Etiology of severe acute watery diarrhea in children in the global rotavirus surveillance network using quantitative polymerase chain reaction

Darwin J. Operario, James A. Platts-Mills, Sandrama Nadan, Nicola Page, Mapaseka Seheri, Jeffrey Mphahlele, Ira Praharaj, Gagandeep Kang, Irene T. Araujo, Jose Paulo G. Leite, Daniel Cowley, Sarah Thomas, Carl D. Kirkwood, Francis Dennis, George Armah, Jason M. Mwenda, Pushpa Ranjan Wijesinghe, Gloria Rey, Varja Grabovac, Chipo BerejenaChibumbya J. Simwaka, Jeannine Uwimana, Jeevan B. Sherchand, Hlaing Myat Thu, Geethani Galagoda, Isidore J.O. Bonkoungou, Sheriffo Jagne, Enyonam Tsolenyanu, Amadou Diop, Christabel Enweronu-Laryea, Sam Aliyah Borbor, Jie Liu, Timothy McMurry, Benjamin Lopman, Umesh Parashar, John Gentsch, A. Duncan Steele, Adam Cohen, Fatima Serhan, Eric R. Houpt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

95 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)220-227
Number of pages8
JournalJournal of Infectious Diseases
Issue number2
Publication statusPublished - 15 Jul 2017


  • Diarrhea
  • PCR
  • Rotavirus
  • Surveillance


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