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    Colonization factors among enterotoxigenic Escherichia coli isolates from children with moderate-to-severe diarrhea and from matched controls in the Global Enteric Multicenter Study (GEMS)

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    Author
    Vidal, R.M.
    Muhsen, K.
    Tennant, S.M.
    Date
    2019
    Journal
    PLoS Neglected Tropical Diseases
    Publisher
    Public Library of Science
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.1371/journal.pntd.0007037
    Abstract
    Background: Enterotoxigenic Escherichia coli (ETEC) encoding heat-stable enterotoxin (ST) alone or with heat-labile enterotoxin (LT) cause moderate-to-severe diarrhea (MSD) in developing country children. The Global Enteric Multicenter Study (GEMS) identified ETEC encoding ST among the top four enteropathogens. Since the GEMS objective was to provide evidence to guide development and implementation of enteric vaccines and other interventions to diminish diarrheal disease morbidity and mortality, we examined colonization factor (CF) prevalence among ETEC isolates from children age <5 years with MSD and from matched controls in four African and three Asian sites. We also assessed strength of association of specific CFs with MSD. Methodology/Principal findings: MSD cases enrolled at healthcare facilities over three years and matched controls were tested in a standardized manner for many enteropathogens. To identify ETEC, three E. coli colonies per child were tested by polymerase chain reaction (PCR) to detect genes encoding LT, ST; confirmed ETEC were examined by PCR for major CFs (Colonization Factor Antigen I [CFA/I] or Coli Surface [CS] antigens CS1-CS6) and minor CFs (CS7, CS12, CS13, CS14, CS17, CS18, CS19, CS20, CS21, CS30). ETEC from 806 cases had a single toxin/CF profile in three tested strains per child. Major CFs, components of multiple ETEC vaccine candidates, were detected in 66.0% of LT/ST and ST-only cases and were associated with MSD versus matched controls by conditional logistic regression (p?0.006); major CFs detected in only 25.0% of LT-only cases weren't associated with MSD. ETEC encoding exclusively CS14, identified among 19.9% of 291 ST-only and 1.5% of 259 LT/ST strains, were associated with MSD (p = 0.0011). No other minor CF exhibited prevalence ?5% and significant association with MSD. Conclusions/Significance: Major CF-based efficacious ETEC vaccines could potentially prevent up to 66% of pediatric MSD cases due to ST-encoding ETEC in developing countries; adding CS14 extends coverage to ~77%. © 2019, Public Library of Science. All rights reserved.
    Sponsors
    This work was supported by Grants 38874 and 38874.01 from the Bill & Melinda Gates Foundation; www.gatesfoundation.org; communicating author MML was the recipient of these grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
    Keyword
    colonization factors
    Global Enteric Multicenter Study (GEMS)
    Developing Countries
    Enterotoxigenic Escherichia coli--pathogenicity
    Escherichia coli Vaccines
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060394589&doi=10.1371%2fjournal.pntd.0007037&partnerID=40&md5=a54de0529348eba6cf07dcfe299013ea; http://hdl.handle.net/10713/8730
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pntd.0007037
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