Etiology of Severe Acute Watery Diarrhea in Children in the Global Rotavirus Surveillance Network Using Quantitative Polymerase Chain Reaction

• Type of Material: Article
• Authors: Darwin Operario, University of Virginia; James A. Platts-Mills, University of Virginia; Sandrama Nadan, Sefako Makgatho Health Sciences University; Nicola Page, Sefako Makgatho Health Sciences University; Mapaseka Seheri, Sefako Makgatho Health Sciences University; Jeffrey Mphahlele, Sefako Makgatho Health Sciences University; Ira Praharaj, Christian Medical College; Gagandeep Kang, Christian Medical College; Irene T. Araujo, Instituto Oswaldo Cruz/Fiocruz; Jose Paulo G. Leite, Instituto Oswaldo Cruz/Fiocruz; Daniel Cowley, Murdoch Children's Research Institute; Sarah Thomas, Murdoch Children's Research Institute; Carl D. Kirkwood, Murdoch Childrens Research Institute; Francis Dennis, Murdoch Childrens Research Institute; George Armah, Noguchi Memorial Institute for Medical Research; Jason M. Mwenda, World Health Organization; Pushpa Ranjan Wijesinghe, World Health Organization; Gloria Rey, World Health Organization; Varja Grabovac, World Health Organization; Chipo Berejena, University of Zimbabwe; Chibumbya Simwaka, University Teaching Hospital; Jeannine Uwimana, Ministry of Health, Kigali, Rwanda; Jeevan B. Sherchand, Tribhuvan University Teaching Hospital; Hlaing Myat Thu, Department of Medical Research, Yangon, Myanmar; Geethani Galagoda, Medical Research Institute, Colombo, Sri Lanka; Isidore J. O. Bonkoungou, Laboratoire National de Santé Publique, Ouagadougou, Burkina Faso; Sheriffo Jagne, National Public Health Laboratories, Fajara, The Gambia; Enyonam Tsolenyanu, Sylvanus Olympio Teaching Hospital, Lomé, Togo; Amadou Diop, Albert Royer National Paediatric Hospital Laboratory, Dakar, Senegal; Christabel Enweronu-Laryea, University of Ghana; Sam-Aliyah Borbor, University of Sierra Leone; Jie Liu, University of Virginia; Timothy McMurry, University of Virginia; Benjamin Lopman, Emory University; Umesh Parashar, Centers for Disease Control and Prevention; John Gentsch, Centers for Disease Control and Prevention; A. Duncan Steele, Bill and Melinda Gates Foundation; Adam L. Cohen, Emory University; Fatima Serhan, World Health Organization; Eric R. Houpt, University of Virginia
• Language: English
• Date: 2017-07-15
• Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option C
• Publication Version: Final Published Version
• Copyright Statement: © The Author 2017.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/infdis/jix294
• Title of Journal or Parent Work: Journal of Infectious Diseases
• ISSN: 0022-1899
• Volume: 216
• Issue: 2
• Start Page: 220
• End Page: 227
• Grant/Funding Information: This work was supported by the Bill & Melinda Gates Foundation (grant number OPP1084328).
• Keywords: Infectious Diseases; VACCINE INTRODUCTION; MULTICENTER; GEMS; Science & Technology; Immunology; DEVELOPING-COUNTRIES; LESS-THAN-5 YEARS; IMPACT; HOSPITALIZATIONS; Life Sciences & Biomedicine; BURDEN; PCR; MORTALITY; rotavirus; DISEASE; diarrhea; Microbiology; surveillance
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Immunology; Health Sciences, Public Health

Abstract

Background. The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction. Methods. We performed quantitative polymerase chain reaction for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14 643 episodes captured by surveillance of children < 5 years of age during 2013-2014 from 16 countries. We used previously developed models of the association between pathogen quantity and diarrhea to calculate pathogen-specific weighted attributable fractions (AFs). Results. Rotavirus remained the leading etiology (overall weighted AF, 40.3% [95% confidence interval {CI}, 37.6%-44.3%] ), though the AF was substantially lower in the Americas (AF, 12.2 [95% CI, 8.9-15.6]), based on samples from a country with universal rotavirus vaccination. Norovirus GII (AF, 6.2 [95% CI, 2.8-9.2] ), Cryptosporidium (AF, 5.8 [95% CI, 4.0-7.6]), Shigella (AF, 4.7 [95% CI, 2.8-6.9] ), heat-stable enterotoxin-producing Escherichia coli (ST-ETEC) (AF, 4.2 [95% CI, 2.0-6.1]), and adenovirus 40/41 (AF, 4.2 [95% CI, 2.9-5.5] ) were also important. In the Africa Region, the rotavirus AF declined from 54.8% (95% CI, 48.3%-61.5%) in rotavirus vaccine age-ineligible children to 20.0% (95% CI, 12.4%-30.4%) in age-eligible children. Conclusions. Rotavirus remained the leading etiology of acute watery diarrhea despite a clear impact of rotavirus vaccine introduction. Norovirus GII, Cryptosporidium, Shigella, ST-ETEC, and adenovirus 40/41 were also important. Prospective surveillance can help identify priorities for further reducing the burden of diarrhea.