Viruses Without Borders

Influenza is finally getting the respect that it deserves. Over the past several years, the scientific, public health and general public profile of this illness has been heightened by several, largely independent, developments. The decrease in number of acute care beds across Canada over the past decade, coupled with an aging population and our extraordinary success in extending the survival of patients with significant chronic illness, has eliminated any cushion in bed occupancy in the hospital system. The flexibility in bed availability to accommodate the predictable seasonal variation in bed demand is gone. Increased illness requiring hospitalization in the winter respiratory season, a large part of which is due to influenza, now pushes the acute health care system beyond capacity. In effect, influenza is a sentinel virus for acute health care capacity. The result is that, on a yearly basis, the press trumpets the Armageddon of emergency room collapse and medical bed deficits, and influenza is identified as the cause. This past winter, Canada-wide influenza activity maps, continually updated, appeared on the weather channel and in the pages of The Medical Post. The arrival of the neuraminidase inhibitors for influenza treatment (1) and the substantial pharmaceutical funding now available for promotion of these drugs created these ’flu maps. The limited efficacy of these new agents for the treatment of influenza can be regretted, and we can hope that therapeutic use will not interfere with a prophylactic role, where the drugs are likely to have a large impact. Although clinical trials and in vitro observations do not suggest resistance emergence is a major problem, widespread use in infected populations will certainly promote resistance. So the marketing of neuraminidase inhibitors also raises the influenza profile and, in fact, promotes a major change in practice by spreading the message that individuals who think that they have the ’flu should see their physician. The third item highlighting influenza received popular press several years ago, and continues to haunt infectious disease epidemiologists and public health officials. This, of course, is the outbreak of “chicken ’flu” in Hong Kong over the Christmas season of 1997 (2). An entirely new influenza virus, an H5N1 strain, not previously isolated in infected humans, emerged. The strain was acquired by exposure to infected chickens and did not transmit readily between humans. Infected individuals were young, with a mortality rate of 30%. The success of the influenza virus as a pathogen is, of course, largely due to its promiscuity in genetic reassortment (3). A reasonable assessment of the Hong Kong outbreak is that we were one genetic reassortment, allowing human-to-human transmission, from pandemic catastrophe. Fortunately, the aggressive, ‘no half measures’ approach of complete destruction of the chicken flocks of Hong Kong successfully limited this outbreak. Influenza outbreaks occur yearly in the winter in temperate climates. Because the virus continually modifies its antigenic structure, long term immunity following infection is elusive. Periodically, previously thought to occur every 10 years, pandemic influenza arises with the introduction of a substantially genetically altered strain that spreads rapidly through the nonimmune world population (2). We are overdue for the next pandemic. The chicken ’flu outbreak in Hong Kong has us looking back to the 1918 influenza pandemic, which caused tens of millions of deaths worldwide, played a major role in ending the first World War, and was characterized by high rates of illness and very high mortality in healthy young adults. Is this the future? Our understanding of what happened in 1918, and why, is incomplete, although expanding through current genetic technology. This virus emerged in the United States (Kansas, in fact) and was transported to Europe with troop movements of World War I. Thus, it is a variation of the observation that new influenza strains emerge from Asia. The extraordinary mortality in young, healthy individuals in the 1918 pandemic has not been adequately explained but is thought to represent unique virulence characteristics of that strain (4). New information elicited from DNA fragments retrieved from Alaskans who died in this epidemic and who were buried in permafrost may answer some of the remaining questions. Influenza primarily causes mortality through secondary bacterial infections in elderly individuals with comorbidities. However, primary influenza pneumonia is a well recognized, clinical presentation, which kills even young healthy people rapidly. We do not yet know whether new therapies will be effective in the treatment of the more severe manifestations at-