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      Human Mucosal IgA Immune Responses against Enterotoxigenic Escherichia coli

      1 , 2 , 3 , 4 , 1 , 5 , *

      Pathogens

      MDPI

      ETEC, mucosal, immunity, experimental infection, IgA, SIgA

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          Abstract

          Infection with enterotoxigenic Escherichia coli (ETEC) is a major contributor to diarrheal illness in children in low- and middle-income countries and travelers to these areas. There is an ongoing effort to develop vaccines against ETEC, and the most reliable immune correlate of protection against ETEC is considered to be the small intestinal secretory IgA response that targets ETEC-specific virulence factors. Since isolating IgA from small intestinal mucosa is technically and ethically challenging, requiring the use of invasive medical procedures, several other indirect methods are used as a proxy for gauging the small intestinal IgA responses. In this review, we summarize the literature reporting on anti-ETEC human IgA responses observed in blood, activated lymphocyte assayss, intestinal lavage/duodenal aspirates, and saliva from human volunteers being experimentally infected with ETEC. We describe the IgA response kinetics and responder ratios against classical and noncanonical ETEC antigens in the different sample types and discuss the implications that the results may have on vaccine development and testing.

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          Most cited references 117

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          Coordinating assembly of a bacterial macromolecular machine.

          The assembly of large and complex organelles, such as the bacterial flagellum, poses the formidable problem of coupling temporal gene expression to specific stages of the organelle-assembly process. The discovery that levels of the bacterial flagellar regulatory protein FlgM are controlled by its secretion from the cell in response to the completion of an intermediate flagellar structure (the hook-basal body) was only the first of several discoveries of unique mechanisms that coordinate flagellar gene expression with assembly. In this Review, we discuss this mechanism, together with others that also coordinate gene regulation and flagellar assembly in Gram-negative bacteria.
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            Proposal for a new inclusive designation for extraintestinal pathogenic isolates of Escherichia coli: ExPEC.

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              Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study.

              Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries. We designed the Global Enteric Multicenter Study (GEMS) to identify the aetiology and population-based burden of paediatric diarrhoeal disease in sub-Saharan Africa and south Asia. The GEMS is a 3-year, prospective, age-stratified, matched case-control study of moderate-to-severe diarrhoea in children aged 0-59 months residing in censused populations at four sites in Africa and three in Asia. We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three randomly selected matched community control children without diarrhoea. From patients with moderate-to-severe diarrhoea and controls, we obtained clinical and epidemiological data, anthropometric measurements, and a faecal sample to identify enteropathogens at enrolment; one follow-up home visit was made about 60 days later to ascertain vital status, clinical outcome, and interval growth. We enrolled 9439 children with moderate-to-severe diarrhoea and 13,129 control children without diarrhoea. By analysing adjusted population attributable fractions, most attributable cases of moderate-to-severe diarrhoea were due to four pathogens: rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli producing heat-stable toxin (ST-ETEC; with or without co-expression of heat-labile enterotoxin), and Shigella. Other pathogens were important in selected sites (eg, Aeromonas, Vibrio cholerae O1, Campylobacter jejuni). Odds of dying during follow-up were 8·5-fold higher in patients with moderate-to-severe diarrhoea than in controls (odd ratio 8·5, 95% CI 5·8-12·5, p<0·0001); most deaths (167 [87·9%]) occurred during the first 2 years of life. Pathogens associated with increased risk of case death were ST-ETEC (hazard ratio [HR] 1·9; 0·99-3·5) and typical enteropathogenic E coli (HR 2·6; 1·6-4·1) in infants aged 0-11 months, and Cryptosporidium (HR 2·3; 1·3-4·3) in toddlers aged 12-23 months. Interventions targeting five pathogens (rotavirus, Shigella, ST-ETEC, Cryptosporidium, typical enteropathogenic E coli) can substantially reduce the burden of moderate-to-severe diarrhoea. New methods and accelerated implementation of existing interventions (rotavirus vaccine and zinc) are needed to prevent disease and improve outcomes. The Bill & Melinda Gates Foundation. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Pathogens
                Pathogens
                pathogens
                Pathogens
                MDPI
                2076-0817
                29 August 2020
                September 2020
                : 9
                : 9
                Affiliations
                [1 ]Department of Clinical Science, University of Bergen, Jonas Lies veg 87, N-5021 Bergen, Norway; saman.riaz@ 123456student.uib.no
                [2 ]Centre for International Health, Department of Global Public Health and Primary Care, University of Bergen, 5020 Bergen, Norway
                [3 ]Centre for Intervention Science in Maternal and Child Health, Centre for International Health, Department of Global Public Health and Primary Care, University of Bergen, 5020 Bergen, Norway; Hans.steinsland@ 123456uib.no
                [4 ]Department of Biomedicine, University of Bergen, 5020 Bergen, Norway
                [5 ]Norwegian National Advisory Unit on Tropical Infectious Diseases, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
                Author notes
                [* ]Correspondence: Kurt.Hanevik@ 123456uib.no ; Tel.: +47-5597-5000; Fax: +47-5597-2950
                Article
                pathogens-09-00714
                10.3390/pathogens9090714
                7558491
                32872549
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                Categories
                Review

                siga, etec, mucosal, immunity, experimental infection, iga

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