gang |display-authors=3 |year=2021 |title=A Predictive Model Based on the Gut Microbiota Improves the Diagnostic Effect in Patients with Cholangiocarcinoma |journal=Frontiers in Cellular and Infection Microbiology |volume=11 |page=751795 |doi=10.3389/fcimb.2021.751795 |pmc=8650695 |pmid=34888258 |doi-access=free |last16=Li |first16=Jialiang}}{{cite web |title=Bile Duct Cancer (Cholangiocarcinoma) Treatment |url=https://www.cancer.gov/types/liver/hp/bile-duct-treatment-pdq#section/all |website=National Cancer Institute |access-date=29 May 2021 |date=23 September 2020}} Because of this, intervention strategies are focused on the prevention 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 the Integrated Opisthorchiasis Control Program, has achieved success in the Lawa Lakes region south of Khon Kaen.{{cite web|last1=Head|first1=Jonathan|title=Deadly dish: the dinner that can give you cancer|url=https://www.bbc.com/news/health-33095945|website=BBC News|access-date=20 November 2016|date=13 June 2015}}

Cooking or deep-freezing (-20 °C for 7 days)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. [https://web.archive.org/web/20050802104259/http://whqlibdoc.who.int/wpro/2004/RS_2002_GE_40(VTN).pdf PDF]. pages 15-17. of food made of fish is an effective method of prevention. Methods for prevention of Opisthorchis viverrini in aquaculture fish ponds have also been proposed.{{Cite journal | last1 = Khamboonruang | first1 = C. | last2 = Keawvichit | first2 = R. | last3 = Wongworapat | first3 = K. | last4 = Suwanrangsi | first4 = S. | last5 = Hongpromyart | first5 = M. | last6 = Sukhawat | first6 = K. | last7 = Tonguthai | first7 = K. | last8 = Lima Dos Santos | first8 = C. A. | title = Application of hazard analysis critical control point (HACCP) as a possible control measure for Opisthorchis viverrini infection in cultured carp (Puntius gonionotus) | journal = The Southeast Asian Journal of Tropical Medicine and Public Health | volume = 28 | pages = 65–72 | year = 1997 | issue = Suppl 1 | pmid = 9656352}}.

Treatment

Treatment of opisthorchiasis is usually accomplished with praziquantel. A single dose of praziquantel of 40 mg/kg is effective against opisthorchiasis (and also against schistosomiasis). 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 of Opisthorchis viverrini-infected hamsters with praziquantel induced a dispersion of parasite antigens, resulting in adverse immunopathological changes following re-infection with Opisthorchis viverrini, a process which has been proposed to initiate and/or promote the development of cholangiocarcinoma in humans.{{cite journal |last1=Young|first1=ND |last2=Campbell|first2=BE |last3=Hall|first3=RS |last4=Jex|first4=AR |last5=Cantacessi|first5=C |last6=Laha|first6=T |last7=Sohn|first7=WM |last8=Sripa|first8=B |last9=Loukas|first9=A |last10=Brindley|first10=PJ |last11=Gasser|first11=RB |title=Unlocking the transcriptomes of two carcinogenic parasites, Clonorchis sinensis and Opisthorchis viverrini |journal=PLOS Neglected Tropical Diseases |date=22 June 2010 |volume=4|issue=6|pages=e719|pmid=20582164|doi=10.1371/journal.pntd.0000719|pmc=2889816 |doi-access=free }} {{open access}} Albendazole can be used as an alternative.{{Cite web|url=https://www.cdc.gov/dpdx/opisthorchiasis/tx.html|title=Opisthorchiasis - Treatment Information|website=CDC - DPDx|date=2013-11-29|access-date=2015-09-07}}

A randomized controlled trial published in 2011 showed that tribendimidine, a broad-spectrum anthelmintic, appears to be at least as efficacious as praziquantel.{{Cite journal | last1 = Soukhathammavong | first1 = P. | last2 = Odermatt | first2 = P. | last3 = Sayasone | first3 = S. | last4 = Vonghachack | first4 = Y. | last5 = Vounatsou | first5 = P. | last6 = Hatz | first6 = C. | last7 = Akkhavong | first7 = K. | last8 = Keiser | first8 = J. | doi = 10.1016/S1473-3099(10)70250-4 | title = Efficacy and safety of mefloquine, artesunate, mefloquine–artesunate, tribendimidine, and praziquantel in patients with Opisthorchis viverrini: A randomised, exploratory, open-label, phase 2 trial | journal = The Lancet Infectious Diseases | volume = 11 | issue = 2 | pages = 110–118 | year = 2011 | pmid = 21111681| url = https://edoc.unibas.ch/22124/1/20170913102834_59b8ec3290166.pdf }} Artemisinin was also found to have anthelmintic activity against Opisthorchis viverrini.{{Cite journal | last1 = Keiser | first1 = J. | last2 = Utzinger | first2 = J. R. | s2cid = 34591129 | doi = 10.1097/QCO.0b013e3282f19ec4 | title = Artemisinins and synthetic trioxolanes in the treatment of helminth infections | journal = Current Opinion in Infectious Diseases | volume = 20 | issue = 6 | pages = 605–612 | year = 2007 | pmid = 17975411 }}.

Epidemiology

Opisthorchiasis is prevalent where raw cyprinid fishes are a staple of the diet.{{cite journal|last1=Sithithaworn|first1=P|last2=Andrews|first2=RH|last3=Nguyen|first3=VD|last4=Wongsaroj|first4=T|last5=Sinuon|first5=M|last6=Odermatt|first6=P|last7=Nawa|first7=Y|last8=Liang|first8=S|last9=Brindley|first9=PJ|last10=Sripa|first10=B|title=The current status of opisthorchiasis and clonorchiasis in the Mekong Basin.|journal=Parasitology International|date=March 2012|volume=61|issue=1|pages=10–6|pmid=21893213|doi=10.1016/j.parint.2011.08.014|pmc=3836690}} Prevalence rises with age; children under the age of 5 years are rarely infected by Opisthorchis viverrini. Males may be affected more than females.{{cite book|last1=Farrar|first1=Jeremy|last2=Hotez|first2=Peter|last3=Junghanss|first3=Thomas|last4=Kang|first4=Gagandeep|last5=Laloo|first5=David|last6=White|first6=Nicholas|title=Manson's tropical diseases.|date=2013|publisher=Saunders [Imprint]|location=Philadelphia|isbn=978-0702051012|edition=New}}{{cite journal|last1=Kaewpitoon|first1=N|last2=Kaewpitoon|first2=SJ|last3=Pengsaa|first3=P|title=Opisthorchiasis in Thailand: review and current status.|journal=World Journal of Gastroenterology|date=21 April 2008|volume=14|issue=15|pages=2297–302|pmid=18416453|doi=10.3748/wjg.14.2297|pmc=2705081|doi-access=free}} The WHO estimates that foodborne trematodiases (infection by worms or "flukes", mainly Clonorchis, Opisthorchis, Fasciola and Paragonimus species) affect 56 million people worldwide and 750 million are at risk of infection.{{cite web|title=Foodborne trematodiases|url=https://www.who.int/mediacentre/factsheets/fs368/en/|archive-url=https://web.archive.org/web/20120915003722/http://www.who.int/mediacentre/factsheets/fs368/en/|url-status=dead|archive-date=September 15, 2012|publisher=World Health Organization|access-date=26 November 2015}}{{cite journal|last1=Sripa|first1=B|last2=Kaewkes|first2=S|last3=Intapan|first3=PM|last4=Maleewong|first4=W|last5=Brindley|first5=PJ|title=Food-borne trematodiases in Southeast Asia epidemiology, pathology, clinical manifestation and control.|journal=Advances in Parasitology|date=2010|volume=72|pages=305–50|pmid=20624536|doi=10.1016/S0065-308X(10)72011-X}} 80 million people are at risk of opisthorchiasis (67 million from infection with Opisthorchis viverrini in Southeast Asia and 13 million from Opisthorchis felineus in Kazakhstan, Russia, and Ukraine).{{cite journal|last1=Keiser|first1=J|last2=Utzinger|first2=J|title=Food-borne trematobiases|journal=Clinical Microbiology Reviews|date=July 2009|volume=22|issue=3|pages=466–83|pmid=19597009|doi=10.1128/cmr.00012-09|pmc=2708390}}{{cite journal|last1=Keiser|first1=J|last2=Utzinger|first2=J|title=Emerging foodborne trematodiasis.|journal=Emerging Infectious Diseases|date=October 2005|volume=11|issue=10|pages=1507–14|pmid=16318688|doi=10.3201/eid1110.050614|pmc=3366753}} In the lower Mekong River basin, the disease is highly endemic, and more so in lowlands, 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.{{cite journal|last1=Johansen|first1=MV|last2=Sithithaworn|first2=P|last3=Bergquist|first3=R|last4=Utzinger|first4=J|title=Towards improved diagnosis of zoonotic trematode infections in Southeast Asia.|journal=Advances in Parasitology|date=2010|volume=73|pages=171–95|pmid=20627143|doi=10.1016/S0065-308X(10)73007-4|isbn=9780123815149}} 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 as Isan.{{cite journal|last1=Upatham|first1=ES|last2=Viyanant|first2=V|last3=Kurathong|first3=S|last4=Brockelman|first4=WY|last5=Menaruchi|first5=A|last6=Saowakontha|first6=S|last7=Intarakhao|first7=C|last8=Vajrasthira|first8=S|last9=Warren|first9=KS|title=Morbidity in relation to intensity of infection in Opisthorchiasis viverrini: study of a community in Khon Kaen, Thailand.|journal=The American Journal of Tropical Medicine and Hygiene|date=November 1982|volume=31|issue=6|pages=1156–63|pmid=6983303|doi=10.4269/ajtmh.1982.31.1156}} Sporadic cases have been reported from Malaysia, Singapore, and the Philippines. 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 in aquaculture.

Research

Using CRISPR 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.{{Cite web|url=https://www.bionity.com/en/news/158791/crispr-cas9-shown-to-limit-impact-of-certain-parasitic-diseases.html|title=CRISPR/Cas9 shown to limit impact of certain parasitic diseases|website=www.bionity.com|language=en|access-date=2019-01-18}}