Effectiveness of Inactivated Influenza Vaccines in Preventing Influenza-Associated Deaths and Hospitalizations among Ontario Residents Aged ≥65 Years: Estimates with Generalized Linear Models Accounting for Healthy Vaccinee Effects

Influenza Division, United States Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
PLoS ONE (Impact Factor: 3.23). 10/2013; 8(10):e76318. DOI: 10.1371/journal.pone.0076318
Source: PubMed


Estimates of the effectiveness of influenza vaccines in older adults may be biased because of difficulties identifying and adjusting for confounders of the vaccine-outcome association. We estimated vaccine effectiveness for prevention of serious influenza complications among older persons by using methods to account for underlying differences in risk for these complications.
We conducted a retrospective cohort study among Ontario residents aged ≥65 years from September 1993 through September 2008. We linked weekly vaccination, hospitalization, and death records for 1.4 million community-dwelling persons aged ≥65 years. Vaccine effectiveness was estimated by comparing ratios of outcome rates during weeks of high versus low influenza activity (defined by viral surveillance data) among vaccinated and unvaccinated subjects by using log-linear regression models that accounted for temperature and time trends with natural spline functions. Effectiveness was estimated for three influenza-associated outcomes: all-cause deaths, deaths occurring within 30 days of pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations.
During weeks when 5% of respiratory specimens tested positive for influenza A, vaccine effectiveness among persons aged ≥65 years was 22% (95% confidence interval [CI], -6%-42%) for all influenza-associated deaths, 25% (95% CI, 13%-37%) for deaths occurring within 30 days after an influenza-associated pneumonia/influenza hospitalization, and 19% (95% CI, 4%-31%) for influenza-associated pneumonia/influenza hospitalizations. Because small proportions of deaths, deaths after pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations were associated with influenza virus circulation, we estimated that vaccination prevented 1.6%, 4.8%, and 4.1% of these outcomes, respectively.
By using confounding-reducing techniques with 15 years of provincial-level data including vaccination and health outcomes, we estimated that influenza vaccination prevented ∼4% of influenza-associated hospitalizations and deaths occurring after hospitalizations among older adults in Ontario.

Download full-text


Available from: Benjamin J Ridenhour, Dec 12, 2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A new vaccine, "Multimeric-001" (M-001) has been recently developed, containing conserved, common linear influenza epitopes that activate both cellular and humoral arms of the immune system against a wide variety of influenza A and B strains. Apart from its direct action, M-001 is an attractive candidate for priming immune responses to seasonal influenza vaccine for the elderly population. The current clinical study was designed to assess M-001's standalone and priming action in participants over 65 years old. Evaluation of standalone action is based on induction of cell mediated immunity (CMI), since M-001 alone does not induce hemagglutinin inhibition (HAI) antibodies.
    Vaccine 08/2014; 32(44). DOI:10.1016/j.vaccine.2014.08.031 · 3.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Influenza vaccination aims at reducing the incidence of serious disease, complications and death among those with the most risk of severe influenza disease. Influenza vaccine effectiveness (VE) through sentinel surveillance data from the PIDIRAC program (Daily Acute Respiratory Infection Surveillance of Catalonia) during 2010-2011, 2011-2012, and 2012-2013 influenza seasons, with three different predominant circulating influenza virus (IV) types [A(H1N1)pdm09, A(H3N2) and B, respectively] was assessed. The total number of sentinel samples with known vaccination background collected during the study period was 3173, 14.7% of which had received the corresponding seasonal influenza vaccine. 1117 samples (35.2%) were positive for IV. A retrospective negative case control design was used to assess vaccine effectiveness (VE) for the entire period and for each epidemic influenza season. An overall VE of 58.1% (95% CI:46.8-67) was obtained. Differences in VE according to epidemic season were observed, being highest for the 2012-2013 season with predominance of IV type B (69.7% ;95% CI:51.5-81) and for the 2010-2011 season, with predominance of the A(H1N1)pdm09 influenza virus strain (67.2% ;95%CI:49.5-78.8) and lowest for the 2011-2012 season with A(H3N2) subtype predominance (34.2% ;95%CI:4.5-54.6). Influenza vaccination prevents a substantial number of influenza-associated illnesses. Although vaccines with increased effectiveness are needed and the search for a universal vaccine that is not subject to genetic modifications might increase VE, nowadays only the efforts to increase vaccination rates of high-risk population and healthcare personnel let reduce the burden of influenza and its complications.
    Human Vaccines and Immunotherapeutics 08/2014; 11(1). DOI:10.4161/hv.36155 · 2.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purposes: To assess the accuracy of estimates using statistical databases of influenza-associated morbidity and mortality, and precisely measure influenza vaccine effectiveness. Principal results: Laboratory testing of influenza is incomplete. Death certificates under-report influenza. Statistical database models are used as an alternative to randomised controlled trials (RCTs) to assess influenza vaccine effectiveness. Evidence of the accuracy of influenza morbidity and mortality estimates was sought from: (1) Studies comparing statistical models. For four studies Poisson and ARIMA models produced higher estimates than Serfling, and Serfling higher than GLM. Which model is more accurate is unknown. (2) Studies controlling confounders. Fourteen studies mostly controlled one confounder (one controlled comorbidities), and limited control of confounders limits accuracy. Evidence for vaccine effectiveness was sought from: (1) Studies of regions with increasing vaccination rates. Of five studies two controlled for confounders and one found a positive vaccination effect. Three studies did not control confounders and two found no effect of vaccination. (2) Studies controlling multiple confounders. Of thirteen studies only two found a positive vaccine effect and no mortality differences between vaccinees and non-vaccinees in non-influenza seasons, showing confounders were controlled. Key problems are insufficient testing for influenza, using influenza-like illness, heterogeneity of seasonal and pandemic influenza, population aging, and incomplete confounder control (co-morbidities, frailty, vaccination history) and failure to demonstrate control of confounders by proving no mortality differences between vaccinees and non-vaccinees in non-influenza seasons. Major conclusions: Improving model accuracy requires proof of no mortality differences in pre-influenza periods between the vaccinated and non-vaccinated groups, and reduction in influenza morbidity and mortality in seasons with a good vaccine match, more virulent strains, in the younger elderly with less immune senescence, and specific outcomes (laboratory-confirmed outcomes, pneumonia deaths). Proving influenza vaccine effectiveness requires appropriately powered RCTs, testing participants with RT-PCR tests, and comprehensively monitoring morbidity and mortality.
    Vaccine 10/2014; 32(51). DOI:10.1016/j.vaccine.2014.08.090 · 3.62 Impact Factor
Show more