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Biological terrorism: understanding the threat, preparation, and medical response.

The thought of an outbreak of disease caused by the intentional release of a pathogen or toxin in an American city was alien just 10 years ago. Many people believed that biological warfare was only in the military's imagination, perhaps to be faced by soldiers on a far-away battlefield, if at all. The "anthrax letters" and the resulting deaths from inhalation anthrax have changed that perception. The national, state, and local governments in the United States are preparing for what is now called "not if, but when and how extensive" biological terrorism. In contrast to the acute onset and first-responder focus with a chemical attack, in a bioterrorist attack, the physician and the hospital will be at the center of the fray. Whether the attack is a hoax, a small food-borne outbreak, a lethal aerosol cloud moving silently through a city at night, or the introduction of contagious disease, the physician who understands threat agent characteristics and diagnostic and treatment options and who thinks like an epidemiologist will have the greatest success in limiting the impact of the attack. As individual health care providers, we must add the exotic agents to our diagnostic differentials. Hospital administrators must consider augmenting diagnostic capabilities and surveillance programs and even making infrastructure modifications in preparation for the treatment of victims of bioterrorism. Above all, we must all educate ourselves. If done correctly, preparation for a biological attack will be as "dual use" as the facility that produced the weapon. A sound public health infrastructure, which includes all of us and our resources, will serve this nation well for the control of the disease, no matter what the cause of the disease.

Biological Warfare↗

Medical counterbioterrorism: the response to provide anthrax prophylaxis to New York City US Postal Service employees.

STUDY OBJECTIVE: We describe and analyze a recent rapid deployment of disaster medical assistance teams and other government agencies to provide medical screening and anthrax prophylaxis to New York City US Postal Service employees potentially exposed to letters contaminated with anthrax spores. METHODS: A description of the response effort is presented. Data were collected on standardized forms and included the numbers of postal employees screened and offered antibiotic prophylaxis, as well as the numbers of patients seen per worker hour by various medical professionals. RESULTS: One hundred members of 5 disaster medical assistance teams and other health professionals were deployed to New York City within 18 hours of activation. Over a 68-hour period, 7,076 patients were evaluated, representing all postal employees in the 6 major postal facilities in New York believed to be at risk for anthrax exposure. Of the total, 2,452 patients were seen during the first 24 hours, 3,875 during the second 24 hours, and the remaining 749 during the last 20 hours of operations. An average of 161 employees were screened per hour. The antibiotic most commonly dispensed was ciprofloxacin, followed by doxycycline and amoxicillin. CONCLUSION: The deployment of disaster medical assistance teams and other agencies to New York City to provide prophylaxis against inhalation anthrax to US Postal Service employees provides lessons for a rapid, efficient, and effective response to acts of bioterrorism. This deployment might also serve as a scaleable model for future events requiring medical prophylaxis.

Anthrax↗

Early statistical detection of anthrax outbreaks by tracking over-the-counter medication sales.

The recent series of anthrax attacks has reinforced the importance of biosurveillance systems for the timely detection of epidemics. This paper describes a statistical framework for monitoring grocery data to detect a large-scale but localized bioterrorism attack. Our system illustrates the potential of data sources that may be more timely than traditional medical and public health data. The system includes several layers, each customized to grocery data and tuned to finding footprints of an epidemic. We also propose an evaluation methodology that is suitable in the absence of data on large-scale bioterrorist attacks and disease outbreaks.

Anthrax↗

Short-course postexposure antibiotic prophylaxis combined with vaccination protects against experimental inhalational anthrax.

Prevention of inhalational anthrax after Bacillus anthracis spore exposure requires a prolonged course of antibiotic prophylaxis. In response to the 2001 anthrax attack in the United States, approximately 10,000 people were offered 60 days of antibiotic prophylaxis to prevent inhalational anthrax, but adherence to this regimen was poor. We sought to determine whether a short course of antibiotic prophylaxis after exposure could protect non-human primates from a high-dose spore challenge if vaccination was combined with antibiotics. Two groups of 10 rhesus macaques were exposed to approximately 1,600 LD50 of spores by aerosol. Both groups were given ciprofloxacin by orogastric tube twice daily for 14 days, beginning 1-2 h after exposure. One group also received three doses of the licensed human anthrax vaccine (anthrax vaccine adsorbed) after exposure. In the ciprofloxacin-only group, four of nine monkeys (44%) survived the challenge. In contrast, all 10 monkeys that received 14 days of antibiotic plus anthrax vaccine adsorbed survived (P = 0.011). Thus postexposure vaccination enhanced the protection afforded by 14 days of antibiotic prophylaxis alone and completely protected animals against inhalational anthrax. These data provide evidence that postexposure vaccination can shorten the duration of antibiotic prophylaxis required to protect against inhalational anthrax and may impact public health management of a bioterrorism event.

Administration, Inhalation↗

Early-phase transmission of Yersinia pestis by unblocked fleas as a mechanism explaining rapidly spreading plague epizootics.

Plague is a highly virulent disease believed to have killed millions during three historic human pandemics. Worldwide, it remains a threat to humans and is a potential agent of bioterrorism. Dissemination of Yersinia pestis, the etiological agent of plague, by blocked fleas has been the accepted paradigm for flea-borne transmission. However, this mechanism, which requires a lengthy extrinsic incubation period before a short infectious window often followed by death of the flea, cannot sufficiently explain the rapid rate of spread that typifies plague epidemics and epizootics. Inconsistencies between the expected rate of spread by blocked rat fleas and that observed during the Black Death has even caused speculation that plague was not the cause of this medieval pandemic. We used the primary vector to humans in North America, Oropsylla montana, which rarely becomes blocked, as a model for studying alternative flea-borne transmission mechanisms. Our data revealed that, in contrast to the classical blocked flea model, O. montana is immediately infectious, transmits efficiently for at least 4 d postinfection (early phase) and may remain infectious for a long time because the fleas do not suffer block-induced mortality. These factors match the criteria required to drive plague epizootics as defined by recently published mathematical models. The scenario of efficient early-phase transmission by unblocked fleas described in our study calls for a paradigm shift in concepts of how Y. pestis is transmitted during rapidly spreading epizootics and epidemics, including, perhaps, the Black Death.

Animals↗

Responding to a bioterrorist attack: environmental investigation of anthrax in New Jersey.

A bioterrorism attack using the United States postal system to deliver a hazardous biological agent to specific targets created multiple environmental and occupational exposure risks along the path of the anthrax-containing letters. On October 18, 2001, a suspected case of cutaneous anthrax was confirmed in a postal worker from the Trenton Processing and Distribution Center where at least four suspect letters were postmarked. Over the next three weeks, a team of investigators collected samples at 57 workplaces in New Jersey as part of a comprehensive environmental investigation to assess anthrax contamination as a result of this bioterrorist attack. A total of 1369 samples were collected with positive sample results found in two mail processing and distribution centers, six municipal post offices, and one private company. This large-scale epidemiological and public health investigation conducted by state and federal agencies included environmental evaluations utilizing general industrial hygiene principles. Issues of sampling strategy, methods, agency cooperation and communication, and site assessment coordination are discussed.

Anthrax↗

Efficacy of chlorine dioxide as a gas and in solution in the inactivation of two trichothecene mycotoxins.

The efficacy of chlorine dioxide (ClO2) in detoxifying two potential bioterrorism agents, the trichothecene mycotoxins verrucarin A and roridin A, was evaluated. In the first experiment, verrucarin A (1, 5, or 10 microg) and roridin A (5 or 10 microg) were each inoculated onto square-inch sections of glass, paper, and cloth and exposed to 1000 ppm of ClO2 for either 24 or 72 h at room temperature. In the second experiment, verrucarin A and roridin A (1 or 2 ppm in water) were treated with 200, 500, or 1000 ppm ClO2 for up to 116 h at room temperature in light and dark conditions (N = 9 per treatment for test and control). A yeast assay using Kluyveromyces marxianuswas used to quantify the toxicity of verrucarin A and roridin A. Additionally, high-performance liquid chromatography was performed on selected samples. Results for the first experiment showed that ClO2 treatment had no detectable effect on either toxin. For the second experiment, both toxins were completely inactivated at all tested concentrations in as little as 2 h after treatment with 1000 ppm ClO2. For verrucarin A, an effect was seen at the 500 ppm level, but this effect was not as strong as that observed at the 1000 ppm level. Roridin A toxicity was decreased after treatment with 200 and 500 ppm ClO2, but this was not significant until the 24-h exposure time was reached. These data show that ClO2 (in solution) can be effective for detoxification of roridin A or verrucarin A at selected concentrations and exposure times.

Bioterrorism↗

Assessment of electrical charge on airborne microorganisms by a new bioaerosol sampling method.

Bioaerosol sampling is necessary to monitor and control human exposure to harmful airborne microorganisms. An important parameter affecting the collection of airborne microorganisms is the electrical charge on the microorganisms. Using a new design of an electrostatic precipitator (ESP) for bioaerosol sampling, the polarity and relative strength of the electrical charges on airborne microorganisms were determined in several laboratory and field environments by measuring the overall physical collection efficiency and the biological collection efficiency at specific precipitation voltages and polarities. First, bacteria, fungal spores, and dust dispersed from soiled carpets were sampled in a walk-in test chamber. Second, a simulant of anthrax-causing Bacillus anthracis spores was dispersed and sampled in the same chamber. Third, bacteria were sampled in a small office while four adults were engaged in lively discussions. Fourth, bacteria and fungal spores released from hay and horse manure were sampled in a horse barn during cleanup operations. Fifth, bacteria in metalworking fluid droplets were sampled in a metalworking simulator. It was found that the new ESP differentiates between positively and negatively charged microorganisms, and that in most of the tested environments the airborne microorganisms had a net negative charge. This adds a signature to the sampled microorganisms that may assist in their identification or differentiation, for example, in an anti-bioterrorism network.

Aerosols↗

Development of evaluation procedures for local exhaust ventilation for United States postal service mail-processing equipment.

Researchers from the National Institute for Occupational Safety and Health (NIOSH) have conducted several evaluations of local exhaust ventilation (LEV) systems for the United States Postal Service (USPS) since autumn 2001 when (a) terrorist(s) employed the mail system for acts of bioterrorism. As a part of the USPS 2002 Emergency Preparedness Plan, the development and installation of LEV onto USPS mail-processing equipment can reduce future exposures to operators from potentially hazardous contaminants, such as anthrax, which might be emitted during the processing of mail. This article describes how NIOSH field testing led to the development of recommended testing procedures for evaluations of LEV capture efficiency for mail-processing equipment, including tracer gas measurements, smoke release observations, air velocity measurements, and decay-rate testing under access hoods.

Air Microbiology↗

Monitoring human exposures to upper-room germicidal ultraviolet irradiation.

After decades of neglect, the resurgence of tuberculosis in the United States between 1985 and 1992 renewed interest in the use of upper room ultraviolet germicidal irradiation to interrupt the transmission of airborne infections. More recently the bioterrorism threat and the appearance of new pathogens with the potential for airborne spread, such as severe acute respiratory syndrome (SARS), have stimulated installations of upper-room irradiation systems. The objective is to flood the entire volume of a room above 6.5 ft with high intensity ultraviolet germicidal irradiation, while minimizing unintentional irradiance below 6.5 ft to avoid eye and skin irritation. Air exchanges between the upper and lower room result in air disinfection of the occupied space. Designers of these systems have adopted the practice of limiting the maximum lower room irradiance at every point to less than the continuous 8-hour time-weighted average threshold limit value, severely limiting the irradiation intensity in the upper room and thereby reducing one of the two major factors determining germicidal effectiveness, the other being room air mixing. The hypothesis of this study is that eye and skin exposure will be well below the recommended safe dose even when maximum eye-level irradiance levels in the room exceed the 8-hour continuous exposure threshold limit. The method employed was to have subjects wear a small photometer that recorded total ultraviolet dose over the period of exposure while subjects went about their normal routine, and comparing this value with a hypothetical dose calculated from the highest measured eye-level irradiance. The results of the study, based on a limited number of observations, confirmed the hypothesis. Observed doses were one-third to a factor of a hundred or more lower than the doses calculated from maximum eye-level irradiances measurements in the occupants' spaces.

Bioterrorism↗

Risks and prevention of nosocomial transmission of rare zoonotic diseases.

Americans are increasingly exposed to exotic zoonotic diseases through travel, contact with exotic pets, occupational exposure, and leisure pursuits. Appropriate isolation precautions are required to prevent nosocomial transmission of rare zoonotic diseases for which person-to-person transmission has been documented. This minireview provides guidelines for the isolation of patients and management of staff exposed to the following infectious diseases with documented person-to-person transmission: Andes hantavirus disease, anthrax, B virus infection, hemorrhagic fevers (due to Ebola, Marburg, Lassa, Crimean-Congo hemorrhagic fever, Argentine hemorrhagic fever, and Bolivian hemorrhagic fever viruses), monkeypox, plague, Q fever, and rabies. Several of these infections may also be encountered as bioterrorism hazards (i.e., anthrax, hemorrhagic fever viruses, plague, and Q fever). Adherence to recommended isolation precautions will allow for proper patient care while protecting the health care workers who provide care to patients with known or suspected zoonotic infections capable of nosocomial transmission.

Animals↗

The past and present threat of rickettsial diseases to military medicine and international public health.

Morbidity and mortality caused by rickettsioses have had a major influence on military activities and public health for >2000 years. The threat posed by the rickettsioses is reviewed, focusing on the impact and epidemiology of those that have adversely influenced wartime operations and the current challenges posed by these diseases. With their uneven worldwide distribution, the discovery of drug-refractory strains of Orientia tsutsugamushi, the increased threat of their use in acts of bioterrorism, frequent deployment of troops to regions of endemicity, and exposures due to increased humanitarian missions, these diseases continue to be a threat to military personnel in the field. Effective strategies to reduce the impact of these diseases include development of effective vaccines, enhanced surveillance, and development of new safe, effective, and odorless repellants. The continuation of a proven, highly productive military infectious disease research program is essential for providing solutions to these daunting tasks.

Animals↗

Smallpox vaccination: a review, part I. Background, vaccination technique, normal vaccination and revaccination, and expected normal reactions.

Because smallpox could be a factor in bioterrorism, the United States has provided guidelines for smallpox vaccination of certain members of the population, including health care workers and first responders, as well as military personnel. A plan for more extensive vaccination, if it is needed in the event of a bioterrorist attack, is being developed under the aegis of the Centers for Disease Control and Prevention. The characteristics of smallpox vaccine, the technique of administration, and the expected reactions to primary vaccination and revaccination are outlined in this article.

Bioterrorism↗

Infectious diseases in cinema: virus hunters and killer microbes.

The world of infectious diseases has been rarely presented in the cinema with accuracy. Apart from random biographies of scientists and retellings of stories about great epidemics from the past, most films focus on the dangers presented by outbreaks of unknown agents that originate from acts of bioterrorism, from laboratory accidents, or even from space. We review these films and underline the possible effect that they have on the public's perception of infection--a perception that, when misguided, could prove to be problematic in times of epidemics.

Bioterrorism↗

Potential applications of conventional and molecular imaging to biodefense research.

Imaging methods that visualize the structure and function of the living body are widely used in patient care and biomedical research, but their full potential has not yet been applied to the study and treatment of the severe illnesses caused by pathogens of biodefense concern. "Conventional" imaging techniques (e.g., radiography, computed tomography, ultrasound, or magnetic resonance imaging) delineate anatomic changes in tissues, whereas "molecular" methods employ magnetic resonance, positron emission tomography, single-photon emission computed tomography, or optical (fluorescence or bioluminescence) imaging to detect biochemical reactions that accompany pathogen replication or host responses. We review the basic principles of these methods, describe the diseases caused by 6 pathogens classified as category A or B bioterror agents (anthrax, plague, tularemia, filoviral hemorrhagic fever, smallpox, and aerosolized equine encephalitis virus infection), and discuss how imaging could be used to study their pathogenesis in laboratory animals and to diagnose and monitor infection in humans.

Bioterrorism↗

Implementation of biosurety systems in a Department of Defense medical research laboratory.

New biosurety regulations and guidelines were implemented in 2003 because of increased concern for the safety and security of biological select agents and toxins (BSAT) that may be used as weapons of mass destruction. Biosurety is defined as the combination of security, biosafety, agent accountability, and personnel reliability needed to prevent unauthorized access to select agents of bioterrorism. These new regulations will lead to increased scrutiny of the use of select biological agents in registered research laboratories, but the regulations may have unintended effects on cost, progress, and perceptions in programs previously considered part of the academic research community. We review the history of biosurety, evolving guidelines, implementation of the regulations, and impacts at the lead research laboratory for medical biological defense for the Department of Defense.

Bioterrorism↗

Public perceptions and risk communications for botulism.

Formative research findings from 10 focus group interviews on botulism are described. Data were collected from a diverse sample of people throughout the United States in 2003, as part of a collaborative multisite initiative sponsored by the Centers for Disease Control and Prevention to improve communications materials on bioterrorism agents. Focus group guides included questions on knowledge, action, emotions, and information seeking in response to a series of scenarios on a hypothetical terrorist attack using botulinum toxin. Data were collected, transcribed, coded, and analyzed using content domains based on risk and health communications theories. Initial participant responses to scenarios were emotional, changing into immediate health and survival concerns conceptualized as information specific to the agent and event. Knowledge about botulism was low, and participants wanted clear, concise, and actionable messages. Broadcast media, the internet, and community-based sources were cited as sources of information. Findings have implications for botulism preparedness messages and for general public risk communications.

Attitude to Health↗

Lessons learned from a regional strategy for resource allocation.

Two qualitative case studies focus on the allocation of CDC funds distributed during 2002 for bioterrorism preparedness in two Texas public health regions (each as populous and complex as many states). Lessons learned are presented for public health officials and others who work to build essential public health services and security for our nation. The first lesson is that personal relationships are the cornerstone of preparedness. A major lesson is that a regional strategy to manage funds may be more effective than allocating funds on a per capita basis. One regional director required every local department to complete a strategic plan as a basis for proportional allocation of the funds. Control of communicable diseases was a central component of the planning. Some funds were kept at the regional level to provide epidemiology services, computer software, equipment, and training for the entire region. Confirmation of the value of this regional strategy was expressed by local public health and emergency management officials in a focus group 1 year after the strategy had been implemented. The group members also pointed out the need to streamline the planning process, provide up-to-date computer networks, and receive more than minimal communication. This regional strategy can be viewed from the perspective of adaptive leadership, defined as activities to bring about constructive change, which also can be used to analyze other difficult areas of preparedness.

Bioterrorism↗