Doan Thuy, Hinterwirth Armin, Arzika Ahmed M, Cotter Sun Y, Ray Kathryn J, O'Brien Kieran S, Zhong Lina, Chow Eric D, Zhou Zhaoxia, Cummings Susie L, Fry Dionna, Oldenburg Catherine E, Worden Lee, Porco Travis C, Keenan Jeremy D, Lietman Thomas M
Francis I. Proctor Foundation, San Francisco, California.
Department of Ophthalmology, University of California San Francisco, San Francisco, California.
Open Forum Infect Dis. 2018 Jul 24;5(8):ofy182. doi: 10.1093/ofid/ofy182. eCollection 2018 Aug.
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.
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.
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).
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.
NCT02048007.
口服阿奇霉素的群体给药长期以来一直用于消除沙眼，目前有人提议用其降低儿童死亡率。每增加一次治疗，观察到的益处似乎就会增加，这表明可能存在社区层面的效应。在此，我们评估对学龄前儿童进行两次半年一次的群体治疗是否会在最后一次给药6个月后影响社区的肠道微生物群。
在这项整群随机对照试验中，尼日尔多萨地区1至60个月大的儿童在村庄层面被随机分组，每6个月接受一剂阿奇霉素或安慰剂。在第二次治疗6个月后收集粪便样本进行宏基因组深度测序。预先设定的主要结局是肠道微生物群的欧几里得PERMANOVA，即社区层面属水平质心之间的有效距离，次要结局是辛普森α多样性。
在阿奇霉素组中，肠道微生物结构与安慰剂组有显著差异（欧几里得PERMANOVA，<0.001）。此外，阿奇霉素组的肠道微生物群多样性显著低于安慰剂组（逆辛普森指数，=0.005）。
对学龄前儿童每隔6个月进行两次阿奇霉素群体给药导致肠道微生物群结构和群落多样性的长期改变。在此，社区中的长期微生物改变并不意味着疾病，但与儿童死亡率的改善有关。
NCT02048007。
