Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa.


Keenan, JD; Bailey, RL; West, SK; Arzika, AM; Hart, J; Weaver, J; Kalua, K; Mrango, Z; Ray, KJ; Cook, C; Lebas, E; O'Brien, KS; Emerson, PM; Porco, TC; Lietman, TM; MORDOR Study Group, ; , COLLABORATORS; Doan, T; Oldenburg, CE; Cotter, SY; Stoller, NE; Vanderschelden, B; Fry, DM; Rosenthal, PJ; Rutherford, GW; Zhou, Z; Zhong, L; Gaynor, BD; Whitcher, JP; Mabey, DCW; Burr, SE; Solomon, AW; Dreger, K; Munoz, B; Coles, CL; Labrique, AB; Sommer, A; Kaur, H; Bloch, EM; Chisambi, A; Kamwendo, Z; Maleta, K; Callahan, EK; Stewart, AE; Kane, S; Abdou, A; Kadri, B; Beido, N; Kasubi, M; Mboera, L; (2018) Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa. The New England journal of medicine, 378 (17). pp. 1583-1592. ISSN 0028-4793 DOI: https://doi.org/10.1056/NEJMoa1715474

This is the latest version of this item. Earlier version may have full text manuscript

[img] Text - Accepted Version
Restricted to Repository staff only until 26 October 2018.
License:

Download (326kB)

Abstract

We hypothesized that mass distribution of a broad-spectrum antibiotic agent to preschool children would reduce mortality in areas of sub-Saharan Africa that are currently far from meeting the Sustainable Development Goals of the United Nations. In this cluster-randomized trial, we assigned communities in Malawi, Niger, and Tanzania to four twice-yearly mass distributions of either oral azithromycin (approximately 20 mg per kilogram of body weight) or placebo. Children 1 to 59 months of age were identified in twice-yearly censuses and were offered participation in the trial. Vital status was determined at subsequent censuses. The primary outcome was aggregate all-cause mortality; country-specific rates were assessed in prespecified subgroup analyses. A total of 1533 communities underwent randomization, 190,238 children were identified in the census at baseline, and 323,302 person-years were monitored. The mean (±SD) azithromycin and placebo coverage over the four twice-yearly distributions was 90.4±10.4%. The overall annual mortality rate was 14.6 deaths per 1000 person-years in communities that received azithromycin (9.1 in Malawi, 22.5 in Niger, and 5.4 in Tanzania) and 16.5 deaths per 1000 person-years in communities that received placebo (9.6 in Malawi, 27.5 in Niger, and 5.5 in Tanzania). Mortality was 13.5% lower overall (95% confidence interval [CI], 6.7 to 19.8) in communities that received azithromycin than in communities that received placebo (P<0.001); the rate was 5.7% lower in Malawi (95% CI, -9.7 to 18.9), 18.1% lower in Niger (95% CI, 10.0 to 25.5), and 3.4% lower in Tanzania (95% CI, -21.2 to 23.0). Children in the age group of 1 to 5 months had the greatest effect from azithromycin (24.9% lower mortality than that with placebo; 95% CI, 10.6 to 37.0). Serious adverse events occurring within a week after administration of the trial drug or placebo were uncommon, and the rate did not differ significantly between the groups. Evaluation of selection for antibiotic resistance is ongoing. Among postneonatal, preschool children in sub-Saharan Africa, childhood mortality was lower in communities randomly assigned to mass distribution of azithromycin than in those assigned to placebo, with the largest effect seen in Niger. Any implementation of a policy of mass distribution would need to strongly consider the potential effect of such a strategy on antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation; MORDOR ClinicalTrials.gov number, NCT02047981 .).

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Research Centre: Malaria Centre
Related URLs:
PubMed ID: 29694816
URI: http://researchonline.lshtm.ac.uk/id/eprint/4647498

Available Versions of this Item

Statistics


Download activity - last 12 months
Downloads since deposit
0Downloads
21Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item