Diarrheal Pathogens Associated With Growth and Neurodevelopment

Abstract

Background: Diarrheal pathogens have been associated with linear growth deficits. The effect of diarrheal pathogens on growth is likely due to inflammation, which also adversely affects neurodevelopment. We hypothesized that diarrheagenic pathogens would be negatively associated with both growth and neurodevelopment.

Methods: We conducted a longitudinal birth cohort study of 250 children with diarrheal surveillance and measured pathogen burden in diarrheal samples using quantitative polymerase chain reaction. Pathogen attributable fraction estimates of diarrhea over the first 2 years of life, corrected for socioeconomic variables, were used to predict both growth and scores on the Bayley-III Scales of Infant and Toddler Development.

Results: One hundred eighty children were analyzed for growth and 162 for neurodevelopmental outcomes. Rotavirus, Campylobacter, and Shigella were the leading causes of diarrhea in year 1 while Shigella, Campylobacter, and heat-stable toxin-producing enterotoxigenic Escherichia coli were the leading causes in year 2. Norovirus was the only pathogen associated with length-for-age z score at 24 months and was positively associated (regression coefficient [RC], 0.42 [95% confidence interval {CI}, .04 to .80]). Norovirus (RC, 2.46 [95% CI, .05 to 4.87]) was also positively associated with cognitive scores while sapovirus (RC, -2.64 [95% CI, -4.80 to -.48]) and typical enteropathogenic E. coli (RC, -4.14 [95% CI, -8.02 to -.27]) were inversely associated. No pathogens were associated with language or motor scores. Significant maternal, socioeconomic, and perinatal predictors were identified for both growth and neurodevelopment.

Conclusions: Maternal, prenatal, and socioeconomic factors were common predictors of growth and neurodevelopment. Only a limited number of diarrheal pathogens were associated with these outcomes.

Keywords: diarrhea; low-income countries; neurodevelopment; stunting.

Figure 1.

Incidence and number of pathogen attributable fraction estimates (AFes) for 0–12 months (A and B) and 13–24 months (C and D). The microbiologic etiology of diarrhea was determined by TaqMan Array Card polymerase chain reaction over the first 2 years of life. A, Proportion of stool samples positive for a given pathogen from birth to 12 months. B, Attributable episode distribution, plotted as median and 95% confidence interval, for a given enteropathogen from birth to 12 months. C, Proportion of stools positive for 13–24 months. D, Attributable episode distribution for 13–24 months. Enteroaggregative Escherichia coli (EAEC) was the most common pathogen detected in stool in the first 12 months of life followed by heat-labile toxin–producing enterotoxigenic E. coli (ETEC), and Campylobacter jejuni/coli. However, the most common causes of diarrhea were rotavirus followed by C. jejuni/coli and Shigella. EAEC remained the leading pathogen detected in the second year of life followed by C. jejuni/coli and Shigella. Shigella was the leading cause of diarrhea in the second year of life, followed by C. jejuni/coli, heat-stable toxin–producing ETEC, and sapovirus. Abbreviations: EAEC, enteroaggregative Escherichia coli; EPEC, enteropathogenic Escherichia coli; LT-ETEC, heat-labile toxin–producing enterotoxigenic Escherichia coli; ST-ETEC, heat-stable toxin–producing enterotoxigenic Escherichia coli; V. cholerae, Vibirio cholerae.

Figure 2.

Number of attributable episodes by month of life. Attributable fraction estimates per month of life are shown for the pathogens analyzed. Bacterial pathogens tended to remain consistent throughout the first 2 years whereas viral pathogens tended to decrease in the second year of life. Abbreviations: C. jejuni/coli, Campylobacter jejuni/coli; EPEC, enteropathogenic Escherichia coli; ST-ETEC, heat-stable toxin–producing enterotoxigenic Escherichia coli; V. cholerae, Vibirio cholerae.