Impact of azithromycin and nitazoxanide on the enteric infections and child growth: Findings from the Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT) trial
Open Access
- 21 December 2023
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 18 (12) , e0294110
Abstract
Background: Early childhood enteric infection with Shigella/EIEC, enteroaggregative E. coli (EAEC), Campylobacter, and Giardia has been associated with reduced child growth, yet a recent randomized trial of antimicrobial therapy to reduce these infections did not improve growth outcomes. To interrogate this discrepancy, we measured the enteric infections from this study. Methods: We leveraged the Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT) trial, a randomized double-blind placebo-controlled trial of antimicrobial therapy with azithromycin and nitazoxanide provided quarterly to infants from 6 to 15 months of age. We tested 5,479 stool samples at time points across the study for 34 enteropathogens using quantitative PCR. Results: There was substantial carriage of enteropathogens in stool. Azithromycin administration led to reductions in Campylobacter jejuni/coli, enteroaggregative E. coli, and Shigella/EIEC (absolute risk difference ranged from -0.06 to 0.24) 2 weeks after treatment however there was no effect after 3 months. There was no difference in Giardia after nitazoxanide administration (ARR 0.03 at the 12 month administration). When examining the effect of azithromycin versus placebo on the subset of children infected with specific pathogens at the time of treatment, a small increase in weight-for-age Z score was seen only in those infected with Campylobacter jejuni/coli (0.10 Z score, 95% CI -0.01–0.20; length-for-age Z score 0.07, 95% CI -0.06–0.20). Conclusion: The antimicrobial intervention of quarterly azithromycin plus or minus nitazoxanide led to only transient decreases in enteric infections with Shigella/EIEC, enteroaggregative E. coli (EAEC), Campylobacter, and Giardia. There was a trend towards improved growth in children infected with Campylobacter that received quarterly azithromycin.Keywords
Funding Information
- Bill and Melinda Gates Foundation (OPP1141342)
This publication has 18 references indexed in Scilit:
- Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort studyThe Lancet Global Health, 2018
- Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT): a protocol for a randomised factorial, double-blind, placebo-controlled trial of azithromycin, nitazoxanide and nicotinamideBMJ Open, 2018
- Relationship between growth and illness, enteropathogens and dietary intakes in the first 2 years of life: findings from the MAL-ED birth cohort studyBMJ Global Health, 2017
- Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control studyThe Lancet, 2016
- The effect of azithromycin on the immunogenicity of oral poliovirus vaccine: a double-blind randomised placebo-controlled trial in seronegative Indian infantsThe Lancet Infectious Diseases, 2016
- Optimization of Quantitative PCR Methods for Enteropathogen DetectionPLOS ONE, 2016
- ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammationNature, 2012
- Azithromycin and Loperamide Are Comparable to Levofloxacin and Loperamide for the Treatment of Traveler's Diarrhea in United States Military Personnel in TurkeyClinical Infectious Diseases, 2007
- A Modified Poisson Regression Approach to Prospective Studies with Binary DataAmerican Journal of Epidemiology, 2004
- Randomized clinical study of nitazoxanide compared to metronidazole in the treatment of symptomatic giardiasis in children from Northern PeruAlimentary Pharmacology & Therapeutics, 2001