2008–2009 Influenza update: A better vaccine match

Last year, some people may have lost their faith in flu shots. The three antigens chosen for the vaccine in advance by the US Centers for Disease Control and Prevention (CDC) did not match very well the influenza strains that ultimately circulated in North America, and the overall protective efficacy of the vaccine was estimated at only 40%.

Nevertheless, vaccination remains the primary preventive measure for both epidemic and pandemic influenza, especially in view of a rising rate of resistance to the oral antiviral agent oseltamivir (Tamiflu).

In the 2008–2009 influenza season, we hope to do better. All three antigens contained in the 2008–2009 vaccine are new. Surveillance data from the Southern Hemisphere during the summer of 2008 show that this vaccine is expected to be a good match for the strains circulating in the Northern Hemisphere. And with 146 million doses expected to be manufactured this season by six companies—the largest number of doses ever manufactured in the United States—enough should be available for all.

GREAT STRIDES HAVE BEEN MADE, BUT FLU IS STILL A PROBLEM

We are making great strides against influenza. Over the last 50 years, the rate of influenzarelated deaths in the United States declined by 95%, from an average seasonal rate of 10.2 deaths per 100,000 population in the 1940s to 0.56 per 100,000 by the 1990s.¹

However, influenza still accounts for about 10% of patients admitted to intensive care units for acute respiratory failure during epidemics.²

Children and the elderly are still hit the hardest: infants age 0 through 23 months and adults age 65 years and older have the highest peak rates of pneumonia and influenza hospitalization and death.³ School-age children (5–18 years) have an indirect role in anticipating the risk to others and can learn to help avoid spreading the virus by washing their hands more, wearing masks, and adopting other hygienic measures.

In the 1918–1919 pandemic, most deaths were from secondary bacterial pneumonia, a fact that has implications for pandemic preparedness. ⁴ Currently, Staphylococcus aureus, particularly methicillin-resistant strains (MRSA), is an important cause of secondary bacterial pneumonia, with a high mortality rate.⁵

UPDATE ON DIAGNOSIS: PCR IS THE BEST TEST

In the hospital, it is important to identify patients who have influenza so that we can give them appropriate antiviral therapy and also protect other patients from getting the flu. Unfortunately, the sensitivity and positive predictive value of fever, cough, and other symptoms for the diagnosis of influenza in hospitalized patients are 40% or less.⁶

Real-time reverse transcriptase polymerase chain reaction (PCR), compared with direct fluorescent antigen detection or cell culture, has the highest sensitivity (98.7%) and specificity (100%) in both children⁷ and the elderly.⁸ Furthermore, cell culture is slow and therefore is not useful in clinical practice. Nasopharyngeal wash sampling appears impractical in nursing home residents, owing to their underlying disabilities, and nasopharyngeal swabs tested by PCR are equally sensitive. ⁸

However, improvements are needed in molecular detection and subtyping of influenza viruses.⁹ If a pandemic breaks out, we will need to identify the virus quickly to have enough time for preventive interventions. The US Food and Drug Administration has recently cleared a new test called the Human Virus Real-Time RT-PCR Detection and Characterization Panel to detect and differentiate between seasonal and novel influenza strains.¹⁰

UPDATE ON INFLUENZA VACCINE

New recommendations in 2008 by the CDC Advisory Committee on Immunization Practices¹¹ include annual vaccination for all children age 5 through 18 years, and either the trivalent inactivated vaccine (ie, the shot) or the live-attenuated vaccine (ie, the Flu-Mist intranasal spray) for healthy people age 2 through 49 years. The CDC recommendations are summarized at www.cdc.gov/flu/professionals/acip/index.htm.

Has the benefit of vaccination in adults been overestimated?

Jackson et al,¹² in an article published in August 2008, suggested that the effect of influenza vaccination on the risk of community-acquired pneumonia in immunocompetent elderly people during influenza season is less than previously estimated. However, some patients in this study who were classified as not having been vaccinated may have actually been vaccinated by other health care providers without notifying their primary care providers. Moreover, influenza infection may cause only a small proportion of cases of pneumonia in this population.

In another study, Eurich et al¹³ suggested that previous observational studies overestimated the benefit of influenza vaccination on reducing deaths in patients with pneumonia outside the flu season. Although they found the incidence of death to be 51% lower in vaccinated than in unvaccinated adults with community-acquired pneumonia (N = 1,813) admitted to six hospitals, they ascribed it to confounding factors, specifically socioeconomic and functional status. This phenomenon was previously called the “frailty bias” or the “healthy user effect.” However, this study included only patients hospitalized with pneumonia and did not include data on vaccine-induced immunity or the cause of pneumonia, and measures of the healthy user effect were rudimentary. In addition, only outcomes during hospitalization were included.

Most experts still believe that vaccination prevents 50% of influenza-related deaths (with a smaller effect on rates of all-cause mortality¹⁴), including deaths in very old people. ¹⁵ A recent review found no basis for the historic concern that the antibody response to the influenza vaccine in people age 60 and older declines more rapidly than in younger people and below seroprotective levels within 4 months of immunization.¹⁶

Nevertheless, discordance between antibody and T-cell responses to influenza vaccine does exist¹⁷ (ie, the vaccine can induce antibodies while not boosting the T-cell-specific response), and we should continue to seek new vaccines that are more effective.