ACIP weighs public demand but comes out against mass smallpox vaccination

July 2002

ATLANTA — With the threat of a bioterrorist incident a real possibility for Americans, demand for smallpox vaccine is high. But the likelihood of significant adverse events makes universal vaccination a bad idea, according to the CDC.

The smallpox vaccine was highly effective in eradicating the disease and would still be used today if a smallpox case were detected. However, the vaccine is also one of the most dangerous vaccines ever used.

So when the Advisory Committee on Immunization Practices (ACIP) gathered to update its smallpox vaccine recommendations in June, the panel had to weigh public demand for the vaccine against the risk of adverse outcomes after vaccination.

The resulting recommendations, which limit the use of vaccine in pre-exposure scenarios to state and local smallpox response and smallpox health care teams under tight restrictions from the FDA, do not provide for mass pre-event vaccination. However, the recommendations allow latitude for state and local health departments to enact a response commensurate with need.

The recommendations will now be sent to the CDC and Department of Health and Human Services for final review before becoming policy. Under the plan, smallpox vaccine would only become available to the public if there was a wide scale smallpox attack and the CDC believed it could not contain the outbreak – a scenario the ACIP hopes never occurs.

Public demand

After Sept. 11th, bioterrorism experts began calling on the CDC and the government to be ready for new threats using biological agents. In an interview with Infectious Disease News last September, D.A. Henderson, MD, then director of the Center for Biodefense at Johns Hopkins University, Baltimore, said the threat of bioterrorism was a very real possibility. “It’s pretty evident from what’s going on that there are more threats out there,” said Henderson, who named anthrax and smallpox as the most dangerous threats.

	Up through the 1970s, when the vaccine was used against naturally occurring disease, some degree of risk was acceptable.
	Source: CDC

Weeks later, a Florida man contracted anthrax after he and several others were exposed to anthrax-laced letters. The attacks eventually spread to New York, New Jersey, Washington, Virginia and Connecticut, and the government and public called for stepped up preparedness efforts.

The CDC responded with a resurrected smallpox plan, first designed in 1972, calling for monitoring for suspected cases, isolation of victims and vaccination of close contacts – or “surveillance and monitoring,” the same strategy used to finally eradicate the disease in the 1970s.

In December, the government purchased an additional 209 million doses of smallpox vaccine from Acambis and Baxter to further bolster its supply. Dilution studies with the 15 million doses of Dryvax (Wyeth) vaccine left over from the 1970s showed that the supply could be stretched five times, and with the 85 million doses donated by Aventis Pasteur, it was evident the government would soon have enough vaccine for the entire U.S. population.

Some experts called for a return to mass vaccination campaigns to reduce the pool of susceptible individuals. Writing in The New England Journal of Medicine, William Bucknell, MD, MPH, of the Boston University School of Public Health, argued that voluntary and widespread vaccination would make controlling an outbreak easier and would deter those who might use smallpox as a weapon.

The public generally agreed with this assessment. According to a Harvard University School of Public Health poll, 59% of Americans said they would want to receive the smallpox vaccine even knowing the risks of vaccination. Of the 33% who said they would not, 81% said they would want to be vaccinated if smallpox was discovered in their community.

Real risk vs. perceived threat

The CDC has expressed skepticism over widespread use of the smallpox vaccine. Up through the 1970s, when the vaccine was used against naturally occurring disease, some degree of risk was acceptable. But now, according to information presented to the ACIP panel, the known risk of smallpox dissemination is low, and the risk of adverse outcomes is high.

“Smallpox is a very good vaccine, but as with all vaccines, it carries certain risks,” said Alan Hinman, MD, MPH, former director of the CDC’s National Immunization Program. “There is no proven risk of actual smallpox exposure. Therefore, the risk of adverse events is unacceptable.”

According to CDC modeling, there is a range of adverse events that could occur after mass vaccination, from mild local reactions to more severe life threatening complications. Even though effective screening would markedly reduce the impact of serious reactions, and even though there are new therapies available to treat those reactions, there would still be some people who would suffer untreatable adverse outcomes, such as encephalitis or death. Additionally, there is an even greater chance of adverse outcomes today because an increased number of individuals have immune deficiencies, including HIV, of which they may not be aware.

And so, when the ACIP decided not to offer smallpox vaccine to the general public, but to make it available to state and federal smallpox response and health care teams, the recommendation was made under the assumption that the risk for smallpox spread is still marginal. But, the panel added, the recommendations are subject to constant review, and states could “expand immunization to additional groups, up to and including their entire population.”

Judging by past experience

Another factor that influenced the ACIP’s thinking was the mode and method of dissemination. The CDC learned from the anthrax attacks that terrorists have the ability to “weaponize” biological agents, including aerosolizing them to increase their infectivity.

“Someone could have aerosol [smallpox] spray. It has been done with anthrax, and it could be done with smallpox,” said Henderson, now a bioterrorism consultant to the Office of Homeland Security.

There is evidence, Henderson continued, that Russian scientists working before the collapse of the Soviet Union were able to add stabilizers to smallpox, making it last longer in the air. Aerosolization was also investigated by the U.S. bioweapons program before it was disbanded in 1971.

“If anthrax can be thought of as a powder that can be weaponized and spread through the air, so can smallpox,” said Henderson.

The suggestion did little to alter the ACIP’s recommendations.

“Regardless of how the attack takes place, diagnosis is distinctive by clinical features, lab testing is distinctive, spread of the disease is much slower than other infectious diseases and transmission is usually predictable,” said Walter Orenstein, MD, director of the National Immunization Program.

Under the ACIP plan, state or local health departments, under guidance from the CDC, would respond to any smallpox case with “surveillance and containment, including ring vaccination.” But, there are some that are worried in an increasingly mobile society and with the possibility for simultaneous attacks, health officials would not be able to track down contacts.

A report by Veronique de Rugy and Charles Pena from the Cato Institute, a think tank on public policy that has been critical of the ACIP plan, called postexposure vaccination “woefully inadequate for countering a direct attack by a thinking enemy intent on inflicting infection, death and panic.”

Many CDC and public health officials disagree, including Henderson. “People do not transmit the disease until after the prodromal stage and after they develop a rash. You normally don’t find these people walking around” because they are very ill, he said.

As well, if a smallpox case were detected in the United States it would draw such media attention that contacts would actively seek vaccination instead of health officials looking for them, added J. Michael Lane, MD, MPH, who is a former professor of medicine at Emory University School of Medicine, Atlanta, and former director of the Bureau of Smallpox Eradication at the CDC.

So while the public demand for smallpox vaccine is still high, the ACIP has sought to make sure that the absolute minimum number of people would receive vaccination. Surveillance and containment has proven successful in the past, and given the low risk of intentional smallpox release, the ACIP decided that limiting vaccine use would significantly reduce the number of individuals who have to suffer needlessly from vaccine adverse reactions.

For more information:

• de Rugy V and Peña CV. No. 434. Policy Analysis. Washington, DC: Cato Institute, 2002. Responding to the threat of smallpox bioterrorism: an ounce of prevention is best approach.