What is the role of the practicing medical professional in the event of a bioterrorism attack and what is the expected response? This may be broken down into three simple steps: Identify, Report, and Refer [3].

The most successful bioterrorist attack in the United States before 2001 occurred in Oregon in 1984, when members of the Rajneesh commune attempted to influence the outcome of an election by infecting the salad bars of 10 restaurants with Salmonella spp. bacteria. They believed that if the local citizens were inflicted with diarrhea, they would not be able to vote. More than 750 people were sickened by the attack, but if this had been done with volatized anthrax spores, there could have been hundreds of fatalities [4,5]. The lead medical investigator admitted that public health officials were unprepared to deal with an attack of greater magnitude.

General antiterrorism training efforts intensified following the New York City World Trade Center bombing in 1993. The Tokyo subway sarin nerve agent release and Oklahoma City federal building bombing, both occurring in 1995, stimulated an additional increase in awareness of bioterrorism. In November 1997, Secretary of Defense William Cohen announced that all U.S. military troops would be immunized against anthrax as a precaution [6]. Additionally, the disclosure that a sophisticated offensive biologic warfare program existed in the former Soviet Union along with information obtained after the 2001 attacks on New York and Washington, D.C., reinforced the need for increased training and education.

The CDC has defined three categories of possible bioterror agents and diseases. Agents are categorized according to their priority as risks to national security [7].

Despite the very different properties of bacteria, viruses, and toxins, most biologic and chemical agents that can be used as weapons share some common characteristics. The most important characteristic is the ability of the agent to be dispersed in aerosols, with a particle size of 1–5 microns. These particles can remain suspended (in certain weather conditions) for hours and, if inhaled, will penetrate the distal bronchioles and terminal alveoli of victims. Particles larger than 5 microns would tend to be filtered out in the upper airway [9]. An indoor or domed stadium is a high-risk potential target for aerosolized biologic or chemical weapon attack.

Many of these agents may also be dispersed by contamination of foodstuffs, as was the case with the 1984 Rajneesh Salmonella attacks, although the effect is localized. It is estimated that less than 1 gram of botulinum toxin could poison 100,000 individuals if added to the commercial milk supply; nearly 600,000 could be poisoned with 10 grams [10]. Parasites (e.g., tapeworm eggs) could presumably be placed into a salad bar, salsa bar, or drinking water dispensers, and symptoms would not be seen until weeks or years after becoming infected [11]. This type of bioterrorist attack could be carried out for many months without being detected. Even after presentation of symptoms, diagnosis may not be rapid because many healthcare professionals are unfamiliar with tapeworm infections [11].

Waterborne dispersion is also a concern; however, the threat of harming large numbers of people by dispersing biologic or chemical agents into reservoirs is often mitigated by water treatment. Nonetheless, there have been successful bioterrorist attacks on drinking water supplies. One such incident occurred in Edinburgh, Scotland, in 1990, when nine individuals in the same apartment complex were infected with Giardia[11]. The apartment complex had an unsecured water supply, which was purposefully contaminated with feces. A bioterrorist might tap into and contaminate a large building's water supply, which is unlikely to undergo additional purification.

Bacterial agents are among the most probable sources of bioterror and include anthrax, brucellosis, plague, tularemia, and Q fever. They are generally easily accessible and fairly simple to spread. Bacteria can cause diseases in humans and animals by two possible means: by invasion of tissues or by production of toxins that cause a pathologic response. In many cases, pathogenic bacteria possess both properties. Fortunately, this group of agents often responds to specific therapy with antibiotics. The following sections will examine the more common bacterial agents in detail.

The anthrax skin infection begins as a raised pruritic lesion or papule that resembles an insect bite. Within one to two days, the lesion develops into a fluid-filled vesicle, which ruptures to form a painless ulcer, 1–3 cm in diameter, with a necrotic area in the center [15,19]. Pronounced edema is often associated with the lesions because of the release of an edema-producing toxin by B. anthracis. The lymph nodes in the area may become involved and enlarged. The incubation period in humans is usually one to seven days but could be prolonged to almost two weeks [15,19]. To describe the lesion in more detail, picture a painless macular eruption that appears within two to five days, most commonly on an exposed portion of the body. The lesion progresses from a red macule to a pruritic papule, then to a single vesicle or ring of vesicles. This is followed by a depressed ulcer and finally a black necrotic eschar that falls off within 7 to 10 days. There is edema associated with the eschar but usually no permanent scarring of the affected area. The cutaneous form of anthrax progresses to systemic disease in 10% to 20% of the cases, with a fatality rate of up to 20% if untreated [15,19]. Laboratory tests of blood products are usually normal if the disease is not disseminated. The systemic symptoms of cutaneous anthrax infection include fever, headache, regional lymph node involvement, and myalgia [19].

Clinical suspicion of plague should prompt immediate treatment of symptomatic patients with two distinct classes of antimicrobials, at least one of which is first-line, until sensitivity patterns of the infecting Y. pestis strain are known. While naturally occurring antimicrobial resistance is rare in Y. pestis, there is potential for engineered resistance as part of a bioterrorism release. Treating initially with two distinct classes of antimicrobials increases the likelihood that the patients will receive at least one effective agent [42]. FDA-approved antimicrobials for treatment and prophylaxis of plague include streptomycin, ciprofloxacin, levofloxacin, moxifloxacin, and doxycycline. Although gentamicin, chloramphenicol, and trimethoprim-sulfamethoxazole are not FDA approved for plague, they are considered to be effective based on clinical experience and animal data [42].

Tularemia is one of the most infectious diseases known; as few as 10 F. tularensis bacteria can cause disease in humans [49,50]. Consequently, it has been widely exploited as a weapon of bioterror. The Japanese studied it for use between 1932 and 1945, the Soviet Union may have used it on the Eastern Front in World War II, and the United States possessed a 450 kg weaponized dry-form stockpile until the use of biologic arsenals was eliminated [49,51]. The most probable dissemination of F. tularensis as a weapon would be as an aerosol [50]. In fact, epidemics have occurred after harvests in Northern Europe, where the organism became aerosolized and infected hundreds of people. The organism is quite hardy and can survive for prolonged periods of time in water, mud, and animal carcasses. Even frozen, F. tularensis is highly infectious, and laboratory workers have become infected while inspecting incubation plates [49]. It is estimated that a 50 kg aerosolized release over a 5 million inhabitant metropolitan area could infect 250,000 people and kill nearly 20,000 [51].

Variola can be used as a biologic weapon in aerosol form or deposited onto surfaces. Because smallpox vaccination of the general population in the United States was discontinued in the 1980s, the use of the smallpox virus as a weapon constitutes a large threat, especially because certain countries may be harboring stockpiles of the agent.

The "ring vaccination" strategy will be the first-line strategy in a smallpox emergency. It vaccinates the contacts of patients with confirmed smallpox and also those who are in close contact with those contacts. This may include [88,89]:

In the United States, there are no licensed vaccines for any of the VHFs, with the exception of yellow fever; some additional VHF vaccines are available in other countries (e.g., Candid #1, an Argentine hemorrhagic fever vaccine available in Argentina). The yellow fever vaccine, 17D, was developed when outbreaks caused widespread disease among workers and military forces in endemic areas [9]. The vaccine is a live attenuated preparation that is very effective when administered to travelers and those in endemic areas [90]. It is not available in large amounts and would not be useful in preventing disease in multiple areas or in large populations. It would also not be useful in a postexposure scenario because yellow fever has an incubation period significantly shorter than the time it takes for the inoculated person to develop the neutralizing antibodies [90].

Botulinum toxins gained widespread recognition as a result of the introduction of botulinum Type A (Botox) into the field of cosmetology. The toxins have been medically significant for many years due to the serious and often fatal consequences of ingesting improperly canned or bottled foods. Botulinum toxins are proteins produced by the anaerobic bacterium Clostridium botulinum and consist of seven separate but related neurotoxins, denoted A through G. All of the strains produce similar effects when ingested or inhaled. They are among the most toxic compounds known, with serotype A having an estimated toxic dose of 0.001 mcg/kg of body weight oral or injected and 0.07 mcg/kg of body weight inhaled [101]. These neurotoxins act by binding at the presynaptic nerve terminals and at the cholinergic autonomic sites. They also block acetylcholine transmission, causing skeletal muscle weakness and paralysis as well as bulbar palsies [102,103]. If effectively dispersed in aerosol form, 1 gram of botulinum toxin has the potential to kill more than 1 million people [104].

Botulinum toxins gained widespread recognition as a result of the introduction of botulinum Type A (Botox) into the field of cosmetology. The toxins have been medically significant for many years due to the serious and often fatal consequences of ingesting improperly canned or bottled foods. Botulinum toxins are proteins produced by the anaerobic bacterium Clostridium botulinum and consist of seven separate but related neurotoxins, denoted A through G. All of the strains produce similar effects when ingested or inhaled. They are among the most toxic compounds known, with serotype A having an estimated toxic dose of 0.001 mcg/kg of body weight oral or injected and 0.07 mcg/kg of body weight inhaled [101]. These neurotoxins act by binding at the presynaptic nerve terminals and at the cholinergic autonomic sites. They also block acetylcholine transmission, causing skeletal muscle weakness and paralysis as well as bulbar palsies [102,103]. If effectively dispersed in aerosol form, 1 gram of botulinum toxin has the potential to kill more than 1 million people [104].

The gastrointestinal signs and symptoms of oral ricin poisoning include abdominal pain, vomiting, gastrointestinal hemorrhage with bloody diarrhea, fluid and electrolyte depletion, hypotension, tachycardia, and eventually hepatic, splenic, pancreatic, and renal necrosis [55]. The incubation period depends on the amount ingested and is usually four to six hours, although some cases have been seen with symptoms beginning within 15 minutes [8]. As noted, the initial dose can be as low as 1 mg, but this is not commonly seen. Death can occur in three to five days from organ failure and hypovolemic shock [55]. However, the death rate for ricin (or at least castor bean) ingestion is less than 2% and depends greatly on the dose [11].

There is no person-to-person transmission of ricin, and secondary transmission of aerosols from victims of ricin poisoning is not documented [55,121]. If ricin is released as an aerosol, careful decontamination will be necessary to prevent re-aerosolization. Ricin-infected patients' clothing and personal effects should be removed and disposed of according to safety regulations. Whenever possible, this should take place prior to arrival at a healthcare facility [116]. Exposed skin can be decontaminated with soap and water and a 0.1% sodium hypochlorite solution, which inactivates the ricin toxin [55]. Eyes may be irrigated with a saline solution.

Other possible clues to a biologic warfare or terrorist attack include [1,102]:

Every medical facility should have a plan in place to delineate how to deliver care in the event of a large-scale bioterrorist event. This disaster plan should be created with input from the infection control committee, administration, emergency department, laboratory directors, and nursing directors [1]. Processes for triage, safe housing, and care for potentially large numbers of affected individuals should be included in the bioterrorism plan. The needs of the facility will vary based on the size of the regional population served. Triage and management planning for large-scale events may include the following [1]: