Intestinal Schistosomiasis Caused by Schistosoma japonicum: A Literature Review
D.J. Rivadeneira1*, H.S. Luo1
1Department of Gastroenterology, Renmin Hospital, Wuhan University, China
Intestinal schistosomiasis caused by the Schistosoma japonicum is located mainly in the East Asian region. Schistosomiasis is part of the neglected tropical diseases that affects mostly the poor population; although its incidence has dropped in these years, schistosomiasis caused by S. japonicum still is a prevalent disease. Adult worms reside in the mesenteric veins and excrete eggs that migrate through the intestinal wall and pass out with the stool. The clinical manifestations depend on the stage of the disease, the intestinal schistosomiasis mostly affects the colon, but it can also affect the small intestine. This review’s purpose is to highlight the background and importance of the intestinal manifestations caused by Schistosoma japonicum.
Neglected tropical diseases (NTD) primarily affect the poorest and most vulnerable populations in the world, they are caused by infectious and parasitic agents1. Currently the NTD are affecting 41.4 billion people, causing approximately 35,000 deaths per day worldwide2. These “neglected” diseases are due to under-financing and low recognition by the pharmaceutical industries3.
Schistosomiasis is a NTD caused by infection with parasitic blood flukes. It is also known as "bilharziasis" after Theodor Bilharz, who first identified the parasite in 18524. The WHO reported that 258 million people worldwide were infected with trematodes of the genus schistosoma, and required treatment and preventive regime5.
The distribution of Schistosoma japonicum (discovered in Japan) is mainly in China, the Philippines and Indonesia. China is endemic for S. japonicum with the oncomelania snail as an intermediate; the invasive snail Biomphalaria straminea is an intermediate host of S. mansoni that was first discovered in 1981 in Southern China6.
Schistosomiasis is a prevalent infection in tropical and subtropical areas, especially in communities without adequate sanitation and safe drinking water7. In Asia the agricultural, fishing, and domestic activities in infested water are the main source of exposure; and introduction of this disease in urban areas is secondary to migration and the rise in eco-tourism8.
Schistosoma mansoni and S. haematobium are found in Africa and Middle East, S. japonicum and S. mekongi are found in the East Hemisphere, and S. intercalatum is found in parts of central Africa9. Schistosomiasis is considered the third most devastating tropical disease in Africa, South America, the Caribbean, Middle East and Asia10.
S. japonicum has been found along the Yangtze River Basin in China, the southern and eastern islands of the Philippines, and in central Sulawesi, Indonesia. According to a Chinese report for the World Health Organization, “S. japonicum infected 45 species of animals and remained endemic in seven provinces“11 and after decades of intensive control this disease still remains a public health problem. China is among the target countries to eliminate schistosomiasis according to the Regional Action Plan for Neglected Tropical Diseases in the Western Pacific (2012-2016), and in 2011 according to the Ministry of Health a decrease of 3.4% was reported compared to the number of cases in 201012. The death estimates due to schistosomiasis need to be re-assessed, as it varies between 24,067 and 200,000 globally per year8.
There are five schistosome species that can cause infection in humans, but the ones that affect the intestinal tract are: S. mansoni found in Africa and South America, S. japonicum in East Asia, S. mekongi in Laos, Cambodia; and S. intercalatum in the West and Central Africa13.
The schistosoma japonicum’s life cycle starts when the eggs are eliminated with feces, hatch in the water and release the larvae (miracidia) that are viable for up to seven days until they penetrate the snail oncomelania14. In the snail there will be two generations of sporocysts and cercariae.
Once released from the snail, the cercariae will swim and penetrate through the skin, shed the tail and become a schistosomulae; they become adult worms and migrate to the mesenteric venules of the small and large intestine14. Finally, the circle starts again when the eggs move toward the lumen of the intestine and pass with the feces. This life cycle includes snails, domestic and wild animals which makes its control and prevention more complicated; therefore, treating the infection and reducing the oncomelania snail burden is not enough15.
The physiopathology of chronic schistosomiasis results from the eggs lodging, inducing immune response, granuloma formation, fibrotic changes, damaging the organs and tissues of the human host16. Adult worms absorb host proteins so if not attacked by the immune system, they can live coated with host antigens for years17. The shed eggs penetrate the bowel adjacent to mesenteric vessels, whereas unshed eggs go back to portal circulation, lodge and induce granulomatous reaction16. In the liver the chronic progression causes periportal fibrosis, called Symmers piperstem fibrosis, if left untreated it will lead to portal hypertension with all the cirrhosis complications18.
Clinical manifestations depend on the burden and stage of the disease, the acute phase occurs when cercariae penetrate the skin and produces dermatitis called the swimmer’s itch19; the chronic phase could present months to years after primary exposure, some do not have a clear history of acute phase or just mild and unspecific symptoms14. After 2-8 weeks of the contact with s. japonicum, the migration and maturation of the schistosomulae may produce a systemic inflammatory reaction called Katayama fever, with flu-like symptoms, hepatosplenomegaly, and eosinophilia20.
Schistosoma japonicum causes intestinal manifestations with fatigue, abdominal pain, cramping, anorexia, diarrhea, and dysentery21. When there is heavy infestation the symptoms could be severe and may lead to intestinal ulceration, bleeding, anemia, intestinal polyps, dysplasia and even bowel strictures14,21,22.
If S. japonicum remains untreated, periportal fibrosis could lead to portal hypertension and gastrointestinal bleeding23. People with hepatitis B or C and chronic hepatic injury due to schistosomiasis have more risk for a rapid progression to liver disease or development of hepatocellular carcinoma24.
For decades the gold standard for diagnosis of schistosomiasis infection has been the detection of eggs in fecal smear and the concentration techniques with Kato-Katz thick smear demonstrate the number of eggs excreted daily25. Among people living in endemic areas the approach should be through egg and antigen detection25.
The egg viability test observes hatching miracidia and assesses the treatment effectiveness, so an active infection is when viable eggs are observed whereas no viable eggs and absence of miracidia correlates with past infection or effective treatment16.
General laboratory examination includes the following and the possible findings are: cell blood count within normal ranges, CBC with anemia or eosinophilia (acute), thrombocytopenia (splenic sequestration), liver function tests could show in the chronic stage a mild elevation of alkaline phosphatase and gamma glutamyl transferase26,27.
For travelers the approach is not the same, serology is the most sensitive test because the parasite burden is low, and it is more useful than egg or antigen detection28. Crude extracts of eggs or adult worms are used as antigen in an ELISA test and antibodies to eggs can be detected from six weeks after exposure29.
Another test is the real-time PCR, in stool samples can be 94% sensitive and 99.9% specific and may offer added value in diagnosing imported schistosomiasis30. The genus-specific PCR can detect all schistosoma species that are infectious to humans and performs very well with feces and urine, but not in serum31.
In chronic hepatoesplenic schistosomiasis due to s. japonicum the ultrasonography can report periportal fibrosis around portal vein like a “bull’s eye, hypertrophy of the left hepatic lobe, atrophy of the right lobe, granulomas, splenomegaly and other portal hypertension signs32. Computed tomography and magnetic resonance imaging can demonstrate heterogeneity of hepatic parenchyma, periportal fibrosis, and the presence of venous collateral pathways33.
Biopsy is an useful diagnostic tool in the setting of intestinal schistosomiasis, it is more sensitive than stool microscopy and it can demonstrate granulomas surrounding eggs even when stool samples are negative34. At an early stage bowel wall biopsy can report mucosal edema, hemorrhage and ulceration, whereas in advanced stage it can detect a thickened bowel wall, polyps, and even strictures34.
The treatment for schistosomiasis has important objectives such as reversing acute or early chronic disease and preventing complications. The treatment in the early chronic stage can reverse periportal fibrosis and portal hypertension, but it cannot reverse late stage fibrosis and cirrhotic complications such as esophageal varices35.
Praziquantel is the drug of choice for the treatment of all schistosoma species, it acts against adult schistosoma worms with the purpose to reduce egg production but has poor activity against immature schistosoma larvae36. Therefore, the treatment is mostly effective from four to six weeks after exposure when the schistosoma is a mature worm, corroborated in an animal study that shows no pharmacological effect within 21 first days26,37.
Praziquantel’s mechanism of action is on the tegumentary and muscular tissue, causing contractions in the parasite that are followed by its death and also it inhibits the egg production in female parasites38,39. The standard dose is 40mg/kg, but for s. japonicum the dose can be 60mg/kg39. A cure rate between 65 to 90% has been described after one regimen40. After treatment, follow up in endemic areas should use stool smear after six weeks of treatment; in nonendemic areas since there is no risk for reinfection the control examination can be delayed three to six months29. If there is presence of viable eggs after the treatment, the same dose of initial therapy should be prescribed41.
Over decades the drug resistance has been a concern; researchers have identified field and experimental isolates that exhibit significantly reduced susceptibility but still the criteria used to classify a resistant strain or evidence of resistance remains controversial42,43.
Schistosoma candidate vaccines are being identified through bioinformatics, OMICs approaches44. At least three vaccines (Sm14, Sm-TSP-2 and SM-p80 antigens) in the near future will go through human clinical trials45, still an efficacious vaccine has not yet been realized.
Strategies to control schistosomiasis in endemic areas include water sanitation, minimizing contact with fresh water, community health-education, eradication of snail species, domestic animals care and treatment, proper work equipment to people at risk of expositiont11. Mass treatment has demonstrated to reduce the prevalence and morbidity of schistosomiasis by keeping the parasite load low and by increasing resistance to reinfection46.
With the fast economy and technology development in China, the surveillance systems for prevention and control have improved and a great progress has been made in the last six decades47. Several interventions to reduce transmission from domestic animals, snails to humans have been adopted as national strategies in China11, 47.
Schistosomiasis is one of the neglected tropical diseases currently affecting mostly the poor population and causing thousands of deaths annually worldwide. Schistosoma japonicum is found in China, Indonesia, Philippines, and its clinical manifestations depend on the acute or chronic phase, but if left untreated irreversible complications occur. The prognosis for the intestinal curation is optimistic after the administration of praziquantel.
Despite the regional governments and the World Health Organization efforts to maintain surveillance and treatment policies, more attention and support should be paid to this endemic disease, ensuring that the affected population not only receives suitable treatment but also the education and preventive measures that will not expose them to suffer this parasitic disease. More support should be done to prevent resistance to praziquantel and develop a secure vaccine accessible to everyone.
We encourage the education to endemic areas’ population to seek medical advice when gastrointestinal manifestations occur, to medical physicians to consider intestinal schistosomiasis as a differential diagnose when referring gastrointestinal symptoms.
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