December 25, 2001

THE DOCTOR'S WORLD
In Offering Anthrax Vaccine, Officials Admit to Unknowns
By LAWRENCE K. ALTMAN, M.D.

Thousands of postal employees and workers on Capitol Hill who took antibiotics because they were exposed to anthrax two months ago now face a difficult new medical decision: whether to take an anthrax vaccine to forestall the slim and theoretical possibility that they may still develop the disease. And the advice they are getting from federal health officials ÷ consult your doctor and decide for yourself ÷ is less helpful than many workers would like.

In defending themselves against growing criticism for not making a firm recommendation, health officials last week were forced to do what they rarely do ÷ confess ignorance about the risks of a disease and its treatment options. It was the latest acknowledgment that government officials had been overconfident in saying they were well prepared for a bioterrorist attack.

For example, on Sept. 21, a few days before the first cases in the outbreak of the deliberate spread of anthrax, Tommy G. Thompson, the health and human services secretary, confidently said on CBS's "60 Minutes," "We're prepared to take care of any contingency, any consequence that develops or any kind of bioterrorism attack."

Now, Mr. Thompson and his experts are improvising ÷ offering as therapy a vaccine that his department had not considered even a month ago. Yet before then, the Capitol physician, Dr. John F. Eisold, had told federal agencies that he would use the vaccine to treat workers exposed on the Hill.

Of the three options Mr. Thompson offered the Capitol Hill and postal workers, only one involved vaccine:

¦Stop antibiotics after 60 days ÷ the previously recommended dosing schedule for anthrax exposure ÷ and then be alert to any possible anthrax symptoms.

¦Extend antibiotic therapy for another 40 days to cover the possibility, shown in animal studies, that anthrax spores may remain in the lungs for more than 60 days.

¦Take the additional antibiotics and the vaccine, in hopes it can build immunity in people who have already been exposed to anthrax, something that is not scientifically proven.

Mr. Thompson did not explain the lack of a fourth option ÷ vaccine alone ÷ or why the 100-day option had not been raised earlier.

Because the vaccine has never been used to prevent anthrax after people have been exposed to spores, its effectiveness in such circumstances is unknown and it is classified as experimental. The Centers for Disease Control and Prevention had to receive permission from the Food and Drug Administration to test this use of the vaccine. Recipients must sign a five-page form that explains the experimental nature of the use and states that they should not consider the vaccine a treatment for anthrax.

Short-term protection from the anthrax vaccine requires three injections over four weeks, and a small number of workers received their first shot late last week.

The vaccine is provided free, but the workers and their health insurance companies will be expected to pay for any medical harm from the vaccine.

Given the uncertainties about the anthrax risk and the risks and benefits of the vaccine, people offered the vaccine looked to medical experts for advice.

In the paternalistic days of yore, these experts might have made recommendations, which would probably have been accepted without question.

Dr. Donald A. Henderson, who as director of the Office of Public Health Preparedness is Mr. Thompson's chief adviser on bioterrorism, said his agency chose not to convene "a group of graybeards to sit in a room behind closed doors and come up with a very firm recommendation."

In this age of consumerism, many more patients want to make decisions about their health ÷ assuming they will have the information they need to do so. And medicine has reluctantly had to acknowledge that it does not have all the information, particularly for rare diseases like anthrax in humans.

Apparently reflecting that cultural transformation, Dr. Henderson said, "We chose to try to be fully open with just what we know, and what we don't know, and to share it with you, just where we come out."

C.D.C. officials now acknowledge there were serious flaws in their efforts to communicate important information about anthrax to health workers and the public. The problems continue. On Friday, the agency scurried to explain the options in separate telecasts with practicing doctors and postal workers.

Many patients want advice from their doctors and public health officials before choosing their own therapies. They often ask the doctors what they would do in the same situation.

But anthrax is rare, and even experts in infectious diseases find that the best they can do is provide educated guesses.

Doctors also rely on recommendations from health officials and published articles. But in the case of the anthrax vaccine, some articles that were used in arriving at the options are in journals published several decades ago and are not readily available to most doctors.

In the uncertainty of medical practice, doctors balance the risks of not treating against those from prescribing drugs, vaccines and other therapies.

In the case of anthrax, if workers do not take antibiotics beyond 60 days, with or without a vaccine, they face a small theoretical risk that they could still get the disease. But taking either antibiotics or the vaccine also poses risks. And the F.D.A. has not approved the use of any antibiotic for longer than 60 days for anthrax.

Antibiotics can cause problems ranging from upset stomachs to more serious allergic reactions and damage to the kidneys and liver. An unknown percentage of workers have stopped antibiotics before the 60-day period because of such adverse effects.

One who did was Deborah Willhite, a senior vice president of the Postal Service. She said she stopped taking antibiotics after 30 days because they irritated her stomach and continuing "was not worth it" because of the threat of "projectile vomiting throughout Washington."

Also, prolonged antibiotic use creates indirect risks to the community at large by promoting resistance of microbes to the drugs.

The vaccine may also carry risks of side effects.

Health officials have said that in the earlier stages of the outbreak some postal workers, many of whom are black, were reluctant to take antibiotics because of a misperception that they were being used as human guinea pigs to test the drugs' effectiveness against anthrax.

The issue was sensitive because of memories of the infamous Tuskegee study on syphilis from 1932 to 1972, which was paid for by the government and supervised in part by the C.D.C. Black men who were being followed in the study to determine the natural course of syphilis were not given the option of receiving penicillin after it was marketed to treat the late stages of the disease.

Health officials now fear that the Tuskegee story may keep some workers from taking the anthrax vaccine.

About a month ago, the C.D.C. requested permission from the Food and Drug Administration to study the new use of the vaccine, previously used to prevent anthrax among veterinarians and more than half a million military personnel.

The option of offering anthrax vaccine to exposed workers "wasn't one that sprang to mind then," said Dr. Jeffrey P. Koplan, the C.D.C. director.

But Dr. Eisold, the Capitol physician, said that in preparing for an anthrax attack, he had decided to vaccinate workers who had been exposed to spores. Dr. Eisold said he had discussed such plans at a meeting at the Central Intelligence Agency with a number of federal agencies that he did not name. Dr. Eisold declined to answer questions.

Earlier this month, the F.D.A. allowed the disease centers to vaccinate workers after exposure to spores. The C.D.C. bought 220,000 doses of anthrax vaccine from the military. On Dec. 15, the disease centers hastily convened a forum at the National Academy of Sciences in Washington to review information about anthrax vaccine and its possible use in exposed workers.

At the forum, Dr. Larry Siegel, the deputy director of the District of Columbia Health Department, said he would not recommend use of the vaccine to workers who were not at great risk of inhalation anthrax. Postal workers are a diverse group, and many of them are skeptical about advice they received from federal health officials in the past, Dr. Siegel said.

After conferring with his health department, Mayor Anthony A. Williams of Washington recommended against the vaccine for postal workers who may have been exposed, saying the 60-day course of antibiotics seemed to provide sufficient protection. No one who has taken the 60- day course of drugs in the recent outbreak has developed anthrax.