From the Francis I. Proctor Foundation (K.S.O., E.L., B.P., Z.L., V.L., E.C., T.D., J.D.K., C.E.O., T.C.P., B.F.A., T.M.L.), the Departments of Ophthalmology (K.S.O., T.D., J.D.K., C.E.O., T.C.P., B.F.A., T.M.L.) and Epidemiology and Biostatistics (K.S.O., C.E.O., T.C.P., T.M.L.), and the Institute for Global Health Sciences (K.S.O., C.E.O., B.F.A., T.M.L.), University of California, San Francisco, San Francisco; and Centre de Recherche et Interventions en Santé Publique, Birni N'Gaoure (A.M.A., R.M., B.A., I.M.B., D.B., N.G., N.H., A.M.K., S.M., M.A.), and Programme Nationale de Santé Oculaire, Niamey (A.A., A.I.) - both in Niger.
N Engl J Med. 2024 Aug 22;391(8):699-709. doi: 10.1056/NEJMoa2312093.
Twice-yearly mass distribution of azithromycin to children is a promising intervention to reduce childhood mortality in sub-Saharan Africa. The World Health Organization recommended restricting distribution to infants 1 to 11 months of age to mitigate antimicrobial resistance, although this more limited treatment had not yet been tested.
We randomly assigned rural communities in Niger to four twice-yearly distributions of azithromycin for children 1 to 59 months of age (child azithromycin group), four twice-yearly distributions of azithromycin for infants 1 to 11 months of age and placebo for children 12 to 59 months of age (infant azithromycin group), or placebo for children 1 to 59 months of age. Census workers who were not aware of the group assignments monitored mortality twice yearly over the course of 2 years. We assessed three primary community-level mortality outcomes (deaths per 1000 person-years), each examining a different age group and pairwise group comparison.
A total of 1273 communities were randomly assigned to the child azithromycin group (1229 were included in the analysis), 773 to the infant azithromycin group (751 included in the analysis), and 954 to the placebo group (929 included in the analysis). Among 382,586 children, 419,440 person-years and 5503 deaths were recorded. Lower mortality among children 1 to 59 months of age was observed in the child azithromycin group (11.9 deaths per 1000 person-years; 95% confidence interval [CI], 11.3 to 12.6) than in the placebo group (13.9 deaths per 1000 person-years; 95% CI, 13.0 to 14.8) (representing 14% lower mortality with azithromycin; 95% CI, 7 to 22; P<0.001). Mortality among infants 1 to 11 months of age was not significantly lower in the infant azithromycin group (22.3 deaths per 1000 person-years; 95% CI, 20.0 to 24.7) than in the placebo group (23.9 deaths per 1000 person-years; 95% CI, 21.6 to 26.2) (representing 6% lower mortality with azithromycin; 95% CI, -8 to 19). Five serious adverse events were reported: three in the placebo group, one in the infant azithromycin group, and one in the child azithromycin group.
Azithromycin distributions to children 1 to 59 months of age significantly reduced mortality and was more effective than treatment of infants 1 to 11 months of age. Antimicrobial resistance must be monitored. (Funded by the Bill and Melinda Gates Foundation; AVENIR ClinicalTrials.gov number, NCT04224987.).
在撒哈拉以南非洲地区，每年两次向儿童发放阿奇霉素是一种很有前途的降低儿童死亡率的干预措施。世界卫生组织建议将发放范围限制在 1 至 11 个月大的婴儿，以减轻抗生素耐药性，尽管这种更有限的治疗方法尚未经过测试。
我们在尼日尔的农村社区中随机分配，接受四种阿奇霉素的分配方案，包括 1 至 59 个月大的儿童（儿童阿奇霉素组）、1 至 11 个月大的婴儿的阿奇霉素和安慰剂，用于 12 至 59 个月大的儿童（婴儿阿奇霉素组），或 1 至 59 个月大的儿童的安慰剂。不知道分组的普查员每两年监测两次死亡率。我们评估了三种主要的社区死亡率结局（每千人年死亡人数），每种结局都检查了不同的年龄组和两两组比较。
共有 1273 个社区被随机分配到儿童阿奇霉素组（1229 个被纳入分析）、773 个到婴儿阿奇霉素组（751 个被纳入分析）和 954 个到安慰剂组（929 个被纳入分析）。在 382586 名儿童中，记录了 419440 人年和 5503 例死亡。与安慰剂组（每千人年死亡 13.9 人；95%置信区间 [CI]，13.0 至 14.8）相比，1 至 59 个月大的儿童的死亡率在儿童阿奇霉素组中较低（每千人年死亡 11.9 人；95%CI，11.3 至 12.6）（阿奇霉素组死亡率降低 14%；95%CI，7%至 22%；P<0.001）。1 至 11 个月大的婴儿在婴儿阿奇霉素组（每千人年死亡 22.3 人；95%CI，20.0 至 24.7）中的死亡率与安慰剂组（每千人年死亡 23.9 人；95%CI，21.6 至 26.2）相比，并无显著降低（阿奇霉素组死亡率降低 6%；95%CI，-8%至 19%）。报告了 5 例严重不良事件：安慰剂组 3 例，婴儿阿奇霉素组 1 例，儿童阿奇霉素组 1 例。
向 1 至 59 个月大的儿童发放阿奇霉素显著降低了死亡率，并且比治疗 1 至 11 个月大的婴儿更有效。必须监测抗生素耐药性。（由比尔和梅琳达·盖茨基金会资助；AVENIR 临床试验。 gov 编号，NCT04224987。）
