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Multicenter Study
. 2017 Jul 15;216(2):220-227.
doi: 10.1093/infdis/jix294.

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

Darwin J Operario  1 , James A Platts-Mills  1 , Sandrama Nadan  2 , Nicola Page  2 , Mapaseka Seheri  3 , Jeffrey Mphahlele  3 , Ira Praharaj  4 , Gagandeep Kang  4 , Irene T Araujo  5 , Jose Paulo G Leite  5 , Daniel Cowley  6 , Sarah Thomas  6 , Carl D Kirkwood  6 , Francis Dennis  7 , George Armah  7 , Jason M Mwenda  8 , Pushpa Ranjan Wijesinghe  9 , Gloria Rey  10 , Varja Grabovac  11 , Chipo Berejena  12 , Chibumbya J Simwaka  13 , Jeannine Uwimana  14 , Jeevan B Sherchand  15 , Hlaing Myat Thu  16 , Geethani Galagoda  17 , Isidore J O Bonkoungou  18 , Sheriffo Jagne  19 , Enyonam Tsolenyanu  20 , Amadou Diop  21 , Christabel Enweronu-Laryea  22 , Sam-Aliyah Borbor  23 , Jie Liu  1 , Timothy McMurry  1 , Benjamin Lopman  24 , Umesh Parashar  25 , John Gentsch  25 , A Duncan Steele  26 , Adam Cohen  27 , Fatima Serhan  27 , Eric R Houpt  1
Affiliations
Multicenter Study

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

Darwin J Operario et al. J Infect Dis. .

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] J Infect Dis. 2017 Nov 15;216(8):1048. doi: 10.1093/infdis/jix441. J Infect Dis. 2017. PMID: 29149343 Free PMC article. No abstract available.

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 14643 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.

Keywords: PCR; diarrhea; rotavirus; surveillance.

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Figures

Figure 1.
Figure 1.
Weighted prevalence of enteropathogens tested by quantitative polymerase chain reaction (A) and pathogen-specific burdens of diarrhea across all World Health Organization regions (B). The weighted prevalence is shown for all pathogens with at least 1 detection (A), while overall weighted attributable fractions are shown for all pathogens for which the 95% confidence interval did not include 0 (B). Abbreviations: EAEC, enteroaggregative Escherichia coli, EIEC, enteroinvasive Escherichia coli; LT-ETEC, heat-labile enterotoxin-producing Escherichia coli; ST-ETEC, heat-stable enterotoxin-producing Escherichia coli; tEPEC, typical enteropathogenic Escherichia coli.
Figure 2.
Figure 2.
Pathogen-specific burdens of diarrhea using quantitative polymerase chain reaction by World Health Organization (WHO) region. Weighted attributable fraction (AF) is shown for each pathogen by WHO region. Pathogens are ordered by the overall AF. All pathogens for which the 95% confidence interval of the overall AF did not include 0 are shown. Abbreviations: EIEC, enteroinvasive Escherichia coli; ST-ETEC, heat-stable enterotoxin-producing Escherichia coli; tEPEC, typical enteropathogenic Escherichia coli.
Figure 3.
Figure 3.
Pathogen-specific burdens of diarrhea using quantitative polymerase chain reaction by age group. Weighted attributable fraction (AF) is shown for each pathogen and age group. Pathogens are ordered by the overall AF. All pathogens for which the 95% confidence interval of the overall AF did not include 0 are shown. Abbreviations: EIEC, enteroinvasive Escherichia coli; ST-ETEC, heat-stable enterotoxin-producing Escherichia coli; tEPEC, typical enteropathogenic Escherichia coli.
Figure 4.
Figure 4.
Impact of rotavirus vaccine (RV) introduction in the African Region for children aged 2–23 months in countries that introduced RV by 2014. Weighted attributable fraction (AF) is shown for each pathogen, stratified by age eligibility to receive RV. Children were considered age eligible if they were born no more than 2 months prior to the country’s month of RV introduction. Pathogens are ordered by the overall AF. All pathogens for which the 95% confidence interval of the overall AF did not include 0 are shown. Abbreviations: EIEC, enteroinvasive Escherichia coli; RV, rotavirus vaccine; ST-ETEC, heat-stable enterotoxin-producing Escherichia coli; tEPEC, typical enteropathogenic Escherichia coli.
Figure 5.
Figure 5.
Rotavirus burden estimates by World Health Organization region using 3 distinct approaches. Rotavirus burden estimates are shown using (1) weighted attributable fractions (AFs) by quantitative polymerase chain reaction (qPCR); (2) weighted AFs by enzyme immunoassay (EIA); and (3) proportion of stools positive for rotavirus by EIA.
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