Epidemiologic Responses to Anthrax Outbreaks: A Review of Field Investigations, 1950–2001

We used unpublished reports, published manuscripts, and communication with investigators to identify and summarize 49 anthrax-related epidemiologic field investigations conducted by the Centers for Disease Control and Prevention from 1950 to August 2001. Of 41 investigations in which Bacillus anthracis caused human or animal disease, 24 were in agricultural settings, 11 in textile mills, and 6 in other settings. Among the other investigations, two focused on building decontamination, one was a response to bioterrorism threats, and five involved other causes. Knowledge gained in these investigations helped guide the public health response to the October 2001 intentional release of B. anthracis, especially by addressing the management of anthrax threats, prevention of occupational anthrax, use of antibiotic prophylaxis in exposed persons, use of vaccination, spread of B. anthracis spores in aerosols, clinical diagnostic and laboratory confirmation methods, techniques for environmental sampling of exposed surfaces, and methods for decontaminating buildings.

he intentional release of Bacillus anthracis in October 2001 greatly challenged the U.S. public health system. Collaborating with partners in other federal, state, and local health agencies, the Centers for Disease Control and Prevention (CDC) responded to these bioterrorism events by relying on experience investigating public health aspects of anthrax over the past 50 years (1). Topics addressed in these investigations included epidemiology, vaccines (2,3), controlling anthrax in industrial and agricultural settings (4), public health response to bioterrorism events (5), B. anthracis contamination of milk and meat (6), identifying B. anthracis-contaminated commercial products (7), decontamination methods for contaminated environmental sites, and laboratory methods, among others.
Field studies conducted by the Epidemic Intelligence Service (EIS) constituted the cornerstone of these investigative efforts (8). When invited by a state health department or national ministry of health, CDC's EIS Officers conduct field investigations, Epidemic-Aids (known as Epi-Aids), in response to acute public health needs in the United States and other countries. Recently, historic documents from >4,000 Epi-Aids (approximately 90% domestic, 10% international) from 1950 to 1999 were made more accessible through the creation of an internal, searchable electronic database. It includes many unpublished CDC reports on early anthrax investigations, which form the basis of this report.
B. anthracis, the gram-positive, spore-forming, rod-shaped bacterium that causes anthrax (9), is most commonly a zoonotic pathogen. Human B. anthracis infections are rare in the United States; the number of cases has decreased steadily from an average of 35 reported cases per year in the 1950s to <1 reported case per year since 1980 (10,11) (Table 1). Most reported cases have been cutaneous. Before October 2001, the last case of inhalational anthrax in the United States occurred in 1976 (12,13).
To answer questions raised when the bioterrorism-related cases of anthrax were identified in October 2001, we reviewed results of field investigations of anthrax. We also identified current questions for which past experience with anthrax provided relatively little information and for which further research is needed.

Methods
CDC anthrax-related field investigations from 1950 to 2001 were identified from several sources. First, the new database of historical Epi-Aid documents  was searched to retrieve all documents in which "anthrax" or "anthracis" appeared either as an assigned keyword or as a text string in a full-text search. Epi-Aid documents related to anthrax investigations in 2000 and 2001 were identified manually in an EIS administrative database. These searches identified a variety of types of documents, including initial requests for epidemiologic assistance, interim progress reports, final reports, and memoranda.
Additional CDC anthrax-related field investigations were identified by two coauthors (PB and AK) who were personally involved in most anthrax investigations conducted by the agency since the 1950s. References describing these additional investigations were located in the MMWR and in published medical articles. To limit this report to a description of CDC's institutional experience, rather than a broader review of publications on anthrax investigations, we excluded (a) anthrax case reports published in the MMWR but unrelated to a CDC field investigation and (b) published reports on anthrax by investigators not affiliated with CDC.
From the unpublished Epi-Aid documents and published reports for each investigation, we abstracted the following information: year, location, number of human and animal cases, clinical form of the disease, occupational or other exposures for human patients, environmental sampling methods and data, and study recommendations.

Results
A total of 49 relevant field investigations ( Table 2) were included in this report: 42 Epi-Aids and 7 other investigations. Detailed reports and MMWR published summaries were available for 39 (93%) of the 42 Epi-Aid field investigations. For three agriculture-related investigations (Epi-Aids 1963-2, 1959-38, 1957, only the initial invitation for epidemiologic assistance was available for review. Of these 49 field investigations, 41 (84%) involved human or animal infections with B. anthracis, 2 were evaluations of decontamination of B. anthracis-contaminated textile mills (1967 and 1972), and 1 was an investigation of bioterrorism threats involving anthrax (1998). In the other 5 investigations, B. anthracis was not found to be the causative organism, despite initial suspicion. Because these investigations include only anthrax cases for which CDC's assistance was requested, they represent only a small proportion of the total number of U.S. cases reported during this period ( Table 1).
Most of the investigations (41/49, 84%) were conducted from 1950 to 1980; only 8 anthrax-related investigations were conducted by CDC from 1980 until the October 2001 bioterrorism events. This trend mirrors the decline in reported U.S. anthrax cases in the latter half of the 20th century (10) ( Table 1).

Site
Among the 41 field investigations involving infection with B. anthracis (Table 2), 24 involved an agricultural setting (farms, contact with livestock, or both), 11 textile mills, 4 B. anthracis-contaminated commercial products, and 1 contaminated cow bones; in 1 instance, the source of infection was not determined. Thirty-eight (93%) of the 41 investigations took place in the United States; other investigations were conducted in Haiti (1974), Paraguay (1986), and Kazakhstan (1998).

Clinical Form and Mechanism of Infection
All U.S. investigations involved cutaneous or inhalational anthrax (Table 3). Excluding large outbreaks in Kazakhstan and Paraguay, investigations in this report include 39 cutaneous and 9 inhalational cases of human anthrax. Among the investigations with available information on age and sex of

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patients, ages ranged from 19 to 67 years (median 40 years), and most cases were in males ( Table 3). Routes of infection were largely a function of setting. Of the 27 cases in textile mills, 21 (78%) were cutaneous, and 6 (22%) were inhalational. Contaminated goat hair or wool was the primary vehicle of infection. Persons working with raw, unprocessed materials were at greatest risk for infection (4). Of the six inhalational cases in textile mills, five were fatal. Three cases of fatal inhalational anthrax were also reported in non-textile mill workers (12,31) (Epi-Aid 1967-43).
Of the 24 investigations in agricultural settings, 9 (38%) included at least one human case. All human cases were acquired cutaneously while a person was handling, performing necropsy on, or disposing of dead animals. The most extensive cross-infection between animals and humans occurred in the 1998 outbreak in Kazakhstan, in which at least 53 human cases occurred; most were cutaneous cases acquired from slaughtering animals (Epi-Aid 1998-83).
Although four investigation reports included concern over possible waterborne transmission ( [15] and Epi-Aids 1966 -12, 1975-6, 1979-95), this route was not identified in any of the reports of human cases, and water contamination was not regarded as a source of infection. However, disease incidence in animals usually coincided with extremes of wet and dry weather conditions.
Gastrointestinal anthrax was documented in one investigation. Of the 53 persons with anthrax in the 1998 Kazakhstan outbreak, 2 were diagnosed with gastrointestinal anthrax after eating contaminated raw meat. In 1968 in Connecticut, 204 kg of B. anthracis-contaminated meat was sold as hamburger before the epizootic investigation; although purchasers of the meat could not be located, no human cases of anthrax were known to have occurred from the contaminated meat (Epi-Aid 1968-78). In addition, in 2000, a Minnesota farm family ate well-cooked meat from a B. anthracis-infected steer. Some family members had gastrointestinal symptoms, but investigators could not confirm or rule out infection with B. anthracis (54).

Human Prophylaxis
In nine outbreaks, 136 persons were documented to have received antibiotic postexposure prophylaxis. In at least five of the investigations, postexposure prophylactic therapy was stopped once additional information about risk became available. None of these reports described subsequent infections in patients who received any prophylaxis. Early prophylactic regimens used penicillin injections, which were later replaced by tetracycline, then doxycycline and quinolones, administered orally or parenterally (Epi-Aids 1966-18, 1999. Prophylactic antibiotics have been recommended in specific cases involving direct physical contact with contaminated material, but are not routinely recommended because the risk for an adverse drug reaction may exceed the risk for infection (Epi-Aid 1975-6). In one report describing a series of events not consistent with public health recommendations, a worker who was potentially exposed to B. anthracis in a rendering plant placed a large bottle of tetracycline on a lunchroom table, and coworkers took various amounts of antibiotics if concerned about potential exposure (Epi-Aid 1979-95).
In a 1962 field investigation, an acellular anthrax vaccine was demonstrated to be 93% effective in reducing the risk for infection with B. anthracis in humans. The vaccine was subsequently recommended for persons who handle imported hair, wool, hides, or bone meal (2).

Occupational Exposures
In 23 of the 27 U.S. investigations involving human anthrax, exposures occurred in occupational settings. The other four investigations involved exposure to contaminated commercial products or to aerosolized B. anthracis spores while a person was passing close to contaminated industrial mills. Among persons exposed in textile mills, most affected workers had direct contact with wool and goat hair as part of their job. However, in 1961, fatal inhalational anthrax occurred in a secretary at a goat hair-processing mill (Epi-Aid 1961-40), and in 1966, cutaneous anthrax occurred in a truck driver who helped unload baled goat hair at a mill (Epi-Aid 1967-43).
In agricultural settings, most cases were in ranchers or other workers who were exposed during the slaughter, butchering, or disposal of B. anthracis-infected animals. During 1957-1971, cutaneous anthrax occurred in six veterinarians after they performed necropsies on infected animals; one veterinarian had not used gloves during the necropsy, another had an anthrax lesion on his wrist (suggesting it was uncovered), and no information is available about glove use by the other veterinarians. Other occupational exposures include the goat hair exposures of a pipe insulator in Ohio (51,52) and a weaver in California (12).

Environmental and Clinical Testing
Specific environmental sampling methods were described in 26 (59%) of the 44 investigations. Sampling methods varied by setting. In textile mills, investigators usually tested samples from raw and processed materials, especially goat hair and wool. In nine investigations, air and surface samples were also tested from numerous locations in and around the mills. In 1978 in North Carolina (Epi-Aid 1978-47), 300 soil samples were taken from the mill premises, the landfill, and private residences near the mill; none tested positive for B. anthracis. Samples were also tested from floor sweepings and vacuum cleaner contents from inside the homes of four mill workers; one sample tested positive for B. anthracis. In 1953 in North Carolina (Epi-Aid 1953-14), two guinea pigs and four mice were exposed to the air near operating machines in the mill for 3½ hours; no test results are available. No reports of the subsequent investigations of textile mills mentioned the use of such animal tests for environmental sampling during an acute epidemic, although primates were experimentally exposed to air from a B. anthraciscontaminated textile mill in South Carolina (55). Animal anthrax in mountainous area led to concern over water supply downstream. In agricultural settings, investigators frequently tested samples of soil, water, and animal carcasses. During a series of anthrax threats and hoaxes in 1998 (38) (Epi-Aid 1999-25), samples from mailed letters were tested for B. anthracis spores by phase microscopy in a university microbiology laboratory, cultured for B. anthracis in Laboratory Response Network Level B laboratories (56), and subjected to rapid antigen testing by the U.S. Army Medical Research Institute for Infectious Diseases. All samples from letters were negative. Environmental samples taken from buildings after telephoned threats of contaminated air-handling systems were also negative. In other investigations, objects tested for B. anthracis were goat hair pipe insulation (52), imported yarn (12), a knitted sweater (Epi-Aid 1967-43-3), goat hair from contaminated horse saddle pads (44), and Haitian goatskin handicrafts at various stages of the manufacturing process (46,47) (Epi-Aid 1974-96).

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With regard to clinical testing in human cases, most detailed reports mention smears and cultures being done on skin lesions and blood samples. Some of these tests were conducted after antibiotics had been started, thereby reducing the likelihood of a positive result. Several of the more recent investigations included serologic tests for antibodies to B. anthracis antigens but did not assess the utility of these clinical assays. Nasal swabs were collected from 37 workers during a 1953 North Carolina textile mill anthrax investigation (Epi-Aid 1953-14); laboratory results are not available. No

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other investigations mentioned use of nasal swabs, and the effectiveness of nasal swabs in detecting B. anthracis infection was not discussed in the reports reviewed.

Decontamination
Several reports recommended specific measures for decontaminating affected areas or materials. A 1953 report suggested that all dirt, dust, and sweepings from a potentially contaminated textile mill be burned (Epi-Aid 1953-14). A 1960 report indicated that a livestock rendering plant was "cleaned up in the recommended manner with 5% hot lye solution" (Epi-Aid 1960-12). A 1967 report recommended installation of a high-temperature furnace at the textile mill for burning wastes (Epi-Aid 1967-43). A 1978 report recommended that potentially contaminated textile mill wastes be soaked in a 5% formaldehyde solution before burial in a landfill (Epi-Aid 1978-65).
The report on Epi-Aid 1972-94 contains the most detail on building-decontamination procedures. In this investigation, an unoccupied New Hampshire textile mill complex slated for demolition was decontaminated. Recommendations were based in part on experience in the earlier decontamination of two South Carolina mill buildings (28); those buildings were subsequently used by another industry for >2 years without any cases of human anthrax being reported. The New Hampshire mill buildings were decontaminated with 9,691 L of liquid formaldehyde that was vaporized and delivered into the interior rooms of the sealed buildings. None of 260 spore strips containing B. anthracis, B. globigii (now known as B. atrophaeus), or B. subtilis placed in treated areas of the mill complex showed growth; 23 of 40 such strips placed in untreated (control) areas showed spore growth. In addition, 2 of 555 surface swabs tested positive before treatment, but none of 599 swabs tested positive after treatment. These data from spore strips and surface swabs suggest that the decontamination process was effective in reducing and possibly eliminating the environmental contamination with B. anthracis.
During a 1974 anthrax epizootic in Texas (Epi-Aid 1975-6), investigators evaluated the disposal of infected animal carcasses by burning them with old tires, wood, and crank case oil. All 21 samples of carcass ashes, underlying soil, and soil up to 1 m from the burn site were negative for B. anthracis.

Cross-Contamination
Two reports mentioned evidence of cross-contamination from a primary contaminated object to another object or site. In a North Carolina textile mill in 1987 (Epi-Aid 1987-77), investigators speculated that the sample of B. anthracis-contaminated Australian wool had been cross-contaminated by B. anthracis-contaminated West Asian cashmere stored in the same room. During another North Carolina anthrax outbreak in 1978 (Epi-Aid 1978-47), one of four vacuum cleaner dust samples from the homes of textile mill workers was positive for B. anthracis, suggesting that workers carried spores on their clothes from the mills to their homes. No cases of anthrax in workers' families were reported, suggesting that exposures to B. anthracis in the home were not clinically significant.

Misidentification of Cutaneous Anthrax
A complete differential diagnosis of the clinical manifestations of anthrax includes many other diseases (57,58). In five investigation reports and one MMWR case report, cutaneous lesions initially diagnosed as possible anthrax were subsequently attributed to other diseases ( Table 2). In 1975, anthrax was initially suspected in a 23-year-old Arizona man, but his illness was quickly determined to be plague (Epi-Aid 1975-115). In 1973, two sisters in California developed vesiculopapular lesions on their fingers after contact with ill lambs. Anthrax was suspected, but the cultures were negative, and the disease was diagnosed as human orf (59). In 1969, investigators determined that a gram-positive spore-forming bacillus from a skin lesion on a Wyoming meat-packing company worker was not B. anthracis, but no definitive species identification could be made (Epi-Aid 1969-78). B. anthracis was initially suspected as the cause of cutaneous lesions in persons in a remote village in Nepal in 1967, but plague was subsequently documented (Epi-Aid 1968-34). In 1965, laboratory samples from a skin lesion of a South Carolina customs inspector who had had contact with imported wool were negative for B. anthracis. Although no definitive diagnosis was made, the clinical picture made anthrax unlikely (Epi-Aid 1966-18). Finally, in 1957, cutaneous lesions on five New York butchers initially considered as possible anthrax were subsequently diagnosed as pyoderma caused by staphylococci, streptococci, or both (Epi-Aid 1958-16).

Recommendations and Impact of Investigations
Field investigation reports usually contain public health recommendations; many of these are appropriate for future anthrax epidemics or exposures. For infections associated with textile mills, a 1974 report stated that "decontamination of the primary source of B. anthracis is not generally held to be practical" (Epi-Aid 1974-77). The reports on textile mill investigations recommended anthrax vaccine with annually scheduled booster inoculations for mill workers at risk; use of personal protective equipment including specific work clothing and respirators, shower facilities, and separate lockers for work and street clothing; physical separation of raw and finished materials to prevent cross-contamination; design of work areas for easy cleaning; and air-exhaust systems designed to prevent the spread of spores. One report recommended that mill employees be "thoroughly indoctrinated" on the cause, nature, and control of anthrax (Epi-Aid 1953-14). In 1999, following multiple bioterrorist threats (38) (Epi-Aid 1999-25), antibiotic prophylaxis was recommended in cases with known or credible risk for direct exposure. For persons with suspected exposure to aerosolized spores, recommendations included isolating exposed clothing in a plastic bag, showering with copious amounts of soap and water, and washing all possibly contaminated materials with a 1:10 bleach dilution (38).

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For infections associated with farms and livestock, reports recommended vaccination of animals at risk, better education of farm workers on anthrax diagnosis and control, thorough destruction by burning of infected animals, prevention of infected livestock from reaching the market, improved supervision of slaughter and meat inspection, and, in some situations, farm quarantine. After the 1974 Texas epizootic (Epi-Aid 1975-06), anthrax vaccine was tested in dairy cattle to assure that the vaccine had no adverse effect on milk safety (6).
Investigations of B. anthracis-contaminated saddle pads (1974), Haitian handicrafts (1974), and imported yarn (1976) led to Consumer Product Safety Commission recommendations for destroying those products (7,39,45). In 1975, cutaneous anthrax developed in a New Jersey gelatin manufacturing plant worker after his exposure to contaminated dry cattle bones; the Occupational Safety and Health Administration levied fines for workplace safety violations (41).
The Haitian investigation also led to a federal ban on importing Haitian goatskin products. A review of such handicrafts collected at U.S. quarantine stations in 1980-1981 found that items continued to be contaminated with B. anthracis (47).
Recommendations to the Haitian Ministry of Health included providing incentives for reporting diseased animals, improving laboratory diagnostic capacity, increasing anthrax vaccination levels among livestock, educating livestock owners about the benefits of anthrax control, and improving the tanning procedures for goatskin drum heads (Epi-Aid 1974-96).

Discussion
In this report we review what has been learned from >40 epidemiologic field investigations of confirmed or suspected anthrax outbreaks in humans or animals during the last 50 years. In the 2001 bioterrorism response, investigators evaluated suspected anthrax cases by using clinical and laboratory diagnostic methods, such as chest radiographs, cultures, and serologic assays, that had been developed and refined during earlier investigations of inhalational and cutaneous anthrax in textile mill workers. In addition, histopathologic and immunohistochemical testing proved essential for diagnosing anthrax in persons who had been placed on antibiotics early and whose cultures were thus negative. Nasal swabs, as used in the 1953 textile mill investigation, are currently considered an unevalu- ated adjunct to environmental sampling for defining exposed populations in bioterrorism investigations (1,60). Nasal swabs were used in the 2001 investigation for defining the aerosol spread of B. anthracis spores in the Hart Senate Office Building and some other settings.
In the 2001 bioterrorism investigation, an anti-protective antigen, enzyme-linked immunosorbent assay (61) was used to confirm B. anthracis infection in several cases. Development of this assay was the culmination of decades of laboratory experience and research associated with past field investigations of anthrax.
Asymptomatic infection was documented in one serologic survey (33) conducted several months after an inhalational anthrax outbreak; however, in past and current investigations, the role of asymptomatic infection in providing protection is unclear. Human-to-human spread was not evident in any of the investigations reviewed.
Investigation into a series of anthrax-related threats and hoaxes in 1998 (Epi-Aid 1999-25) also helped lay the groundwork for the recent response. In that investigation, guidelines for risk assessment and postexposure antibiotic prophylaxis were developed, and coordination with first responders and law enforcement was emphasized (38). The investigation also led to revised immunization recommendations (5), which discuss the use of vaccine for postexposure prophylaxis.
In response to the bioterrorism events of 2001, additional guidelines were published on investigating and responding to B. anthracis exposures. These address clinical testing, use of antibiotic prophylaxis, closing of potentially contaminated buildings, and postexposure treatment options (1,62,63). Current recommendations for the use of anthrax vaccine are based in large part on a field trial conducted in 1962 (2,5). During the 2001 response, vaccination recommendations were expanded to at-risk populations; the 1962 vaccine efficacy study forms part of the justification for considering the vaccine for postexposure prophylaxis. Currently, the Advisory Committee on Immunization Practices recommends that vaccine be used in combination with antibiotics (ciprofloxacin, doxycycline, or penicillin) following a B. anthracis bioterrorism exposure, if vaccine is available (5). Vaccination is a critical component of the nation's preparedness and response activities for B. anthracis bioterrorism.
In past field investigations, the primary risk factor for human cutaneous anthrax has been direct physical contact with infected animals or commercial products containing B. anthracis spores. Ranchers, butchers, and veterinarians were at risk for such contact when working with infected animals. All the commercial products causing human infection were of animal origin; most were made from imported goat skin or hair.
For inhalational anthrax, the main risk factor was exposure to aerosolized spores, especially in or near a textile mill that processes goat hair. While it is unclear why some workers become infected while others in the same dusty environment do not, several factors may increase the likelihood for infection. First, direct work with unprocessed goat hair may create a heavier exposure to B. anthracis spores. Second, a weakened immune system may increase a person's susceptibility to infection (64). Two of the patients with inhalational anthrax probably had chronic pulmonary disease. In the 1957 investigation, sarcoidosis was present (31). In the 1966 investigation of a metal shop worker (Epi-Aid 1967-43), investigators noted the worker's "chronic cigarette cough" and suggested that his alcoholism, diabetes, and pancreatitis might have made him more susceptible than his healthy coworkers.
Over the past 50 years, a series of recommendations have focused mainly on preventing occupationally acquired anthrax, especially in textile mills and agricultural settings. For example, in 1962, anthrax vaccine was recommended for persons who handle imported hair, wool, hides, or bonemeal (2). More recently, it was recommended that veterinarians obtain diagnostic specimens but not perform necropsies on animals suspected to have died from anthrax (36). The National Institute for Occupational Safety and Health has been actively involved in many recent anthrax-related investigations (15,65). Some documents mentioned insects as possible vectors in the spread of B. anthracis. While mechanical spread of B. anthracis organisms by stable flies has been demonstrated in guinea pigs (66), the importance of insects as vectors in epizootics has not been determined. One hypothesis suggests that insect bites might allow superficial organisms an effective access point for intradermal infection. Insects, particularly horseflies, were explicitly mentioned in 12 investigations for their possible role in transmission; however, no evidence exists that biting flies contribute to transmission of disease from animals to humans.
Past methods for decontaminating buildings relied upon formaldehyde gas, now known to be carcinogenic. The recent decontamination of B. anthracis-contaminated buildings was accomplished with chlorine dioxide gas, by using the methods developed for decontaminating textile mill buildings. Pre-and posttreatment environmental sampling strategies developed in several of the earlier field investigations, including the systematic use of surface swabs and spore strips, were also used in the response to recent events. In these events, the wide dispersion from envelopes of small airborne particles containing spores led to higher than expected levels of cross-contamination, making decontamination more difficult (65).
Several limitations should be considered in interpreting the results of this review. CDC conducts field investigations only when invited by a state health department or ministry of health. Anthrax cases that did not actively involve CDC staff, such as those investigated solely by state or local health departments, were excluded; therefore, this is not a complete report of U.S. anthrax case investigations. However, CDC staff have consulted at least by telephone on almost every case of human anthrax reported in the United States since the 1950s (A. Kaufmann, pers. comm.). A manuscript reviewing the characteristics of all anthrax cases reported in the United States since 1955 is in preparation (D. Ashford, pers. comm.).

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Second, this review examines CDC's experience with field investigations involving anthrax; laboratory-based anthrax research was not included unless it was related to a field investigation. Third, final laboratory results were not available for some field investigations.

Conclusion
Much useful knowledge, ranging from the diagnosis of anthrax to the use of vaccine to protect populations, has been gained from these past investigations. However, many questions remain. Further research is needed to determine the lowest infectious dose, define what constitutes a true exposure for which antibiotic prophylaxis is warranted (especially in light of possible drug side effects), and determine whether spores delivered in an envelope create a residual risk after the primary contamination event. Other areas in which more research is needed include developing better rapid environmental testing methods (67), identifying optimal decontamination methods for a variety of contaminated settings, assessing B. anthracis spore background rates in selected settings, and determining the level of risk associated with a low degree of exposure to aerosols containing B. anthracis.
During the past 50 years, the scientific knowledge acquired in these field investigations has greatly improved the nation's ability to respond to anthrax outbreaks. New and unique challenges have been raised by the recent intentional release of B. anthracis. Further efforts to improve knowledge about anthrax, both in its natural setting and in the context of bioterrorism, are urgently needed.