Clostridioides difficile colonization among very young children in resource-limited settings

• Type of Material: Article
• Authors: Stephanie A Brennhofer, University of Virginia; Elizabeth McQuade, Emory University; Jie Liu, University of Virginia; Richard L Guerrant, University of Virginia; James A Platts-Mills, University of Virginia; Cirle A Warren, University of Virginia
• Language: English
• Date: 2022-07-01
• Publisher: ELSEVIER SCI LTD
• Publication Version: Final Published Version
• Copyright Statement: © 2022 The Author(s)
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.cmi.2022.01.022
• Title of Journal or Parent Work: CLINICAL MICROBIOLOGY AND INFECTION
• Volume: 28
• Issue: 7
• Start Page: 996
• End Page: 1002
• Keywords: Diarrhoea; INFECTION; Enteropathy; Children; Low-resource settings; Infectious Diseases; ENTEROPATHY; Microbiology; Life Sciences & Biomedicine; ANTIBIOTICS; EXPOSURE; Clostridioides difficile; Science & Technology; C. difficile
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Public Health

Abstract

Objectives: To describe the epidemiology and risk factors for Clostridioides difficile (C. difficile) colonization among young children in eight low-resource settings. Methods: We tested 41 354 monthly non-diarrhoeal and diarrhoeal stools for C. difficile toxin genes (TcdA and TcdB) using quantitative PCR (qPCR) in 1715 children from birth to age two years in a multisite birth cohort study. We estimated the prevalence, cumulative incidence, and seasonality of C. difficile colonization and investigated the associations of C. difficile detection with risk factors of infection, markers of enteropathy, and growth. Results: The prevalence of C. difficile detection was lower in diarrhoeal (2.2%; n = 151/6731) compared to non-diarrhoeal stools (6.1%; n = 2106/34 623). By 24 months of age, the cumulative incidence of C. difficile varied widely by site, with 17.9% (n = 44; Pakistan) to 76.3% (n = 148; Peru) of children having at least one positive stool. Only Bangladesh and Pakistan had seasonal differences in C. difficile detection. Female sex (adjusted risk ratio (aRR): 1.18; 95% CI: 1.02–1.35), cephalosporin use in the past 15 days (aRR: 1.73; 95% CI: 1.39–2.16), and treated water (aRR: 1.24; 95% CI: 1.02–1.50) were risk factors for C. difficile positivity. The presence of C. difficile was significantly associated with elevated faecal myeloperoxidase, neopterin, and α-1-antitrypsin, but no associations were found between C. difficile and child growth at 24 months of age. Discussion: C. difficile colonization among children ages 0–2 years was variable across low-resource settings. Significant elevation of intestinal inflammation and barrier disruption markers associated with C. difficile detection suggests a subclinical impact of colonization.