Experts have estimated that the next influenza pandemic could cause as many as 200,000 deaths and 750,000 hospitalizations in the United States. In addition, tens of millions of other victims might require outpatient treatment. The economic cost – from the increased public health and medical requirements alone – could approach $200 billion.
At present, there are only three weapons that can be used against pandemic influenza: pharmaceuticals; non-pharmacological public health interventions; and vaccinations. The latter would likely be the most widely used “weapon,” but also would be the weapon of last resort, if only because the current state of vaccine technology, combined with the costly and complex logistical processes involved, makes it very unlikely that – in the near term, at least – vaccinations will become the “silver bullet” that would fell this formidable threat.
Identifying the pandemic virus is the first obstacle that has to be overcome. Although the current medical focus is on the H5N1 Avian Influenza virus, a different avian virus could be the real culprit. Influenza viruses are very unreliable replicators, and routinely mutate in totally unexpected ways. Moreover, the transformation from a relatively benign virus to a pandemic one is not likely to be an instantaneous transition. This means that vaccines developed from viruses isolated early in a pandemic may be less effective than vaccines developed from viruses collected at a later stage. Unfortunately, delay also is an enemy. It can be taken for granted, in fact, that any delay, no matter what the cause, will translate into more deaths and additional disabilities.
Fatal Delays and the Swine Flu Precedent
The most important steps in preparing a harvested virus for vaccine development involve first, purifying the virus, and then incorporating the modifications needed to best induce the protective immune response. Newer technologies have allowed both of these processes to be streamlined to some extent, but each might still require a minimum of two or three weeks, and perhaps longer. Again, though: More delay equals more deaths.
Ensuring the safety of vaccines is both necessary and prudent – but produces additional delays. Here it should be remembered that the fallout several years ago from the possible linkage between the Swine Flu vaccine and a neurological disease known as Guillain-Barre Syndrome essentially ensured that a vaccine that has not been fully tested will not be permitted on the market in this country.
The current lack of manufacturing capacity also will cause delays. There simply are not enough factories National and state plans have to address – in advance – how the initial allotments of vaccine will be distributed; at the national level, this may require some type of geographic triage. – not just in the United States, but anywhere in the world – that have the ability to mass-produce the vaccines likely to be needed in a true pandemic. Moreover, most existing plants are outside the United States – in a number of other countries, each of which will have its own needs, priorities, and political as well as medical agendas.
In addition, even if more plants could be built, there still would be issues of substrate – i.e., the growth medium – that would have to be addressed. Conventional vaccine production uses embryonated eggs – one egg for each dose of vaccine. To produce 100 million doses of killed influenza virus vaccine would require, therefore, 100 million embryonated eggs.
In previous pandemics, two doses may have been required to provide the protection needed. Again, however, advances are possible. Moreover, recent research into adjuvant (augmentation) therapy looks promising, and the use of such adjuvants may significantly stretch the supply of vaccines that would or could be produced in a reasonable period of time.
It should be recognized, though, that production is not an all-or-nothing phenomenon. Once mass production begins, supplies will undoubtedly increase, but what is available on “Day One” of a pandemic will be substantially less than the quantity likely to be available three months later.
Political Factors and Other Complications
There is an important political dimension to the problem that also will come into play. National and state plans have to address – in advance – how the initial allotments of vaccine will be distributed and dispensed. At the national level, this may require some type of geographic triage. In addition, numerous difficult and emotional as well as political questions would be raised. One example: Is New York City, with its crucial economic role, of greater value than Houston, or Los Angeles?
However, because it is likely that most regions of the country will be affected at least to some degree by the time an effective vaccine becomes widely available, perhaps distribution should be based on the demographics of the disease, with areas that have more susceptible populations receiving larger quantities of the vaccine – but how the susceptibility factor could or would be measured is far from clear.
National vaccine distribution plans will likely have a cascading effect. One common assumption is that first responders and healthcare workers should and will receive first priority. An argument could be made, however, that those groups would have only intermittent exposure to the disease, and also would have greater access to personal protective equipment.
There remain many other unanswered questions. One example: Should states be allowed to determine their own priorities? At present there seems to be only one certainty: An open dialogue with the public leading to the answers to these and many other questions sure to be asked would not only be advisable but also would be most beneficial if the questions are asked, and answered, well before the start of a pandemic.
Dr. Jerry Mothershead is the Physician Advisor to the Medical Readiness and Response Group of Battelle Memorial Institute. An emergency medicine physician, he also is adjunct faculty at the Uniformed Services University of the Health Sciences in Bethesda, Md. A graduate of the U. S. Naval Academy, Dr. Mothershead served on active duty in the U.S. Navy in a broad spectrum of clinical, operational, and management positions for over 28 years, and has served in an advisory capacity to numerous local, state, and federal agencies in the fields of antiterrorism, disaster preparedness, and consequence management.