Researchers step up battle against ongoing anthrax threat

Washington -- Anthrax is once again in the headlines: new suspicions, new rulings, new research.

Slightly more than two years after some tainted letters caused five deaths and significant nationwide panic, the question remains: Is the United States more ready today than it was in 2001?

Some answers are encouraging.

"We are significantly more prepared than we were two years ago," said Jerome Hauer, MPH, who, until recently, directed the Office of Public Health Emergency Preparedness and is now an assistant professor at the George Washington University School of Medicine and Health Sciences in Washington, D.C.

There are also nagging doubts.

"Given that there has already been an attack and we don't have anyone in jail, I would have to say we have not made as much progress as I think we should have in the last two years," said Lawrence Wein, PhD, professor of management science at Stanford University Graduate School of Business, Stanford, Calif. Dr. Wein and colleagues have drafted a plan to thwart an anthrax attack and presented it to federal emergency preparedness officials.

Regardless of the viewpoint, the discussion is timely.

In late December 2003, a federal debate erupted over the effectiveness of the anthrax vaccine against the deadly inhaled form of the disease, and a halt on mandatory military vaccinations was ordered by a U.S. district court judge. Many were surprised by this ruling and questioned the rationale behind it.

"Medically, it is a bad idea," said Brian Strom, MD, MPH, professor of public health and preventive medicine at the University of Pennsylvania School of Medicine, Philadelphia. Dr. Strom led an Institute of Medicine committee that assessed the safety and efficacy of the anthrax vaccine.

"We reviewed the data in great detail," he said. "The vaccine is reasonably safe and effective."

"The court's decision was based on misinformation," Hauer said. "This is not an experimental vaccine, and to stop the vaccine puts our troops at risk."

The Food and Drug Administration also released a statement to counter the court ruling, announcing that the anthrax vaccine was licensed and provided protection against all forms of the disease -- cutaneous, inhalational and gastrointestinal.

Meanwhile, reports emerged that al Qaeda is interested in obtaining adequate supplies of anthrax to use in bioterrorist attacks. This news seemed less surprising but still critically important.

"If al Qaeda was able to get to the point where they had sufficient quantity and sufficient mechanism of distribution, they would use it. There is no question in my mind," Hauer said.

Anthrax is considered an almost ideal bioterrorist weapon. Unlike smallpox, which is believed to be another top bioterrorism threat, a release of anthrax can be targeted more precisely and, because it is not contagious, it will not spread to endanger the entire world, said Alex Neyfakh, PhD, professor of medicinal chemistry at the University of Illinois, Chicago. Dr. Neyfakh and colleagues received a $15.7 million grant last fall to develop drugs to undermine this lethal microbe.

In addition, anthrax develops quickly and within a day or two becomes untreatable with antibiotics. Its early symptoms are also easily mistaken for a more innocuous ailment, Dr. Neyfakh said.

And while anthrax can be defeated by many antibiotics, it is relatively easy to select a strain that could be unaffected by the most commonly employed antibiotics, he added.

Arming the nation

Successfully deflecting an anthrax attack will require several tactics, and the nation is in varying stages of readiness regarding each, Hauer said. "You have to think about detection, reporting, countermeasures or treatment, and vaccines."

The U.S. Dept. of Homeland Security has employed a BioWatch system around the country to detect large-scale attacks, Hauer said.

While the system is generally effective, it cannot detect small-scale attacks, and air samples take 12 to 24 hours to analyze -- a long time considering the need for rapid antibiotic treatment.

And while the federal government is poised to distribute antibiotics to cities around the country within six to 12 hours of an alert, the cities are not necessarily prepared to move the antibiotics quickly to distribution points, Hauer said.

While federal assistance can be offered in the event of an attack on one city, if several cities are targeted, federal resources could become severely strained, he added.

The government is also funding research, including that at the University of Chicago, to develop better treatments and a better vaccine that would buy time in the event of an attack.

While the current vaccine, which is now reserved for the military, lab workers and those in other high-risk professions, is regarded as safe and effective, an updated version is being sought. The current vaccine requires six injections and an annual booster, and the Centers for Disease Control and Protection is seeking a way to halve the number of injections while continuing a high level of protection. Findings in an ongoing study are not expected for three years.

But other promising research findings are opening new possible treatment routes. For example, the anthrax genome was decoded by researchers at the National Institute of Allergy and Infectious Diseases and the Institute of Genomic Research.

Researchers at the University of Michigan, the Institute for Genomic Research and The Scripps Research Institute have discovered how anthrax creates the spores that allow it to survive extremes in temperature and the explosive force of a bomb. Yet once inside a living host, anthrax can begin infecting cells in as little as 10 minutes.

They found that anthrax devotes up to one-third of its genes to spore production.

Another research team, this one led by scientists at Beth Israel Deaconess Medical Center and Harvard Medical School, identified a group of small molecules that inhibit inhalation anthrax's deadly toxins.

"Unlike most types of bacteria, Bacillus anthracis has the ability to produce large amounts of a toxin that can kill the patient even after antibiotics have destroyed the bacteria," said Lewis Cantley, PhD, chief of the Division of Signal Transduction at Beth Israel Deaconess.

The hope is that this finding will lead to the development of a protease inhibitor drug that could be used in combination with antibiotics to treat anthrax cases later in the course of the disease, when antibiotics alone are no longer effective.

Labs around the nation, grant funds in hand, are gearing up to tackle anthrax. To most it's a new research topic.

"Before 2001 maybe two labs in the country were working with anthrax. It wasn't a big deal," Dr. Neyfakh said. Now it is.