Elsevier

The Lancet

Volume 383, Issue 9936, 28 June–4 July 2014, Pages 2253-2264
The Lancet

Seminar
Human schistosomiasis

https://doi.org/10.1016/S0140-6736(13)61949-2Get rights and content

Summary

Human schistosomiasis—or bilharzia—is a parasitic disease caused by trematode flukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological effects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fitness, to organ-specific effects such as severe hepatosplenism, periportal fibrosis with portal hypertension, and urogenital inflammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the field and clinics, and integrated environmental and health-care management will be needed to ensure elimination.

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

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.

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