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

Karen L. Kotloff, James P. Nataro, William C. Blackwelder, Dilruba Nasrin, Tamer H. Farag, Sandra Panchalingam, Yukun Wu, Samba O. Sow, Dipika Sur, Robert F. Breiman, Abu S.G. Faruque, Anita K.M. Zaidi, Debasish Saha, Pedro L. Alonso, Boubou Tamboura, Doh Sanogo, Uma Onwuchekwa, Byomkesh Manna, Thandavarayan Ramamurthy, Suman KanungoJohn B. Ochieng, Richard Omore, Joseph O. Oundo, Anowar Hossain, Sumon K. Das, Shahnawaz Ahmed, Shahida Qureshi, Farheen Quadri, Richard A. Adegbola, Martin Antonio, M. Jahangir Hossain, Adebayo Akinsola, Inacio Mandomando, Tacilta Nhampossa, Sozinho Acácio, Kousick Biswas, Ciara E. O'Reilly, Eric D. Mintz, Lynette Y. Berkeley, Khitam Muhsen, Halvor Sommerfelt, Roy M. Robins-Browne, Myron M. Levine

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Summary Background Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries. We designed the Global Enteric Multicenter Study (GEMS) to identify the aetiology and population-based burden of paediatric diarrhoeal 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 13â€̂129 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, Campylobacter jejuni). 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 Cryptosporidium (HR 2·3; 1·3-4·3) in toddlers aged 12-23 months. Interpretation Interventions targeting five pathogens (rotavirus, Shigella, ST-ETEC, Cryptosporidium, typical enteropathogenic E coli) can substantially reduce the burden of moderate-to-severe diarrhoea. New methods and accelerated implementation of existing interventions (rotavirus vaccine and zinc) are needed to prevent disease and improve outcomes. Funding The Bill & Melinda Gates Foundation.

Original languageEnglish
Pages (from-to)209-222
Number of pages14
JournalThe Lancet
Issue number9888
Publication statusPublished - 2013


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