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      Epidemiology and Impact of Campylobacter Infection in Children in 8 Low-Resource Settings: Results From the MAL-ED Study

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      Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
      Oxford University Press
      Campylobacter, children, risk factors, growth, inflammation

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          Abstract

          In a multisite birth cohort study, we document a high burden of Campylobacter infection using enzyme immunoassay, demonstrate an association between Campylobacter and linear growth shortfalls and both increased intestinal permeability and intestinal and systemic inflammation, and identify potential interventions.

          Abstract

          Background.  Enteropathogen infections have been associated with enteric dysfunction and impaired growth in children in low-resource settings. In a multisite birth cohort study (MAL-ED), we describe the epidemiology and impact of Campylobacter infection in the first 2 years of life.

          Methods.  Children were actively followed up until 24 months of age. Diarrheal and nondiarrheal stool samples were collected and tested by enzyme immunoassay for Campylobacter. Stool and blood samples were assayed for markers of intestinal permeability and inflammation.

          Results.  A total of 1892 children had 7601 diarrheal and 26 267 nondiarrheal stool samples tested for Campylobacter. We describe a high prevalence of infection, with most children (n = 1606; 84.9%) having a Campylobacter-positive stool sample by 1 year of age. Factors associated with a reduced risk of Campylobacter detection included exclusive breastfeeding (risk ratio, 0.57; 95% confidence interval, .47–.67), treatment of drinking water (0.76; 0.70–0.83), access to an improved latrine (0.89; 0.82–0.97), and recent macrolide antibiotic use (0.68; 0.63–0.74). A high Campylobacter burden was associated with a lower length-for-age Z score at 24 months (−1.82; 95% confidence interval, −1.94 to −1.70) compared with a low burden (−1.49; −1.60 to −1.38). This association was robust to confounders and consistent across sites. Campylobacter infection was also associated with increased intestinal permeability and intestinal and systemic inflammation.

          Conclusions. Campylobacter was prevalent across diverse settings and associated with growth shortfalls. Promotion of exclusive breastfeeding, drinking water treatment, improved latrines, and targeted antibiotic treatment may reduce the burden of Campylobacter infection and improve growth in children in these settings.

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          Most cited references28

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          Campylobacter jejuni: molecular biology and pathogenesis.

          Campylobacter jejuni is a foodborne bacterial pathogen that is common in the developed world. However, we know less about its biology and pathogenicity than we do about other less prevalent pathogens. Interest in C. jejuni has increased in recent years as a result of the growing appreciation of its importance as a pathogen and the availability of new model systems and genetic and genomic technologies. C. jejuni establishes persistent, benign infections in chickens and is rapidly cleared by many strains of laboratory mouse, but causes significant inflammation and enteritis in humans. Comparing the different host responses to C. jejuni colonization should increase our understanding of this organism.
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            Experimental Campylobacter jejuni infection in humans.

            Two strains of Campylobacter jejuni ingested by 111 adult volunteers, in doses ranging from 8 x 10(2) to 2 x 10(9) organisms, caused diarrheal illnesses. Rates of infection increased with dose, but development of illness did not show a clear dose relation. Resulting illnesses with strain A3249 ranged from a few loose stools to dysentery, with an average of five diarrheal stools and a volume of 509 mL. Infection with strain 81-176 was more likely to cause illness, and these illnesses were more severe, with an average of 15 stools and 1484 mL of total stool volume. All patients had fecal leukocytes. The dysenteric nature of the illness indicates that the pathogenesis of C. jejuni infection includes tissue inflammation. Ill volunteers developed a serum antibody response to the C. jejuni group antigen and were protected from subsequent illness but not infection with the same strain.
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              Antibiotics, pediatric dysbiosis, and disease.

              Antibiotics are by far the most common medications prescribed for children. Recent epidemiological data suggests an association between early antibiotic use and disease phenotypes in adulthood. Antibiotic use during infancy induces imbalances in gut microbiota, called dysbiosis. The gut microbiome's responses to antibiotics and its potential link to disease development are especially complex to study in the changing infant gut. Here, we synthesize current knowledge linking antibiotics, dysbiosis, and disease and propose a framework for studying antibiotic-related dysbiosis in children. We recommend future studies into the microbiome-mediated effects of antibiotics focused on four types of dysbiosis: loss of keystone taxa, loss of diversity, shifts in metabolic capacity, and blooms of pathogens. Establishment of a large and diverse baseline cohort to define healthy infant microbiome development is essential to advancing diagnosis, interpretation, and eventual treatment of pediatric dysbiosis. This approach will also help provide evidence-based recommendations for antibiotic usage in infancy.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press
                1058-4838
                1537-6591
                01 November 2016
                07 August 2016
                07 August 2016
                : 63
                : 9
                : 1171-1179
                Affiliations
                [1 ]Haydom Lutheran Hospital , Haydom, Tanzania
                [2 ]Division of Infectious Diseases and International Health, University of Virginia , Charlottesville
                [3 ]Fogarty International Center, National Institutes of Health
                [4 ]Foundation for the National Institutes of Health , Bethesda
                [5 ]Bloomberg School of Public Health, Johns Hopkins University , Baltimore, Maryland
                [6 ]Haukeland University Hospital , Bergen, Norway
                [7 ]Armed Forces Research Institute of Medical Sciences , Bangkok, Thailand
                [8 ]University of Venda , Thohoyandou, South Africa
                [9 ]International Centre for Diarrhoeal Disease Research , Dhaka, Bangladesh
                [10 ]Aga Khan University , Karachi, Pakistan
                [11 ]Christian Medical College , Vellore, India
                [12 ]Asociación Benéfica PRISMA , Iquitos, Peru
                [13 ]Clinical Research Unit and Institute of Biomedicine, Federal University of Ceara , Fortaleza, Brazil
                Author notes
                [a]

                See Appendix for a complete list of investigators.

                Correspondence: J. A. Platts-Mills, Division of Infectious Diseases and International Health, University of Virginia, PO Box 801340, Charlottesville, VA 22908 ( jp5t@ 123456virginia.edu ).
                Article
                ciw542
                10.1093/cid/ciw542
                5064165
                27501842
                53d9e371-88f8-4d1f-bcb2-4fb94c7014f4
                © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 April 2016
                : 2 August 2016
                Funding
                Funded by: Bill & Melinda Gates Foundation;
                Funded by: Foundation for the National Institutes of Health;
                Funded by: National Institutes of Health;
                Funded by: Fogarty International Center;
                Funded by: National Institutes of Health;
                Award ID: 5K23-AI114888-02
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                Infectious disease & Microbiology
                campylobacter,children,risk factors,growth,inflammation
                Infectious disease & Microbiology
                campylobacter, children, risk factors, growth, inflammation

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