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Distance to Health Centers and Effectiveness of Azithromycin Mass Administration for Children in Niger: A Secondary
Dennis L Chao1, Ahmed M Arzika2, Amza Abdou3
1Bill & Melinda Gates Foundation, Seattle, Washington.
Importance:
The MORDOR (Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance) trial demonstrated that mass azithromycin administration reduced mortality by 18% among children aged 1 to 59 months in Niger. The identification of high-risk subgroups to target with this intervention could reduce the risk of antimicrobial resistance.
Objective:
To evaluate whether distance to the nearest primary health center modifies the effect of azithromycin administration to children aged 1 to 59 months on child mortality.
Design, Setting, And Participants:
The MORDOR cluster randomized trial was conducted from December 1, 2014, to July 31, 2017; this post hoc secondary analysis was conducted in 2023 among 594 clusters (communities or grappes) in the Boboye and Loga departments in Niger. All children aged 1 to 59 months in eligible communities were evaluated.
Interventions:
Biannual (twice-yearly) administration of a single dose of oral azithromycin or matching placebo over 2 years.
Main Outcomes And Measures:
A population-based census was used to monitor mortality and person-time at risk (trial primary outcome). Community distance to a primary health center was calculated as kilometers between the center of each community and the nearest health center. Negative binomial regression was used to evaluate the interaction between distance and the effect of azithromycin on the incidence of all-cause mortality among children aged 1 to 59 months.
Results:
Between December 1, 2014, and July 31, 2017, a total of 594 communities were enrolled, with 76 092 children (mean [SD] age, 31 [2] months; 39 022 [51.3%] male) included at baseline, for a mean (SD) of 128 (91) children per community. Median (IQR) distance to the nearest primary health center was 5.0 (3.2-7.1) km. Over 2 years, 145 693 person-years at risk were monitored and 3615 deaths were recorded. Overall, mortality rates were 27.5 deaths (95% CI, 26.2-28.7 deaths) per 1000 person-years at risk in the placebo arm and 22.5 deaths (95% CI, 21.4-23.5 deaths) per 1000 person-years at risk in the azithromycin arm. For each kilometer increase in distance in the placebo arm, mortality increased by 5% (adjusted incidence rate ratio, 1.05; 95% CI, 1.03-1.07; P < .001). The effect of azithromycin on mortality varied significantly by distance (interaction P = .02). Mortality reduction with azithromycin compared with placebo was 0% at 0 km from the health center (95% CI, -19% to 17%), 4% at 1 km (95% CI, -12% to 17%), 16% at 5 km (95% CI, 7% to 23%), and 28% at 10 km (95% CI, 17% to 38%).
Conclusions And Relevance:
In this secondary analysis of a cluster randomized trial of mass azithromycin administration for child mortality, children younger than 5 years who lived farthest from health facilities appeared to benefit the most from azithromycin administration. These findings may help guide the allocation of resources to ensure that those with the least access to existing health resources are prioritized in program implementation.
Trial Registration:
ClinicalTrials.gov Identifier: NCT02047981.
Insights
Mass azithromycin administration significantly reduced child mortality in Niger. Children living farthest from health centers experienced the greatest mortality reduction, suggesting targeted interventions for remote populations.
Area of Science:
- Global Health
- Infectious Diseases
- Pediatrics
Background:
- Mass azithromycin administration in children aged 1 to 59 months in Niger (MORDOR trial) reduced overall mortality by 18%.
- Identifying high-risk subgroups for azithromycin administration can mitigate antimicrobial resistance risks.
- Understanding geographical access to healthcare is crucial for optimizing public health interventions.
Purpose of the Study:
- To investigate if proximity to primary health centers influences the effectiveness of mass azithromycin administration on child mortality.
- To determine if children residing farther from health facilities benefit more from azithromycin treatment.
- To inform resource allocation for child mortality reduction programs.
Main Methods:
- A secondary analysis of the MORDOR cluster randomized trial (2014-2017) involving 594 communities in Niger.
- Data included biannual azithromycin or placebo administration to children aged 1-59 months over two years.
- Mortality was monitored via census; distance to the nearest health center was calculated. Negative binomial regression analyzed the interaction between distance and azithromycin's effect on mortality.
Main Results:
- Overall mortality rates were 27.5 deaths/1000 person-years in the placebo arm and 22.5 deaths/1000 person-years in the azithromycin arm.
- Each kilometer increase in distance from a health center was associated with a 5% increase in mortality in the placebo group.
- Azithromycin's mortality reduction effect was significantly modified by distance, with greater benefits observed in children living farther from health centers (e.g., 28% reduction at 10 km).
Conclusions:
- Children under 5 living farthest from health facilities experienced the most significant mortality reduction from mass azithromycin administration.
- These findings support prioritizing resource allocation to improve access for remote populations.
- Targeted mass drug administration strategies can enhance child survival in resource-limited settings.
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