Seasonal Influenza Vaccine and Increased Risk of Pandemic A/H1N1‐Related Illness. Part 2

The primary focus of analyses presented here is estimation of the effect of receipt of the 2008–2009 TIV on risk of developing ILI during a documented pH1N1 outbreak. Symptom experience since 1 April 2009 was elicited. ILI was defined at the analysis stage as a report of fever and cough plus 1 of the following symptoms during that period: headache, general aches, sore throat, or prostration. Corresponding control subjects were participants who had been symptomatic in the period since 1 April 2009 who did not meet the ILI case definition or who were asymptomatic. Participants aged 6 months as of 31 December 2008 were excluded at the analysis stage, because they would not have been eligible to receive the vaccine.

On the basis of results of serologic tests, the sensitivity, specificity, and positive and negative predictive values for the ILI case definition were explored. Odds ratios (ORs) for seasonal influenza vaccine effect (2008–2009 and 2007–2008) on ILI were computed via logistic regression analysis, with adjustment for combinations of age, chronic conditions, Aboriginal status, and household density (calculated as the number of household members/number of sleeping rooms). We also accounted for within‐household clustering while assessing vaccine effect by using generalized‐linear‐mixed models (GLMMs) for binary outcomes, adjusting for the same covariates [6]. Because surveillance data suggested that children experienced higher pH1N1 attack rates and that older adults were at lower risk [7, 8], we explored vaccine effects stratified for participants aged <20 years and <50 years. We also explored the effect of TIV receipt on pH1N1 infection defined by HI and/or MN seropositive status.

  • Human Subject Consideration
  • The initial telephone survey was conducted as a public health–mandated outbreak investigation, with verbal consent provided at interview. The serologic component was reviewed and approved by the Research Ethics Board of the University of British Columbia, and individual written consent was obtained for blood sample collection and analysis.

    Respiratory specimen surveillance.Respiratory virus testing by the BC Centre for Disease Control for the local community included 30 specimens collected during the period 29 April through 5 June 2009. pH1N1 was confirmed in 14 of these 30 specimens by reverse‐transcription polymerase chain reaction (RT‐PCR). Other respiratory viruses detected in the local community during that period included coronavirus (in 2 specimens) and rhinovirus or enterovirus (in 2 specimens).

    Of the 30 specimens submitted, 9 were from households of the affected elementary school that also participated in the telephone survey; pH1N1 was detected in 6 (67%) of the 9 specimens from survey participants. Five (56%) of these 9 specimens were from patients living on a reserve; pH1N1 was detected in 4 (80%) of the 5 specimens. Of note, surveillance data indicated the last detection of seasonal influenza (A/H3N2) in the local health area was in February 2009.

    Serologic test results.In total, 135 households with at least 1 member with ILI identified during the community survey were invited to participate in the serologic study. Ultimately, 42 households contributed serologic specimens, resulting in 106 individual serum samples available for analysis, including 58 (54%) from households associated with the affected elementary school (n=45) or on a reserve (n=29). Details of the sero‐survey participants are shown in Table A1 in the Appendix.

    In total, 44 (42%) of the 106 serologic survey participants reported ILI during the study period. Of the 106 serum samples, 28 (26%) had HI titers to pH1N1 40 (denoting seropositivity), and of these, 22 (79%) were from persons who had reported ILI. Among the 106 serologic survey participants overall, there was strong correlation between log‐transformed HI and MN titers (ρ=0.92). Of the 28 specimens with an HI titer 40, all but 3 had MN titers 80 and exceeding HI. Of the 3 participants whose specimens yielded MN titers less than the HI titers, none reported ILI.