No abstract

No abstract

No abstract

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.

NCT02048007.

Background Mass azithromycin distributions have been shown to reduce mortality in preschool children, although the factors mediating this mortality reduction are not clear. This study was performed to determine whether mass distribution of azithromycin, which has modest antimalarial activity, reduces the community burden of malaria. Methods and findings In a cluster-randomized trial conducted from 23 November 2014 until 31 July 2017, 30 rural communities in Niger were randomized to 2 years of biannual mass distributions of either azithromycin (20 mg/kg oral suspension) or placebo to children aged 1 to 59 months. Participants, field staff, and investigators were masked to treatment allocation. The primary malaria outcome was the community prevalence of parasitemia on thick blood smear, assessed in a random sample of children from each community at study visits 12 and 24 months after randomization. Analyses were performed in an intention-to-treat fashion. At the baseline visit, a total of 1,695 children were enumerated in the 15 azithromycin communities, and 3,029 children were enumerated in the 15 placebo communities. No communities were lost to follow-up. The mean prevalence of malaria parasitemia at baseline was 8.9% (95% CI 5.1%–15.7%; 52 of 552 children across all communities) in the azithromycin-treated group and 6.7% (95% CI 4.0%–12.6%; 36 of 542 children across all communities) in the placebo-treated group. In the prespecified primary analysis, parasitemia was lower in the azithromycin-treated group at month 12 (mean prevalence 8.8%, 95% CI 5.1%–14.3%; 51 of 551 children across all communities) and month 24 (mean 3.5%, 95% CI 1.9%–5.5%; 21 of 567 children across all communities) than it was in the placebo-treated group at month 12 (mean 15.3%, 95% CI 10.8%–20.6%; 81 of 548 children across all communities) and month 24 (mean 4.8%, 95% CI 3.3%–6.4%; 28 of 592 children across all communities) ( P = 0.02). Communities treated with azithromycin had approximately half the odds of parasitemia compared to those treated with placebo (odds ratio [OR] 0.54, 95% CI 0.30 to 0.97). Parasite density was lower in the azithromycin group than the placebo group at 12 and 24 months (square root–transformed outcome; density estimates were 7,540 parasites/μl lower [95% CI −350 to −12,550 parasites/μl; P = 0.02] at a mean parasite density of 17,000, as was observed in the placebo arm). No significant difference in hemoglobin was observed between the 2 treatment groups at 12 and 24 months (mean 0.34 g/dL higher in the azithromycin arm, 95% CI −0.06 to 0.75 g/dL; P = 0.10). No serious adverse events were reported in either group, and among children aged 1 to 5 months, the most commonly reported nonserious adverse events (i.e., diarrhea, vomiting, and rash) were less common in the azithromycin-treated communities. Limitations of the trial include the timing of the treatments and monitoring visits, both of...

Background The Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial found that biannual mass distribution of azithromycin to children younger than 5 years in Niger reduced the primary outcome of all-cause mortality by 18%. We aimed to determine the causes of mortality among deceased children using verbal autopsy. MethodsIn this 2-year cluster-randomised controlled trial, 594 community clusters in Niger were randomly allocated (1:1 ratio) to receive biannual mass distributions of either oral azithromycin (approximately 20 mg per kg of bodyweight) or placebo targeted to children aged 1-59 months. Participants, study investigators, and field workers were masked to treatment allocation. Between Nov 23, 2014, and July 31, 2017, 3615 child deaths were recorded by use of biannual house-to-house censuses, and verbal autopsies were done between May 26, 2015, and May 17, 2018, to identify cause of death. Cause-specific mortality, as assessed by verbal autopsy, was a prespecified secondary outcome. This trial is completed and is registered with ClinicalTrials.gov, NCT02047981.

BackgroundMass azithromycin distribution reduces under-5 child mortality. Trachoma control programs currently treat infants aged 6 months and older. Here, we report findings from an infant adverse event survey in 1–5 month olds who received azithromycin as part of a large community-randomized trial in Niger.Methods and principal findingsActive surveillance of infants aged 1–5 months at the time of treatment was conducted in 30 randomly selected communities from within a large cluster randomized trial of biannual mass azithromycin distribution compared to placebo to assess the potential impact on child mortality. We compared the distribution of adverse events reported after treatment among azithromycin-treated versus placebo-treated infants. From January 2015 to February 2018, the caregivers of 1,712 infants were surveyed. Approximately one-third of caregivers reported at least one adverse event (azithromycin: 29.6%, placebo: 34.3%, risk ratio [RR] 0.86, 95% confidence interval [CI] 0.68 to 1.10, P = 0.23). The most commonly reported adverse events included diarrhea (azithromycin: 19.3%, placebo: 28.1%, RR 0.68, 95% CI 0.49 to 0.96, P = 0.03), vomiting (azithromycin: 15.9%, placebo: 21.0%, RR 0.76, 95% CI 0.56 to 1.02, P = 0.07), and skin rash (azithromycin: 12.3%, placebo: 13.6%, RR 0.90, 95% CI 0.59 to 1.37, P = 0.63). No cases of infantile hypertrophic pyloric stenosis were reported.ConclusionsAzithromycin given to infants aged 1–5 months appeared to be safe. Inclusion of younger infants in larger azithromycin-based child mortality or trachoma control programs could be considered if deemed effective.Trial registrationClinicalTrials.gov NCT02048007.