MORDOR II Burkina Faso: Longitudinal Trial

The investigators' previous MORDOR I research demonstrated a significant reduction in all-cause child mortality after biannual mass azithromycin distribution. In three sub-Saharan Africa countries, (including Niger, Tanzania, and Malawi) mass azithromycin treatment over 2 years resulted in a 14% reduction in child mortality. Moreover, 1 in 5-6 deaths were shown to be averted within Niger alone1. Similar findings were demonstrated in a previous study for trachoma control in Ethiopia with mass azithromycin distribution. This study in rural Ethiopia noted a nearly 50% decrease in all-cause childhood mortality5. However, neither of these studies evaluated the longitudinal impact azithromycin has on the gut microbiome. The MORDOR II trial in Burkina Faso will further evaluate the efficacy of biannual azithromycin treatment. The under-5 child mortality rate in Burkina Faso is approximately 110 per 1,000 live births. Major causes of child mortality in this area are infectious mostly due to malaria, diarrhea, and upper respiratory tract infections. In addition, malnutrition contributes to a high burden of child mortality and morbidity within this region as well. By treating underlying conditions, the use of routine antibiotic treatment could reduce diverse health outcomes leading to morbidity and mortality. The investigative team proposes to conduct this study alongside the MORDOR II trial in the town of Nouna where a majority of childhood deaths are attributable to infectious causes and malnutrition.

The World Health Organization is considering adopting the presumptive use of azithromycin and other antibiotics as a recommendation to reduce childhood mortality in areas with a high infectious disease burden2. Many questions remain unanswered surrounding the use of mass antibiotic treatment in areas with high child morbidity and mortality. This study will add to the current knowledge of mass azithromycin distribution from our previous MORDOR I research. The investigators propose to evaluate how azithromycin will impact childhood growth and to assess the changes that occur in the intestinal microbiome following a single dose of azithromycin treatment. The goal is to contribute more scientific literature that could assist future guidelines regarding antibiotic use.

The role of antibiotics on child growth is unclear. Recent studies indicate that antibiotic use could impact child growth, but a previous study in Niger failed to find a statistically significant correlation between antibiotic treatment with azithromycin and stunting, underweight, or MUAC of pre-school aged children. Longitudinal studies have been recommended to further investigate the role of antibiotics on child growth6. Meanwhile some studies suggest antibiotics may create modifications in the gut microbiota impacting nutrient absorption and weight gain7.The investigative team proposes to measure child growth through anthropometric measurements longitudinally over a 6-month period to see if azithromycin treatment impacts child development. We hypothesize that children receiving a dose of azithromycin will have more growth and development in terms of height, weight, and mid-upper arm circumference compared to children who receive placebo.

The investigators propose a longitudinal study designed to improve our knowledge about the changes in the intestinal microbiome following the course of a single dose of antibiotic in a setting with high childhood mortality and morbidity. More specifically, we propose to follow 500 children for a 6-month time period that are between the ages of 8 days old and 59 months old. Children in this age bracket are at the highest risk for mortality from infectious causes, and furthermore, they are at the highest risk for malnutrition. This group of children would receive the greatest benefit from this intervention. The causal changes in the microbiome are vastly understudied in regards to changes in the gut microbiome following a course of antibiotics. The investigators hypothesize that children receiving a dose of azithromycin will have a higher prevalence of pneumococcal resistance in nasopharyngeal samples, decreased bacterial diversity, and a higher likelihood of identification of bacterial resistance genes in stool and nasopharyngeal samples.

A small group of 50 children (25 per arm) will be followed more intensely within the first 2 weeks of treatment to evaluate macrolide resistance. The investigators hypothesize that children receiving azithromycin will have a greater presence of macrolide genetic resistant determinants.

Inclusion criteria

• Between 8 days and 59 months old
• Primary residence within catchment area of study site
• Available for full 6 month study
• No known allergy to macrolides/azalides
• Appropriate written informed consent from at least one parent or guardian
• Able to feed orally

Exclusion criteria

• <8 days old or >59 months
• Primary residence outside catchment area of study site
• Not available for full 6 month study
• Known allergy to macrolides/azalides
• No written informed consent from at least one parent or guardian
• Unable to feed orally