The Avian Flu

I have posted a number of comments on Avian flu in past months. You can find them linked to my del.icio.us bookmarks. I think some summing up might be in order.

As of now, there seems to be a spreading epidemic of H5N1 flu among wild birds that is infecting domestic poultry in Asia and now Europe. Efforts to combat the spread of this disease in poultry have already cost billions of dollars.

There have been a relatively small number of cases reported in which humans have contracted the disease from birds. Many of these people have died, but so far it seems that it is difficult for the virus to travel from person to person.

On the other hand, the virus mutates rapidly, and the more birds are infected, and the more infected birds come in contact with people, the higher the risk of a strain developing that will be epidemic or pandemic in humans. This can occur either by mutations accumulating in the virus, or by reassortment of the viral genes in persons infected with both human and bird flu.

The threat from the H5N1 flu is that the current human population has not yet been exposed to a flu virus with these surface proteins, and so there is no immunity. There are other flu viruses out there that would be just as dangerous if they got loose in the human population. Flu viruses survive in animal host populations, and there don't seem to be any other flus out there as poised to jump into man. Still, unless science and technology develop a great deal, that will happen eventually.

Flu is with us always, and the annual outbreak of the disease kills many people. Pandemics, caused by the unleashing of a new strain of the flu virus against which there is no immunity, occurs periodically. Of course, the pandemic requires both that the new virus evolves into something that is relatively easily transmitted from person to person, and viral strains differ in their virulance among those who catch the disease.

Three pandemics occurred in the 20th century, and the worst killed an estimated 50 to 100 million people in 1918. The situation could be worse today. Modern transportation would allow the virus to travel faster. Population densities are much greater, not only putting more people at risk, but increasing the contact rate between those infected and new victims. While the portion of people too poor to protect themselves has gone down, there are still billions of people below any reasonable poverty line. And there are now large numbers of people with weakened immune systems.

Of course, we might also be lucky. The next new virus might not be especially communicable or might not be especially virulent or lethal. There have been 10 pandemics in the last 300 years, and most have not been as serious as that of 1918.

A major pandemic would likely sweep the earth in two or three successive years, reaping havoc each time. Of course, the problem would not only be that many people would die, but also that huge numbers would be too sick to work for a while, and very large numbers would require medical attention. First line health workers tend to be most exposed to the disease, and high levels of illness among them would make the provision of health care more difficult. The social implications of billions of sick people, hundreds of millions seeking hospitalization, and tens of millions dead would be very large.

Fears of a pandemic of swine flu developed in 1976, and the United States embarked on an ambitious program to deal with the threat. Fortunately, the virus did not cause a major epidemic. Unfortunately, the program got out of hand, and large amounts of money were wasted, tens of millions of people were immunized against a disease that did not really ocnstitute such a threat, and there were many complications attributed to the unnecessary immunizations. Very well intentioned people lead the effort which went so far out of control.

Part of the problem is that there are big delays and uncertainties in mounting a program of this kind. The development of a new vaccine, the production of billions of doses of the vaccine, and the implementation of mass immunization campaigns all take time and money.

Still, experience suggests that there are many pitfalls in preparing for flu epidemics and pandemics. The only response is to put fully trained people hard to work on the problem, to encourage them to learn from the past, and to give them the resources they need.

The current situation seems to be complicated by the lack of suitable medical technology. There are only a few antiviral medicines developed to be effective against flu. Apparently the bird flu is resistant to two of these (perhaps because they have been used in poultry foods in Asia). Thus only Tamiflu is available to doctors to treat the disease in patients. Without Tamilflu, treatment is limited to dealing with symptoms or complications of the disease -- important, but not as cost-effective as preventing the disease in the first place, or curing it quickly when it occurs.

Tamiflu is a proprietary drug. While an Indian firm has announced it is going to go ahead and produce a generic version, there are no plans for the United States nor other developed nations to seek alternative sources. The company owning the IPR can produce only a limited amount of the drug.

For the United States, the current supply will not cover the 10 million front line health workers, much less the victims of a possible pandemic. European countries are somewhat better off, but they too will not have enough. The developing world is out in the cold. The U.S. government has ordered more Tamiflu, and Congress has passed legislation to pay for a stockpile, but it is back in the queue for delivery of the drug.

Vaccines would be great, and some progress has been made in developing a vaccine against H5N1 flu. That work will be useful, but until a pandemic strain actually emerges, it will probably not be possible to fully develop a vaccine against it.

Commecial ventures have not found vaccine production very profitable. Part of the problem seems to be the liability a vaccine maker faces from side effects of immunization. Part of the problem is perhaps that people are willing to pay more to deal with a disease that they have and are suffering from, than to protect against a disease that they might get in the future. In any case, it seems that firms may not have invested adequately in improving vaccine production technology. The production technology has not advanced as much in the last 50 years as one might have wished. New approaches are under development, but it is not clear that they will be perfected in time to prevent an bird flu pandemic.

It is estimated that it will take two doses of the new vaccine to provide protection against the new flu, when that flu occurs. It may be that the vaccine will not be 100 percent effective, so large numbers of people may have to be immunized to cut down on the spread of the disease. Thus, experts fear that hundreds of millions of doses might be needed to achieve herd immunity in the United States' human population. There seems no likelihood of those amounts of a vaccine being available in the next year or two. (Remember the flu vaccine shortfall last year.)

Therefore, in the United States, there is little likelihood that enough vaccine or medicine would be available to prevent an epidemic if the rest of the world suffers a pandemic. One therefore hopes that both Tamiflu and the vaccine (when it becomes available) would be allocated so as to do the most good.

There is little likelihood that a world pandemic, focused in poor countries, could be prevented if and when the feared virus does emerge. Neither the vaccine nor Tamilflu would seem likely to be available in sufficient quantities for that to happen. Nor would the public health systems in poor nations be up to the job. Still, WHO and the world public health community are working hard on the problem.

The United States government has been shown to be unprepared for 9/11 and for Katrina. It appears that the government has not made adequate preparations against a flu pandemic in recent years. The current Administration is now making very visible moves to prepare for a possible flu pandemic, perhaps alerted by its recent failures. President Bush met with industry leaders, an international meeting was held in the State Department, legislation was introduced to fund medical stockpiles, a draft pandemic flu plan is being dusted off and published, and Secretary Leavitt of HHS is traveling to Asian nations in the front line against this flu. Unfortuantely, key people in the Administration's line of control seem to have political rather than public health backgrounds.

The best that can be hoped is that proper preparations will made, but that the threatened pandemic does not occur this time. Unfortunately, the recent activities of this Administration may prove to be too little and too late. There is also, of course, a chance that the fear will outrun the reality of the threat -- that lots of money, time and effort will be wasted. Worse, the government may be seen as crying wolf, making it harder to generate proper concern in the future when new threats of pandemics arise, as they surely will.