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

Background Lower respiratory tract infection (LRTI) is a leading cause of infant morbidity and mortality globally. LRTI may be caused by viral or bacterial infections, individually or in combination. We investigated associations between LRTI and infant nasopharyngeal (NP) viruses and bacteria in a South African birth cohort. Methods In a case-control study of infants enrolled in the Drakenstein Child Health Study (DCHS), LRTI cases were identified prospectively and age-matched with controls from the cohort. NP swabs were tested using quantitative real-time polymerase chain reaction (qPCR) and 16S rRNA gene amplicon sequencing. We calculated adjusted Conditional Odds Ratios (aORs) for qPCR targets and used mixed effects models to identify differentially abundant taxa between LRTI cases and controls and explore viral-bacterial interactions. Results 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], or high-density (> 6.9 log 10 copies/mL) Streptococcus pneumoniae [1.53, 1.01-2.32] were associated with LRTI. Using 16S sequencing, LRTI was associated with increased relative abundance of Haemophilus (q = 0.0003) and 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 were present at lower relative abundance in cases than controls. In samples positive for parainfluenza virus or HRV, Haemophilus was present at higher relative abundance in cases. Conclusions The associations between bacterial taxa and LRTI are strikingly similar to those identified in high-income countries, suggesting a conserved phenotype. RSV was the major virus associated with LRTI. H. influenzae appears to be the major bacterial driver of LRTI, acting synergistically with viruses. The Gram-positive bacteria Dolosigranulum and Corynebacteria may protect against LRTI, while Staphylococcus was associated with reduced risk of RSV-related LRTI. Funding National Institutes of Health of the USA, Bill and Melinda Gates Foundation, National Research Foundation South Africa, South African Medical Research Council, L'Oréal-UNESCO For Women in Science South Africa, Australian National Health and Medical Research Council.

Succession and determinants of the early life nasopharyngeal microbiota in a South African birth cohort.

BACKGROUND: Bacteria colonizing the nasopharynx play a key role as gatekeepers of respiratory health. Yet, dynamics of early life nasopharyngeal (NP) bacterial profiles remain understudied in low- and middle-income countries (LMICs), where children have a high prevalence of risk factors for lower respiratory tract infection. We investigated longitudinal changes in NP bacterial profiles, and associated exposures, among healthy infants from low-income households in South Africa. METHODS: We used short fragment (V4 region) 16S rRNA gene amplicon sequencing to characterize NP bacterial profiles from 103 infants in a South African birth cohort, at monthly intervals from birth through the first 12 months of life and six monthly thereafter until 30 months. RESULTS: Corynebacterium and Staphylococcus were dominant colonizers at 1 month of life; however, these were rapidly replaced by Moraxella- or Haemophilus-dominated profiles by 4 months. This succession was almost universal and largely independent of a broad range of exposures. Warm weather (summer), lower gestational age, maternal smoking, no day-care attendance, antibiotic exposure, or low height-for-age z score at 12 months were associated with higher alpha and beta diversity. Summer was also associated with higher relative abundances of Staphylococcus, Streptococcus, Neisseria, or anaerobic gram-negative bacteria, whilst spring and winter were associated with higher relative abundances of Haemophilus or Corynebacterium, respectively. Maternal smoking was associated with higher relative abundances of Porphyromonas. Antibiotic therapy (or isoniazid prophylaxis for tuberculosis) was associated with higher relative abundance of anerobic taxa (Porphyromonas, Fusobacterium, and Prevotella) and with lower relative abundances of health associated-taxa Corynebacterium and Dolosigranulum. HIV-exposure was associated with higher relative abundances of Klebsiella or Veillonella and lower relative abundances of an unclassified genus within the family Lachnospiraceae. CONCLUSIONS: In this intensively sampled cohort, there was rapid and predictable replacement of early profiles dominated by health-associated Corynebacterium and Dolosigranulum with those dominated by Moraxella and Haemophilus, independent of exposures. Season and antibiotic exposure were key determinants of NP bacterial profiles. Understudied but highly prevalent exposures prevalent in LMICs, including maternal smoking and HIV-exposure, were associated with NP bacterial profiles. Video Abstract.