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

SCORE studies on the impact of drug treatment on morbidity due to <i>Schistosoma mansoni</i> and <i>Schistosoma haematobium</i> infection

The Schistosomiasis Consortium for Operational Research (SCORE) was funded in 2008 to improve the evidence base for control and elimination of schistosomiasis-better understanding of the systemic morbidities experienced by children in schistosomiasis-endemic areas and the response of these morbidities to treatment, being essential for updating WHO guidelines for mass drug administration (MDA) in endemic areas. This article summarizes the SCORE studies that aimed to gauge the impact of MDA-based treatment on schistosomiasis-related morbidities. Morbidity cohort studies were embedded in the SCORE's larger field studies of gaining control of schistosomiasis in Kenya and Tanzania. Following MDA, cohort children had less undernutrition, less portal vein dilation, and increased quality of life in Year 5 compared with baseline. We also conducted a pilot study of the Behavioral Assessment System for Children (BASC-2) in conjunction with the Kenya gaining control study, which demonstrated beneficial effects of treatment on classroom behavior. In addition, the SCORE's Rapid Answers Project performed systematic reviews of previously available data, providing two meta-analyses related to morbidity. The first documented children's infection-related deficits in school attendance and achievement and in formal tests of learning and memory. The second showed that greater reductions in egg output following drug treatment correlates significantly with reduced odds of most morbidities. Overall, these SCORE morbidity studies provided convincing evidence to support the use of MDA to improve the health of school-aged children in endemic areas. However, study findings also support the need to use enhanced metrics to fully assess and better control schistosomiasis-associated morbidity

Impact of different mass drug administration strategies for gaining and sustaining control of <i>Schistosoma mansoni</i> and <i>Schistosoma haematobium</i> infection in Africa

This report summarizes the design and outcomes of randomized controlled operational research trials performed by the Bill & Melinda Gates Foundation-funded Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) from 2009 to 2019. Their goal was to define the effectiveness and test the limitations of current WHO-recommended schistosomiasis control protocols by performing large-scale pragmatic trials to compare the impact of different schedules and coverage regimens of praziquantel mass drug administration (MDA). Although there were limitations to study designs and performance, analysis of their primary outcomes confirmed that all tested regimens of praziquantel MDA significantly reduced local; Schistosoma; infection prevalence and intensity among school-age children. Secondary analysis suggested that outcomes in locations receiving four annual rounds of MDA were better than those in communities that had treatment holiday years, in which no praziquantel MDA was given. Statistical significance of differences was obscured by a wider-than-expected variation in community-level responses to MDA, defining a persistent hot spot obstacle to MDA success. No MDA schedule led to elimination of infection, even in those communities that started at low prevalence of infection, and it is likely that programs aiming for elimination of transmission will need to add supplemental interventions (e.g., snail control, improvement in water, sanitation and hygiene, and behavior change interventions) to achieve that next stage of control. Recommendations for future implementation research, including exploration of the value of earlier program impact assessment combined with intensification of intervention in hot spot locations, are discussed

Introgressive Hybridization of Schistosoma haematobium Group Species in Senegal: Species Barrier Break Down between Ruminant and Human Schistosomes

The file attached is the Published/publisher’s pdf version of the article.Copyright: © 2013 Webster et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Cytokine responses to the anti-schistosome vaccine candidate antigen glutathione-S-transferase vary with host age and are boosted by praziquantel treatment.

BACKGROUND: Improved helminth control is required to alleviate the global burden of schistosomiasis and schistosome-associated pathologies. Current control efforts rely on the anti-helminthic drug praziquantel (PZQ), which enhances immune responses to crude schistosome antigens but does not prevent re-infection. An anti-schistosome vaccine based on Schistosoma haematobium glutathione-S-transferase (GST) is currently in Phase III clinical trials, but little is known about the immune responses directed against this antigen in humans naturally exposed to schistosomes or how these responses change following PZQ treatment. METHODOLOGY: Blood samples from inhabitants of a Schistosoma haematobium-endemic area were incubated for 48 hours with or without GST before (n = 195) and six weeks after PZQ treatment (n = 107). Concentrations of cytokines associated with innate inflammatory (TNFα, IL-6, IL-8), type 1 (Th1; IFNγ, IL-2, IL-12p70), type 2 (IL-4, IL-5, IL-13), type 17 (IL-17A, IL-21, IL-23p19) and regulatory (IL-10) responses were quantified in culture supernatants via enzyme-linked immunosorbent assay (ELISA). Factor analysis and multidimensional scaling were used to analyse multiple cytokines simultaneously. PRINCIPAL FINDINGS: A combination of GST-specific type 2 (IL-5 and IL-13) and regulatory (IL-10) cytokines was significantly lower in 10-12 year olds, the age group at which S. haematobium infection intensity and prevalence peak, than in 4-9 or 13+ year olds. Following PZQ treatment there was an increase in the number of participants producing detectable levels of GST-specific cytokines (TNFα, IL-6, IL-8, IFNγ, IL-12p70, IL-13 and IL-23p19) and also a shift in the GST-specific cytokine response towards a more pro-inflammatory phenotype than that observed before treatment. Participant age and pre-treatment infection status significantly influenced post-treatment cytokine profiles. CONCLUSIONS/SIGNIFICANCE: In areas where schistosomiasis is endemic host age, schistosome infection status and PZQ treatment affect the cellular cytokine response to GST. Thus the efficacy of a GST-based vaccine may also be shaped by the demographic and epidemiological characteristics of targeted populations

Circulating CD14brightCD16+ 'intermediate' monocytes exhibit enhanced parasite pattern recognition in human helminth infection.

Circulating monocyte sub-sets have recently emerged as mediators of divergent immune functions during infectious disease but their role in helminth infection has not been investigated. In this study we evaluated whether 'classical' (CD14brightCD16-), 'intermediate' (CD14brightCD16+), and 'non-classical' (CD14dimCD16+) monocyte sub-sets from peripheral blood mononuclear cells varied in both abundance and ability to bind antigenic material amongst individuals living in a region of Northern Senegal which is co-endemic for Schistosoma mansoni and S. haematobium. Monocyte recognition of excretory/secretory (E/S) products released by skin-invasive cercariae, or eggs, of S. mansoni was assessed by flow cytometry and compared between S. mansoni mono-infected, S. mansoni and S. haematobium co-infected, and uninfected participants. Each of the three monocyte sub-sets in the different infection groups bound schistosome E/S material. However, 'intermediate' CD14brightCD16+ monocytes had a significantly enhanced ability to bind cercarial and egg E/S. Moreover, this elevation of ligand binding was particularly evident in co-infected participants. This is the first demonstration of modulated parasite pattern recognition in CD14brightCD16+ intermediate monocytes during helminth infection, which may have functional consequences for the ability of infected individuals to respond immunologically to infection

Artificial Induction of Concomitant Immunity against Schistosoma mansoni in Mice

Program year: 1983-1984Digitized from print original stored in HDRBefore attempting to artificially induce a state of concomitant immunity, the theory why concomitant immunity exists in vivo must be examined. Most likely, due to their common genetic material, the adult worms and schistosomula have some sort of common antigenic determinant on their teguments. An antibody specific for some such common antigeni determinant would therefore direct an immune response against both an adult worm and a schistosomulum. As the adult worm has the abilty to evade host immune responses, it would be only slightly or not at all affected by this immune response. The young schistosomule, however, would be unable to escape the host’s immune action and therefore most likely be killed. Thus, when a host is sufficiently sensitized to an antigen present on the schistosomule’s tegument, it repels the infection. In natural infections, the host’s immune system is not quick enough to respond to such an antigen and mount an immune response directed against the schistosomule before the parasite is able to develop immune evasion capabilities. Therefore, in order to attempt to artificially induce concomitant immunity, an antigenic determinant from the schistosomule could be isolated and injected into a non-infected "host” in order to attempt to sensitize that individual to the antigen prior to the cercarial attack so that when such an attack occured, the individual’s immune response could easily repel it. Thus, it seems as if the problem could be solved with simple vaccination techniques using cercaria to sensitize individuals against cercaria. However. whole schistosomules that have been either killed or irradiated and then injected into an individual fail to induce proper immunological sensitization against cercaria to prevent infection. It would therefore seem that in order to evoke the host's immune system to sensitivity, a specific antigen must be used. Also, in order to concur with in vivo models, this specific antigen must also be associated with the adult worm. However, because of the adult worm's evasive abilities and the lack of definitive knowledge of how these abilities work, it is not clear if the host even mounts a successful antibody response against the adult worm. The purpose of this research is to discern whether there are antigens on the worm that the host recognizes as foreign and mounts an antibody response against. Understanding in this area can lead to a more full understanding of concomitant immunity and therefore a greater possibility of artificially inducing it

Developing and validating a screening tool for female genital schistosomiasis in urban Zambia

BackgroundThe World Health Organization estimates that 56 million women and girls live with female genital schistosomiasis (FGS) in sub-Saharan Africa. FGS is often confused with symptoms of other genital abnormalities, and gold standard diagnosis with colposcopy is infeasible in most health facilities. Schistosomiasis haematobium is endemic in Zambia, yet routine screening or diagnostic efforts for FGS remain unavailable. Our study aimed to develop and pilot test a feasible FGS screening algorithm to implement in Zambian government clinics.Methodology/Principal FindingsWe recruited 499 women from a longitudinal cohort of HIV-negative adult women in Lusaka and Ndola, Zambia. We used demographic, risk factor, and symptom data collected from standardized surveys, gynecological exams, and laboratory tests to develop a screening algorithm for FGS among a derivation cohort (n=349). After cross-validation using 5-fold iterative resampling, the algorithm was applied in a holdout sample of the cohort (n=150). The prevalence of FGS (ascertained by expert review) was 23.4% in the study population. The screening algorithm included childhood and travel exposure to rivers and streams; testing positive for visual inspection of the cervix with acetic acid; hematuria; reporting less than the median average age at sexual debut (&lt;17 years); when asked what diseases can be transmitted via freshwater exposure, reporting ‘none’; being born outside of Lusaka or Copperbelt Province; and reporting occupation as ‘Housekeeper’. The screening algorithm had reasonable discrimination in the derivation cohort (area under the curve [AUC]=0.69, 95% confidence interval [CI]: 0.66-0.79, p-value&lt;0.001). Using a score cut off ≥ 2 the risk algorithm in the derivation cohort had 77% sensitivity, 48% specificity, 35% positive predictive value, and 85% negative predictive value.Conclusions/SignificanceGiven the prevalence of FGS and associated morbidities, improved screening for FGS is imperative. We developed a simple screening algorithm to improve the diagnosis and treatment of FGS among adult women in Zambian government clinics