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)

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

T Regulatory Cell Levels Decrease in People Infected With Schistosoma mansoni on Effective Treatment

Schistosomiasis mansoni is usually a chronic infection that leads to long-term, systemic exposure to schistosome antigens. Experimental Schistosoma mansoni infection is associated with immunoregulatory mechanisms, including T regulatory cells (Treg) that may help control morbidity and dampen resistance to re-infection. We now show that some schistosomiasis mansoni patients have high proportions of CD3+/CD4+/CD25high Treg. On effective treatment with praziquantel, these high Treg percentages decrease, and fewer of the remaining Treg express CD45RO. The proportion of Treg in S. mansoni-infected patients is inversely related to their percentage of activated, putative effector T cells (CD3+/CD4+/CD25medium/HLA-DR+ cells). We conclude some, but not all, schistosomiasis mansoni patients develop high percentages of circulating Treg, and effective treatment both decreases the levels of these cells and changes their phenotypes, possibly because of the removal of constant exposure to antigens from intravascular, egg-producing adult worms

Risk Factors for Kala-Azar in Bangladesh

Since 1990, South Asia has experienced a resurgence of kala-azar (visceral leishmaniasis). To determine risk factors for kala-azar, we performed cross-sectional surveys over a 3-year period in a Bangladeshi community. By history, active case detection, and serologic screening, 155 of 2,356 residents had kala-azar with onset from 2000 to 2003. Risk was highest for persons 3–45 years of age, and no significant difference by sex was seen. In age-adjusted multivariable models, 3 factors were identified: proximity to a previous kala-azar patient (odds ratio [OR] 25.4, 95% confidence interval [CI] 15–44 within household; OR 3.2 95% CI 1.7–6.1 within 50 m), bed net use in summer (OR 0.7, 95% CI 0.53–0.93), and cattle per 1,000 m2 (OR 0.8, 95% CI 0.70–0.94]). No difference was seen by income, education, or occupation; land ownership or other assets; housing materials and condition; or keeping goats or chickens inside bedrooms. Our data confirm strong clustering and suggest that insecticide-treated nets could be effective in preventing kala-azar

T Regulatory Cell Levels Decrease in People Infected With Schistosoma mansoni on Effective Treatment

Schistosomiasis mansoni is usually a chronic infection that leads to long-term, systemic exposure to schistosome antigens. Experimental Schistosoma mansoni infection is associated with immunoregulatory mechanisms, including T regulatory cells (Treg) that may help control morbidity and dampen resistance to re-infection. We now show that some schistosomiasis mansoni patients have high proportions of CD3+/CD4+/CD25high Treg. On effective treatment with praziquantel, these high Treg percentages decrease, and fewer of the remaining Treg express CD45RO. The proportion of Treg in S. mansoni-infected patients is inversely related to their percentage of activated, putative effector T cells (CD3+/CD4+/CD25medium/HLA-DR+ cells). We conclude some, but not all, schistosomiasis mansoni patients develop high percentages of circulating Treg, and effective treatment both decreases the levels of these cells and changes their phenotypes, possibly because of the removal of constant exposure to antigens from intravascular, egg-producing adult worms