Parasites and Pestilence
ParaSite: Schistosoma Mekongi
Schistosoma mekongi is a parasitic blood-fluke found exclusively in the Mekong river basin of Laos and Cambodia in South-east Asia. Humans are the definitive host for the parasite, which causes damage to the liver, spleen, gastrointestinal tract, and esophagus. The intermediate host is the Neotricula aperta snail, which is the origin of the name for the disease, “snail fever.” S. mekongi infection has also been call Mekong Schistosomiasis. The adult worms feed on nutrients found in the blood; globulins and red blood cells, through anaerobic glycolysis (4), thus depriving the host of these nutrients.
S. mekongi cases were first reported in 1957 in Laos and 1968 in Cambodia (2)(16). Due to many similar characteristics with the close relative S. japonicum, S. mekongi was first identified as a unique species in 1978 (17).
Though similar to S. japonicum, the clinical presentation of disease due to S. mekongi is milder (7). Acute pathology includes a rash at the site of penetration of the skin, known as cercarial dermatitis or swimmers’ itch.
Image 1: Schistosoma cercerial dermatitis
Longstanding infection as experienced by those who inhabit endemic regions results in chronic symptoms. The most common symptom of infection is portal hypertension. Other signs and symptoms include (3) (5) (6) (15):
Portal vein enlargement
Schistosoma eggs lodged in the capillaries of organ tissue can lead to cirrhosis, especially of the lung and liver in chronically infected patient. Additionally, eggs can become lodged in or near the nerve tissue, causing CNS symptoms. Deaths are most often due to ascites (build up of fluid in the peritoneal cavity) and esophageal bleeding (15).
Transmission occurs seasonally, during the dry period; March through June in Laos, and February through April in Cambodia (15). The dry season allows the rocks which line the Mekong riverbanks to be partially exposed, leaving a number of suitable crevices in the rock for the snail to inhabit. The parasite is transmitted from the intermediate snail host to the human host during exposure to water which is home to the intermediate snail host. S. mekongi circariae are freed from the body of the snail into the water, and chemotax to the human host. The circariae then burrow through the skin and enter the blood stream.
Other than humans, other animals which serve as a reservoir for S. mekongi are dogs and domestic pigs (12) (14).
In this region, the vector capable of hosting and transmitting the parasite is the snail Neotricula aperta. These marine snails live along the banks of the Mekong River.
Image 2: Shells of the intermediate host snail
Incubation periods vary depending on the stage of the lifecycle. Within the snail host, the larvas develop and reproduce for over 32 weeks in this species of schistosome before emerging as developed cercariae (9).
In the mammalian host, the extended incubation before infectious eggs are shed differentiates differentiates S. japonicum from S. mekongi. Experiments have found that the prepatent period between schistosomulum maturation and adult worms producing eggs is 7-8 days longer in the mouse for S. mekongi versus S. japonicum (17). Eggs are quite stable, and can survive up to a week outside of water (4).
Physical characteristics of these blood-fluke are unlike among trematodes. Adult worms are dioecious, where males and females are morphologically different. Male worms can grow up to 2.2 cm, while females grow up to 2.6 cm (7). Adults have both an oral and ventral sucker which attaches to the venous wall, preventing blood flow from dislodging the parasite. The worms are an off-white color, and the male possesses a gynecophoric channel; a trough running laterally in which the female rests. This is known as eternal copulation, and is most commonly found in the mesenteric venous plexus.
Image 3: Male and female worms in eternal copulation
The nearly spherical embyronated eggs produced by the mating worms are small compared to other schistosoma, with a diminutive spine on the lateral axis. On average, 95 of these eggs are produced per mating couple per day, a substantially lower fecundity than other schistosomes; S. japonicum mating pairs produce 250 eggs per day (18). The shape of the eggs, small and lacking a pronounced spine, facilitates circulation.
Image 4: S. mekongi egg
Miracidium are hatched from embyronated eggs in contact with water, and survive as free swimming larva in the water while questing for the snail intermediate host.
Within the snail, miracidium develop into primary sporocysts, which through asexual reproduction create secondary sporocysts germ cells. These germ cells then migrate to the heptatopancreas of the snail, where further asexual division yields cercaria.
Cercarium are the larval stage infectious to humans, and are morphologically distinct from the other larval stages based on their bifurcated tail and the presence of embryonic suckers used to attach and penetrate the human host.
Image 5: Schistosoma cerceria
Eggs hatch on contact with water, so when human feces containing S. mekongi eggs contaminate a water supply, the embyronated eggs hatch, releasing miricida into the water. The miricidia then invade the snail host, questing for it based on light and chemical signals. The larva then penetrate the snail, wherein they develop into the larval stage through asexual reproduction, the resulting organisms are known as sporocysts. The process by which these sporocyst larva develop into circariae is known as cercariogeneis, and can last over 32 weeks (9). These larva are characterized by a forked tail and suckers. Once this stage of development is complete, the cercariae emerge from the snail, following a circadian rhythm. The cercariae begin emerging at sunrise and finish roughly six hours later. On average, only 42 cercariae are released from the snail per day, quite low compared to S. haematobium which can release up to 2,000 cercariae per day, and S. mansoni, which can release up to 15,000 (9) (11).
Image 6: Life cycle of S. mekongi
The free swimming cerceriae then chemotax to the human skin submerged in the water, and burrow through the skin using proteolytic enzymes into the circulatory system. While penetrating the skin, the cercariae lose their forked tails, becoming a stage known as schistosomulum, which then migrates through the blood stream until they reach the superior and inferior mesenteric veins and canals of the hepatic portal system. Maturation takes roughly one month. There the worms latch onto the vein with suckers, and if both male and female are present, begin to produce embryonated eggs.
These eggs then either penetrate into the intestines to be evacuated in feces, or are swept by circulating blood and become lodged in other areas of the body, such as the liver, lungs, or other organs, causing disease. During more prolonged infection, the worms can migrate farther from their original site nearest the liver. Adult schistosoma worms live on average 3-5 years, but have been known to live up to 30 (4). On average, an infected person will shed less than 150 eggs per gram of stool. In the environment, the eggs remain viable for roughly a week (15).
Infection is verified by the presence of eggs in stool samples. S. mekongi eggs are differentiated from those of S. japonicum based on size. S. mekongi eggs are smaller, ranging from 30-55 μm in diameter, while S. japonicum eggs range 50-65μm (7).
Image 7: Fecal smear with S. mekongi eggs
Immunoassays are ineffective at differentiating between active or past infection, as well as cross-reactive with other helminth parasite infections (14).
Drug therapy is available to treat the parasitic infection. Indeed, universal treatment campaigns have been pursued in Laos and Cambodia since 1989 and 1996, respectively. A single dose of the anti-parasitic drug praziquantel, delivered at 40 mg/kg (15), is effective at clearing the infection via paralysis of worms and destruction of the tegument encasing the worm. The drug is ineffective at killing either eggs or immature worms. There is no treatment for the scarring that the eggs can cause, but reducing the production of eggs through the elimination of mating worms will limit further cirrhosis. A single dose of praziquantel is 70-100% effective at eliminating all egg excretion in 4-6 weeks (4).
The range of S. mekongi is restricted to that of its intermediate host, thus is only found near the Mekong River, in the peninsula of South-East Asia. Transmission occurs most frequently during the dry season, where environmental changes create lower water levels, fostering the population of snails, and human interaction with water is more frequent (10). Additionally, the rate of disease due to S. mekongi infection is higher among children than in adults (4).
Image 8: Mekong river delta
Endemic regions in Cambodia were mapped in a public health intervention through the use of questionnaires addressing four common signs of schistosoma endemicity (13); blood in the stool- due to gastrointestinal damage of eggs, apparent organomegaly- the increased size of organs due to cirrhosis, snail environments- to determine the presence of the intermediate host, and scarring on the abdominal wall- a sign of a local treatment of the organomegaly common to schistosomiasis. When used in Laos, surveys found that the prevalence of schistosomiasis range broadly, from 15.3-92.5%, where the average prevalence across the region was 42.2%. The endemic regions are usually focused around a point of contamination, where the environment is such that there are many infected snails posing a risk of transmitting cercariae to exposed humans.
Image 9: Range of S. mekongi
As of 2002, these numbers estimate that 60,000 people are at risk in the river delta of Laos, with a case prevalence of 11,000. Meanwhile the 80,000 people are at risk in Cambodia (15).
The close association of humans and water in this region in conjunction with lack of access to sanitation facilities led to everyday activities being at risk for exposure to the parasite. Risk factors for infection include laundering, fishing, bathing, and swimming, or any other activity that exposes skin to circariae-ridden water. Though the poverty in these countries makes the costs of sanitation facilities prohibitively expensive, there have been successful control methods to reduce the transmission and morbidity of schistosomiasis.
The control measure of universal treatment campaigns in Laos (1989) and Cambodia (1996) have drastically reduced the impact of S. mekongi in the region (15). Both prevalence of infection and morbidity have decreased, and while the poverty rampant in the region makes interventions which would eliminate the parasite unlikely, the control measures used were successful in reducing the prevalence and infection rates to a low level of endemicity. Universal treatment supplied people living in endemic regions with the recommended dose of praziquantel.
However, the distribution of drugs alone has been unsuccessful in completely eliminating S. mekongi from the region. This is not only due to the funding needed to improve sanitation, but also due to the ecological landscape of the snail. It would be difficult to apply molluscicidal chemicals to the vast rocky outcroppings to either eliminate or treat all infected snails, a necessary step in completely halting disease transmission. Additionally, these chemicals are expensive and require extensive logistics to properly execute. The chemicals are also toxic to other aquatic life, is an environmental and economic concern (11). Other challenges have been the shift from the universal treatment employed in early elimination efforts to the cheaper selective treatment currently employed. This method requires the implementation of a reliable and sensitive surveillance to rapidly report and treat endemic resurgence.
There is evidence that people living in endemic regions acquire immunological resistance to schistosomes after repeated exposure. This has lead to research into a vaccine against schistosomiasis, though no vaccine specific to S. mekongi is currently in development (4).
Education, along with selective treatment and surveillance, is another strategy to fight infection. People living in endemic areas need to be informed of the risks of contaminated water for use in daily activities, and of the circadian rhythm of cercariae emergence. Water should be avoided at high risk times, the morning and during the dry season, unless strictly necessary. External support for treatment, education, and surveillance are needed to maintain elimination efforts in these impoverished countries.
Useful Web Links:
Image 1: Schistosomiasis_itch.jpeg (JPEG Image, 700x469 pixels) - Scaled (57%). Available at: http://upload.wikimedia.org/wikipedia/commons/2/27/Schistosomiasis_itch.jpeg [Accessed February 27, 2009].
Image 2: Vecteurs et lutte anti vectorielle. Available at: http://vecteursetlutte.ifrance.com/Utilitaires/Mollusques.htm [Accessed February 27, 2009].
Image 3: Parasitic Worm Schistosoma mekongi Cambodia Laos Vietnam. Available at: http://www.expat-advisory.com/cambodia/phnom-penh/parasitic-worm-schistosoma-mekongi-more-widespread-than-previously-thought.php [Accessed February 27, 2009].
Image 4: Schistosomiasis - Microscopy Findings. Available at: http://www.dpd.cdc.gov/dpdx/HTML/Frames/S-Z/Schistosomiasis/body_Schistosomiasis_mic1.htm [Accessed February 27, 2009].
Image 5: Research - Immunology - CII - University of York. Available at: http://www.york.ac.uk/res/cii/research/immunology.shtml [Accessed February 27, 2009].
Image 6: KIZA - Transmissie Schistosomiasis. Available at: http://www.kiza.nl/kiza/index.php?aid=2486&sid=414&tid=84 [Accessed February 27, 2009].
Image 7: Picasa Web Albums - ID & International - Parasitology Volume 2 for web. Available at: http://picasaweb.google.com/idintl/ParasitologyVolume2ForWeb#5194396249491756658 [Accessed February 27, 2009].
Image 8: riparian.jpg (JPEG Image, 321x494 pixels) - Scaled (54%). Available at: http://cantho.cool.ne.jp/mekong/outline/riparian.jpg [Accessed February 27, 2009].
Image 9: SRG Schistosomiasis Distribution. Available at: http://www.path.cam.ac.uk/~schisto/schistosoma/schisto_distribution.html [Accessed February 27, 2009].