In the JournalsPerspective

Experts suggest more frequent mass distribution of azithromycin

Earlier this year, researchers published results from a trial conducted in more than 1,500 communities in sub-Saharan Africa showing that biannual mass distribution of azithromycin to preschool children significantly reduced child mortality rates.

Now, 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.

According to the previously reported results, the intervention led to a 14% reduction in postneonatal childhood mortality. Travis C. Porco, PhD, 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. Azithromycin may also have collateral benefits against a number of infectious diseases including malaria, diarrhea, and pneumonia,” they wrote.

Image of child holding pills.  
Mass administration of azithromycin to preschool children in sub-Saharan Africa was shown to reduce mortality rates.
Source: Adobe Stock

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 a placebo.

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

When assessing 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.

“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 postdistribution. Where feasible, quarterly distributions could be assessed.”

There are questions about the impact that a mass dosage strategy would have on the growing problem of antibiotic resistance, of which unnecessary prescribing and overuse of antibiotics are contributing factors, according to experts.

WHO spokesman Tarik Jašarević told Infectious Disease News that the agency is looking into the “potential use of azithromycin mass drug administration (MDA) as an intervention to improve child survival,” including an assessment of the impact the intervention would have on antimicrobial resistance. He said WHO is reviewing all available studies and data, including the results from the MORDOR trial, and that it has “commissioned reviews of the clinical efficacy of azithromycin MDA.”

“The Guidelines Development Group, established earlier this year, will review the commissioned work, along with all the available published data in a review meeting in late January 2019,” Jaarevi said. “We expect a formal recommendation on the potential use of azithromycin MDA as a child survival intervention will be forthcoming after this meeting.” – by Marley Ghizzone

Disclosures: The authors report no relevant financial disclosures.

Earlier this year, researchers published results from a trial conducted in more than 1,500 communities in sub-Saharan Africa showing that biannual mass distribution of azithromycin to preschool children significantly reduced child mortality rates.

Now, 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.

According to the previously reported results, the intervention led to a 14% reduction in postneonatal childhood mortality. Travis C. Porco, PhD, 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. Azithromycin may also have collateral benefits against a number of infectious diseases including malaria, diarrhea, and pneumonia,” they wrote.

Image of child holding pills.  
Mass administration of azithromycin to preschool children in sub-Saharan Africa was shown to reduce mortality rates.
Source: Adobe Stock

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 a placebo.

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

When assessing 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.

“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 postdistribution. Where feasible, quarterly distributions could be assessed.”

There are questions about the impact that a mass dosage strategy would have on the growing problem of antibiotic resistance, of which unnecessary prescribing and overuse of antibiotics are contributing factors, according to experts.

WHO spokesman Tarik Jašarević told Infectious Disease News that the agency is looking into the “potential use of azithromycin mass drug administration (MDA) as an intervention to improve child survival,” including an assessment of the impact the intervention would have on antimicrobial resistance. He said WHO is reviewing all available studies and data, including the results from the MORDOR trial, and that it has “commissioned reviews of the clinical efficacy of azithromycin MDA.”

“The Guidelines Development Group, established earlier this year, will review the commissioned work, along with all the available published data in a review meeting in late January 2019,” Jaarevi said. “We expect a formal recommendation on the potential use of azithromycin MDA as a child survival intervention will be forthcoming after this meeting.” – by Marley Ghizzone

Disclosures: The authors report no relevant financial disclosures.

    Perspective

    Photo of Amesh Adalja

    The take-home message in this study is that mass distribution of azithromycin in certain geographic locales, which has already been shown to impact mortality, has an immediate beneficial effect within 3 months of administration.

    If the mortality decrease is achieved so rapidly, more frequent distribution — if feasible — makes sense because there is likely more benefit than can be realized.

    This mortality benefit of azithromycin is an important finding, and it is an important research priority to understand the mechanism of mortality decrease: Is it via pneumonia treatment, diarrhea treatment, an immunomodulatory effect or some other reason? It is also essential to track azithromycin resistance in the population so a continual risk-benefit calculus can be performed.

    Amesh A. Adalja, MD

    Senior scholar
    Johns Hopkins Center for Health Security

    Disclosure: Adalja reports no relevant financial disclosures.