When watching the news in recent weeks and months, you might think that the world has become inordinately fascinated with sick chickens. Our concern is not of potential Thanksgiving turkey shortages, but instead one of human health. Although many people have died from avian influenza, these deaths are not in and of themselves responsible for the widespread fear and international attention. Rather, we fear that these deaths are the harbingers of the world-wide influenza pandemic that is apparently long overdue. Is this fear justified, or are scientists just crying wolf? Is there actually fire behind the pandemic smoke? Does the media have a role in manipulating (or justly inciting) our fears?

Although many of us consider ‘getting the flu’ a minor inconvenience – at worst a week in bed and time off work – even common strains of influenza can be lethal in high-risk populations. Young children and the elderly are particularly susceptible, and often the cause of death is actually associated bacterial pneumonia [1]. Influenza pandemics occur when a new strain emerges that is different enough from previous strains that our immune systems cannot recognize it, rendering us defenseless. Another criteria for pandemic status is that the virus must be easily transmissible, and potent enough that very few viral particles are required for an infection to occur. The flu we try to avoid every winter is optimized for human-human transmission. It invades the respiratory tract, and becomes aerosolized, enabling it to spread with every sneeze and cough. At present, avian influenza (H5N1) is not easily transmissible, and only people with large amounts of direct contact with diseased poultry have become infected.

The pathogenicity, or lethality, of influenza strains is largely determined by the expression of two different molecules, hemaglutinin and neuraminidase [1, 2]. A successful infection requires that the virus must first enter a cell and then use the host cell machinery to reproduce itself. Hemaglutinin and neuraminidase are required for optimal function of the influenza virus, and are used in the entry and subsequent reproduction of the virus. The name given to the current strain of avian influenza, H5N1, identifies which type of hemaglutinin (H5) and neuraminidase (N1) are used by this particular strain.

New strains of influenza form through two major mechanisms: Antigenic drift and antigenic shift. Antigenic drift occurs through accumulating mutations and environmental influences, and these gradual changes are why we get the flu every couple of years: changes accumulate until the body can no longer recognize the strain and consequently, it loses its ability to defend itself. This gradual drift is also why influenza vaccines have to be re-formulated every year. Antigenic shift is a result of the recombination of genetic material from different strains, and can occur whenever an animal or human is infected with two different strains at once. When two strains of virus meet and re-combine, the resultant virus is different from either parent strain similar to the way that a baby is different from its parents. This process can result in rapid, dramatic shifts in the characteristics and pathogenicity of a virus.

The most lethal influenza pandemic known to date, the 1918 Spanish Flu, resulted from the adaptation of solely avian strains [2, 3]. However, we know that certain species, such as pigs, can be dually infected with both an avian and a human strain of influenza at the same time [2, 3]. This increases the likelihood of a recombination event resulting in a sufficiently altered virus that our immune system can no longer recognize. Similarly, a human concurrently infected with a human and an avian influenza could facilitate the generation of a new strain, potentially serving as an incubator for a ‘new and improved’ virus. For example, the close contact that exists between humans and animals in rural settings (such as backyard farms), and live markets, represents the ideal breeding ground for new strains of influenza.

Public health officials and researchers are particularly concerned about the H5N1 strain of avian influenza for several reasons, first and foremost being its lethality in humans. The United Nations’ World Health Organization (WHO) cites a 50% mortality rate among patients developing severe respiratory symptoms, though this number is likely to be biased due to sample size and incomplete reporting [4]. H5N1 also mutates quickly and easily recombines with human strains of influenza [4]. The viral particles are excreted from infected bird feces for at least 10 days, thus providing ample opportunity for contact. Additionally, anecdotal reports from outbreaks suggested that common housecats could become lethally infected with avian influenza, and experimental infection has confirmed this [5]. Felines became infected after eating infected birds, and excreted infectious viral particles in their feces [5]. Thus people may be exposed to H5N1 through handling infected poultry, but potentially also via their family pet, although this is entirely conjecture at present.

So, what can be done? Vaccines are only protective against the influenza strain used to develop them, or a closely related strain. Most vaccines contain pieces of dead virus, or occasionally a live but attenuated (or weakened) virus that is no longer infectious. Research is currently underway to develop vaccines against the H5N1 strain; however, if it undergoes a major mutation it will take at least four months to develop an effective vaccine. Additionally, the WHO has suggested vaccinating humans in contact with poultry against the current human influenza strains, in an effort to prevent dual infection. Certain anti-viral medications, such as Tami-flu, may be effective provided the virus is not given opportunity to mutate into a resistant form; though, drug resistance could develop rapidly, should it be used inappropriately. Certainly the rapid culling and quarantine of infected birds has been beneficial in prior outbreaks. Important to consider though, is that the rural setting of most at-risk areas may obstruct the prompt reporting and allow the spread of disease in domestic birds. The natural reservoir of avian influenza is in migratory wild birds, rendering attempts to vaccinate domestic birds nearly pointless and possibly dangerous, as it would force continued viral mutation and resistance. Nevertheless, vaccination has been approved and is planned for parts of the EU in response to the recent spread of H5N1-infected poultry.

With all of the “potential” danger touted by the media, one wonders if it is actually doing us a disservice – sensationalizing human deaths and promoting a doomsday scenario in pursuit of headlines. A cynic would observe that the manufacturers of anti-viral treatments obviously benefit from this media coverage, and would recommend purchasing company stock. The 1918 influenza pandemic was worsened by war-time conditions, such as trenches, that facilitated the spread of disease. In addition, modern antibiotics would certainly lessen the deaths due to influenza-associated pneumonia. Thus, it seems unlikely an influenza pandemic as deadly as that of 1918 will ever occur, although the possibility certainly exists. The SARS epidemic taught us that globalization is an enormous obstacle to containing highly infectious diseases. Perhaps we should be grateful that the “doomsday” media coverage is forcing the kind of public notice and political attention that will be needed to respond quickly should a true pandemic occur. At the very least, one would hope that modern medicine and some of the lessons learned from previous outbreaks would help to contain and manage a pandemic, and prevent a world-wide crisis.

References
1. de la Barrera, C.A. and G. Reyes-Teran, Influenza: forecast for a pandemic. Arch Med Res, 2005. 36(6): p. 628-36.
2. Belshe, R.B., The origins of pandemic influenza–lessons from the 1918 virus. N Engl J Med, 2005. 353(21): p. 2209-11.
3. Taubenberger, J.K., et al., Characterization of the 1918 influenza virus polymerase genes. Nature, 2005. 437(7060): p. 889-93.
4. World Health Organization. Avian Influenza Fact Sheet. 2004.
5. Rimmelzwaan, G.F., et al., Influenza A Virus (H5N1) Infection in Cats Causes Systemic Disease with Potential Novel Routes of Virus Spread within and between Hosts. Am J Pathol, 2006. 168(1): p. 176-83.