Avian influenza preparedness: the answer is always no

November 2005

“The answer is always no!” says the actor, David Spade, in a generally inane and annoying series of television ads extolling the virtues of Capital One credit cards.

That is the answer, too, to the seemingly unending series of articles in professional journals, titles of talks at professional meetings and television news segments dealing with the spread of avian influenza viruses.

Much of the news coverage, especially in the public media, seems more than a little unbalanced, and warns of the carnage to come if this virus picks up the ability to spread easily from person to person. It’s of little wonder that the public is being whipped into a state of near panic. It’s of little wonder, too, that there is a lot of stockpiling of oseltamivir going on. Even the president speaks of using the armed forces to enforce quarantine measures should confirmed cases occur in humans in a specific geographic area.

Against this background of public information and misinformation, where do we stand today? Outbreaks of avian influenza continue to occur in domestic birds, especially chickens, ducks and a few other species in Southeast Asia, particularly in Vietnam, Thailand, parts of China and Indonesia. Human cases continue to occur at a low level in those countries, and almost all of them are traceable to direct contact with chickens or ducks. There are still only one or two cases of possible human-to-human spread.

Spread to other areas

In the past three months, there has been a surprisingly rapid spread of the virus from Mongolia to eastern Russia, across the Ural Mountains to western Russia and now into the Middle East and Eastern Europe. It is theorized that this rapid spread has occurred on the wings of migratory birds. Even the United Kingdom has encountered the virus, in a shipment of exotic birds from the Far East. Most of the countries involved have made all the appropriate efforts to contain the virus within the immediate locations in which it has been identified. A major concern, however, is that it will spread easily to Africa, where it will be essentially uncontrollable. Of great interest is the fact that there have NOT been any recorded human cases in the dramatic spread through western Asia and Europe.

It seems only a matter of time until the virus arrives in the Americas. If it doesn’t occur this fall, it will likely occur during the spring bird migration in 2006. All the dire predictions notwithstanding, no one really knows whether H5N1 will be the next pandemic virus. It is certainly the most likely candidate we have seen in many years, and there is certainly reason for concern but not panic.

A number of influenza experts, who happen not to be on the national news circuit, are concerned that the threat of H5N1 virus has been greatly overexaggerated.

So, enough national whining and wringing of hands! What would it take to turn the answer into “yes, we are as prepared as we can be”?

What follows is surely an incomplete list, but it contains the major needs that occur to me, and likely most readers.

• Improved global influenza surveillance: This has already improved dramatically in the past 30 years, but there is always room for further improvement, particularly in less developed parts of the world.
• National pandemic influenza preparedness plan: Flesh out the existing plan down to the operational level. The current plan is a useful skeleton, but it now needs to be detailed, so that it is clear to all concerned.
• State emergency preparedness plans: Update current plans to include pandemic influenza preparedness. Each state should have such a plan, and it should be field tested in one or more mock drills to identify the inevitable problems. State emergency preparedness plans should include quarantine powers as well as the power to close schools, cancel public gatherings, close offices and virtually isolate a community, if needed. It seems to me that it would be vastly better to have these powers reside at the state level, than people wielded by the U.S. armed forces. Furthermore, if the origin of a pandemic in the United States was multicentric, as was the case in the United States in 1957, “quarantine” would be of little or no use. Social “distancing,” however, could at least slow down and possibly limit spread.
• Antiviral drugs: Virtually, the entire focus has been on oseltamivir (Tamiflu, Roche), and probably with good reason. Roche has now made the interesting corporate decision to stop exporting the drug for private use in the United States, unless influenza has been identified in a community. Private stockpiling has been and should continue to be discouraged. Zanamivir (Relenza, GlaxoSmithKline) has been relegated seemingly to the back burner, because it has not been approved for prophylaxis, only for treatment. Few people doubt, however, that zanamivir would be effective for prophylaxis; the requisite studies have simply not been done. Other improved neuraminidase inhibitors are under development, and should be brought along as quickly as possible. Needless to say, the present national stockpile of oseltamivir is woefully inadequate. The IDSA and the Society for Healthcare Epidemiology of America have recommended increasing the stockpile to a size sufficient to treat 25% to 40% of the population. I would agree, but it will take many years to reach such a goal.

Immunogenicity testing of currently available H5N1 vaccine, produced by Sanofi Pasteur, moves along at a snail’s pace. Although it proved immunogenic in test results announced several months ago, the results were not at all reassuring. Two separate doses of 90 µg were necessary to provide satisfactory antibody levels. Apparently H5 is simply not a very good immunogen, not at all comparable with, for example, H2. At a U.S. production capacity of 300 million doses of monovalent vaccine containing 15 µg of hemagglutinin, there will not be enough vaccine to immunize even 20% of the U.S. population, let alone export any vaccine to less developed nations. Furthermore, a two-dose schedule is simply not feasible when facing a threatened pandemic. The obvious answer is some antigen-sparing technique, likely including an adjuvant, that could sharply reduce the amount of antigen necessary for optimal immunogenicity.

For reasons I don’t understand, the NIAID is moving slowly, if at all, on the use of adjuvants, and the FDA is on record as stating that an adjuvanted vaccine would be a “new product,” and would therefore require full safety and efficacy field trials. That is effectively a death knell for adequate supplies of an effective vaccine should a pandemic occur anytime in the next several years. News on the vaccine front is not at all encouraging.

Will there be an H5N1 pandemic? No one knows of course, but so many “experts” are predicting one that it does make one wonder a bit. Influenza is, after all, always full of surprises.