Disease Watch Focus: Schistosomiasis
CAUSATIVE AGENTS. Human schistosomiasis is caused by the digenetic trematodes Schistosoma haematobium, Schistosoma intercalatum, Schistosoma japonicum, Schistosoma mansoni and Schistosoma mekongi. Infection occurs when larval forms of the parasites, known as cercariae, are released from aquatic snails (such as those of the genera Bulinus, Oncomelania, Biomphalaria and Neotricula) and penetrate the skin during water contact. Once inside a human host, cercariae transform into schistosomula and are transported to the portal circulation of the liver, where they mature and mate. Adult worms of S. intercalatum, S. japonicum, S. mansoni and S. mekongi migrate to the mesenteric vessels, and those of S. haematobium move to the veins that drain the urinary system. Parasite eggs are deposited in several tissues, primarily the liver, the bladder and the urinary tract. The presence of eggs in tissues elicits granulomatous reactions, causing disease. Chronic infection results in periportal fibrosis of the liver, calcification of the bladder and other sequelae. Genital schistosomiasis might increase the risk of HIV infection . Eggs are released into the excreta and, on reaching water, hatch into miracidia (another larval form of the parasite), which infect the intermediate snail hosts.
DISTRIBUTION. An estimated 200 million people in 74 countries have schistosomiasis, 85% of whom live in sub-Saharan Africa where S. haematobium, S. intercalatum and S. mansoni are endemic . S. haematobium, and S. mansoni are also found in Egypt and the arabian peninsula. S. haematobium has been reported in the Mahgreb region (Morocco, Algeria, Tunisia and Mauritania). S. mansoni is endemic in north-east Brazil, and is also present in Venezuela, Suriname and the Caribbean. S. japonicum is endemic in China and the Philippines, and is also found in Sulawesi, Indonesia. S. mekongi is found in Cambodia and Laos.
CURRENT GLOBAL STATUS. The burden of disease is disputed because original estimates  did not consider symptoms, sequelae and the chronic nature of schistosomiasis. A World Health Organization expert committee  concluded that yearly deaths could be as high as 200,000, compared with 15,000 as had been reported . An analysis of these discrepancies indicates there is underestimation, making schistosomiasis second only to malaria among tropical diseases as a cause of morbidity (C.M. Michaud, W.S. Gordon and M.H. Reich, manuscript in preparation). A strategy of morbidity control through chemotherapy has resulted in successful control in Brazil, the Mahgreb region, the Middle East, China and the Philippines. There is a threat of resurgent transmission in China due to ecological changes owing to the construction of the 'Three Gorges' dam, and in the Philippines owing to inadequate support for public health interventions. Economic development has virtually eliminated transmission of the disease from the Caribbean and Mauritius.
NEW BASIC KNOWLEDGE. The contribution of schistosomiasis to morbidity and mortality in sub-Saharan Africa has been quantified using reported symptoms, available and predicted prevalence of infection data, and associating the prevalence of infection to the prevalence of pathology . Although co-infection with HIV-1 alters the cellular immune response , it does not affect the outcome of treatment [8, 9]. The importance of genetic factors in disease is being elucidated — the relatedness of individuals might explain the variations in egg counts , and polymorphisms of the interferon (IFN)- g gene are associated with periportal fibrosis . Sequencing of the S. mansoni  and S. japonicum  genomes will further this work and provide information on new targets for diagnostics, drugs and vaccines, as well as being invaluable for understanding parasite biochemistry, development and diversity. Methods to manipulate gene expression and elucidate gene function are being developed. A fluorescent dye was used to localize gene activity in the excretory system of adult worms . RNA interference with the SGTP1 gene reduces glucose uptake in the larval stage of S. mansoni .
NEW TOOLS AND INTERVENTION METHODS. Twenty years after introduction, praziquantel remains the drug of choice. It is efficacious even though treatment failure  and resistance have been reported . Rapid diagnosis in the field, especially of intestinal schistosomiasis, continues to be difficult. As population-wide chemotherapy is the control strategy, identification of individuals with low intensity infection is problematic. The utility of new tests [18, 19] in endemic settings remains to be determined. Vaccines might provide the long term solution to schistosomiasis, and many antigens that target schistosomula have been identified . An antioxidant enzyme against the adult stage of the parasite also offers the possibility of a therapeutic vaccine . In October 2003, a review of the status of candidate vaccines concluded that GST28 (Ref. 22) and Sm14 (Ref. 23) should continue towards clinical trial, and recommended a collaborative approach for antigen discovery.
NEW STRATEGIES AND POLICIES. After reviewing data on the use of praziquantel, and taking into account the possible risk of serious morbidity to women, the WHO now recommends that infected pregnant and lactating women be offered immediate treatment and should not be excluded from community-based treatment programmes . All those at risk of morbidity and contributing to transmission should receive treatment. A Schistosomiasis Control Initiative (see Online links) is to be implemented in six African countries. One desirable outcome would be to convince policy makers and public health authorities in highly endemic countries that control is feasible by creating an infrastructure for public health interventions.
CONCLUSIONS AND FUTURE OUTLOOK
Conclusions and future outlook Sequencing of the S. mansoni and S. japonicum genomes, manipulating gene expression and understanding gene function, promise faster identification of targets for diagnostics, drugs and vaccines. Sequencing of the S. haematobium genome is also required. A collaborative approach to antigen discovery could also lead to a vaccine. It is expected that new drugs will be discovered and that the available tools for schistosomiasis control can be used to relieve endemic populations of the burden of schistosomiasis.
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