Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study.

Background Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries. We designed the Global Enteric Multlcenter Study (GEMS) to identify the aetiology and population-based burden of paediatric diarrhoea] disease in sub-Saharan Africa and south Asia. Methods The GEMS is a 3-year, prospective, age-stratified, matched case-control study of moderate-to-severe diarrhoea in children aged 0-59 months residing in censused populations at four sites in Africa and three in Asia. We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three randomly selected matched community control children without diarrhoea. From patients with moderate-to-severe diarrhoea and controls, we obtained clinical and epidemiological data, anthropometric measurements, and a faecal sample to identify enteropathogens at enrolment; one follow-up home visit was made about 60 days later to ascertain vital status, clinical outcome, and interval growth. Findings We enrolled 9439 children with moderate-to-severe diarrhoea and 13129 control children without diarrhoea. By analysing adjusted population attributable fractions, most attributable cases of moderate-to-severe diarrhoea were due to four pathogens: rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli producing heat- stable toxin (ST-ETEC; with or without co-expression of heat-labile enterotoxin), and Shigella. Other pathogens were important in selected sites (eg, Aeromonas, Vibrio cholerae O1, Campylobacterjejuni). Odds of dying during follow-up were 8.5-fold higher in patients with moderate-to-severe diarrhoea than in controls (odd ratio 8.5, 95% CI 5.8-12.5, p<0.0001); most deaths (167 [87.9%]) occurred during the first 2 years of life. Pathogens associated with increased risk of case death were ST-ETEC (hazard ratio [HR] 1.9; 0.99-3-5) and typical enteropathogenic E coli (HR 2-6; 1.6-4.1) in infants aged 0-11 months, and Cn/ptosporidium (HR 2.3; 1.3-4.3) toddlers aged 12-23 months. Interpretation Interventions targeting five pathogens (rotavirus, Shigella, ST-ETEC, Cryptosporidium, typical enter pathogenic E coli) can substantially reduce the burden of moderate-to-severe diarrhoea. New methods a accelerated implementation of existing interventions (rotavirus vaccine and zinc) are needed to prevent disease and improve outcomes. Funding The Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]