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

## TL;DR

This study explores how viruses and bacteria in the nose of South African infants are linked to lower respiratory infections, finding similar patterns to those in high-income countries.

## Contribution

The study identifies specific viral and bacterial associations with LRTI in South African infants, revealing conserved patterns across different regions.

## Key findings

- Respiratory Syncytial Virus (RSV) was strongly associated with LRTI in infants.
- Haemophilus influenzae was identified as a major bacterial driver of LRTI, interacting with viruses.
- Gram-positive bacteria like Dolosigranulum and Corynebacterium may protect against LRTI.

## Abstract

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.

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.

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 log10 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.

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.

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.