Mass antibiotic dosing to reduce child mortality works better when not limited to infants
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Key takeaways:
- Studies have tested whether mass antibiotic dosing can reduce childhood mortality.
- WHO recommended the intervention in some areas of sub-Saharan Africa, but only in infants, which may reduce its effect.
Mass antibiotic administration to children in sub-Saharan Africa reduced mortality rates, but there was little benefit when dosing was limited to infants aged 1 to 11 months, as recommended by WHO, according to results from the AVENIR trial.
“In some areas of sub-Saharan Africa, nearly 10% of children do not reach their fifth birthday,” Kieran S. O’Brien, PhD, MPH, assistant professor at the Francis I. Proctor Foundation at the University of California, San Francisco, and colleagues wrote. “Although no single intervention will close that gap, twice-yearly mass distribution of azithromycin to children 1 to 59 months of age may contribute.”
As Healio previously reported, the MORDOR trial found communities in Niger that distributed oral azithromycin to children experienced 13.5% lower childhood mortality. In 2020, WHO recommended that communities in sub-Saharan Africa with high rates of childhood mortality consider mass administration of azithromycin, but only among infants aged 1 to 11 months to limit antimicrobial resistance.
The goals of the AVENIR trial, the results of which were published this week in The New England Journal of Medicine, were to replicate the results of the MORDOR trial and to assess the effectiveness of the WHO guidelines limiting antibiotic distribution to infants.
O’Brien and colleagues randomly assigned communities in Niger to receive four twice-yearly distributions of azithromycin or placebo from November 2020 to July 2023. There were 1,229 communities that distributed the antibiotic to children aged 1 to 59 months; 751 communities that gave azithromycin to infants aged 1 to 11 months and placebo to children aged 12 to 59 months; and 929 communities that distributed placebo to children aged 1 to 59 months.
The researchers collected 419,440 person-years of data. During the study period, 5,503 of 382,586 total participants died.
Overall, children aged 1 month to 59 months who received azithromycin for the entire trial had a 14% lower mortality rate than the placebo group, which was consistent with the results of the MORDOR trial (P < .001). The child azithromycin group also had a 13% lower mortality rate than placebo among children aged 12 months to 59 months.
“Among infants 1 to 11 months of age, mortality was not significantly lower” in the infant azithromycin group than the placebo group, the authors wrote. Further, children who only received azithromycin as infants had a similar risk for mortality as the placebo group, meaning there is “no indirect benefit for older children when only infants are treated,” according to the researchers.
Although five serious adverse events were reported, including three in the placebo group and one each in the azithromycin infant and child groups, none were deemed related to treatment.
O’Brien and colleagues will continue to evaluate the prevalence of antimicrobial resistance in the communities included in the trial.
“The AVENIR trial showed that twice-yearly azithromycin distribution to children 1 to 59 months of age reduced mortality, even in communities with lower mortality that were receiving seasonal malaria chemoprevention,” the researchers wrote. “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.”
References:
- O’Brien KS, et al. N Engl J Med. 2024;doi:10.1056/NEJMoa2312093.
- WHO. WHO guideline on mass drug administration of azithromycin to children under five years of age to promote child survival. https://www.who.int/publications/i/item/9789240009585. Published Aug. 27, 2020. Accessed Aug. 22, 2024.
Perspective
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Ramanan Laxminarayan, PhD, MPH
Mass drug administration with antibiotics offers promise in reducing mortality, as first seen at scale in the MORDOR trial. However, although the MORDOR trial showed a statistically significant effect of an 18.1% lower mortality in Niger, effects were not statistically significant in Malawi or Tanzania. The study was repeated in Niger, where expanded malaria chemoprevention was expected to reduce the effect of azithromycin prophylaxis. Indeed, the size of the effect did fall to 14% but remained statistically significant.
The general concern has been of the potential for losing a valuable first-line antibiotic —azithromycin — as a treatment option. Given that there are few comparable drugs at a similar price point or in the drug development pipeline, this is a serious concern, and one that is not addressed by this new study. Given the significant value of azithromycin prophylaxis in countries like Niger with high childhood mortality, there may be a limited scope to deploy these measures. A focus on the areas of highest potential benefit and an expansion of other interventions, including childhood nutrition, could ameliorate the need for antibiotic chemoprophylaxis.
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