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Infectious Disease Threats

This chapter examines the differences between naturally occurring infectious disease threats and threats posed by biological weapons. There is considerable knowledge and experience in diagnosing and treating naturally occurring infectious diseases in the United States and around the world. Bioterrorism poses specific and complex problems that do not exist within the context of natural infectious disease. For example, the concentration of a disease agent used in a bioterrorist attack is likely to be much higher than is the concentration found in any natural setting. Moreover, if a “weapons-grade” agent (for example, a highly refined preparation of Bacillus anthracis spores designed to disperse readily in the environment) is used, the remediation of a building will present special epidemiological, technological, operational, and social considerations, as this and later chapters illustrate.

ABILITY OF MICROORGANISMS TO INFECT PEOPLE

The human race is continually exposed to microorganisms. Our water, soil, and air are laden with microorganisms that adapt continuously to the environments; a small proportion of those organisms cause infectious diseases. Within buildings, microorganisms can circulate through the air, reaching locations distant from the source. In hospitals, for example, medical staff, clinical staff, patients, and visitors are continuously exposed to microorganisms, as they are in natural settings. Fortunately, humans have evolved complex systems to defend against pathogenic or disease-producing microorganisms that often can prevent infection from becoming established.



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Reopening Public Facilities after a Biological Attack: A Decision Making Framework 2 Infectious Disease Threats This chapter examines the differences between naturally occurring infectious disease threats and threats posed by biological weapons. There is considerable knowledge and experience in diagnosing and treating naturally occurring infectious diseases in the United States and around the world. Bioterrorism poses specific and complex problems that do not exist within the context of natural infectious disease. For example, the concentration of a disease agent used in a bioterrorist attack is likely to be much higher than is the concentration found in any natural setting. Moreover, if a “weapons-grade” agent (for example, a highly refined preparation of Bacillus anthracis spores designed to disperse readily in the environment) is used, the remediation of a building will present special epidemiological, technological, operational, and social considerations, as this and later chapters illustrate. ABILITY OF MICROORGANISMS TO INFECT PEOPLE The human race is continually exposed to microorganisms. Our water, soil, and air are laden with microorganisms that adapt continuously to the environments; a small proportion of those organisms cause infectious diseases. Within buildings, microorganisms can circulate through the air, reaching locations distant from the source. In hospitals, for example, medical staff, clinical staff, patients, and visitors are continuously exposed to microorganisms, as they are in natural settings. Fortunately, humans have evolved complex systems to defend against pathogenic or disease-producing microorganisms that often can prevent infection from becoming established.

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework In some circumstances, precautions can be taken when it is known that defenses are compromised—for example, during surgical procedures and when people are likely to be exposed to particularly dangerous pathogens. The choice of precautions depends on the potential route of exposure and infection, and it can range from wearing a mask in an area where airborne pathogens could be a high threat; to wearing gloves and protective clothing to avoid direct transmission of pathogens; to isolating patients in clean rooms where air is filtered, food and water sterilized, surfaces disinfected, and anyone who enters is masked and gowned to avoid exposure or transmission. Many biological agents considered to be the most serious disease threats enter the body via the respiratory system. In some cases, only direct environmental exposure would cause disease (there is no person-to-person transmission). For example, B. anthracis spores can be inhaled, ingested with contaminated food or water, or contacted by the skin on contaminated surfaces. In many cases, infected people pose no risk to others. In other cases—such as smallpox and plague—the risk of inhalation from intentionally contaminated environments is complicated with the risk of interpersonal transmission. Successful introduction of an agent via the airway is possible under specific conditions. The optimal size for a particle that contains the infectious microorganism is about 5 micrometers (µm) for efficient penetration to the lower airway (within the lung). However, smaller or larger (up to 12 µm) particles can cause disease by entering the upper respiratory tract (Davis, CUBRC, Inc., 2004 personal communication). To cause disease, in most cases, the pathogenic agent must enter and multiply in the cells of the host’s body. In the laboratory, each intact and complete bacterial or viral particle has the ability to multiply. However, virulence and infectivity can vary within a bacterial or viral population and among different strains of the same species. In the host, successful infection, multiplication, and resulting disease can be a rare event. Normally, host defenses are overcome only when challenged simultaneously by many of the same type of pathogenic microorganism; the number needed to cause disease is called the infectious dose. If the agent begins to multiply in an infected cell, the cell will be altered to become a potential target of the immune system. The likelihood that an infection will lead to disease depends on how many microorganisms infect the host initially, the nature of the agent (some are naturally better able to overcome the host’s defenses), and the state of the host’s immune system, which varies within a population. For example, young children and elderly people often have weaker immune systems than healthy adults do. In addition, there is an increasing number of people who are more susceptible than average in the U.S. population because they are immunocompromised, either due to a genetic deficiency, because of a metabolic disease, or as a side effect of therapy for an illness such as cancer.

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework INFECTIOUS DISEASE AS A WEAPON The events of September 11, 2001, produced an increased awareness of the United States’ vulnerability to acts of terrorism. While the nation was dealing with the aftermath of the 9/11 attacks, an anthrax attack (Amerithrax) occurred, turning the hypothetical threat of bioterrorism into reality (Atlas, 2001, 2002). Although those attacks were not the first instance of bioterrorism in the United States, they made many more Americans aware of and concerned about the threat. Previous bioterrorism in the United States and elsewhere was not as well publicized and did not produce such widespread public reaction. In 1984, the Rajneesh cult spread Salmonella typhimurium on salad bars in The Dalles, Oregon, in an attempt to influence the outcome of an election by making the opposition ill and unable to vote. The resulting illnesses initially were thought to be a case of natural foodborne disease, but later the event was recognized as an act of bioterrorism (Torok et al., 1997). In the early 1990s, the Aum Shinrikyo cult experimented with the release of B. anthracis spores and botulinum toxin in Japan before carrying out a chemical agent attack in the Tokyo subway with sarin (Smithson and Levy, 2000; Wheelis, 2003). Biological weapons also have been used in various criminal acts during the past century—for example, the infamous assassination of a Bulgarian emigré in London using ricin and contamination of muffins with Shigella dysenteriae at a hospital in Texas (Carus, 2001; Kolavic et al., 1997). There also have been many hoaxes, including many hundreds of letters claiming to contain anthrax sent between 1997 and 2001 to abortion clinics and other organizations (Cole, 2003). The United States, the Soviet Union, Canada, Great Britain, South Africa, Iraq, Japan, and others have had national biological weapons programs, and there has been limited use of biological weapons in warfare dating back to B.C. 600 (NRC, 2004; Wheelis, 1999a, b). An important current concern regarding bioterrorism is that terrorist groups might recruit scientists and acquire biological weapons material previously associated with national programs. Particular worry is attached to the former Soviet Union, which continued its program after 1972 despite signing the Biological Weapons Convention and agreeing to eliminate its program. The Soviet biological effort was massive: It employed over 50,000 “bioweaponeers” and produced hundreds of tons of weapons (Alibek, 1999; Davis, 1999), and the fate of some of those scientists and materials and the knowledge they produced is not known (Alibek, 1999). The general properties of many of the more widely known biological threat agents are listed in Table 2-1. That list, adapted from the appendix of the U.S. Army Medical Research Institute of Infectious Disease’s (USAMRIID’s) Medical Management of Biological Casualties Handbook (USAMRIID, 2001), shows that a wide range of agents have been considered for use in military programs. The term weaponized agent is now broadly interpreted to mean a biological

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework TABLE 2-1 Biological Weapons Characteristics Disease Human Transmission Infective Dose, Aerosol Incubation Period Duration of Illness Lethalitya Persistence Vaccine Efficacy, Aerosol Exposure Inhalation anthrax No 8000-50,000 Spores 1-6 Days 3-5 Days; usually fatal if untreated High Very stable; spores remain viable for >40 years in soil 2-Dose efficacy against ≤1000 LD50b in monkey Brucellosis No 10-100 Organisms 5-60 Days (usually 1-2 months) Weeks to months <5% Untreated Very stable No vaccine Cholera Rare 10-500 Organisms 4 Hours-5 days (usually 2-3 days) ≥1 Week Low with treatment; high without Unstable in aerosols, fresh water; stable in saltwater No data on aerosol Glanders Low Assumed low 10-14 Days via aerosol Death in 7-10 days in septicemic form >50% Very stable No vaccine Pneumonic plague High 100-500 Organisms 2-3 Days 1-6 Days (usually fatal) High unless treated within 12-24 hours Up to 1 year in soil; 270 days in live tissue 3 Doses, not protective against 118 LD50 in monkey Tularemia No 10-50 Organisms 2-10 Days (average 3-5) ≥2 Weeks Moderate if untreated Months in moist soil, other media 80% Protection against 1-10 LD50 Q Fever Rare 1-10 Organisms 10-40 Days 2-14 Days Very low Months on wood, 94% Protection Smallpox High Assumed low (10-100 organisms) 7-17 days (average 12) 4 Weeks High to moderate Very stable Vaccine protects against large doses in primates

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework Venezuelan equine encephalitis Low 10-100 Organisms 2-6 Days Days to weeks Low Relatively unstable TC 83 vaccine protects against 30-500 LD50 in hamster Viral hemorrhagic fever Moderate 1-10 Organisms 4-21 Days Death in 7-16 days High for Zaire strain; moderate for Sudan Relatively unstable, depending on agent No vaccine Botulism No LD50 for type A: 0.001 µg/kgc 1-5 Days Death in 24-72 hours; lasts months if not lethal High, without respiratory support Weeks in nonmoving water and food 3-Dose efficacy: 100% against 25-250 LD50 in primates Staph enterotoxin B No Incapacitation: 0.03 µg/person 3-12 Hours after inhalation Hours <1% Resistant to freezing No vaccine Ricin No LD50 in mice: 18-24 Hours 3-5 mmg/kgc for ingestion Days; death within 10-12 days High Stable No vaccine T-2 Mycotoxins No Moderate 2-4 Hours Days to months Moderate Years at room temperature No vaccine aApproximate case fatality rate. bLD50, - The amount of toxin or microorganism sufficient to kill 50 percent of a population of animals within a certain time. cµg/kg, micrograms per kilogram body weight. SOURCE: Adapted from USAMRIID, 2001.

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework agent that has been processed to enhance its stability, infectivity, or environmental half-life or the ease of its dissemination. The properties and characteristics of biological weapons can vary, depending on formulation. Altered characteristics (such as particle size, electrostatic charge, viability, suspension time in air, particle agglomeration/flocculation rates, and ability to penetrate target organisms) must be considered during decontamination and in decision making about reoccupation of buildings. For example, agents that settle to the floor quickly might require only surface decontamination and could be less likely to disperse widely than are agents that remain suspended in air for a long time. Such characteristics can have serious implications for the need to decontaminate and the processes used. AGENTS OF CONCERN TO NATIONAL SECURITY AND PUBLIC HEALTH Several federal agencies have created lists that categorize biological agents, based on the risks those agents pose to the public. Each list is a little different. For example, the U.S. Department of Agriculture lists focus on threats to plants and animals; the U.S. Centers for Disease Control and Prevention (CDC) lists focus on threats to human health. The CDC’s Category A list identifies organisms that pose a risk to national security because they can be easily disseminated or transmitted from one person to another. The infections caused by Category A organisms result in high mortality rates and have the potential for major public health consequences. They also could cause social disruption and would require special action for public health preparedness. Category A includes anthrax (B. anthracis), plague (Yersinia pestis), smallpox (variola major), tularemia (Francisella tularensis), viral hemorrhagic fevers (filoviruses such as Ebola and Marburg or arenaviruses such as Lassa or Machupo), and botulism (Clostridium botulinum toxin). CDC’s Category B agents are moderately easy to disseminate, result in moderate morbidity rates and low mortality rates, and require specific enhancements of CDC’s diagnostic capacity and enhanced disease surveillance. The Category B agents include brucellosis (Brucella species), the epsilon toxin of Clostridium perfringen, food safety threats (Salmonella spp., Escherichia coli O157:H7, Shigella spp.), glanders (Burkholderia mallei), melioidosis (Burkholderia pseudomallei), psittacosis (Chlamydia psittaci), Q fever (Coxiella burnetii), ricin from Ricinus communis (castor beans), staphylococcal enterotoxin B, typhus fever (Rickettsia prowazekii), viral encephalitides (alphaviruses such as Venezuelan equine encephalitis, Eastern equine encephalitis, Western equine encephalitis), and water safety threats (Vibrio cholerae, Cryptosporidium parvum). CDC’s third list (Category C) includes pathogens that could be engineered for mass dissemination in the future because of availability, ease of production and dissemination, and potential for high morbidity and mortality rates and major

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework health consequences. The Category C agents include emerging infectious-disease threats such as Nipah virus and hantavirus. The CDC categories are based on threats to human health and not on the difficulties each organism might present for decontamination. CDC does offer some guidance on persistence of naturally occurring varieties of disease-causing organisms. For example, it suggests that both variola virus (CDC, 2004a) and Y. pestis (CDC, 2004b) become inactive after short periods. The USAMRIID information reproduced in Table 2-1 is based on the perspective of organisms as potential weapons and reveals that even organisms that generally are short lived in the environment can sometimes persist for weeks, months, or years. For example, smallpox can survive over extended periods in scabs and after lyophilization; Y. pestis can live for at least a year in soil. The biological agents used in future acts of terrorism in public facilities could be specifically prepared to persist for extended periods. In the former Soviet Union, preparations of both smallpox and plague which were intended for biological warfare were stable for months (Alibek, 1999). BIOLOGICAL AGENTS CONSIDERED IN THIS REPORT This report provides guidelines for determining when a facility that has been contaminated with a harmful biological agent is safe for reoccupation. At the first meeting of the Committee on Standards and Policies for Decontaminating Public Facilities Affected by Exposure to Harmful Biological Agents, the study sponsors asked the committee to consider three agents: variola major virus (smallpox), B. anthracis (anthrax), and Y. pestis (plague). Those agents were chosen because they could be among the most dangerous and because they can be used to exemplify the decontamination requirements for other substances. B. anthracis is an endospore-forming bacterium, which makes it especially persistent in the environment. Y. pestis does not form endospores and naturally is less persistent in the environment, as are some other non-spore-forming bacteria such as B. pseudomallei (glanders), B. pseudomallei (melioidosis), and Brucella spp. (brucellosis). Smallpox virus was chosen to represent the entire class of viral infectious agents, such as viral hemorrhagic fever viruses and Eastern equine encephalitis virus. Examination of toxins, such as botulinum toxin and ricin, was not included in the charge to the committee, but decontamination of toxin-affected spaces can be similar to the decontamination of areas exposed to harmful chemical agents. The charge to the committee called for consideration of transmissible and nontransmissible organisms; the agents described above cover both categories. Contagious is a commonly used word but its meaning is not as precise as transmissible, so the latter term is used in this report. Transmissibility is a term that is accepted among medical and biological weapons experts to have the precise meaning of “able to be passed from person to person.”

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework Anthrax Anthrax is a zoonotic disease—that is, communicable from animals to humans under natural conditions—that occurs primarily in herbivorous animals. It is caused by infection with B. anthracis, a gram-positive endospore-forming rod. B. anthracis has three known virulence factors: an antiphagocytic capsule and three proteins—edema factor, lethal factor, and protective antigen. Animals most frequently acquire anthrax by ingesting plant material contaminated with soil that contains B. anthracis spores. Humans usually acquire anthrax from the environment or from natural transmission through contact with infected animals or contaminated animal products. Although anthrax is an infectious disease, it is not normally transmissible. At least 66 people were killed by inhalational anthrax after the accidental release of B. anthracis spores from a Soviet military compound in Sverdlovsk in 1979 (Meselson et al., 1994). The attack in 2001, in which weapons-grade preparations of B. anthracis spores were sent by mail, resulted in 11 cases of cutaneous anthrax with no fatalities and in 11 cases of inhalational anthrax with 5 deaths (Atlas, 2001). Human infection with B. anthracis can result from inhalation of spores (inhalational anthrax), by inoculation of spores into the skin (cutaneous anthrax), or by ingestion of spores (gastrointestinal anthrax). CDC (2001) defines a confirmed case of anthrax as: A clinically compatible case of cutaneous, inhalational, or gastrointestinal illness that is laboratory confirmed by isolation of B. anthracis from an affected tissue or site, or other laboratory evidence of B. anthracis infection based on at least two supportive laboratory tests. Inhalational anthrax begins with nonspecific symptoms—fever, cough, myalgia, and malaise. Onset of disease occurs 1 day to several weeks after inhalation of spores; the time of onset can depend on the dose. The initial nonspecific symptoms of inhalational anthrax typically are followed by the sudden onset of respiratory distress with dyspnea, cyanosis, and stridor in 2-3 days. Radiographical examination normally shows mediastinal widening that is indicative of hemorrhagic mediastinitis or pleural effusion. The anthrax toxins cause necrosis of the lymphatic tissue, leading to septicemia caused by the release of large numbers of B. anthracis into the circulatory system. Most cases of inhalational anthrax progress rapidly to death. The fatality rate may reach 95% even with antibiotic therapy, and autopsies typically reveal widespread hemorrhage and necrosis of multiple organs. The fatality rate in 2001 was 50% among the victims who contracted inhalational anthrax after exposure to weapons-grade anthrax spores. Because inhalational anthrax is not transmissible, standard infection control

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework procedures are adequate and patient isolation is not required. Prophylaxis with the antibiotics doxycycline or ciprofloxacin before disease onset is effective—thousands of people were treated with those antibiotics after the 2001 attack. Vaccination also can protect against anthrax and has been used among U.S. military personnel. If untreated, B. anthracis spores can persist in the environment almost indefinitely. Environmental surface decontamination can be achieved using 0.5% hypochlorite (CDC, 1999) and that procedure typically is used in clinical and research laboratories. The principal risk factor for inhalational anthrax previously was exposure to aerosolized spores related to textile mill processing of goat hair. Investigators could not determine why some workers became infected and others did not. Factors likely to increase infection rates included more intense exposure to B. anthracis spores through direct contact with unprocessed goat hair, weakened immune system, or concurrent disease (two patients with inhalational anthrax were suffering from chronic pulmonary disease). Other hypothesized risk factors included smoking and alcoholism. Although the investigations provided valuable information about diagnosis and the appropriate use of a vaccine to protect at-risk populations, they have not answered questions about the lowest infectious dose, the definition of a true exposure that warrants prophylaxis, and whether spores delivered in an envelope can create a residual risk after primary contamination. More research on anthrax in the natural setting is needed to define the risks from naturally occurring B. anthracis (Bales et al. 2002). More than 95% of naturally occurring cases of anthrax are cutaneous. Inoculation of spores under the skin is necessary to establish infection. A small papule forms within hours to days, and then an ulcer, surrounded by vesicles, forms about a day later. Initial infection is not readily diagnosed because it resembles localized inflammation. Progression of cutaneous anthrax results in a painless eschar with edema. The fatality rate in untreated cases is 20%. However, the recovery rate from cutaneous anthrax is nearly 100% if it is treated with antibiotics such as penicillin or doxycycline. Primary risk factors for cutaneous anthrax are direct physical contact with infected animals or commercial products contaminated with B. anthracis spores. Ranchers, farmers, butchers, and veterinarians are the professionals most at risk. The commercial products linked to human anthrax infection mostly are items made from imported goat skin or goat hair. Humans contract gastrointestinal anthrax from ingesting undercooked contaminated meat. Gastrointestinal anthrax begins with nonspecific symptoms of nausea, vomiting, and fever, followed in most cases by severe abdominal pain. Mortality can reach 50%. The number of anthrax cases reported in the United States decreased from an average of 35 per year in the 1950s to less than 1 per year since 1980. Most cases have been cutaneous anthrax. The last reported case of inhalational anthrax before October of 2001 was in 1976. A home craftsman acquired inhalational

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework anthrax from imported animal-origin yarn (Suffin et al., 1978). Bales and colleagues (2002) identified 49 anthrax-related field investigations conducted by CDC between 1950 and 2001. That work reports on 41 investigations to identify factors that could guide the public health response to an intentional release of B. anthracis. Agricultural settings (farms, contact with livestock, or both) accounted for 24 anthrax outbreaks; 11 were related to textile mills. Six outbreaks occurred in nonagricultural settings and involved such materials as anthrax-contaminated commercial products and contaminated cow bones. Thirty-eight of the 41 investigations were done in the United States; the rest were in Haiti, Paraguay, and Kazakhstan. Although most of the 2001 anthrax exposures were recognized as they occurred and were traced to letters received in the mail, the first cases in Florida were not. The first indication of a problem was a patient arriving at the emergency room. An investigation subsequently pointed to the American Media International (AMI) building in Boca Raton, Florida. That case serves as an example of a delay between exposure and hazard identification that can be significant epidemiologically for defining and treating exposed populations. By the time patients display symptoms of inhalational anthrax, the disease can have progressed beyond treatment. Delays also influence decontamination: The period between agent release and identification can allow local spread of the agent. Secondary contamination also can occur as the agent is tracked on shoes, clothing, and other objects to locations remote from the original release site. When 63-year-old Robert Stevens died of inhalational anthrax in Florida October 5, 2001, a massive investigation began. An Associated Press report from October 7, 2001, stated that before the AMI building was identified as the source, “More than 50 health and law enforcement officials have fanned out across Palm Beach to track his movements over the past two months and look for other possible cases. Officials are going over medical records in four North Carolina counties that he might have visited recently.” Only after extensive investigation was the AMI building identified as the source of Stevens’ contact with the B. anthracis spores. Plague Plague is an infectious disease of animals and humans caused by the bacterium Y. pestis, a nonmotile, non-lactose-fermenting, gram-negative coccobacillus. Y. pestis has several virulence factors that cause host cell damage and protect the bacterial cells from phagocytosis and other host defense mechanisms. Most cases of plague in humans occur as bubonic plague, which results when plague-infected fleas bite humans. Clinical bubonic plague is characterized by enlarged, tender lymph nodes; fever; chills; and prostration. Patients typically develop symptoms of bubonic plague 2-8 days after being bitten by an infected flea. There is a sudden onset of fever, chills, and weakness and the development of an acutely swollen tender lymph node (known as a bubo) up to 1 day later. The

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework bubo, which typically is 1-10 cm and extremely painful, often develops in the groin, axilla, or cervical regions. Bubonic plague normally is not transmissible. However, in some cases, the bacteria spread systemically to cause septicemic plague, which is characterized by fever, chills, prostration, abdominal pain, shock, and bleeding into the skin and other organs. Septicemic plague can lead to a transmissible secondary pneumonia. It can result in sudden and intense clinical shock without signs of localized infection. Gangrene of acral regions, such as the digits and nose, also can occur in advanced septicemic plague. That process is believed to be responsible for the epithet “Black Death” that became associated with septicemic plague during the Middle Ages in Europe. Direct inhalation of Y. pestis also can cause primary pneumonia (pneumonic plague). The pneumonic form is transmissible; it spreads as an aerosol from person to person. Pneumonic plague is characterized by fever, chills, cough, bloody sputum, retrosternal chest pain (from the enlarged lymph nodes in the mediastinum), and difficulty breathing. Those symptoms lead to rapid clinical shock and death if they are not treated early. If untreated, the mortality rate for pneumonic plague exceeds 50% (Ingelsby et al., 2000). However, if antibiotic and supportive therapies are administered within 24 hours of the onset of symptoms, the death rate can be reduced. Aerosol spread of Y. pestis that could cause widespread pneumonic plague is considered a major bioterrorist threat (Inglesby et al., 2000). During World War II, Japan carried out biological weapons attacks using plague-infected fleas. In the case of a bioterrorist attack with Y. pestis, individuals would be likely to show signs of illness in 1-6 days. Symptoms include fever with cough and dyspnea and sometimes production of bloody, watery, or, less commonly, purulent sputum. Gastrointestinal symptoms, including nausea, vomiting, abdominal pain, and diarrhea, also can occur. Inglesby and colleagues (2000) have described the epidemiology of plague. In nature, plague is an enzootic infection of rats, ground squirrels, prairie dogs, and other rodents. Historically, rats and their fleas have been the primary source of human infections—infected rat fleas were the sources of Y. pestis that caused major outbreaks of plague during the Middle Ages. Rat control has greatly limited the reservoir for Y. pestis, resulting in great diminution of plague. Rock squirrels and their fleas are the most frequent sources of human infection in the southwestern United States. For the Pacific states, the California ground squirrel and its fleas are the most common source. Many other rodent species—prairie dogs, wood rats, chipmunks, and other ground squirrels and their fleas—suffer plague outbreaks, and some species occasionally serve as sources of human infection. Deer mice and voles are thought to maintain the disease in animal populations but contribute less as sources of human infection. Other infrequent sources of infection include wild rabbits and wild carnivores that contract their infections from wild rodent outbreaks. Domestic cats (and sometimes dogs) could

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework readily contract plague from flea bites or from eating infected wild rodents. Cats can serve as a source of infection and sometimes are responsible for outbreaks of pneumonic plague. Today there are typically 1000-2000 cases of plague annually worldwide (Perry and Fetherson, 1997). Most are cases of bubonic plague. During the 1980s, epidemic outbreaks of plague associated with domestic rats occurred annually in Africa, Asia, or South America. Almost all reported cases during the decade occurred in rural places among people living in small towns and villages or in agricultural areas, rather than in larger, more developed, towns and cities. Cases of pneumonic plague were found September 22, 1994, in the city of Surat, Gujarat, India. By September 26, 1994, several hundred pneumonic plague cases and numerous deaths had occurred (Ramalingaswami, 2001; Shah, 1997). Of the 390 plague cases reported in the United States in the last half of the twentieth century, 84% were bubonic, with a fatality rate of 14%; 13% were septicemic, with a 22% fatality rate; and 2% were pneumonic, with a 57% fatality rate (CDC, 1997). During the 1980s, an average of 18 plague cases was reported in the United States each year. Most occurred in people under the age of 20, and the case-to-fatality rate was 14%. The preferred treatment drug for plague infection has been streptomycin. If it is administered early, overall mortality can be reduced to a range of 5-14%. Gentamicin and other antibiotics, including doxycycline, also can be effective. Given the available evidence, the Working Group on Civilian Biodefense (Inglesby et al., 2000) recommended that people who live or work in close contact with people who have confirmed or suspected pneumonic plague should receive antibiotic prophylaxis. Those who have less than 48 hours of antibiotic treatment should follow “respiratory droplet precautions”—wearing gowns, gloves, and eye protection—and wear a surgical mask. The working group also recommended avoidance of unnecessary close contact with patients with pneumonic plague until the patients have had at least 48 hours of antibiotic therapy and have shown clinical improvement. The use of standard respiratory droplet precautions also was recommended. Given the available information, the working group (Inglesby et al., 2000) concluded that there was no evidence that residual plague bacilli pose an environmental threat to the population after the dissipation of the primary aerosol—although the group did not explicitly consider Y. pestis delivered in advanced weaponized formulations. Unlike B. anthracis, Y. pestis does not form endospores. Y. pestis also is sensitive to degradation by sunlight and heat and does not survive long outside the host. In laboratory settings, simple surface decontamination with bleach is sufficient and effective. According to the consensus position, there is no evidence to suggest environmental risk to humans in such settings, and thus environmental decontamination of an area exposed to an aerosol of plague is not necessary. In the World Health Organization (WHO) analysis (Inglesby et al., 2000), in the worst-case scenario, a plague aerosol was estimated

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework to be effective and infectious only for 1 hour. Although the data supporting those judgments is no longer available, it is suspected that the WHO committee that made the recommendations was not explicitly considering advanced weaponized formulations of Y. pestis. Smallpox Smallpox has been a great scourge of humankind. The disease was responsible for the deaths of about one-third of the European population during the Middle Ages. The smallpox virus particle is a complex structure about 300 nanometers (nm) in diameter, which is large enough to be viewed with a light microscope. The viral particle consists of DNA, protein, and lipids, with trace amounts of RNA. Several enzymes involved in RNA synthesis and modification are included. Smallpox belongs to the Poxviridae family, which is among the few DNA viruses that replicate in the cytoplasm of the infected cell. The virus most commonly enters the body via the airway. It is thought to infect the respiratory mucosa and spread locally to regional lymph nodes. After multiplying to high titer in the lymph nodes, the virus enters the bloodstream, causing a primary viremia. The viremia seeds many internal organs, such as the liver and spleen, where the virus undergoes multiple rounds of replication. When the titer is high enough, a secondary viremia ensues and the virus targets the skin and mucosa of the gastrointestinal tract. The ensuing rash is characteristic of the disease, progressing from macules to papules, vesicles, and finally to pustules that eventually scab. The rash begins on the head and trunk and progresses to the extremities. All of the lesions are at nearly the same stage in any one area of the body, and the lesions lead to the characteristic scarring. The time from infection to rash is about 2 weeks, which corresponds with the incubation period, during which the patient is asymptomatic. For 3-4 days, just before rash onset, there is dry cough, fever, and malaise, the so-called prodrome. Smallpox belongs to the genus Variola. The mortality rate for variola major is about 40%. However, if the rash becomes hemorrhagic, mortality is close to 100%. Another form, variola minor or alastrim, has a low mortality rate of 3%. Humans are the only natural host; the absence of an animal reservoir allowed WHO to eliminate the disease through a worldwide program of vigorous, targeted immunization (Fenner et al., 1998). Because smallpox is highly transmissible and the lyophilized form of the virus is stable at room temperature, smallpox was developed as a biological weapon in the former Soviet Union (Davis, 1999). Under the terms of a WHO agreement, smallpox preparations were to have been destroyed or placed in one of two repositories, the CDC in Atlanta, Georgia or in Russia. Whether there are additional stocks of smallpox beyond the official U.S. and Russian sites is not known. Before the invasion of Iraq in 2003, there was considerable concern that there might be smallpox stocks there (Davis, 1999). However, to date, there is no

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework evidence for the existence of smallpox in Iraq after 1992. Because smallpox was endemic in many areas of the world, old clinical specimens from patients might still exist and could serve as the source of a weapons-grade version of smallpox. A live, attenuated virus, vaccinia—a close relative to smallpox—is an effective vaccine. The smallpox vaccine has not changed much since it was invented by Dr. Edward Jenner in the late eighteenth century. Although quite effective in protecting against smallpox, the vaccine can cause serious side effects, which can be deadly or cause severe sequellae. Immunosuppressed or immunodeficient people are at significant risk if exposed to the vaccinia virus vaccine. Reimmunization with the vaccinia virus every several years has been recommended for maximum protection. Because of the sequellae associated with immunization and the large number of people whose systems are immunodepressed, prophylactic immunization of the general population has not been seen as a viable public health strategy. Even an attempt to immunize frontline health care providers and first responders was not met with enthusiastic, widespread acceptance. Clearly, a safer vaccine is needed. Significant effort is being expended in this area and a more attenuated vaccinia virus, modified vaccinia ankara, is being tested. Development of an effective antiviral drug would be a highly desirable complement to vaccines. The drug most studied currently is cidofovir, which has been approved by the U.S. Food and Drug Administration for the treatment of cytomegalovirus. Cidofovir is nephrotoxic, so development of additional effective drugs is needed. Although USAMRIID (2001) lists smallpox as stable, its persistence depends on environmental conditions and possibly on its formulation into weapons. In its natural form, variola major is sensitive to environmental conditions and has a short half-life outside of a human host. However, drying the virus renders it stable, and additional efforts to weaponize a dried form could be possible. Weaponized smallpox could be quite stable in indoor environments and so would present decontamination challenges similar to those posed by B. anthracis. NATURAL BACKGROUND Several potential agents of bioterrorism occur naturally worldwide. Although smallpox has been eradicated from all of its natural reservoirs, anthrax, plague, and tularemia are zoonoses endemic in many parts of North America. Botulinum spores are found in soil the world over: They have been recovered from agricultural products in marine sediments and from the intestines of animals and fish (Chin, 2000). Plague is a zoonosis that occurs between rodents and fleas. Wild rodent plague is endemic in the western half of the United States. The bacterial infection can be transferred to other animals, including rabbits, and to other wild and domestic carnivores, which can transmit the infection to humans. Although the bacterium can remain viable for several weeks in water and moist grains, it is killed by several hours’ exposure to sunlight (Chin, 2000). Background concen-

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework trations of plague in the environment are not likely to compromise decontamination efforts or to lead to false alarms. Tularemia, another zoonosis, occurs throughout North America in a cycle of transmission between rabbits and ticks. Humans can become infected by drinking contaminated water; inhaling dust from contaminated soil, grain, or hay; or from contact with the pelts or paws of infected animals. Because tularemia cannot persist in the environment, its natural background is not likely to compromise decontamination efforts. As far as we know, although botulinum spores persist in the soil, they do not pose a public health threat. Although the incidence of anthrax in humans and livestock has been decreasing in industrialized countries, it still occurs sporadically in bison and white-tailed deer in parts of Canada, and it is hyper-endemic in white-tailed deer in southwest Texas (Hugh-Jones, 1999). B. anthracis spores can remain viable in soil and dust for decades, especially around gravesites or near the carcasses of infected or diseased animals. Because of the resilient nature of anthrax spores in the environment and the possibility that they could confound decontamination assessment in areas where the disease is endemic in animals, determination of the environmental background is important. Naturally occurring outbreaks of B. anthracis in animals have been sporadic in North America over the past few centuries. The first recorded case in the United States occurred in the 1780s. By the 1800s, anthrax was reported in the eastern United States and along the Mississippi River. The disease is believed to have spread across the country on the cattle trails. The incidence of the disease in animals gradually increased until the late 1950s, after which it declined rapidly because of the use of the Sterne veterinary vaccine. The incidence of naturally occurring outbreaks of B. anthracis in animals has varied by time and place. A retrospective analysis of anthrax in the United States for 1900-2000 indicates that the occurrence in livestock at the county level was associated with chernozem soils, which are rich in calcium and have a neutral to alkaline pH. Those soils are found most often in prairies, grasslands, and areas of cereal grain cultivation. Counties with chernozem soil were found to be 4.7 times more likely to have outbreaks of the disease, and the death rate for livestock during outbreaks was 21 times higher than outbreaks occurring on nonchernozem soils. The study also assessed the incidence of outbreaks in close proximity to a cattle trail. Although death rates showed no difference, counties within 10 miles of a cattle trail were 2.3 times more likely to have outbreaks of B. anthracis (K. Smith, presentation to the committee, March 29, 2004). Officials at CDC have noted the importance of determining natural background for B. anthracis in establishing realistic thresholds for cleanup efforts, particularly in areas where outbreaks in animals have occurred in the past (Roos, 2004). Although a study of B. anthracis spore contamination between outbreaks in endemic regions of northern Canada (Dragon et al., 2001) reported high environmental concentrations of spores, they appeared limited to scavenger feces and

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework to sites where diseased carcasses had been found. Although epidemiological investigations were done for “occupational” outbreaks in textile mills and among veterinarians, and in agricultural settings with human and animal cases, there have been few systematic studies of the natural background of B. anthracis spores in the environment. Investigations of epizootics—outbreaks of disease affecting many animals of kind at the same time—detailed in a CDC (1961) report included soil sampling programs in Mississippi, Louisiana, Wyoming, Louisiana, and Arkansas. Positive samples were associated with moist soil and an alkaline pH. Pepper and Gentry (2002) reviewed the literature on the ecology and persistence of B. anthracis and other Bacillus species in soil. The authors pointed out the need for additional research on the conditions that favor B. anthracis survival in soil, the determination of whether it undergoes a growth cycle, and whether B. anthracis virulence genes could be transferred to other soil microorganisms. The Center for Environmental Biotechnology at Lawrence Berkeley National Laboratory in California is creating the first database of naturally occurring airborne bacteria from samples collected throughout the United States. The study, funded by the Department of Homeland Security, will identify background strains and concentrations of bacteria contained in aerosols from major metropolitan centers. The database will provide information by season and geographic region and thus facilitate a better understanding of background bacteria in the air we breathe (Krotz, 2004). The information also will be useful for comparison with data from environmental sensors, for example, to help scientists determine whether a detected pathogen might have come from a natural source or is a result of an intentional release. Although the foregoing information suggests that over time humans and animals have been exposed to naturally occurring B. anthracis and have either avoided infection or become infected and survived to develop immunity, the committee cautions that such cases are not useful for establishing “acceptable” residual contamination in public buildings, for several reasons. Preparation of biological agents for use as weapons could vary and alter the infectivity of the agents with respect to the natural form. Given the variability in infectivity and virulence in biological agents that is attributable to natural variation or to processing as weapons, we should not presume that the results of the epidemiological studies described here can be extrapolated to human exposure to B. anthracis spores during an act of bioterrorism. Although crudely prepared B. anthracis spores might have characteristics that closely resemble the natural form, they are not likely to be found as natural background in indoor facilities. Therefore, the concept of natural background is not applicable to the case of B. anthracis in indoor facilities. In areas where there is a natural background of B. anthracis, such as woolen mills, the people occupying the space might have developed immunity to the

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework agent as a result of constant exposure. Occupants of public facilities where there is no detectable background are unlikely to do so and might be more susceptible to the agent regardless of preparation. CONCLUSION Although individuals in some areas encounter harmful agents that occur naturally in the environment and show few or no health effects, for two reasons we caution against extrapolation for determining an acceptable amount of residual contamination by harmful agents released during a bioterrorist attack. First, it is unlikely that a detectable natural background of the harmful agent would be present in indoor public facilities. Indoor air-monitoring equipment installed in many facilities has not detected those agents. In the past century, there have been few known cases of anthrax, smallpox, plague, or Ebola in which the disease was acquired through exposure to a natural background concentration of the agent. The exceptions have been in workers who acquired anthrax at woolen mills and in people who acquired smallpox, plague, or Ebola in hospitals where infected patients were being treated. Second, microorganisms of the same species can vary in infectivity and virulence as a result of variations among strains or because of the weaponization processes that alter their characteristics. The fact that people can tolerate a background concentration of naturally occurring pathogens does not guarantee that they will tolerate a similar concentration in weaponized form. Thus, even though scientists have extensive experience with disinfection of contaminated facilities, such as microbiology laboratories or hospital wards, there is limited knowledge about decontamination of facilities that have been intentionally contaminated with biological agents. FINDINGS AND RECOMMENDATIONS Finding 2-1 Naturally occurring infectious-disease hazards provide much information that is useful for biodefense consequence management planning, but weaponized biological agents could pose special threats that are distinct from those attributable to naturally occurring hazards, especially when it comes to decontamination. Recommendation 2-1 Decontamination decisions and plans should consider the natural characteristics of a specific pathogen and the weaponization characteristics of that agent. Weaponized agents can vary in infectivity and virulence as a result of formulation, and the presence of a natural background of weaponized agents (such as weaponized B. anthracis) is unlikely in indoor public facilities. Given the uncertainties in the characteristics of the weaponized agents, it is impossible to estab-

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework lish acceptable thresholds below which exposure to such weaponized agents would pose zero risk. REFERENCES Alibek, K. 1999. Biohazard: The Chilling True Story of the Largest Covert Biological Weapons Program in the World—Told from Inside by the Man Who Ran It. New York: Dell Publishing. Atlas, R.M. 2001. Bioterrorism before and after September 11. Critical Reviews in Microbiology 27:355-379. Atlas, R. 2002. Bioterrorism: from threat to reality. Annual Reviews in Microbiology 56: 167-185. Bales, M.E., L. Dannenberg, P.S. Brachman, A.F. Kaufmann, P.C. Klatsky, and D.A. Ashford. 2002. Epidemiologic response to anthrax outbreaks: field investigations, 1950-2001. Emerging Infectious Diseases 8(10): 1163-1174. Carus, W.S. 2001. Bioterrorism and Biocrimes: The Illicit Use of Biological Agents Since 1990. Working Paper, Center for Counterproliferation Research. Washington, DC: National Defense University. CDC (U.S. Communicable Disease Center). 1961. Final Report from Department of Health, Education and Welfare, United States Public Health Service, Bureau of State Services, Communicable Disease Center to Department of Defense, Department of the Army, Chemical Corps, Fort Detrick, Frederick, Maryland. Contract Number FD6-404-6302. CDC (U.S. Centers for Disease Control and Prevention). 1997. Fatal human plague—Arizona and Colorado, 1996. Morbidity and Mortality Weekly Report 46(27): 380-382. CDC. 1999. Bioterrorism alleging use of anthrax and interim guidelines for management—United States, 1998. Morbidity and Mortality Weekly Report 48: 69-74. CDC. 2001. Update: investigation of anthrax associated with intentional exposure and interim public health guidelines. Morbidity and Mortality Weekly Report 50(41): 889-893. CDC. 2004a. Frequently Asked Questions About Smallpox. [Online]. Available at: http://www.bt.cdc.gov/agent/smallpox/disease/faq.asp (accessed on November 16, 2004). CDC. 2004b. Frequently Asked Questions About Plague. [Online] Available at: http://www.bt.cdc.gov/agent/plague/faq.asp (accessed on November 16, 2004). Chin, J., ed. 2000. Control of Communicable Diseases Manual, 17th edition. Washington, DC: American Public Health Association. Cole, L.A. 2003. The Anthrax Letters. Washington, D.C.: Joseph Henry Press. Davis, C.J. 1999. Nuclear blindness: an overview of the biological weapons programmes of the former Soviet Union/Russia and Iraq. Emerging Infectious Diseases 5(4): 509-512. Dragon, D.C., R.P. Rennie, and B.T. Elkin. 2001. Detection of anthrax spores in endemic regions of northern Canada. Journal of Applied Microbiology 91: 435-441. Fenner, F., D.A. Henderson, I. Arita, Z. Jezek, and I.D. Ladnyi. 1998. Smallpox and Its Eradication. Geneva: World Health Organization. Hugh-Jones, M. 1999. 1996-97 global anthrax report. Journal of Applied Microbiology 87(2): 189-191. Inglesby, T.V., D.T. Dennis, D.A. Henderson, J.G. Bartlett, M.S. Ascher, E. Eitzen, A.D. Fine, A.M. Friedlander, J. Hauer, J.F. Koerner, M. Layton, J. McDade, M.T. Osterholm, T. O’Toole, G. Parker, T.M. Perl, P.K. Russell, M. Schoch-Spana, and K. Tonat. 2000. Plague as a biological weapon. Medical and public health management. Journal of American Medical Association 283: 2281-2290. Kolavic, S.A., A. Kimura, S.L. Simons, L. Slutsker, S. Barth, and C.E. Haley. 1997. An outbreak of Shigella dysenteriae type 2 among laboratory workers due to intentional food contamination. Journal of American Medical Association 278(5): 396-398.

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Reopening Public Facilities after a Biological Attack: A Decision Making Framework Krotz, D. 2004. Cataloging airborne bacteria, city by city. Lawrence Berkeley National Lab Science Beat: March 24, 2004. [Online] Available at: http://www.lbl.gov/Science-Articles/Archive/sb-ESD-cataloging-bacteria.html. Meselson, M., J. Guillemin, M. Hugh-Jones, A. Langmuir, I. Popova, A. Shelokov, and O. Yampolskaya. 1994. The Sverdlovsk anthrax outbreak of 1979. Science 266: 1202-1208. NRC (National Research Council). 2004. Biotechnology Research in an Age of Terrorism. Washington, DC: The National Academies Press Pepper, I.L. and T.J. Gentry. 2002. Incidence of Bacillus anthracis in soil. Soil Science 167: 627-635. Perry, R.D., and J.D. Fetherson. 1997. Yersinia pestis—etiologic agent of plague. Clinical Microbiology Reviews 10: 35-66. Ramalingaswami, V. 2001. Psychosocial effects of the 1994 plague outbreak in Surat, India. Military Medicine 166: 29-30. Roos, R. 2004. CDC seeks to determine natural background level of anthrax. University of Minnesota Center for Infectious Disease Research & Policy (CIDRAP) News: Nov 16, 2004. [Online] Available at: http://www.cidrap.umn.edu/index.html. Shah, G. 1997. Public Health and Urban Development: The Plague in Surat. Thousand Oaks, California: Sage Publications. Smithson, A.E., and L.A. Levy. 2000. Ataxia:* The chemical and biological terrorism threat and U.S. response. Washington, DC: Henry L. Stimson Center. Suffin, S.C., W.H. Carnes, and A.F. Kaufmann. 1978. Inhalation anthrax in a home craftsman. Human Pathology 9: 594-597. Torok, T.J., R.V. Tauxe, R.P. Wise, J.R. Livengood, R. Sokolow, S. Mauvais, K.A. Birkness, M.R. Skeels, J.M. Horan, and L.R. Foster. 1997. A large community outbreak of salmonellosis caused by intentional contamination of restaurant salad bars. Journal of the American Medical Association. 278(5): 389-395. USAMRIID (U.S. Army Medical Research Institute of Infectious Diseases). 2001. Medical Management of Biological Casualties Handbook, Fourth Edition. Fort Detrick, Frederick, Maryland: USAMRIID. Wheelis, M. 1999a. Biological Warfare Before 1914. Pp. 8-34 in Biological and Toxin Weapons: Research, Development and Use from the Middle Ages to 1945, E. Geissler and J.E.v.C. Moon, Eds. Oxford: Oxford University Press. Wheelis, M. 1999b. Biological Sabotage in World War I. Pp. 35-62 in Biological and Toxin Weapons: Research, Development and Use from the Middle Ages to 1945, E. Geissler and J.E.v.C. Moon, Eds. Oxford: Oxford University Press. Wheelis, M. 2003. A Short History of Biological Warfare and Weapons. In M.I. Chevrier, K. Chomiczewski, M.R. Dando, H. Garrigue, G. Granaztoi, and G.S. Pearson, eds. The Implementation of Legally Binding Measures to Strengthen the Biological and Toxin Weapons Convention. ISO Press Amsterdam.