@article{656,
  author = {Ahmed Arzika and Abdou Amza and Ramatou Maliki and Bawa Aichatou and Ismael Bello and Diallo Beidi and Nasser Galo and Nasser Harouna and Alio Karamba and Sani Mahamadou and Moustapha Abarchi and Almou Ibrahim and Carolyn Brandt and Elodie Lebas and Brittany Peterson and Zijun Liu and Catherine Oldenburg and Thuy Doan and Travis Porco and Benjamin Arnold and Thomas Lietman and Kieran O'Brien},
  title = {Spillover of Azithromycin Mass Drug Administration and Child Survival: A Secondary Analysis of a Cluster-Randomized Clinical Trial.},
  abstract = {<p><b>IMPORTANCE: </b>World Health Organization guidelines on azithromycin mass drug administration for child survival target infants aged 1 to 11 months, although prior studies included those aged 1 to 59 months. The AVENIR trial suggested that infants aged 1 to 11 months have lower mortality if children aged 12 to 59 months in the same household are also included.</p><p><b>OBJECTIVE: </b>To assess the possibility of a spillover effect by examining the association of azithromycin and mortality among children aged 1 to 11 months in subgroups defined by the presence of a child aged 12 to 59 months in the same household.</p><p><b>DESIGN, SETTING, AND PARTICIPANTS: </b>This exploratory secondary analysis of the AVENIR (Azithromycine Pour la Vie des Enfants au Niger: Implementation et Recherche) adaptive cluster-randomized clinical trial was performed in 3000 rural and periurban communities in Niger. AVENIR communities were randomized to 3 arms and followed up for 2 years (November 24, 2020, to July 31, 2023). Study arms consisted of children aged 1 to 59 months receiving azithromycin (child arm); infants aged 1 to 11 months receiving azithromycin with placebo to children aged 12 to 59 months (infant arm); and children aged 1 to 59 months receiving placebo (placebo arm). Participants, investigators, data collectors, and data analysts were masked to randomization.</p><p><b>INTERVENTION: </b>A single 20-mg/kg dose of oral azithromycin or placebo administered by study staff biannually.</p><p><b>MAIN OUTCOMES AND MEASURES: </b>All-cause mortality in infants aged 1 to 11 months (deaths per 1000 person-years) measured through biannual census. Subgroups were defined by the presence of a child aged 12 to 59 months in the household recorded during the census.</p><p><b>RESULTS: </b>After exclusions, 2883 communities and 98 969 infants aged 1 to 11 months were included in the analysis. Among the 23 770 infants in allocation 1 at baseline, mean (SD) age was 6.2 (3.1) months and 11 974 (50.4%) were female. Mortality was 18.5 (95% CI, 16.7-20.4) deaths per 1000 person-years in the child arm, 22.3 (95% CI, 20.0-24.7) in the infant arm, and 23.9 (95% CI, 21.6-26.2) in the placebo arm. The incidence rate ratio comparing mortality in the child and infant arms among children with an older sibling was 0.78 (95% CI, 0.65-0.93) compared with 0.91 (95% CI, 0.73-1.15; P = .26 for interaction) among those without. Comparing the infant and placebo arms, the incidence rate ratio among children with an older sibling was 0.96 (95% CI, 0.81-1.14) compared with 0.90 (95% CI, 0.71-1.12; P = .61 for interaction) among those without.</p><p><b>CONCLUSIONS AND RELEVANCE: </b>In this secondary analysis of a cluster-randomized clinical trial, interaction for the presence of a older sibling was not statistically significant, but results were consistent with lower mortality among infants aged 1 to 11 months living with older, treated children.</p><p><b>TRIAL REGISTRATION: </b>ClinicalTrials.gov Identifier: NCT04224987.</p>},
  year = {2025},
  journal = {JAMA network open},
  volume = {8},
  pages = {e2519693},
  month = {07/2025},
  issn = {2574-3805},
  doi = {10.1001/jamanetworkopen.2025.19693},
  language = {eng},
}