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      Environmental Predictors of Schistosomiasis Persistent Hotspots following Mass Treatment with Praziquantel

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          Abstract.

          Schistosomiasis control programs rely heavily on mass drug administration (MDA) campaigns with praziquantel for preventative chemotherapy. Areas where the prevalence and/or intensity of schistosomiasis infection remains high even after several rounds of treatment, termed “persistent hotspots” (PHSs), have been identified in trials of MDA effectiveness conducted by the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) in Kenya, Mozambique, Tanzania, and Côte d’Ivoire. In this analysis, we apply a previously developed set of criteria to classify the PHS status of 531 study villages from five SCORE trials. We then fit logistic regression models to data from SCORE and publically available georeferenced datasets to evaluate the influence of local environmental and population features, pre-intervention infection burden, and treatment scheduling on PHS status in each trial. The frequency of PHS in individual trials ranged from 35.3% to 71.6% in study villages. Significant relationships between PHS status and MDA frequency, distance to freshwater, rainfall, baseline schistosomiasis burden, elevation, land cover type, and village remoteness were each observed in at least one trial, although the strength and direction of these relationships was not always consistent among study sites. These findings suggest that PHSs are driven in part by environmental conditions that modify the risk and frequency of reinfection.

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          Most cited references35

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          Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk.

          An estimated 779 million people are at risk of schistosomiasis, of whom 106 million (13.6%) live in irrigation schemes or in close proximity to large dam reservoirs. We identified 58 studies that examined the relation between water resources development projects and schistosomiasis, primarily in African settings. We present a systematic literature review and meta-analysis with the following objectives: (1) to update at-risk populations of schistosomiasis and number of people infected in endemic countries, and (2) to quantify the risk of water resources development and management on schistosomiasis. Using 35 datasets from 24 African studies, our meta-analysis showed pooled random risk ratios of 2.4 and 2.6 for urinary and intestinal schistosomiasis, respectively, among people living adjacent to dam reservoirs. The risk ratio estimate for studies evaluating the effect of irrigation on urinary schistosomiasis was in the range 0.02-7.3 (summary estimate 1.1) and that on intestinal schistosomiasis in the range 0.49-23.0 (summary estimate 4.7). Geographic stratification showed important spatial differences, idiosyncratic to the type of water resources development. We conclude that the development and management of water resources is an important risk factor for schistosomiasis, and hence strategies to mitigate negative effects should become integral parts in the planning, implementation, and operation of future water projects.
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            Sm16, a major component of Schistosoma mansoni cercarial excretory/secretory products, prevents macrophage classical activation and delays antigen processing

            Background Schistosoma mansoni cercariae penetrate the skin by releasing excretory/secretory (E/S) products known as 0-3hRP, which are associated with immune modulation through Toll like receptor (TLR) signalling. Furthermore, these secretions contain Sm16, which when given to cells as a recombinant protein inhibits human monocyte derived cytokine responses to TLR4 and TLR3 ligands. Nonetheless, the extent and mechanism(s) of these inhibitory effects remain largely uncharacterized. Methods Murine bone marrow derived macrophages were exposed to different fractions of 0-3hRP, obtained via ultracentrifugation, or recombinant Sm16. These cells were exposed to the parasite molecules in combination with different TLR ligands, or Interferon gamma, and tested for the production of the cytokines IL-10 and IL-12p40, and their ability to process antigen. Results The immunomodulatory function of 0-3hRP is enriched predominantly in the pellet fraction, which contains a greater proportion of Sm16, also corroborating the ability of recombinant Sm16 to inhibit macrophage activation in response to TLR ligands. We further demonstrate that Sm16 blocks classical activation of macrophages to LPS or IFN-γ stimulation in vitro, and that inhibition of macrophage classical activation is independent of TLR2 recognition. Finally we show that Sm16 shares the altered intracellular processing observed for 0-3hRP, and is able to delay antigen processing by macrophages. Conclusions Collectively, our findings show that Sm16 is a major component of S. mansoni cercarial E/S products, and is partly responsible for its immune-regulatory properties. Moreover, we propose that the mechanism employed by Sm16 to exert its inhibitory function is likely to be linked with alteration of endosomal trafficking and is not dependent on particular TLR receptors. Finally, we suggest that accumulation of Sm16 in the skin after percutaneous infection with S. mansoni cercariae could contribute to limiting dermal inflammation. Electronic supplementary material The online version of this article (doi:10.1186/s13071-014-0608-1) contains supplementary material, which is available to authorized users.
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              Spatial distribution of schistosomiasis and treatment needs in sub-Saharan Africa: a systematic review and geostatistical analysis.

              Schistosomiasis affects more than 200 million individuals, mostly in sub-Saharan Africa, but empirical estimates of the disease burden in this region are unavailable. We used geostatistical modelling to produce high-resolution risk estimates of infection with Schistosoma spp and of the number of doses of praziquantel treatment needed to prevent morbidity at different administrative levels in 44 countries.
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                Author and article information

                Journal
                Am J Trop Med Hyg
                Am. J. Trop. Med. Hyg
                tpmd
                tropmed
                The American Journal of Tropical Medicine and Hygiene
                The American Society of Tropical Medicine and Hygiene
                0002-9637
                1476-1645
                February 2020
                30 December 2019
                30 December 2019
                : 102
                : 2
                : 328-338
                Affiliations
                [1 ]Center for the Ecology of Infectious Disease, University of Georgia, Athens, Georgia;
                [2 ]University of Georgia College of Public Health, Athens, Georgia;
                [3 ]Schistosomiasis Consortium for Operational Research and Evaluation (SCORE), Center for Tropical and Emerging Global Diseases (CTEGD), University of Georgia, Athens, Georgia;
                [4 ]Odum School of Ecology, University of Georgia, Athens, Georgia;
                [5 ]Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio;
                [6 ]Department of Microbiology, University of Georgia, Athens, Georgia
                Author notes
                [* ]Address correspondence to Joseph W. Walker, Center for the Ecology of Infectious Disease, 203 D.W. Brooks Dr., Athens, GA 30602. E-mail: joewalker127@ 123456gmail.com

                Financial Support: These studies received financial support from the University of Georgia Research Foundation, Inc., which was funded by the Bill & Melinda Gates Foundation for the SCORE project.

                Authors’ addresses: Author Contact Information: Joseph W. Walker, Center for the Ecology of Infectious Disease, University of Georgia, Athens, GA, University of Georgia College of Public Health, Athens, Georgia, United States, E-mail: joewalker127@ 123456gmail.com . Nupur Kittur, Sue Binder, Jennifer D. Castleman, Carl H. Campbell Jr., and Daniel G. Colley, Schistosomiasis Consortium for Operational Research and Evaluation (SCORE), Center for Tropical and Emerging Global Diseases (CTEGD), University of Georgia, Athens, GeorgiA, United States, E-mails: nkittur@ 123456uga.edu , suebinder1@ 123456gmail.com , jdcastle@ 123456uga.edu , ccamp@ 123456uga.edu , and dcolley@ 123456uga.edu . John M. Drake, Odum School of Ecology, University of Georgia, Athens, GeorgiA, United States, E-mail: jdrake@ 123456uga.edu . Charles H. King, Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OHio, E-mail: chk@ 123456cwru.edu .

                Article
                tpmd190658
                10.4269/ajtmh.19-0658
                7008331
                31889506
                ea6d147f-4030-4550-a7ac-8ac72de1391d
                © The American Society of Tropical Medicine and Hygiene

                This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 05 September 2019
                : 06 November 2019
                Page count
                Pages: 11
                Categories
                Articles

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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