Background: Group A streptococcus (GAS) is a major human pathogen and an important cause of maternal and neonatal sepsis. Methods: We performed an adhoc analysis of a double-blind, placebo-controlled randomized-trial (ratio 1:1) in The Gambia to determine the impact of one oral dose (2g) of intra-partum azithromycin on maternal and neonatal GAS carriage. Breast milk, nasopharyngeal and vaginal swabs were collected at different time points during the 4 weeks following the intervention. All samples were processed using conventional microbiology techniques. Whole genome sequencing (WGS) of GAS isolates was performed using the Illumina MiSeq platform. Results: We randomized 829 mothers who delivered 843 babies. In mothers, GAS carriage was lower in the azithromycin arm in breast milk (0.28% vs 2.48%, Prevalence Ratio (PR)=0.11, 95% CI 0.01-0.90) and the nasopharynx (0.28% vs 1.93%, PR=0.15, 95%CI 0.02-1.19), but not in the vaginal tract (1.99% vs 1.93%, PR=1.03, 95%CI 0.37-2.91). Among neonates, GAS carriage in the nasopharynx was slightly lower in the azithromycin arm (0.57% vs 1.91%, PR=0.30, 95% CI 0.06-1.42). Prevalence of azithromycin-resistant GAS was similar in both arms, except for a higher prevalence in the vaginal tract among women who received azithromycin (1.99% vs 0.28%, PR=7.24, 95%CI 0.87-56.92). WGS revealed 10 of 44 GAS isolates to be Streptococcus dysgalactiae subspecies equisimilis expressing Lancefield group A carbohydrate (SDSE(A)). All SDSE(A) isolates were azithromycin-resistant, harbouring macrolide resistant genes msr(D) and mef(A). Conclusions: Oral intra-partum azithromycin reduced prevalence of GAS carriage among mothers and neonates. Azithromycin-resistant SDSE(A) carriage was observed among participants receiving azithromycin.
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