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EPIDEMIOLOGY OF SHIGELLA INFECTIONS AND DIARRHEA IN THE FIRST TWO YEARS OF LIFE USING CULTURE-INDEPENDENT DIAGNOSTICS IN 8 LOWRESOURCE SETTINGS
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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 uniformly
increased through the second year of life and was associated with intestinal inflammation.
Culture missed most clinically relevant cases of severe diarrhea and dysentery.
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