HEALTH & SCIENCE

Smallpox vaccine hazards dictate cautious approach

With the greater number of immunocompromised people today, there are more public health concerns with immunization policy than in past years.

By Susan J. Landers, AMNews staff. Aug. 19, 2002. Additional information

Washington -- Physicians receiving or administering the smallpox vaccine as part of a federal plan to counter bioterrorism should be aware that the recipient of the vaccine isn't the only one at risk for complications.

"There is a significant possibility of person-to-person transmission," noted Scott D. Deitchman, MD, MPH, chair of the AMA's bioterrorism subcommittee and a member of the AMA Council on Scientific Affairs.

The risk is substantial, as the vaccination site will harbor a large amount of live virus capable of replicating, he said. The risk subsides when the site scabs over, two weeks or more after immunization.

The vaccine itself is probably the "least safe human vaccine," said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at a July 25 briefing on smallpox vaccination sponsored by the Alliance for Health Reform.

Complications can result in death for vaccine recipients as well as for those they come into contact with.

Physicians will need to counsel patients about the risk of spreading the vaccinia virus used in the smallpox vaccine either to other members of their households or to other parts of their own bodies, said Dr. Deitchman.

They will have to warn against scratching the very itchy site, keeping the site covered with a dressing, washing hands after changing the dressing and putting the used dressing in a sealed plastic bag, he said. Additional difficulties could arise when trying to protect small children from complications.

Risks posed by the vaccine have led physician groups, including the AMA and the Infectious Diseases Society of America, to advise against a broad vaccination campaign before there is any evidence that the disease has made an appearance in the country.

The federal government was debating at press time just how many people should be vaccinated against the disease, which has been eradicated in its natural state but is now feared as a possible agent of bioterrorism. A decision is expected in the weeks ahead.

One plan recommended by the Centers for Disease Control and Prevention's vaccine advisory committee calls for the inoculation of the physicians and nurses who would be expected to care for smallpox victims with additional inoculation of close contacts of an infected person should the need arise.

The efforts could begin with the immunization of between 10,000 and 20,000 health care personnel as early as this fall.

The federal government is now developing a document that will be sent to about 100,000 physicians and nurses explaining the vaccine and its problems, said D. A. Henderson, MD, principal science adviser to Health and Human Services Secretary Tommy Thompson.

Dr. Henderson, who played a large role in the eradication of the disease in the 1970s, also spoke at the July 25 briefing.

A different population

The risks posed by the vaccine are serious and include tissue necrosis and encephalitis. One complication, progressive vaccinia, can result when the virus continues to multiply throughout the body, said Samuel Katz, MD, professor of pediatrics at Duke University, Durham, N.C. Dr. Katz is also the Infectious Diseases Society of America's liaison to the CDC's vaccine advisory committee.

When the smallpox vaccine was discontinued in 1972, little was said about its complications, said Dr. Henderson. "And today's population has a very different perception of risk than did the population back in the 1960s," he said.

"Now there is a feeling that every vaccine should be totally safe, although none is," he noted. "And we aren't willing to accept very much of a risk."

Using data from the mid-1960s, the CDC calculated a death rate of one per 1 million people vaccinated. But for today's vastly different population the death rate would likely be higher.

Now there are many more people with compromised immune systems, and it is this group that is at greatest risk for serious complications such as progressive vaccinia. "People whose immune systems are suppressed, especially if it involves cell-mediated immunity, may not be able to contain this virus appropriately," said Dr. Katz.

The spread of AIDS, the increase in organ transplantation and the thousands of people with cancer who are on immunosuppressant drugs all will make a big difference, noted Dr. Katz.

Today also, for reasons no one seems to understand, there are many more children who have eczema than there were in the 1960s.

The skin condition places the children at greater vulnerability from another rampant infection, eczema vaccinata, which they can contract either from the vaccine itself or from someone recently vaccinated.

Fortunately, there is a medication, vaccinia immune globulin, available to treat these children. But unfortunately, there aren't many doses of VIG currently available. VIG can only be derived from those recently vaccinated for smallpox and, except for a small number of smallpox researchers and subjects in clinical trials, no one falls into this category.

The United States halted smallpox vaccinations in 1972, and the last known case of naturally transmitted smallpox occurred in Somalia in 1977.

However, the United States is gearing up to produce more VIG, and new federal contracts with pharmaceutical companies were in the works in late July, Dr. Fauci reported.

The search is also on for a safer form of the vaccine, perhaps one that uses killed virus, rather than a live, multiplying virus, but its development will likely take several years, said Dr. Katz.

One problem is the lack of an appropriate animal model. "Smallpox is a human infection, and there is no experimental animal that mimics the human infection," he noted. More exciting perhaps is the ongoing work on antiviral compounds to treat patients with smallpox or patients who have bad reactions to the vaccine. One drug, cidofovir, has been found to be effective in mice against mouse pox. But would it be effective in man? We don't know yet, said Dr. Katz.

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As the federal government debates the formulation of a smallpox vaccination policy, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, identified the following factors:

• The vaccine, although efficacious, is the least safe human vaccine and is unlicensed.
• Vaccine will soon be available in sufficient quantities to vaccinate the entire U.S. population if needed, generally providing full immunity for at least three to five years. Level of immunity beyond that time is uncertain.
• Postexposure smallpox vaccination within four to five days may prevent or ameliorate the disease.

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Article, "Smallpox as a Biological Weapon: Medical and Public Health Management," JAMA, June 9, 1999 (vol. 281, issue 22) (http://jama.ama-assn.org/issues/v281n22/ffull/jst90000.html)

Article, "Smallpox: Clinical and Epidemiologic Features," Emerging Infectious Diseases, July-August 1999 (vol. 5, issue 4) (http://www.cdc.gov/ncidod/EID/vol5no4/henderson.htm)

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Copyright 2002 American Medical Association. All rights reserved.