{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:12:14Z","timestamp":1791958334411,"version":"4.3.4"},"reference-count":64,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,7]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n                  <jats:p>\n                    Mass azithromycin distribution has been shown to reduce all-cause child mortality in several settings in the Sahel by 14\u201318%. A trial in Niger found that mass azithromycin distribution to children ages 1\u201359 months old reduced cause-specific mortality because of malaria, dysentery, meningitis, and pneumonia. However, this study was done in the absence of seasonal malaria chemoprevention (SMC). Here, we assess the effect of mass azithromycin distribution on cause-specific child mortality in a setting receiving SMC. The Child Health with Azithromycin Treatment trial was a cluster-randomized, placebo-controlled trial of 341 communities in Nouna District, Burkina Faso. Eligible children (ages 1\u201359 months old) received a single oral 20-mg\/kg dose of azithromycin or matching placebo. Six rounds of distribution occurred over a 36-month period. An enumerative census was conducted during each twice-yearly distribution, during which vital status for all children in the community was collected. Verbal autopsy was performed to assess cause of death. Of 1,086 deaths recorded in the trial, verbal autopsy results were available for 992 (91%). The most common causes of death were infectious, including malaria (34%), diarrhea (24%), and pneumonia (9%). Children living in communities receiving azithromycin had significant reduction in malaria mortality (incidence rate ratio, 0.67; 95% CI, 0.50\u20130.90;\n                    <jats:italic>P<\/jats:italic>\n                    = 0.008). Other infectious causes of mortality, including diarrhea and pneumonia, were lower in communities receiving azithromycin but were not statistically significantly different. Mass azithromycin distribution for child mortality has benefits in the context of SMC for reducing mortality, including for malaria mortality.\n                  <\/jats:p>","DOI":"10.4269\/ajtmh.25-0482","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T15:33:37Z","timestamp":1763480017000},"page":"85-91","source":"Crossref","is-referenced-by-count":3,"title":["Mass Azithromycin Distribution and Cause-Specific Mortality among Children Ages 1\u201359 Months Old: A Secondary Analysis of a Cluster-Randomized Controlled Trial"],"prefix":"10.4269","volume":"114","author":[{"given":"Ali","family":"Si\u00e9","sequence":"first","affiliation":[{"name":"Centre de Recherche en Sant\u00e9 de Nouna, Nouna, Burkina Faso;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamadou","family":"Ouattara","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Sant\u00e9 de Nouna, Nouna, Burkina Faso;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamadou","family":"Bountogo","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Sant\u00e9 de Nouna, Nouna, Burkina Faso;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boubacar","family":"Coulibaly","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Sant\u00e9 de Nouna, Nouna, Burkina Faso;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Boudo","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Sant\u00e9 de Nouna, Nouna, Burkina Faso;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Ouedraogo","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Sant\u00e9 de Nouna, Nouna, Burkina Faso;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Gebreegziabher","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"},{"name":"Department of Epidemiology & Biostatistics, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyu","family":"Hu","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Lebas","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin F.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"},{"name":"Department of Ophthalmology, University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Lietman","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"},{"name":"Department of Epidemiology & Biostatistics, University of California, San Francisco, California;"},{"name":"Department of Ophthalmology, University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine E.","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"Francis I. Proctor Foundation, University of California, San Francisco, California;"},{"name":"Department of Epidemiology & Biostatistics, University of California, San Francisco, California;"},{"name":"Department of Ophthalmology, University of California, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"N Engl J Med","first-page":"1583","article-title":"Azithromycin to reduce childhood mortality in sub-Saharan Africa","volume":"378","author":"Keenan","year":"2018"},{"key":"b2","series-title":"JAMA","first-page":"482","article-title":"Mass azithromycin distribution to prevent child mortality in Burkina Faso: The CHAT randomized clinical trial","volume":"331","author":"Oldenburg","year":"2024"},{"key":"b3","series-title":"Lancet Global Health","first-page":"288","article-title":"Cause-specific mortality of children younger than 5 years in communities receiving biannual mass azithromycin treatment in Niger: Verbal autopsy results from a cluster-randomised controlled trial","volume":"8","author":"Keenan","year":"2020"},{"key":"b4","series-title":"Nat Commun","first-page":"881","article-title":"Estimating the potential public health impact of seasonal malaria chemoprevention in African children","volume":"3","author":"Cairns","year":"2012"},{"key":"b5","series-title":"Malar J","first-page":"103","article-title":"Impact of seasonal malaria chemoprevention on hospital admissions and mortality in children under 5 years of age in Ouelessebougou, Mali","volume":"19","author":"Issiaka","year":"2020"},{"key":"b6","series-title":"Am J Trop Med Hyg","first-page":"20","article-title":"Systematic review and meta-analysis of seasonal malaria chemoprevention","volume":"110","author":"Thwing","year":"2024"},{"key":"b7","series-title":"Antimicrob Agents Chemother","first-page":"3485","article-title":"Multiple antibiotics exert delayed effects against the Plasmodium falciparum apicoplast","volume":"51","author":"Dahl","year":"2007"},{"key":"b8","series-title":"J Biol Chem","first-page":"2494","article-title":"In vitro efficacy, resistance selection, and structural modeling studies implicate the malarial parasite apicoplast as the target of azithromycin","volume":"282","author":"Sidhu","year":"2007"},{"key":"b9","series-title":"PLoS Med","first-page":"e1002835","article-title":"Biannual mass azithromycin distributions and malaria parasitemia in pre-school children in Niger: A cluster-randomized, placebo-controlled trial","volume":"16","author":"Arzika","year":"2019"},{"key":"b10","series-title":"Malar J","first-page":"389","article-title":"Biannual versus annual mass azithromycin distribution and malaria seroepidemiology among preschool children in Niger: A sub-study of a cluster randomized trial","volume":"18","author":"Oldenburg","year":"2019"},{"key":"b11","series-title":"Malar J","first-page":"360","article-title":"Effect of a single dose of oral azithromycin on malaria parasitaemia in children: A randomized controlled trial","volume":"20","author":"Coulibaly","year":"2021"},{"key":"b12","series-title":"BMC Infect Dis","first-page":"285","article-title":"Malaria positivity following a single oral dose of azithromycin among children in Burkina Faso: A randomized controlled trial","volume":"22","author":"Brogdon","year":"2022"},{"key":"b13","series-title":"Trials","first-page":"675","article-title":"A double-masked placebo-controlled trial of azithromycin to prevent child mortality in Burkina Faso, West Africa: Community Health with Azithromycin Trial (CHAT) study protocol","volume":"20","author":"Si\u00e9","year":"2019"},{"key":"b14","series-title":"Glob Health Action","first-page":"5284","article-title":"The Health and Demographic Surveillance System (HDSS) in Nouna, Burkina Faso, 1993\u20132007","volume":"3","author":"Si\u00e9","year":"2010"},{"key":"b15","series-title":"J Am Stat Assoc","first-page":"1036","article-title":"Probabilistic cause-of-death assignment using verbal autopsies","volume":"111","author":"McCormick","year":"2016"},{"key":"b16","series-title":"N Engl J Med","first-page":"2197","article-title":"Effect of Adding azithromycin to seasonal malaria chemoprevention","volume":"380","author":"Chandramohan","year":"2019"},{"key":"b17","series-title":"Malar J","first-page":"303","article-title":"Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: Comparative in\u00a0vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin","volume":"9","author":"Capan","year":"2010"},{"key":"b18","series-title":"Am J Trop Med Hyg","first-page":"696","article-title":"Mass azithromycin and malaria parasitemia in Niger: Results from a community-randomized trial","volume":"97","author":"O\u2019Brien","year":"2017"},{"key":"b19","series-title":"Malar J","first-page":"284","article-title":"The impact on malaria of biannual treatment with azithromycin in children age less than 5 years: A prospective study","volume":"18","author":"Bloch","year":"2019"},{"key":"b20","series-title":"Am J Trop Med Hyg","first-page":"1329","article-title":"Effects of biannual azithromycin mass drug administration on malaria in Malawian children: A cluster-randomized trial","volume":"103","author":"Hart","year":"2020"},{"key":"b21","series-title":"Emerg Infect Dis","first-page":"941","article-title":"Short-term malaria reduction by single-dose azithromycin during mass drug administration for trachoma, Tanzania","volume":"20","author":"Schachterle","year":"2014"},{"key":"b22","series-title":"Pediatr Infect Dis J","first-page":"506","article-title":"Annual versus biannual mass azithromycin distribution and malaria parasitemia during the peak transmission season among children in Niger","volume":"37","author":"Oldenburg","year":"2018"},{"key":"b23","series-title":"Am J Trop Med Hyg","first-page":"846","article-title":"Impact of mass azithromycin distribution on malaria parasitemia during the low-transmission season in Niger: A cluster-randomized trial","volume":"90","author":"Gaynor","year":"2014"},{"key":"b24","series-title":"J Infect","first-page":"106107","article-title":"Burden of child mortality from malaria in high endemic areas: Results from the CHAMPS network using minimally invasive tissue sampling","volume":"88","author":"Ogbuanu","year":"2024"},{"key":"b25","series-title":"Int J Epidemiol","first-page":"509","article-title":"Effect of misclassification of causes of death in verbal autopsy: Can it be adjusted?","volume":"30","author":"Chandramohan","year":"2001"},{"key":"b26","series-title":"BMC Health Serv Res","first-page":"212","article-title":"Distance to primary care facilities and healthcare utilization for preschool children in rural northwestern Burkina Faso: Results from a surveillance cohort","volume":"21","author":"Oldenburg","year":"2021"},{"key":"b27","series-title":"Clin Infect Dis","first-page":"1288","article-title":"Indication for antibiotic prescription among children attending primary healthcare services in rural Burkina Faso","volume":"73","author":"Si\u00e9","year":"2021"},{"key":"b28","series-title":"Lancet","first-page":"3027","article-title":"Global, regional, and national causes of under-5 mortality in 2000\u201315: An updated systematic analysis with implications for the Sustainable Development Goals","volume":"388","author":"Liu","year":"2016"},{"key":"b29","series-title":"Malar J","first-page":"421","article-title":"A systematic review and synthesis of the strengths and limitations of measuring malaria mortality through verbal autopsy","volume":"16","author":"Herrera","year":"2017"},{"key":"b30","series-title":"BMJ Glob Health","first-page":"e005218","article-title":"Accuracy of verbal autopsy, clinical data and minimally invasive autopsy in the evaluation of malaria-specific mortality: An observational study","volume":"6","author":"Rakislova","year":"2021"},{"key":"b31","series-title":"Am J Trop Med Hyg","first-page":"1295","article-title":"Effect modification by baseline mortality in the MORDOR azithromycin trial","volume":"103","author":"Oron","year":"2020"},{"key":"b32","series-title":"Am J Trop Med Hyg","first-page":"1291","article-title":"Efficacy of mass azithromycin distribution for reducing childhood mortality across geographic regions","volume":"103","author":"Porco","year":"2020"},{"key":"b1","series-title":"N Engl J Med","first-page":"1583","article-title":"Azithromycin to reduce childhood mortality in sub-Saharan Africa","volume":"378","author":"Keenan","year":"2018"},{"key":"b2","series-title":"JAMA","first-page":"482","article-title":"Mass azithromycin distribution to prevent child mortality in Burkina Faso: The CHAT randomized clinical trial","volume":"331","author":"Oldenburg","year":"2024"},{"key":"b3","series-title":"Lancet Global Health","first-page":"288","article-title":"Cause-specific mortality of children younger than 5 years in communities receiving biannual mass azithromycin treatment in Niger: Verbal autopsy results from a cluster-randomised controlled trial","volume":"8","author":"Keenan","year":"2020"},{"key":"b4","series-title":"Nat Commun","first-page":"881","article-title":"Estimating the potential public health impact of seasonal malaria chemoprevention in African children","volume":"3","author":"Cairns","year":"2012"},{"key":"b5","series-title":"Malar J","first-page":"103","article-title":"Impact of seasonal malaria chemoprevention on hospital admissions and mortality in children under 5 years of age in Ouelessebougou, Mali","volume":"19","author":"Issiaka","year":"2020"},{"key":"b6","series-title":"Am J Trop Med Hyg","first-page":"20","article-title":"Systematic review and meta-analysis of seasonal malaria chemoprevention","volume":"110","author":"Thwing","year":"2024"},{"key":"b7","series-title":"Antimicrob Agents Chemother","first-page":"3485","article-title":"Multiple antibiotics exert delayed effects against the Plasmodium falciparum apicoplast","volume":"51","author":"Dahl","year":"2007"},{"key":"b8","series-title":"J Biol Chem","first-page":"2494","article-title":"In vitro efficacy, resistance selection, and structural modeling studies implicate the malarial parasite apicoplast as the target of azithromycin","volume":"282","author":"Sidhu","year":"2007"},{"key":"b9","series-title":"PLoS Med","first-page":"e1002835","article-title":"Biannual mass azithromycin distributions and malaria parasitemia in pre-school children in Niger: A cluster-randomized, placebo-controlled trial","volume":"16","author":"Arzika","year":"2019"},{"key":"b10","series-title":"Malar J","first-page":"389","article-title":"Biannual versus annual mass azithromycin distribution and malaria seroepidemiology among preschool children in Niger: A sub-study of a cluster randomized trial","volume":"18","author":"Oldenburg","year":"2019"},{"key":"b11","series-title":"Malar J","first-page":"360","article-title":"Effect of a single dose of oral azithromycin on malaria parasitaemia in children: A randomized controlled trial","volume":"20","author":"Coulibaly","year":"2021"},{"key":"b12","series-title":"BMC Infect Dis","first-page":"285","article-title":"Malaria positivity following a single oral dose of azithromycin among children in Burkina Faso: A randomized controlled trial","volume":"22","author":"Brogdon","year":"2022"},{"key":"b13","series-title":"Trials","first-page":"675","article-title":"A double-masked placebo-controlled trial of azithromycin to prevent child mortality in Burkina Faso, West Africa: Community Health with Azithromycin Trial (CHAT) study protocol","volume":"20","author":"Si\u00e9","year":"2019"},{"key":"b14","series-title":"Glob Health Action","first-page":"5284","article-title":"The Health and Demographic Surveillance System (HDSS) in Nouna, Burkina Faso, 1993\u20132007","volume":"3","author":"Si\u00e9","year":"2010"},{"key":"b15","series-title":"J Am Stat Assoc","first-page":"1036","article-title":"Probabilistic cause-of-death assignment using verbal autopsies","volume":"111","author":"McCormick","year":"2016"},{"key":"b16","series-title":"N Engl J Med","first-page":"2197","article-title":"Effect of Adding azithromycin to seasonal malaria chemoprevention","volume":"380","author":"Chandramohan","year":"2019"},{"key":"b17","series-title":"Malar J","first-page":"303","article-title":"Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: Comparative in\u00a0vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin","volume":"9","author":"Capan","year":"2010"},{"key":"b18","series-title":"Am J Trop Med Hyg","first-page":"696","article-title":"Mass azithromycin and malaria parasitemia in Niger: Results from a community-randomized trial","volume":"97","author":"O\u2019Brien","year":"2017"},{"key":"b19","series-title":"Malar J","first-page":"284","article-title":"The impact on malaria of biannual treatment with azithromycin in children age less than 5 years: A prospective study","volume":"18","author":"Bloch","year":"2019"},{"key":"b20","series-title":"Am J Trop Med Hyg","first-page":"1329","article-title":"Effects of biannual azithromycin mass drug administration on malaria in Malawian children: A cluster-randomized trial","volume":"103","author":"Hart","year":"2020"},{"key":"b21","series-title":"Emerg Infect Dis","first-page":"941","article-title":"Short-term malaria reduction by single-dose azithromycin during mass drug administration for trachoma, Tanzania","volume":"20","author":"Schachterle","year":"2014"},{"key":"b22","series-title":"Pediatr Infect Dis J","first-page":"506","article-title":"Annual versus biannual mass azithromycin distribution and malaria parasitemia during the peak transmission season among children in Niger","volume":"37","author":"Oldenburg","year":"2018"},{"key":"b23","series-title":"Am J Trop Med Hyg","first-page":"846","article-title":"Impact of mass azithromycin distribution on malaria parasitemia during the low-transmission season in Niger: A cluster-randomized trial","volume":"90","author":"Gaynor","year":"2014"},{"key":"b24","series-title":"J Infect","first-page":"106107","article-title":"Burden of child mortality from malaria in high endemic areas: Results from the CHAMPS network using minimally invasive tissue sampling","volume":"88","author":"Ogbuanu","year":"2024"},{"key":"b25","series-title":"Int J Epidemiol","first-page":"509","article-title":"Effect of misclassification of causes of death in verbal autopsy: Can it be adjusted?","volume":"30","author":"Chandramohan","year":"2001"},{"key":"b26","series-title":"BMC Health Serv Res","first-page":"212","article-title":"Distance to primary care facilities and healthcare utilization for preschool children in rural northwestern Burkina Faso: Results from a surveillance cohort","volume":"21","author":"Oldenburg","year":"2021"},{"key":"b27","series-title":"Clin Infect Dis","first-page":"1288","article-title":"Indication for antibiotic prescription among children attending primary healthcare services in rural Burkina Faso","volume":"73","author":"Si\u00e9","year":"2021"},{"key":"b28","series-title":"Lancet","first-page":"3027","article-title":"Global, regional, and national causes of under-5 mortality in 2000\u201315: An updated systematic analysis with implications for the Sustainable Development Goals","volume":"388","author":"Liu","year":"2016"},{"key":"b29","series-title":"Malar J","first-page":"421","article-title":"A systematic review and synthesis of the strengths and limitations of measuring malaria mortality through verbal autopsy","volume":"16","author":"Herrera","year":"2017"},{"key":"b30","series-title":"BMJ Glob Health","first-page":"e005218","article-title":"Accuracy of verbal autopsy, clinical data and minimally invasive autopsy in the evaluation of malaria-specific mortality: An observational study","volume":"6","author":"Rakislova","year":"2021"},{"key":"b31","series-title":"Am J Trop Med Hyg","first-page":"1295","article-title":"Effect modification by baseline mortality in the MORDOR azithromycin trial","volume":"103","author":"Oron","year":"2020"},{"key":"b32","series-title":"Am J Trop Med Hyg","first-page":"1291","article-title":"Efficacy of mass azithromycin distribution for reducing childhood mortality across geographic regions","volume":"103","author":"Porco","year":"2020"}],"container-title":["The American Journal of Tropical Medicine and 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