Lessons from anthrax

A Yale Medicine roundtable.

At the 2001 annual meeting of the American Association for the Advancement of Science last February in San Francisco, an audience member asked a panel of experts on bioterrorism why the world had yet to see a major biological attack. After a moment’s pause, a response came from Stephen Morse, Ph.D., director of the Center for Public Health Preparedness at Columbia University. “Nobody really knows the answer to that,” he said. “I suspect there have been a number of barriers, some cultural, some technical, to pulling this off. Clearly, there have been a number of groups as well as countries that have been interested. It is only a matter of time before the motivation and the knowledge of those people who wish to use bio will reach the point where you will see a real attack happen. I think, unfortunately, it is probably not that far in the future.”

September 11 dispelled any doubts about barriers to perpetrating a major terror attack, and the ensuing rash of anthrax exposures made the notion of biological warfare real to Americans. The use of the mail to deliver anthrax, however, was a scenario no one on the panel of soldiers, scientists and scholars had envisioned. As we closed this issue of Yale Medicine in early December, we wondered what Yale’s experts in the field might be doing to try to anticipate the unanticipated. Associate Editor John Curtis asked faculty and alumni in medicine, public health and microbiology to comment on the anthrax scare and bioterrorism more generally. Below are highlights of their responses.

The discussants

FRANK J. BIA, M.D., professor of medicine (infectious disease) and laboratory medicine; co-director of the Yale International Health Program.

JONATHAN B. BORAK, M.D., associate clinical professor of medicine and epidemiology, board-certified toxicologist, member of the National Research Council’s committee on chemical warfare agents.

RAVI V. DURVASULA, M.D., assistant clinical professor in the division of epidemiology of microbial diseases and medical director of Yale University Health Services; Durvasula has worked on projects aimed at developing pathogen countermeasures for use in bioterrorist attacks.

ROBERT HEIMER, Ph.D. ’88, principal investigator of the Yale Emerging Infections Program, associate professor of epidemiology and public health and of pharmacology.

STEPHEN C. JOSEPH, M.D. ’63, M.P.H., former commissioner of health for New York City, former assistant secretary of defense for health affairs and a founding principal in the health consulting firm Black Dog Associates in Santa Fe, N.M.

RICHARD M. SATAVA, M.D., professor of surgery, former program manager of the Advanced Biomedical Technologies Program of Defense Advanced Research Projects Agency.

ANDRE N. SOFAIR, M.D., M.P.H. ’97, HS ’90, assistant professor of medicine; one of Sofair’s research interests is the development of surveillance systems to assist in the clinical recognition of unexplained infectious diseases.

As of November 24, five people have died and 13 others have become infected with anthrax in its inhalation or cutaneous form. Given these cases, how serious is the threat of biological terrorism?

DURVASULA: The threat of bioterrorism should be considered very real. We now know that a bioterrorist attack can be launched successfully in the U.S., that high-grade, highly infectious agents can be readily released in our country, that perpetrators of these acts may go undetected, that the health care system is entirely unprepared for such attacks and that otherwise innocuous routes such as the mail may be used.

BORAK: The hoof-and-mouth infection that wiped out much of the beef herd in England in 2000 could have been an example of bioterrorism and could be readily reproduced in this country. There is an incredible ease about delivering enteric pathogens to the food sources in our very open society. Think of one person—a truck driver for a supermarket chain who sprays vegetables prior to delivery.

HEIMER: Although bioterrorism is a threat because its sources and the potential for more terrorist dissemination are unknown, the health of the American public is far more threatened by infectious agents whose disease burden could be reduced by concerted public health action. While we need to solve the criminal issue of anthrax terrorism, public health money could be more wisely spent combating the spread of preventable diseases.

JOSEPH: This is a new world we are in. This is going to be a method by which war is waged, either by rogue states or terrorist groups that can’t engage a major power like the United States on a conventional battlefield. It is not a threat anymore—it is a reality.

SOFAIR: To a certain degree we don’t really know. The threat to the general public appears to be very small. People are at risk in certain occupations—the military, government offices, the media.

What other pathogens might pose a threat from bioterrorists? Smallpox? Tularemia? Q fever? Ebola? Plague?

DURVASULA: Potential agents include bacteria such as the anthrax bacillus or plague bacillus, viruses such as smallpox or agents of hemorraghic fever, or even toxins such as staphylococcal toxin or botulinum. The greatest threat in terms of mass lethality is posed by those agents that can be aerosolized and for which treatments are limited and natural immunity is low. Therefore, in addition to anthrax, smallpox virus, plague bacillus and Francisella tularensis (the agent of tularemia) are considered potential agents.

JOSEPH: Perhaps an even greater problem is modified organisms, from strains of smallpox which might be resistant to current vaccines, to the chimera organisms we know the Soviets were working on. Chimera organisms could be developed to give a one-two punch, where a second illness would break out after the first illness.

SATAVA: The real danger is from “designer agents,” which have been created by genetic mutation to have an entirely new strain that is not detectable by current screening methods, or Trojan horses—common harmless bacteria to which undetectable deadly changes have been made.

What can we learn from the anthrax scare this fall?

JOSEPH: We were very fortunate in two ways. It was a noncontagious agent and the mechanism of dispersion used was relatively inefficient and very small-scale.

In general, our disaster management programs in the states involve three sectors: law enforcement/military, disaster management/environmental protection, and public health/clinical medicine. Traditionally, the public health and clinical part of that triad has been sort of a dragging dog. It is the law enforcement—and in some cases the military—that runs the operation. Except for industrial or chemical events, the health problems have been largely surgical triage and response. In the biological and chemical warfare world we are now in, that changes. The subtleties, complexities and degrees of uncertainty are so different that public health and clinical medicine need to take a much more expanded and important role.

HEIMER: We need to broaden existing ER and primary-care surveillance. Quick response means quick detection of suspect cases, rapid diagnosis, proper identification of and prophylaxis for those exposed. Immediate attempts to trace the source of infection and, in the case of agents that can be transmitted easily from person to person, the contacts of the index case must become routine parts of such surveillance schemes.

BORAK: We have a society that is not sufficiently prepared for some of these eventualities. We are one year away from having enough vaccine for smallpox. One has to ask whether that is a wise delay.

SATAVA: The current scare exposes to the general public the grave concern the military has had about weapons of mass destruction and, especially, biological warfare agents over the past decade. The military has been conducting intensive research in the past five years. However, this is an extremely complex threat and one which involves our civilian population here at home rather than armed forces abroad. For the first time, our country is vulnerable to threats, even from rogue terrorists, and has found that homeland defense is lacking.

What needs to be done to prepare our public health infrastructure to deal with biological warfare?

JOSEPH: The infrastructure at the municipal and county levels is underfunded. It’s weak. It is not well coordinated with the clinical sector or the law enforcement sector. It often doesn’t do a good job with the media. In all sorts of ways we need to beef up everything, from computerized information systems that link horizontally as well as vertically, to increased laboratory resources, to tighter relationships between the clinical and public health sides.

We are very fortunate because of that doc in Florida who made the diagnosis in the first case. I had always postulated that the first-line person was going to be someone on call at a community hospital at midnight on a Sunday and would not recognize what he or she saw.

BORAK: I have been trying to push the American College of Occupational and Environmental Medicine to develop models so that corporations can use their existing facilities as adjuncts to the public health system. Most large corporations already deal with trying to get most of their employees to take flu shots. Let’s assume that it was necessary to vaccinate the entire population of a city. There is no way the city’s department of public health is going to do it. They don’t have the capacity. You could find the 50 or 100 largest employers and simply deputize them. You could ask corporate medical directors, “Can you develop a system so that any one of your facilities would be able to provide, within 48 hours, vaccinations for every employee and his or her immediate family?” It is a system that already exists. It just doesn’t know it exists.

SOFAIR: We need to realize that our nation is not immune to threats, both internally and from abroad. The public health infrastructure seems to be lacking. The relationship between the medical profession and the public health infrastructure is not as strong as it could be. The level of understanding of public health and medical risk by government officials is not what it should be.

In general the public health infrastructure has to be strengthened to conduct surveillance for unusual illness, detect trends in unusual illness and educate medical professionals in those surveillance structures. General surveillance needs to be beefed up. If there’s not a strong public health structure to tie occurrences together, there will be a delay in recognition of a bioterrorism event. We need to strengthen and centralize laboratory facilities to help in the detection of these sorts of agents, have rapid turnaround time of good and accurate laboratory testing and strengthen communication between public health and the medical profession. Public health needs to educate the medical profession about what they do and there needs to be a better liaison between the two.

SATAVA: Monitoring of trends by symptomatology to provide early warning. A more effective identification methodology. Training of the civilian health care and first responder—EMT, fire, police—populations to have a high index of suspicion and to take protective measures. A real-time rapid dissemination of validated threats. A national-level quarantine plan, though that may not be possible based upon the mobility of our population.

What can this medical school do to better educate students and physicians to deal with biological terrorism?

SATAVA: Stronger emphasis on clinical application of microbiology from the bioterrorist perspective, and instruction on the practical aspects of mass casualty triage, decontamination and quarantine procedures in the management of suspected bioterrorist (or naturally occurring) epidemics.

BIA: Our curriculum in medical microbiology is readily adaptable to dealing with the pathogenic features of potential bioterrorist agents. Much more difficult are the terrorism pieces. What conditions breed terrorism? How do lack of adequate health care, poverty and instability foster terrorism? This is not just a “wet bench” problem. It involves the social sciences—the very disciplines that physicians tend to avoid as “soft.”

HEIMER: Broadly speaking, a better understanding of public health (as opposed to the health of individuals) would be helpful.

DURVASULA: Several measures have been taken at both the medical school and university levels to educate students and physicians in the acute setting. These unfortunate events may result in increased attention given to the area of bioterrorism in curricula at both the med school and the public health school. Certainly, organisms such as anthrax and plague, which are given little attention in microbiology courses, may get additional emphasis. However, a more meaningful approach may involve greater attention to public health systems that deal with emergency response and containment of infectious diseases. This infrastructure has been greatly reduced over the years in the U.S., and an increased emphasis on educating students and resident physicians about such practices is warranted. Principles of public health and disease containment are as applicable to bioterrorist attacks as they are to epidemics of TB and multidrug-resistant microbes.

JOSEPH: Part of the curriculum needs to be based on the clinical and public health requirements for a response to attacks. I didn’t learn that in medical school. I learned about anthrax as kind of a medical museum piece among people who made piano keys or felt sorters in the wool hat industry. The world has changed.

SOFAIR: Medical schools need to teach physicians about public health: What is public health? What is surveillance? How does one use the public health infrastructures that exist when there is an unusual occurrence? How does one work with the FBI or CDC?

We need to think about which diseases we teach the students about. We need to teach students how to recognize something unusual, even if it is presenting in a common syndrome. Many of the agents that may be used in a bioterrorist attack may present as a pneumonia, or an encephalitis, and may be indistinguishable from more common etiologies without a high index of suspicion. We have to teach them not to be satisfied with thinking about the top one, two or three diagnoses. That is really a challenge in a medical system where people are rushed. And we need to teach our medical students how to take a good exposure history. What kind of work do people do? What sort of travel have they done? What kind of hobbies do they have? What people have they been exposed to?

Since the first case of anthrax was diagnosed this fall in Florida, information released to the public has been at times contradictory and at times inaccurate and incomplete. How can the federal government better coordinate its communications regarding biological threats?

JOSEPH: Public health people have to learn how to get out in front and make sure that political figures and the media are passing along good, consistent and useful information that helps the medical and public health process along.

HEIMER: Speaking with a single voice is not necessarily speaking the truth. A free society needs multiple sources of information and an appreciation that contradictory messages are a necessary part of a free society’s emerging response to the unknown. Only totalitarian states can choose a single path and adhere to it regardless of what new information becomes available.

SATAVA: The government has taken the correct steps in consolidating the information stream through a central agency, the Office of Homeland Security directed by Tom Ridge. While there is no way to prevent the media from publicizing what it believes to be accurate information, there should be one designated person from homeland security who is the final authority that validates the information given in press releases. Perhaps President Bush should specifically state that no information regarding bioterrorism is valid unless released by homeland security. This might give some reassurance even though the press and public are distrustful of government.

Are there ways of safeguarding potential conduits for bioterrorism? In the case of anthrax, this might mean irradiating the mail. What other channels are vulnerable and how might they be protected?

HEIMER: It’s hard to comprehend all the possibilities. Life is not without risks, and if we considered all the possible risks and tried to prevent them, we would still be living in caves. The proper question is, “How should we respond when a new threat emerges?”

SATAVA: The solution to bioterrorism is not technology. I am not convinced that a huge investment in many of these preventive measures—which can drain our economy—is capable of preventing such acts from occurring. The solution is to eliminate the root cause, or perceived root cause, which may be impossible. Temporizing solutions, such as tearing up the Al Qaeda network, are essential in the near term, but better long-term solutions on a multinational level are also required.

JOSEPH: There will be a follow-up attempt. It may be next week. It may be next month. It may be in the United States. It may be at some United States’ interest abroad. It may be in another country. But the next attempt is likely not to be as constrained as this one was.

Is the hoarding of antibiotics a public health threat in and of itself? How can people protect themselves without resorting to prophylactic use of antibiotics?

JOSEPH: I never understood why everyone went immediately to Cipro instead of alternative drugs that are cheaper and more available. Cipro is now firmly in the public’s mind. It raises all the issues of mass overlaying of antibiotics on a population, most of whom don’t need it.

DURVASULA: The hoarding of Cipro is a public health nightmare since it may lead to a shortage. There are numerous reports that people are taking the medications erratically, because of unpleasant side effects. This is a recipe for disaster in terms of emergence of antibiotic resistance. With the current anthrax scare and potential future bioterrorist threats, society may easily slide backward in the effort to use antibiotics wisely, creating a far greater epidemic of antibiotic resistance.

HEIMER: Compared to the overprescribing of antibiotics for all forms of viral disease, the current overuse of Cipro is a blip on the radar. For health threats, it makes sense that health officials at the municipal and state levels, with the backing of experts at the CDC, be given the forum they need to articulate who, if anyone, in their community needs medical prophylaxis. Individuals in this society are free to accept or disregard this advice, but it’s important that the advice offered is medically sound and inclusive of all those at risk.

SATAVA: The bioterrorist threat cannot be solved with stockpiling of antibiotics or vaccination against all possible agents. I don’t believe that anyone can protect themselves against bioterrorism, just as we cannot protect against nuclear holocaust. Bioterrorism has become a fact of life, and we as a nation must adjust, accept that we might possibly be subject to a horrific act and go on with our lives. In the meantime, we should develop only those technologies and response systems which have a high likelihood of mitigating specific areas of risk. YM