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Cited by 3,560Viral gastroenteritis research and epidemiologyChild Nutrition and Water AccessSalmonella and Campylobacter epidemiology

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

Kotloff, Karen L, Nataro, James P, Blackwelder, William C, Nasrin, Dilruba, Farag, Tamer H, Panchalingam, Sandra, Wu, Yukun, Sow, Samba O +35 more·2013·The Lancet
DOI 10.1016/s0140-6736(13)60844-2
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Abstract

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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  • Previous water treatment and sanitation intervention trials conducted in urban informal settlements or peri-urban settings have typically only based effectiveness on demonstrated reductions in child diarrhea and/or improvements in child growth.

    “Previous water treatment and sanitation intervention trials conducted in urban informal settlements or peri-urban settings have typically only based effectiveness on demonstrated reductions in child diarrhea and/or improvements in child growth 110,112-114 .”

    From Urban informal settlements as hotspots of antimicrobial resistance and the need to curb environmental transmission. (2020) · cites this paper as [110]

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Authors
Kotloff, K. L., Nataro, J. P., Blackwelder, W. C., Nasrin, D., Farag, T. H., Panchalingam, S., Wu, Y., Sow, S. O., Sur, D., Breiman, R. F., Faruque, A. S., Zaidi, A. K., Saha, D., Alonso, P. L., Tamboura, B., Sanogo, D., Onwuchekwa, U., Manna, B., Ramamurthy, T., Kanungo, S., Ochieng, J. B., Omore, R., Oundo, J. O., Hossain, A., Das, S. K., Ahmed, S., Qureshi, S., Quadri, F., Adegbola, R. A., Antonio, M., Hossain, M. J., Akinsola, A., Mandomando, I., Nhampossa, T., Acácio, S., Biswas, K., O'Reilly, C. E., Mintz, E. D., Berkeley, L. Y., Muhsen, K., Sommerfelt, H., Robins-Browne, R. M., & Levine, M. M.
Affiliations
  • University of Maryland, Baltimore (US)
  • Centre Pour le Développement des Vaccins-Mali (ML)
  • National Institute of Cholera and Enteric Diseases (IN)
  • Centers for Disease Control and Prevention (US)
  • International Centre for Diarrhoeal Disease Research (BD)
  • Aga Khan University (PK)
  • Medical Research Council (GB)
  • Hospital Clínic de Barcelona (ES)
  • Kenya Medical Research Institute (KE)
  • GlaxoSmithKline (Belgium) (BE)
  • Manhiça Health Research Centre (MZ)
  • United States Department of Veterans Affairs (US)
  • Norwegian Institute of Public Health (NO)
  • Royal Children's Hospital (AU)
Corresponding author
Kotloff, Karen L
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2013-07
Volume
382
Issue
9888
Pages
209-222
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(13)60844-2
OpenAlex
W2114053580
Cited by
3,560
References
2
Citations by year
2026: 170 · 2025: 230 · 2024: 241 · 2023: 274 · 2022: 284 · 2021: 321 · 2020: 307 · 2019: 328 · 2018: 313 · 2017: 325 · 2016: 281 · 2015: 230 · 2014: 195 · 2013: 56 · 2012: 3
FWCI
185.54
Type
journal article
Language
en
Open access
closed
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Viral gastroenteritis research and epidemiology
  • Health Sciences › Nursing › Nutrition and Dietetics › Child Nutrition and Water Access
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
Keywords
paediatric diarrhoea, rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli, heat-labile enterotoxin, Shigella, Aeromonas, Vibrio cholerae O1, Campylobacter jejuni, enteropathogenic Escherichia coli, child mortality, population attributable fraction, sub-Saharan Africa, South Asia
MeSH terms
Asia, Western, Bacterial Infections, Child, Preschool, Developing Countries, Diarrhea, Diarrhea, Infantile, Female, Humans, Infant, Male, Prospective Studies, Rotavirus Infections, Case-Control Studies, Cost of Illness, Africa South of the Sahara

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