Opisthorchiasis
Encyclopedia
Opisthorchiasis is an 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 or $120 million per year can cost Northeast Thailand only.
Infection of Opisthorchis viverrini and of other liver flukes in Asia affect the poor and poorest people
. Opisthorchiasis have received less attention in comparison of other diseases and it is a neglected disease in Asia.
fishes are a staple of the diet of humans. The prevalence
of human infection can be as high as 70% in some regions, for example in Khon Kaen Province
in Thailand. The parasite establishes in the bile duct
s of the liver as well as extrahepatic ducts and the gall bladder of the mammalian (definitive) host.
Children under the age of 5 are rarely infected by Opisthorchis viverrini.
In the Lao People's Democratic Republic, the prevalence of opisthorchiasis was:
In Thailand, the prevalence of opisthorchiasis was:
Opisthorchis viverrini was thought to be the only species of liver fluke
in Thailand, but PCR techniques have revealed also Clonorchis sinensis
in (central) Thailand in 2008.
Another reference from 2002 lists worldwide number of cases about 9 million (without year of estimation). In Thailand, about 7.3 million. About 50 million people are at risk of infection.
In 2005, 67.3 million of people worldwide are at risk of infection.
Keiser & Utzinger (2005) have speculated that aquaculture
development is the key risk factor for foodborne trematodiases including opisthorchiasis caused by Opisthorchis viverrini.
(caused by Clonorchis sinensis
), so the disease should be referred as clonorchiasis.
About 80% of infected people have no symptoms, though they can have eosinophilia
. This is when the infection is weak and there are less than 1000 eggs in one gram in feces.
When there are 10.000-30.000 eggs in one gram of feces, then the infection is heavy. Symptoms of heavier infections with Opisthorchis viverrini may include: diarrhoea, pain in epigastric and pain in the upper right quadrant, lack of appetite (anorexia
), fatigue, yellowing of the eyes and skin (jaundice
) and mild fever
.
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
), enlarged non-functional gall-bladder and also cholangitis, which can lead to periductal fibrosis
, cholecystitis
and cholelithiasis, obstructive jaundice
, hepatomegaly
and/or fibrosis of the periportal system.
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. Indeed, Clonorchis sinensis and Opisthorchis viverrini are both categorized by the International Agency for Research on Cancer
(IARC) as Group 1 carcinogens.
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 carcinogen
s. 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. In regions where Opisthorchis viverrini is highly endemic, the incidence of cholangiocarcinoma is unprecedented. 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. Of all cancers worldwide from 2002, 0.02% were cholangiocarcinoma caused by Opisthorchis viverrini.
The cancer of the bile ducts caused by opisthorchiasis occur in the ages 25–44 years in Thailand.
there is need to find eggs of Opisthorchis viverrini in feces using Kato technique
.
An antigen
89 kDa of Opisthorchis viverrini can be detected by ELISA
test.
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. The lowest quantity of DNA that could be amplified from individual adults of Opisthorchis viverrini was estimated to 0.6 pg.
or treatment of liver fluke infection/disease. Although effective prevention could be readily achieved by persuading people to consume cooked fish (via education programs), the ancient cultural custom to consume raw, undercooked or freshly pickled fish persists in endemic areas. Cooking or deep-freezing (-20 °C for 7 days) of food made of fish is sure method of prevention. Methods for prevention of Opisthorchis viverrini in aquaculture
fish ponds were proposed by Khamboonruang et al. (1997).
for opisthorchiasis treatment in 1951-1968.
Thus, currently, the control of opisthorchiasis relies predominantly on anthelmintic
treatment with praziquantel
. The single dose of praziquantel of 40 mg/kg is effective against opisthorchiasis and also against schistosomiasis
. A randomised-controlled trial published in 2011 showed that the broad-spectrum anti-helminthic, tribendimidine, appears to be at least as efficacious as praziquantel.
Artemisinin
was also found to have anthelmintic
activity against Opisthorchis viverrini.
Despite the efficacy of this compound, the lack of an acquired immunity to infection predisposes humans to reinfections in endemic regions. In addition, under experimental conditions, the short-term treatment of Opisthorchis viverrini-infected hamster
s with praziquantel (400 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.
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. 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.
Opisthorchis
Opisthorchis is a genus of flukes in the family Opisthorchiidae.-Species:Species in the genus Opisthorchis include:* Opisthorchis felineus * Opisthorchis gomtii Mehra, 1941* Opisthorchis parasiluri Long & Lee...
(specifically, Opisthorchis viverrini
Opisthorchis viverrini
Opisthorchis viverrini, common name Southeast Asian liver fluke, is a trematode parasite from the family Opisthorchiidae that attacks the area of the bile duct. Infection is acquired when people ingest raw or undercooked fish. It causes the disease opisthorchiasis...
and Opisthorchis felineus
Opisthorchis felineus
Opisthorchis felineus, or cat liver fluke is a trematode parasite that infects the liver in mammals. It was first discovered in 1884 in a cat's liver by Sebastiano Rivolta of Italy. In 1891, Russian scientist K.N. Vinogradov found it in a human, and named the parasite a "Siberian liver fluke"...
).
Medical care and loss of wage
Wage
A wage is a compensation, usually financial, received by workers in exchange for their labor.Compensation in terms of wages is given to workers and compensation in terms of salary is given to employees...
s caused by Opisthorchis viverrini in Laos and in Thailand costs about $120 million annually or $120 million per year can cost Northeast Thailand only.
Infection of Opisthorchis viverrini and of other liver flukes in Asia affect the poor and poorest people
Poverty
Poverty is the lack of a certain amount of material possessions or money. Absolute poverty or destitution is inability to afford basic human needs, which commonly includes clean and fresh water, nutrition, health care, education, clothing and shelter. About 1.7 billion people are estimated to live...
. Opisthorchiasis have received less attention in comparison of other diseases and it is a neglected disease in Asia.
Prevalence
Opisthorchiasis is prevalent in geographical regions where raw cyprinidCyprinid
The family Cyprinidae, from the Ancient Greek kyprînos , consists of the carps, the true minnows, and their relatives . Commonly called the carp family or the minnow family, its members are also known as cyprinids...
fishes are a staple of the diet of humans. The prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
of human infection can be as high as 70% in some regions, for example in Khon Kaen Province
Khon Kaen Province
-History:The first city of the area was established in 1783 when Rajakruluang settled there with 330 people. King Rama I made Rajakruluang the first governor of the area when establishing tighter connections with the Isan area. The main city was moved six times until in 1879 it reached its modern...
in Thailand. The parasite establishes in the bile duct
Bile duct
A bile duct is any of a number of long tube-like structures that carry bile.Bile, required for the digestion of food, is excreted by the liver into passages that carry bile toward the hepatic duct, which joins with the cystic duct to form the common bile duct, which opens into the intestine.The...
s of the liver as well as extrahepatic ducts and the gall bladder of the mammalian (definitive) host.
Children under the age of 5 are rarely infected by Opisthorchis viverrini.
In the Lao People's Democratic Republic, the prevalence of opisthorchiasis was:
- 40% in 1992 causing about 1 744 000 people infected
In Thailand, the prevalence of opisthorchiasis was:
- scaterred reports by Verdun & Bruyant (1908), Leiper (1911), Prommas (1927), Bedier & Chesneau (1929)
- The national control programme have started in Thailand in 1950.
- 25% in 1953 causing about 2 million infected people. The first widespread report of opisthorchiasis in Thailand was in 1953.
- 1965: over 3.5 millions infected people
- 14% in 1980-1981 causing about 7 million infected people.
- 63.6% in 1984-1987, but another WHOWhoWho may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...
report mention prevalence 35% in Nort-east Thailand for 1984. - 35.6% in 1988
- 30% in 1989
- The decline of opisthorchiasis was caused by opisthorchiasis control programme, that includes health education including mass distributionMass distributionMass distribution is a term used in physics and mechanics and describes the spatial distribution of mass within a solid body. In principle, it is relevant also for gases or liquids, but on earth their mass distribution is almost homogeneous.-Astronomy:...
of cooking pots and using praziquantelPraziquantelPraziquantel is an anthelmintic effective against flatworms. Praziquantel is not licensed for use in humans in the UK; it is, however, available as a veterinary anthelmintic, and is available for use in humans on a named-patient basis....
, that was available since 1984. - 15.2% in 1991 causing 7 million infected people. About 45 million people were at risk of infection. 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.
- 12% in 1996
- In 1992-1996 the National Public Health Development Plan used the strategy by the Faculty of Tropical Medicine, Mahidol UniversityMahidol UniversityMahidol University is a public research university in Bangkok, Thailand. Established back in 1888 as School of Medical Practitioners, Siriraj Hospital and reorganized in 1943 as University of Medical Sciences . The university originally focused on Health Sciences but also expanded to other...
against opisthorchiasis. - 7% in 2000
- 9.4% in 2001 In Thailand, the prevalence of opisthorchiasis is 9.4 % in 2001, causing about 6 million people are infected with Opisthorchis viverrini.
Opisthorchis viverrini was thought to be the only species of liver fluke
Liver fluke
Liver flukes are a polyphyletic group of trematodes .Adults of liver flukes are localized in the liver of various mammals, including humans. These flatworms can occur in bile ducts, gallbladder, and liver parenchyma. They feed on blood...
in Thailand, but PCR techniques have revealed also Clonorchis sinensis
Clonorchis sinensis
Clonorchis sinensis, the Chinese liver fluke, is a human liver fluke in the class Trematoda, Phylum Platyhelminthes. This parasite lives in the liver of humans, and is found mainly in the common bile duct and gall bladder, feeding on bile...
in (central) Thailand in 2008.
Another reference from 2002 lists worldwide number of cases about 9 million (without year of estimation). In Thailand, about 7.3 million. About 50 million people are at risk of infection.
In 2005, 67.3 million of people worldwide are at risk of infection.
Keiser & Utzinger (2005) have speculated that aquaculture
Aquaculture
Aquaculture, also known as aquafarming, is the farming of aquatic organisms such as fish, crustaceans, molluscs and aquatic plants. Aquaculture involves cultivating freshwater and saltwater populations under controlled conditions, and can be contrasted with commercial fishing, which is the...
development is the key risk factor for foodborne trematodiases including opisthorchiasis caused by Opisthorchis viverrini.
Symptoms
Symptoms of opisthorchiasis (caused by Opisthorchis spp.) are indistinguishable from clonorchiasisClonorchiasis
Clonorchiasis is an infectious disease caused by the Chinese liver fluke, Clonorchis sinensis.Clonorchiasis is a known risk factor for the development of cholangiocarcinoma, a neoplasm of the biliary system....
(caused by Clonorchis sinensis
Clonorchis sinensis
Clonorchis sinensis, the Chinese liver fluke, is a human liver fluke in the class Trematoda, Phylum Platyhelminthes. This parasite lives in the liver of humans, and is found mainly in the common bile duct and gall bladder, feeding on bile...
), so the disease should be referred as clonorchiasis.
About 80% of infected people have no symptoms, though they can have eosinophilia
Eosinophilia
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...
. This is when the infection is weak and there are less than 1000 eggs in one gram in feces.
When there are 10.000-30.000 eggs in one gram of feces, then the infection is heavy. Symptoms of heavier infections with Opisthorchis viverrini may include: diarrhoea, pain in epigastric and pain in the upper right quadrant, lack of appetite (anorexia
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
), fatigue, yellowing of the eyes and skin (jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
) and mild fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
.
These parasites are long-lived and cause heavy chronic infections may led to accumulation of fluid in legs (edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
) and in the peritoneal cavity
Peritoneal cavity
The peritoneal cavity is a potential space between the parietal peritoneum and visceral peritoneum, that is, the two membranes that separate the organs in the abdominal cavity from the abdominal wall...
(ascites
Ascites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
), enlarged non-functional gall-bladder and also cholangitis, which can lead to periductal fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
, cholecystitis
Cholecystitis
-Signs and symptoms:Cholecystitis usually presents as a pain in the right upper quadrant. This is known as biliary colic. This is initially intermittent, but later usually presents as a constant, severe pain. During the initial stages, the pain may be felt in an area totally separate from the site...
and cholelithiasis, obstructive jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, hepatomegaly
Hepatomegaly
Hepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...
and/or fibrosis of the periportal system.
Importantly, both experimental and epidemiological evidence strongly implicates Opisthorchis viverrini infections in the etiology of a malignant cancer of the bile ducts (cholangiocarcinoma
Cholangiocarcinoma
Cholangiocarcinoma is a cancer of the bile ducts which drain bile from the liver into the small intestine. Other biliary tract cancers include pancreatic cancer, gallbladder cancer, and cancer of the ampulla of Vater...
) in humans which has a very poor prognosis. Indeed, Clonorchis sinensis and Opisthorchis viverrini are both categorized by the International Agency for Research on Cancer
International Agency for Research on Cancer
The International Agency for Research on Cancer is an intergovernmental agency forming part of the World Health Organisation of the United Nations....
(IARC) as Group 1 carcinogens.
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
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
to damage by carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
s. Chronic hepatobiliary damage is reported to be multi-factorial and considered to arise from a continued mechanical irritation of the epithelium
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
by the flukes present, particularly via their suckers, metabolites and excreted/secreted antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s as well as immunopathological processes. In regions where Opisthorchis viverrini is highly endemic, the incidence of cholangiocarcinoma is unprecedented. 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. Of all cancers worldwide from 2002, 0.02% were cholangiocarcinoma caused by Opisthorchis viverrini.
The cancer of the bile ducts caused by opisthorchiasis occur in the ages 25–44 years in Thailand.
Diagnosis
For medical diagnosisMedical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
there is need to find eggs of Opisthorchis viverrini in feces using Kato technique
Kato technique
The Kato technique is a laboratory method for preparing human stool samples prior to searching for parasite eggs.- Indications :...
.
An antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
89 kDa of Opisthorchis viverrini can be detected by ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...
test.
A PCR test capable of amplifying a segment of the internal transcribed spacer region of ribosomal DNA
Ribosomal DNA
Ribosomal DNA codes for ribosomal RNA. The ribosome is an intracellular macromolecule that produces proteins or polypeptide chains. The ribosome itself consists of a composite of proteins and RNA. As shown in the figure, rDNA consists of a tandem repeat of a unit segment, an operon, composed of...
for the opisthorchiid and heterophyid flukes eggs taken directly from faeces was developed and evaluated in a rural community in central Thailand. The lowest quantity of DNA that could be amplified from individual adults of Opisthorchis viverrini was estimated to 0.6 pg.
Prevention
Currently, there is no effective chemotherapy to combat cholangiocarcinoma, such that intervention strategies need to rely on the preventionPreventive medicine
Preventive medicine or preventive care refers to measures taken to prevent diseases, rather than curing them or treating their symptoms...
or treatment of liver fluke infection/disease. Although effective prevention could be readily achieved by persuading people to consume cooked fish (via education programs), the ancient cultural custom to consume raw, undercooked or freshly pickled fish persists in endemic areas. Cooking or deep-freezing (-20 °C for 7 days) of food made of fish is sure method of prevention. Methods for prevention of Opisthorchis viverrini in aquaculture
Aquaculture
Aquaculture, also known as aquafarming, is the farming of aquatic organisms such as fish, crustaceans, molluscs and aquatic plants. Aquaculture involves cultivating freshwater and saltwater populations under controlled conditions, and can be contrasted with commercial fishing, which is the...
fish ponds were proposed by Khamboonruang et al. (1997).
Treatment
There was unsuccessful use of chloroquineChloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...
for opisthorchiasis treatment in 1951-1968.
Thus, currently, the control of opisthorchiasis relies predominantly on anthelmintic
Anthelmintic
Anthelmintics or antihelminthics are drugs that expel parasitic worms from the body, by either stunning or killing them. They may also be called vermifuges or vermicides .-Pharmaceutical classes:...
treatment with praziquantel
Praziquantel
Praziquantel is an anthelmintic effective against flatworms. Praziquantel is not licensed for use in humans in the UK; it is, however, available as a veterinary anthelmintic, and is available for use in humans on a named-patient basis....
. The single dose of praziquantel of 40 mg/kg is effective against opisthorchiasis and also against schistosomiasis
Schistosomiasis
Schistosomiasis is a parasitic disease caused by several species of trematodes , a parasitic worm of the genus Schistosoma. Snails often act as an intermediary agent for the infectious diseases until a new human host is found...
. A randomised-controlled trial published in 2011 showed that the broad-spectrum anti-helminthic, tribendimidine, appears to be at least as efficacious as praziquantel.
Artemisinin
Artemisinin
Artemisinin , also known as Qinghaosu , and its derivatives are a group of drugs that possess the most rapid action of all current drugs against falciparum malaria. Treatments containing an artemisinin derivative are now standard treatment worldwide for falciparum malaria...
was also found to have anthelmintic
Anthelmintic
Anthelmintics or antihelminthics are drugs that expel parasitic worms from the body, by either stunning or killing them. They may also be called vermifuges or vermicides .-Pharmaceutical classes:...
activity against Opisthorchis viverrini.
Despite the efficacy of this compound, the lack of an acquired immunity to infection predisposes humans to reinfections in endemic regions. In addition, under experimental conditions, the short-term treatment of Opisthorchis viverrini-infected hamster
Hamster
Hamsters are rodents belonging to the subfamily Cricetinae. The subfamily contains about 25 species, classified in six or seven genera....
s with praziquantel (400 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.
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. 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.