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New Insights: Pandemic and Non-Pandemic Influenza
Abstract & Commentary
By Joseph F. John, Jr., MD, FACP, FIDSA, FSHEA, Associate Chief of Staff for Education, Ralph H. Johnson Veterans Administration Medical Center; Professor of Medicine, Medical University of South Carolina, Charleston, SC, is Associate Editor for Infectious Disease Alert.
Dr. John is a consultant for Cubist, Genzyme, and bioMerieux and is on the speaker's bureau for Cubist, GSK, Merck, Bayer, and Wyeth.
Sources: Murata Y, et al. Pulmonary complications of interpandemic influenza in hospitalized adults. J Infect Dis 2007; 195:1029-1037.
Morens DM, Fauci AS. The 1918 influenza pandemic: insights for the 21st Century. J Infect Dis 2007; 195:1018-1028.
Rizzo C, et al. Trends for influenza-related deaths during pandemic and epidemic seasons, Italy, 1969-2001. Emerg Infect Dis 2007;13(5):694-699.
"Today, nearly a century after the event, mysteries surrounding the 1981 influenza pandemic remain largely unexplained." David M.Morens & Antohon S. Fauci--2007
Why do people die with influenza? three new articles seemingly disparate relate to this age-old question. Consider first the complications of influenza in most routine years, those without pandemic disease. Murata, Walsh and Falsey from Rochester General Hospital right in a historic hotbed for influenza study, have done an in depth study of severe influenza — severe enough to cause hospitalization and pulmonary complications. Using careful means to diagnose influenza A, from 1999-2003, what they call interpandemic years, they studied 193 patients admitted to the hospital. The mean age of the cohort was 75, 55% female, mostly white individuals. Over three-fourth had received influenza vaccine. During the study, both H3N2 and H1N1 influenza A strains were circulating. H3N2 was most likely to cause hospitalization. Most patients (81%) had underlying cardiovascular disease. No patient had HIV/AIDS.
Acute radiologic disease was present in 101 subjects. Most of these had atelectasis versus infiltrates in the lower bases. About 10% had positive blood cultures. Sputum when positive for grew Streptococcus pneumoniae (3), Hemophilus pneumoniae(1), Staphylococcus aureus (4), Moraxella catarrhalis (3) and Gram-negative rods(5).
When radiologic findings of acute versus no acute disease were compared with regard to demographic and clinical characteristics, acute disease patients were likely to have (univariate analysis) more days of illness before admission and frailty and to have (multivariate analysis) cardiovascular disease. Patients with non- acute disease were more likely to have wheezing on examination. Patients with non-acute disease were more likely to have received steroids but there was no difference between the groups with regard to antibiotic or antiviral use, nor to the need for ICU admission (about 10%).
Eleven patients died mostly with severe underlying pulmonary or cardiac disease. Three of the deaths occurred in the non-acute group. Four died of respiratory failure.
In a study by Rizzo et al, the focus was excess deaths in Italy associated with Influenza. For the 32 influenza seasons studied Influenza caused an estimated 57,243 deaths with an excess mortality averaging 15/100,000. Some years there was no excess mortality. Older age was responsible for most influenza-related deaths during epidemic seasons. In the 1969-1970 pandemic season, H3N2-associated deaths were spread across all age groups. Interestingly, the overall number of excess deaths during the pandemic year was 1-9 times higher in Italy than in other European, North American and Asian countries.
These data from these 2 original studies are useful to understand the morbidity and mortality of acute influenza primarily during non pandemic years. Excess mortality during routine years, however, does not approach that during pandemic seasons. Why does pandemic influenza kill so readily? To answer that question the Director of the National Institutes for Allergy and Infectious Diseases, Anthony Fauci, and his colleague David Morens have written a perspective on the 1918 pandemic, the great influenza (also see John Barry's book The Great Influenza for a gripping account of those years). They note that Taubenberger and colleagues sequenced the entire 8-segment genome of the 1918 virus (see Nature 2005;437:889-93) using the RNA actually recovered from the lungs of those early victims. That virus evolved not by gene reassortment that is the great threat with the current H5N1 avian strain but by a process known as genome adaption, a new mechanism of generating novel viruses.
Morens and Fauci make some interesting points in their perspective.
Together these articles paint a vivid picture of influenza. Pandemics may only be predictable to the extent that they are NOT predictable. During non-pandemic years people do die at an excess rate but mostly due to underlying cardiac and pulmonary disease. Vaccines may not be highly protective in all adults, even to the degree that about 10% of infected, vaccinated octogenarians will be admitted to hospital. Recovering bacteria to incriminate a microbial etiology in causing radiologic disease is not routine, but culture of blood and sputum, in the opinion of most infectious diseases physicians, is still of likely utility.
There have been volumes written already about the dire threat of pandemic influenza. From the current review by Morens and Fauci, however, it is clear that we can not predict when the next pandemic will occur, its severity or its pattern. Multiple influenza viruses already circulate and cause disease yearly, and influenza B continues to cause episodic disease. Current influenza A strains are more likely to be resistant to first-line antivirals and we are probably too dependent on newer anti-influenza drugs like oseltamivir.
Recent table-top exercises and mock outbreaks have both shown that our capacity even in well equipped cities pales in relation to the number of affected individuals that may present during the initial phase of a pandemic. Nevertheless, we have to continue to rely on public health insights to prepare for pandemic disease, including pandemics that may be the result of new agents or bioterror. We must mobilize better for the assault and not fall prey to Michael Osterholm's premonition that after the fact we will not regret "how well government, business and public health leaders prepared the world for the catastrophe when they had clear warning." (Osterholm T. Foreign Affairs 2005; 84:24-37).