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Key Points: Question: Does twice-annual mass azithromycin distribution prevent all-cause childhood mortality among children in Burkina Faso aged 1 to 59 months in the setting of seasonal malaria chemoprevention distribution? Findings: In this randomized trial of twice-yearly mass azithromycin distribution, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years) in the azithromycin group compared with 588 deaths over 58 547 person-years (10.0 deaths/1000 person-years) in the placebo group. The difference was not statistically significant. Meaning: Communities with mass azithromycin distribution had lower child mortality than controls, although the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference. Importance: Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions. Objective: To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention. Design, Setting, and Participants: This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities. Interventions: Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023. Main Outcomes and Measures: The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census. Results: A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P =.07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months. Conclusions and Relevance: Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03676764 This cluster randomized placebo-controlled trial examines the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality in rural Burkina Faso. [ABSTRACT FROM AUTHOR]

Background: Antibiotic use during early infancy has been linked to childhood obesity in high-income countries. We evaluated whether a single oral dose of azithromycin administered during infant-well visits led to changes in infant growth outcomes at 6 months of age in a setting with a high prevalence of undernutrition in rural Burkina Faso. Methods and findings: Infants were enrolled from September 25, 2019, until October 22, 2022, in a randomized controlled trial designed to evaluate the efficacy of a single oral dose of azithromycin (20 mg/kg) compared to placebo when administered during well-child visits for prevention of infant mortality. The trial found no evidence of a difference in the primary endpoint. This paper presents prespecified secondary anthropometric endpoints including weight gain (g/day), height change (mm/day), weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z-score (LAZ), and mid-upper arm circumference (MUAC). Infants were eligible for the trial if they were between 5 and 12 weeks of age, able to orally feed, and their families were planning to remain in the study area for the duration of the study. Anthropometric measurements were collected at enrollment (5 to 12 weeks of age) and 6 months of age. Among 32,877 infants enrolled in the trial, 27,298 (83%) were followed and had valid anthropometric measurements at 6 months of age. We found no evidence of a difference in weight gain (mean difference 0.03 g/day, 95% confidence interval (CI) −0.12 to 0.18), height change (mean difference 0.004 mm/day, 95% CI −0.05 to 0.06), WAZ (mean difference −0.004 SD, 95% CI −0.03 to 0.02), WLZ (mean difference 0.001 SD, 95% CI −0.03 to 0.03), LAZ (mean difference −0.005 SD, 95% CI −0.03 to 0.02), or MUAC (mean difference 0.01 cm, 95% CI −0.01 to 0.04). The primary limitation of the trial was that measurements were only collected at enrollment and 6 months of age, precluding assessment of shorter-term or long-term changes in growth. Conclusions: Single-dose azithromycin does not appear to affect weight and height outcomes when administered during early infancy. Trial registration: ClinicalTrials.govNCT03676764 Ali Sié and colleagues present pre-specified anthropometric outcomes from a randomized controlled trial that assessed the impact of a single-dose of oral azithromycin on infant mortality in Burkina Faso. Author summary: Why was this study done?: Antibiotics have been linked to obesity in children in nonrandomized studies in high-income settings. In low-income settings, malnutrition is a strong risk factor for child mortality, and interventions that increase weight gain may be beneficial. Single-dose azithromycin has previously been shown to reduce child mortality in sub-Saharan Africa, and it is possible that some of this effect is via weight gain. Why did the researchers do and find?: We conducted a randomized controlled trial in which infants aged 5 to 12 weeks were randomly assigned to a single dose of azithromycin or a matching placebo. The primary outcome of the parent trial was all-cause mortality, and the trial found no evidence of a benefit of azithromycin for prevention of mortality. Infants were followed until 6 months of age and had anthropometric measurements, including height, weight, and mid-upper arm circumference, collected. We found no evidence of a difference in any anthropometric endpoint in infants randomized to azithromycin compared to placebo. What do these findings mean?: Single-dose azithromycin does not appear to affect growth when administered to healthy infants who are 5 to 12 weeks of age. Growth outcomes were only measured at 6 months of age, and thus, any shorter or longer-term effects of azithromycin would not be detected by this study. This study only considered a single dose of azithromycin, as is used for prevention of child mortality and trachoma, and thus, it is possible that higher doses or longer duration of antibiotics could have a different effects on child growth. [ABSTRACT FROM AUTHOR]

Background: Azithromycin is a broad-spectrum antibiotic that has moderate antimalarial activity and has been shown to reduce all-cause mortality when biannually administered to children under five in high mortality settings in sub-Saharan Africa. One potential mechanism for this observed reduction in mortality is via a reduction in malaria transmission.Methods: We evaluated whether a single oral dose of azithromycin reduces malaria positivity by rapid diagnostic test (RDT). We conducted an individually randomized placebo-controlled trial in Burkina Faso during the high malaria transmission season in August 2020. Children aged 8 days to 59 months old were randomized to a single oral dose of azithromycin (20 mg/kg) or matching placebo. At baseline and 14 days following treatment, we administered a rapid diagnostic test (RDT) to detect Plasmodium falciparum and measured tympanic temperature for all children. Caregiver-reported adverse events and clinic visits were recorded at the day 14 visit.Results: We enrolled 449 children with 221 randomized to azithromycin and 228 to placebo. The median age was 32 months and 48% were female. A total of 8% of children had a positive RDT for malaria at baseline and 11% had a fever (tympanic temperature ≥ 37.5 °C). In the azithromycin arm, 8% of children had a positive RDT for malaria at 14 days compared to 7% in the placebo arm (P = 0.65). Fifteen percent of children in the azithromycin arm had a fever ≥ 37.5 °C compared to 21% in the placebo arm (P = 0.12). Caregivers of children in the azithromycin group had lower odds of reporting fever as an adverse event compared to children in the placebo group (OR 0.41, 95% CI 0.18-0.96, P = 0.04). Caregiver-reported clinic visits were uncommon, and there were no observed differences between arms (P = 0.32).Conclusions: We did not find evidence that a single oral dose of azithromycin reduced malaria positivity during the high transmission season. Caregiver-reported fever occurred less often in children receiving azithromycin compared to placebo, indicating that azithromycin may have some effect on non-malarial infections. Trial registration Clinicaltrials.gov NCT04315272, registered 19/03/2020. [ABSTRACT FROM AUTHOR]