Nasopharyngeal Microbiota in South African Infants With Lower Respiratory Tract Infection: A Nested Case-Control Study of the Drakenstein Child Health Study

Abstract

Background. Lower respiratory tract infections (LRTIs) in infants are caused by viral and bacterial infections. We investigated associations between LRTI and nasopharyngeal (NP) viruses and bacteria in South African infants. Methods. In a birth cohort, LRTI cases were identified prospectively and age-matched with controls. NP swabs were tested using polymerase chain reaction and 16S RNA gene sequencing. We calculated adjusted conditional odds ratios (aORs) and used mixed-effects models to identify differentially abundant taxa and explore viral–bacterial interactions. Results. A total of 888 case-control samples were tested. Respiratory syncytial virus (RSV) (aOR, 5.69 [95% confidence interval, 3.03–10.69]), human rhinovirus (HRV) (1.47 [1.03–2.09]), parainfluenza virus (3.46 [1.64–7.26]), adenovirus (1.99 [1.08–3.68]), enterovirus (2.32 [1.20–4.46]), Haemophilus influenzae (1.72 [1.25–2.37]), Klebsiella pneumoniae (2.66 [1.59–4.46]), and high-density Streptococcus pneumoniae (1.53 [1.01–2.32]) were associated with LRTI. LRTI was associated with decreased relative abundance of Dolosigranulum (q =.001), Corynebacterium (q =.091), and Neisseria (q =.004). In samples positive for RSV, Staphylococcus and Alloprevotella relative abundance was higher in controls compared to cases. In samples positive for parainfluenza virus or HRV, Haemophilus relative abundance was higher in cases. Detection of cytomegalovirus (CMV) in controls was associated with reduced Corynebacterium, Dolosigranulum, and Staphylococcus. Conclusions. The associations between bacteria, viruses and LRTIs are similar to those from high-income countries. Haemophilus is a major bacterial driver of LRTIs, acting synergistically with viruses. Dolosigranulum and Corynebacterium may reduce LRTI risk, while Staphylococcus may reduce the risk of RSV-related LRTIs. CMV is associated with dysbiotic nasopharyngeal microbiota.