Key pathogens burden diarrhea in the developing world

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1. Most attributable cases of moderate-to-severe diarrhea were due to four pathogens: Totavirus, Cryptosporidium, Enterotoxigenic escherichia coli producing heat- stable toxin (ST-ETEC), and Shigella. 

2. Moderate-to-severe diarrhea conferred an 8.5 fold increased risk of death among study participants.

Evidence Rating Level: 3 (Fair)

Study Rundown: This study documents the significant burden of disease that childhood diarrhea represents in developing countries. Moreover, it suggests that diarrhea contributes to the causal pathway to childhood death, not just directly through dehydration but also indirectly through the substantial nutritional insult it incurs. Four pathogens, rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli producing heat- stable toxin (ST-ETEC), and Shigella are responsible for most cases of diarrhea in the countries studied. Public health measures that specifically target these pathogens, including rotavirus vaccination campaigns, could substantially morbidity and mortality. However, further research is necessary to determine how proven interventions such as rotavirus vaccination and zinc supplementation might be delivered to the most susceptible children in these countries.

Click to read the study in The Lancet

Relevant Reading: Global, regional, and national causes of childhood mortality

In-Depth [prospective case control study]: This study aimed to assess the population-based burden, microbiological etiology, and adverse clinical effects of diarrhea in developing countries. Between 2007 and 2011, the study enrolled children aged 0-59 months who lived in censused populations and sought care for moderate-to-severe diarrhea at medical facilities serving seven sites in sub-Saharan Africa (Kenya, Mali, Mozambique, The Gambia) and South Asia (Bangladesh, India, Pakistan). Case controls, matched by age, sex, and residence were randomly selected on home visits and enrolled within 14 days of the index case. Upon enrollment, demographic, epidemiological, and clinical information was collected on each child. Stool samples were collected and tested for common bacterial and viral serotypes, and all participants were visited 60 days after enrollment to collect follow-up data. Conditional logistic regression was conducted to assess associations of diarrhea with potential pathogens; pathogen-specific disease burden was estimated using adjusted population attributable fractions calculated from odds ratios and pathogen prevalence in a given area.

Four pathogens were significantly associated with moderate-to-severe diarrhea at all seven study sites: rotavirus, Cryptosporidium, Shigella, and ST-ETEC. Estimated incidence of moderate-to-severe diarrhea was highest in India, followed by Kenya and Mali. At follow-up, 190 (2.0%) deaths were detected in the 9439 children enrolled with moderate-to-severe diarrhea, and 37 (0.3%) deaths were detected in the 13129 control children. Most of these deaths occurred in infants (56%) and toddlers (32%). Mortality in children with diarrhea was highest in the Mozambique site, followed by The Gambia and Kenya. Compared with controls, diarrhea cases had significantly (8.5 times) increased risk of dying during the follow-up period; risk of death varied inversely with height-for-age at enrollment. Among children who experienced diarrhea and were still alive at follow-up, linear growth was significantly delayed.

By Elizabeth Kersten and Andrew Bishara

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