Bioterrorism: An Update with a Focus on Anthrax

Philip S. Brachman

From the Rollins School of Public Health, Emory University, 1518 Clifton Road, NE, Room 742, Atlanta, GA 30322 (e-mail: pbrachm{at}sph.emory.edu).

Abbreviations: CDC, Centers for Disease Control and Prevention

The current problem with anthrax, a disease of antiquity with a reputation that has exceeded its actual impact on human health, has brought into reality the meaning of bioterrorism. No matter how prepared a population may be, bioterrorism cannot be prevented. The first case or cases will occur and will serve to alert the authorities to initiate the preexisting plan to limit the quantitation of the bioterrorist event.

Although much effort may have been expended in developing a response to a bioterroristic event, it is likely that deficiencies will become apparent as the plan is implemented, partly because some aspects of any plan will vary depending on the agent involved. This is portrayed by the current bioterroristic anthrax event. Although not the preferred method of testing a plan, lessons will be learned from the current activities, necessitating corrections and additions to the plans. This will strengthen our ability to respond more effectively and efficiently to another bioterroristic attack.

Bioterrorism is the use or threatened use of biologic agents against a person, group, or larger population to create fear or illnesses for purposes of intimidation, gaining an advantage, interruption of normal activities, or ideologic objectives. The resultant reaction is dependent upon the actual event and the population involved and can vary from a minimal effect to disruption of ongoing activities and emotional reaction, illness, or death. Bioterrorism is distinct from biologic warfare. Although there may be similarities in agents considered for use in the desired effect or the method of dispersion, the anticipated results are different.

A review of the published reports of bioterroristic events in the United States shows a hundredfold increase in the reports from the early 1900s to the present time (1Go). The majority of these reports have been hoaxes as distinct from an actual event. The most prevalent agent threatened in these hoaxes has been Bacillus anthracis. The current episode is the first documented instance in which B. anthracis has been used successfully.

FEATURES OF BIOTERRORISM

In considering bioterroristic agents, one characteristic perpetrators look for is an agent known for causing morbidity, possible mortality, and perhaps a disease that is difficult to diagnosis and to treat. The more severe the morbidity and mortality the greater the fear created. Other qualities of an agent include accessibility, reproducibility, stability, and dispersibility.

The organism must be available. Prior to 1996, it was not difficult to obtain most biologic agents from commercial sources, but new federal regulations were instituted that made it illegal for biologic supply companies to provide certain pathogenetic organisms.

The agent, once obtained, has to be reproducible; that is, the perpetrators have to be able to produce the quantity of organisms they need. This takes knowledge, materials, and equipment. Purification may be important. Once prepared, the agent has to be stable so that the desired characteristics do not change. The infecting dose of the agent is another important consideration and will vary according to the agent and the route of dissemination as well as by the host's susceptibility. Another characteristic is the incubation period. A short incubation period makes detection before symptoms occur more difficult, a potential desirable quality to the perpetrators. Other agent qualities are difficulty in identification and in eliminating the agent once it has been released.

The route of dispersion will determine the number of people exposed to the agent. Aerosol dispersion can expose the greatest number of people over time, but it is very difficult to meet the criteria necessary for widespread distribution. The agent has to be infectious by the inhalation route unless the aim is to contaminate a food or water supply by an aerosol. The airborne particles have to be less than 5 µm in size in order to be inhaled and deposited in the alveoli. If the aerosol created is colorless and odorless, it may not be detected until symptoms develop. Creating an aerosol takes a significant level of kinetic energy; this is where some perpetrators have failed in their attempts. Without an adequate energy force, a true aerosol cannot be created. Other environmental factors that can influence the success of aerosol dispersion include the direction and velocity of the wind, humidity, sunlight, radiation, and the possibility of the presence of other airborne pollutants. However, as the recent anthrax bioterroristic event demonstrated, aerosol dispersion on a smaller scale can occur with an appropriately prepared agent.

Dispersion through food or water allows a greater likelihood of reaching a specific group of people, as was demonstrated in The Dalles, Oregon, bioterrorism episode (2Go). Other routes of dispersion that have been attempted are through medicines, medical fluids, blood, and insect vectors, but these are less efficient in meeting the perpetrators' objectives.

Important host factors include susceptibility of the host and symptoms that make it difficult to arrive at a clinical diagnosis. Other factors are potential complex therapeutic measures and inadequate or no preventive measures.

The agents that have been primarily considered can be categorized by their pathogenicity. Those bioterroristic agents that are considered to be the most pathogenic include Variola major (smallpox), B. anthracis (anthrax), Yersinia pestis (plague), Clostridium botulinum (botulism), Francisella tularensis (tularemia), and some hemorrhagic fever viruses such as Ebola, Lassa, and Marborg.

The next level of agents includes Coxiella brunetti (Q fever), Brucella species (brucellosis), Pseudomonas mallei (glanders), and some encephalitis-causing viruses. Additionally, there are some other microorganisms of lesser toxicity that have been used in bioterroristic events such as Vibrio cholera, Salmonella, Shigella, and Staphylococcus.

BIOTERRORISM RESPONSE

The Centers for Disease Control and Prevention (CDC) has developed a plan for the public health and medical response to a bioterroristic event (3Go). In developing this plan, CDC collaborated with an extensive group of other agencies, organizations, and persons and prepared a plan incorporating actions at all levels of responsibility. They have prepared written and website documents and have participated in meetings and training sessions to disseminate their recommended plans. Training exercises include tabletop exercises, held to educate people with responsibilities in carrying out the plan and to point out deficiencies for subsequent modification.

The public health response to a bioterrorist event must be epidemiologically directed and oriented. There must be extremely close collaboration between the many different agencies at the federal, state, and local levels. The main areas involved in reacting to a bioterroristic event include planning, detection, diagnosis, investigation, treatment, communications, and training (4Go).

In the planning phase, attention must be given to close collaboration among the multiple partners that have responsibilities for implementing the plans. The partners at the federal, state, and local levels must assist in developing the plans as well as in carrying out the responsibilities. Jurisdictions must be defined and responsibilities assigned. In the United States, the federal agencies involved comprise those in Health and Human Services, including CDC, the National Institutes of Health, the Food and Drug Administration, the Agency for Health Care Research and Quality, and the Office of Emergency Preparedness. Other federal agencies include the Department of Agriculture, the Department of Commerce, and the Justice Department. In reality, all of the federal departments may have input into the preparedness plan. Of equal importance are the state and local agencies with responsibilities similar to those at the federal level. This overlap is where problems can occur. Administrative authority and leadership must be carefully and clearly defined. All persons involved in the response plan must know what their responsibilities are, when they should initiate their activities, where they should direct them, and how to implement them.

As previously indicated, it is not realistic to think that we can prevent the first case or cases in a bioterroristic event from occurring, but how we react subsequently is critical. The main objective must be to keep the quantitation of the event to a minimum. There are many disciplines that must be involved in these plans, but a critically important area is that of administration. Administrators must provide management skills that create the environment in which there can be successful accomplishment of the objectives. Other important professions include epidemiologists, laboratorian personnel, surveillance personnel, environmentalists, heath care personnel, behavior scientists, communication and public relations specialists, and support personnel. Resources, such as adequate and responsive laboratory facilities and supplies; access to computers; and other forms of communication, transportation, and finances must be available.

The second area of the response plan is that of detection. A critical activity here is public health surveillance, which can be either passive or active but must be sensitive and specific. The basic, routine, passive public health surveillance system in place throughout the United States is the first level of our detection system. It is the responsibility of all health care professionals who see patients and make diagnoses to report not only reportable diseases, but also any unusual number of cases of any disease or health event that they observe. Others who should be brought into the surveillance loop for potential bioterroristic events are the 911 services, police and fire departments, medical examiners, emergency room personnel, walk-in clinics, hospitals, poison control centers, public health personnel, pharmacies, veterinarians, the media, and all citizens. It is necessary to develop among all of these groups sensitivity to an unusual situation or occurrence of a case or cases of an unusual illness so that they will report the event to the appropriate authorities. Sensitivity will be more important than specificity. It will be necessary to develop case definitions for the reporting of diseases of concern in the bioterroristic response system.

Novel surveillance systems must be considered in planning for defense against bioterrorism. One such system is syndromic surveillance. Syndromic surveillance should include such syndromes as dyspnea, pneumonia, rash, nausea and/or vomiting, diarrhea, encephalitis, and other unexplained or unusual illnesses or deaths. While syndromic surveillance may be questioned, its usefulness must be evaluated.

All of these data sources must be linked together with communications going from bottom to top as well as from top to bottom. Computers can improve the efficiency of the surveillance system and provide support for the accumulation of data from multiple sources with regular analysis and dissemination of reports. The use of e-mail and pagers will improve communications at all levels of involvement.

Clues that should generate a report include an unusual agent associated with single or multiple illnesses in one or more areas. The agent may have an unusual genetic feature or physical or chemical property. Another clue could be a higher morbidity and mortality than expected for a known disease agent. In addition, a larger-than-expected number of persons with the same syndrome, or illness, or cause of death in the same or different areas could be a clue. There may also be an unusual presentation of the disease involving an unusual population or geographic area, such as a disease occurring at an unusual time of the year (e.g., influenza in the United States in July). An unusual method of transmission or a concurrent animal disease could also signal a bioterroristic event. The need to differentiate between a bioterroristic event and a new, emerging infection is apparent in considering events over the past 25 years. During this time, we have witnessed a number of new, emerging infections that initially had characteristics that resembled those of a bioterroristic event, such as hantavirus disease in the southwestern United States in the 1980s or West Nile virus in the northeast in 1999.

The next area of bioterrorism response is that of diagnosis. It is apparent from the current anthrax bioterrorism event that health care professionals must be educated about diseases to which they not have been exposed during their education because of the nonexistence or rarity of the diseases. Current educational programs for health care professionals must include discussion of rare diseases if actual cases cannot be seen. Appropriate laboratories have to be available, with trained personnel and proper equipment to make the diagnosis of unusual agents. It is not practical that every diagnostic laboratory be able to perform all diagnostic tests. Laboratories for routine diagnosis must be available at the local level and have easy access to a district, a state, or a regional laboratory in which more specific tests can be performed. There are several laboratories in the country, including at CDC, that can be used as the final reference.

We need to continue to improve our ability to perform rapid screening and identification of biologic agents. For example, the use of molecular biology is an important technology for demonstrating associations between strains isolated at different locations and/or at different times. There should be computerization of laboratory diagnostic results, including that of molecular typing so that organisms can be compared rapidly over great distances. These are areas that are being developed and researched throughout the country.

The next areas in the response plan are the investigations that should be initiated at the local level with rapid and ready support from state and federal agencies. There needs to be clarification from the beginning about who has the responsibility for directing and conducting the investigations, since a bioterroristic event will bring into the investigative arena more than just the public health agency. Epidemiologists trained and experienced in the techniques of applied epidemiology are central to any response plan. They must be readily and rapidly available and be knowledgeable about bioterroristic agents. The Epidemic Intel-ligence Service officers from CDC serve this function, with some located at state health departments and others located at CDC or at their field stations and on call to be deployed into the field (5Go). There would be benefit in having at least one Epidemic Intelligence Service officer in every state health department and in health departments of large metropolitan areas. Resources and information must be shared. Adequate laboratory support must be available so that the specimens collected, either clinically or from the environment, can be processed expeditiously by using modern technology with reports generated as soon as possible. This again brings in the need for a network of laboratories because any one laboratory may not be able to maintain a state of readiness to process an extraordinarily large number of specimens.

There needs to be a rapid assessment of the most preferred method of treatment using the most up-to-date and reasonable knowledge to prevent death, contain the spread of disease, and prevent further cases. Recommendations should be updated as new information becomes available. The establishment of the National Pharmaceutical Stockpile developed and maintained by CDC is a major factor in this area. There should be agreement concerning the items in the stockpile and clear guidelines about how requests can be made for release of the items.

Communication is a major aspect of the bioterrorism response plan not only for control and prevention purposes but to temper the fear and hysteria that results from bioterroristic events. One cannot prevent fear and hysteria, but communication and education can help modulate it and dampen its effect on the population. The information for dissemination must be specifically prepared for the group at which it is directed, whether it be a professional group or the general public, whether local, state, national, or international. The media has an important responsibility to assist in the dissemination of information; the Internet has become a major instrument for this. The public relations personnel should be given the responsibility for preparation and release of this information, for which there must be a single and well-informed source.

The last, but not the least important, aspect of the bioterroristic response is that of training. All categories of involved personnel must be trained concerning their own responsibilities. This can be accomplished through written materials, Internet material, and educational programs. Tabletop exercises, that is, field trials of the response plan, can be very effective not only in educating the responders but in identifying the deficiencies in the plans.

ANTHRAX

The history of anthrax goes back to biblical times, when at least one of the plagues is reported to have been anthrax (6Go). In the Middle Ages, there were reported epidemics of anthrax in Europe involving animals and humans. In the 1800s, ragpicker's disease in several European countries and woolsorter's disease (inhalational anthrax), especially in England, were occupational health problems. Woolsorter's disease was such a problem that, in 1919, England built a formaldehyde disinfecting station in Liverpool, where all imported wools had to be disinfected before they could be processed further. This resulted in a significant reduction in the occurrence of inhalational anthrax in England.

Anthrax has been reported in many countries, primarily involving animals such as cattle, sheep, and goats. Human cases have been primarily cutaneous, but in a number of countries, epidemics of gastrointestinal anthrax have also been reported. Except for woolsorter's disease in England, inhalational anthrax has been reported only occasionally. In modern times, the largest epidemic of human anthrax occurred in Zimbabwe from 1978 to 1985, during which time more than 10,000 cases were reported, primarily of cutaneous anthrax, but with occasional gastrointestinal cases (7Go). These cases were associated with an epizootic of anthrax among cattle in the country.

Data concerning the worldwide incidence of human anthrax are not exacting due to inadequate surveillance, but estimates have been made. During the first half of the twentieth century, it was estimated that the worldwide annual occurrence of human anthrax was approximately 20,000–100,000 cases (8Go). During the latter part of the twentieth century, it was estimated that there were approximately 2,000 annual cases. The majority of these cases were cutaneous, with occasional gastrointestinal cases being reported; inhalational cases were only rarely reported (6Go).

In the United States, anthrax has been primarily a disease associated with industrial contact with imported animal products, primarily goat hair, wool, and hides (6Go). Agricultural cases have been reported among persons who have contact with diseased animals, such as farmers, veterinarians, animal pathologists, and their support staff. From 1955 to 2000, CDC records indicated that 235 cases of human anthrax were reported, with 224 cases being cutaneous anthrax and 11 inhalational anthrax. Of the 235 cases, 182 were associated with industries that process imported animal products, primarily goat hair (113 cases); wool (34 cases); goat skins (16 cases); and meat, bone, and unknown (19 cases). Fifty-three cases were agriculturally related. Between 1900 and 2000, 18 cases of inhalational anthrax were reported, 16 of which were fatal (9Go). Most were isolated cases except for five cases reported in 1957 that occurred over a 9-week period as part of an epidemic of nine cases (four were cutaneous cases) in one goat hair-processing mill (10Go).

An unusual event occurred in 1979 when an epidemic of inhalational anthrax occurred in Sverdlovsk, Russia, due to the accidental release of an aerosol containing B. anthracis spores being processed in a governmental facility that was producing microbiologic agents for purposes of biologic warfare (11Go). There were 77 cases of inhalational anthrax reported, with 66 deaths. From data available, estimates were made that the median lethal dose of spore-bearing particles less than 5 µm in size was 4,100. This "experiment in nature" is proof that B. anthracis can be disseminated as an infectious aerosol over a human population.

A human anthrax vaccine was developed by the Army Chemical Corps in the 1950s that was field tested in four goat hair-processing mills in the late 1950s (12Go). Volunteers were randomly assigned to the vaccine or placebo group, inoculated and followed for 2 years. Each participant was evaluated 24–48 hours after receipt of the vaccine or placebo, and a minimal number of significant reactions were noted. The results showed a 92.5 percent efficacy in preventing cutaneous anthrax. Although five cases of inhalational anthrax occurred in one of the field trial mills (two in placebo recipients and three among nonparticipants), the results were not statistically significant in view of the small number of events to address the efficacy of the vaccine in preventing inhalation anthrax. After the conclusion of the field trial, the vaccine was made available to all of the employees in the participating mills and all other goat hair-processing mills in the United States. The decrease in cases of human anthrax in the United States has been the result of use of the vaccine, improved industrial processing of imported animal products, a reduction in the use of imported animal products, and improved animal husbandry.

The recent bioterroristic event in the United States has resulted in 18 confirmed cases of anthrax (including seven cutaneous cases and 11 inhalational cases) and four suspect cutaneous cases that have had their onsets from September 22 to November 13, 2001 (13Go). Cases have occurred in Boca Raton, Florida; New York City; Washington, DC; Trenton, New Jersey; and Oxford, Connecticut. All of the cutaneous cases have recovered, although several of them, including a child aged 7 months, had a rather severe and prolonged clinical illness. Among the inhalational cases, there have been five deaths (case-fatality = 45 percent). A major factor in the recovery of six of the 11 inhalational cases has been the prompt and aggressive therapy they received, including large intravenous doses of two to three antibiotics, rapid introduction of respiratory assistance, and careful monitoring of the body electrolytes and metabolites (14Go).

There are some new clinical features of the inhalational cases that have been reported.

Sixty percent of the inhalational cases had pulmonary effusions present, which were reported in a few of the previous cases in this country. Since the initial symptoms do resemble those of influenza, it is important to note that the symptom complex seen in the current cases does not include rhinitis, whereas this symptom is commonly seen in influenza. Additionally, whereas the case-fatality of the previous 18 cases of inhalational anthrax in the United States was 88 percent, the current rate among the current cases is 45 percent. This may reflect differences in dose or in the infecting strain or the institution of prompt and aggressive treatment for the recent cases.

Persons with cutaneous anthrax infections and those potentially exposed to infectious aerosols have been treated with antibiotics for 60 days and some for up to 100 days. This period of treatment was selected based on previous animal experiments in which the incubation periods were prolonged in primates who were exposed to B. anthracis aerosols after which antibiotic treatment was initiated. When treatment was stopped after several weeks, some primates developed inhalational anthrax (15Go), (16Go). Additional evidence was developed from the Sverdlovsk epidemic, in which some exposed citizens were placed on prophylactic antibiotics and some developed inhalational anthrax when they stopped taking these drugs (11Go).

The use of anthrax vaccine among persons potentially exposed to infectious aerosols has also been recommended, and some people have accepted this recommendation. This is based on experiments in which exposed primates subsequently treated with antibiotics and vaccinated had higher survival rates than did those primates who only received either vaccine or antibiotics (16Go). A number of the exposed postal workers were given prophylactic antibiotics and vaccinated. No cases of anthrax have occurred among these persons, but it is not possible to ascribe this to these prophylactic measures, since there is no comparison group. CDC has indicated that they will be followed for 2 years.

Another potential therapeutic measure is the use of anthrax immunoglobulin. Such a product was prepared in horses in the early 1900s, and although it was reported to be used successfully, serum reactions were a significant complication. Sera collected from vaccinated military personnel are being prepared for testing and potential future use (17Go).

In some of the exposed facilities, nasal cultures were obtained from persons in the immediate environment where contaminated letters (see below) were opened or processed, and a number of these persons had positive nasal cultures but were asymptomatic. Colonization has been demonstrated among some goat-hair mill employees where studies revealed that 15 percent of those cultured were positive for B. anthracis from either nasal swabs or throat washings without any concurrent or subsequent disease (18Go). Since these employees were not subsequently studied, it is not known whether they became carriers and/or were subclinically infected. It was not possible to study the nasally colonized persons in the recent event further since they were placed on 60 days of prophylactic antibiotics.

Questions have arisen about whether subclinical infections resulting in immunity could be playing a role in the current terroristic event. Workers in the goat-hair mill did develop subclinical infections as demonstrated by serologic studies in which 15 percent (11 of 72) of the workers who had no history of clinical anthrax or having been vaccinated developed antibodies (19Go).

Epidemiologically, it appears that all of the current bioterrorism cases were the result of direct or indirect contact with contaminated mail processed through the United States postal system (14Go). From available data, it is hypothesized that all of the cases could be related to two separate postmark dates at two postal facilities, one the Hamilton postal facility in Trenton, New Jersey, and the other the Brentwood postal facility in Washington, DC. The first diagnosed case occurred in Florida, in which a suspicious letter was delivered to the AMI Publishing Company in Boca Raton, where it was opened by a photo editor aged 63 years who developed inhalational anthrax and died (20Go). One other inhalational employee who worked in the AMI mail room recovered. It is hypothesized that B. anthracis was disseminated throughout the AMI building by this letter, by other contaminated letters, or by movement of air and/or people. Low-level environmental contamination was found in a postal facility that processed mail for the AMI building. It appears that, possibly, the contaminated letter or letters were processed through the Hamilton, New Jersey, postal facility at the same time as the other contaminated letters (see below). The company has, at least temporarily, moved into another building.

Letters processed in the Hamilton postal facility in Trenton, New Jersey, and delivered to the offices of NBC, CBS, ABC, and the New York Post in New York City resulted in the occurrence of four cases of cutaneous anthrax, but no deaths (19Go). The immediate environments in which the letters were opened were contaminated, but no dissemination occurred to other parts of the buildings. The internal environment of the Hamilton postal facility was contaminated from these letters, and there were two inhalational and two cutaneous cases among employees in this facility (20Go).

The two letters, one addressed to Senator Tom Daschle and one to Senator Patrick Leahy, were processed in the Brentwood postal facility in Washington, DC. The letter to Senator Daschle was delivered to his office in the Hart Senate Office Building and resulted in nasal colonization of a number of persons in proximity to the letter opening (20Go). This resulted in the dissemination of B. anthracis spores to distant areas within the Hart building. The letter to Senator Leahy was identified as mail was being held after the Daschle letter was opened and examined in special facilities at the US Army Biomedical Research Laboratory. The B. anthracis preparations in these two letters have been shown by epidemiologic and environmental studies to have the potential for widespread aerosol dispersion. They have been reported to be of "weapons grade" quality, that is, very pure and concentrated, and containing primarily B. anthracis-bearing particles 1 µm in size. Processing of these letters resulted in aerosolization of B. anthracis spores throughout the Brentwood postal facility that resulted in four cases of inhalational anthrax, with two deaths occurring among workers in this facility. The envelopes identified as the source of B. anthracis in these episodes were all tightly taped at the edges. There may have also been other contaminated letters processed in these postal facilities at the same time but not identified. The environmental contamination of these postal facilities suggests that B. anthracis spores came through the paper envelope or through minute tears in the envelope that occurred during the mechanical processing of the mail. It has been shown by some simulated experimental work in Canada that Bacillus globigii spores can escape from an envelope as it is opened and contaminate the environment (21Go).

Two other cases of inhalational anthrax, a New York City hospital employee aged 61 years and a Connecticut woman aged 94 years, are more difficult to explain (B. Kournikakis et al., Defence Research Establishment, unpublished manuscript). The two contaminated Senate letters were initially processed through the Hamilton postal facility, where the environment became contaminated with B. anthracis. This facility also processes mail distributed to a Wallingford, Connecticut, postal facility, through which the mail of the 94-year-old woman was processed (12Go). The Wallingford postal facility was also shown to be contaminated with B. anthracis. Careful examination of sorting records at the Hamilton facility revealed that less than 1 minute after the Leahy letter was processed, mail for the Wallingford facility was processed that could have resulted in contaminating mail going to the Wallingford facility. Processing of this mail resulted in environmental contamination of the Wallingford facility and possible tertiary contamination of mail distributed from this facility. An envelope addressed to a person who lived 4 miles (2.5 km) from the 94-year-old woman was positive for B. anthracis, although no illness was associated with this letter. Mail found in this woman's apartment was not contaminated with B. anthracis. It is possible that the same scenario explains the source of infection for the New York City case involving the 61-year-old hospital employee. This hypothesis is based on circumstantial evidence, but can explain these two cases. This suggests that these two persons may have been exposed to a lower dose of organisms and/or that they had a decreased level of immunity.

One case of inhalational anthrax occurred in a postal worker in another federal office building in Washington, and the source of his infection is considered to have also been contaminated mail processed through the Brentwood postal facility. The B. anthracis organisms isolated from all patients and the environments have all been reported to be the same genotype (genotype 62), which is also the same genotype as the Ames stock strain from the Department of Agriculture diagnostic laboratory in Ames, Iowa (21Go).

A question has been raised about whether anthrax vaccine, if available, should be used as a preexposure protection measure. CDC has indicated that laboratory workers processing specimens that may be contaminated with B. anthracis would be one high-priority group that should be vaccinated. Other population groups who, in their role in responding to terroristic events may be exposed to B. anthracis, have also been suggested as potential vaccine recipients, but no specific recommendations have been made as yet.

An aspect of bioterrorism events exemplified by this event is the copycat phenomenon. CDC surveyed state and territorial health departments and reported that approximately 7,000 reports had been received between September 11 and October 17, 2001, that required 4,800 follow-up telephone calls and that, in 1,050 instances, laboratories tested suspicious material, none of which were identified as containing B. anthracis (13Go).

Why has the current bioterroristic event been so successful in creating fear and disruption? It occurred without warning, using a biologic agent associated with a rare disease that has a high case-fatality rate, disseminated through the mail system, exposing populations not easily definable. Most persons are susceptible, and the earliest symptoms resemble a common respiratory disease, such as influenza, making diagnosis difficult. In addition, the organism is hardy and can persist in the environment for prolonged periods.

There are aspects of this bioterrorist event about which we know very little. Although using letters to theoretically expose people to B. anthracis has been the most common practice in postbioterroristic events, did the perpetrators of this event recognize the possibility of dispersion through a sealed envelope as it was processed through an automated mail-handling system? Did they hypothesize that opening a letter could not only contaminate the immediate environment, but also distant environments by means of air currents and human traffic? Did they recognize the difficulties in decontamination of large environments such as an office building? There are also questions concerning the B. anthracis organisms used, where they came from, and how they were prepared for dissemination. We do not have any new data concerning the infecting dose of B. anthracis.

Where do we go from here? It is hoped that we have learned a great deal about how to deal with and react to a bioterroristic event. There are aspects of this event that should help us prepare for future such occurrences as well as provide guidance for other pubic health programs. The need for a clearer administrative organization, including designation of the in-charge agency or person and who should do what when, and closer collaboration between participating agencies is apparent. Providing more forthcoming, regular, and accurate information for the public is important in order to update and educate the population and to help alleviate anxiety and fear. The importance of trained and readily available epidemiologists has been demonstrated. We have learned a great deal about conducting field investigations when time is of the essence. Our ability to identify microorganisms rapidly should be significantly strengthened as we explore new diagnostic procedures. We have also learned more about the clinical features of anthrax and the importance of rapid treatment.

As new resources and technology become available for strengthening our response to bioterrorism, there will be spin-off effects. We will strengthen our practice of public health at the federal level as well as at state and local levels. Public health surveillance will be improved as novel surveillance systems are implemented. Laboratories will be strengthened, and rapid methods of communication will be introduced at all levels. Research in many areas related to the response to bioterrorism will be funded that will have an impact on the continued evolution of public health practice.

NOTES

(Reprint requests to Dr. Brachman at this address).

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Received for publication March 28, 2002. Accepted for publication April 2, 2002.