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The impact of endemic infections on protective immunity is critical to inform vaccination strategies. In this study, we assessed the influence ofSchistosoma mansoniinfection on host responses in a Ugandan fishing cohort given a Hepatitis B (HepB) vaccine. Concentrations of schistosome-specific circulating anodic antigen (CAA) pre-vaccination showed a significant bimodal distribution associated with HepB titers, which were lower in individuals with high CAA. We established that participants with high CAA had significantly lower frequencies of circulating T follicular helper (cTfh) subpopulations pre- and post-vaccination and higher regulatory T cells (Tregs) post-vaccination. Polarization towards higher frequencies of Tregs: cTfh cells can be mediated by changes in the cytokine environment favoring Treg differentiation. In fact, we observed higher levels of CCL17 and soluble IL-2R pre-vaccination (important for Treg recruitment and development), in individuals with high CAA that negatively associated with HepB titers. Additionally, alterations in pre-vaccination monocyte function correlated with HepB titers, and changes in innate-related cytokines/chemokine production were associated with increasing CAA concentration. We report, that by influencing the immune landscape, schistosomiasis has the potential to modulate immune responses to HepB vaccination. These findings highlight multipleSchistosoma-related immune associations that could explain abrogated vaccine responses in communities with endemic infections.Author SummarySchistosomiasis drives host immune responses for optimal pathogen survival, potentially altering host responses to vaccine-related antigen. Chronic schistosomiasis and co-infection with hepatotropic viruses are common in countries where schistosomiasis is endemic. We explored the impact ofSchistosoma mansoni(S. mansoni) infection on Hepatitis B (HepB) vaccination of individuals from a fishing community in Uganda. We demonstrate that high schistosome-specific antigen (circulating anodic antigen, CAA) concentration pre-vaccination, is associated with lower HepB antibody titers post-vaccination. We show higher pre-vaccination levels of cellular and soluble factors in instances of high CAA that are negatively associated with HepB antibody titers post-vaccination, which coincided with lower frequencies of circulating T follicular helper cell populations (cTfh), proliferating antibody secreting cells (ASCs), and higher frequencies of regulatory T cells (Tregs). We also show that monocyte function is important in HepB vaccine responses, and that high CAA is associated with alterations in the early innate cytokine/chemokine microenvironment. Our findings suggest that in individuals with high CAA and likely high worm burden, schistosomiasis creates and sustains an environment that is polarized against optimal host immune responses to the vaccine, which puts many endemic communities at risk for infection against HepB and other diseases that are preventable by vaccines.

Schistosomiasis is a major neglected tropical disease (NTD) affecting both humans and animals. The morbidity and mortality inflicted upon livestock in sub-Saharan Africa has been largely overlooked, in part due to a lack of validated sensitive and specific tests, which do not require specialist training or equipment to deliver and interpret. Inexpensive, non-invasive, and sensitive diagnostic tests for livestock-use would also facilitate both prevalence mapping and appropriate intervention programmes. The aim of this study was to assess the sensitivity and specificity of the currently available point-of-care circulating cathodic antigen test (POC-CCA), designed for Schistosoma mansoni detection in humans, for the detection of intestinal livestock schistosomiasis caused by Schistosoma bovis and Schistosoma curassoni. POC-CCA, together with the circulating anodic antigen (CAA) test, miracidial hatching technique (MHT) and organ and mesentery inspection (for animals from abattoirs only), were applied to samples collected from 195 animals (56 cattle and 139 small ruminants (goats and sheep) from abattoirs and living populations) from Senegal. POC-CCA sensitivity varied by ruminant group and by location/parasite species: sensitivity was greater in Barkedji (cattle: mean 81% (95% credible interval (CrI): 55%-98%); small ruminants: 49% (29%-87%), where livestock were primarily infected by S. curassoni, than in Richard Toll (cattle: 62% (41%-84%); small ruminants: 12% (1%-37%), where S. bovis was the main parasite species. Mean POC-CCA specificity across sites in small ruminants was 91% (77%-99%) with little variation between locations/parasites (Barkedji: 91% (73%-99%); Richard Toll: 88% (65% - 99%). Specificity could not be assessed in cattle owing to the low number of uninfected cattle surveyed. Overall, our results indicate that, whilst the current POC-CCA does represent a potential diagnostic tool for animal schistosomiasis, future work is needed to develop a livestock-specific affordable and field-applicable diagnostic tests to enable determination of the true extent of livestock schistosomiasis.Author summarySchistosomiasis is a debilitating neglected tropical and zoonotic disease, infecting over 230 million people and multiple millions of animals worldwide, most notably amongst the poorest regions and populations. The potential contribution of livestock schistosomiasis to disease transmission in human populations has implications for the design of effective disease management and elimination programmes. However, our understanding of the true prevalence, transmission and impact of animal schistosomiasis is severely limited, in part due to a lack of inexpensive, accessible, sensitive and specific diagnostic tools. As a point-of-care circulating cathodic antigen (POC-CCA) diagnostic test is now in widespread use to assess intestinal schistosomiasis caused by Schistosoma mansoni in humans, we hypothesised that the same test could be used to detect livestock intestinal schistosomiasis caused by Schistosoma bovis and Schistosoma curassoni. The aim of this study was thus to evaluate the sensitivity and specificity of the POC-CCA for the detection of intestinal livestock schistosomiasis in Senegal. POC-CCA sensitivity varied by ruminant group and by location/parasite species, while POC-CCA specificity in small ruminants, at least, did not vary across sites. We conclude that the currently-available POC-CCA does represent a potential diagnostic tool for animal schistosomiasis, but that the factors determining test performance warrant further investigation.