ARLINGTON, VA—The packed ballpark was tense with excitement. The home team was up by two runs with two outs in the top of the ninth. Nobody paid the slightest attention to a truck that stopped briefly outside the park. Even if anyone had seen it, they couldn't have known that during its brief stop the truck released an aerosolized cloud of anthrax spores that were now wafting over the crowd on a balmy breeze.
Two days later, people presented at local hospital emergency departments with nasal congestion and fever. The illness was initially diagnosed as influenza. But in succeeding days, more and more people became ill. Then deaths began to be reported. Finally, 5 days after the exposure occurred, a hospital laboratory identified anthrax as the cause of the outbreak, and antibiotic treatment was begun in those who had been exposed. Even so, of the 20,000 people estimated to have been at the ball game, 4000 died.
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Bioterrorism experts wonder how many physicians would recognize the subject of this photomicrograph, x100: Bacillus anthracis chains and red infected cells in animal tissue. (Photo Credit: © Kent Wood/Photo Researchers Inc)
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This description of a bioterrorist incident, related by Thomas V. Inglesby, MD, to a crowded auditorium last month, is fictional. But his message is that it could happen—and the United States had better be prepared.
Inglesby is a fellow at the Johns Hopkins Center for Civilian Biodefense Studies in the School of Hygiene and Public Health. The center, established in August 1998, is headed by Donald A. Henderson, MD, internationally known for his leadership in eradicating smallpox.
The anthrax scenario and another describing an outbreak of smallpox, presented at the meeting by Tara J. O'Toole, MD, a senior fellow at the center, were created to draw attention to the issues involved and the preparations necessary to mount the needed countermeasures. They were part of the program during the first National Symposium on Medical and Public Health Response to Bioterrorism, convened here by the Hopkins Center, the Department of Health and Human Services (HHS), and 12 other sponsoring organizations. More than 900 concerned public health professionals, physicians, and others attended, and 300 more had to be turned away for lack of room. The organizers plan to make the meeting an annual event.
FUNDS APPROPRIATED
The issue of bioterrorism gained momentum in May 1998 when President Clinton clarified the responsibilities of the federal agencies involved in fighting it. This January, he said he intended to ask Congress for about $2.85 billion to counter the threat, with the funds going to the Federal Bureau of Investigation, National Security Agency, military intelligence officers, and similar groups.
Congress is also concerned. It passed legislation last year appropriating $158 million for HHS, as well as $1 million to fund the Hopkins Center. HHS Secretary Donna Shalala said here that the department's portion of the increased antibioterrorism funds the administration was proposing to Congress included $72 million for the next fiscal year, which will be added to the $158 million currently being spent in preparations. The funds will be used especially to expand activities against anthrax and smallpox "so we can quickly respond to a suspected biological agent."
The Centers for Disease Control and Prevention (CDC) has received $51 million to begin creating stockpiles of antibiotics and to develop a modern smallpox vaccine. The responsiblity of creating plans for coordinating health and medical assistance has been given to the Office of Emergency Preparedness in the US Public Health Service.
Henderson said the purpose of this meeting was "to give physicians and public health communities a serious in-depth review of the realities involved in a bioterrorist attack. There is a need for expert input from physicians who treat disease as well as physicians in public health. Based on an understanding of the complex problems such an attack poses," he said, "we hope that an effective response will emerge. To remain unprepared is to invite disaster." The Hopkins Center has set up a working group to develop recommendations for medical and public health action in the event of a bioterrorist attack.
AGENTS OF CHOICE
Thousands of agents could be used by a bioterrorist. But when factors such as ease of production, infectivity, toxicity, and ability to retain aerosol dissemination are taken into account, the list narrows considerably. "An effective biological weapon has to be able to be produced in large enough quantities; it has to have the ability to infect large numbers of individuals; it has to remain stable when stored; and it has to retain virulence after aerosol dissemination," said COL Gerald Parker, PhD, commander of the US Army Medical Research Institute of Infectious Diseases at Fort Detrick, Md.
Parker summarized the steps involved in identifying the agents that pose the greatest threat. "Ultimately, only a few [agents] make suitable biological weapons, capable of causing mass casualties," he said. "Although we cannot ignore the fact that there are several other pathogens, such as the agents that cause plague, botulism, and viral hemorrhagic fever, and the plant toxin ricin," said Parker, "two agents lead the pack—anthrax and smallpox."
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The gram-positive anaerobic bacterium Clostridium botulinum, shown here in a transmission electron micrograph, is listed among the possible agents of biological terrorism. (Photo Credit: A. B. Dowsett/Science Photo Library)
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Anthrax spores remain stable for years and retain their infectivity after dissemination. The disease has an 80% case-fatality rate. It can be successfully treated with antibiotics if suspected before symptoms develop—quinolones are the agents of choice—but adequate supplies must be available and planning must be done for prioritizing who will receive these drugs. The US military uses a vaccine against anthrax, but none is available for the civilian population.
Although anthrax is not transmitted from person to person, smallpox is highly contagious. With a case-fatality rate of 30% or more, Henderson says the smallpox virus represents "one of the most serious bioterrorist threats to the civilian population." In a susceptible and mobile society, secondary and tertiary spread of the disease can be expected. During the incubation period of 12 to 14 days, an infected individual can transmit the virus to many others. In the scenario O'Toole presented, although the virus was released in only one location in one city, within weeks cases were occurring worldwide and 15,000 people died.
REINTRODUCE IMMUNIZATION
Routine smallpox immunization ended in the United States in 1972 and, with the eradication of the disease, was discontinued in the rest of world in 1980. Any immunity conferred by the vaccine has waned by now. Vaccination is the only means by which the disease can be prevented, but there are only about 6 million doses of smallpox vaccine in the United States and "some of that may have deteriorated," said Henderson.
Moreover, facilities for making the vaccine no longer exist. A vaccine prepared from virus cultivated on human cells must be developed and stockpiled in sufficient quantity to contain an outbreak, said Henderson, who estimated that a cell-cultured vaccine could be developed in about 3 years at a cost of $120 million.
The stocks of smallpox virus held at the CDC in Atlanta and at the State Research Center of Virology and Biotechnology in Koltsovo, Russia, are scheduled to be destroyed this summer. The World Health Organization is to give the final nod of approval at its annual meeting in the spring.
But, said Henderson at the meeting here, in contrast to what was believed for some years (JAMA.1993;270:2908 and 1995;273:446), it is now known that other stores of smallpox virus remain in the former Soviet Union and the concern is that barriers to prevent its dissemination outside that region are not high enough. There is no guarantee that the virus may not have been obtained by other countries known to be developing biological weapons programs, notably North Korea, Iran, Iraq, Syria, and Libya. At the same time, "There's no intelligence that we know of that has confirmed that smallpox virus is outside the former Soviet Union," said the Hopkins Center's Inglesby.
In a recent article (Science. 1999;283:1279-1282), Henderson noted that Ken Alibek, PhD, a former first deputy chief of research and production for the Russian biological weapons program, had weaponized smallpox virus in intercontinental ballistic missiles and in bombs.
All in all, there exists "a volatile situation with potentially serious consequences," Henderson wrote. And, he stated, "The provision of funds to HHS is consonant with the general belief that the most effective step now is to strengthen the public health and infectious disease infrastructure."
Preparations to combat bioterrorism will carry, as a bonus, widespread benefits to health, said Margaret Hamburg, MD, HHS assistant secretary for planning and evaluation, at the Arlington meeting. "The things we need to adequately prepare for a bioterrorist event have broad value across a range of infectious diseases," she noted. "So the good news is that if we advance our public health infrastructure to make it truly robust and functioning, if we forge links between public health and medicine, we will also be protecting the health of this nation and the world against a range of naturally occurring infectious diseases."
