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

KL Kotloff, JP Nataro, WC Blackwelder, D Nasrin… - The lancet, 2013 - thelancet.com
KL Kotloff, JP Nataro, WC Blackwelder, D Nasrin, TH Farag, S Panchalingam, Y Wu, SO Sow…
The lancet, 2013thelancet.com
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 …
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.
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