The nasopharyngeal microbiome in South African children with lower respiratory tract infection: a nested case-control study of the Drakenstein Child Health Study

Lower respiratory tract infections (LRTI) are a major contributor to infant morbidity and mortality in low- and middle-income countries. The aetiology of LRTI includes both bacterial and viral infections, which may act synergistically. We investigated associations between infant nasopharyngeal (NP) viruses, bacteria and LRTI in a South African birth cohort.In a case-control study of infants enrolled in the Drakenstein Child Health Study, LRTI cases were identified prospectively and age-matched with controls. NP swabs were tested using quantitative real-time polymerase chain reaction (qPCR) and 16S rRNA gene amplicon sequencing. The viruses respiratory syncytial virus (RSV), human rhinovirus (HRV), parainfluenza virus, adenovirus, and enterovirus and the bacteria Haemophilus influenzae, Klebsiella pneumoniae and high-density.Streptococcus pneumoniae were associated with LRTI. LRTI was associated with increased relative abundance of Haemophilus and decreased relative abundance of Dolosigranulum and Neisseria. In samples from infants positive for RSV, Staphylococcus and Alloprevotella were present at higher relative abundance in controls compared to cases. In samples positive for parainfluenza virus or HRV, Haemophilus was present at higher relative abundance in cases. Our findings of viral and bacterial associations with LRTI are similar to those previously observed in high-income countries. Haemophilus appears to be the major bacterial driver of LRTI, acting synergistically with less virulent viruses. The Gram-positive bacteria Dolosigranulum and Corynebacteria may protect against LRTI, while Staphylococcus may reduce the risk of RSV-related LRTI.