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 unevaluated adjunct to environmental sampling for defining exposed populations in bioterrorism investigations (1
). 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 recent 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
). Current recommendations for the use of anthrax vaccine are based in large part on a field trial conducted in 1962 (2
). 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
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
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.). 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.