Mass Azithromycin Distribution and Community Microbiome: A Cluster-Randomized Trial.

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TitleMass Azithromycin Distribution and Community Microbiome: A Cluster-Randomized Trial.
Publication TypeJournal Article
Year of Publication2018
AuthorsDoan T, Hinterwirth A, Arzika AM, Cotter SY, Ray KJ, O'Brien KS, Zhong L, Chow ED, Zhou Z, Cummings SL, Fry D, Oldenburg CE, Worden L, Porco TC, Keenan JD, Lietman TM
JournalOpen Forum Infect Dis
Date Published2018 Aug

Background: Mass distributions of oral azithromycin have long been used to eliminate trachoma, and they are now being proposed to reduce childhood mortality. The observed benefit appears to be augmented with each additional treatment, suggesting a possible community-level effect. Here, we assess whether 2 biannual mass treatments of preschool children affect the community's gut microbiome at 6 months after the last distribution.

Methods: In this cluster-randomized controlled trial, children aged 1-60 months in the Dossa region of Niger were randomized at the village level to receive a single dose of azithromycin or placebo every 6 months. Fecal samples were collected 6 months after the second treatment for metagenomic deep sequencing. The prespecified primary outcome was the Euclidean PERMANOVA of the gut microbiome, or effectively the distance between the genus-level centroid at the community level, with the secondary outcome being the Simpson's α diversity.

Results: In the azithromycin arm, the gut microbial structures were significantly different than in the placebo arm (Euclidean PERMANOVA, < .001). Further, the diversity of the gut microbiome in the azithromycin arm was significantly lower than in the placebo arm (inverse Simpson's index, = .005).

Conclusions: Two mass azithromycin administrations, 6 months apart, in preschool children led to long-term alterations of the gut microbiome structure and community diversity. Here, long-term microbial alterations in the community did not imply disease but were associated with an improvement in childhood mortality.

Clinical Trials Registration: NCT02048007.

Alternate JournalOpen Forum Infect Dis
PubMed ID30151409
PubMed Central IDPMC6101535
Grant ListK08 EY026986 / EY / NEI NIH HHS / United States
R25 MH083620 / MH / NIMH NIH HHS / United States