TY - JOUR
T1 - Epidemiology of shigella infections and diarrhea in the first two years of life using culture-independent diagnostics in 8 low-resource settings
AU - Rogawski Mcquade, Elizabeth T.
AU - Shaheen, Fariha
AU - Kabir, Furqan
AU - Rizvi, Arjumand
AU - Platts-Mills, James A.
AU - Aziz, Fatima
AU - Kalam, Adil
AU - Qureshi, Shahida
AU - Elwood, Sarah
AU - Liu, Jie
AU - Lima, Aldo A.M.
AU - Kang, Gagandeep
AU - Bessong, Pascal
AU - Samie, Amidou
AU - Haque, Rashidul
AU - Mduma, Estomih R.
AU - Kosek, Margaret N.
AU - Shrestha, Sanjaya
AU - Leite, Jose Paulo
AU - Bodhidatta, Ladaporn
AU - Page, Nicola
AU - Kiwelu, Ireen
AU - Shakoor, Sadia
AU - Turab, Ali
AU - Soofi, Sajid Bashir
AU - Ahmed, Tahmeed
AU - Houpt, Eric R.
AU - Bhutta, Zulfiqar
AU - Iqbal, Najeeha Talat
N1 - Funding Information:
The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) was carried out as a collaborative project supported by the Bill and Melinda Gates Foundation (https://www. gatesfoundation.org/; OPP1131125), the Foundation for the National Institutes of Health, and the National Institutes of Health, Fogarty International Center. This work was supported by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (https://www. niaid.nih.gov/; grant K01AI130326 to ETRM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2020 Rogawski McQuade et al.
PY - 2020/8
Y1 - 2020/8
N2 - Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR: 1.75, 95% CI: 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR: 1.15, 95% CI: 1.03, 1.29), low maternal education (<10 years, RR: 1.14, 95% CI: 1.03, 1.26), initiating complementary foods before 3 months (RR: 1.10, 95% CI: 1.01, 1.20), and malnutrition (RR: 0.91, 95% CI: 0.88, 0.95 per unit increase in weight-for-age z-score) were risk factors for Shigella. There was a linear dose-response between Shigella quantity and myeloperoxidase concentrations. The burden of Shigella varied widely across sites, but uni-formly increased through the second year of life and was associated with intestinal inflam-mation. Culture missed most clinically relevant cases of severe diarrhea and dysentery.
AB - Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR: 1.75, 95% CI: 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR: 1.15, 95% CI: 1.03, 1.29), low maternal education (<10 years, RR: 1.14, 95% CI: 1.03, 1.26), initiating complementary foods before 3 months (RR: 1.10, 95% CI: 1.01, 1.20), and malnutrition (RR: 0.91, 95% CI: 0.88, 0.95 per unit increase in weight-for-age z-score) were risk factors for Shigella. There was a linear dose-response between Shigella quantity and myeloperoxidase concentrations. The burden of Shigella varied widely across sites, but uni-formly increased through the second year of life and was associated with intestinal inflam-mation. Culture missed most clinically relevant cases of severe diarrhea and dysentery.
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U2 - 10.1371/journal.pntd.0008536
DO - 10.1371/journal.pntd.0008536
M3 - Article
C2 - 32804926
AN - SCOPUS:85090079168
SN - 1935-2727
VL - 14
SP - 1
EP - 17
JO - PLoS neglected tropical diseases
JF - PLoS neglected tropical diseases
IS - 8
M1 - e0008536
ER -