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Inactivated Influenza Vaccines for Prevention of Community-Acquired Pneumonia: The Limits of Using Nonspecific Outcomes in Vaccine Effectiveness Studies

Ferdinands, Jill M.; Gargiullo, Paul; Haber, Michael; Moore, Matthew; Belongia, Edward A.; Shay, David K.

doi: 10.1097/EDE.0b013e3182953065
Infectious Diseases

Background: One to 4 million cases of community-acquired pneumonia (CAP) occur annually in the United States, resulting in 600,000 hospitalizations and 45,000 deaths. Influenza infection facilitates secondary bacterial infections, and influenza vaccination may prevent CAP directly by preventing influenza pneumonia or indirectly by preventing secondary bacterial CAP.

Methods: We investigated how influenza vaccination could affect incidence of CAP using deterministic probability and stochastic simulation models. The models included likely influential factors, including vaccine effectiveness (VE) against influenza, rates of influenza in the unvaccinated, vaccination coverage, and the relative risk (RR) of pneumonia, given influenza infection. To estimate effectiveness of influenza vaccine against CAP, we assumed mean VE against influenza of 55% and vaccine coverage of 38%.

Results: Given our baseline parameters, influenza vaccine had a mean effectiveness against CAP of 7% (95% confidence interval = 0–25%). Effectiveness of influenza vaccine against CAP increased as its effectiveness against influenza increased, as RR of pneumonia after influenza infection increased, and as rates of influenza among unvaccinated persons increased.

Conclusions: No matter how effective vaccine may be in preventing influenza infection, it is only modestly effective at preventing CAP. Because of the large annual burden of CAP, a vaccine that is only moderately effective in preventing influenza infection has the potential to prevent a substantial number of CAP cases. This modeling approach may be useful for planning influenza vaccine-probe studies and evaluating the effectiveness of other interventions targeted against infections that manifest in nonspecific outcomes.

Supplemental Digital Content is available in the text.

From the aNational Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA; bBattelle Memorial Institute, Atlanta, GA; cDepartment of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA; and dMarshfield Clinic Research Foundation, Marshfield, WI.

E.A.B. receives research support from MedImmune. Funding was provided to E.A.B. by the US Centers for Disease Control and Prevention. No other authors declare conflicts of interest. Internal funds from the Centers for Disease Control and Prevention supported this work.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article ( This content is not peer-reviewed or copy-edited; it is the sole responsibility of the author.

Correspondence: Jill M. Ferdinands, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, MS A20, Atlanta, GA 30333. E-mail:

Received April 4, 2012

Accepted October 23, 2012

Copyright © 2013 Wolters Kluwer Health, Inc. All rights reserved.