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Age-based targeting of biannual azithromycin distribution for child survival in Niger: an adaptive cluster-randomized
Kieran S O'Brien1, Ahmed M Arzika2,3, Abdou Amza3
1Francis I. Proctor Foundation, University of California, San Francisco, USA.
Insights
This study investigates biannual azithromycin distribution in Niger to determine its impact on child mortality and antimicrobial resistance. Findings will inform public health policies for child survival interventions.
Area of Science:
- Global Health
- Infectious Diseases
- Pediatrics
Background:
- Biannual azithromycin distribution to children aged 1-59 months reduced mortality by 14% in a prior trial.
- The World Health Organization suggests targeting this intervention to children aged 1-11 months to mitigate antimicrobial resistance.
- This study aims to evaluate the effects of age-based azithromycin distribution on mortality and resistance.
Purpose of the Study:
- To determine the impact of targeting biannual azithromycin distribution to children aged 1-11 months versus 1-59 months on child mortality.
- To assess the effect of age-based azithromycin distribution strategies on the selection of antimicrobial resistance.
Main Methods:
- A cluster-randomized, placebo-controlled, response-adaptive trial (AVENIR) in Niger involving 3350 communities.
- Randomization to three arms: azithromycin for 1-11 months, azithromycin for 1-59 months, or placebo for 1-59 months.
- Monitoring of all-cause mortality rates and antimicrobial resistance markers (macrolide resistance genes) in nasopharyngeal and rectal samples.
Main Results:
- Primary mortality outcomes compare all-cause mortality rates across intervention arms for different age groups (1-59 months, 1-11 months, 12-59 months).
- Primary resistance outcomes include the prevalence and load of macrolide resistance genes in children aged 1-59 months after two years of distribution.
Conclusions:
- The trial's results will provide crucial evidence for public health decision-making regarding azithromycin distribution strategies.
- Findings will guide policies aimed at optimizing child survival while addressing concerns about antimicrobial resistance in high-mortality settings.
Background:
Biannual distribution of azithromycin to children 1-59 months old reduced mortality by 14% in a cluster-randomized trial. The World Health Organization has proposed targeting this intervention to the subgroup of children 1-11 months old to reduce selection for antimicrobial resistance. Here, we describe a trial designed to determine the impact of age-based targeting of biannual azithromycin on mortality and antimicrobial resistance.
Methods:
AVENIR is a cluster-randomized, placebo-controlled, double-masked, response-adaptive large simple trial in Niger. During the 2.5-year study period, 3350 communities are targeted for enrollment. In the first year, communities in the Dosso region will be randomized 1:1:1 to 1) azithromycin 1-11: biannual azithromycin to children 1-11 months old with placebo to children 12-59 months old, 2) azithromycin 1-59: biannual azithromycin to children 1-59 months old, or 3) placebo: biannual placebo to children 1-59 months old. Regions enrolled after the first year will be randomized with an updated allocation based on the probability of mortality in children 1-59 months in each arm during the preceding study period. A biannual door-to-door census will be conducted to enumerate the population, distribute azithromycin and placebo, and monitor vital status. Primary mortality outcomes are defined as all-cause mortality rate (deaths per 1000 person-years) after 2.5 years from the first enrollment in 1) children 1-59 months old comparing the azithromycin 1-59 and placebo arms, 2) children 1-11 months old comparing the azithromycin 1-11 and placebo arm, and 3) children 12-59 months in the azithromycin 1-11 and azithromycin 1-59 arms. In the Dosso region, 50 communities from each arm will be followed to monitor antimicrobial resistance. Primary resistance outcomes will be assessed after 2 years of distributions and include 1) prevalence of genetic determinants of macrolide resistance in nasopharyngeal samples from children 1-59 months old, and 2) load of genetic determinants of macrolide resistance in rectal samples from children 1-59 months old.
Discussion:
As high-mortality settings consider this intervention, the results of this trial will provide evidence to support programmatic and policy decision-making on age-based strategies for azithromycin distribution to promote child survival.
Trial Registration:
This trial was registered on January 13, 2020 (clinicaltrials.gov: NCT04224987 ).
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