The Evaluation of the Effectiveness of the Trivalent Influenza Vaccine for the Prevention of Hospitalizations Due to Influenza Pneumonia; Results from the Rapid Empiric Treatment with Oseltamivir Study (RETOS) Emily Pacholski MPHc, Joannis Baez Gonzalez MD, Lisandra Rodriguez Hernandez MD, Diana Otero MD, Katherin Rivera Contreras MD, Murali Kolikonda MD, Robert Kelley PhD, Julio Ramirez MD, Ruth Carrico PhD, Timothy Wiemken PhD Division of Infectious Diseases, University of Louisville ABSTRACT MATERIALS AND METHODS, CONTINUED RESULTS, CONTINUED REFERENCES BACKGROUND: Due to frequent antigenic drift of influenza viruses, the influenza vaccine needs to be updated and the population re-vaccinated every year (2). However, there is controversy over the effectiveness of the trivalent influenza vaccine. Accordingly, the objective of this study was to evaluate the effectiveness of the trivalent influenza vaccine for the prevention of hospitalization due to influenza pneumonia. METHODS: This was a secondary analysis of the RETOS study database. Influenza as an etiology of pneumonia was defined by PCR. Influenza vaccination status for the current season was obtained through a questionnaire upon enrollment into the RETOS study. Vaccine effectiveness was evaluated using a logistic regression model, where the vaccine effectiveness (VE) was defined as one minus the odds ratio. RESULTS: A total of 769 hospitalized patients with pneumonia were included in this analysis. A total of 510 (66%) patients received the influenza vaccine for the current season prior to hospitalization. The overall VE was not statistically significant (VE: 23%, 95% CI: -18% - 49%, P=0.224). CONCLUSIONS: This study indicates that the trivalent influenza vaccine does not prevent hospitalization due to influenza pneumonia. In the upcoming season, the quadrivalent influenza vaccine will become available. Accordingly, its effectiveness to prevent hospitalizations due to influenza pneumonia should be evaluated and compared to the trivalent influenza vaccine. INTRODUCTION Study Design and Population This was a secondary analysis of the Rapid Empiric Treatment with Oseltamivir Study (RETOS, database. Consecutive patients with Lower Respiratory Tract Infections (LRTI) admitted to 4 hospitals from December April 2011, and 8 hospitals from December April 2011, were enrolled. Nasopharyngeal and oropharyngeal swabs were obtained from each patient. Clinical information was collected from medical records. Study Definitions  LRTI was defined as a one sign of acute infection (e.g. subjective/objective fever and/or chills) and 2 new respiratory symptoms (e.g. cough, shortness of breath, change in sputum production).  LRTI was stratified as community-acquired pneumonia (CAP), acute exacerbation of chronic obstructive pulmonary disease (AECOPD), or acute bronchitis.  CAP was defined as the presence of a new pulmonary infiltrate on chest radiograph at the time of hospitalization that was associated with at least one of the following three criteria: 1.New or increased cough 2.An abnormal temperature ( 37˚C) 3.Leukocytosis, leukopenia, or left shift  Influenza was defined by a positive reverse transcriptase polymerase chain reaction Laboratory Methods  Nasopharyngeal swabs: tested for influenza and other respiratory viruses using the Luminex xTAG respiratory viral panel PCR.  Oropharyngeal swabs: tested for atypical pathogens via real- time PCR.  Blood cultures and urine antigen testing for S. pneumoniae and Legionella pneumophila serogroup 1 were performed as part of the standard of care work-up. Statistically Analysis A logistic regression model was used to calculate the odds ratio and associated confidence intervals of hospitalized patients with CAP given the trivalent influenza vaccine versus those without the trivalent influenza vaccine. The vaccine effectiveness was calculated as 1 minus the odds ratio. R v was used for the analysis. RESULTS A total of 769 hospitalized patients with CAP were included in this analysis. Baseline patient characteristics and outcomes based on receiving the trivalent influenza vaccine can be seen in Table 1. Out of these patients, 66% (510 patients) received the influenza vaccine for the current season prior to hospitalization. Out of these 510 patients, 68 were diagnosed with influenza CAP. Figure 1 summarizes the results of patients who received and did not receive the trivalent Influenza vaccine, and the number of corresponding influenza pneumonia cases from those groups. The overall vaccine effectiveness was not statistically significant (VE: 23%, 95% CI: -18%-49%, P=0.224). Table 2 summarizes these obtained statistical results as well as the corresponding odds ratio. Table 1: Characteristics and outcomes of CAP patients vaccinated and not vaccinated with the trivalent influenza vaccine Table 2: Effectiveness of the trivalent influenza vaccine for prevention of hospitalization due to influenza CAP CONCLUSIONS  This study indicates that the trivalent influenza vaccine is not effective for the prevention of hospitalization due to influenza pneumonia.  This ineffectiveness could have been due to a poor immune response to the influenza vaccine or an imperfect match between the vaccine and circulating influenza strain.  The quadrivalent influenza vaccine will become available in this upcoming season, accordingly its effectiveness should be evaluated 1. Ferdinands JM, Gargiullo P, Haber M, Moore M, Belongia EA, Shay DK. Inactivated influenza vaccines for prevention of community-acquired pneumonia: the limits of using nonspecific outcomes in vaccine effectiveness studies. Epidemiology Jul;24(4): Osterholm MT, Nicholas SK, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infectious Diseases. 2012;12: Thompson MG et al. Updated Estimates of Mortality Associated with Seasonal Influenza through the Influenza Season. MMWR 2010; 59(33): According to the CDC’s Morbidity and Mortality Weekly Report (MMWR), influenza-associated deaths have generally been increasing. For instance, the season carried about 3,000 deaths and increased in the influenza season to about 49,000 deaths (3). While the burden of influenza associated deaths varies from year to year, community-acquired pneumonia (CAP) is a well-described complication of influenza and aids in the increased number of cases and hospitalizations (1). There is a vaccine available to prevent influenza infection, but there is significant controversy regarding the effectiveness of this trivalent influenza vaccine. Thus, the objective of this study was to evaluate the effectiveness of the trivalent influenza vaccine for the prevention of hospitalizations due to influenza CAP. MATERIALS AND METHODS Figure 1: Study pathway and number of cases