Mass antibiotic dosing reduces child mortality in sub-Saharan Africa

The global child mortality rate has declined 56% since 1990, but 15,000 children aged younger than 5 years still die every day, and young children in Africa are almost eight times likelier to die than those born in Europe, according to WHO.

The divide is even wider in sub-Saharan Africa, where close to 8% of children die before their fifth birthday, many from treatable illnesses like diarrhea, malaria and pneumonia.

In a new study published today in The New England Journal of Medicine, researchers reported findings from a cluster-randomized trial they conducted in more than 1,500 communities in three sub-Saharan African countries to test the hypothesis that mass distributing broad-spectrum antibiotics to preschool children could reduce child mortality.

Image of child holding pills.
Mass administration of azithromycin to preschool children in sub-Saharan Africa reduced mortality rates, but the effect could be negated or even reversed by antibiotic resistance, researchers said.
Source: Adobe Stock

The approach appears to work. According to Thomas Lietman, MD, distinguished professor in the Francis I. Proctor Foundation for Research Ophthalmology at the University of California, San Francisco, and colleagues, the overall annual mortality rate in communities where children received two doses of oral azithromycin was 13.5% lower than in communities where they received placebo. Lietman and colleagues did not investigate how azithromycin reduced mortality in these communities but hypothesized that it likely reduced the incidence of respiratory infections, diarrhea and malaria.

The effect was greatest in Niger, which has one of the highest child mortality rates in the world. Lietman and colleagues reported that child mortality was 18.1% lower in Nigerien communities where children received azithromycin compared with those where they did not. Smaller, nonsignificant differences were seen in Malawi (5.7%) and Tanzania (3.4%).

The study, which was conducted between December 2014 and February 2017, included more than 190,000 children aged 1 to 59 months. According to Lietman and colleagues, the effect was greatest among children aged 1 to 5 months, who saw a 24.9% reduction in mortality.

But there are questions about the impact that such a strategy would have on antibiotic resistance. In their study, Lietman and colleagues acknowledged that using antibiotics for “nonspecific” reasons is discouraged and said any implementation of a policy to mass distribute antibiotics would have to account for the impact on drug resistance. They noted past studies that showed how widespread use of azithromycin for trachoma facilitated resistance and said that resistance emerging during mass distributions of the drug could potentially curb or even reverse any benefit on mortality rates.

Amesh Adalja, MD, senior scholar in the Johns Hopkins Center for Health Security, said the impact of mass distributing antibiotics could be substantial and would need to be monitored proactively.

Amesh Adalja
Amesh Adalja

“How big an impact on antibiotic resistance such a strategy could have — on target and off-target bacteria — remains to be seen and will be impacted by how frequently such distributions occur, baseline resistance and other uses of macrolide antibiotics,” Adalja told Infectious Disease News.

“In certain contexts, the benefits will outweigh the risks and this strategy should be welcomed. However, there will need to be an ongoing risk calculus performed to determine when [or] if such strategies should be started, stopped or continued.”

Lietman and colleagues have not yet observed a waning effect on mortality throughout the trial — in fact, they reported that the impact grew over 4 years. But they said a follow-up study is warranted to see if the effect changes with subsequent rounds of treatment, and Lietman told Infectious Disease News that they will be monitoring drug resistance for 2 more years in Niger. – by Gerard Gallagher

Reference:

Keenan JD, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1715474.

Disclosures: Adalja and Leitman report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

The global child mortality rate has declined 56% since 1990, but 15,000 children aged younger than 5 years still die every day, and young children in Africa are almost eight times likelier to die than those born in Europe, according to WHO.

The divide is even wider in sub-Saharan Africa, where close to 8% of children die before their fifth birthday, many from treatable illnesses like diarrhea, malaria and pneumonia.

In a new study published today in The New England Journal of Medicine, researchers reported findings from a cluster-randomized trial they conducted in more than 1,500 communities in three sub-Saharan African countries to test the hypothesis that mass distributing broad-spectrum antibiotics to preschool children could reduce child mortality.

Image of child holding pills.
Mass administration of azithromycin to preschool children in sub-Saharan Africa reduced mortality rates, but the effect could be negated or even reversed by antibiotic resistance, researchers said.
Source: Adobe Stock

The approach appears to work. According to Thomas Lietman, MD, distinguished professor in the Francis I. Proctor Foundation for Research Ophthalmology at the University of California, San Francisco, and colleagues, the overall annual mortality rate in communities where children received two doses of oral azithromycin was 13.5% lower than in communities where they received placebo. Lietman and colleagues did not investigate how azithromycin reduced mortality in these communities but hypothesized that it likely reduced the incidence of respiratory infections, diarrhea and malaria.

The effect was greatest in Niger, which has one of the highest child mortality rates in the world. Lietman and colleagues reported that child mortality was 18.1% lower in Nigerien communities where children received azithromycin compared with those where they did not. Smaller, nonsignificant differences were seen in Malawi (5.7%) and Tanzania (3.4%).

The study, which was conducted between December 2014 and February 2017, included more than 190,000 children aged 1 to 59 months. According to Lietman and colleagues, the effect was greatest among children aged 1 to 5 months, who saw a 24.9% reduction in mortality.

But there are questions about the impact that such a strategy would have on antibiotic resistance. In their study, Lietman and colleagues acknowledged that using antibiotics for “nonspecific” reasons is discouraged and said any implementation of a policy to mass distribute antibiotics would have to account for the impact on drug resistance. They noted past studies that showed how widespread use of azithromycin for trachoma facilitated resistance and said that resistance emerging during mass distributions of the drug could potentially curb or even reverse any benefit on mortality rates.

Amesh Adalja, MD, senior scholar in the Johns Hopkins Center for Health Security, said the impact of mass distributing antibiotics could be substantial and would need to be monitored proactively.

Amesh Adalja
Amesh Adalja

“How big an impact on antibiotic resistance such a strategy could have — on target and off-target bacteria — remains to be seen and will be impacted by how frequently such distributions occur, baseline resistance and other uses of macrolide antibiotics,” Adalja told Infectious Disease News.

“In certain contexts, the benefits will outweigh the risks and this strategy should be welcomed. However, there will need to be an ongoing risk calculus performed to determine when [or] if such strategies should be started, stopped or continued.”

Lietman and colleagues have not yet observed a waning effect on mortality throughout the trial — in fact, they reported that the impact grew over 4 years. But they said a follow-up study is warranted to see if the effect changes with subsequent rounds of treatment, and Lietman told Infectious Disease News that they will be monitoring drug resistance for 2 more years in Niger. – by Gerard Gallagher

Reference:

Keenan JD, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1715474.

Disclosures: Adalja and Leitman report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.