Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2025 Apr 8;112(6):1355-1363.
doi: 10.4269/ajtmh.24-0723. Print 2025 Jun 4.

Costs, Coverage, and Acceptability of Azithromycin Mass Administration to Children 1-11 Versus 1-59 Months Old to Reduce Mortality: A Cluster-Randomized Trial in Niger

Ahmed M Arzika  1 , Ramatou Maliki  1 , Abdou Amza  2 , Alio Karamba  1 , Nasser Gallo  1 , Bawa Aichatou  1 , Ismael I Sara  1 , Diallo Beidi  1 , Laminou M Haroun  1 , Farissatou Oumarou  1 , Carolyn Brandt  3 , Brittany Peterson  3 , Elodie Lebas  3 , Emily Colby  3 , William Nguyen  3 , Zijun Liu  3 , Benjamin F Arnold  3   4   5 , Thomas M Lietman  3   4   5   6 , Meagan C Fitzpatrick  7 , Kieran S O'Brien  3   4   5   6
Affiliations
Randomized Controlled Trial

Costs, Coverage, and Acceptability of Azithromycin Mass Administration to Children 1-11 Versus 1-59 Months Old to Reduce Mortality: A Cluster-Randomized Trial in Niger

Ahmed M Arzika et al. Am J Trop Med Hyg. .

Abstract

Azithromycin mass drug administration (MDA) for 1- to 59-month-olds reduces child mortality. However, guidelines restrict eligibility to 1- to 11-month-olds because of concerns about antimicrobial resistance. This cluster-randomized implementation trial was conducted in parallel with a larger efficacy trial and compared implementation outcomes between these approaches. Rural communities in Niger were randomly assigned to receive biannual azithromycin MDA for either 1- to 59-month-olds or 1- to 11-month-olds over 1 year. The primary outcome was the community-level cost per dose delivered. Secondary outcomes included reach (coverage), as well as acceptability, appropriateness, and feasibility according to participants and providers. In November 2020, 40 eligible communities were randomly assigned to each arm, with 37 communities in the 1- to 59-month arm and 39 communities in the 1- to 11-month arm contributing to analyses. The mean cost per dose delivered was $6.50 lower (95% CI -$10.40 to -$3.70; P-value <0.001) in the 1- to 59-month arm ($1.60; 95% CI $1.00 to $2.30) compared with the 1- to 11-month arm ($8.20; 95% CI $7.60 to $8.80). Treatment coverage was similar by arm and exceeded 90% in both distributions. More caregivers in the 1- to 59-month arm found the intervention acceptable (mean difference 4.2%; 95% CI 0 to 8.4%; P-value 0.04) and appropriate (3.4%; 95% CI 0.1 to 6.8%; P-value 0.04) compared with the 1- to 11-month arm. When combining arms, all groups indicated that including 1- to 59-month-olds was more acceptable, appropriate, and feasible than restricting to 1- to 11-month-olds. No serious adverse events were reported. Overall, including 1- to 59-month-olds resulted in a lower cost per dose delivered than restricting to 1- to 11-month-olds. Community groups perceived both interventions to be acceptable, appropriate, and feasible, but they strongly preferred the 1- to 59-month treatment.

PubMed Disclaimer

Conflict of interest statement

Disclosures: Ethical approval was obtained from the Institutional Review Boards (IRB) at the Niger Ministry of Health (Comité Nationale Éthique pour la Recherche en Santé, N 041/2020/CNERS) and the University of California, San Francisco (19-28387). At the community level, verbal consent was obtained from community and health center leaders before the study started. At the individual level, informed consent was obtained from caregivers before study procedures were conducted. Written informed consent was obtained from caregivers for children aged 30–42 days, and verbal consent was obtained for children older than 42 days. The University of California, San Francisco IRB required written consent for the youngest age group because of concerns about the potential for macrolide-associated infantile hypertrophic pyloric stenosis. Age was verified using the child’s health card when available or via caregiver reports guided by a calendar of events. Consent conversations were conducted in local languages, including Zarma, Hausa, and Peul, by fluent study team members. A Data and Safety Monitoring Committee provided independent oversight and reviewed the study protocol, procedures, and participant safety in the concurrent effectiveness and implementation trials. The trial was conducted in accordance with the Declaration of Helsinki and was registered at clinicaltrials.gov (NCT04224987).

Authors’ contributions: A. M. Arzika, R. Maliki, E. Lebas, W. Nguyen, B. F. Arnold, T. M. Lietman, M. C. Fitzpatrick, and K. S. O’Brien contributed to the study conception and design. A. M. Arzika, R. Maliki, A. Amza, E. Lebas, B. Peterson, E. Colby, W. Nguyen, M. C. Fitzpatrick, and K. S. O’Brien provided oversight for study implementation. R. Maliki, K. Alio, N. Gallo, B. Aichatou, I. S. Sara, D. Beidi, L. M. Haroun, F. Oumarou, B. Peterson, C. Brandt, E. Colby, W. Nguyen, and Z. Liu contributed to study implementation. Z. Liu and B. F. Arnold contributed to randomization. B. Peterson and C. Brandt led data analysis. K. S. O’Brien wrote the first draft of the manuscript, and all authors contributed to its review and revision. B. Peterson, C. Brandt, and K. S. O’Brien have directly accessed and verified the data underlying the manuscript. All authors had full access to all study data and accept responsibility to submit this manuscript for publication.

Figures

Figure 1.
Figure 1.
Trial profile. Consolidated Standards of Reporting Trials participant flow diagram.
Figure 2.
Figure 2.
Overall perceptions of acceptability, appropriateness, and feasibility of 1- to 59-month versus 1- to 11-month treatment among community health workers, Centres de Santé Integrés leaders, and caregivers. Note that this figure does not display a by-arm comparison; rather, this figure shows the stated preference for 1- to 59-month or 1- to 11-month treatment by community group in both arms combined. Supplemental Table 9 provides additional details.
See this image and copyright information in PMC

References

    1. Keenan JD. et al. ; MORDOR Study Group, 2018. Azithromycin to reduce childhood mortality in sub-Saharan Africa. N Engl J Med 378: 1583–1592. - PMC - PubMed
    1. Keenan JD. et al. , 2019. Longer-term assessment of azithromycin for reducing childhood mortality in Africa. N Engl J Med 380: 2207–2214. - PMC - PubMed
    1. O’Brien KS. et al. ; AVENIR Study Group, 2024. Azithromycin to reduce mortality—An adaptive cluster-randomized trial. N Engl J Med 391: 699–709. - PubMed
    1. Doan T. et al. , 2019. Gut microbiome alteration in MORDOR I: A community-randomized trial of mass azithromycin distribution. Nat Med 25: 1370–1376. - PubMed
    1. Keenan JD. et al. ; MORDOR-Niger Study Group, 2020. 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. Lancet Glob Health 8: e288–e295. - PMC - PubMed

Publication types

LinkOut - more resources