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      Symptomatic and Asymptomatic Campylobacter Infections Associated with Reduced Growth in Peruvian Children


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          Although diarrheal illnesses are recognized as both a cause and effect of undernutrition, evidence for the effect of specific enteropathogens on early childhood growth remains limited. We estimated the effects of undernutrition as a risk factor for campylobacteriosis, as well as associations between symptomatic and asymptomatic Campylobacter infections and growth.

          Methodology/Principal Findings

          Using data from a prospective cohort of 442 children aged 0–72 months, the effect of nutritional status on the incidence of Campylobacter infection was estimated using uni- and multivariate Poisson models. Multivariate regression models were developed to evaluate the effect of Campylobacter infection on weight gain and linear growth. Overall, 8.3% of diarrheal episodes were associated with Campylobacter (crude incidence rate = 0.37 episodes/year) and 4.9% of quarterly asymptomatic samples were Campylobacter positive. In univariate models, the incidence of Campylobacter infection was marginally higher in stunted than non-stunted children (IRR 1.270, 95% CI (0.960, 1.681)(p = 0.095). When recent diarrheal burdens were included in the analysis, there was no difference in risk between stunted and unstunted children. Asymptomatic and symptomatic Campylobacter infections were associated with reduced weight gain over a three-month period (65.5 g (95% CI: −128.0, −3.0)(p = 0.040) and 43.9 g (95% CI:−87.6, −1.0)(p = 0.049) less weight gain, respectively). Symptomatic Campylobacter infections were only marginally associated with reduced linear growth over a nine month period (−0.059 cm per episode, 95% CI: −0.118, 0.001)(p = 0.054), however relatively severe episodes were associated with reduced linear growth (−0.169 cm/episode, 95% CI −0.310, −0.028)(p = 0.019).


          Our findings suggest that Campylobacter is not as benign as commonly assumed, and that there is evidence to support expanding the indications for antibiotic therapy in campylobacteriosis in children.

          Author Summary

          Campylobacter is a common cause of diarrheal disease among children at risk for growth failure in the developing world. We evaluated risk factors for Campylobacter infection as well as the association between symptomatic and asymptomatic Campylobacter infections and child growth over three and nine-month periods. Undernourished (stunted) children were more likely to experience a Campylobacter infection, but adjusting for a recent history of diarrheal disease attenuated this relationship. Both symptomatic and asymptomatic infections were associated with poorer weight gain and symptomatic Campylobacter infections were marginally associated with poorer linear growth on an order similar to what has been reported for other bacterial pathogens and less than what has been reported for some protozoal and parasitic infections. In a subset of severe infections that made up about twenty percent of total illnesses, the associations were poorer growth were of greater magnitude. Campylobacter infections are frequently viewed as benign, but our study suggests that this is not always the case. Rapid diagnostics for Campylobacter jejuni and coli could attenuate acquired linear growth deficits in populations where campylobacteriosis is highly endemic by facilitating improved case management.

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          Most cited references13

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          Increased short- and long-term risk of inflammatory bowel disease after salmonella or campylobacter gastroenteritis.

          Various commensal enteric and potentially pathogenic bacteria may be involved in the pathogenesis of inflammatory bowel diseases (IBD). We compared the risk of IBD between a cohort of patients with documented Salmonella or Campylobacter gastroenteritis and an age- and gender-matched control group from the same population in Denmark. We identified 13,324 patients with Salmonella/Campylobacter gastroenteritis from laboratory registries in North Jutland and Aarhus counties, Denmark, from 1991 through 2003, and 26,648 unexposed controls from the same counties. Of these, 176 exposed patients with IBD before the infection, their 352 unexposed controls, and 80 unexposed individuals with IBD before the Salmonella/Campylobacter infection were excluded. The final study cohort of 13,148 exposed and 26,216 unexposed individuals were followed for up to 15 years (mean, 7.5 years). A first-time diagnosis of IBD was reported in 107 exposed (1.2%) and 73 unexposed individuals (0.5%). By age, gender, and comorbidity adjusted Cox proportional hazards regression analysis, the hazard ratio (95% confidence interval) for IBD was 2.9 (2.2-3.9) for the whole period and 1.9 (1.4-2.6) if the first year after the Salmonella/Campylobacter infection was excluded. The increased risk in exposed subjects was observed throughout the 15-year observation period. The increased risk was similar for Salmonella (n = 6463) and Campylobacter (n = 6685) and for a first-time diagnosis of Crohn's disease (n = 47) and ulcerative colitis (n = 133). In our population-based cohort study with complete follow-up, an increased risk of IBD was demonstrated in individuals notified in laboratory registries with an episode of Salmonella/Campylobacter gastroenteritis.
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            Contribution of enteric infection, altered intestinal barrier function, and maternal malnutrition to infant malnutrition in Bangladesh.

            Malnourished children are at increased risk for death due to diarrhea. Our goal was to determine the contribution of specific enteric infections to malnutrition-associated diarrhea and to determine the role of enteric infections in the development of malnutrition. Children from an urban slum in Bangladesh were followed for the first year of life by every-other-day home visits. Enteropathogens were identified in diarrheal and monthly surveillance stools; intestinal barrier function was measured by serum endocab antibodies; and nutritional status was measured by anthropometry. Diarrhea occurred 4.69 ± 0.19 times per child per year, with the most common infections caused by enteric protozoa (amebiasis, cryptosporidiosis, and giardiasis), rotavirus, astrovirus, and enterotoxigenic Escherichia coli (ETEC). Malnutrition was present in 16.3% of children at birth and 42.4% at 12 months of age. Children malnourished at birth had increased Entamoeba histolytica, Cryptosporidium, and ETEC infections and more severe diarrhea. Children who became malnourished by 12 months of age were more likely to have prolonged diarrhea, intestinal barrier dysfunction, a mother without education, and low family expenditure. Prospective observation of infants in an urban slum demonstrated that diarrheal diseases were associated with the development of malnutrition that was in turn linked to intestinal barrier disruption and that diarrhea was more severe in already malnourished children. The enteric protozoa were unexpectedly important causes of diarrhea in this setting. This study demonstrates the complex interrelationship of malnutrition and diarrhea in infants in low-income settings and points to the potential for infectious disease interventions in the prevention and treatment of malnutrition.
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              Effects of Cryptosporidium parvum infection in Peruvian children: growth faltering and subsequent catch-up growth.

              The authors conducted a 2-year (1989-1991) community-based longitudinal study in a shantytown in Lima, Peru, to examine the effect of Cryptosporidium parvum infection on child growth during the year following the onset of infection. A cohort of children, aged 0-3 months at recruitment, was followed monthly for anthropometrics, weekly for stool samples, and daily for diarrheal status. Data from 185 children in the cohort permitted a comparison of growth in C. parvum-infected and noninfected children. The analyses fitted smooth, flexible curves with a linear random-effects model to estimate growth differences between C. parvum-infected and noninfected children. Children infected with C. parvum experienced growth faltering, both in weight and in height, for several months after the onset of infection, followed by a period of catch-up growth. Younger children took longer to catch up in weight than did older children. Catch-up growth, however, did not occur in children infected between ages 0 and 5 months. These children did not catch up in height, and one year after infection they exhibited an average deficit of 0.95 cm (95% confidence interval (CI) 0.38-1.53) relative to noninfected children of similar age. Stunted children who became infected also did not catch up in either weight or height, and one year after infection they exhibited a height deficit of 1.05 cm (95% CI 0.46-1.66) relative to noninfected, stunted children of similar age. These results indicate that Cryptosporidium parvum has a lasting adverse effect on linear (height) growth, especially when acquired during infancy and when children are stunted before they become infected.

                Author and article information

                Role: Editor
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, USA )
                January 2013
                31 January 2013
                : 7
                : 1
                [1 ]Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
                [2 ]Duke Global Health Institute, Duke University, Durham, North Carolina, United States of America
                [3 ]Biomedical Research, Asociación Benéfica PRISMA, Iquitos, Peru
                [4 ]U.S. Naval Medical Research Unit Six, Lima, Peru
                [5 ]Department of Tropical Medicine, Tulane School of Public Health, New Orleans, Louisiana, United States of America
                University of California San Diego School of Medicine, United States of America
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MK PPY MPO. Performed the experiments: CBC RB DT MG. Analyzed the data: GL WP MK RO. Contributed reagents/materials/analysis tools: DT MG. Wrote the paper: GL MK.


                This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                Page count
                Pages: 9
                The study was funded by the National Institute of Health (K01-TW05717 to MK) and GL was supported by T32HD046405. The funding agency had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Research Article
                Global Health
                Infectious Diseases
                Gastrointestinal Infections
                Public Health
                Child Health

                Infectious disease & Microbiology
                Infectious disease & Microbiology


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