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

The Lancet  
Jul 20, 2013  Volume 382  Number 9888  p181 – 284  e1
http://www.thelancet.com/journals/lancet/issue/current

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 SG Faruque, Anita KM Zaidi, Debasish Saha, Pedro L Alonso, Boubou Tamboura, Doh Sanogo, Uma Onwuchekwa, Byomkesh Manna, Thandavarayan Ramamurthy, Suman Kanungo, John 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
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2960844-2/abstract

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 13 129 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.