STANFORD, Calif. -- Anthrax first became a household name for many Americans in September 2001, when 22 cases of bioterrorism-related anthrax, including five deaths, were identified on the East Coast. Although the incidents were relatively isolated, they raised an important question: How should the healthcare system respond to a bioterrorist anthrax attack?

Nearly four years later, researchers may be closer to an answer. A study by researchers at CHP/PCOR, the VA Palo Alto Health Care System and the University of Toronto has found that the timely use of both antibiotics and vaccination is the most cost-effective way to treat people potentially exposed to anthrax.

"Our findings make clear that combination therapy with antibiotics and vaccination is better then either treatment alone," said Douglas K. Owens, senior investigator at the VA Palo Alto and a core faculty member at CHP/PCOR. "And the best strategy is actually the least expensive."

Owens is senior author of the study paper that appears in the April 19 issue of the Annals of Internal Medicine. As he and his co-authors note, their findings highlight "the critical need for distribution systems that can provide prophylaxis and vaccination rapidly for hundreds of thousands, perhaps millions, of exposed people."

Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. Anthrax spores can be used as a bioterrorist weapon, and the Centers for Disease Control and Prevention has identified anthrax as one of the few biological agents capable of crippling a developed region through death and disease.

"Anthrax has been weaponized; it's lethal and it's available," said Owens. "As we point out in our paper, a serious anthrax attack could be catastrophic."

If inhalational anthrax is left untreated, the mortality rate approaches 100 percent. A report from the World Health Organization estimated that the aircraft release of anthrax over a city of 5 million people (just over half the size of New York) would result in 250,000 deaths.

Owens and his colleagues -- including CHP/PCOR research associate Dena Bravata and center director Alan Garber -- evaluated the cost-effectiveness of different methods of defending against such an attack. For their study, they simulated a large-scale aerosolized anthrax attack over a U.S. metropolitan area. They then developed a decision model to compare the costs, harms and benefits of four post-attack strategies: no vaccination or antibiotics, vaccination alone, antibiotics alone, or vaccination and antibiotics. They also compared two pre-attack strategies: vaccination or no vaccination.

There are no well-established estimates of the probability of an attack or the probability of exposure for any given type of attack, so the researchers chose estimates based on reviews of literature and expert opinions. They estimated the probability of surviving clinical anthrax from past studies and recent U.S. anthrax cases.

After reviewing several strategies, the researchers found that the combination of vaccination and antibiotics was the most effective option for preventing death and disease and was the least costly. The combination, which cost $46,099 per person, resulted in a four-month gain of life and savings of $355 per person when compared with vaccination alone.

"The savings associated with preventing cases of inhalational anthrax offset the cost of using both vaccination and antibiotics," said lead author Robert Fowler, MD, a former Stanford postdoctoral scholar who is now at the University of Toronto.

The researchers also determined that widespread pre-attack vaccination was not particularly cost-effective. For a city of 5 million people, assuming a low of probability of attack, the incremental cost of a vaccination plan could be between $500 million and $1 billion without appreciable health benefits.

The authors emphasized that without an adequate distribution system, no strategy to combat bioterrorism can be effective. "There must be a way to get antibiotics to a very large number of people very rapidly; otherwise you won't get the benefits that we predict," said Owens. His hope, he added, is that these findings will help the country get more prepared for a possible bioterrorist attack.

"We hope the findings in our study are never put to the test, and there's never an attack," Owens said. "At the same time, if this helps get people more prepared that would be a very good outcome."

The study was funded by the Sunnybrook and Women's College Health Sciences Centre, University of Toronto, the Homer Laughlin Fund, the Agency for Healthcare Research and Quality, and the U.S. Department of Veterans Affairs.

The study findings were covered in news articles in the Atlanta Journal-Constitution, ABCNews.com, Reuters Health and HealthDay News.