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This week at Infection Landscapes we begin to cover another group of trematodes, the liver flukes.We will cover two species separately as their life cycles and landscape epidemiology are different enough to warrant distinct entries. The first liver fluke species we will cover is Clonorchis sinensis.
The Worm. Clonorchis sinensis is a flatworm in the class Trematoda.
This helminth's life cycle requires two intermediate hosts and a definitive host. This is a human parasite and humans constitute the definitive host species in its life cycle. Let's consider this life cycle.
Embryonated ova are expunged from an infected definitive host (human) and are infectious to the first intermediate host, i.e. freshwater snails, most commonly Parafossarulus spp. As the freshwater snails are the first intermediate host, the embryonated eggs must encounter a water environment to move to the next stage of development, which means that the human feces must come into contact with this water source. The eggs are eaten by the freshwater snails, and subsequently the miracidia emerge and relocate to the hepatopancreas, where they develop into sporocysts. After approximately 3 weeks of development in the hepatopancreas, cercariae are fully formed and exit the snail. These cercariae are highly motile in water, similar to the analogous stage of schistosomes. However, C. sinensis cercariae do not penetrate human skin. Rather, C. sinensis cercariae seek out a second intermediate host. When the cercariae encounter a fish of the Cyprinidae family, which are important freshwater food fish in many parts of the world, they burrow into the muscle tissue of the fish, or simply locate under the scales, and encyst. They subsequently transform into the metacercariae, which the infectious stage for humans. Alternatively, the cercariae can also encyst under the exoskeleton in the muscle tissue of freshwater crustaceans, such as crabs or crayfish. Human infection occurs following the ingestion of undercooked fish or crustaceans that harbor encysted metacercariae. These metacercariae then excyst in the small intestine and migrate up the bile duct where they will continue to develop into adult flukes over the course of several weeks. Adults live in the lumen of the bile duct in the liver and are thought to feed directly on the bile. C. sinensis adults contain both male and female reproductive organs, so no sex pairing is required of these trematodes to produce and fertilize the eggs. Embryonated eggs pass out of the common bile duct and into the small intestine and are eventually expunged in the feces of the host. The graphic below produced by the Centers for Disease Control and Prevention nicely depicts this trematode's complex life cycle:
The Snail. Freshwater snails are the first intermediate hosts of C. sinensis. There are several genera capable of filling this role, but the most common is Parafossarulus, and the most common species in endemic areas is Parafossarulus manchouricus.
These snails are aquatic, breathe with gills, and are ciliary feeders. They are widely distributed throughout Asia.
The Fish. The Cyprinidae family of fish serve as the second intermediate hosts of C. sinensis. This fish family is the largest and is comprised of the carps and minnows. They are freshwater fish and, being toothless, primarily eat gastropods and aquatic vegetation, though some will eat algae, small fish, or other molluscs. Given their great diversity, wide geographic distribution (extensive in Europe, Asia, Africa, and North America), and preferred food, and given that these fish are one of the most important food fish for humans in much of the world, including much of Asia, these fish are an ideal intermediate host for C. sinensis.
In addition to these fish, crustaceans, such as crabs and crayfish, are also capable of serving as the second intermediate hosts.
The Disease. Most infections with C. sinensis are asymptomatic. Pathogenesis stems from this trematode locating in the bile duct:
Acute illness typically involves moderate, non-specific symptoms: abdominal pain, diarrhea, nausea. In high volume infections the proliferation of adults can progress to more severe pathology for two reasons. First, the large number of adult trematodes can consume substantive amounts of bile and subsequently disrupt the digestion and absorption of dietary nutrients. Second, in high volume infections the bile duct can become blocked usually due to the large egg volume produced by the adults, which can lead to inflammation, secondary bacterial infection (cholangitis), fibrosis, and hyperplasia.
In chronic infections, weight loss, lack of energy, and chronic diarrhea are common due to the ongoing digestive interruption, and carcinoma can develop in the bile duct due to the chronic obstruction and tissue damage.
The Epidemiology and the Landscape. C. sinensis is the most prevalent liver fluke in the world with approximately 30 million people currently infected, but it is not the most widely distributed (Fasciola hepatica is the most geographically widespread liver fluke). C. sinensis is endemic in East and Southeast Asia, particularly in Japan, Korea, China, Vietnam, Laos, and Cambodia.
We do not have good surveillance data describing concrete measures of the burden of disease. However, areas of high endemicity do correspond to a relatively high incidence of cholangiocarcinoma.
The landscape epidemiology of liver flukes in general, and C. sinensis in particular, differs from that of the schistosomes in that cercariae do not infect their definitive host directly, but rather require a second intermediate host, which transfers the metacercariae passively (through consumption) to the definitive host. This means that the point of intersection between pathogen and host in the landscape is fundamentally different and derives from a unique ecological framework. Whereas, schistosome transmission occurs simply by way of contact with cercariae-infested freshwater bodies, C. sinensis trematodes require a more nuanced and specific engagement of the human host with the aquatic environment, i.e. through the harvesting of food from the water. However this terrain, as narrowly described so far, is not sufficient by itself for infection transmission. In addition, the physical landscape that defines the geography and structure of C.sinensis ecology must intersect the uniquely human social landscape for transmission to occur and the life cycle to be completed. This is because human feces must first contaminate the same water sources that humans then subsequently harvest for food. This can happen through 1) poor sanitation and water infrastructure, 2) the use of human feces for the fertilization of crops, or 3) both.
Moreover, eating metacercariae-infested fish (or crustaceans) need not transmit the infection to humans, but does because of the method of preparation of the fish. In many places where C. sinensis is endemic, raw fish is a key ingredient in some local delicacies, so food preparation, as determined by cultural preference, becomes another aspect of the social landscape that converges with the physical landscape to effect transmission.
Unfortunately this, too, can be a difficult practice to disengage since human feces serves as a very rich fertilizer and, thus, can form a critical component to subsistence farming in many parts of the world where other fertilizers or farming technologies are cost prohibitive. And, of course, without an affordable substitute, refraining from human feces fertilization could very well lead to starvation. As such, this may not be a viable option for some subsistence farmers.
This week at Infection Landscapes we begin to cover another group of trematodes, the liver flukes.We will cover two species separately as their life cycles and landscape epidemiology are different enough to warrant distinct entries. The first liver fluke species we will cover is Clonorchis sinensis.
The Worm. Clonorchis sinensis is a flatworm in the class Trematoda.
Clonorchis sinensis
This helminth's life cycle requires two intermediate hosts and a definitive host. This is a human parasite and humans constitute the definitive host species in its life cycle. Let's consider this life cycle.
Embryonated ova are expunged from an infected definitive host (human) and are infectious to the first intermediate host, i.e. freshwater snails, most commonly Parafossarulus spp. As the freshwater snails are the first intermediate host, the embryonated eggs must encounter a water environment to move to the next stage of development, which means that the human feces must come into contact with this water source. The eggs are eaten by the freshwater snails, and subsequently the miracidia emerge and relocate to the hepatopancreas, where they develop into sporocysts. After approximately 3 weeks of development in the hepatopancreas, cercariae are fully formed and exit the snail. These cercariae are highly motile in water, similar to the analogous stage of schistosomes. However, C. sinensis cercariae do not penetrate human skin. Rather, C. sinensis cercariae seek out a second intermediate host. When the cercariae encounter a fish of the Cyprinidae family, which are important freshwater food fish in many parts of the world, they burrow into the muscle tissue of the fish, or simply locate under the scales, and encyst. They subsequently transform into the metacercariae, which the infectious stage for humans. Alternatively, the cercariae can also encyst under the exoskeleton in the muscle tissue of freshwater crustaceans, such as crabs or crayfish. Human infection occurs following the ingestion of undercooked fish or crustaceans that harbor encysted metacercariae. These metacercariae then excyst in the small intestine and migrate up the bile duct where they will continue to develop into adult flukes over the course of several weeks. Adults live in the lumen of the bile duct in the liver and are thought to feed directly on the bile. C. sinensis adults contain both male and female reproductive organs, so no sex pairing is required of these trematodes to produce and fertilize the eggs. Embryonated eggs pass out of the common bile duct and into the small intestine and are eventually expunged in the feces of the host. The graphic below produced by the Centers for Disease Control and Prevention nicely depicts this trematode's complex life cycle:
The Snail. Freshwater snails are the first intermediate hosts of C. sinensis. There are several genera capable of filling this role, but the most common is Parafossarulus, and the most common species in endemic areas is Parafossarulus manchouricus.
Parafossarulus manchouricus
These snails are aquatic, breathe with gills, and are ciliary feeders. They are widely distributed throughout Asia.
The Fish. The Cyprinidae family of fish serve as the second intermediate hosts of C. sinensis. This fish family is the largest and is comprised of the carps and minnows. They are freshwater fish and, being toothless, primarily eat gastropods and aquatic vegetation, though some will eat algae, small fish, or other molluscs. Given their great diversity, wide geographic distribution (extensive in Europe, Asia, Africa, and North America), and preferred food, and given that these fish are one of the most important food fish for humans in much of the world, including much of Asia, these fish are an ideal intermediate host for C. sinensis.
In addition to these fish, crustaceans, such as crabs and crayfish, are also capable of serving as the second intermediate hosts.
The Disease. Most infections with C. sinensis are asymptomatic. Pathogenesis stems from this trematode locating in the bile duct:
Acute illness typically involves moderate, non-specific symptoms: abdominal pain, diarrhea, nausea. In high volume infections the proliferation of adults can progress to more severe pathology for two reasons. First, the large number of adult trematodes can consume substantive amounts of bile and subsequently disrupt the digestion and absorption of dietary nutrients. Second, in high volume infections the bile duct can become blocked usually due to the large egg volume produced by the adults, which can lead to inflammation, secondary bacterial infection (cholangitis), fibrosis, and hyperplasia.
In chronic infections, weight loss, lack of energy, and chronic diarrhea are common due to the ongoing digestive interruption, and carcinoma can develop in the bile duct due to the chronic obstruction and tissue damage.
The Epidemiology and the Landscape. C. sinensis is the most prevalent liver fluke in the world with approximately 30 million people currently infected, but it is not the most widely distributed (Fasciola hepatica is the most geographically widespread liver fluke). C. sinensis is endemic in East and Southeast Asia, particularly in Japan, Korea, China, Vietnam, Laos, and Cambodia.
We do not have good surveillance data describing concrete measures of the burden of disease. However, areas of high endemicity do correspond to a relatively high incidence of cholangiocarcinoma.
The landscape epidemiology of liver flukes in general, and C. sinensis in particular, differs from that of the schistosomes in that cercariae do not infect their definitive host directly, but rather require a second intermediate host, which transfers the metacercariae passively (through consumption) to the definitive host. This means that the point of intersection between pathogen and host in the landscape is fundamentally different and derives from a unique ecological framework. Whereas, schistosome transmission occurs simply by way of contact with cercariae-infested freshwater bodies, C. sinensis trematodes require a more nuanced and specific engagement of the human host with the aquatic environment, i.e. through the harvesting of food from the water. However this terrain, as narrowly described so far, is not sufficient by itself for infection transmission. In addition, the physical landscape that defines the geography and structure of C.sinensis ecology must intersect the uniquely human social landscape for transmission to occur and the life cycle to be completed. This is because human feces must first contaminate the same water sources that humans then subsequently harvest for food. This can happen through 1) poor sanitation and water infrastructure, 2) the use of human feces for the fertilization of crops, or 3) both.
Moreover, eating metacercariae-infested fish (or crustaceans) need not transmit the infection to humans, but does because of the method of preparation of the fish. In many places where C. sinensis is endemic, raw fish is a key ingredient in some local delicacies, so food preparation, as determined by cultural preference, becomes another aspect of the social landscape that converges with the physical landscape to effect transmission.
Control and Prevention.
Snail Control
As with the schistosomes, early (and some ongoing) attempts at liver fluke elimination 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 the transmission of C. sinensis 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. Nevertheless, the use of some plants in specific aquatic environments has been quite successful. For example, planting Sarcoca dodecandra, i.e. the gopo berry shrub, in water sources kills any snails present.
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.
Food Preparation
Thorough cooking of all freshwater fish and crustaceans is very important for blocking transmission of C. sinensis to humans. Cooking kills the metacercariae and, thus, directly prevents infection in humans. Cooking is probably the most effective method of control and prevention of C. sinensis infection. However, in many places where this helminth is endemic, certain local delicacies require raw fish as central ingredients. As such, consistent cooking of fish in each household becomes an individual choice that may be superseded by cultural dietary norms and preferences.
Farming Practice
Finally, changing agricultural practices that rely on human feces for fertilization of crops could help reduce infection with C. sinensis in some agricultural subsistence communities.
Unfortunately this, too, can be a difficult practice to disengage since human feces serves as a very rich fertilizer and, thus, can form a critical component to subsistence farming in many parts of the world where other fertilizers or farming technologies are cost prohibitive. And, of course, without an affordable substitute, refraining from human feces fertilization could very well lead to starvation. As such, this may not be a viable option for some subsistence farmers.