Abstract
The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1–59 months). Mass azithromycin reduces Campylobacter spp. force of infection by 29% (hazard ratio = 0.71, 95% CI: 0.56, 0.89; P = 0.004) but serological measures show no significant differences between groups for other pathogens against a backdrop of high transmission. Results align with a recent microbiome study in the communities. Given significant sequelae of Campylobacter infection among preschool aged children, our results support an important mechanism through which biannual mass distribution of azithromycin likely reduces mortality in Niger.
Highlights
The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007)
Leaveone-out sensitivity analyses showed overall estimates were unbiased and no single community had undue influence on the analysis (Supplementary Fig. 15). In this analysis of IgG antibody response to malarial, bacterial, and protozoan pathogens we found that biannual mass distribution of azithromycin to children 1–59 months reduced Campylobacter seroprevalence and seroconversion rates
A reduction in IgG responses to Campylobacter jejuni among children who received azithromycin is consistent with the trial’s earlier report of reduced mortality in azithromycin-treated communities attributed to dysentery[3]
Summary
The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1–59 months). Studies that further clarify the mechanisms of mortality reduction from azithromycin could help identify complementary interventions or identify alternative interventions that lead to similar benefits but have lower potential to select for antimicrobial resistance[7] In this pre-specified, secondary analysis of the MORDOR Niger trial, our objectives were to assess the effect of biannual mass distribution of azithromycin to preschool-aged children on serological measures of malaria, bacterial, and protozoan infections. Not a first line treatment, azithromycin has antimicrobial activity against enteric protozoans Cryptosporidium[22] and Giardia[23,24]
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