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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.
Lancet. 2013 Jul 20; 382(9888):209-22.Lct

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.

Authors+Show Affiliations

Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA. kkotloff@medicine.umaryland.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23680352

Citation

Kotloff, Karen L., et al. "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." Lancet (London, England), vol. 382, no. 9888, 2013, pp. 209-22.
Kotloff KL, Nataro JP, Blackwelder WC, et al. 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. Lancet. 2013;382(9888):209-22.
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., ... Levine, M. M. (2013). 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. Lancet (London, England), 382(9888), 209-22. https://doi.org/10.1016/S0140-6736(13)60844-2
Kotloff KL, et al. 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. Lancet. 2013 Jul 20;382(9888):209-22. PubMed PMID: 23680352.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Kotloff,Karen L, AU - Nataro,James P, AU - Blackwelder,William C, AU - Nasrin,Dilruba, AU - Farag,Tamer H, AU - Panchalingam,Sandra, AU - Wu,Yukun, AU - Sow,Samba O, AU - Sur,Dipika, AU - Breiman,Robert F, AU - Faruque,Abu Sg, AU - Zaidi,Anita Km, AU - Saha,Debasish, AU - Alonso,Pedro L, AU - Tamboura,Boubou, AU - Sanogo,Doh, AU - Onwuchekwa,Uma, AU - Manna,Byomkesh, AU - Ramamurthy,Thandavarayan, AU - Kanungo,Suman, AU - Ochieng,John B, AU - Omore,Richard, AU - Oundo,Joseph O, AU - Hossain,Anowar, AU - Das,Sumon K, AU - Ahmed,Shahnawaz, AU - Qureshi,Shahida, AU - Quadri,Farheen, AU - Adegbola,Richard A, AU - Antonio,Martin, AU - Hossain,M Jahangir, AU - Akinsola,Adebayo, AU - Mandomando,Inacio, AU - Nhampossa,Tacilta, AU - Acácio,Sozinho, AU - Biswas,Kousick, AU - O'Reilly,Ciara E, AU - Mintz,Eric D, AU - Berkeley,Lynette Y, AU - Muhsen,Khitam, AU - Sommerfelt,Halvor, AU - Robins-Browne,Roy M, AU - Levine,Myron M, Y1 - 2013/05/14/ PY - 2013/5/18/entrez PY - 2013/5/18/pubmed PY - 2013/8/2/medline SP - 209 EP - 22 JF - Lancet (London, England) JO - Lancet VL - 382 IS - 9888 N2 - 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. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/23680352/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(13)60844-2 DB - PRIME DP - Unbound Medicine ER -