This (Keenan JD, et al. Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa. The New England journal of medicine. 2018;378(17):1583-92 Open Access) is a new multicenter cluster randomized trial of giving all infants in a community regular azithromycin. If that sounds crazy, just wait… azithromycin (or placebo) was given to all the infants in the included communities twice a year, if they were between 1 and 59 months of age. The study was based on observations that children in trachoma prevention trials (using azithromycin) had lower mortality; this study was designed to see if that was a real effect. Communities in Malawi, Tanzania and Niger were enrolled in this stunning, massive, effort, which included hundreds of thousands of infants.
The other stunning fact, that this study reminds us of, is the enormous post-neonatal infant mortality in these countries. In the country with the highest placebo mortality, Niger, the mortality rate was over 27 per 1000 patient years, that is nearly 3% of all their young kids die each year.
The intervention, azithromycin syrup in a single dose twice a year, was studied in the trial which was called MORDOR, which you may recognize from Lord of the Rings as Tolkien’s name for the kingdom of evil, which he derived from the old English word for murder morþor . I guess because the official language of Niger is French they tortured the acronym production machine until it came up with “Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance”.
The result of the trial was actually the opposite of morþor: there was a significant reduction in mortality, especially in Niger, and especially in the youngest kids, in whom the subgroup analysis showed that babies between 1 and 5 months of age had a 25% reduction in mortality with azithromycin compared to placebo. That is a reduction in mortality among all the infants in the community, which is the 3rd time I am going to use the word stunning in this post.
This intervention will probably have some impact on macrolide resistance, but with such infrequent dosing perhaps that will be minimal, and perhaps this might save many thousands of lives in the world’s poorest countries, if we can ensure that those at highest risk can have access. Azithromycin is quite cheap, and was provided for this Bill and Melinda Gates Foundation funded trial by Pfizer. I’d like to believe that their motivation was altruistic, and that they will provide azithromycin free or at production cost for future trials or usage, if the benefit can be shown to be maintained and that resistance does not become a problem. “you may say I’m a dreamer… but I’m not the only one“