Cause-specific mortality of children younger than 5 years in communities receiving biannual mass azithromycin treatment in Niger: verbal autopsy results from a cluster-randomised controlled trial

Abstract

Background The Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial found that biannual mass distribution of azithromycin to children younger than 5 years in Niger reduced the primary outcome of all-cause mortality by 18%. We aimed to determine the causes of mortality among deceased children using verbal autopsy. MethodsIn this 2-year cluster-randomised controlled trial, 594 community clusters in Niger were randomly allocated (1:1 ratio) to receive biannual mass distributions of either oral azithromycin (approximately 20 mg per kg of bodyweight) or placebo targeted to children aged 1-59 months. Participants, study investigators, and field workers were masked to treatment allocation. Between Nov 23, 2014, and July 31, 2017, 3615 child deaths were recorded by use of biannual house-to-house censuses, and verbal autopsies were done between May 26, 2015, and May 17, 2018, to identify cause of death. Cause-specific mortality, as assessed by verbal autopsy, was a prespecified secondary outcome. This trial is completed and is registered with ClinicalTrials.gov, NCT02047981.

Impact of azithromycin mass drug administration on the antibiotic-resistant gut microbiome: a randomized, controlled trial

“…Better defining the impact of azithromycin MDA on childhood morbidity and mortality was the aim of the MORDOR (Mortality reduction after oral azithromycin) clinical trial, which randomised 1533 communities across three sub-Saharan African countries to four biannual rounds of azithromycin treatment or placebo 21 Secondary analyses found the impact of treatment to be most pronounced in the first three months post-treatment and in children aged 1-5 months 21,22 . Despite Niger reporting the most significant effect on childhood mortality, there were no significant differences in the causes of mortality between the two study arms in this country 23 . In both the treatment and placebo arms, malaria (28%), pneumonia (16%) and diarrhoea (14-15%) accounted for the majority of verbal autopsy-confirmed deaths.…”

Global emerging resistance in pediatric infections with TB, HIV, and gram-negative pathogens

“…While the unnecessary use of antibiotic agents in the community is a major risk factor for the development of resistance, well targeted mass-distributed antimicrobial agents may have a beneficial effect in LMIC, resulting in a reduction of infections and mortality. The mass distribution of azithromycin over 3 years in over 300 communities in Niger resulted in a third fewer deaths from meningitis and dysentery in children aged 1-59 months, and a fifth fewer deaths secondary to malaria and pneumonia [88]. The Mortality Reduction after Oral Azithromycin (MORDOR) study published in 2018, a randomised trial assessing the effect of broadspectrum antibiotic therapy on childhood mortality in sub-Saharan Africa, demonstrated that azithromycin resulted in a 13.5% lower mortality rate compared with placebo in Niger, Malawi and Tanzania.…”

Single-dose azithromycin for child growth in Burkina Faso: a randomized controlled trial

“…Biannual oral mass azithromycin distribution to children aged 1–59 months has been shown to reduce all-cause child mortality in some settings in sub-Saharan Africa [ 1 – 4 ]. The primary mechanism is likely via reduction in infectious burden [ 5 ]. Undernutrition is an underlying cause in as many as 50% of child deaths [ 6 ].…”