Last Updated

14 Dec 2002

Source: USA Today, July 31, 2002.

U.S. readies offensive against smallpox threat

By Anita Manning, USA TODAY

In Texas, volunteers are rolling up their sleeves for science, letting themselves be immunized with smallpox vaccine that has been sitting in lab freezers for 40 years. At the National Institutes of Health in Maryland, researchers are planning to test old stocks of smallpox vaccine on children ages 2 to 5. More studies are underway to test a new vaccine being made as fast as possible under a contract with the U.S. government.

The Sept. 11 terrorist attacks revealed a vulnerability in national defense made more apparent weeks later with the discovery of anthrax-laced letters that shut down post offices and office buildings on the East Coast. Suddenly, the threat of bioterrorism was real.

Now, federal health officials, while stressing there is no hint of an increased threat, are accelerating research and pushing for a plan to protect Americans from bioterrorism. The greatest fear is smallpox.

Clinical trials will tell scientists whether the nation's supplies of smallpox vaccine, both new and old, are safe and effective. But the question on many minds is, who will be vaccinated and when?

Those answers are expected in a matter of weeks from the Department of Health and Human Services, where physicians and analysts are weighing the science, politics and sheer logistics of a plan to use a relatively dangerous vaccine on lots of people to protect against a disease that no one has seen in decades.

'Ring vaccination'

A panel of vaccine experts, the Advisory Committee on Immunization Practices (ACIP), is recommending that, unless there is an imminent threat or actual release of smallpox, the following are the only people who ought to receive vaccine:

• Smallpox response teams trained to investigate the first cases, should there be any. Each state is to assemble at least one team as part of local, state and national bioterrorism planning.

• Smallpox medical teams at hospitals that are to be designated by bioterrorism and public health authorities as smallpox isolation and care facilities.

In the event of a single case of smallpox, the patient would be isolated. Anyone he or she had been near -- other passengers on an airplane or everyone who attended the same football game, for example -- would be vaccinated. Then, anyone who had close contact with those people also would be vaccinated. The plan, which was used to eradicate smallpox more than 20 years ago, is called "ring vaccination," because ever-widening circles of immunity are put in place to contain the infection.

The ACIP's recommendation involves immunizing responder teams and staff at selected U.S. hospitals -- perhaps as many as 20,000. But much wider vaccination is being considered in scenarios that would include half a million people or more.

Smallpox, caused by the variola virus, once circulated widely in the world. It causes high fever, headache, backache and pustules in the mouth and over the face and arms, spreading to the trunk and legs. Before smallpox was eradicated, 30% of those infected died of the airborne disease, but there were some rarer forms that were nearly always fatal.

The last case to occur naturally was in 1977 in Somalia, and the World Health Organization declared smallpox eradicated in 1980. The only official stocks of the virus are in labs in Russia and at the Centers for Disease Control and Prevention in Atlanta. But scientists have feared for years that unofficial stores have been secretly stockpiled for nefarious purposes.

Routine childhood vaccination in the USA stopped in 1971, while vaccination of military personnel was phased out in 1989 and 1990. Others who have continued to be vaccinated are laboratory scientists who have conducted research on viruses in the same family as variola, called Orthopoxviruses, and health care workers involved in clinical trials of the vaccine.

No one knows whether people vaccinated a generation ago are still immune, although some experts believe that vaccination may offer some protection for as long as 20 or 30 years.

That's one of the questions to be answered by an upcoming study by the National Institutes of Health. Volunteers who were vaccinated years ago as children will be revaccinated to see whether there is a "take," judged by development of a sore and a scab at the puncture site. No reaction could indicate that immunity remains from the earlier vaccine.

Federal officials insist there is no new threat of a smallpox attack, but there has been a great urgency to get a plan approved. Fueling arguments for more wide-scale vaccination are predictions, based on mathematical models, that a multi-city attack could result in thousands of deaths and financial chaos.

Last month, Douglas Holtz-Eakin, chief economist at the White House Council of Economic Advisers, presented a doomsday scenario suggesting that, in the worst case, a smallpox attack could cause death and illness, shut down transportation and commerce, send the gross domestic product plunging 90%, and cost $177 billion per week.

"Economic first-responders play an important role when the economic costs of a smallpox attack are considered," he said. That could include vaccinating truck drivers, airline pilots, railroad employees, even warehouse workers and retail grocery clerks, he said.

In fact, Teamsters spokesman Rob Black says the union has discussed the possibility of vaccinating truck drivers for smallpox.

"Teamster truck drivers cross our country every day. If these workers have fears of smallpox, if there is an incident of bioterrorism, to have these Teamster members not transporting the goods that keep our country going could obviously have a very bad effect on our economy," he says.

While the Teamsters aren't lobbying for vaccination, he says, they have "weighed in" on it with HHS. "With more than 350,000 truckers we represent, we would certainly support having our members vaccinated," he says, "assuming that all of the medical hurdles were worked out."

Those "medical hurdles" are giving many people pause and present much of the argument for moderate use of the vaccine before any outbreak, says Julie Gerberding, director of the CDC.

The smallpox vaccine contains a live virus called vaccinia, a far less dangerous cousin of the smallpox virus. For people with healthy immune systems, the vaccinia virus prompts a protective immune response, but it can cause severe illness in those with weak immune systems or those who have had eczema. And for up to two weeks, newly vaccinated people can pass the vaccinia virus along to others.

"When there are cases of smallpox, the benefits of immunization outweigh the risks, but in a situation where we do not have smallpox cases, we have to be more thoughtful about it," Gerberding says.

For more than a month, the CDC, part of Health and Human Services, has been receiving comments in response to the ACIP proposal on its Web site, www.cdc .gov. The ACIP's goal was to come up with a plan that protects the people at highest risk in a smallpox attack without causing needless harm from a vaccine that can have serious side effects, especially when introduced into a society with a large number of immune-compromised people, she says.

"We've heard from a variety of groups," Gerberding says. "Often, we're finding that initially people are quite enthusiastic about vaccination, but as they hear about the hazards of the vaccine," the enthusiasm wanes.

Millions of doses of vaccine

Current U.S. supplies include 15.4 million doses of powdered Dryvax vaccine, made before 1982 by Wyeth, and about 80 million doses of liquid frozen vaccine produced in the 1960s and recently donated to the government by Aventis Pasteur. Both were produced under manufacturing methods no longer allowed. In the past year, the federal government has contracted with an English vaccine maker, Acambis, to produce an additional 209 million doses of smallpox vaccine. That vaccine likely will be purer than the older vaccine, but whether it is less likely to cause side effects is not known.

"We don't expect that will be the case," says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. "It's still the (live) virus, and it's likely a lot of the viral components are causing the reaction, not necessarily any contamination" from old production methods.

No smallpox vaccine is approved by the Food and Drug Administration, though in an outbreak, vaccines would be used. Any use of them before an emergency requires specific procedures, including review of the process for vaccination and follow-up by a special board, appointment of a clinical investigator at each clinic and informed consent of each patient.

FDA approval of vaccine isn't likely until the end of 2003, says CDC's Harold Margolis, and procedures for "large-scale vaccination in the half-million range or higher aren't in place at this point."