The Duration of Protection from Azithromycin Against Malaria, Acute Respiratory, Gastrointestinal, and Skin Infections When Given Alongside Seasonal Malaria Chemoprevention: Secondary Analyses of Data from a Clinical Trial in Houndé, Burkina Faso, and Bougouni, Mali.
Azithromycin
Sahel
child mortality
duration of protection
seasonal malaria chemoprevention
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
05 10 2021
05 10 2021
Historique:
received:
29
09
2020
pubmed:
9
1
2021
medline:
21
10
2021
entrez:
8
1
2021
Statut:
ppublish
Résumé
Mass drug administration (MDA) with azithromycin (AZ) is being considered as a strategy to promote child survival in sub-Saharan Africa, but the mechanism by which AZ reduces mortality is unclear. To better understand the nature and extent of protection provided by AZ, we explored the profile of protection by time since administration, using data from a household-randomized, placebo-controlled trial in Burkina Faso and Mali. Between 2014 and 2016, 30 977 children aged 3-59 months received seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine and either AZ or placebo monthly, on 4 occasions each year. Poisson regression with gamma-distributed random effects, accounting for the household randomization and within-individual clustering of illness episodes, was used to compare incidence of prespecified outcomes between SMC+AZ versus SMC+placebo groups in fixed time strata post-treatment. The likelihood ratio test was used to assess evidence for a time-treatment group interaction. Relative to SMC+placebo, there was no evidence of protection from SMC+AZ against hospital admissions and deaths. Additional protection from SMC+AZ against malaria was confined to the first 2 weeks post-administration (protective efficacy (PE): 24.2% [95% CI: 17.8%, 30.1%]). Gastroenteritis and pneumonia were reduced by 29.9% [21.7; 37.3%], and 34.3% [14.9; 49.3%], respectively, in the first 2 weeks postadministration. Protection against nonmalaria fevers with a skin condition persisted up to 28 days: PE: 46.3% [35.1; 55.6%]. The benefits of AZ-MDA are broad-ranging but short-lived. To maximize impact, timing of AZ-MDA must address the challenge of targeting asynchronous morbidity and mortality peaks from different causes.
Sections du résumé
BACKGROUND
Mass drug administration (MDA) with azithromycin (AZ) is being considered as a strategy to promote child survival in sub-Saharan Africa, but the mechanism by which AZ reduces mortality is unclear. To better understand the nature and extent of protection provided by AZ, we explored the profile of protection by time since administration, using data from a household-randomized, placebo-controlled trial in Burkina Faso and Mali.
METHODS
Between 2014 and 2016, 30 977 children aged 3-59 months received seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine and either AZ or placebo monthly, on 4 occasions each year. Poisson regression with gamma-distributed random effects, accounting for the household randomization and within-individual clustering of illness episodes, was used to compare incidence of prespecified outcomes between SMC+AZ versus SMC+placebo groups in fixed time strata post-treatment. The likelihood ratio test was used to assess evidence for a time-treatment group interaction.
RESULTS
Relative to SMC+placebo, there was no evidence of protection from SMC+AZ against hospital admissions and deaths. Additional protection from SMC+AZ against malaria was confined to the first 2 weeks post-administration (protective efficacy (PE): 24.2% [95% CI: 17.8%, 30.1%]). Gastroenteritis and pneumonia were reduced by 29.9% [21.7; 37.3%], and 34.3% [14.9; 49.3%], respectively, in the first 2 weeks postadministration. Protection against nonmalaria fevers with a skin condition persisted up to 28 days: PE: 46.3% [35.1; 55.6%].
CONCLUSIONS
The benefits of AZ-MDA are broad-ranging but short-lived. To maximize impact, timing of AZ-MDA must address the challenge of targeting asynchronous morbidity and mortality peaks from different causes.
Identifiants
pubmed: 33417683
pii: 6071007
doi: 10.1093/cid/ciaa1905
pmc: PMC8492219
doi:
Substances chimiques
Antimalarials
0
Drug Combinations
0
Azithromycin
83905-01-5
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2379-e2386Subventions
Organisme : European Union
ID : MR/R010161/1
Organisme : Wellcome Trust Master's Fellowship in Public Health and Tropical Medicine
ID : 205311/Z/16/Z
Organisme : U.K. Medical Research Council, Department for International Development, National Institute for Health Research, and the Wellcome Trust
ID : MR/K007319/1
Organisme : Medical Research Council
ID : MR/K007319/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.
Références
PLoS One. 2008 May 21;3(5):e2227
pubmed: 18493597
Nat Med. 2019 Sep;25(9):1370-1376
pubmed: 31406349
BMC Med Res Methodol. 2016 Mar 08;16:29
pubmed: 26956373
Pharmacol Ther. 2014 Aug;143(2):225-45
pubmed: 24631273
Malar J. 2015 Mar 10;14:108
pubmed: 25881046
Lancet Infect Dis. 2018 Jun;18(6):583
pubmed: 29856346
PLoS Negl Trop Dis. 2019 May 23;13(5):e0007315
pubmed: 31120903
Clin Infect Dis. 2019 May 30;68(12):2114-2116
pubmed: 30561577
Drugs. 1992 Nov;44(5):750-99
pubmed: 1280567
N Engl J Med. 2018 Apr 26;378(17):1583-1592
pubmed: 29694816
J Infect Dis. 2014 Aug 15;210(4):585-92
pubmed: 24652498
PLoS Med. 2019 Jun 25;16(6):e1002835
pubmed: 31237871
Sci Rep. 2017 Aug 23;7(1):9168
pubmed: 28835659
BMJ. 2009 Sep 07;339:b3244
pubmed: 19736281
Antimicrob Agents Chemother. 2013 Apr;57(4):1736-42
pubmed: 23357769
Malar J. 2018 Jun 8;17(1):228
pubmed: 29884184
Am J Trop Med Hyg. 2019 Mar;100(3):691-695
pubmed: 30608051
PLoS One. 2019 Jan 22;14(1):e0210645
pubmed: 30668609
JAMA. 2009 Sep 2;302(9):962-8
pubmed: 19724043
Clin Infect Dis. 2011 Apr 1;52(7):883-8
pubmed: 21427395
Nat Med. 2019 Sep;25(9):1332-1334
pubmed: 31501607
Clin Infect Dis. 1998 Jan;26(1):146-50
pubmed: 9455524
Clin Infect Dis. 1999 Jan;28(1):74-81
pubmed: 10028075
Cochrane Database Syst Rev. 2011 Feb 16;(2):CD006688
pubmed: 21328286
Int J Epidemiol. 2004 Dec;33(6):1286-92
pubmed: 15569662
Lancet Glob Health. 2020 Feb;8(2):e288-e295
pubmed: 31981558
Antimicrob Agents Chemother. 2007 Oct;51(10):3485-90
pubmed: 17698630
Int J Epidemiol. 2001 Dec;30(6):1286-93; discussion 1294-5
pubmed: 11821330
Am J Trop Med Hyg. 2014 May;90(5):846-51
pubmed: 24615132
N Engl J Med. 2019 Jun 06;380(23):2197-2206
pubmed: 30699301
J Infect Dis. 2014 Aug 15;210(4):514-6
pubmed: 24652497
BMC Med Res Methodol. 2017 Apr 21;17(1):72
pubmed: 28431516
Open Forum Infect Dis. 2018 Jul 24;5(8):ofy182
pubmed: 30151409