A Schistosomiasis Research Agenda

There is a long and rich history of research and control in the field of schistosomiasis that has resulted in major scientific and public health accomplishments. Examples of such findings and accomplishments include immunologic regulation in chronic infections [1], the association of helminth infections with Th1-regulating Th2-type immune responses [2], the critical role of interleukin-13 in fibrogenesis [3], and the development and validation of the “dose pole” for determining praziquantel dosages in the field [4],[5]. Perhaps in part because of this broad and successful history, those who work on schistosomiasis come from a wide variety of backgrounds and interests. While such variety is enriching to the field, it sometimes results in diverse opinions about which of the many research opportunities should be pursued. Such diversity, we believe, has at times led to a divisiveness that has harmed overall progress in the field. Partly in response to such events, we have worked with as many of those interested in schistosomiasis as we could identify to develop what we feel is a comprehensive and cohesive agenda for schistosomiasis research (Image 1)

Human schistosomiasis

Human schistosomiasis-or bilharzia-is a parasitic disease caused by trematode fl ukes 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 eff ects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fi tness, to organ-specifi c eff ects such as severe hepatosplenism, periportal fi brosis with portal hypertension, and urogenital infl ammation 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 fi eld and clinics, and integrated environmental and health-care management will be needed to ensure elimination. © Chataway et al. Open Access article distributed under the terms of CC BY

Impact of two rounds of praziquantel mass drug administration on Schistosoma mansoni infection prevalence and intensity: a comparison between community wide treatment and school based treatment in western Kenya

AbstractThis study compared the effectiveness of the community-wide treatment and school-based treatment approaches in the control of Schistosoma mansoni infections in villages with ⩾25% prevalence in western Kenya. Stool samples from first year students, 9–12year olds and adults (20–55years) were analyzed by the Kato–Katz technique for S. mansoni eggs. After two rounds of treatment, S. mansoni prevalence and intensity levels significantly declined in both treatment approaches. Prevalence comparisons between the two approaches did not show any significant differences following treatment. However, infection intensity levels in the 9–12year old school-attending pupils were significantly higher in the community-wide treatment arm than in the school-based treatment arm. Nevertheless, significant reductions in S. mansoni infection prevalence and intensity levels were achieved among school-age children regardless of the treatment approach used

Insights from quantitative and mathematical modelling on the proposed WHO 2030 goal for schistosomiasis

Schistosomiasis remains one of the neglected tropical diseases (NTDs) impacting millions of people around the world. The World Health Organization (WHO) recently proposed a goal of elimination as a public health problem (EPHP) for schistosomiasis to be reached by 2030. Current WHO treatment guidelines for achieving EPHP focus on targeting school-aged children. The NTD Modelling Consortium has developed mathematical models to study schistosomiasis transmission dynamics and the impact of control measures. Our modelling insights on Schistosoma mansoni have shown that EPHP is likely to be attainable in low to moderate prevalence settings using the current guidelines. However, as prevalence rises within high prevalence settings, EPHP is less likely to be achieved unless both school-aged children and adults are treated (with coverage levels increasing with the adult burden of infection). We highlight the challenges that are faced by treatment programmes, such as non-adherence to treatment and resurgence, which can hinder progress towards achieving and maintaining EPHP. Additionally, even though EPHP may be reached, prevalence can still be high due to persisting infections. Therefore, without interruption of transmission, treatment will likely have to continue to maintain EPHP. Further modelling work is being carried out, including extending our results to S. haematobium. By providing these modelling insights, we aim to inform discussions on the goals and treatment guidelines for schistosomiasis.</ns4:p

Five-year impact of different multi-year mass drug administration strategies on childhood Schistosoma mansoni-associated morbidity:A combined analysis from the schistosomiasis consortium for operational research and evaluation cohort studies in the Lake Victoria Regions of Kenya and Tanzania

The WHO recommends mass treatment with praziquantel as the primary approach for; Schistosoma mansoni; -related morbidity control in endemic populations. The Schistosomiasis Consortium for Operational Research and Evaluation implemented multi-country, cluster-randomized trials to compare effectiveness of community-wide and school-based treatment (SBT) regimens on prevalence and intensity of schistosomiasis. To assess the impact of two different treatment schedules on; S. mansoni; -associated morbidity in children, cohort studies were nested within the randomized trials conducted in villages in Kenya and Tanzania having baseline prevalence ≥ 25%. Children aged 7-8 years were enrolled at baseline and followed to ages 11-12 years. Infection intensity and odds of infection were reduced both in villages receiving four years of annual community-wide treatment (CWT) and those who received biennial SBT over 4 years. These regimens were also associated with reduced odds of undernutrition and reduced odds of portal vein dilation at follow-up. However, neither hemoglobin levels nor the prevalence of the rare abnormal pattern C liver scores on ultrasound improved. For the combined cohorts, growth stunting worsened in the areas receiving biennial SBT, and maximal oxygen uptake as estimated by fitness testing scores declined under both regimens. After adjusting for imbalance in starting prevalence between study arms, children in villages receiving annual CWT had significantly greater decreases in infection prevalence and intensity than those villages receiving biennial SBT. Although health-related quality-of-life scores improved in both study arms, children in the CWT villages gained significantly more. We conclude that programs using annual CWT are likely to achieve better overall; S. mansoni; morbidity control than those implementing only biennial SBT

Schistosoma mansoni Enhances Host Susceptibility to Mucosal but Not Intravenous Challenge by R5 Clade C SHIV

Parasitic infections have been postulated to increase host susceptibility to HIV-1. We previously demonstrated that rhesus monkeys with active schistosomiasis were significantly more likely to become systemically infected after intrarectal exposure to an R5-tropic clade C simian-human immunodeficiency virus then were parasite-free control animals. However, we could not address whether parasites exert their effect at the mucosal level or systemically. To address the latter possibility, we measured the virus doses needed to achieve systemic infection after intravenous exposure of parasite-free or parasite-positive monkeys using the identical virus stock. None of the viral parameters tested in these two groups of monkeys were statistically significantly different. These results suggest that schistosomiasis modulates susceptibility to immunodeficiency virus acquisition predominantly at the mucosal level. Treatment for parasitic infections in populations at higher risk for HIV-1 acquisition could represent a cost-effective approach to slow the spread of HIV-1, which is predominantly transmitted through mucosal routes