MORDOR II: Persistence of Benefit of Azithromycin for Childhood Mortality

Background. MORDOR I found that 2 years of biannual mass azithromycin administration reduced post-neonatal childhood mortality by 18% in Niger. Over time, this benefit could increase with each distribution or wane due to antibiotic resistance. Here in MORDOR II, we treated communities in both arms for an additional year with azithromycin, resulting in a randomized comparison of the first versus the third year of treatment. Methods. MORDOR I-Niger originally randomized 594 communities to 4 biannual distributions of either azithromycin or placebo to children aged 1-59 months. In MORDOR II, all communities received 2 additional biannual azithromycin distributions. All-cause mortality was assessed during a biannual census by enumerators masked to original assignment. Results. Mean azithromycin coverage was 91.3% (SD ±7.2%) in the communities receiving the first year and 92.0% (±6.6%) in those receiving the third year of azithromycin. Mortality was 24.0 per 1,000 person-years (95% CI, 22.1—26.3) in communities randomized to the first year, and 23.3 per 1,000 person-years (95% CI, 21.4—25.5) in those randomized to the third year of treatment, with no significant difference between arms (p=0.55). In communities originally receiving placebo, mortality decreased 13.3% (95% CI, 5.8%—20.2%, p=0.007) when treated with azithromycin. In communities continuing to receive azithromycin, the mortality reduction was not significantly different in the third year (-3.6%, 95% CI, -12.3%—4.5%, p=0.50). Conclusions. We found no evidence that the effect of mass azithromycin on childhood mortality waned in the third year of treatment. Childhood mortality fell significantly when placebo-treated communities were provided azithromycin.