Bioterrorism Preparedness and Response: Title and subTitle BreakClinicians and Public Health Agencies as Essential Partners

Beginning in mid-September 2001, the United States experienced unprecedented biological attacks involving the intentional distribution of Bacillus anthracis spores through the postal system.¹ The full impact of this bioterrorist activity has not been assessed, but already the toll is large. A total of 22 persons have developed anthrax and 5 have died as a direct result.^{2 - 5} More than 10 000 persons were advised to take postexposure prophylactic treatment because they were at known or potential risk for inhalational anthrax; in addition, more than 20 000 others started such treatment until the investigation provided reassurance that exposure was unlikely and treatment could be stopped; thousands more were victims of hoaxes or false alarms, and still more were worried coworkers, friends, and family members of those directly affected.⁶ The impact was not limited to the United States. Hoaxes involving threatening letters or powder-containing envelopes were reported from several countries; mail cross-contaminated with B anthracis was distributed to some US embassies, and persons in remote corners of the world were advised to take prophylactic antimicrobial treatment.

In this issue of THE JOURNAL, 3 patients who acquired anthrax as a consequence of these attacks are described in detail.^{7 - 9} They are unique from the other recent patients with anthrax in that their infection cannot be directly linked to an occupational exposure. At the time they first sought medical attention, none could provide a history suggestive of exposure to B anthracis, and other causes were considered more likely to explain their illnesses. In retrospect, the source of the infant's exposure was inferred when anthrax spores were found in his mother's workplace. For the other 2 patients, exposure to cross-contaminated mail remains a plausible but unproven hypothesis. Despite intensive investigations, the sources of their infections may never be known. These stories teach the important lesson that anyone—active elderly persons, healthy infants, and hard-working private citizens—could be infected during a bioterrorist event. Hence, the safety of all persons, regardless of age, health status, location, or occupation, must be addressed in bioterrorism preparedness and response programs.

From the public health perspective, recognition and response to the recent bioterrorist attacks has evolved in a series of overlapping phases at each location. The initial phase involved detection and then confirmation of a case of anthrax or a powder-containing envelope, followed by rapid deployment of public health and law enforcement personnel and other needed resources to the site. The second phase has been characterized by full-scale investigations as well as interventions to prevent additional cases. Longer-term consequence management, including follow-up of affected individuals and remediation of contaminated sites that could pose an occupational health risk, are major activities in the current phase. In all these phases, clinicians have proven to be essential partners, which is a lesson that must be incorporated into future bioterrorism preparedness and response efforts and professional education programs.

In most situations, alert clinicians actually initiated the first phase of the response by obtaining the appropriate laboratory tests, recognizing that a patient might have anthrax, and notifying health officials. Emergency physicians, outpatient primary care physicians and other practitioners, dermatologists, and pediatricians participated in the early recognition of infected patients, illustrating their critical role in surveillance for bioterrorism. Radiologists, infectious diseases specialists, pulmonologists, surgeons, hospitalists, critical care specialists, laboratorians, pathologists, and many other specialists also contributed to the diagnosis and management. Together, these clinicians have created a remarkably effective detection system for identifying and reporting cases. Their collective efforts provided an early warning to public health and law enforcement agencies that signaled the need for large-scale interventions to protect thousands of others at risk.

For this frontline surveillance system to function at its best, all clinicians, regardless of their specialty, must have enough basic information about the clinical manifestations of infections caused by the select agents of bioterrorism to raise their suspicion when they see a patient with a compatible illness. In addition, clinicians must know how to diagnose these conditions and when and how to report their suspicion to local public health and law enforcement officials. In the current response scenario, obtaining an accurate occupational history was vital in assessing anthrax risk; all clinicians need this skill to be prepared for similar scenarios in the future.

Enhancing the knowledge and skills of clinicians is not just a matter of 1-time educational programs. Bioterrorism-related infections hopefully will remain rare events, and creative ongoing strategies will be required to sustain attention to potential new cases when the current phase of alarm and interest ebbs. Furthermore, better systems are needed for public health agencies to alert all clinicians when an attack is suspected or documented, facilitate real-time reporting, and disseminate credible information required for optimal exposure risk assessment, diagnosis, and treatment. Such efforts will simultaneously result in an improved capacity to detect and respond to naturally occurring emerging and reemerging infectious diseases.

Frontline clinicians faced a challenge that often was even more difficult than diagnosing anthrax—that of excluding the diagnosis among the many worried patients with concerns about potential exposure or among those who sought care for rashes or illnesses suggestive of the diagnosis. In the absence of clinical algorithms or rapid diagnostic tests, their clinical judgment helped reassure patients and avert the distraction that initiating unneeded response efforts would have otherwise entailed. For the future, developing clinical algorithms and laboratory testing protocols and reagents that rapidly and accurately identify all pathogens in the differential diagnosis of the suspicious illness, not just the select agents of bioterrorism, is important but will take time.

Primary care clinicians certainly have played a key role in managing postexposure prophylactic treatment interventions and their complications in the second phase of the response to the recent bioterrorist attacks. The initial distribution of antimicrobial drugs was usually coordinated through public health agencies, but often involved local clinicians as well. Those in outpatient settings have provided adherence counseling and advice about managing adverse events and other complications. Some clinicians also helped patients make decisions about their personal risk and the need for anthrax vaccine or additional days of antimicrobial prophylaxis. Patients with special concerns or underlying illnesses have solicited consultation about antimicrobial treatment from their obstetricians, pediatricians, and other medical specialists.

Many of the individualized preventive treatment decisions had to be made in the context of an inadequate or evolving evidence base. Input from clinicians directly involved in the affected areas and from professional medical societies and other organizations proved to be extremely useful for the development of the Centers for Disease Control and Prevention's interim treatment guidelines.^{10 - 16} Clinicians also assisted many patients with decisions about anthrax vaccine treatment options, even though they had little advance warning or information about the program. Mechanisms to anticipate and more quickly respond to the needs of those caring for the diverse population of affected patients is another priority for enhancing bioterrorism response capacity as part of preparation for future events.

Clinicians are actively engaged in the current phase of the response (long-term consequence management and remediation) and are likely to be even more engaged in the future. The possibility of late onset of inhalational anthrax among exposed persons, even though considered unlikely by most experts, requires heightened concern about febrile illnesses, chest pain, sweats, profound fatigue, and other symptoms in persons who were exposed to B anthracis. Likewise, clinicians must be alert to the possibility of long-term adverse events attributable to antimicrobial treatment and vaccination. Prophylactic anitimicrobial treatment is not likely to cause frequent serious late-onset adverse events, but there is inadequate experience with 60 or more days of antimicrobial treatment and anthrax vaccine among the diverse populations represented in the treated group. During the next 24 months, the Centers for Disease Control and Prevention plans to survey the health status of the 10 000 people whose exposure history suggested a need for prolonged prophylactic antimicrobial treatment, but local clinicians will be the most important resource for detecting adverse events, recognizing their association with prophylactic treatment for anthrax, and reporting them to health officials and the Food and Drug Administration. Other occupational and mental health issues that will require the services of additional medical specialists may emerge among exposed persons over the next months to years.

Although it is tempting to respond as if the current anthrax threat is coming to an end, the criminal(s) who perpetrated these acts of bioterrorism has not been apprehended. The country remains at risk for additional exposures and infections with this deadly pathogen and perhaps with other agents. The importance of individual clinicians in bioterrorism preparedness and response was not fully appreciated by many until the current attacks occurred. Hopefully, the lessons learned during the past 4 months will motivate local health departments, health care organizations, and clinicians to engage in collaborative programs to enhance their communication and local preparedness and response capabilities. Knowledgeable clinicians, operating in the framework of a health care delivery system that is fully prepared to support the necessary diagnostic and treatment modalities to manage affected patients, and seamless linkages to local public health agencies will provide a strong foundation for detecting, responding to, and combating bioterrorism and other infectious disease threats to public health in the future.