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

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.

Keywords: Campylobacter; children; growth; inflammation; risk factors.

Figure 1.

Campylobacter prevalence in diarrheal and nondiarrheal surveillance stool samples. Histogram shows proportions of diarrheal (black) and surveillance (gray) stool samples positive for Campylobacter by enzyme immunoassay by age at each site.

Figure 2.

Site-level sensitivity analysis of risk factors for Campylobacter detection in surveillance stool samples. Risk ratios with 95% confidence intervals (CIs) are shown for risk factors of interest as identified in the overall model (Table 1). All estimates are adjusted for age, sex, season, and the factors shown in the figure. Factors that did not vary at each site were excluded. Abbreviation: WAZ score, weight-for-age Z score.

Figure 3.

Timing and class of antibiotic use and Campylobacter detection in surveillance stool samples. Risk ratios and 95% confidence intervals (CIs) are derived from a single model adjusted for age, sex, site, season, and all shown windows for antibiotic use.

Figure 4.

Association between Campylobacter burden and length attainment at 24 months. A, Left, Difference in model-predicted 24-month length-for-age Z (LAZ) score between 10th and 90th percentiles of Campylobacter burden and median Campylobacter burden, overall and at each site. Right, Campylobacter burden expressed as proportion of surveillance stool samples tested that were positive for Campylobacter. B, Same estimates for overall 10th and 90th percentiles of Campylobacter burden by age interval. Abbreviation: CI, confidence interval.

Figure 5.

Association between Campylobacter detection and fecal markers of intestinal permeability and inflammation (A) and systemic inflammation (B). A, Difference in the log concentrations of neopterin, α-1-antitrypsin, and myeloperoxidase from surveillance stool samples associated with Campylobacter detection. B, Difference in model-predicted mean α-1-acid glycoprotein (AGP) concentrations between 10th and 90th percentiles of Campylobacter burden and median Campylobacter burden, both overall and at each site; blood samples were obtained at 7, 15, and 24 months of age. Abbreviation: CI, confidence interval.