Abstract
Community-level mass treatment with azithromycin has been associated with a mortality benefit in children. However, antibiotic exposures result in disruption of the gut microbiota and repeated exposures may reduce recovery of the gut flora. We conducted a nested cohort study within the framework of a randomized controlled trial to examine associations between mass drug administration (MDA) with azithromycin and the gut microbiota of rural Malawian children aged between 1 and 59 months. Fecal samples were collected from the children at baseline and 6 months after two or four biannual rounds of azithromycin treatment. DNA was extracted from fecal samples and V4-16S rRNA sequencing used to characterize the gut microbiota. Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria were the dominant phyla while Faecalibacterium and Bifidobacterium were the most prevalent genera. There were no associations between azithromycin treatment and changes in alpha diversity, however, four biannual rounds of treatment were associated with increased abundance of Prevotella. The lack of significant changes in gut microbiota after four biannual treatments supports the use of mass azithromycin treatment to reduce mortality in children living in low- and middle-income settings.
Highlights
Azithromycin is a broad-spectrum, macrolide antibiotic characterized by a long intra- and extracellular half-life
Reduced risks of diarrhea and acute lower respiratory infections related to azithromycin mass drug administration (MDA) for trachoma control have been reported in Tanzanian children [4, 5]
The proportion of male children was comparable between those whose fecal samples were included in this nested study and all enrolled participants
Summary
Azithromycin is a broad-spectrum, macrolide antibiotic characterized by a long intra- and extracellular half-life. The World Health Organization (WHO) recommends mass azithromycin treatment at the community level as one of the key strategies. Azithromycin and the Gastrointestinal Microbiome of Malawian Children for the elimination of trachoma as a public health problem [2]. Studies of mass azithromycin distribution for trachoma control in endemic areas indicate that mass treatment has secondary effects, which include reductions in child morbidity and mortality [3–6]. The specific mechanism through which azithromycin reduced mortality in children is not understood, several studies have reported a reduction in the community burden of nasopharyngeal carriage of Streptococcus pneumoniae [8– 10] and a reduction in the abundance of Campylobacter spp. in the gut [11]. Reduced risks of diarrhea and acute lower respiratory infections related to azithromycin mass drug administration (MDA) for trachoma control have been reported in Tanzanian children [4, 5]. Azithromycin may reduce morbidity and mortality by reducing carriage of pathogenic bacteria
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