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      Risk factors for Cryptosporidium infection in low and middle income countries: A systematic review and meta-analysis

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          Abstract

          Background

          Cryptosporidium infection causes gastrointestinal disease and has a worldwide distribution. The highest burden is in developing countries.

          Objectives

          We sought to conduct a systematic review and meta-analysis to identify Cryptosporidium risk factors in Low and Middle Income countries (LMICs).

          Methods

          Medline Ovid and Scopus databases were searched with no restriction on year or language of publication. All references were screened independently in duplicate and were included if they presented data on at least 3 risk factors. Meta-analyses using random effects models were used to calculate overall estimates for each exposure.

          Results

          The most frequently reported risk factors in the 15 included studies were overcrowding, household diarrhoea, poor quality drinking water, animal contact, open defecation/ lack of toilet and breastfeeding. The combined odds ratio for animal contact was 1.98 (95%CI: 1.11–3.54) based on 11 studies and for diarrhoea in the household 1.98 (95%CI: 1.13–3.49) based on 4 studies. Open defecation was associated with a pooled odds ratio of 1.82 (95%CI: 1.19–2.8) based on 5 studies. Poor drinking water quality was not associated with a significant Cryptosporidium risk, odds ratio 1.06 (95%CI: 0.77–1.47). Breastfeeding was protective with pooled odds ratio 0.4 (95%CI: 0.13–1.22), which was not statistically significant.

          Conclusions

          Based on the included studies, crowded living conditions, animal contact and open defecation are responsible for the majority of Cryptosporidium cases in LMICs. Future studies investigating Cryptosporidium risk factors should have a good study design and duration, include appropriate number of cases, select suitable controls, investigate multiple relevant risk factors, fully report data and perform multivariate analysis.

          Author summary

          Cryptosporidium is a parasite that causes diarrhoea and is transmitted through faecal contamination of water and food. Though it occurs in developed nations, it is much more prevalent in developing countries and is associated with high mortality in children under 2 years old. In this review, we looked at published studies on factors that increase the risk of contracting cryptosporidiosis in Low and Middle Income Countries. These factors could be targeted to limit the transmission of the disease. Based on the selected studies, the most important risk factors identified were contacts with animals and presence of infected people in the household. Open defecation was also contributing to the risk of infection by this parasite transmitted through the faecal oral route. Breastfeeding was protective from the infection. Poor drinking water was not responsible for causing the disease.

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          Most cited references29

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          A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium.

          Cryptosporidium spp are well recognised as causes of diarrhoeal disease during waterborne epidemics and in immunocompromised hosts. Studies have also drawn attention to an underestimated global burden and suggest major gaps in optimum diagnosis, treatment, and immunisation. Cryptosporidiosis is increasingly identified as an important cause of morbidity and mortality worldwide. Studies in low-resource settings and high-income countries have confirmed the importance of cryptosporidium as a cause of diarrhoea and childhood malnutrition. Diagnostic tests for cryptosporidium infection are suboptimum, necessitating specialised tests that are often insensitive. Antigen-detection and PCR improve sensitivity, and multiplexed antigen detection and molecular assays are underused. Therapy has some effect in healthy hosts and no proven efficacy in patients with AIDS. Use of cryptosporidium genomes has helped to identify promising therapeutic targets, and drugs are in development, but methods to assess the efficacy in vitro and in animals are not well standardised. Partial immunity after exposure suggests the potential for successful vaccines, and several are in development; however, surrogates of protection are not well defined. Improved methods for propagation and genetic manipulation of the organism would be significant advances. Copyright © 2015 Elsevier Ltd. All rights reserved.
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            Use and misuse of population attributable fractions.

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              Cryptosporidium pathogenicity and virulence.

              Cryptosporidium is a protozoan parasite of medical and veterinary importance that causes gastroenteritis in a variety of vertebrate hosts. Several studies have reported different degrees of pathogenicity and virulence among Cryptosporidium species and isolates of the same species as well as evidence of variation in host susceptibility to infection. The identification and validation of Cryptosporidium virulence factors have been hindered by the renowned difficulties pertaining to the in vitro culture and genetic manipulation of this parasite. Nevertheless, substantial progress has been made in identifying putative virulence factors for Cryptosporidium. This progress has been accelerated since the publication of the Cryptosporidium parvum and C. hominis genomes, with the characterization of over 25 putative virulence factors identified by using a variety of immunological and molecular techniques and which are proposed to be involved in aspects of host-pathogen interactions from adhesion and locomotion to invasion and proliferation. Progress has also been made in the contribution of host factors that are associated with variations in both the severity and risk of infection. Here we provide a review comprised of the current state of knowledge on Cryptosporidium infectivity, pathogenesis, and transmissibility in light of our contemporary understanding of microbial virulence.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysis
                Role: ConceptualizationRole: Funding acquisition
                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
                7 June 2018
                June 2018
                : 12
                : 6
                : e0006553
                Affiliations
                [1 ] Norwich Medical School, University of East Anglia, Norwich, United Kingdom
                [2 ] NIHR Health Protection Research Unit in Gastrointestinal Infections, University of East Anglia, Norwich, United Kingdom
                Christian Medical College, Vellore, INDIA
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-2323-4323
                Article
                PNTD-D-18-00168
                10.1371/journal.pntd.0006553
                6014672
                29879110
                d23ca5d4-8fc9-4c99-a566-ece5ea636beb
                © 2018 Bouzid 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
                : 20 February 2018
                : 22 May 2018
                Page count
                Figures: 7, Tables: 2, Pages: 13
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100000272, National Institute for Health Research;
                Award Recipient :
                Funded by: European Union Seventh Framework programme
                Award ID: 311846
                Award Recipient :
                The study was funded by the National Institute for Health Research, Health Protection Research Unit in Gastrointestinal Infections and the European Union Seventh Framework programme under the AQUAVALENS project (Grant Agreement number 311846). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Organisms
                Eukaryota
                Protozoans
                Parasitic Protozoans
                Cryptosporidium
                Biology and Life Sciences
                Organisms
                Eukaryota
                Protozoans
                Cryptosporidium
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Meta-Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Medicine and Health Sciences
                Parasitic Diseases
                Cryptosporidiosis
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Diarrhea
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Diarrhea
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Diarrhea
                Research and Analysis Methods
                Research Assessment
                Systematic Reviews
                Medicine and Health Sciences
                Women's Health
                Maternal Health
                Breast Feeding
                Medicine and Health Sciences
                Pediatrics
                Neonatology
                Breast Feeding
                Ecology and Environmental Sciences
                Natural Resources
                Water Resources
                Earth Sciences
                Marine and Aquatic Sciences
                Water Quality
                Custom metadata
                vor-update-to-uncorrected-proof
                2018-06-22
                All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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