Biannual mass distribution of azithromycin to children reduces mortality rates

A new study published in NEJM has reported that biannual mass distribution of azithromycin to preschool children significantly reduced child mortality rates. The study included more than 1,500 communities in sub-Saharan Africa.

Results from a secondary analysis of the MORDOR trial have shown that much of the protective effect came in the first 3 months after distribution, suggesting that in places where it is feasible distributing the broad-spectrum antibiotic more frequently than twice a year could be considered.

MORDOR was a cluster-randomized trial conducted in more than 1,500 communities in Malawi, Niger, and Tanzania between December 2014 and February 2017. Children aged 1 to 59 months who weighed at least 3,800 g were randomly assigned to receive biannual azithromycin or placebo.

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According to the previously reported results, the intervention led to a 14% reduction in postneonatal childhood mortality. Travis C. Porco, Ph.D., MPH, a professor at the University of California, San Francisco, and colleagues said it is still unclear exactly how azithromycin had its effect.

Trachoma programs have distributed more than 700 million doses of single-dose oral azithromycin to eliminate the strains of chlamydia that cause the blinding disease. This study did not investigate the mechanism by which azithromycin reduced mortality. Before the trial, experts thought a protective effect would most likely be due to reductions in respiratory infections, diarrhea, and malaria, in that order

For the secondary analysis, Porco and associates compared survival time after treatment in the azithromycin and placebo-treated communities, and the distribution of time of death posttreatment, the season of treatment and season of death in participants who died.

When assessing the timing of mortality among children who had died, the researchers observed that those in the treatment group were less likely to die early compared with those in the placebo group.

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“We were unable to demonstrate that the season of distribution was an effect modifier, so we cannot recommend specific timing for treatments,” they wrote. “We were able to demonstrate that the greatest protection was found in the first 3 months post-distribution where feasible, quarterly distributions could be assessed.”

The study concluded that Mass azithromycin distribution to post-neonatal, pre-school children may reduce childhood mortality in sub-Saharan Africa, particularly in high mortality areas such as Nigeria.

The question arises regarding the impact of mass dosage strategy on the increasing problem of antibiotic resistance. Any policy recommending mass distribution of oral azithromycin for childhood mortality would need to consider not only cost but also the potential for antibiotic resistance.

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https://www.nejm.org/doi/10.1056/NEJMoa1715474