Nasopharyngeal microbiota in South African infants with lower respiratory tract infection: a nested case-control study of the Drakenstein Child Health Study

Background Lower respiratory tract infections (LRTI) in infants are commonly caused by viral and bacterial infections, alone or in combination. We investigated associations between LRTI and infant nasopharyngeal (NP) viruses and bacteria in South African infants. Methods In a case-control study of infants enrolled in a birth cohort, LRTI cases were identified prospectively and age-matched with controls. NP swabs were tested using quantitative real-time polymerase chain reaction and 16S rRNA gene amplicon sequencing. We calculated adjusted Conditional Odds Ratios (aORs) and used mixed effects models to identify differentially abundant taxa and explore viral-bacterial interactions. Results Samples from a total of 444 LRTI episodes and 444 matched control timepoints were tested. Respiratory Syncytial Virus (RSV) [aOR: 5.69, 95%CI 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=0.001), Corynebacterium (q=0.091) and Neisseria (q=0.004). 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 CMV in controls was associated with reduced Corynebacterium, Dolosigranulum and Staphylococcus. Conclusions The associations between bacterial taxa and viruses and LRTI are similar to those from high-income countries. Haemophilus is a major bacterial driver of LRTI, acting synergistically with viruses. Dolosigranulum and Corynebacteria may reduce LRTI risk, while Staphylococcus may reduce the risk of RSV-related LRTI. CMV infection is associated with a dysbiotic nasopharyngeal microbiota.