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Opisthorchis viverrini (Pathogen – Liver Trematodes)

Organism:
O. viverrini has been reported to infect a significant portion of the population in northern Thailand and Laos. In some areas, the prevalence was 100% for age groups older than 10 years, and it is estimated that 10 million people are infected. Although the overall prevalence rate has been reported to be 35%, there are some areas where the rate is greater than 90%. There is an association between infection with O. viverrini and carcinoma of the bile duct epithelium (cholangiocarcinoma).

http://upload.wikimedia.org/wikipedia/commons/0/0b/Opisthorchis_viverrini_egg.png http://ruby.fgcu.edu/courses/davidb/50249/web/Opisthorchisviverrini183.jpg
Eggs (operculated, knob at abopercular end)
http://www.stanford.edu/class/humbio103/ParaSites2003/Opisthorchiasis/gphx/2.jpg http://www.nri.org/publications/pahhg_newsletter/issue_2/images/opisthorchis.jpg
Adult worm Chronic infection in liver

                                                                           

 
Life Cycle:
Adult worms in distal bile ducts produce eggs that are carried by the bile to the intestinal lumen and to the outside environment in the feces. The eggs are brownish yellow, oval, and operculated; have opercular shoulders; and may have a comma‑shaped appendage at the abopercular end. The egg size averages 27 by 15 μm. The life cycle is similar to that of C. sinensis, requiring developmental periods in susceptible snails and finally in freshwater fish, in which the metacercariae encyst. Metacercariae excyst in the duodenum of the mammalian host and migrate to the intrahepatic bile ducts, where they develop to mature adults. The adult worms are transparent and leaf‑shaped and measure approximately 8 to 12 mm long.  The length‑to‑width ratio is similar to that seen with C. sinensis; therefore, the two can be confused.  The life span of O. viverrini can exceed 20 years.

Acquired:
Humans become infected by ingesting the metacercariae in uncooked fish.

Epidemiology:
Public health education should be used to advise the at‑risk population in areas of endemicity about the hazards of eating uncooked fish. This approach has not met with much success because of the difficulty in disrupting established cultural and dietary traditions. Also, defecation in or near ponds or lakes should be prevented, as should the application of night soil where the intermediate hosts are abundant. Community‑based therapy of opisthorchiasis will significantly decrease the prevalence of infection; however, therapy alone will not solve the problem because of the high rates of reinfection due to cultural habits. Mass treatment can be undertaken with praziquantel as a single dose of 40 to 50 mg/kg at bedtime.

Clinical Features:
     As with C. sinensis, the pathologic changes are confined mainly to the biliary tract system and morbidity is significantly associated with the worm burden of the host.  Intensity of infection is correlated with clinical signs of abdominal pain, flatulence, weakness, hepatomegaly, cholangitis, chronic cholecystitis, cholelithiasis, and obstructive jaundice.  Patients with heavy worm burdens may have severe cirrhosis, ascites, pedal edema, and acute abdominal pain.  There may be severe jaundice, secondary infection of the biliary system (as seen with C. sinensis), cholangitis, and hepatomegaly.  The bilirubin transaminase is tends to be elevated, while the serum albumin is low.
 A large number of individuals with O. viverrini infection have cholangiocarcinomas, which were also seen at autopsy. The biliary epithelium may be highly susceptible to malignant transformation because of chronic proliferation due to O. viverrini infection. There is a significant relationship between the intensity of infection and cholangiocarcinoma and a high prevalence of the disease among males. There is a definite relationship between a high risk of liver cancer and infestation with O. viverrini in northeastern Thailand.   However, in other areas of the country where liver cancer is high, there is little to no exposure to O. viverrini infection.  Case‑control studies suggest that exposure to exogenous and possibly endogenous nitrosamines in food or tobacco in betel nut cigarettes may play a role in the development of hepatocellular carcinoma, while infestation with O. viverrini and chemical interaction of nitrosamines may also be etiologic factors in the development of cholangiocarcinoma.  Carcinomas of the biliary tract are rare cancers developing from the epithelial or blast‑like cells lining the bile ducts.  A variety of known predisposing factors, including infection with the liver fluke O. viverrini have been identified.  Chronic inflammatory processes, generation of active oxygen radicals, altered cellular detoxification mechanisms, activation of oncogenes, functional loss of tumor suppressor genes, and dysregulation of cell proliferation and apoptotic mechanisms have been identified as important contributors to the development of cholangiocarcinomas.  Approximately 20,000 worms have been recovered from a single individual at autopsy.

Clinical Specimen:
Stool:  Confirmation of the infection depends on finding the small, operculated eggs in a routine stool examination; multiple stool examination may be required to find the eggs.

Laboratory Diagnosis:
Stool:  The routine sedimentation concentration is recommended.  Since the eggs are operculated they cannot be recovered from the zinc sulfate flotation method.  The eggs of C. sinensis and O. viverrini are similar in size and shape to those of Heterophyes heterophyes and Metagonimus yokogawai and cannot be readily differentiated from them. If a patient has not resided in or recently visited areas where infections are endemic, the infection is probably due to C. sinensis or O. viverrini. The infection may be confirmed by detecting eggs in the bile fluid (duodenal aspirate), by recovering adult worms, or from the clinical history. Some strains of C. sinensis produce eggs that have a comma‑shaped appendage at the abopercular end. Multiple egg measurements are usually required to determine size differences; however, absolute identification among the small trematode eggs can be very difficult.  Eggs can also be seen in duodenal drainage material or, if the Enterotest capsule is used, in the mucus removed from the string.  Definitive identification usually requires examination of adult worms recovered after therapy or during surgery or autopsy.
In patients with biliary obstruction, eggs will not be found in the stool specimens; needle aspiration, surgery, or autopsy specimens may be required to confirm their presence.  In these patients, biliary obstruction must be differentiated from enlarged gallbladder, cholangitis with jaundice, liver carcinoma, and cholangiocarcinoma.  Cholangiography, ultrasonography, and liver scans may reveal lesions consistent with liver fluke infection.
In general, immunologic procedures are not readily available; however, they have been developed and have been used in the research setting.  A multiplex PCR approach has proven to be species-specific, sensitive and a rapid method for the accurate diagnosis of clonorchiasis and/or opisthorchiasis.  This test can be used for the detection of metacercariae in infected fish or adult worms or eggs from patients in endemic areas.

Organism Description:
Egg:  The eggs are brownish yellow, oval, and operculated; have opercular shoulders; and may have a comma‑shaped appendage at the abopercular end. The egg size averages 27 by 15 μm. Frequently, the eggs contain a comma‑shaped appendage at the abopercular end.  Eggs of O. viverrini can resemble those of many other intestinal and liver trematodes.

Laboratory Report:
Opisthorchis typeeggs recovered

Treatment:
In patients with asymptomatic and mild to moderate cases, 75 mg of praziquantel per kg given three times after meals in a single day or a single dose of 40 mg/kg has been reported to be 100 and 90% effective, respectively (Med Letter).  In those with heavy infections, a single dose of 50 mg/kg produces a cure rate of 97%. No eggs are recovered in the stool after about a week; however, clinical symptoms and gallbladder dysfunction may take several months to resolve.  Any side effects can be minimized by administration of the single‑dose regimen at bedtime.
 Mebendazole has also been given at 30 mg/kg/day for 3 or 4 weeks, with cure rates of 89 and 94% respectively.  No adult worms were recovered after therapy.
It is important to remember that only 5% to 10% of cases are relieved with praziquantel alone and that relapsing cholangitis and obstructive jaundice may require the use of antimicrobials.  In complicated cases, surgery may also be required.  Unfortunately, cholangiocarcinoma associated with O. viverrini infection carries a poor prognosis.
Garcia, L.S. 2007.  Diagnostic Medical Parasitology, 5th ed., ASM Press, Washington, D.C.

Control:
Public health education should be used to advise the at‑risk population in areas of endemicity about the hazards of eating uncooked fish. This approach has not met with much success because of the difficulty in disrupting established cultural and dietary traditions. Also, defecation in or near ponds or lakes should be prevented, as should the application of night soil where the intermediate hosts are abundant. Community‑based therapy of opisthorchiasis will significantly decrease the prevalence of infection; however, therapy alone will not solve the problem because of the high rates of reinfection due to cultural habits. Mass treatment can be undertaken with praziquantel as a single dose of 40 to 50 mg/kg at bedtime.