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      Cognitive deficits and educational loss in children with schistosome infection—A systematic review and meta-analysis

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          Abstract

          Background

          By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits.

          Methodology/Principal findings

          This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains—learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5–19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits in scholastic achievement was sensitive to ROB. Schistosoma infection-related deficits in learning and memory tests were invariant by ROB and study design.

          Conclusion/Significance

          Schistosoma infection/non-treatment was significantly associated with educational, learning, and memory deficits in SAC. Early treatment of children in Schistosoma-endemic regions could potentially mitigate these deficits.

          Trial registration

          ClinicalTrials.gov CRD42016040052

          Author summary

          Empirical evidence for cognitive or educational benefits of anti- Schistosoma treatment is currently uncertain, despite the recommended practice of wide-scale deworming with praziquantel. We addressed this knowledge gap by synthesizing information from 30 relevant epidemiologic studies reporting on 38,992 children between 5–19 years old from 14 countries. In those studies, Schistosoma infection or non-dewormed status was associated with educational loss and cognitive deficits. Specifically, there were small to moderate deficits in both school attendance and scholastic achievement. Similarly, Schistosoma infection or non-dewormed status was associated with deficits in learning and memory domains of psychometrically tested cognitive function. However, there was no evidence of Schistosoma infection- or non-deworming-associated deficits on tests of innate intelligence or reaction-time. Overall, compared to Schistosoma-uninfected or to dewormed children, the presence of Schistosoma infection or non-dewormed status was associated with educational, learning, and memory deficits in school-aged children. The combined evidence suggests that early treatment of children in Schistosoma-endemic regions could mitigate these deficits.

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          Most cited references55

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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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            Newcastle-Ottawa Scale: comparing reviewers’ to authors’ assessments

            Background Lack of appropriate reporting of methodological details has previously been shown to distort risk of bias assessments in randomized controlled trials. The same might be true for observational studies. The goal of this study was to compare the Newcastle-Ottawa Scale (NOS) assessment for risk of bias between reviewers and authors of cohort studies included in a published systematic review on risk factors for severe outcomes in patients infected with influenza. Methods Cohort studies included in the systematic review and published between 2008–2011 were included. The corresponding or first authors completed a survey covering all NOS items. Results were compared with the NOS assessment applied by reviewers of the systematic review. Inter-rater reliability was calculated using kappa (K) statistics. Results Authors of 65/182 (36%) studies completed the survey. The overall NOS score was significantly higher (p < 0.001) in the reviewers’ assessment (median = 6; interquartile range [IQR] 6–6) compared with those by authors (median = 5, IQR 4–6). Inter-rater reliability by item ranged from slight (K = 0.15, 95% confidence interval [CI] = −0.19, 0.48) to poor (K = −0.06, 95% CI = −0.22, 0.10). Reliability for the overall score was poor (K = −0.004, 95% CI = −0.11, 0.11). Conclusions Differences in assessment and low agreement between reviewers and authors suggest the need to contact authors for information not published in studies when applying the NOS in systematic reviews.
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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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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: ValidationRole: Writing – review & editing
                Role: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                12 January 2018
                January 2018
                : 12
                : 1
                : e0005524
                Affiliations
                [1 ] Department of Psychiatry, College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan, United States of America
                [2 ] Department of Epidemiology & Biostatistics, University of Georgia, Athens, Georgia, United States of America
                [3 ] Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom
                [4 ] Center for Research and Development, Angeles University Foundation, Angeles City, The Philippines
                [5 ] Center for Global Health and Diseases, PAHO/WHO Collaborating Centre for Research and Training for Schistosomiasis Elimination, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America
                Ministère de la Santé Publique et de la Lutte contre les Endémies, NIGER
                Author notes

                The authors have declared no competing interests exist.

                Author information
                http://orcid.org/0000-0003-2164-8802
                Article
                PNTD-D-16-01885
                10.1371/journal.pntd.0005524
                5766129
                29329293
                16c2ae6d-6419-40d2-b586-526309c9a0d1
                © 2018 Ezeamama 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.

                History
                : 15 October 2016
                : 23 March 2017
                Page count
                Figures: 1, Tables: 4, Pages: 23
                Funding
                Funded by: Schistosomiasis Consortium for Operational Research and Evaluation (SCORE).
                Award Recipient :
                Funded by: Schistosomiasis Consortium for Operational Research and Evaluation (SCORE).
                Award Recipient :
                This work was supported by Schistosomiasis Consortium for Operational Research and Evaluation (SCORE), University of Georgia, Athens, GA, USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Infectious disease & Microbiology
                Infectious disease & Microbiology

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