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      Associations between infection intensity categories and morbidity prevalence in school-age children are much stronger for Schistosoma haematobium than for S. mansoni

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          Abstract

          Background

          World Health Organization (WHO) guidelines for measuring global progress in schistosomiasis control classify individuals with Schistosoma spp. infections based on the concentration of excreted eggs. We assessed the associations between WHO infection intensity categories and morbidity prevalence for selected S. haematobium and S. mansoni morbidities in school-age children.

          Methodology

          A total of 22,488 children aged 6–15 years from monitoring and evaluation cohorts in Burkina Faso, Mali, Niger, Uganda, Tanzania, and Zambia from 2003–2008 were analyzed using Bayesian logistic regression. Models were utilized to evaluate associations between intensity categories and the prevalence of any urinary bladder lesion, any upper urinary tract lesion, microhematuria, and pain while urinating (for S. haematobium) and irregular hepatic ultrasound image pattern (C-F), enlarged portal vein, laboratory-confirmed diarrhea, and self-reported diarrhea (for S. mansoni) across participants with infection and morbidity data.

          Principal findings

          S. haematobium infection intensity categories possessed consistent morbidity prevalence across surveys for multiple morbidities and participants with light infections had elevated morbidity levels, compared to negative participants. Conversely, S. mansoni infection intensity categories lacked association with prevalence of the morbidity measures assessed.

          Conclusions/significance

          Current status infection intensity categories for S. haematobium were associated with morbidity levels in school-age children, suggesting urogenital schistosomiasis morbidity can be predicted by an individual’s intensity category. Conversely, S. mansoni infection intensity categories were not consistently indicative of childhood morbidity at baseline or during the first two years of a preventive chemotherapy control program.

          Author summary

          Infections with Schistosoma parasites are commonly classified by the presence and concentration of excreted Schistosoma eggs. Guidelines put forward by the World Health Organization (WHO) include classifications of S. haematobium infections assessed by urine filtration into light and heavy infections and S. mansoni infections assessed by Kato-Katz thick smears into light, moderate, and heavy infections. Past evidence has demonstrated an association between intensity of infection with morbidity for severe morbidities, but this was before recognition of the effect of light-intensity infections on morbidity and was done in treatment naïve populations. In these analyses, we assessed the associations between the WHO classifications for infection intensity and a wide array of S. haematobium and S. mansoni morbidity indicators in school-age children ascertained in monitoring and evaluation cohorts before and after initiation of deworming. Our analyses found a high correlation with S. haematobium intensity categories and morbidity indicators, especially microhematuria, but weaker correlation between S. mansoni intensity categories and morbidity indicators. The results indicate that, on the aggregate, the intensity categories represent a person’s S. haematobium-related morbidity but are poor at representing a person’s S. mansoni-related morbidity.

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          Most cited references60

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          Human schistosomiasis.

          Human schistosomiasis--or bilharzia--is a parasitic disease caused by trematode flukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological effects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fitness, to organ-specific effects such as severe hepatosplenism, periportal fibrosis with portal hypertension, and urogenital inflammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the field and clinics, and integrated environmental and health-care management will be needed to ensure elimination. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Reassessment of the cost of chronic helmintic infection: a meta-analysis of disability-related outcomes in endemic schistosomiasis.

            Schistosomiasis is one of the world's most prevalent infections, yet its effect on the global burden of disease is controversial. Published disability-adjusted life-year (DALY) estimates suggest that the average effect of schistosome infection is quite small, although this is disputed. To develop an evidenced-based reassessment of schistosomiasis-related disability, we did a systematic review of data on disability-associated outcomes for all forms of schistosomiasis. We did structured searches using EMBASE, PUBMED, and Cochrane electronic databases. Published bibliographies were manually searched, and unpublished studies were obtained by contacting research groups. Reports were reviewed and abstracted independently by two trained readers. All randomised and observational studies of schistosomiasis morbidity were eligible for inclusion. We calculated pooled estimates of reported disability-related effects using weighted odds ratios for categorical outcomes and standardised mean differences for continuous data. 482 published or unpublished reports (March, 1921, to July, 2002) were screened. Of 135 selected for inclusion, 51 provided data for performance-related symptoms, whereas 109 reported observed measures of disability-linked morbidities. Schistosomiasis was significantly associated with anaemia, chronic pain, diarrhoea, exercise intolerance, and undernutrition. By contrast with WHO estimates of 0.5% disability weight assigned to schistosomiasis, 2-15% disability seems evident in different functional domains of a person with schistosomiasis. This raised estimate, if confirmed in formal patient-preference studies, indicates a need to reassess our priorities for treating this silent pandemic of schistosomiasis.
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              A weakly informative default prior distribution for logistic and other regression models

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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                25 May 2021
                May 2021
                : 15
                : 5
                : e0009444
                Affiliations
                [1 ] Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
                [2 ] Swiss Tropical and Public Health Institute, Basel, Switzerland
                [3 ] University of Basel, Basel, Switzerland
                [4 ] SCI Foundation, London, United Kingdom
                [5 ] RTI International, Washington DC, United States of America
                [6 ] Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, United States of America
                [7 ] Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom
                [8 ] United States Agency for International Development, Washington DC, United States of America
                [9 ] Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
                Wellcome Sanger Institute, UNITED KINGDOM
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-9486-1850
                https://orcid.org/0000-0003-0584-5961
                https://orcid.org/0000-0002-3866-2232
                https://orcid.org/0000-0002-9886-9980
                https://orcid.org/0000-0001-8349-9270
                https://orcid.org/0000-0002-7154-5505
                https://orcid.org/0000-0003-1180-8980
                https://orcid.org/0000-0002-1830-5668
                Article
                PNTD-D-21-00023
                10.1371/journal.pntd.0009444
                8183985
                34033646
                92aad8bc-e1e6-438a-8f5d-31db650bcfc9

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 5 January 2021
                : 4 May 2021
                Page count
                Figures: 4, Tables: 4, Pages: 18
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: 13122
                The Schistosomiasis Control Initiative (now the SCI Foundation) was supported by the Bill and Melinda Gates Foundation (grant 13122). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Health Care
                Health Statistics
                Morbidity
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Invertebrates
                Helminths
                Schistosoma
                Schistosoma Mansoni
                Biology and Life Sciences
                Zoology
                Animals
                Invertebrates
                Helminths
                Schistosoma
                Schistosoma Mansoni
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Invertebrates
                Helminths
                Schistosoma
                Schistosoma Haematobium
                Biology and Life Sciences
                Zoology
                Animals
                Invertebrates
                Helminths
                Schistosoma
                Schistosoma Haematobium
                Biology and Life Sciences
                Physiology
                Reproductive Physiology
                Eggs
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Urine
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Urine
                Biology and Life Sciences
                Physiology
                Body Fluids
                Urine
                Biology and Life Sciences
                Anatomy
                Cardiovascular Anatomy
                Blood Vessels
                Veins
                Portal Veins
                Medicine and Health Sciences
                Anatomy
                Cardiovascular Anatomy
                Blood Vessels
                Veins
                Portal Veins
                Biology and Life Sciences
                Anatomy
                Renal System
                Bladder
                Medicine and Health Sciences
                Anatomy
                Renal System
                Bladder
                Medicine and Health Sciences
                Medical Conditions
                Parasitic Diseases
                Helminth Infections
                Schistosomiasis
                Medicine and Health Sciences
                Medical Conditions
                Tropical Diseases
                Neglected Tropical Diseases
                Schistosomiasis
                Custom metadata
                vor-update-to-uncorrected-proof
                2021-06-07
                Data cannot be shared publicly because this was not part of the IRB submissions. Though, we are working to make these data publicly available. As of now, inquires regarding the data and potential use can be sent to the Schistosomiasis Control Initiative Foundation at info@ 123456schisto.org.uk .

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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