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

Shantelle Claassen-Weitz; Yao Xia; Luke Hannan; Sugnet Gardner-Lubbe; Kilaza S Mwaikono; Stephanie Harris Mounaud; William C Nierman; Lesley Workman; Felix S Dube; Samantha Africa; Fadheela Patel; Veronica Allen; Lemese Ah Tow Edries; Heather J Zar; Mark P Nicol

doi:10.1093/cid/ciaf184

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

Clin Infect Dis. 2025 Apr 17:ciaf184. doi: 10.1093/cid/ciaf184. Online ahead of print.

Authors

Shantelle Claassen-Weitz¹, Yao Xia^{2

3}, Luke Hannan⁴, Sugnet Gardner-Lubbe⁵, Kilaza S Mwaikono^{6

7}, Stephanie Harris Mounaud⁸, William C Nierman⁹, Lesley Workman^{10

11}, Felix S Dube^{11

12}, Samantha Africa¹, Fadheela Patel¹, Veronica Allen¹, Lemese Ah Tow Edries¹, Heather J Zar^{9

10

11}, Mark P Nicol^{1

2}

Affiliations

¹ Division of Medical Microbiology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
² Marshall Centre, Division of Infection and Immunity, School of Biomedical Sciences, University of Western Australia, Perth, Australia.
³ Center for Artificial Intelligence and Machine Learning, School of Science, Edith Cowan University, Joondalup, Australia.
⁴ Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town, South Africa.
⁵ Department of Statistics and Actuarial Science, Faculty of Economic and Management Sciences, Stellenbosch University, Stellenbosch, South Africa.
⁶ Computational Biology Group and H3ABioNet, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa.
⁷ Department of Science and Laboratory Technology, Dar es Salaam Institute of Technology, Dar es Salaam, Tanzania.
⁸ J. Craig Venter Institute, Rockville, Maryland, USA.
⁹ Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, Cape Town, South Africa.
¹⁰ SAMRC Unit on Child & Adolescent Health, University of Cape Town, Cape Town, South Africa.
¹¹ Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
¹² Department of Molecular and Cell Biology, Faculty of Sciences, University of Cape Town, Cape Town, South Africa.

PMID: 40241660
DOI: 10.1093/cid/ciaf184

Abstract

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.

Keywords: 16S rRNA gene; Haemophilus; RSV; bacterial; infant; low- and middle-income country; lower respiratory tract infection; microbiota; nasopharyngeal; qPCR; viral.