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September 2002 “Whenever an epidemic of influenza passes through a community, there is a sharp peak of deaths from various causes among the aged. Any elderly person rendered frail by physical disability is likely to succumb to an attack of influenza. This was heavily underlined during the 1951 influenza outbreak in Great Britain. In Liverpool the epidemic passed like an angel of death amongst the old. During the peak week there were more deaths than in the worst week of the 1918-19 pandemic. An investigation of the saving of life that might be effected by appropriate immunization of the aged against influenza would seem to be a very worthwhile project.” These words were written in 1953 by Sir Macfarlane Burnet. Now half a century later, how far along are we in the “very worthwhile project” that he so warmly recommended? One of the first efforts in that direction happened to be the first scientific paper that I ever wrote, then a fledgling EIS officer assigned to the Influenza Surveillance Unit at the CDC. The paper represented a characterization of the excess mortality associated with the “Asian” influenza epidemics of 1957-58 and 1960. My co-authors were two senior statisticians at CDC, and one of my favorite mentors, Alex Langmuir, painstakingly led me through six or seven different revisions of the manuscript before he put his stamp of approval on it. It was a necessary, albeit demanding, learning experience! Old-timers will recall that the Asian influenza pandemic caused an early wave of influenza in the fall of 1957, followed by a wholly unanticipated second wave in the winter and spring months of 1958. All was quiet during the 1958-59 season, but a major outbreak again occurred during the 1959-60 season. Using standard mortality data, and estimating excess mortality by the methods then in use at the CDC, we determined that these three “waves” of Asian influenza resulted in 86,000 excess deaths, two-thirds of which occurred in individuals 65 or older. Underlying chronic disease significantly increased the risk of death, and the major conditions were determined to be cardiovascular-renal disease, certain bronchopulmonary diseases and diabetes mellitus. Other conditions that seemingly enhanced the risk of dying during the influenza epidemic included rheumatic heart disease and pregnancy.
Our report became the foundation of recommendations for use of influenza vaccine in the United States in the 1960s, and these have remained essentially unchanged for the last 40 years. They have been polished and focused more clearly over the years by further studies, to be sure, but the basic thrust of the recommendations has remained unchanged. We had to point out in that report, however, that we could only “infer” that influenza immunization of these high-risk populations would reduce the toll of excess mortality; there was no data to prove it. That has changed, and in very substantial ways. Since 1980, a broad body of evidence has emerged suggesting that influenza vaccine is effective in reducing hospitalization and mortality in the institutionalized elderly. Data further suggest that it is efficacious and cost-effective in healthy elderly, in the elderly with chronic high-risk underlying conditions and that it is efficacious and cost-effective in healthy working adults. Put another way, there is now evidence to substantiate essentially all of the recommendations for use of influenza vaccine made by the ACIP and the ACP-ASIM. Just within the last two months, several more reports have appeared that should satisfy even the most skeptical minds. Lee et. al. (Ann Intern Med. 2002;137:225-231) carried out an economic analysis of influenza vaccination and antiviral treatment in healthy working adults and found that any strategy that included influenza vaccination was cost-effective. The several antiviral treatments available were cost-effective as well, although they pointed out that comparative trials would be needed to determine the optimal treatment strategy. Nichols and Goodman reported (Vaccine. 2002;20:S21-S24) on the cost-effectiveness of influenza vaccine in healthy elderly people between 65 and 74 years of age, as studied in the large HMO in the Minneapolis/St. Paul area over six consecutive influenza seasons in the 1990s; vaccination was associated with a 36% decrease in hospitalization for influenza or pneumonia and a 40% reduction in death. All vaccination scenarios were cost-effective. Hak and co-workers reported (Clin Infect Dis. 2002:35;370-377) on the influence of high-risk medical conditions on the effectiveness of influenza vaccination among the elderly in three large managed-care populations during two epidemic years. Vaccination was associated with a 48% reduction in hospitalization or death in the first year and a 31% reduction in the second year. Furthermore, the absolute risk reduction was 2.4-4.7-fold higher among those with high-risk conditions as compared with healthy elderly. In year one, there was a good match between the vaccine strain of influenza H3N2; in year two, the first appearance of the A/Sydney H3N2 virus, the match was clearly less than optimal, although there was still substantial protection. Thus, the “project” recommended by Sir Macfarlane Burnet could confidently be considered accomplished, but full implementation of the findings remains an elusive goal. In an editorial that accompanied the report by Hak et al, Greg Poland asks, “If you could halve the mortality rate, would you do it?” and wonders what in the world is taking us so long to achieve near universal influenza immunization of the elderly (Clin Infect Dis. 2002:35;378-380). (See related story: “CDC will again recommend tiered influenza vaccine delivery”) “Systems” approaches are always cited as one way to achieve higher rates of immunization in offices and clinics; the use of standing orders in hospitals and chronic care facilities is another. Vaccine availability in a timely fashion must be assured. Medicare reimbursement for influenza immunization must be addressed and should meet the cost; it is wholly counterproductive for the federal government to recommend immunization of the elderly out of one side of its mouth and out of the other side tell physicians that they won’t pay the full cost, and therefore, you will pay for it. The live-attenuated influenza vaccine is still pending before the FDA; it seems unlikely now that this product will be available during the coming season; when available, however, its use in children and in adults will be widespread because of its ease of administration. Poland concluded his comments by answering his own question: “Now is the time to get it right”! We’re getting there, although we surely could move faster. For more information: |
