Abstract:
Background Enteropathogen infections in early childhood not only cause diarrhoea but contribute to poor growth. We
used molecular diagnostics to assess whether particular enteropathogens were associated with linear growth across
seven low-resource settings.
Methods We used quantitative PCR to detect 29 enteropathogens in diarrhoeal and non-diarrhoeal stools collected
from children in the first 2 years of life obtained during the Etiology, Risk Factors, and Interactions of Enteric
Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite cohort
study. Length was measured monthly. We estimated associations between aetiology-specific diarrhoea and subclinical
enteropathogen infection and quantity and attained length in 3 month intervals, at age 2 and 5 years, and used a
longitudinal model to account for temporality and time-dependent confounding.
Findings Among 1469 children who completed 2 year follow-up, 35 622 stool samples were tested and yielded valid
results. Diarrhoeal episodes attributed to bacteria and parasites, but not viruses, were associated with small decreases in
length after 3 months and at age 2 years. Substantial decrements in length at 2 years were associated with subclinical,
non-diarrhoeal, infection with Shigella (length-for-age Z score [LAZ] reduction –0·14, 95% CI –0·27 to –0·01),
enteroaggregative Escherichia coli (–0·21, –0·37 to –0·05), Campylobacter (–0·17, –0·32 to –0·01), and Giardia (–0·17,
–0·30 to –0·05). Norovirus, Cryptosporidium, typical enteropathogenic E coli, and Enterocytozoon bieneusi were also
associated with small decrements in LAZ. Shigella and E bieneusi were associated with the largest decreases in LAZ
per log increase in quantity per g of stool (–0·13 LAZ, 95% CI –0·22 to –0·03 for Shigella; –0·14, –0·26 to –0·02 for
E bieneusi). Based on these models, interventions that successfully decrease exposure to Shigella, enteroaggregative E coli,
Campylobacter, and Giardia could increase mean length of children by 0·12–0·37 LAZ (0·4–1·2 cm) at the MAL-ED sites.
Interpretation Subclinical infection and quantity of pathogens, particularly Shigella, enteroaggregative E coli,
Campylobacter, and Giardia, had a substantial negative association with linear growth, which was sustained during
the first 2 years of life, and in some cases, to 5 years. Successfully reducing exposure to certain pathogens might
reduce global stunting.
