Dr. Sencer is Director Emeritus of the Federal Centers for Disease Control and Prevention (CDC) and Dr. Dixon is the former head of CDC's Hospital Infections Branch. Neither is currently affiliated with CDC.
Disclaimer: Drs. Dixon and Sencer have not consulted with the Centers for Disease Control and Prevention in the preparation of this article and the opinions expressed and actions proposed are those of the authors.

Before October 2001 there was a lively debate in the medical world about whether the U.S. public health system should put significant amounts of its limited resources into preparations for a possible bioterrorist attack. The issues are well summarized by two articles published on TheDoctorWillSeeYouNow. In the first, entitled "Bioterrorism — Are we Prepared?", Dr. Martin Carey argues that the U.S. faces "a real threat" of terrorist attack using smallpox, anthrax, or some other biological agent. In the second ("Scare Stories Can Be Dangerous to Your Health") Drs. Cohen, Seidel and Gould disagree, asking instead: "Is it hype?"

Now the debate is not whether or not but how — how to prepare for and respond to the next attack.

All this has changed since the September 11 terrorism and the anthrax attacks that occurred shortly afterward. Now the debate is not whether or not but how — how to prepare for and respond to the next attack.

The anthrax attacks and their aftermath continue to rewrite what is known about the clinical and public health approaches to epidemics caused by anthrax and bioterrorism in general. Four points are already clear:
  • Doctors, ER staff and other front line medical professionals should now routinely consider whether patients have been the victims of an attack by biological agents. In the recent series of anthrax attacks, several people died primarily because those treating them, quite understandably, never considered anthrax infection as a possible diagnosis.
  • Other specialists may be the first to encounter a bioterrorist victim. It was a pediatric dermatologist who determined, early in the anthrax epidemic, that the infant daughter of a television network employee had the characteristic lesion of cutaneous (skin) anthrax.
  • In any bioterrorist attack or new epidemic, the first cases may be hard to recognize. Many unusual infections produce initial symptoms and signs that resemble those of more common conditions. Bioterrorism agents will not necessarily have tell-tale signs that can be counted on to raise an alarm.
  • Illnesses caused by naturally occurring, emerging infections are likely to present the same kinds of treatment and management problems as those caused by bioterrorism. Public health policies and medical treatments that are aimed at one group of infections will also be generally effective against another.

There is no easy answer to all of the problems presented by bioterrorist attack. A good first step for both professionals and patients would be, we believe, for every doctors' office, clinic and hospital to adopt a new screening protocol for every patient:
  1. identify patients who may have been exposed to dangerous pathogens,
  2. order infection control precautions that will prevent spread to others,
  3. collect clinical information and laboratory specimens,
  4. immediately notify public health authorities, and
  5. arrange appropriate treatment and follow-up care.

These simple actions are the critical first steps toward protecting all of us against bioterrorism and other dangerous infections. Once they have been taken, appropriate investigations and actions can proceed. Without them, important epidemics may not be recognized promptly and many people could be put at risk.

Infectious Agents To Watch
There are hundreds, if not thousands, of microorganisms or their toxic products that could be used as agents for bioterrorism (BT) or biowarfare (BW). Many of these are already available from commercial or natural sources.

For example, Bacillus anthracis, the microorganism causing anthrax, was relatively easy to obtain from commercial, academic and government laboratories until recently. And not only from labs — naturally occurring anthrax is still present in many parts of the world. Viable anthrax spores contaminate sites in the United States and occasional outbreaks of anthrax may occur because of exposure to these sites or imported animal products.

Many of the agents that can be used in BT and BW attacks can also be produced in large quantities and more cheaply than, for example, nuclear or chemical agents. Microbiologic agents have the added advantage that they can affect very large populations, and in such small quantities that they can be easily hidden and transported.

Only a few of the many potential agents are believed, however, to represent a real threat. This is because most potential agents cannot cause the kinds of diseases or disabilities that will incapacitate an enemy or terrorize a population. And many cannot be converted into a form that allows them to be delivered efficiently or to cause high infection rates (i.e., they are difficult to "weaponize"). Immunizations are available for other potential BT and BW agents, while preventive or early treatments can blunt the effects of others.

As a result, at the present time, only about 25 types of biologic agents have been identified as likely threats. Of those, seven have been given the highest priority ("Category A" agents) by the Federal Centers for Disease Control and Prevention (CDC):
  • Variola major (smallpox)
  • Bacillus anthracis (anthrax)
  • Yersinia pestis (plague)
  • Clostridium botulinum toxin (botulism)
  • Francisella tularensis (tularemia)
  • Viral hemorrhagic fever agents, which include the Filoviruses, which produce illnesses such as Ebola and Marburg hemorrhagic fevers
  • Arenaviruses, causing illnesses such as Lassa (Lassa fever), Junin (Argentine hemorrhagic fever) and related illnesses
Lower priority ("Class B") agents also pose significant risk. Several have been used in bioterrorism attacks (Salmonella was employed in 1984 to contaminate foods in salad bars in an Oregon community) or have been developed for use in warfare (e.g., Burkhnolderia mallei, which causes a disease called glanders in animals).

More detailed descriptions of these agents and the diseases they cause are available from CDC, USAMRIID, and the Johns Hopkins Center for Biodefense Studies.

Most of the practical steps taken to reduce the risk of infection from likely BT and BW agents have focused on naturally occurring microorganisms and toxins. But bioengineering might produce microorganisms that are new agents — agents that are transmitted differently, have unusual clinical effects or are not controlled by current vaccines or other treatments. This makes it even more important for medical professionals to recognize and properly manage every single case of potential infection.

A New Approach
To catch every possible case, doctors must change their routine. With an awareness of BT and BW and by adding a new screening routine, doctors will be better able to help victims of the next attack and, hopefully, prevent an epidemic.

Your doctor or nurse do not need to become experts on bioterrorism or on all the Category A microorganisms. Instead, they need to consider the possibility that you may be suffering from a BT infection or attack. You, the patient, can help too. If you are worried that your illness is somehow unusual and perhaps caused by a BT agent, you should voice these concerns to your doctor.

In Table 1, we present some of the basic features of the Class A agents. They are not meant to become the basis of self-diagnosis. Just keep them in the back of your mind in case you come down with an unusual illness and be sure to tell your doctor your suspicions. Note that the information in Table 1 was based on research on naturally occurring disease and that agents used today for BT or BW may behave differently than they did in natural settings.

Table 1.
Features of Possible Bioterrorism Agents.
Disease Mortality Rate Typical
Incubation Period
Anthrax, Inhalation High without treatment Usual 1-7 d
Up to 60 d
Restricted availability
Supportive Standard (barrier) only
Anthrax, Cutaneous Low Usual 1-7 d
Up to 60 d
Restricted availability
Antibiotic Standard
Contact for draining lesions
Smallpox Moderate Usual 10-12 days
Rarely as early as 3 or late as 17 days
Effective before and after exposure
Restricted availability
Immune globulin
Experimental antiviral
Highly contagious;
Plague (pneumonic) 100% untreated 1-4 days Licensed, limited availability Antibiotics Highly contagious;
Botulism High without treatment 12-36 hours
- Occasionally longer
No - Antitoxin
- Supportive
Tularemia (pulmonary) Moderate without treatment Usually 3-5 days; varies with strain and innoculum Limited availability; not post-exposure
Antibiotics Standard
Antibiotics Standard
Viral hemorrhagic fevers Varies according to virus, ranging from <1% to 50-90% Varies according to virus, ranging from 1-2 days to a week or more Limited availability: Yellow Fever vaccine
Several other vaccines under development
Antiviral agents show some promise for some viral infections
Most are highly contagious:

There are several other, less common agents that are sometimes listed as potential BT and BW agents:
  • Ricin, a toxin derived from the beans of the castor plant, which rapidly produces breathing problems
  • T-2 Mycotoxins, a group of compounds produced by a common grain mold, which can cause severe skin and mucous membrane toxicity beginning almost immediately after exposure
  • Staphylococcal enterotoxin B, which produces fever, chills, headache, myalgia and cough several hours after exposure
  • Glanders and melioidosis, bacterial infections that occur naturally and affect horses (glanders) and humans (melioidosis)
  • Q Fever, caused by the rickettsia Coxiella burnetti, a naturally occurring animal disease that has occasionally caused human disease
Looking for Zebras
"When you hear hoof beats, it's probably a horse, not a zebra" is a maxim that is told to medical students. Things are what they appear to be and the straightforward, common sense explanation is usually the most likely. One problem with bioterrorism is that it is a zebra. Though rarely will a patient with vague or confusing symptoms be a BT victim, the consequences of failing to identify quickly such a case are serious. Because some BT and emerging infections can be highly contagious, screening needs to begin even before the patient is seen by a doctor — as soon as the receptionist first answers the phone or the nurse welcomes a patient to the office. The challenge for the public health system is to remain on the lookout for the extremely rare and unusual without causing too many false alarms, ordering too many useless tests or unnecessarily frightening too many patients.

Op-Ed Epilogue

What are the lessons learned as a result of the anthrax attack?
First, public health officials need to communicate better, both to professionals and to the public.

Our audiences want to hear technical information from persons versed in the subject matter. Health information should come from health authorities; law enforcement information from the enforcers; political information from the politicians.

Nontraditional methods of communicating to the professions must be improved. The journal, Emerging Infectious Diseases, an online journal, had an authoritative report on cases of inhalation anthrax in November, 2001. The article was peer reviewed but had limited readership. The delay in publication in traditional journals would have lessened its timeliness. The Internet is a magnificent source of timely information but it is difficult for the physician suddenly thrust into a role in bioterrorism to sift the grain from the chaff. It is a legitimate role of government to provide authoritative information, and the CDC and many state and local health departments rose to the occasion. The New York City Department of Health, in particular, conducted an aggressive information dissemination policy.

We must recognize that it is all right to say, "I don't know." Early attempts to explain away the first anthrax case as waterborne led the public and the professions to distrust information emanating from the U.S. Department of Health and Human Services. One new truth is that we don't know all we need to know about biological agents when they are introduced in a nontraditional manner.

As noted above, the anthrax attack that occurred in late 2001 has forced a reconsideration of both the clinical features of that condition as well as the method of transmission. Although relatively few serious inhalational anthrax cases occurred, it seems that exposures to the epidemic strain caused lower death rates than expected among patients diagnosed and treated promptly. With multidrug antibiotic regimens and supportive care, survival of patients (60%) was markedly higher (<15%) than previously reported. The importance of early diagnosis and treatment was confirmed.

The attack had even more lessons for the public health community. Most experts agreed, after the first few cases, that the attack was not an assault from a nation with the capability of mass destruction but rather was probably from a domestically based terrorist. Public health authorities were surprised that such a highly sophisticated, weaponized strain had been prepared under those circumstances and that the strain so effectively contaminated diverse locations.

A model for an outbreak of anthrax would have been wrong. Who would have put the porousness of paper into the equation? Yet it was the ability of the spores to escape from sealed envelopes that contributed to the loss of credibility of the scientists by the postal workers.

What went right?
The system worked. Cases were diagnosed, reported, investigated and the information made available. State and local health departments, while stressed by inadequate resources, coped with the cases and rumors and devoted endless laboratory hours processing materials suspected of being anthrax. The few false positives were environmental samples tested by kits that have not had adequate evaluation.

What needs to be done?
There needs to be a recognized health spokesperson. The role of the Surgeon General has been marginalized by the political nature of the position. The Surgeon General has little staff. Unless these deficiencies can be corrected, the Director of CDC should be the designated spokesperson.

There needs to be clear plans for combating bioterrorism. These plans should not be carved in stone but subject to continuous revision.

The infrastructure of the public health system needs to be continuously strengthened. Modern communication systems and upgraded laboratories are important but trained personnel are essential.

The state and local health departments need to continue their efforts to communicate with the health professions on a regular basis, while the health professions need to recognize the value and role of their official health agencies. Efforts to improve the public health infrastructure must include efforts to strengthen ties between public health departments and their communities, especially practicing physicians. State and local health officials can be very helpful to practicing physicians — and vice versa — but few on either side of the chasm separating the two realms seem to realize it.

Traditional surveillance techniques need to be augmented by syndromic surveillance methods such as monitoring emergency room visits, EMS calls and drug sales.

Some will argue that the necessary expenditures will reduce the amount of funds for needed health services. This is a short-sighted approach, since all of the stated needs have benefits that go beyond bioterrorism. Better communication, better planning and better infrastructure add up to better disease prevention. And everyone in the health profession and the public should value prevention.