Thursday, July 19, 2012

Liver Flukes Part 2: Fascioliasis

This week at Infection Landscapes we will cover another group of liver flukes, the trematodes Fasciola hepatic and Fasciola gigantica, which cause fascioliasis. These liver flukes cause enzootic disease, so human disease results from zoonotic infection. Globally, Fasciola liver flukes are also the most widely distributed, although they do not cause the largest overall burden of liver fluke disease.

The Worm. As mentioned above, these two Fasciola species are trematode flatworms.

Fasciola hepatica adult

F. hepatica and F. gigantica have very similar life cycles (although they probably have different intermediate host preferences based on the differences in the geographic distribution of freshwater nails), so we will consider their life cycle in common.

Unembryonated eggs are passed in the feces of an infected definitive host, the natural reservoir of which is ruminants. The eggs embryonate in freshwater and miracidia emerge over the course of one to two weeks. These miracidia then seek out and penetrate their intermediate hosts, freshwater snails. After entry into the snail, the miracidia migrate to the hepatopancreas where the develop first into sporocysts, then into rediae, and finally into cercariae. The motile cercariae exit the snail and seek out the littoral zone, attach to vegetation, usually aquatic, and encyst. Encysted, the cercariae develop into metacercariae, which is infective to the definitive host. When these encysted metacercariae are eaten by a ruminant (or human) incidental to the ingestion of the food vegetation, infection is initiated. Infection can also occur by drinking water contaminated with encysted metacercariae, which is also fairly common. The metacercariae excyst in the small intestine, penetrate the epithelium of the gut, and migrate intraperitoneally to the liver. The metacercariae then gain the liver directly by piercing the collagenous capsule surrounding it. Development is completed in the liver tissue and requires approximately four months to adulthood. At this point, the adults typically reside in the bile ducts. These trematodes feed directly on the liver tissue and on the epithelium of the bile ducts. Tens to hundreds of thousands of eggs can be produced per day, depending on the infection volume, and infections can last years. A nice graphic below produced by the Centers for Disease Control and Prevention depicts the life cycle:

The Snail. Freshwater snails of the family Lymnaeidae serve as the intermediate host for F. hepatica. There are many species in this family that are capable of serving as the intermediate host. One of the most common freshwater snail host species is Galba truncatula:

Galba truncatula

This freshwater snail is an air breather and prefers shallow lentic or wetland environments.

The Disease. Most light infections are asymptomatic. Clinical disease presents in two forms, acute and chronic. 

Acute disease results from the the migration of the metacercariae through liver tissue (or other organ tissue if other organs are invaded). Common symptoms in acute disease include fever, abdominal discomfort, hepatomegaly and/or splenomegaly, anemia, nausea, anorexia, and jaundice, though this last symptom may or may not present.   

Chronic disease results from the adult trematodes taking up residence in the bile ducts. Their presence induces inflammation and an epithelial hyperplasia of the bile duct, which, in concert with the adults' large size, obstruct the passage of bile from the liver.

Symtpoms include chronic and pronounced abdominal pain, nausea, hepatomegaly, and a greater likelihood of jaundice. Calculi formation in the gall bladder and bile ducts is also common in chronic disease, which further contributes to intolerance of foods with high fat content.

The Epidemiology and the Landscape. Globally, there are between 2 and 3 million people infected with Fasciola spp. The occurrence of human fascioliasis is highly variable across geography, but livestock farming is central to the epidemiology and ecology of this infection. The greatest burden in the world occurs in the Andean region of Peru, Ecuador, and Bolivia, where the prevalence in some communities can range between 75% and 100%. Prevalence can also be locally high in parts of some Caribbean islands, particularly Cuba and Puerto Rico. On the other hand, while animal husbandry is quite common across much of the southern cone of South America, North America, and much of Asia, these are typically areas of very low endemicity or only sporadic incidence. Countries of the Mediterranean can have high levels of endemicity depending on the specific region. For example, some communities in the Nile delta, Turkey, and Iberian Peninsula have relatively high prevalence. In Asia, the greatest prevalence occurs in Iran, while countries in east Asia only demonstrate sporadic human cases.

In contrast to human fascioliasis, enzootic disease is very widely distributed across all of Africa, Asia, and the Americas, demonstrating endemicity in livestock in most regions of the world where livestock is present.

Animal husbandry underlies the ecology and epidemiology of fascioliasis. Human infection is fundamentally zoonotic, passed to humans from their livestock animals (although, in hyper- or holoendemic areas transmission between humans via contaminated water sources may play a significant role). Most frequently, the natural reservoirs are sheep or cattle, though many other ruminants are capable of becoming infected. Nevertheless, there is great geographic variation in the occurrence of human fascioliasis even among countries or regions that exhibit similar levels of livestock farming. Therefore, while the presence of livestock is a necessary, and perhaps defining, component of the landscape for the transmission of F. hepatica to humans, it is not sufficient for transmission. Critically there must also be regular points of contact between livestock and surface water. Moreover, the surface water must comprise an appropriate lentic environment with sufficient vegetation in the littoral zones and the presence of the appropriate snail populations:

As such, areas of high endemicity typically demonstrate a lack of adequate protection of surface water, which allows regular contamination of the water by livestock animals. The effects of such contaminated water may be less among communities that do not draw domestic water supplies from surface water, but those that do are at much greater risk because their water supply has not been protected, and also because of the poorer water infrastructure and sanitation overall.

Finally, the degree of subsistence on vegetation obtained in the littoral zone (e.g. watercress) will also contribute to the prevalence of human fascioliasis, as this is the most direct mode of transmission and the one which largely defines the infection ecology for ruminants.

Control and Prevention.

Snail Control

As with other trematodes, early (and some ongoing) attempts at fascioliasis control focused on gastropod control in various surface water sources. Typically, these control campaigns have involved the chemical treatment of freshwater sources to eliminate the local snail population, thus blocking transmission of Fasciola spp. at the intermediate host. However, two important problems make gastropod control unrealistic in many settings. 

First, the chemical treatment of water sources can have much broader ecologic impact than what is intended by the public health initiative. Introducing toxic agents into surface water may kill the snails, but it can also harm other organisms in the aquatic ecosystem and result in unanticipated and detrimental ecologic effects. Some investigations have explored the possibility of introducing biologic mechanisms of control to supplant chemical treatment with more "natural" mechanisms. However, these approaches can also be dangerous if the natural biologic mechanisms involve the introduction of non-native invasive species into the aquatic environment. 

Second, whether chemical or natural, snails in most areas prove robust to elimination. Both their high reproductive capacity and diffuse distribution within the aquatic system usually allow some members of the population to survive, which can then re-populate the local environment fairly quickly.

Environmental Maintenance and Livestock Surveillance

Focusing on the aquatic environment can be a useful approach to preventing human fascioliasis. For example, thinning aquatic plants in the littoral zones of surface water can remove a major exposure point for humans and their livestock. This is especially relevant for agricultural and pastoral communities that may come into frequent contact with these zones. However, any such "aquatic gardening" should be conducted in an ecologically informed and sensitive way so that the larger lentic ecosystem is not damaged by the helminth control measure. In addition, direct protection of the water supply can be effective in blocking transmission. Restricting contact between livestock and the water sources used for household consumption or crops is the primary means of water protection. However, in communities hyperendemic for fascioliasis, protecting the water supply from livestock will not be sufficient to block transmission. These communities also face the problem of water contamination with human feces. Hyperendemic areas are also typically areas of poor sanitation and water infrastructure, so blocking transmission in this setting will be more difficult without infrastructural development.

Surveillance of cattle for infection with Fasciola spp. can dramatically help to reduce the burden of disease in livestock, which can then secondarily reduce the burden in humans. A good surveillance system will employ regular serology screening to monitor infection in livestock animals and administer treatment to the infected animals. However, this kind of surveillance is very expensive as it requires laboratory technicians and supplies, highly trained field personnel, and veterinary treatment on a large scale. While high income countries with sporadic cases may be able to afford these methods, they will obviously be cost prohibitive in low income areas, which are precisely the areas where the greatest number of human cases occur. 


  1. Fascioliasis  is one of the largest flukes in the world. Its prevalence of this parasite is highest in areas where extensive sheep and cattle raising occurs and where dietary practices include the consumption of raw aquatic vegetables. Its spread can be controlled by
    Keeping domestic animal herds separate from the growing sites of aquatic vegetation, washing the aquatic vegetables. As with C. Sinesis, this parasite can be eliminated but not eradicated because it can grow in hosts i.e sheep and cattle.

    1. Yes Jatinder, Individual people can protect themselves from Fascioliasis by not eating raw watercress and other water plants, especially from endemic grazing areas. As always, travelers to areas with poor sanitation should avoid food and water that might be contaminated (tainted). Vegetables grown in fields that might have been irrigated with polluted water should be thoroughly cooked, as should viscera from potentially infected animals.

  2. Jatinder - it is clear that decreasing the prevalence of infection, from 100% in areas of Peru for example, is plausible. I think elimination would be too difficult in hyper-endemic areas, because of the possibility of contamination of the water supply with human feces.
    I would like to know what percentage of infected persons develop acute and chronic disease.

  3. in areas of high endemicity, i believe separating the ruminants from the main water source and the boiling of water before consumption will greatly affect the prevalence of infection as well as encourage the people at risk to cook and wash their vegetable. Besides prevention, what is the usual treatment for fasciolisis....

  4. I would be interested in evaluating a program that was intended to combat this disease. It seems like one for which we would have to carefully consider tradeoffs. If a key point of prevention becomes modifying animal husbandry practices, limiting livestock access to water, etc. any program to prevent fascioliasis may have significant effects on the economies, ways of life, and cultural practices of communities involved.

    What are some previous programs that have been implemented to combat fascioliasis "on the ground." Have they been formally evaluated?

  5. I came across that cattle acquire resistance to challenge infection with F. hepatica and F. gigantica when they have been sensitized with primary patent or drug-abbreviated infection. Resistance to fasciolosis was also documented in rats. However, sheep and goats are not resistant to re-infection with F. hepatica. These studies may help us to better understand the immune response to F. hepatica in host and are necessary in development of vaccine against the parasite. What do you think?

    1. I would be interested to know more about this. It seems that adult cattle are pretty much universally resistant to clinical infection, but I can't find much information about the mechanism of that resistance. I wonder what the functional differences are between sheep and goat immune systems and those of cattle and rats.

  6. Jatinder, can you tell me where you came across the information about resistance fasciolosis and also are there any documentated cases of human being resistant to re-infection....

  7. I remember reading that during my medical school from a book that I dont have now. I think this phenomenon is not just true for this parasite but also attempts are being for various infectious diseases. What do others think?

  8. I think that this article has interesting information on vaccination and resistance in cattle/sheep:
    Let me know if this answers your questions.

    1. Stephanie, that is an interesting article you looked up. I read the abstract and it sounds pretty intriguing to know that there are peculiar differences among the Fasciola species with respect to an immunologic response. This has opened up an interesting aspect to consider as medications/vaccines can then be specifically targeted, and produced.

  9. Nice! Interesting detail that I have been looking for on the Internet and that I found in your post. You made my day ;-)
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  10. Water seems to be the main source for transmission of the Fasciola species; perhaps giving (portable/ non-portable) water filtration devices to the livestock farmers that are easily attachable to faucets or tanks which store drinking water would be a simplier solution than actually altering the environment which can have unforseen consequences.

    1. I don’t think it’s as simple as proving water filtration devices. These devices typically are for purifying water for drinking but what of cattle eating vegetation in the water? I think you would first have to prevent all direct contact between lifestock and the infected waters, as well as humans and the infected waters. Then, you can add a water filtration system for human and livestock drinking. But if the livestock further need the vegetation from the water, you would probably have to pick it carefully and then wash it. It sounds like a huge hassle.

      On another note, the same way we blanket give prophylaxis during de-worming campaigns at the start of school, if a person were found to be infected with these liver flukes, there should be a related campaign to give that person enough treatment for him and his cattle/livestock. It would be two birds with one stone and I think we would help with the problem because we are giving prophylaxis treatment to the natural reservoir (ruminant too).


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