Abstract
Childhood diarrhea in low-resource settings has been variably linked to linear growth shortfalls. However, the association between etiology-specific diarrhea and growth has not been comprehensively evaluated. We tested diarrheal stools collected from the Performance of Rotavirus and Oral Polio Vaccines in Developing Countries study from 2011 to 2013 in Dhaka, Bangladesh, by quantitative polymerase chain reaction for a broad range of enteropathogens to characterize diarrhea etiology and examine the association between etiology-specific diarrhea and linear growth and systemic inflammation. Pathogen-specific burdens of diarrhea were determined using attributable fractions. Linear regression was used to examine associations of pathogen-specific diarrhea with length-for-age z scores (LAZ) and serum C-reactive protein. There was no relationship between all-cause diarrhea and length at 12 months (change in 12-month LAZ per episode, −0.01, 95% confidence interval (CI): −0.06, 0.03). However, Cryptosporidium (change in 12-month LAZ per attributable episode, −0.23, 95% CI: −0.50, 0.03), Campylobacter jejuni/coli (change of −0.16, 95% CI: −0.32, −0.01), and Shigella/enteroinvasive Escherichia coli diarrhea (change of −0.12, 95% CI: −0.26, 0.03) were associated with linear growth deficits. Diarrhea attributable to C. jejuni/coli and Shigella/enteroinvasive E. coli were associated with elevated C-reactive protein. The association between diarrhea and linear growth appears to be pathogen-specific, reinforcing the need for pathogen-specific interventions.
Highlights
Despite a reduction since 1990 in acute mortality attributable to diarrhea in children under age 5 years, diarrhea incidence has declined more slowly [1]
Quantitative polymerase chain reaction has increased the specificity of pathogen attribution because higher pathogen quantities are more strongly associated with diarrhea [15]
The Performance of Rotavirus and Oral Polio Vaccines in Developing Countries study (PROVIDE) is a longitudinal birth cohort study developed to understand the relationship between environmental enteric dysfunction and oral vaccine performance using a randomized trial of oral vaccines [17]
Summary
Despite a reduction since 1990 in acute mortality attributable to diarrhea in children under age 5 years, diarrhea incidence has declined more slowly [1]. The association between etiology-specific diarrhea and child growth has not been comprehensively evaluated, and previous studies have focused on one or a few pathogens [6–11]. Campylobacter, Shigella, enterotoxigenic Escherichia coli, and Cryptosporidium have been variably identified as agents of diarrhea associated with growth shortfalls. These studies have defined etiology-specific diarrhea as any episode of diarrhea in which the pathogen of interest is detected without adjustment for subclinical carriage of enteropathogens, and use of increasingly sensitive detection methods has revealed a striking burden of subclinical enteric infection in these settings [12]. We tested all available stool specimens collected from diarrheal episodes identified via household surveillance in the first year of life, using qPCR for a broad range of enteropathogens. We estimated pathogen-specific burdens of diarrhea and the association between etiology-specific diarrhea and both linear growth and systemic inflammation in this cohort
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