title: The Effects of Live Attenuated Influenza Vaccine on Nasopharyngeal Bacteria in Healthy 2 to 4 Year Olds. A Randomized Controlled Trial.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: 1 School of Cellular and Molecular Medicine and.
authors.forename: Valtyr
authors.initials: V
authors.lastname: Thors
authors.affiliation: 2 School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom; and.
authors.forename: Hannah
authors.initials: H
authors.lastname: Christensen
authors.affiliation: 1 School of Cellular and Molecular Medicine and.
authors.forename: Begonia
authors.initials: B
authors.lastname: Morales-Aza
authors.affiliation: 3 Public Health Laboratory Bristol, Public Health England, Bristol, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Vipond
authors.affiliation: 3 Public Health Laboratory Bristol, Public Health England, Bristol, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Muir
authors.affiliation: 1 School of Cellular and Molecular Medicine and.
authors.forename: Adam
authors.initials: A
authors.lastname: Finn
mesh_terms: D002353:Carrier State / Q000382:microbiology; D002675:Child, Preschool; D005260:Female; D006193:Haemophilus influenzae / Q000187:drug effects*; D006801:Humans; D007252:Influenza Vaccines / Q000494:pharmacology*; D007251:Influenza, Human / Q000517:prevention & control; D008297:Male; D001936:Moraxella catarrhalis / Q000187:drug effects*; D009305:Nasopharynx / Q000382:microbiology*; D016133:Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000187:drug effects*; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D014613:Vaccines, Attenuated / Q000494:pharmacology
chemical_list: D007252:Influenza Vaccines; D014613:Vaccines, Attenuated
keywords: bacterial colonization; bacterial density; children; live attenuated influenza vaccine