When research from UC San Francisco showed that routine treatment of children in sub-Saharan Africa with a common antibiotic could reduce deaths among children under five, the World Health Organization (WHO) quickly recommended the treatment – ​​but only for infants between the ages of one and 11 months.

Now researchers at UCSF have shown that treating babies is not enough. The antibiotic must be given to all children up to the age of five to achieve its full benefit. And the benefit is considerable: it reduces child mortality by 14 percent in a region where one in ten children dies before their fifth birthday.

The WHO recommended limiting the use of the antibiotic azithromycin over concerns that wider use could lead to antibiotic resistance. But research shows that the youngest and most vulnerable children – those under one year old – are better protected from respiratory and other potentially fatal infections if their older siblings are also treated and thus do not transmit those infections.

The results are clear. By treating the older children, you can protect the younger children who are particularly at risk.”

Kieran S. O’Brien, PhD, MPH, lead author of the study, epidemiologist and assistant professor at the Francis I. Proctor Foundation at UCSF

The results will appear online on August 21 in the New England Journal of Medicine.

Concerns about antibiotic resistance

Azithromycin is a broad-spectrum antibiotic that is effective against a wide spectrum of pathogens, including those that cause respiratory infections, diarrhea and malaria, which are among the leading causes of death among children in sub-Saharan Africa.

The first study in 2018 involved nearly 200,000 children in three African countries: Niger, Malawi and Tanzania. The children received a single dose of oral azithromycin or a placebo four times over two years.

This reduced mortality by almost 14% overall in children under five years of age and by 25% in babies under five months of age. And in 2020, the WHO endorsed the mass administration of azithromycin to children under one year of age. However, research had not shown that targeted administration to infants alone would significantly reduce mortality.

In this recently published follow-up study, titled AVENIR (Azithromycin pour la Vie des Enfants au Niger; Implementation and Recherche), researchers tested the approach in different age groups to see if they could demonstrate its benefit when applied exclusively to young children.

The study, conducted in collaboration with the Niger Ministry of Health and the Centre de Recherche et Interventions en Santé Publique in Niger, repeated the same dosing regimen but limited it to a single country, Niger, which has a higher child mortality rate than the other two countries in the original study.

They found that the mortality rate among children under five only decreased significantly when all children were treated.

Infants are exposed to pathogens at home

The researchers found that most of the infants had older siblings in the household. These older children spend more time outside the household playing with other children, increasing the likelihood of infecting their younger, more vulnerable siblings.

While the authors acknowledged that antibiotic resistance was a legitimate concern, they stressed that the intervention was limited to a small proportion of the population and only lasted for a few years, and the risk of developing resistance was outweighed by the opportunity to save lives.

Thomas M. Lietman, MD, the study’s lead author and an ophthalmologist at UCSF, hopes the study will encourage WHO to recommend the treatment for children up to 5 years of age.

“In medicine, we are taught not to use antibiotics indiscriminately because of the risk of antibiotic resistance. But we found that if this is done systematically, child mortality can be reduced,” said Lietman, the lead author of the original study. “How can you deny a treatment that reduces mortality by 14% in areas where 10% of children do not reach their fifth birthday?”