An Illustrative Case

An example may help you understand the pathology of clonorchiasis and how it is diagosed.

CASE:

A 19-year-old Korean woman who had immigrated to the United States seven months previously was admitted presenting with nausea, vomiting (clear emesis) and right upper quadrant and epigastric pain that varied between being constant and cramping.

Upon physical examination, the patient was found to have a temperature.

Some laboratory values were elevated:
White blood cell count
Serum alanine transaminase (ALT)
Total serum bilirubin
Serum alkaline phosphatase (ALP)
Serum aspartate transaminase (AST)
Serum lipase

A soft black common bile duct stone was removed during endoscopic retrograde cholangiopancreatography, and intrahepatic ducts with areas of stricture and possible proximal dilatation were noted. Ultrasound examination revealed a dilated common bile duct and multiple, markedly dilated tubular structures in the liver. The patient was treated with praziquantel for a bile duct disorder that was probably caused by Clonorchis sinensis infection. Her gastrointestinal symptoms responded well to this treatment.

Taxonomy and Morphology

Trematodes, members of Phylum Platyhelminthes, also called flukes, cause a variety of clinical infections in humans worldwide. The parasites are named trematodes because of their conspicuous suckers, which are the organs of attachment (trematode means "pierced with holes"). All of the flukes that cause infections in humans are contained in the group called "digenetic trematodes."

Depending on their habitat in the infected host (generally a vertebrate), flukes can be classified as blood flukes, liver flukes, lung flukes, and intestinal flukes. Flukes causing most human infections are Schistosoma species (blood fluke), Paragonimus westermani (lung fluke), and Clonorchis sinensis (liver fluke). Some less clinically important flukes are Fasciola hepatica and Opisthorchis viverrini, which are liver flukes, and Fasciolopsis buski, Heterophyes heterophyes, and Metagonimus yokogawai, which are all intestinal flukes.

Features of Digenic Trematodes

• The sexes of the parasites are not separate (monecious). In other words,they are mostly hermaphroditic with the male and female reproductive organs existing complete in each fluke. One exception is the schistosomes, which are diecious.
• The flukes are oviparous and lay diagnostically operculated eggs. Once again, an exception is schistosome eggs, which are not operculated.
• They are unsegmented, dorsoventrally flattened, and leaf-shaped.
• The alimentary canal is incomplete, with the anus being absent.
• The excretory system is bilaterally symmetric.
• They bear two suckers, one on the ventral surface of the body (ventral sucker) and one around the mouth (oral sucker). These serve as organs of attachment for the fluke.

Taxonomy

• Class Trematoda
o Subclass Digenea (the digenetic trematodes)
 Order Opisthorchiformes
 Family Opisthorchiidae
 Clonorchis sinensis


There are three main species of Oriental liver fluke that affect humans:

• Clonorchis sinensis is common in China, Taiwan, Korea, Japan and Vietnam, and is often carried by domestic dogs and cats. The reservoir for this disease is various freshwater snails, while the vector is usually uncooked freshwater fish. C. sinensis is the most common "Oriental liver fluke" infection.

• Opisthorchis felineus is widespread in Eastern Europe, particularly in Poland, and is carried by a variety of wild and domestic animals.

• Opisthorchis viverrini is exxtremely common in Thailand, especially the north, and again is mostly carried by domestic dogs and cats.

C. sinensis is oblong, flat, transparent, and relatively small (10-25 mm in length, 3-5 mm in width). It has a pointed anterior and rounded posterior end.

Treatment

You may well ask, once you've got me, how do you get rid of me?

First of all, the following diagnostic tests can help a victim be SURE that he or she is suffering from clonorchiasis. A medical history should be taken including questions on diet, travel, and regions where the patient has previously resided. A physical assessment will include gentle palpation of the liver. An Elisa blood test (77% sensitive) may be admistered.

Medical tests may include endoscopy and examination of a stool (faeces) sample for eggs. Microscopic demonstration of eggs in the stool or in duodenal aspirate is the most practical diagnostic method. Radiological and sonographic assesments are also becoming increasingly popular, but different imaging modalities present various risks, including a high number of false positives. The adult fluke can also be recovered surgically.

There are a number of anthelmintic medications which work in different ways. In most cases a single dose is used, but for severe infections or more resilient worms, longer-term treatment may be required. Praziquantel or albendazole are the drugs of choice to manage clonorchiasis (by eradicating the parasite) and of course treatment for the secondary effects of parasitemia may be necessary.

• Albendazole (Brands: Eskazole, Zental) is used to treat hydatid disease and larval taeniasis (beef tape worm) infection, and for some tapeworm infections by adult worms. It works by inhibiting metabolism in the cells of the worm, leading to their immobilization and death. The dead worms are broken down by the body’s immune system.

• Praziquantel (Brands: Biltricide) is used to treat blood flukes, lung flukes, liver flukes and intestinal flukes, and the majority of tapeworms. It is the drug of choice for treating clonorchiasis. This drug increases cell membrane permeability in susceptible worms, resulting in loss of their intracellular calcium, massive contractions, and paralysis of the worm's musculature. This is followed by attachment of phagocytes to the parasite and its subsequent death.

The praziquantel tab should be swallowed whole with some liquid during meals. Keeping the tab in mouth may result in a bitter taste, which can produce nausea or vomiting.

Cholangitis is treated with intravenous antibiotics. Other complications resulting from clonorchiasis may require additional interventions, including surgery.

Life Cycle

Clonorchis sinensis is a small fluke (10 to 25 mm) that lives in the biliary tree of its host-- not actually in the liver-- for a period of as much as fifty years. The fluke feeds on mucosal secretions in the biliary tree and passes operculated eggs into the faeces. Once the eggs reach fresh water they are ingested by an intermediate snail host.

The flukes develop and multiply within the snail and the cercariae are released and penetrate freshwater fish. Infection of humans occurs after eating pickled, salted, raw or dried fish infected with the metacercariae. The larvae are released in the duodenum and they proceed to enter the bile duct. They then migrate to second-order bile ducts where the flukes mature into the adult forms in about one month.


Life cycle.

To give more detail, the embryonated eggs are discharged in the biliary ducts and in the stool of an infected host. Then, once they reach fresh water, the eggs are ingested by a suitable operculate snail intermediate host; more than 100 species of snails can serve as intermediate hosts, making eradication or control of the reservoir nearly impossible. In this first intermediate host), the eggs hatch to produce a miracidium. Inside the snail, the miracidia multiply asexually through a single generation of sporocysts and two generations of rediae to form a fork-tailed cercariae.

The cercariae are released from the snail and after a short period of free-swimming time in water, they come in contact with and penetrate the flesh of freshwater cyprinid fish (such as grass carp or pond smelt, both popular food fish in Asia), where they lose their tails and encyst in the scale or muscle of the fish as metacercariae. Infection of humans occurs by ingestion of undercooked, salted, pickled, or smoked freshwater fish "vector".

After ingestion, the metacercariae excyst in the host's duodenum and ascend the biliary tract by way of the ampulla of Vater. The maturation of the larvae, as mentioned previously, takes approximately 1 month. The adult flukes (measuring 10 to 25 mm by 3 to 5 mm) reside in the small and medium sized biliary ducts. In addition to humans, carnivorous animals including both wildlife and domestic animals can serve as reservoir hosts, making transmission particularly easy and control difficult.

Clinical Presentation in Humans

Most of the pathologic manifestations of clonorchiasis result from the inflammation and intermittent obstruction of the biliary ducts caused by the adult flukes. In the acute phase of the disease, abdominal pain, nausea, diarrhea, and eosinophilia can be major symptoms. There may be elevation in levels of alkaline phosphatase, alanine aminotransferase, transaminase, and bilirubin levels.

Chlonorchiasis is often an asymptomatic infection, but patients with a severe infestation may develop cholangiohepatitis and liver failure. Clinical manifestations are usually apparent if the worm load increases to 500-1000 flukes. In long-standing infections, cholangitis, cholelithiasis, pancreatitis, and cholangiocarcinoma can develop, which can be fatal if treatment is left too late. Interestingly, the occurrence of biliary stones in conjunction with clonorchiasis is associated with an increased incidence of carrying Salmonella typhi.

Abdominal x-rays may also demonstrate intrahepatic calcification. Percutaneous transhepatic cholangiography and CT scanning will reaveal dilatation of the peripheral intrahepatic bile ducts, and in severe cases, occasional cholangiocarcinoma. Round filling defects up to several millimeters in diameter may be caused by the adult worms.

The parasite causes thickening of the lining of the bile duct and an inflammatory response in the surrounding liver tissue. In heavy infections, the bile duct epithelium can also be deeply eroded, and the parasite's eggs will enter the liver tissue; in such cases the eggs become surrounded by a fibrotic capsule or granuloma. Particularly heavy infections can also result in stenosis-- narrowing or blockage-- of the bile ducts. Since the parasites can live for years and the number of parasites tends to increase as a person ages, the damage to the liver and bile duct tends to accumulate over time and can result in death.

As with many trematodes, diagnosis of the infection depends on recovering and identifying the parasite's eggs in a stool sample. Characteristic sonographic findings include diffuse dilatation of small intrahepatic ducts with minimal or absent dilatation of the extrahepatic ductal system. Increase in echogenicity and thickening of the involved bile duct walls are also present.

Epidemiology

Endemic areas for Clonorchis sinensis are in Asia including Korea, China, Taiwan, and Vietnam. Clonorchiasis has occasionally been reported in non-endemic areas (including the United States). In such cases, the infection is usually found in Asian immigrants, or following ingestion of imported, undercooked or pickled freshwater fish containing metacercariae.


Geographic distribution.

The trematode responsible for clonorchiasis is found throughout much of East Asia from Indochina to Japan as a common parasite of man and fish-eating mammals. An estimated 19 million people are infected in the heavily populated regions of China (especially the southern provinces), Taiwan, Hong Kong, the Red River delta in Indochina, Korea and Japan.

The incidence in China and Japan has been decreasing in recent decades, but Hong Kong still has a very high incidence, as well as the adjacent Kwangtung Province of South China where fish farming is a major industry. Although it may persist in immigrants for decades, the disease has not become endemic in the United States because suitable intermediate hosts are lacking in America.

Several Hawaiians have acquired clonorchiasis by eating infected raw, frozen, or salted fish shipped from China or Japan. More commonly, however, it is modern day immigrants from China and East Asia who are occasionally seen in Hawaiian and mainland U.S. hospitals with cholangiohepatitis caused by C. sinensis.

Public Health and prevention strategies focus on controlling the use of "night soil" (fertilizer contaminated with human feces), which is used to fertilize fish ponds to increase fish production; unfortunately, this practice also stimulates snail growth with an increased number of secondary hosts for C. sinensis. The other obvious countermeasures are to avoid eating raw fish and using contaminated water for consumption.

A Little Historical Background

I thought you might be interested in learning some of my historical background. Clonorchis sinensis is the most important of the liver flukes that infect humans. The fluke is found throughout East Asia and is chiefly responsible for the many patients with cholangiohepatitis seen in the Orient. C. sinensis was first described by McConnell in 1875 in the bile ducts of a Chinese carpenter in Calcutta, but the earliest historical record of clonorchiasis dates back to an ancient corpse buried in 278 B.C. in the West Han Dynasty in China.

What is Clonorchiasis?

That's the disease caused by me, the Chinese liver fluke. I'm a parasite. You can read about me in my profile, but just to reiterate, clonorchiasis is a chronic infection caused by Clonorchis sinensis (that's me!), or the liver fluke, a parasitic worm 10 to 25 mm long that lives in the bile ducts of the liver in humans and other mammals. Clonorchiasis is a common disease in China, Vietnam, Korea, and Japan and is acquired by eating freshwater fish containing the fluke larvae.

Fluke infections are diseases of the digestive tract and other organ systems caused by several different species of parasitic flatworms (Trematodes) that have complex life cycles involving hosts other than human beings. Trematode comes from a Greek word that means "having holes" and describes the external suckers that the adult flukes use to draw nutrients from their hosts. Fluke infections are contracted by eating uncooked fish, plants, or animals from fluke-infected waters. The symptoms vary according to the type of fluke infection.

In humans, fluke infections can be classified according to those diseases caused by liver flukes and those caused by lung flukes. Diseases caused by liver flukes include fascioliasis, opisthorchiasis, and clonorchiasis. Cases of liver fluke infection have been reported in Europe and the United States, as well as the Middle East, China, Japan, and Africa. Diseases caused by lung flukes include paragonimiasis. Paragonimiasis is a common infection in the Far East, Southeast Asia, Africa, Central and South America, Indonesia, and the Pacific Islands.

It is estimated that between 40 million and 100 million people worldwide suffer from either liver or lung fluke infections.

In their adult stage, liver and lung flukes are symmetrical in shape and look somewhat like long, plump leaves or blades of grass. They enter through the mouth and can infect any person at any age.

The symptoms of fluke infection differ somewhat according to the type of fluke involved. All forms of liver and lung fluke infection, however, have the following characteristics:

• Most persons who becomeinfected do not develop symptoms (asymptomatic)
• The early symptoms of an acute fluke infection are not unique to these diseases alone (nonspecific symptoms)
• Infection does not confer immunity against re-infection by the same species or infection by other species of flukes.

This blog was created as a project for a class at Stanford University: Human Biology 103, Parasites and Pestilence. Its goal is to provide basic information about the parasite and the disease in these early posts, and to continue updating as news and research about clonorchiasis continue to be produced. Some navigational aids:

• Graphic credits, links and references are posted under "Comments" for each section. Any images used will be taken down immediately if their owners email a request.
• The "favorite books" section of the profile also includes helpful sources that were used in creating this blog.
• The "Archives" section for May 2004 will contain all of the basic information, so please navigate from there if you are new to the site.
• Please email me with questions or comments! We would welcome your feedback.