Effect of intra-partum azithromycin on the development of the infant nasopharyngeal microbiota: A post hoc analysis of a double-blind randomized trial
Bakary Sanyang,
Thushan I. de Silva,
Abdoulie Kanteh,
Abdoulie Bojang,
Jarra Manneh,
Wouter A.A. de Steenhuijsen Piters,
Chikondi Peno,
Debby Bogaert,
Abdul Karim Sesay,
Anna Roca
Affiliations
Bakary Sanyang
Disease Control and Elimination, Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, Gambia; The Genomics Core Lab, Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, Gambia; Corresponding authors at: Disease Control & Elimination — Deputy Theme Leader, Medical Research Council Unit The Gambia, Atlantic Boulevard, Fajara, PO Box 273 Banjul, Gambia.
Thushan I. de Silva
The Florey Institute and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK; Vaccines and Immunity, Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, Gambia
Abdoulie Kanteh
The Genomics Core Lab, Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, Gambia
Abdoulie Bojang
Disease Control and Elimination, Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, Gambia
Jarra Manneh
The Genomics Core Lab, Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, Gambia
Wouter A.A. de Steenhuijsen Piters
Department of Paediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, the Netherlands; Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Chikondi Peno
Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
Debby Bogaert
Department of Paediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, the Netherlands; Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
Abdul Karim Sesay
The Genomics Core Lab, Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, Gambia
Anna Roca
Disease Control and Elimination, Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, Gambia; London School of Hygiene and Tropical Medicine, London, UK; Corresponding authors at: Disease Control & Elimination — Deputy Theme Leader, Medical Research Council Unit The Gambia, Atlantic Boulevard, Fajara, PO Box 273 Banjul, Gambia.
Summary: Background: Sepsis is a leading cause of neonatal death. Intrapartum azithromycin reduces neonatal nasopharyngeal carriage of potentially pathogenic bacteria, a prerequisite for sepsis. Early antibiotic exposure has been associated with microbiota perturbations with varying effects. This study aims to understand the effect of intrapartum azithromycin intervention on the developing nasopharyngeal microbiota of the child. Methods: Using 16S rRNA gene sequencing, we analysed the microbiota of 343 nasopharyngeal samples collected from birth to 12 months from 109 healthy infants selected from a double-blind randomized placebo-controlled clinical trial conducted in the Gambia (PregnAnZI-1). In the trial, 829 women were given 2g oral azithromycin or placebo (1:1) during labour with the objective of reducing bacterial carriage in mother and child during the neonatal period. The post-hoc analysis presented here assessed the effect of the intervention on the child nasopharyngeal microbiota development. Findings: 55 children were from mothers given azithromycin and 54 from mothers given placebo. Comparing arms, we found an increase in alpha-diversity at day-6 (p = 0·018), and a significant effect on overall microbiota composition at days 6 and 28 (R2 = 4.4%, q = 0·007 and R2 = 2.3%, q = 0·018 respectively). At genus level, we found lower representation of Staphylococcus at day-6 (q = 0·0303) and higher representation of Moraxella at 12 months (q = 0·0443). Unsupervised clustering of samples by microbial community similarity showed different community dynamics between the intervention and placebo arms during the neonatal period. Interpretation: These results indicate that intrapartum azithromycin caused short-term alterations in the nasopharyngeal microbiota with modest overall effect at 12 months of age. Further exploration of the effects of these variations on microbiome function will give more insight on the potential risks and benefits, for the child, associated with this intervention. Funding: This work was jointly funded by the Medical Research Council (UK) (MC_EX_MR/J010391/1/MRC), Bill & Melinda Gates Foundation (OPP1196513), and MRCG@LSHTM Doctoral Training Program.
