A disease outbreak anywhere is a risk everywhere.”
-Dr. Tom Frieden, Director U.S. CDC
We read a lot about the dangers of using too many antibiotics. The popularity of “organic foods” is due in part to their claim to be from “antibiotic-free” animals and plants. Concern about the increasing antibiotic resistance of germs due to antibiotic overuse is real as is frequently described in scientific journals as well as the general press. Why, then, would the New England Journal of Medicine publish an article describing the benefits of random, mass distribution of an oral antibiotic to nearly 100,000 children who had no symptoms or diagnosis! Maybe because that effort reduced the death rate of children aged 1-5 months by 25%!
As you’ll remember in my last blog, I was impressed by Bill Gate’s knowledge of the medical literature because during his presentation he cited this antibiotic clinical trial which had been published that very same week. Well, full disclosure, he knew about the study because his foundation funded it! This study is the kind of innovative medical study related to global health that the Bill & Melinda Gates Foundation supports. I think it is worthwhile to review the details of the study, if just to remind us that antibiotics are good, that medical science advances on the shoulders of previous work, and that sometimes simple answers, like putting iodine into salt or fluoride into water, can prevent a whole lot of disease.
Previous studies in sub-Saharan Africa showed that blindness caused by trachoma, an infectious disease, could be reduced markedly through the mass distribution of an oral antibiotic, azithromycin. Other studies suggested that the same antibiotic could prevent other infectious deaths like malaria, infectious diarrhea, and pneumonia. It is known that azithromycin affects the transmission of infectious disease, so that treatment of one person might have benefits on others in the same community. The data in two of these studies of trachoma prevention in Ethiopia suggested that mass distribution of azithromycin “might” reduce childhood deaths. Since death (after the neonatal period) is a relatively rare event, even in these settings, the trial had to be conducted in a large population. Hence the need for a large grant to carry it out.
A single dose of oral azithromycin was given to 97,047 children aged from 1 month to 5 years in three African countries during a twice-yearly census. 93,191 children in different communities of the same countries were given a placebo. Over the two-year study the “treated” children received 4 oral doses of azithromycin, each about 6 months apart. Children were identified by the name of the head of the household and GPS coordinates of their location for subsequent censuses. Approval for the study was obtained from 9 ethics committees in 6 countries (3 in the US, 1 in the UK, and 2 in Africa).
The average reduction of annual death rates of children receiving a single dose of the antibiotic every 6 months was 13.5% . Children aged 1 month to 5 months receiving the antibiotic had a mortality rate reduction of 25%. At the conclusion of the trial all the children in the communities of Niger, which has one of the highest child mortality rates in the world and a mortality rate reduction of 18% for all ages in this study, were offered treatment with azithromycin.
This study is a beautiful example of the testing of a simple hypothesis, generated by the results of previous work, using innovative methods, requiring a large population for validity, and implemented by a multi-national team of medical scientists with a large grant from a private foundation that resulted in clear benefits for better global health.
I, for one, am happy to trumpet some good news about antibiotics and this example of “medical research for all” at its best.
Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa, NEJM 378;17, April 26, 2018