Ahmed M Arzika, Abdou Amza, Ramatou Maliki, Bawa Aichatou, Ismael Mamane Bello, Diallo Beidi, Nasser Galo, Nasser Harouna, Alio M Karamba, Sani Mahamadou, Moustapha Abarchi, Almou Ibrahim, Carolyn Brandt, Elodie Lebas, Brittany Peterson, Zijun Liu, Catherine E Oldenburg, Thuy Doan, Travis C Porco, Benjamin F Arnold, Thomas M Lietman, Kieran S O'Brien
{"title":"阿奇霉素大量用药的外溢与儿童生存：一项集群随机临床试验的二次分析。","authors":"Ahmed M Arzika, Abdou Amza, Ramatou Maliki, Bawa Aichatou, Ismael Mamane Bello, Diallo Beidi, Nasser Galo, Nasser Harouna, Alio M Karamba, Sani Mahamadou, Moustapha Abarchi, Almou Ibrahim, Carolyn Brandt, Elodie Lebas, Brittany Peterson, Zijun Liu, Catherine E Oldenburg, Thuy Doan, Travis C Porco, Benjamin F Arnold, Thomas M Lietman, Kieran S O'Brien","doi":"10.1001/jamanetworkopen.2025.19693","DOIUrl":null,"url":null,"abstract":"<p><strong>Importance: </strong>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><strong>Objective: </strong>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><strong>Design, setting, and participants: </strong>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><strong>Intervention: </strong>A single 20-mg/kg dose of oral azithromycin or placebo administered by study staff biannually.</p><p><strong>Main outcomes and measures: </strong>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><strong>Results: </strong>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><strong>Conclusions and relevance: </strong>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><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT04224987.</p>","PeriodicalId":14694,"journal":{"name":"JAMA Network Open","volume":"8 7","pages":"e2519693"},"PeriodicalIF":9.7000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246876/pdf/","citationCount":"0","resultStr":"{\"title\":\"Spillover of Azithromycin Mass Drug Administration and Child Survival: A Secondary Analysis of a Cluster-Randomized Clinical Trial.\",\"authors\":\"Ahmed M Arzika, Abdou Amza, Ramatou Maliki, Bawa Aichatou, Ismael Mamane Bello, Diallo Beidi, Nasser Galo, Nasser Harouna, Alio M Karamba, Sani Mahamadou, Moustapha Abarchi, Almou Ibrahim, Carolyn Brandt, Elodie Lebas, Brittany Peterson, Zijun Liu, Catherine E Oldenburg, Thuy Doan, Travis C Porco, Benjamin F Arnold, Thomas M Lietman, Kieran S O'Brien\",\"doi\":\"10.1001/jamanetworkopen.2025.19693\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Importance: </strong>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. 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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><strong>Intervention: </strong>A single 20-mg/kg dose of oral azithromycin or placebo administered by study staff biannually.</p><p><strong>Main outcomes and measures: </strong>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><strong>Results: </strong>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. 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Spillover of Azithromycin Mass Drug Administration and Child Survival: A Secondary Analysis of a Cluster-Randomized Clinical Trial.
Importance: 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.
Objective: 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.
Design, setting, and participants: 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.
Intervention: A single 20-mg/kg dose of oral azithromycin or placebo administered by study staff biannually.
Main outcomes and measures: 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.
Results: 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.
Conclusions and relevance: 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.
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