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CHAPTER 9:  Bioterrorism      41 storage facilities.35 Vesicants cause damage to eyes, skin, mucous membranes, and potentially the lungs if exposed to high concentrations. Sulfur mustards [bis(2-chloroethyl) sulfide] make up the most common vesicants used, although the nitrogen mustards were also produced, but never used militarily. 33 Other vesicant agents are phosgene oxime, a solid that liquefies at 35°C (95°F); this agent does not cause blisters but produces severe skin erythema. 23,35 Lewisite, an arsenical compound that smells like geraniums and that was developed in 1918, too late for use in World War I and thus never deployed, is also included in this category. Both lewisite and phosgene oxime produce symptoms on immediate contact. 34-36 Sulfur mustard skin symptoms are delayed in onset for 4 to 8 hours, leading to blistering similar to second-degree burns within 2 to 18 hours of initial exposure. 33 Ocular damage from vapor exposure to all these agents is common, leading to incapacitation of the victims exposed. Corneal vesicle formation and sloughing of epithelium occur. The primary goal of therapy is copious irrigation with water to dilute and remove the chemical, and then monitoring the patient with serial eye examinations, pulmonary monitoring, and careful attention to skin care. The mustard agents may produce a systemic toxicity, with marrow suppression as a delayed component presenting with a falling white blood cell count and increased risk of infection 3 to 5 days after exposure.  BIOTOXINS The biotoxins differ from biologic agents in that the toxins do not rep licate in the body and a sufficient dose needed to cause disease must be delivered. These agents produce unusual symptoms, some with delayed onset. Clues to biotoxin exposure are presented in Table 8-5. With many biotoxins, the lethal dose in 50% of exposed subjects is quite low (Table 8-6), allowing small amounts to potentially be made into a high-risk weaponized aerosol and dispersed intentionally.  BOTULINUM TOXIN Inhalational botulism has been described in humans only after an accidental laboratory exposure. It is estimated that the lethal dose in 50% of exposed subjects for inhalation botulism is 1 to 3 nanograms/kg. Three days after performing an autopsy on a lab animal that died of botulism, three technicians developed tightness in the throat, difficulty swallowing, and symptoms characterized as a cold without a fever. They developed ocular paresis, rotatory nystagmus, dilated pupils, dysarthria, TABLE 8-5 Indications of a Possible Biotoxin Exposure •   Occurrence of a disease or syndrome that rarely occurs naturally •   Multiple victims of a similar disease with no classic risk factors •   Epidemiology suggesting a point source or localized exposure •   Possible animal and human morbidity in the same area •   High mortality in an otherwise healthy population TABLE 8-6 Lethality of Biotoxins Agent LD50 (micrograms/kg) Botulinum toxin 0.001 Tetanus toxin 0.002 Staphylococcal enterotoxin B 0.02 Diphtheria toxin 0.10 Ciguatoxin 0.4 Ricin 3.0 Tetrodotoxin 8.0 Saxitoxin 10.0 Trichothecene toxin 1200 Abbreviation: LD50 = lethal dose in 50% of exposed subjects. ataxia, and generalized weakness. All recovered within 2 weeks with antitoxin treatment. 23 Diagnosis requires the recognition of the clinical presentation, with early subtle cranial nerve palsies, typically presenting with difficulty swallowing, palsies of extraocular muscles, and trouble speaking.

f exposed subjects. ataxia, and generalized weakness. All recovered within 2 weeks with antitoxin treatment. 23 Diagnosis requires the recognition of the clinical presentation, with early subtle cranial nerve palsies, typically presenting with difficulty swallowing, palsies of extraocular muscles, and trouble speaking. 37 Treatment with antitoxin will prevent progression of the disease but will not reverse paralysis once it occurs. Administer the antitoxin based on clinical suspicion as early as possible; do not wait for the results of laboratory tests. The heptavalent antitoxin against all subtypes of botulism is available by contacting the Centers for Disease Control and Prevention. 37 Give one vial of antitoxin IV in suspected cases of botulism. Supportive care, including mechanical ventilation, is frequently needed and may be required for 90 days or more in cases presenting with diaphragmatic paralysis before receiving the antitoxin. Antibiotics only have a role in wound botulism and are not indicated in inhalational botulism.  RICIN Ricin toxin gained notoriety when it was used as the agent to assassinate Bulgarian activist Georgi Markov. At autopsy, a pellet containing ricin was removed from a small wound in the back of his leg. The pellet was fired from a specially designed umbrella into his leg while he waited at a London bus stop. 23 Ricin is a toxin derived from the castor bean, Ricinus communis.38 Ricin is not toxic by ingestion and must either be injected or inhaled as an aerosolized powder to produce disease. Ricin is taken up by cells in many tissues and causes destruction of RNA, leading to cell death. With inhalation exposure, pulmonary symptoms occur after about an 8-hour postexposure delay. Inflammation, exudates, and pulmonary edema occur, producing a necrotizing pneumonitis. After parenteral administration, local pain occurs, followed in a few hours by weakness and flu-like symptoms. Fifteen to 24 hours later, nausea, vomiting, fever, and localized lymphadenopathy proximal to the injec tion site may occur. After 48 hours, a sepsis-like syndrome occurs with hypotension, leukocytosis, disseminated intravascular coagulation, and multiorgan system failure (involving the liver, kidneys, heart, lungs, and GI hemorrhage). In Georgi Markov’s case, death occurred by deterioration to complete atrioventricular dissociation. 23 The differential diag nosis includes other causes of sepsis, but in the setting of an intentional attack, staphylococcal enterotoxin B must also be considered. Aggressive supportive care in an intensive care unit is warranted for all cases. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Bioterrorism Joe Suyama INTRODUCTION AND EPIDEMIOLOGY Bioterrorism is the release, or the threat of a release, of a biologic agent among a civilian population for the purpose of causing illness or death in humans, animals, or agriculture that results in the spread of fear and disruption of daily life. Such an occurrence is a low-probability but highimpact event. In the past century, the specter of bioterrorism was largely monitored by concerned government and military leaders, but in 2001, civilian emergency responders and healthcare institutions in the United States were thrust into the medical, psychological, and public health response to a real bioterrorist incident with very little training or preparation. In 2001, the U.S. Postal Service was used to deliver let ters containing spores of Bacillus anthracis. The ensuing environmental contamination and health impact was widespread, resulting in CHAPTER Tintinalli_Sec02_p0019-0052.indd 41 7/30/19 4:59 PM

a real bioterrorist incident with very little training or preparation. In 2001, the U.S. Postal Service was used to deliver let ters containing spores of Bacillus anthracis. The ensuing environmental contamination and health impact was widespread, resulting in CHAPTER Tintinalli_Sec02_p0019-0052.indd 41 7/30/19 4:59 PM 42 SECTION 2: Disaster Management could have a similar human impact if used in a nefarious manner (e.g., hanta virus). The intentional etiology of future outbreaks may be apparent only through real-time epidemiologic cohort evaluation. Thus, this chapter will also emphasize the need for public health, ED, and emer gency management coordination, which is critical for: 1. Recognizing an event that is happening 2. Responding to the event by protecting healthcare assets from harm and managing illness 3. Scaling up internal and external resources (medical surge) 4. Integrating with other assets to meet the needs of the event RECOGNITION  PUBLIC HEALTH SURVEILLANCE Methods for potentially detecting a biologic event include the recognition of unusual epidemiologic phenomena, such as a high incidence of nonspecific illness, clusters or large numbers of rapidly fatal cases, or steep infection curves identified through public health surveillance systems. 9 For this reason, it is imperative to foster relationships with local public health entities through preparedness activities, drills, and real-time communication. Since 2001, preparedness efforts have included Joint Commission–mandated community-wide drills. In addition, through Emergency Management coordination between public and private entities, front-line ED staff are now able to receive routine and urgent communication through robust public health–based Health Alert Network systems. From a surveillance perspective, information shared through networks between public health, ED, and emergency management coordi nators, can include relevant data from: 1. Public health surveillance systems that can detect unusual patterns of signs, symptoms, or disease in the community 2. Sampling technologies (of which there are numerous types related to different jurisdictions and agencies) that detect the actual release of an agent of concern in the community The surveillance systems currently in use are based on collecting and analyzing public health information and/or patient diagnostic information in specific communities. It is intuitive that this has been enhanced by the widespread adoption of electronic health records. Information is sought from many disparate sources, including hospitals, clinics, nursing homes, pharmacies, emergency medical service systems, inde pendent laboratories, medical examiners, and general businesses (e.g., absenteeism rates). Information collected from EDs often is based on symptom complexes (syndromic surveillance). Other surveillance and risk assessment tools have been developed but must be further developed to improve their worth to the emergency medical and public health responders. Air sampling systems to detect inhalation agents have been implemented in some communities and for specific agencies, events, or facilities across the United States. The most well known is the BioWatch program, 13 which uses strategically placed sensors in specific communities. These sensors operate on the principle of drawing air samples across filters that are subsequently analyzed for some agents of concern. 14,15  ED SCENARIOS Based on historical cases, the following scenarios are the most likely ways in which a bioterrorist event would be detected clinically in the ED: 1. A patient presents with signs, symptoms, or real-time diagnostic results that obviously indicate a suspect disease process (e.g., small pox rash). 2.

14,15  ED SCENARIOS Based on historical cases, the following scenarios are the most likely ways in which a bioterrorist event would be detected clinically in the ED: 1. A patient presents with signs, symptoms, or real-time diagnostic results that obviously indicate a suspect disease process (e.g., small pox rash). 2. A patient presents with protean symptoms, but an astute clinician establishes enough criteria through the history, physical exam, shortturnaround laboratory results, and public health corroborative information to designate the patient as a presumptive case until diagnostic confirmation can be accomplished (e.g., Ebola infection). 22 diagnosed cases of anthrax infections: 11 cases of inhalational and 11 cases of cutaneous anthrax. 1 Five patients died as a direct result of this intentional release of anthrax spores that was determined to have unnatural particle size characteristics. 2 Communities on the eastern seaboard of the United States were severely affected, with thousands of people receiving prophylaxis for anthrax. 3 Fear then spread across the nation, as concern increased for a wider delivery of anthrax. In this century, there is growing angst in the scientific and medical communities regarding the potential for biologic agents to be modified using now common geneediting tools such as CRISPR, resulting in the creation of organisms with an even greater potential to cause harm and spread fear. Preparedness efforts against emerging or resurging infectious dis eases, including the pandemic H1N1 influenza response in 2009 and the international Ebola campaign in 2014, have enhanced our individual and systemic ability to effectively care for patients with austere infectious diseases. However, the intentional aspect of bioterrorism and the specter of directed harm to the public and to healthcare providers creates a different playing field that may hinder detection and response efforts, create a greater psychological burden to the public and responders, and possibly confound the treatment of patients due to organism enhancements or atypical presentation of naturally occurring infections. Biological agents with the potential to be used for bioterrorism are classified into two groups: biologically produced toxins and infectious organisms. Biologic toxins generally have properties similar to chemical agents. The health impact does not depend upon an incubation period to manifest disease in humans. Infectious organisms are further subdi vided into two categories: contagious (propagating person to person) and noncontagious. Contagious agents have additional ramifications, both for protection of the healthcare workforce as well as propagation of the disease beyond the initially exposed population. The contagious agents of greatest concern, such as smallpox, plague (pneumonic), and certain viral hemorrhagic fevers, are infectious from person-to-person through airborne or droplet transmission. Until proven otherwise, however, the primary response to a suspected biological agent release should consider the agent to be both highly infectious and contagious. This will allow for the highest level of environmental, administrative, and personal protection to be deployed to ensure the safety of first responder and the healthcare teams. AGENTS OF CONCERN The Federal Select Agent Program has compiled a list of agents that have been determined to have the “potential to pose a severe threat to the public, animal, or plant health. ” 6 Certain characteristics make individual organisms on this list particularly attractive as weapons for generating widespread fear, illness, or death among civilian populations. Thus, the Centers for Disease Control and Prevention has further characterized certain select agents based on four general criteria 7: 1.

h. ” 6 Certain characteristics make individual organisms on this list particularly attractive as weapons for generating widespread fear, illness, or death among civilian populations. Thus, the Centers for Disease Control and Prevention has further characterized certain select agents based on four general criteria 7: 1. Potential for public health impact 2. Delivery potential (an estimation of the ease for development and dissemination, including the potential for person-to-person trans mission of infection) 3. Public perception (fear) of the agent 4. Special requirements for public health preparedness (diagnostic, logistic, etc.) Using the above criteria, organisms can be broken down into three categories based on their overall potential to cause harm 8 (Table 9-1; Figures 9-1 to 9-3). Class A agents have the most severe potential and include viruses and bacteria such as variola major (smallpox), B. anthracis (anthrax), and Y ersinia pestis (plague). Class B agents are considered to have less potential for causing widespread illness and death or are more difficult to disseminate, and Class C agents are those that, as technology improves, could emerge as future threats. Many other common or emerging pathogens could be used to cause intentional injury and death. This chapter focuses on Class A agents, but applies also to a wide range of additional bacteria and viruses that Tintinalli_Sec02_p0019-0052.indd 42 7/30/19 4:59 PM

that, as technology improves, could emerge as future threats. Many other common or emerging pathogens could be used to cause intentional injury and death. This chapter focuses on Class A agents, but applies also to a wide range of additional bacteria and viruses that Tintinalli_Sec02_p0019-0052.indd 42 7/30/19 4:59 PM CHAPTER 9:  Bioterrorism      43 TABLE 9-1 Infectious Agents of Concern* as Defined by the Centers for Disease Control and Prevention (adapted from https://emergency.cdc.gov/bioterrorism/index.asp) Biologic Agent Disease Caused Incubation Period Signs and Symptoms Class A agents Variola major Smallpox (Figure 9-1) 7–19 d, usually 12 d Initially fever, severe myalgias, delirium, prostration; followed within 2 d by papular rash on the face spreading to extremities (affecting palms and soles) and then to trunk (lesser extent than chickenpox); lesions progress at same rate, becoming vesicular and then pustular with subsequent scab formation Bacillus anthracis Cutaneous anthrax (Figure 9-2) 1–12 d, usually <5 d Small painless or pruritic papule enlarging into eschar with surrounding vesicles and edema; sepsis possible, less common Oropharyngeal/GI anthrax 1–6 d Sore throat, ulcers on base of tongue, marked unilateral neck swelling, dysphagia, abdominal pain, vomiting, GI bleeding progressing to sepsis if untreated; mesenteric adenopathy on CT Injection anthrax Usually <5 d Fever and chills, groups of small blisters or papules that may itch at the injection site, followed by a painless skin sore with black center and subsequent deep abscess formation Inhalational anthrax (Figure 9-3) Usually <1 wk First stage is nonspecific (fever, cough, headache, malaise, fatigue); second stage (severe dyspnea, chest pain, shock) with rapid progression to death within 24 h after respiratory symptoms develop; hemorrhagic mediastinitis with widened mediastinum on radiograph. Progression to CNS involvement can occur after systemic spread. If suspected as a diagnosis, consider threat of intentional release of anthrax spores.

nea, chest pain, shock) with rapid progression to death within 24 h after respiratory symptoms develop; hemorrhagic mediastinitis with widened mediastinum on radiograph. Progression to CNS involvement can occur after systemic spread. If suspected as a diagnosis, consider threat of intentional release of anthrax spores. Yersinia pestis Bubonic plague 2–7 d Initially fever, chills, painful swollen lymph node(s); node progresses to bubo (sometimes suppurative) Pneumonic plague 1–4 d Fever, chills, cough, dyspnea, nausea, vomiting, abdominal pain; clinical condition consistent with gram-negative sepsis Primary septicemic plague 2–7 d The clinical condition is consistent with gram-negative sepsis, disseminated intravascular coagulation (secondary septicemic plague may occur after bubo formation) Clostridium botulinum Foodborne botulism 12–36 h, as early as 2 h GI symptoms followed by symmetric cranial neuropathies, blurred vision, progressing to descending paralysis and respiratory dysfunction Inhalational botulism† 6–72 h, usually 5 d Symmetric cranial nerve palsies followed by descending paralysis; death occurs from upper airway obstruction and diaphragmatic respiratory failure Francisella tularensis Tularemia 1–21 d based on type of infection Depends on route of exposure: all usually involve abrupt nonspecific febrile illness; inhalation exposure progressing to pleuropneumonitis; cutaneous exposure developing glandular or ulceroglandular lesions; ingestion developing oropharyngeal lesions/tonsillitis Filoviruses and arenaviruses (Ebola virus) Viral hemorrhagic fevers 2 d–3 wk, depending on virus Initial nonspecific febrile illness, sometimes with rash; progresses to bloody vomiting, diarrhea, shock Class B agents Coxiella burnetii Q fever 2–3 wk Fever, myalgias, headache, 30% develop pneumonia, rarely lethal (2%) Brucella species Brucellosis 2–4 wk Fever, myalgias, back pain; CNS infections and endocarditis possible Burkholderia mallei Glanders 10–14 d Local infection: ulcers, suppurative; pneumonia, pulmonic abscesses, sepsis possible Burkholderia pseudomallei Melioidosis 2 d to years reported Local infection: nodule; pneumonia, pulmonic abscesses, sepsis Alpha viruses (Venezuelan equine encephalitis, Eastern equine encephalitis, Western equine encephalitis) Encephalitis Variable Fever, headache, aseptic meningitis, encephalitis, focal paralysis, seizures Rickettsia prowazekii Typhus fever 7–14 d Fever, headache, rash Toxins (ricin, Staphylococcus, enterotoxin B) Toxic syndromes — — Chlamydia psittaci Psittacosis 6–19 d Fever, headache, dry cough, pneumonia, endocarditis Food safety threats (Salmonella species, Escherichia coli O157:H7) — — — Water safety threats (Vibrio cholera, Cryptosporidium parvum) — — — Class C threats Emerging threat agents (Nipah virus, hantavirus) — — — Note: Incubation periods should be interpreted with some caution. Data in some instances are limited and in others may be based on natural outbreaks. Intentional releases or engineered organisms could cause variations in expected disease parameters. *Narayanan N, Lacy CR, Cruz JE, et al: Disaster preparedness: biological threats and treatment options. Pharmacotherapy 38: 217, 2018. †Inhalational botulism may not be preceded by GI symptoms. Inhalational and foodborne botulisms are caused by botulinum toxin, not the bacteria itself. Tintinalli_Sec02_p0019-0052.indd 43 7/30/19 4:59 PM

CR, Cruz JE, et al: Disaster preparedness: biological threats and treatment options. Pharmacotherapy 38: 217, 2018. †Inhalational botulism may not be preceded by GI symptoms. Inhalational and foodborne botulisms are caused by botulinum toxin, not the bacteria itself. Tintinalli_Sec02_p0019-0052.indd 43 7/30/19 4:59 PM 44 SECTION 2: Disaster Management 3. After evaluation, a patient is admitted or released, but not suspected as being a victim of bioterrorism. That patient’s course then unexpectedly worsens, and diagnostic test results (blood cultures, immu noassays) or postmortem findings subsequently establish a diagnosis. 4. Multiple patients present over a defined period with similar symptoms or historical characteristics in the same geographical area. Further investigation, through public health or diagnostic testing, establishes concern for an intentional outbreak. Scenario 3 is how the inhalational anthrax index case was diagnosed in Florida during the fall of 2001. 16 The initial inhalational anthrax infection in a postal worker was recognized as in scenario 2. Emergency physicians should have an operational knowledge of the biologic agents of concern or understand where to readily access this information. This knowledge should include basic pathologic principles for each agent, modes of dissemination and transmission, disease signs and symptoms, diagnostic testing, treatment (medications, immunizations, or prophy laxis), and infection control practices (Table 9-1 and Table 9-2).  CLINICAL FEATURES Unless the release of an agent is openly announced or the terrorist is caught in the process of delivering the agent, initial indications of an event may be subtle. Early symptoms of most agents of concern are not readily distinguished from more common, less threatening infectious diseases. Fever, myalgias, and malaise could be the initial presenting symptoms of a victim of bioterrorism (anthrax and others) or of influenza, parainfluenza, or many other common illnesses. 18 During the anthrax dissemination incident in 2001, several anthrax-infected postal workers were evaluated by physicians early in their illness. Their relatively nonspecific symptoms were attributed to other causes, and they were discharged home without appropriate antibiotic therapy. 19 Two postal workers in this cohort died from inhalational anthrax. The similarity in early symptoms also creates another response issue: Once an attack becomes public, patients with any of those common symptoms or concerns without true risk or exposure may seek rapid evaluation in EDs, clinics, or private offices. Extreme patient volumes with diagnostic and triage challenges should be anticipated. Real-time diagnostic studies to reliably confirm or exclude the pres ence of potential agents of concern are not available for all Centers for Disease Control and Prevention–designated agents; this actually does not differ from most common infectious processes. In some cases, specialized confirmatory testing by state or federal laboratories may be required, 20 and diagnostic methodologies continue to evolve. Therefore, clinicians should command sufficient knowledge to initiate available and appropriate test ordering, medical interventions, and reporting when they are suspicious of a patient’s clinical presentation. Public health authorities with jurisdiction over the involved communities should be consulted early for current diagnostic recommendations and further testing (both patient and environmental). Be prepared to appropriately respond to notification of a potential disease by another health or medical professional. Carefully query the reporting source for specific information before considering further actions.

lted early for current diagnostic recommendations and further testing (both patient and environmental). Be prepared to appropriately respond to notification of a potential disease by another health or medical professional. Carefully query the reporting source for specific information before considering further actions. Questions to be asked include the methodology of the testing that produced the concern (specimen collection technique and the sen sitivity and specificity of the test procedure) and the turnaround time of available confirmatory testing.  RESPONSE TO A BIOTERRORISM INCIDENT An adequate response to a bioterrorist event of any magnitude requires effective coordination of many disparate health and medical entities beyond the ED. Although emergency physicians play a critical role in these types of events, many other essential functions must be addressed by individuals and organizations representing public health, mental health, law enforcement, emergency management, and others. Every receiving facility and ED should have standard operating procedures to manage a bioterrorism threat or actual incident. These should be incorporated into the all-hazards emergency operations plan, with bioterrorism-specific procedures in an attached incident-specific annex. Initial actions taken by the emergency physician can be pivotal to the success of the hospital performance and the overall community response. When bioterrorism is confirmed or suspected, prompt emergency operations plan activation should initiate the following: 1. Activation of processes and procedures (including preplanned surge capacity configuration) as appropriate and as listed in incidentspecific annexes to the emergency operations plan. 2. Implementation of appropriate infection control procedures, which may extend to how patients are received in the ED, with provision of appropriate protective equipment and requisite training for health care workers. FIGURE 9-1. Smallpox. FIGURE 9-2. Ulcer and eschar of cutaneous anthrax. FIGURE 9-3. Chest radiograph with widened mediastinum characteristic of inhalational anthrax. Tintinalli_Sec02_p0019-0052.indd 44 7/30/19 4:59 PM

D, with provision of appropriate protective equipment and requisite training for health care workers. FIGURE 9-1. Smallpox. FIGURE 9-2. Ulcer and eschar of cutaneous anthrax. FIGURE 9-3. Chest radiograph with widened mediastinum characteristic of inhalational anthrax. Tintinalli_Sec02_p0019-0052.indd 44 7/30/19 4:59 PM CHAPTER 9:  Bioterrorism      45 TABLE 9-2 Class A Agents: Treatment, Prophylaxis, and Vaccination* (adapted from https://emergency.cdc.gov/bioterrorism/index.asp) Biologic Agent Vaccination Prophylaxis Treatment Variola major Vaccinia vaccination: currently not recommended for general public use because of its association with limited numbers of deaths and complications in immunocompromised individuals and those with eczema; useful in preventing disease if given within 4 d of exposure Vaccinia immune globulin: best given within 2–3 d of exposure; limited supplies are available, and it is available through the CDC as an IND; consider giving to those exposed who have contraindications to vaccine. Cidofovir and brincidofovir are available for postexposure prophylaxis. Supportive. In vitro studies have shown cidofovir has antiviral properties against variola. Although not FDA approved, brincidofovir and tecovirimat have shown promise in animal models. Tecovirimat is only available through the CDC via the SNS. Bacillus anthracis Anthrax vaccination: Three-part series vaccination at 0, 2 wk, and 4 wk. Annual boosters may be required Ciprofloxacin or doxycycline for 60 d is preferred, but alternatives exist. In addition, amoxicillin and penicillin V potassium for penicillin-susceptible strains; anthrax vaccine adsorbed BioThrax is now approved for both preexposure prophylaxis and postexposure prophylaxis. Combination-drug IV regimen with protein synthesis inhibitors (e.g., linezolid) and bactericidal agents (e.g., ciprofloxacin and meropenem) for presumed or proven meningitis concurrent with illness. Two-drug regimen for illness when meningitis ruled out. Consider antitoxin administration for systemic anthrax infection (raxibacumab, obiltoxaximab, or anthrax immune globulin). Uncomplicated cutaneous infection can be treated using single-drug therapy. Yersinia pestis No current vaccine is available Ciprofloxacin or doxycycline; alternative: chloramphenicol; prophylaxis for 10 d. Recommended for close contacts within 2 m. Streptomycin or gentamicin preferred choices; alternatives: doxycycline, ciprofloxacin, chloramphenicol. Clostridium botulinum No current vaccine is available Not applicable. Heptavalent botulinum antitoxin is available (must coordinate with CDC) and should be provided within 24 h of symptom onset; antitoxin may preserve remaining neurologic function but does not reverse paralysis; may require prolonged, assisted mechanical ventilation and supportive care. Francisella tularensis No current vaccine is available Ciprofloxacin or doxycycline for 14 d. Streptomycin or gentamicin preferred choices; alternatives: doxycycline, ciprofloxacin, chloramphenicol. Filoviruses (e.g., Ebola virus) and arenaviruses Ebola trials with rVSV-ZEBOV Not applicable. Supportive therapy; ribavirin may have applicability in arenaviruses. Favipiravir, ZMapp, and brincidofovir are currently under investigation. Note: Due to multiple ongoing efforts, some new or adjusted therapies may be available in the near future. Readers are encouraged to check peer-reviewed literature because this is a dynamic field. Specific recommendations exist for some agents and may entail use of therapies traditionally reserved for nonpregnant adults. In some cases, these entail use under Emergency Use Authorization, which is beyond the scope of this chapter.

rs are encouraged to check peer-reviewed literature because this is a dynamic field. Specific recommendations exist for some agents and may entail use of therapies traditionally reserved for nonpregnant adults. In some cases, these entail use under Emergency Use Authorization, which is beyond the scope of this chapter. Abbreviations: CDC = Centers for Disease Control and Prevention; FDA = Food and Drug Administration; IND = investigational new drug; rVSV-ZEBOV = recombinant vesicular stomatitis virus–Zaire Ebola virus; SNS = Strategic National Stockpile. *Narayanan N, Lacy CR, Cruz JE, et al: Disaster preparedness: biological threats and treatment options. Pharmacotherapy 38: 217, 2018. 3. Notification of key departments, including hospital administration, infection control and infectious diseases, security, environmental services, and the hospital laboratory. 4. Information flow to all hospital personnel regarding the suspected agent, its characteristics (including potential for person-to-person transmission), and actions to protect the patients and staff. 5. Coordination of hospital media messages to internal and external entities (other hospitals, public health, emergency management) to avoid dissemination of conflicting information. 6. Notification to the local public health agency, with confirmation that law enforcement was notified by them. The local public health agency has the responsibility to notify regional or state public health departments and the Centers for Disease Control and Prevention. With some agents and/or situations, the U.S. Depart ment of Health and Human Services would notify the World Health Organization, because the potential impact could be global, and this reporting is mandatory under International Health Regulations admin istrated by the World Health Organization. INFECTION CONTROL AND DECONTAMINATION Initiate infection control guidelines for the diagnosed or suspected agent (Table 9-3). This is essential to protect clinicians, hospital staff, visitors, and other patients. It is also critical in maintaining the ability of the TABLE 9-3 Class A Agents: Guidelines for Personal Protective Equipment for Clinical Care in the ED (adapted from https:// www.cdc.gov/infectioncontrol/pdf/guidelines/isolationguidelines.pdf) •   Unknown biological hazard: During a bioterrorism event, until the pathogen is understood and its transmission pattern defined, employ standard, contact, and airborne precautions. •   Anthrax: Cutaneous infection: standard precautions. However, contact precautions are recommended for uncontained copious drainage. Respiratory tract and GI tract infections: standard precautions. •   Ebola: If the epidemiology of transmission is consistent with natural disease, droplet precautions can be substituted for airborne precautions. Otherwise, consider Ebola a potential airborne pathogen during a bioterrorism event. •   Smallpox: Combined use of standard, contact, and airborne precautions for initial care and for up to 3–4 wk until scabs heal over. Airborne precautions are recommended when possible, but in the event of mass exposures, barrier precautions and containment within a designated area are paramount. When possible, only immune healthcare workers should care for smallpox patients. •   Pneumonic plague: Standard precautions. However, droplet precautions are needed until patients have received 48 h of antibiotic therapy. •  Botulinum  toxin: Standard precaution. •   Tularemia:  Standard  precautions. Although  person-to-person  spread is rare, laboratory  workers  are at high risk of infection  if exposed  during specimen handling. Tintinalli_Sec02_p0019-0052.indd 45 7/30/19 4:59 PM

il patients have received 48 h of antibiotic therapy. •  Botulinum  toxin: Standard precaution. •   Tularemia:  Standard  precautions. Although  person-to-person  spread is rare, laboratory  workers  are at high risk of infection  if exposed  during specimen handling. Tintinalli_Sec02_p0019-0052.indd 45 7/30/19 4:59 PM 46 SECTION 2: Disaster Management hospital to continue its regular medical commitment to the community. The Association for Professionals in Infection Control and Epidemiol ogy has published guidelines for hospital infection control in response to a bioterrorism event. 23 Most agents of concern require only standard precautions (gloves, mucous membrane protection when potential for splashing exists, and a gown when the potential exists for soiling), but meticulous attention to detail is required. The more troubling agents are those that are contagious through airborne or droplet transmission. Disease containment for a case of pneumonic plague requires droplet protection and patient isolation. Smallpox requires airborne and contact precautions and, therefore, full patient isolation. If a contagious disease is spreading within the community, procedures must be instituted to screen everyone entering the healthcare facility for active disease. This screening should ideally take place in an appro priately established “screening facility” before entering or immediately upon entry into the hospital building. Administratively, isolation of large numbers of infectious patients may be necessary. Current hospital configurations often prohibit largescale containment of patients in official isolation rooms, but entire wings could be adapted (using fire doors and manipulation of ventilation/air pressure within hospital smoke compartments) to serve as isolation wards. Plans to provide adequate separation from other, noninfected patients, to designate and train specific staff to care for these patients, and to furnish proper personal protective equipment should be devel oped in the emergency operations plan annex. Another important initial consideration for ED personnel is whether patient decontamination is indicated. Decontamination is a consider ation only if a patient presents shortly after acute exposure to a sub stance (toxin or organism) suspected or confirmed as a biologic agent, in contrast to the presentation of the patient who has already devel oped symptoms of an infectious disease. If a realistic concern exists, simply disrobing the patient and showering with soap and warm water should be adequate decontamination, but this must be accomplished in a controlled environment before patient entry into the healthcare facility. Clothing and personal belongings should be secured to assist with the public health and law enforcement investigations. Avoid using decon tamination agents, such as diluted bleach, due to their potential for harm. MANAGEMENT Specific therapies for individual Class A agents are listed in Table 9-2. From a population perspective, morbidity and mortality are primar ily minimized by preventing exposure and providing prophylaxis and immunization as appropriate. Treatment of infected and symptomatic patients may involve specific pharmaceuticals or general supportive care. Depending on the agent involved, prophylaxis or immunization of the hospital staff may be warranted. Prophylaxis, immunization, or treatment may be indicated even without obvious signs of disease or definitive information about exposure. This makes emergency physicians heavily reliant on the public health sector to stratify patient risk based on exposure and to provide evidence-based prophylaxis and treatment.

ranted. Prophylaxis, immunization, or treatment may be indicated even without obvious signs of disease or definitive information about exposure. This makes emergency physicians heavily reliant on the public health sector to stratify patient risk based on exposure and to provide evidence-based prophylaxis and treatment. With specific agents (e.g., anthrax), large community-based efforts have been developed with federal support related to the dispensing of postexposure prophylaxis. Preexposure prophylaxis for the general public is not recommended without a contemporaneous biological attack in the community. 25 A 2003 preexposure initiative to vaccinate healthcare workers and will ing civilians against smallpox was discontinued after only a minority of the target cohort actually accepted vaccinations. The risk of potential life-threatening side effects, such as generalized vaccinia and potential cardiac sequelae, complicates the recommendations for smallpox vac cination in the absence of known circulating disease. When patients present to the ED who are potentially exposed but not physically ill (worried well), the patient interaction may require sophisticated explanations as to why the individual is or is not receiv ing a particular therapy. Preprinted instructions indicating category of risk stratification and why the patient was placed in that category can increase efficiency and be helpful for patients being screened and immediately released. These instructions should clearly indicate how the disease is transmitted, measures that prevent spread, and early signs and symptoms of disease with appropriate steps if they should occur. Establish appropriate follow-up with a public health agency. Note any change in the epidemiology of the incident (e.g., a new site tests positive for the agent) or if new information becomes available on the etiologic agent itself (e.g., antibiotic resistance patterns). Patients may need to be rapidly recontacted to change therapy. Entering all patients into a reliable longterm surveillance database should be a task for the public health agency, but hospitals and EDs could facilitate this process. Pharmaceuticals recommended for some bioterrorism agents are normally not approved for children or for pregnant or lactating women. In many situations, these recommendations are relaxed when the risk of infection and its consequences exceeds the risks of the medication or vaccine. In addition, some unique treatments (e.g., ciprofloxacin for anthrax prophylaxis in children) have received U.S. Food and Drug Administration approval. MEDICAL SURGE CAPACITY AND CAPABILITY One critical issue in providing treatment to victims of bioterrorism is the development of adequate medical surge. 26 This issue is complicated by current healthcare industry practices that minimize staff, maintain justin-time inventory, and limit hospital bed capacity. Medical surge capacity is developed by first maximizing individual healthcare facility capacity and capabilities (through an effective emergency operations plan) and then by coordinating regional resources to address and match patient needs to available resources. State and federal assistance should also be included in planning but not relied upon to assist initially. Federal agencies distinguish medical surge capacity from surge capability, which similarly can pose challenges. 26 Medical surge capability refers to the ability to manage patients requiring unusual or very specialized medical evalua tion and care. It is intuitively obvious, for example, that even one patient presenting with signs and symptoms of smallpox would present highly unusual challenges affecting any hospital’s continuity of operations.

capability refers to the ability to manage patients requiring unusual or very specialized medical evalua tion and care. It is intuitively obvious, for example, that even one patient presenting with signs and symptoms of smallpox would present highly unusual challenges affecting any hospital’s continuity of operations.  INTEGRATION WITH PUBLIC HEALTH AGENCIES In any suspected or confirmed case of bioterrorism, emergency physi cians can expect to interface with multiple diverse agencies in an ongo ing fashion, the most critical of which is the local public health agency. In most communities, public health epidemiologists are assigned the task of defining the size and scope of an incident, the at-risk population, and other incident parameters. This type of information becomes criti cal to hospitals for the evaluation and treatment of patients and in anticipating medical surge and continuity of operations requirements. The most important assistance public health can provide to all clinicians is in the development of a community-wide patient evaluation and treatment protocol. Evaluation and treatment protocols provide criteria to stratify individual and population risk for exposure and guide steps for specific evaluation and treatment. The protocol also should include recommended testing, treatment, patient instructions, tracking of atrisk cohorts, and public education. A single evaluation and treatment protocol provides a uniform method across a community to evaluate patients presenting with possible exposure. This is important not only for individual practitioners but also for the public. An iterative process is critical to deploy during these events, and it should be expected that these protocols will evolve as the event progresses. For example, during the 2001 anthrax incident, the initial epidemiologic investigation in the Washington, D.C., metropolitan area used nasal swabs in suspect exposures. This practice was misunderstood by some clinicians and the public as having individual diagnostic utility, when in fact it was merely an epidemiologic surveillance tool. Anxiety and confusion resulted when individuals received nasal swabbing at some healthcare locations and were (correctly) told it was not useful for diagnosis at other medical facilities. Because no early standardized protocol was developed by the public health system, hospitals implemented their own individual pro tocols to limit variation between clinicians practicing within individual hospitals. The resultant variability between institutions, however, caused great consternation for patients and providers. Tintinalli_Sec02_p0019-0052.indd 46 7/30/19 4:59 PM