Cross-sectional interview study of fertility, pregnancy, and urogenital schistosomiasis in coastal Kenya: Documented treatment in childhood is associated with reduced odds of subfertility among adult women.

BACKGROUND: Previous research has documented an increased risk of subfertility in areas of sub-Saharan Africa, as well as an ecological association between urogenital schistosomiasis prevalence and decreased fertility. This pilot project examined reproductive patterns and the potential effects of childhood urogenital Schistosoma haematobium infection and individual treatment experience on adult subfertility among women who were long-term residents in an S. haematobium-endemic region of coastal Kenya. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed findings from 162 in-depth interviews with women of childbearing age in a rural, coastal community, linking them, if possible, to their individual treatment records from previous multi-year longitudinal studies of parasitic infections. Reproductive histories indicated a much local higher local rate of subfertility (44%) than worldwide averages (8-12%). Although, due to the very high regional prevalence of schistosomiasis, a clear relationship could not be demonstrated between a history of S. haematobium infection and adult subfertility, among a convenience sub-sample of 61 women who had received documented treatment during previous interventional trials, a significant association was found between age at first anti-schistosomal treatment and later fertility in adulthood, with those women treated before age 21 significantly less likely to have subfertility (P = 0.001). CONCLUSIONS/SIGNIFICANCE: The high subfertility rate documented in this pilot study suggests the importance of programs to prevent and treat pelvic infections in their early stages to preclude reproductive tract damage. The available documented treatment data also suggest that early anti-schistosomal treatment may prevent the fertility-damaging effects of urogenital schistosomiasis, and lend support for programs that provide universal treatment of children in S. haematobium-endemic regions.

Systematic review of community-based, school-based, and combined delivery modes for reaching school-aged children in mass drug administration programs for schistosomiasis.

BACKGROUND: The mainstay of current schistosomiasis control programs is mass preventive chemotherapy of school-aged children with praziquantel. This treatment is delivered through school-based, community-based, or combined school- and community-based systems. Attaining very high coverage rates for children is essential in mass schistosomiasis treatment programs, as is ensuring that there are no persistently untreated subpopulations, a potential challenge for school-based programs in areas with low school enrollment. This review sought to compare the different treatment delivery methods based both on their coverage of school-aged children overall and on their coverage specifically of non-enrolled children. In addition, qualitative community or programmatic factors associated with high or low coverage rates were identified, with suggestions for overall coverage improvement. METHODOLOGY/PRINCIPAL FINDINGS: This review was registered prospectively with PROSPERO (CRD 42015017656). Five hundred forty-nine publication of potential relevance were identified through database searches, reference lists, and personal communications. Eligible studies included those published before October 2015, written in English or French, containing quantitative or qualitative data about coverage rates for MDA of school-aged children with praziquantel. Among the 22 selected studies, combined community- and school-based programs achieved the highest median coverage rates (89%), followed by community-based programs (72%). School-based programs had both the lowest median coverage of children overall (49%) and the lowest coverage of the non-enrolled subpopulation of children. Qualitatively, major factors affecting program success included fear of side effects, inadequate education about schistosomiasis, lack of incentives for drug distributors, and inequitable distribution to minority groups. CONCLUSIONS/SIGNIFICANCE: This review provides an evidence-based framework for the development of future schistosomiasis control programs. Based on our results, a combined community and school-based delivery system should maximize coverage for both in- and out-of-school children, especially when combined with interventions such as snacks for treated children, educational campaigns, incentives for drug distributors, and active inclusion of marginalized groups. TRIAL REGISTRATION: ClinicalTrials.gov CRD42015017656.

Change in children's school behavior after mass administration of praziquantel for Schistosoma mansoni infection in endemic areas of western Kenya: A pilot study using the Behavioral Assessment System for Children (BASC-2).

BACKGROUND: Schistosomiasis is a parasite-related chronic inflammatory condition that can cause anemia, decreased growth, liver abnormalities, and deficits in cognitive functioning among children. METHODOLOGY/PRINCIPAL FINDINGS: This study used the Behavior Assessment System for Children (BASC-2) to collect data on thirty-six 9-12 year old school-attending children's behavioral profiles in an Schistosoma mansoni-endemic area of western Kenya, before and after treatment with praziquantel for S. mansoni infection. BASC-2 T scores were significantly reduced post-treatment (p < 0.05) for each of the 'negative' behavior categories including externalizing problems (hyperactivity, aggression, and conduct problems that are disruptive in nature), internalizing problems (anxiety, depression, somatization, atypicality, and withdrawal), school problems (academic difficulties, included attention problems and learning problems), and the composite behavioral symptoms index (BSI), signifying improved behavior. While the observed improvement in the 'positive' behavior category of adaptive skills (adaptability, functional communication, social skills, leadership, and study skills) was not statistically significant, there were significant improvements in two adaptive skills subcategories: social skills and study skills. CONCLUSION/SIGNIFICANCE: Results of this study suggest that children have better school-related behaviors without heavy S. mansoni infection, and that infected children's behaviors, especially disruptive problem behaviors, improve significantly after praziquantel treatment.

HS3ST1 genotype regulates antithrombin's inflammomodulatory tone and associates with atherosclerosis.

The HS3ST1 gene controls endothelial cell production of HSAT+ - a form of heparan sulfate containing a specific pentasaccharide motif that binds the anticoagulant protein antithrombin (AT). HSAT+ has long been thought to act as an endogenous anticoagulant; however, coagulation was normal in Hs3st1-/- mice that have greatly reduced HSAT+ (HajMohammadi et al., 2003). This finding indicates that HSAT+ is not essential for AT's anticoagulant activity. To determine if HSAT+ is involved in AT's poorly understood inflammomodulatory activities, Hs3st1-/- and Hs3st1+/+ mice were subjected to a model of acute septic shock. Compared with Hs3st1+/+ mice, Hs3st1-/- mice were more susceptible to LPS-induced death due to an increased sensitivity to TNF. For Hs3st1+/+ mice, AT treatment reduced LPS-lethality, reduced leukocyte firm adhesion to endothelial cells, and dilated isolated coronary arterioles. Conversely, for Hs3st1-/- mice, AT induced the opposite effects. Thus, in the context of acute inflammation, HSAT+ selectively mediates AT's anti-inflammatory activity; in the absence of HSAT+, AT's pro-inflammatory effects predominate. To explore if the anti-inflammatory action of HSAT+ also protects against a chronic vascular-inflammatory disease, atherosclerosis, we conducted a human candidate-gene association study on >2000 coronary catheterization patients. Bioinformatic analysis of the HS3ST1 gene identified an intronic SNP, rs16881446, in a putative transcriptional regulatory region. The rs16881446G/G genotype independently associated with the severity of coronary artery disease and atherosclerotic cardiovascular events. In primary endothelial cells, the rs16881446G allele associated with reduced HS3ST1 expression. Together with the mouse data, this leads us to conclude that the HS3ST1 gene is required for AT's anti-inflammatory activity that appears to protect against acute and chronic inflammatory disorders.

Divergent Effects of Schistosoma haematobium Exposure on Intermediate-Host Snail Species Bulinus nasutus and Bulinus globosus from Coastal Kenya.

AbstractSchistosoma haematobium infection causes urogenital schistosomiasis, a chronic inflammatory disease that is highly prevalent in many parts of sub-Saharan Africa. Bulinid snails are the obligate intermediate hosts in the transmission of this parasite. In the present study, Bulinus globosus and Bulinus nasutus snails from coastal Kenya were raised in the laboratory and exposed to miracidia derived from sympatric S. haematobium specimens to assess the species-specific impact of parasite contact and infection. The snails' subsequent patterns of survival, cercarial shedding, and reproduction were monitored for up to 3 months postexposure. Schistosoma haematobium exposure significantly decreased the survival of B. globosus, but not of B. nasutus. Although both species were capable of transmitting S. haematobium, the B. globosus study population had a greater cumulative incidence of cercarial shedders and a higher average number of cercariae shed per snail than did the B. nasutus population. The effects of prior parasite exposure on snail reproduction were different between the two species. These included more numerous production of egg masses by exposed B. nasutus (as compared with unexposed snails), contrasted to decreased overall egg mass production by parasite-exposed B. globosus. The interspecies differences in the response to and transmission of S. haematobium reflect clear differences in life histories for the two bulinid species when they interact with the parasite, which should be taken into account when planning control interventions aimed at reducing each host snails' contribution to local transmission of Schistosoma infection.