We did a systematic search of PubMed, Medline, Google Scholar, and Embase for relevant studies, with the wildcard search terms “schistosome*”, “bilharz*”, and related subject headings for reports published between Jan 1, 2006 and Dec 31, 2013. Selection of studies was not limited by language. Reports were independently reviewed for inclusion by at least two authors. Older references were included on the basis of their importance.
SeminarHuman schistosomiasis
Introduction
Schistosomiasis—also known as bilharzia—is an infectious disease that affects more than 230 million people worldwide, according to conservative estimates.1, 2 It is caused by trematode parasites of the genus Schistosoma;3 the adult male and female worms live within the veins of their human host, where they mate and produce fertilised eggs. The eggs are either shed into the environment through faeces or urine, or are retained in host tissues where they induce inflammation and then die. The eggs that reach freshwater will hatch, releasing free-living ciliated miracidia that then infect a suitable snail host. In the snail, the parasite undergoes asexual replication through mother and daughter sporocyst stages, eventually shedding tens of thousands of cercariae (the form infectious for human beings) into the water. The asexual portion of the lifecycle in the snail (figure 1) requires 4–6 weeks before infectious cercariae are released. After cercariae penetrate the skin of the mammalian host, the maturing larvae (schistosomula) need about 5–7 weeks before becoming adults and producing eggs. These intervals (in both the snail and human being) are termed prepatent periods, when the infection is ongoing but release of cercariae (from snails) or eggs (from humans) cannot be detected. Cercariae can remain infective in freshwater for 1–3 days, but deplete their energy reserves greatly over a few hours.4 Eggs—whether excreted or retained in the body—die within 1–2 weeks after being released by the female worm.
Three main species of schistosomes infect human beings, Schistosoma haematobium, Schistosoma mansoni, and Schistosoma japonicum. S haematobium and S mansoni both occur in Africa and the Middle East, whereas only S mansoni is present in the Americas. S japonicum is localised to Asia, primarily the Philippines and China. Three more locally distributed species also cause human disease: Schistosoma mekongi, in the Mekong River basin, and Schistosoma guineensis and Schistosoma intercalatum in west and central Africa (figure 2). Each species has a specific range of suitable snail hosts, so their distribution is defined by their host snails' habitat range. S mansoni and S haematobium need certain species of aquatic freshwater Biomphalaria and Bulinus snails, respectively. S japonicum uses amphibious freshwater Oncomelania spp snails as its intermediate host.
Schistosomes live an average of 3–10 years, but in some cases as long as 40 years, in their human hosts.6, 7 Adult male and female worms live much of this time in copula, the slender female fitted into the gynaecophoric canal of the male, where she produces eggs and he fertilises them (appendix). Adult worms digest erythrocytes and although most of their energy is obtained by glucose metabolism,8, 9 egg production is dependent on fatty acid oxidation10—both glucose and fatty acids being derived from the host. They live within either the perivesicular (S haematobium) or mesenteric (S mansoni, S japonicum, and others) venules. Schistosomes have no anus and cannot excrete waste products, so they regurgitate waste into the bloodstream. Some of these expelled products are useful for blood-based and urine-based diagnostic assays. S japonicum and S mekongi are zoonoses that also infect a wide range of mammalian hosts, including dogs, pigs, and cattle, which greatly complicates control and elimination efforts. Although S mansoni can infect rodents and non-human primates, human beings are thought to be its predominant mammalian reservoir. Understanding the schistosome lifecycle (figure 1) and the parasite's movement between intermediate (snail) and definitive (mammalian) hosts is fundamental to the control and elimination of human schistosomiasis. Environmental changes can either increase11 or decrease12 transmission. Changes in snail habitat and predators are crucial determinants of transmission, and prepatent periods can affect the efficacy of treatment regimens.13 Effective treatment of people (such that their excreta do not contain eggs), the prevention of sewage contamination of freshwater, the elimination of intermediate host snails, and the prevention of human contact with water containing infected snails can help to prevent transmission.
Although still in its infancy, studies of schistosome genomics will prove crucial for identification of candidates for drug targets and prophylactic vaccines.14 Schistosome populations are very genetically heterogeneous15, 16 and genomic characterisation of human schistosomes can be used to establish epidemiological patterns of transmission, including insights into interspecies hybridisation among some schistosome species. For example, in areas with high transmission of both S haematobium and the S bovis parasites of cattle, bidirectional introgressive hybridisation occurs, yielding schistosomes of mixed heritage in people and snails.17 The implications of these findings are unclear for human disease, but these populations of hybrid schistosomes could prove problematic if they can replace existing species and parasite strains or extend intermediate host ranges.
Section snippets
Epidemiology
In regions endemic for schistosomiasis the most prevalent form of the disease is chronic schistosomiasis, resulting from repeated exposure to infectious cercariae. In such settings, a child's initial infection often occurs by age 2 years with the burden of infection increasing in intensity during the next 10 years as new worms colonise the child's body. Typically, the highest prevalence and intensities of infection occur in young adolescents (figure 3), after which both intensity and prevalence
Pathogenesis and morbidity
All evidence suggests that schistosome eggs, and not adult worms, induce the morbidity caused by schistosome infections.22 Many eggs are not excreted and become permanently lodged in the intestines or liver (for S mansoni, S japonicum, and S mekongi) or in the bladder and urogenital system (for S haematobium). There, the eggs induce a granulomatous host immune response largely characterised by lymphocytes (which mainly produce T-helper-2 cytokines; eg, interleukins 4, 5, and 13), eosinophils,
Comorbidities
Schistosomiasis often occurs alongside other infectious diseases, with a wide range of co-infecting organisms. In addition to its direct morbidities, schistosomiasis can affect immunological and physiological relations between the host and co-infecting pathogens. Thus, better control of schistosomiasis could provide adjunctive benefits in such areas. The most compelling example might be the effect of schistosomiasis on susceptibility to HIV infection. Among women with female genital
Diagnosis
The diagnostic standard for active schistosomiasis is viable eggs in urine (S haematobium), faeces (S japonicum, S mansoni), or tissue biopsies. At present, the presence of infecting schistosomes cannot be ruled out definitively because of the low sensitivity of standard urine and faecal examinations.71 Microscopic examination of polycarbonate filters for eggs in the urine, urine dipstick assays for heme,72, 73 or the Kato-Katz faecal examination for schistosome eggs74 are recommended by WHO
Treatment
Praziquantel is the drug of choice for schistosomiasis. It is effective against all Schistosoma species, but its mechanism of action is not clearly understood. For full efficacy it needs an effective host antibody response.86, 87 Praziquantel acts against adult schistosome worms, but has poor activity against immature schistosome larvae. A standard dose of 40 mg/kg is thought effective for treatment of S haematobium and S mansoni and can safely be used in pregnancy after the first trimester.
Immunology
Immune responses during schistosomiasis can be thought of in terms of three topics: immunopathogenesis, resistance to reinfection, and immunodiagnostics. All three are affected by the development and establishment of chronic infection in the presence of chronic antigenic exposure. Faced with multiple antibody and cellular immune responses, adult schistosome worms persist in the bloodstream for decades, seemingly impervious to attack from immune effector mechanisms. This immune evasion by adult
Burden of disease
Official estimates113 of the prevalence of Schistosoma infection were based on insensitive egg-detection techniques, which substantially under-represent active infection.114, 115, 116 Schistosomiasis initiated by infection in early life persists into adulthood, even after infection terminates.117 Thus, although more than 230 million people are thought to be actively infected with schistosomes,1 a similar number are in a post-infection stage but continue to have residual morbidity. As a result,
Mapping and surveillance
Implementation of population-based control programmes by WHO guidelines requires prevalence estimates, to decide where to use school-based versus community-based delivery of praziquantel. A crucial consideration for the effective integration of preventive chemotherapy for neglected tropical diseases is whether schistosoma infection overlaps with filariasis, onchocerciasis, intestinal worm infections, and trachoma,122 which are all targeted for control through preventive chemotherapy. Climate
Control and elimination
It is an exciting time for control and elimination of schistosomiasis. In 1984, the WHO endorsed a strategy to control morbidity caused by schistosomiasis through preventive chemotherapy with praziquantel.133 Because of its excellent tolerability and generally good ability to either cure or drastically reduce egg output (70–90%),134, 135 praziquantel can be distributed yearly (or in alternate years) by moderately trained school teachers or community health workers to obtain sufficient coverage
Conclusion
Schistosomiasis is an ancient human disease with effects worldwide, particularly in the poorest communities. Effective early treatment is possible, thereby preventing the substantial immune-mediated effects of Schistosoma infection on human health. New diagnostic tests and new approaches to treatment implementation are aimed at local, then regional elimination, thus changing the public health agenda from curative approaches to a truly preventive strategy.
Search strategy and selection criteria
References (150)
- et al.
Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010
Lancet
(2012) - et al.
Human schistosomiasis
Lancet
(2006) - et al.
The energy production of the adult Schistosoma mansoni is for a large part aerobic
Mol Biochem Parasitol
(1985) - et al.
Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk
Lancet Infect Dis
(2006) - et al.
Population genetic structure of Schistosoma mansoni and Schistosoma haematobium from across six sub-Saharan African countries: implications for epidemiology, evolution and control
Acta Trop
(2013) - et al.
Katayama syndrome
Lancet Infect Dis
(2007) Hepatosplenic schistosomiasis: a model for the study of portal hypertension
Ann Hepatol
(2002)- et al.
Schistosoma mansoni: assessment of morbidity before and after control
Acta Trop
(2000) - et al.
A review of female genital schistosomiasis
Trends Parasitol
(2012) - et al.
Community-based study of genital schistosomiasis in men from Madagascar
Lancet
(2000)
Semen quality in Schistosoma haematobium infected men in Madagascar
Acta Trop
Human schistosomiasis and anemia: the relationship and potential mechanisms
Trends Parasitol
Schistosomiasis japonica, anemia, and iron status in children, adolescents, and young adults in Leyte, Philippines 1
Am J Clin Nutr
Nutritional status improves after treatment of Schistosoma japonicum-infected children and adolescents
J Nutr
Empiric deworming to delay HIV disease progression in adults with HIV who are ineligible for initiation of antiretroviral treatment (the HEAT study): a multi-site, randomised trial
Lancet Infect Dis
Health implications of chronic hepatosplenomegaly in Kenyan school-aged children chronically exposed to malarial infections and Schistosoma mansoni
Trans R Soc Trop Med Hyg
Multiplex real-time PCR for the detection and quantification of Schistosoma mansoni and S. haematobium infection in stool samples collected in northern Senegal
Trans R Soc Trop Med Hyg
Use of sentinel snails for the detection of Schistosoma haematobium transmission on Zanzibar and observations on transmission patterns
Acta Trop
Transmission control for schistosomiasis - why it matters now
Trends Parasitol
Development and validation of a ‘tablet pole’ for the administration of praziquantel in sub-Saharan Africa
Trans R Soc Trop Med Hyg
Treatment of schistosomiasis in African infants and preschool-aged children: downward extension and biometric optimization of the current praziquantel dose pole
In Health
Schistosomiasis in African infants and preschool children: let them now be treated!
Trends Parasitol
Oral artemether for prevention of Schistosoma mansoni infection: randomised controlled trial
Lancet
Resistance of Schistosoma mansoni to praziquantel: is there a problem?
Trans R Soc Trop Med Hyg
Interpreting low praziquantel cure rates of Schistosoma mansoni infections in Senegal
Trends Parasitol
The immune dependence of chemotherapy
Parasitol Today
Schistosomiasis
Nat Rev Microbiol
The schistosomes and their intermediate hosts
The survival of the cercariae of Schistosoma mansoni in relation to water temperature and glycogen utilization
Parasitology
Schistosomiasis mansoni in Yemeni in California: duration of infection, presence of disease, therapeutic management
Am J Trop Med Hyg
Developmental bilharziasis caused by Schistosoma mansoni discovered 37 years after infestation
Bull Soc Pathol Exot
Forty years of helminth biochemistry
Parasitology
Fatty acid oxidation is essential for egg production by the parasitic flatworm Schistosoma mansoni
PLoS Pathog
China's new strategy to block Schistosoma japonicum transmission: experiences and impact beyond schistosomiasis
Trop Med Int Health
Artemisinins for schistosomiasis and beyond
Curr Opin Investig Drugs
SchistoDB: an updated genome resource for the three key schistosomes of humans
Nucleic Acids Res
Genetic diversity of schistosomes and snails: implications for control
Parasitology
Bidirectional introgressive hybridization between a cattle and human schistosome species
PLoS Pathog
Urinary tract morbidity in schistosomiasis haematobia: associations with age and intensity of infection in an endemic area of Coast Province, Kenya
Am J Trop Med Hyg
Effect of targeted mass treatment on intensity of infection and morbidity in schistosomiasis mansoni: seven-year follow-up of a community in Machakos, Kenya
Trans Assoc Am Physicians
Closing the praziquantel treatment gap: new steps in epidemiological monitoring and control of schistosomiasis in African infants and preschool-aged children
Parasitology
Impact of polyparasitic infections on anemia and undernutrition among Kenyan children living in a Schistosoma haematobium-endemic area
Am J Trop Med Hyg
Immunopathogenesis of human schistosomiasis
Parasite Immunol
The immunobiology of schistosomiasis
Nat Rev Immunol
Th2 responses in schistosomiasis
Semin Immunopathol
Studies on granuloma formation. IV. In vivo antigenicity of schistosome egg antigen in lung tissue
J Immunol
Idiotypic sensitization in utero of children born to mothers with schistosomiasis or Chagas' disease
J Clin Invest
B cell sensitization to helminthic infection develops in utero in humans
J Immunol
Schistosomal colonic disease
Gut
Endoscopic findings and clinicopathologic characteristics of colonic schistosomiasis: a report of 46 cases
World J Gastroenterol
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