The effects of live attenuated influenza vaccine on nasopharyngeal bacteria in healthy 2 to 4 year olds. a randomized controlled trial
Open accessAbstract
RATIONALE: Viral infections of the upper respiratory tract may influence the commensal nasopharyngeal bacteria. Changes in the bacterial niche could affect transmission dynamics. Attenuated vaccine viruses can be used to investigate this empirically in humans. OBJECTIVES: To study the effects of mild viral upper respiratory infections on nasopharyngeal bacterial colonization using live attenuated influenza vaccine (LAIV) as a surrogate. METHODS: We used trivalent LAIV to evaluate the effects of viral infection on bacterial carriage and density of Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, and Staphylococcus aureus. A total of 151 healthy children were randomized 1:1 to receive the vaccine starting either at recruitment (n = 74) or 28 days later (n = 77) in a stepped wedge fashion, allowing comparisons between recipients and nonrecipients as well as whole-group comparisons pre- and postvaccination. Bacterial carriage and density were determined using quantitative polymerase chain reaction assays. MEASUREMENTS AND MAIN RESULTS: A total of 151 children were recruited, 77 in the LAIV group and 74 in the control group. LAIV recipients (n = 63 analyzed) showed an apparent transient increase in H. influenzae carriage but no further significant differences in carriage prevalence of the four bacterial species compared with controls (n = 72 analyzed). S. pneumoniae density was substantially higher in vaccine recipients (16,687 vs. 1935 gene copies per milliliter) 28 days after the first dose (P < 0.001). Whole-group multivariable analysis (prevaccine, after one dose, and after two doses) also showed increases in density of other species and H. influenzae carriage prevalence. CONCLUSIONS: In the absence of any safety signals despite widespread use of the vaccine, these findings suggest that bacterial density, and thus transmission rates among children and to people in other age groups, may rise following attenuated influenza infections without associated clinical disease. LAIV could therefore be used as an experimental tool to elucidate the dynamics of transmission of nasopharyngeal bacteria.
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- Authors
- Thors, V., Christensen, H., Morales-Aza, B., Vipond, I., Muir, P., & Finn, A.
- Affiliations
- University of Bristol (GB)
- School of Cellular and Molecular Medicine and
- Public Health England (GB)
- Corresponding author
- Thors, Valtyr
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-06
- Volume
- 193
- Issue
- 12
- Pages
- 1401-1409
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- PMC
- PMC4910891
- OpenAlex
- W2229704027
- Cited by
- 44
- References
- 23
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 6 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 7 · 2018: 9 · 2017: 5 · 2016: 1
- FWCI
- 6.88
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion, other-oa)
- Explore Bristol Research (acceptedVersion, other-oa)
- Funders
- National Institute for Health Research Health Protection Research Unit
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Keywords
- live attenuated influenza vaccine, nasopharyngeal bacteria, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, bacterial carriage, bacterial density, upper respiratory viral infection, bacterial transmission, children, vaccine safety
- MeSH terms
- Moraxella catarrhalis, Carrier State, Child, Preschool, Female, Haemophilus influenzae, Humans, Influenza, Human, Influenza Vaccines, Male, Nasopharynx, Staphylococcus aureus, Streptococcus pneumoniae, Vaccines, Attenuated, Polymerase Chain Reaction
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