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Clonorchis (Opisthorchis) sinensis (Pathogen – Liver Trematodes)

McConnell was the first to describe the adult worms and pathologic changes caused by C. sinensis, in a Chinese patient who died in Calcutta, India. The complete life cycle was developed in a number of publications by Iijima in 1887, Saito in 1898, Kobayashi in 1914, and Muto in 1918 (Beaver). C. sinensis is also known as the Chinese or oriental liver fluke.    



Eggs (operculated, knob at abopercular end)

                                                                                    Adult worm


Life Cycle:
Adult worms deposit eggs in the bile ducts, and the eggs are discharged with the bile fluid into the feces and passed out into the environment. The eggs are fully embryonated when laid and measure 28 to 35 μm by 12 to 19 μm. The eggs are ovoid, with a thick, pale brownish yellow shell and an operculum. There are distinct opercular shoulders surrounding the operculum. Frequently, the eggs contain a comma‑shaped appendage at the abopercular end. Eggs are ingested by the snail host, at which time the miracidium hatches to infect the snail. There are more than 100 species of snails that can serve as the second intermediate host for C. sinensis.  The snails generally live in ponds used for commercial fish raising, lakes, and slow‑moving water, and the overall infection rate is relatively low. Sporocyst and redia generations are produced before cercariae are released to encyst in the skin or flesh of freshwater fish. Humans become infected by ingesting the metacercariae in uncooked fish.
Metacercariae excyst in the duodenum, enter the common bile duct, and travel to the distal bile capillaries, where the worms mature. The life cycle takes approximately 3 months to complete in humans. Reservoir hosts include dogs, cats, pigs, mink, rats, and other fish‑eating mammals.

Humans become infected by ingesting the metacercariae in uncooked fish.

Humans, dogs, cats, and other fish‑eating mammals are reservoir hosts and, in some areas, the sole cause for continual transmission. The infection is found in China, Japan, Korea, Malaysia, Singapore, Taiwan, and Vietnam, and it is estimated that 7 million individuals are infected, with 4.7 million in China and approximately 1 million in Korea. Natives of Hawaii have also been found to harbor the infection, which was contracted through the ingestion of frozen, pickled, or dried fish imported from areas of endemicity. Human infections result from the widely prevalent practice of consumption of metacercaria‑infested freshwater fish eaten uncooked, pickled, smoked, salted, or dried. The traditional eating habits which are a part of a cultural heritage are very difficult to change. In the past few years, clonorchiasis has often been reported in the United States, Canada, France, and Australia in refugee immigrants from areas of endemic infection.

Clinical Features:
     In light infections, the patient generally experiences no symptoms. In heavier infections acquired over time, the patient may experience dull pain and abdominal discomfort that may last for 1 to 2 h, often in the afternoon. As the disease progresses, the duration of pain lengthens and the pain may become so severe that the patient is unable to work. Patients who have had the disease for a long time will have liver enlargement with some degree of functional impairment that is secondary to biliary obstruction. Acute infections caused by ingestion of large numbers of metacercariae will, within a month, cause fever, chills, diarrhea, epigastric pain, enlarged tender liver, and possibly jaundice. The acute symptoms last for about 1 month and subside at about the time when eggs are detected in the stool. In chronic infections, cholangitis, cholelithiasis, pancreatitis, and cholangiocarcinoma are common complications and can lead to death.
Cholangiocarcinoma is a malignant tumor that arises from the bile duct epithelium and is the second most prevalent liver cancer after hepatocellular carcinoma.  The tumor usually occurs in patients 60 to 80 years of age and rarely in patients younger than 40.  There appears to be no direct link between infection and carcinoma, although one of the first steps in malignant transformation may be induced by the biliary tract hyperplasia caused by the worms. Patients with primary sclerosing cholangitis (PSC) have a substantial predisposition for bile duct carcinoma.  Although the exact mechanisms are not well defined, long‑standing inflammation can lead to cholangiocarcinoma in patients with chronic C. sinensis infection.  PSC is an uncommon disease, characterized by stricturing, fibrosis, and inflammation of the biliary tree, which is closely associated with chronic inflammatory bowel disease, particularly ulcerative colitis. 
In general, the complications of clonorchiasis are the results of biliary obstruction.  As the worms mature in the distal bile ducts, an inflammatory response is seen in the biliary epithelium. The extent of pathologic changes is related to the intensity and duration of infection. The lesions are confined mainly to the biliary system and are the result of mechanical irritation and toxins produced by the worms. In light infections, there appears to be little or no change in liver parenchyma, whereas heavy infections cause thickening and localized dilations of the bile ducts with hyperplasia of the mucinous glands. As a result, the biliary tract may become obstructed, causing bile retention, infiltration of lymphocytes and eosinophils, and fibrosis. The adenomatous changes may persist for many years in patients with light infections. The infections have been associated with obstructive jaundice, which may be aggravated by biliary stones and liver abscesses. Many patients infected with C. sinensis have recurrent pyogenic cholangitis. There is no direct evidence that infection with C. sinensis causes chronic bacterial infection. Acute pancreatitis, cholecystitis, and cholelithiasis may be the result of worm invasion. Cirrhosis is probably related to malnutrition rather than parasitic infections. Computed tomographic (CT) evaluation has shown that in the presence of diffuse mild intrahepatic bile duct dilation, enlargement of the body or tail (or both) of the pancreas, with a cluster of small cystic changes within the pancreatic parenchyma, provides strong evidence of C. sinensis pancreatitis.  This infection may survive in the human host for more than 20 years.

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 fully embryonated when laid and measure 28 to 35 μm by 12 to 19 μm. The eggs are ovoid, with a thick, pale brownish yellow shell and an operculum. There are distinct opercular shoulders surrounding the operculum. Frequently, the eggs contain a comma‑shaped appendage at the abopercular end.

Laboratory Report:
Clonorchis sinensis eggs recovered

Praziquantel is the drug of choice for treatment of C. sinensis infections.  It has very few or limited side effects but is not recommended for use during pregnancy.  The recommended dose is 75 mg/kg after meals three times a day for 1 or 2 days (Medical letter).  These regimens yielded 85 and 100% cure rates, respectively.  The majority of patients do well, with the exception of those who have pyogenic cholangitis, obstructive jaundice or cholangiocarcinoma.  Albendazole may be used as an alternative drug.  Once cholangiocarcinoma is diagnosed, complete resection with negative histological margins provides the greatest chance for long-term survival.  Unfortunately, cholangiocarcinoma responds poorly to chemotherapy. 
Garcia, L.S. 2007.  Diagnostic Medical Parasitology, 5th ed., ASM Press, Washington, D.C.

The life cycle can be broken and infection can be prevented in humans by thorough cooking of all freshwater fish. Although cultural habits are difficult to change, public health education can be used to modify them. Night soil used without disinfection for fertilizer should not be applied in lakes or ponds containing susceptible snails. It has been suggested that night soil should be stored prior to use; eggs of C. sinensis die within 2 days when stored at 26°C.