Preparing for Biological and Chemical Attacks - Critical Biological And Chemical Agents

Biological Agents

THREAT DELINEATION. The first step in preparing for biological or chemical attacks is to detect threats. The CDC has gone to great lengths to identify and prioritize biological and chemical weapons agents. Priorities are based less on the likelihood of an agent's use than on its potential to cause widespread catastrophe. Agents have traditionally been evaluated based on military concerns and troop protection, but civilian populations differ in many ways from military populations, having a wider age range and a wider range of health conditions. In general, civilian populations are more vulnerable, and consequences of an attack would be more severe. This means that military priority lists cannot simply be carried over and applied to civilian threats.

In 1999 Congress began to upgrade public health capabilities to respond to potential biological and chemical attacks, making the CDC the lead agency for overall public health planning. The CDC, in turn, formed a Bioterrorism Preparedness and Response Office to focus on several areas of preparedness, including planning, improved surveillance and epidemiological capabilities, rapid laboratory diagnostics, enhanced communications, and medical therapeutics stockpiling.

To focus the preparedness efforts properly, the first step was to identify and prioritize critical biological and chemical agents. Many biological agents affect human beings, but relatively few, authorities reasoned, have the potential to create public health catastrophes that would severely strain U.S. public health and medical systems, so the CDC sought a new threat-assessment method that could be reviewed, reproduced, and standardized.

On June 3–4, 1999, the CDC convened a meeting of national experts to review the threat potential of various biological and chemical agents to civilian populations. The experts included academic infectious disease experts, national public health experts, CDC personnel, civilian and military intelligence experts, and law enforcement officials. They identified agents they believed had the potential for great public health impact based on subjective assessments in four general categories: overall public health impact (the death or disease rates), dissemination potential (how much the disease could spread), public perception of its impact, and the special preparedness needed for each agent. These criteria were weighted on a scale from zero to three for each agent in order to evaluate the potential threat from each. A factor given the most weight received a three (+++), and the factor given the least weight received a zero (0). Final category assignments—A, B, or C threat status—were based on the ratings the agents received in each of the four areas. (See Table 5.1.)

Category A agents have the greatest potential for causing disruption, disease, and mass casualties, and require the broadest public health preparedness, including improved surveillance, laboratory diagnosis, and medication stockpiling. Examples of Category A agents are those that cause smallpox, anthrax, plague, botulism, and tularaemia.

Category B agents have the potential for large-scale catastrophe but generally would cause fewer cases of severe illness and death than Category A agents. They would have a smaller public health and medical impact, have lower public awareness, and require fewer special preparedness measures. Although these, too, should receive heightened awareness from the medical and emergency communities, along with more surveillance and improved laboratory diagnostic capabilities, these are not needed for Category B agents on the order suggested for Category A agents. In Category B are some agents that the CDC and its experts know have undergone development as weapons but that otherwise do not meet Category A criteria, as well as some agents of concern for food and water safety. Examples of Category B agents include organisms that cause Q fever, brucellosis, and glanders, as well as food- or waterborne agents such as salmonella and E. coli pathogens.

Category C agents do not currently appear to present a high bioterrorism threat but may emerge as future threats as scientific knowledge about them improves. These agents are addressed by the CDC's overall preparedness efforts—efforts intended to improve detection and treatment of unexplained illnesses and emerging infectious diseases. Category C agents include the Nipah virus, hantaviruses, yellow fever, and multidrug-resistant tuberculosis.

The agents were categorized based on the evaluation criteria applied to them, especially in Categories A and B. For example, the public health impact of smallpox (Cate-gory A) ranks higher than that of brucellosis (Category B) because the mortality for those untreated is higher for the former (about 30%) than the latter (about 2%). In addition, smallpox has a higher dissemination potential because it can be transmitted from person to person. It ranks higher for special public health preparedness, as well, because additional vaccine must be made and stockpiled, and improved surveillance, educational, and diagnostic efforts are necessary. Other Category A threats, such as inhalation anthrax and plague, also have higher public impact ratings than brucellosis because of their higher morbidity (illness) and mortality (death) rates. Although mass production of Category B agents Vibrio cholerae (the organism causing cholera) and Shigella spp (the cause of shigellosis) would be easier than that of anthrax spores, these agents produce lower morbidity and

TABLE 5.1

Critical biological agents that pose a risk to national security
SOURCE: Ali S. Kahn, Alexandra M. Levitt, and Michael J. Sage, "BOX 3. Critical Biological Agents," in "Biological and Chemical Terrorism: Strategic Plan for Preparedness and Response," Morbidity and Mortality Weekly Report, vol. 49, no. RR-4, April 21, 2000, http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4904a1.htm (accessed September 23, 2004)
Category A
The U.S. public health system and primary health-care providers must be prepared to address varied biological agents, including pathogens that are rarely seen in the United States. High-priority agents include organisms that pose a risk to national security because they can be easily disseminated or transmitted person-to-person; cause high mortality, with potential for major public health impact; might cause public panic and social disruption; and require special action for public health preparedness (Box 2).
Category A agents include
variola major (smallpox); Bacillus anthracis (anthrax); Yersinia pestis (plague); Clostridium botulinum toxin (botulism); Francisella tularensis (tularaemia); filoviruses, — Ebola hemorrhagic fever, — Marburg hemorrhagic fever; and arenaviruses, — Lassa (Lassa fever), — Junin (Argentine hemorrhagic fever) and related viruses.
Category B
Second highest priority agents include those that are moderately easy to disseminate; cause moderate morbidity and low mortality; and require specific enhancements of CDC's diagnostic capacity and enhanced disease surveillance.
Category B agents include
Coxiella burnetti (Q fever); Brucella species (brucellosis); Burkholderia mallei (glanders); alphaviruses, — Venezuelan encephalomyelitis, — eastern and western equine encephalomyelitis; ricin toxin from Ricinus communis (castor beans); epsilon toxin of Clostridium perfringens; and Staphylococcus enterotoxin B. A subset of List B agents includes pathogens that are food- or waterborne. These pathogens include but are not limited to Salmonella species, Shigella dysenteriae, Escherichia coli O157:H7, Vibrio cholerae, and Cryptosporidium parvum.
Category C
Third highest priority agents include emerging 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 and major health impact.
Category C agents include
Nipah virus, hantaviruses, tickborne hemorrhagic fever viruses, tickborne encephalitis viruses, yellow fever, and multidrug-resistant tuberculosis.
Preparedness for List C agents requires ongoing research to improve disease detection, diagnosis, treatment, and prevention. Knowing in advance which newly emergent pathogens might be employed by terrorists is not possible; therefore, linking bioterrorism preparedness efforts with ongoing disease surveillance and outbreak response activities as defined in CDC's emerging infectious disease strategy is imperative.

mortality, so their public health impact, or dissemination threat, would be less. Although infectious doses of these bacteria are very low, it would be very difficult for a terrorist to use them effectively. The total amount of bacteria required, as well as the advanced state of current water purification and food-processing techniques, would limit these agents' effectiveness for intentional, large-scale water or food contamination.

PREPAREDNESS ACTIVITIES. In addition to identifying major biological agents and threats, the CDC (in its publication Morbidity and Mortality Weekly, vol. 49, no. RR-4, April 21, 2000) provided nine basic steps to prepare public health agencies for biological attacks:

1. Enhance epidemiologic capacity to detect and respond to biological attacks
2. Supply diagnostic reagents to state and local public health agencies
3. Establish communication programs to ensure delivery of accurate information
4. Enhance bioterrorism-related education and training for health-care professionals
5. Prepare educational materials that will inform and reassure the public during and after a biological attack
6. Stockpile appropriate vaccines and drugs
7. Establish molecular surveillance for microbial strains, including unusual or drug-resistant strains
8. Support the development of diagnostic tests
9. Encourage research on antiviral drugs and vaccines

Enhancing epidemiologic capacity means adding additional resources to trace the source and spread of dis-ease. Supplying diagnostic reagents means providing chemical compounds to state and local public health agencies for a variety of medical purposes ranging from detection to prevention.

Chemical Agents

THREAT DELINEATION. Chemical agents can range from warfare agents to toxic substances in common commercial use. The fact that chemical warfare technologies are increasingly available, coupled with the relative ease with which chemical agents can be produced, increases the U.S. government's concern that terrorist states or groups may use them in the future.

The CDC takes a similar approach to combating chemical threats as it does to biological ones, providing many of the same resources to state and local public health agencies and emergency services teams. However, the CDC's identification and prioritization of critical chemical agents differs from that of biological agents. Because hundreds of new chemicals are introduced inter-nationally each month, the categories of chemical agents are necessarily more generic than for biological agents.

The CDC identifies and prioritizes chemical agents according to criteria including the following:

• Are the agents already known to be used as weapons?
• Are they readily available to hostile states and terrorists?
• Are they likely to cause morbidity or mortality?
• Are they likely to cause panic or disruption?
• Do they require special actions for public health preparedness?

Table 5.2 lists the CDC's chemical agent categories, along with notable examples of each. The chemical agents most likely to be used are nerve agents (tabun, sarin, soman, GF, and VX), blood agents (hydrogen cyanide and cyanogen chloride), blister agents (lewisite, mustards, and phosgene oxime), and heavy metals (arsenic, lead, and mercury).

PREPAREDNESS ACTIVITIES. The CDC provides recommendations to help public health agencies prepare for potential chemical attacks. First, agencies should take a generic approach to the treatment of chemical agent injuries, treating those exposed according to clinical syndrome, or the group of symptoms they have, rather than the specific agent. These syndromes include burns and trauma, cardio-respiratory failure, neurological damage, and shock. Those who respond and treat affected individuals must also communicate with the authorities responsible for environmental sampling for, and decontamination of areas affected by, such chemical agents.

The CDC's five steps in preparing public health agencies for chemical attacks are listed in their publication Morbidity and Mortality Weekly (vol. 49, no. RR-4, April 21, 2000):

• Enhance epidemiologic capacity for detecting and responding to chemical attacks
• Enhance awareness of chemical terrorism among emergency medical service personnel, police officers, firefighters, physicians, and nurses
• Stockpile chemical antidotes
• Develop and provide bioassays for detection and diagnosis of chemical injuries
• Prepare educational materials to inform the public during and after a chemical attack

Enhancing epidemiological capacity refers to mapping the origin and spread of disease symptoms. Bioassays are intended to determine the relative strength of a chemical agent by comparing its effect on a test organism with that of a standard-strength preparation.

Laboratory Response Network

The CDC has described five key focus areas of state and local efforts to prepare for biological and chemical attacks:

TABLE 5.2

Chemical agents that might be used by terrorists
SOURCE: Ali S. Kahn, Alexandra M. Levitt, and Michael J. Sage, "BOX 5. Chemical Agents," in "Biological and Chemical Terrorism: Strategic Plan for Preparedness and Response," in Morbidity and Mortality Weekly Report, vol. 49, no. RR-4, April 21, 2000, http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4904a1.htm (accessed September 23, 2004)
Chemical agents that might be used by terrorists range from warfare agents to toxic chemicals commonly used in industry. Criteria for determining priority chemical agents include chemical agents already known to be used as weaponry; availability of chemical agents to potential terrorists; chemical agents likely to cause major morbidity or mortality; potential of agents for causing public panic and social disruption; and agents that require special action for public health preparedness (Box 4).
Categories of chemical agents include nerve agents, — tabun (ethyl N, N-dimethylphosphoramidocyanidate), — sarin (isopropyl methylphosphanofluoridate), — soman (pinacolyl methyl phosphonofluoridate), — GF (cyclohexylmethylphosphonofluoridate), — VX (o-ethyl-[S]-[2-diisopropylaminoethyl]-methylphosphonothiolate); blood agents, — hydrogen cyanide, — cyanogen chloride; blister agents, — lewisite (an aliphatic arsenic compound, 2-chlorovinyldichloroarsine), — nitrogen and sulfur mustards, — phosgene oxime; heavy metals, — arsenic, — lead, — mercury; Volatile toxins, — benzene, — chloroform, — trihalomethanes; pulmonary agents, — phosgene, — chlorine, — vinyl chloride; incapacitating agents, — BZ (3-quinuclidinyl benzilate); pesticides, persistent and nonpersistent; dioxins, furans, and polychlorinated biphenyls (PCBs); explosive nitro compounds and oxidizers, — ammonium nitrate combined with fuel oil; flammable industrial gases and liquids, — gasoline, — propane; poison industrial gases, liquids, and solids, — cyanides, — nitriles; and corrosive industrial acids and bases, — nitric acid, — sulfuric acid.

1. Preparedness and prevention
2. Detection and surveillance
3. Diagnosis and characterization of biological and chemical agents
4. Response
5. Communication

Perhaps the most technically challenging of the five focus areas is the third: diagnosis and characterization of biological and chemical agents. For that reason, the CDC and its partners created two multilevel laboratory response networks, one for biological terrorism and one for chemical terrorism. These networks link state-of-theart clinical labs to state and local public health agencies in all states, districts, territories, and selected cities and counties. Each network is a three-level hierarchy of laboratories, according to their respective capabilities. The Laboratory Network for Biological Terrorism consists of three types of laboratories:

1. National Laboratories are responsible for specialized strain characterizations, bioforensics, select agent activity, and handling highly infectious biological agents.
2. Reference Laboratories are responsible for investigation and/or referral of specimens.
3. Sentinel Laboratories play a key role in the early detection of biological agents.

National Laboratories are those run by the CDC or by the U.S. Army Medical Research Institute of Infectious Diseases. There are over a hundred Reference Laboratories across the United States and in Australia and Canada, and some 25,000 designated Sentinel Laboratories.

The Laboratory Network for Chemical Terrorism consists of three levels as well, designated as Levels 1, 2, and 3. All sixty-two laboratories in the network perform Level 1 duties, which are:

• Working with hospitals in their jurisdiction
• Knowing how to properly collect and ship clinical specimens
• Ensuring that specimens, which can be used as evidence in a criminal investigation, are handled properly and chain-of-custody procedures are followed
• Being familiar with chemical agents and their health effects
• Training on anticipated clinical sample flow and shipping regulations
• Working to develop a coordinated response plan for their respective state and jurisdiction

Of the sixty-two chemical terrorism network laboratories, forty-one also participate in Level 2 activities in which laboratory personnel are trained to detect exposure to a limited number of toxic chemical agents in human blood or urine. In Level 3 laboratories, which comprise five of the total sixty-two, personnel are trained to detect exposure to an expanded number of chemicals in human blood or urine, plus analyses for mustard agents, nerve agents, and other toxic chemicals.