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    Monday, May 20, 2002

    A Pox on All Those Poxes

    A couple of readers e-mailed me about my previous post on smallpox vaccination. One correctly pointed out that if universal smallpox vaccination were offered, those who couldn’t be immunized would be protected by herd immunity. This is most certainly true. Another brought up the possibility of genetically redesigned smallpox that would be resistant to the vaccine. That, I think is less likely given the large size of the smallpox virus and the cross-immunity of the vaccine for several types of pox viruses. I thought the smallpox vaccine issue, however, deserved more attention.


    First, some historical perspective, straight from the horse’s mouths:

    On the disease:

    The havoc of the plague had been far more rapid: but the plague had visited our shores only once or twice within living memory; and the small pox was always present, filling the church-yards with corpses, tormenting with constant fears all whom it had not yet stricken, leaving on those whose lives it spared the hideous traces of its power, turning the babe into a changeling at which the mother shuddered, and making the eyes and cheeks of the betrothed maiden objects of horror to the lover.
    -Macaulay, Thomas Babington. History of England, chapter XX. London; 1848

    On innoculation and vaccination:

    The small pox, so fatal and so general amongst us, is here rendered entirely harmless by the invention of ingrafting, which is the term they give it. There is a set of old women who make it their business to perform the operation every autumn….The old woman comes with a nutshell full of the matter of the best sort of smallpox, and asks what veins you please to have opened. She immediately rips open that you offer to her with a large needle…and puts into the vein as much venom as can lie upon the head of her needle, and after binds up the little wound with a hollow bit of shell.
    -Montagu, Mary Wortley. Letter to Sara Chiswell, 1717. [Reprinted in Letters of Lady Mary Wortley Montagu, letter 31. 1779.]

    Medicine has never before produced any single improvement of such utility. You have erased from the calendar of human afflictions one of its greatest.
    -Thomas Jefferson, letter to Edward Jenner, 1801.

    Smallpox and smallpox vaccine. The greatest scourge of mankind and the greatest medical intervention to ever be introduced. Smallpox, with its thirty percent mortality rate, is the only infectious disease to have been completely eradicated from nature, and now it only exists (we hope) in laboratories in the United States and Siberia. Last week, the World Health Organization voted not to destroy those laboratory stocks. We'll never know all the politics behind that decision, but they claim that it was to allow further research into better vaccines and better treatment of smallpox. Destroying the last remaining virus stockpiles would, of course, render the need for vaccination and treatment needless. Needless, that is, unless they have good reason to think that somewhere, someone else has some smallpox virus that they plan to use for evil ends. If the latter is the case, then the CDC should stop dithering and debating and offer the vaccine to the public, for surely it won't be matter of "if" they use it, but of "when".

    When the CDC developed its current recommendation of quarantine and “ring vaccination” in the event of a smallpox bioterrorist attack, there was not enough vaccine available to vaccinate everyone in the country. Ring vaccination refers to the policy of vaccinating all exposed people , all contacts of exposed people, and all contacts of those contacts to try to contain the infection. It is, to say the least, logistically difficult. Given the limited vaccine supply, it was the best that could be offered. But now, we know we have other options. Last month, researchers announced that diluted vaccine can confer as much protection as the traditional dose. They calculated that using diluted vaccine could potentially increase the known available useable store of vaccine from 15 million doses to 150 million doses or more. At around the same time, Aventis, the maker of smallpox vaccine, found some 90 million doses in one of their warehouses. With dilution, that stock could be stretched to 900 million doses, four times the number needed to vaccinate the entire US population. The company has donated it to the United States, but so far no one has offered universal vaccination to its citizens.

    The smallpox vaccine actually isn’t made from the smallpox virus at all, but from the cowpox virus, vaccinia. (Thus the word “vaccine.”) Like the smallpox virus, the cowpox virus is a very large and complex viral molecule. It’s very close in structure to the smallpox virus; close enough to fool the body’s immune system into thinking cowpox and smallpox are the same virus, but different enough not to have the same lethality, or even to naturally infect people. The vaccine is what is called an “attenuated vaccine”, which means that it consists of live virus grown over and over in animal cells until it loses its potency without losing its ability to induce immunity. In a way, this is an advantage to us as we prepare to defend against those who would manipulate such things to cause us harm. Because the vaccine is a large virus molecule, produced in a cell culture, it’s difficult to guess what part of it would need manipulating to make the smallpox virus capable of escaping the immune system, while maintaining its virulence and lethality. I’m not saying that it couldn’t be done, only that it would be extremely difficult and unlikely.

    The fact that it is a live virus also means that there are more side effects from being vaccinated. A successful vaccine causes a local reaction and scarring at the site of innoculation. It also can cause fever and malaise. Because it is administered by scratching the virus into the skin, the virus can also be picked up and transferred to other parts of the body easily. For example, scratch the site of the injection then rub your eye, and you could get a cowpox infection in your eye. It can also result in a diffuse cowpox rash that is annoying but not fatal.

    The vaccine is not without some serious side effects. Because it is a live virus vaccine it cannot be given to those who have inadequate immune systems, (HIV infection, chemotherapy for cancer, certain arthritis drugs, long term steroid use, and pregnancy). It also is not recommended for people with atopic dermatitis or eczema. For some reason they are prone to a widespread skin involvement by the vaccinia virus. These same people are also at risk for complications if exposed to people who have been immunized. They would, however, also benefit from widespread public immunization in that they would be less likely to come into contact with a natural case of smallpox, which would certainly be fatal for them.

    Although the rate of side effects with smallpox vaccine is higher than we have become accustomed to with our modern immunizations, the incidence of severe complications is still extremely low, especially when compared to the thirty percent death rate from natural smallpox infection. The two most serious adverse reactions are encephalitis and progressive vaccinia, both of which can result in death. Encephalitis occurs when the cowpox virus infects the brain. It happens in roughly 12 out of one million people who are vaccinated for the first time, and in two out of one million who are vaccinated for a second time. Of those who are unfortunate enough to get this, 15% to 25% die, and another 25% have neurological deficits. Progressive vaccinia occurs when the vaccinia virus causes a serious local reaction at the site of the innoculation. The skin and muscle die, and the reaction can spread, and be potentially fatal. It occurs at a rate of 1 to 2 per one million first time recipients of the vaccine, and 6 to 7 per one million repeat vaccine recipients. It seems to be limited to people with defective cellular immunity, a condition that is not always recognized and is entirely different from the other usual immune deficiencies.

    Overall, the CDC estimates that there would be about one death per one million first-time vaccine recipients, and one death per four million people receiving the vaccine for the second time. That means that if we assume the highest fatality rate, we could expect about 290 deaths nationwide if every man, woman, and child in the United States were vaccinated. The actual number would probably be lower since those with contraindications would be excluded from getting the vaccine, and a significant number of us would have the lower mortality rate of second time recipients. Compare that to the fatality rate of having smallpox. Thirty out of every one hundred infected people die. From a general population standpoint, if a city is struck with a smallpox epidemic, and its citizens aren’t vaccinated, we can expect to lose five percent of the population. That would be 5,000 people in a city of 100,000. Expand that to several large cities and the loss would be devastating.

    The CDC says it expects to have 286 million doses of vaccine available by the end of the year. That’s still enough to vaccinate the US population, but by far less than could be available with the use of dilution. It also says it is debating a revision of its smallpox vaccination guidelines. They’re going to hold public forums to get our input, then discuss it among themselves again.They won’t reach a decision on recommendations until sometime in June. Meanwhile, the rest of us are kept out here at risk. Given the tenor of the times, it would be in everyone's best interest to speed the process. It would be far better for them to handle smallpox like the public health risk that it is. Educate the public on the risks of both the disease and the vaccine, and let each individual decide whether or not to be vaccinated. It’s the least we deserve.

    Clarification: My wording wasn't clear in the paragraph about smallpox mortality. The death rate is 30% in people who are actually infected. Not everyone in a city with a smallpox contagion is going to catch it, so the overall mortality for a population center would be less than that. In any given population that undergoes an epidemic of smallpox, the best guess is that the overall mortality of that population would be about 5%.
     

    posted by Sydney on 5/20/2002 07:09:00 AM 0 comments

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