Pathogen-specific burdens of community diarrhoea in developing countries (MAL-ED): a multisite birth cohort study

Summary

Background

Most aetiologic studies of diarrhoea in developing countries have examined severe disease presenting for care, while pathogen-specific estimates of diarrhoea burden through community-based surveillance are limited.

Methods

We performed a birth cohort study with intensive community surveillance for diarrhoea as well as routine collection of non-diarrhoeal stools from eight sites in South America, Africa and Asia. Stools were analysed for a broad range of enteropathogens using culture, enzyme immunoassay, and PCR.

Findings

A total of 7,318 diarrhoeal and 24,310 non-diarrhoeal stools from 2,145 children aged 0-24 months were tested. Pathogen detection was common in non-diarrhoeal stools and increased during diarrhoea. Norovirus GII (adjusted attributable fraction (AF) 5·2; 95% CI 3·0-7·1), rotavirus (4·8; 4·5-5·0), Campylobacter (3·5; 0·4-6·3), astrovirus (2·7; 2·2-3·1), and Cryptosporidium (2·0; 1·3-2·6) exhibited the highest attributable burdens of diarrhoea in the first year of life. The major pathogens associated with diarrhoea in the second year of life were Campylobacter (7·9; 3·1-12·1), norovirus GII (5·4; 2·1-7·8), rotavirus (4·9; 4·4-5·2), astrovirus (4·2; 3·5-4·7), and Shigella (4·0; 3·6-4·3). Rotavirus had the highest AF for sites without rotavirus vaccination (RV) and the fifth highest AF for sites with RV. There was substantial variation in pathogens based on geography, severity, and season. Bloody diarrhoea was primarily associated with Campylobacter and Shigella, fever and vomiting with rotavirus, and vomiting with norovirus GII.

Interpretation

Detection of enteropathogens in the absence of diarrhoeal symptoms was common. There was substantial heterogeneity in pathogen-specific burdens of diarrhoea, with important determinants including age, geography, season, rotavirus vaccine usage, and symptomatology. We observed a high burden of disease associated with Campylobacter, norovirus GII, and astrovirus.