A large-scale trial conducted in sub-Saharan Africa has demonstrated that mass distribution of azithromycin to children aged 1 to 59 months significantly reduces all-cause mortality. The study, known as the AVENIR trial, challenges current World Health Organization (WHO) guidelines that recommend limiting such distributions to infants in high-mortality settings due to concerns about antimicrobial resistance (AMR).
The research, led by Kieran O'Brien from the University of California, San Francisco, involved over 382,000 children across 1273 communities in Niger. The trial compared outcomes in groups receiving azithromycin (a single observed dose of 20mg/kg in an oral suspension) to those receiving a placebo, with distributions occurring twice yearly.
Key Findings from the AVENIR Trial
The results indicated a 14% lower mortality rate in the child group (1 to 59 months) receiving azithromycin compared to the placebo group (11.0 deaths per 1000 person-years [95% CI 11.3 to 12.6] vs 13.9 deaths [13.0-14.8]). However, the mortality among infants 1 to 11 months of age was not statistically significantly lower with azithromycin than placebo.
"Overall the AVENIR trial showed that twice-yearly azithromycin distribution in children 1 to 59 months of age reduce morality, even in communities with lower mortality than were receiving seasonal malaria chemoprevention. The trial provides evidence that limiting distributions to infants 1 to 11 months of age is not as effective as including all children 1 to 59 months of age," O'Brien and colleagues declare.
Implications for Public Health
The findings suggest that a broader approach to azithromycin distribution could be more effective in reducing childhood mortality in sub-Saharan Africa. This is particularly relevant given the high burden of infectious diseases in the region and the potential for significant public health impact.
In an accompanying editorial, Kathryn Maitland and Sarah Walker noted that the WHO's subsequent conditions "set the bar very high for future implementation." Results from the trial by O'Brien and colleagues, they indicate, "challenge most of the current recommendations for mass distribution of azithromycin except for one—the specter of increased antimicrobial resistance."
Balancing Mortality Reduction and AMR Risks
While the study demonstrates the potential benefits of widespread azithromycin use, researchers emphasize the importance of monitoring for AMR. The WHO's more restricted guidelines are based on valid concerns about the development and spread of resistant bacteria, which could ultimately undermine the effectiveness of the antibiotic.
The investigators acknowledge that AMR must be monitored with such programs, but nonetheless argue for its wider application.
