RAPiDT Manual for MFRs

The RaPiD-T program is designed to increase essential capabilities that must be possessed by first responders in the event of a Weapon of Mass Destruction release. Should such an attack occur upon our population, the calm competent responses on the part of law enforcement, EMS, hospital, and HAZMAT/Fire professionals will be critical to minimize casualties and to preserve essential services. The specific components of this program are R-recognition, P-protection, D-decontamination, and T-triage/treatment. Recent experiences have indicated that first responders are particularly susceptible to secondary contamination by a number of these agents. In addition to the injury and illness of the target population, it is the precisely the secondary contamination of first responders that increases the terror potential of these substances. The ability of these munitions to rapidly produce illness and injury of large numbers of victims and simultaneously weaken the EMS, hospital, law enforcement systems will most probably create terror in our society. Terrorist groups who are willing to use these weapons are currently attempting to procure these weapons to further their goals. The availability of required knowledge and raw materials to international and domestic terrorist groups make it imperative for first responders to increase their skills in this area.

Weapons of Mass Destruction are defined as substances capable of relatively undetected dissemination and high toxicity such that large numbers of people may be exposed from a single release. It is important to recognize that the release of such a weapon does not entail the destruction of anything but the people exposed. They may then be more aptly named weapons of mass casualties as there are no large destructive explosions associated with an attack of this sort. In this way, weapons of mass destruction are quite stealthy. Substances capable of such effects may be divided into chemical weapons, biological-toxicological weapons, and radiological material. Chemical weapons are subdivided into several categories base upon the effects the agent has upon the body. Biological-toxicological weapons are naturally-occurring, disease producing organisms or substances that are purified and prepared for mass aerosol or food/water distribution. Radioactive isotopes are used in the construction of nuclear weapons that are quite detectable at the time of their release. This program is not intended to prepare the user for management of a nuclear detonation. The scope of this manual is limited to the effects of radiation exposure from unshielded sources upon the human body. The inherent difficulty in the construction of a fission bomb makes the likely-hood of radiation source exposure much more likely.

Despite the great lethality and limited detectability of these munitions, the United States has the knowledge required to manage casualties of this sort. Chemical weapons have been part of modern warfare since World War I and many substances are common industrial hazardous materials. Biological weapons are, after all, really just diseases that are intentionally and efficiently spread. Radiation sources are also part of our world and have applications in medicine, and industry. Weapons of mass destruction are different only in that they are unexpected and are designed for high lethality. Because recognition of a sudden epidemic of similar symptoms in the target population is the first and most critical step in the management, law enforcement and EMS personnel are in a unique position to view the community at large. The recognition of an unexpected epidemic in a population who could be exposed in a common site, combined with awareness of the types of munitions most available could be the difference between life and death for both the exposed victims as well as the first responder.

During the Persian Gulf War, American soldiers faced the specter of Saddam Husseins chemical and biological weapons arsenal. We now know that the Iraqi arsenal included substances such as Botulinum Toxin, Anthrax spores, Aflatoxin, Sarin/Soman nerve poisons, and Mustard. These munitions were loaded in delivery vehicles such as SCUD missiles, gravity bombs, and artillery shells, aimed at American and coalition soldiers. Potentially, these agents had the capability to deliver mass casualties to the coalition forces, and significantly alter the course of the war. For some years now, the medical community of the United States Military has trained its professionals to recognize and manage the toxidromes of the likely agents used in just such a conflict. Because of the extreme toxicitys associated with these munitions, every soldier in the military is trained and equipped with chemical-biological countermeasures, and many military vehicles are designed with the threat in mind. Needless to say, the coalition nations, not to mention the individual soldier, breathed a heavy sigh of relief when the truce was called without a deliberate attack utilizing these weapons of mass destruction. For the most part, the United States watched the events of the war with curiosity, and patriotism.

In 1994 and again in 1995, the Aum Shinrikyo cult successfully executed two terrorist attacks in Japan using chemical weapons. The first of these attacks occurred in the Tokyo suburb of Matsumoto. A judge who was trying a cult member was threatened and his residence subsequently attacked with the use of heated Sarin vapor, delivered from a vehicle. This attack resulted in 200 casualties and 7 deaths. Included in the total were a significant number of health care professionals-but not the judge! Publicity of the Matsumoto incident was initially suppressed by a concerned Japanese government. Later, in 1995, the Aum Shinrikyo again struck at the heart of Tokyo in the now infamous subway attack. In this attack, cult members placed perforated Sarin containing packets at strategic locations of the Tokyo subway. Sarin is about four times heavier than air and the vapor was accumulated in the lower reaches of the subway. Approximately 5,500 casualties, (1,000 hospitalized) resulted from this incident and again, 132 medical professionals numbered significantly among the victims in which twelve deaths occurred. A recent report from Keio University Hospital cites the time for the majority of the treating physicians in the Emergency Department to become symptomatic from their contaminated patients as about 45 minutes. The actions of the Aum Shinrikyo represent the first time deaths in a civilian population had been caused by the terrorist use of a chemical weapon. The United States took notice of the capabilities of these munitions. Chemical and biological weapons had previously been the domain of the military physician, but times have changed. The success of the Aum Shinrikyo attack has focused world attention on the use of war agents against civilian populations.

Chemical weapons have been part of the modern battlefield since the first use of Chlorine gas at Ypres, Belgium in 1915. Dr. Fritz Haber, a Nobel Prize winning German chemist, was instrumental in the development of this new type of weapon. The effect of this new munition was so impressive that a chemical arms race existed during the first World War with Phosgene, Cyanide, Mustard, and Lewisite being developed by American, British and German scientists prior to the end of the war. A new class of chemical weapons, the G-agents, were developed by German scientists, during the buildup preceding World War II. Although these weapons were not used on the World War II battlefield, once their potential was recognized, they quickly became part of the arsenals of the developed nations. Sarin (GB), the agent used in 1994--95 by the Aum Shinrikyo cult, was first synthesized in 1936 by Dr. Gerhard Schrader. It is the ability for a private group to manufacture and deliver a weapon of mass destruction against an unprepared populace that has caused the recent focus on these agents. Although once the realm of experimental, and Nobel Prize-winning chemistry, the 60 to 100 year old technology required, and the precursors needed have become commonplace in the industrial and academic world.

Biological weapons are actually something of a misnomer. Disease has always been part of any military campaign and, in the pre-antibiotic era, was typically responsible for a greater share of casualties than the tip of the spear. Many attempts at contamination of an enemys water and food date to antiquity. A modern biological weapon is merely the intentional culture, purification, and weaponization of a known disease producing organism or toxin. Unit 731 of the Imperial Japanese army was the first military unit expressly designed for the purposes of creation of bio-weapons. From 1932-1944, Unit 731 operated near Chang-Teh, Manchuria. American, British, and Australian prisoners of war, along with an alarming number of Chinese civilians, were used as subjects in the development of plague, cholera, and botulinum weapons. Biological weapons were not used on the WWII battlefield, mainly because of the lack of protective measures and the problem of containment. The capability of these agents, however, did not go unnoticed by the victors, as the USSR and Americans took possession the records, and scientists associated with the Unit 731 program to start their own programs. Like chemical weapons, the technology required to create a bio-weapon is now commonplace, and the precursors naturally occur, or are easily attainable. Perhaps the most ominous feature of the biological weapons is their stealth. Because all that is required is contamination of the air, water, or foodstuffs, there would be no explosion, or discernable cloud, smoke, or odor associated with the discharge of the weapon. The recognition of a sudden epidemiological event by the medical community is the first line of detection.

A 1992 incident in Oregon in which Salmonella was intentionally spread by followers of the Bhagwan Shree Rajneesh focused attention on the American medical establishment and the ability to effectively deal with a biological terrorist incident in America. Because disease-producing organisms occur naturally, the biological weapons must be differentiated from naturally occurring outbreaks. Delays in recognition of a bio-weapon discharge can be expected because many physicians in the United States are unfamiliar with the etiological agents used in bacterial warfare. In addition, victims will present in a haphazard manner to various health care facilities as they become sick. The recognition of a biological weapon will, therefore, be dependent upon diagnosis of an unfamiliar epidemic condition by physicians of various specialties, and facilities. Effective treatment may therefore lag for potentially treatable victims because of the lack of this focused knowledge. In addition, biological agents are typically odorless and tasteless and may be placed in food or water supplies as well as transmitted by droplet aerosol, further complicating the recognition of the site of contamination. The cultures of many organisms may also be obtained from the environment, or low security laboratories, so that prohibition of the precursors may not be feasible. With commonly available culture and dispersal equipment, the possibility to infect a very large number of victims is possible with a minimum of expense and knowledge.

Because of these successful attacks and a careful assessment of the changing world climate, former Senator Sam Nunn refers to weapons of mass destruction as the most significant threat to American society in our lifetimes. In 1996, mass casualty drills conducted both in New York City and Los Angeles were modeled on the Japanese Sarin tragedy and the results clearly showed the lack of preparedness of our medical system with respect to the capabilities of these agents. For medical professionals, basic familiarity with the various munitions will be increasingly important. The recognition and management of an attack is incumbent upon the local pre-hospital and medical professionals. As we will discuss, the toxicity of the chemical and biological is significant and represents a major medical threat. Inconsistencies with common epidemiological or toxicological presentations, and recognition of the signs and symptoms of chemical weapons casualties are seminal to the discharge of this responsibility. Referral to the appropriate authorities will be essential to save lives, and to bring the perpetrator of the attack to justice. It is the medical professional whose action or inaction will determine the survival of the victims of such a weapon.

As the Aum Shinrikyo experience clearly demonstrates, the transmission of chemical and biological weapons is important to understand. Intended victims of an attack are termed the primary casualties, and are expected to congregate at medical facilities, with or without decontamination. There is a common misconception that EMS will be able to respond, and to decontaminate victims of these munitions. Historical data tell us that around 80% of victims involved in a HAZMAT mass casualty scenario will seek their own transportation to the perceived site of maximal care, i.e. the hospital or clinic. Secondary casualties are considered those individuals whom are exposed by the initial victims, namely the health care provider. The large numbers of health care professionals incapacitated by the Aum Shinrikyos attack proved the medical professions vulnerability to these extremely toxic agents. Although chemical and biological weapons are targeted at specific segments of the population, the loss of the healthcare provider will magnify the effect of these munitions. This subtlety is not lost on the terrorist. To foment additional terror in the target population, it is becoming more common to target the healthcare provider with secondary weapons as the recent experience in Ireland, the Middle East, as well as the Atlanta abortion clinic bombings demonstrated. Chemical and biological weapons expose the unprotected and unaware health care professional, and threaten the viability of our EMS and hospital system. For these reasons, we in the medical community can no longer afford blissful ignorance of these issues.

The recognition of weapons of mass destruction is based upon some degree of familiarity with the types of effects the agent has upon the human body. A great deal of specific knowledge may be required to ultimately diagnose and treat a specific munition but the recognition of basic symptom complexes combined with the good judgement already common in law enforcement, EMS, Fire/HAZMAT, and hospital personnel is all that is required for the first step.

Because weapons of mass destruction cause their effects by exposure of the target population at a common site, a number of normally healthy victims from such a site is the first warning of a release. In the 1987 salmonella outbreak in The Dalles Oregon, a religious cult group led by the Bhagwan Shree Rajneesh intentionally spread the microbe on salad bars throughout the town as depicted in the photo on the right. Although it would be possible for a single restaurant to cause such an outbreak, it would be highly unlikely for a simultaneous outbreak to occur at multiple sites. Although first responders may not know the initially know identity of the microbe, or the treatments required, the occurrence of this unusual event bears investigation. Because individual doctors at individual hospitals may only see a portion of the community, it may be difficult for the medical authorities to recognize such an event. Merely taking the appropriate history along with awareness of weapons of mass destruction is all that is required to recognize the event. It is the first responders that possess the necessary view of the community to best serve as early warning.

In addition to a common site of exposure, a common route of exposure is the next most important concept to understand. Weapons of mass destruction do not cause death by large explosions or deadly projectiles, rather, these substances must enter the body and derange the normal physiology in some way. The best routes to expose a large number of individuals are to use a respiratory aerosol or to contaminate food or water supplies. In the salmonella incident cited above, food supplies were contaminated and gastrointestinal symptoms predominated. A respiratory aerosol refers to the intentional formation of a cloud of suspended particles inspired into the lungs and absorbed by the victim. Also possible is contact absorption of the compound by exposed skin. A common route of possible exposure is critical to determine by first responders. Although all three routes of exposure of important to consider, it is by the respiratory route that biological and chemical weapons have their greatest potential effect. Unexpected respiratory symptoms noted in a large number of previously healthy individuals are therefore clearly cause for concern.

The final important concept for recognition is that the victims will develop severity of symptoms based upon the level of exposure not on their state of health. We are all aware of natural epidemics of flu and colds that affect the population. As first responders, we know that the very old, the very young, and the chronically ill individuals among the population will be the most affected. A weapon of mass destruction, however, will have its effect primarily upon those most highly exposed. Severe symptoms and death in previously young healthy individuals without corresponding illness in the less healthy individuals of the community is a significant piece of information. Although the three points described above do not definitely establish a weapon release, the combination of these phenomena should trigger an evaluation by higher authorities of the potential of a terrorist act.

Protection from a weapon of mass destruction is an imperative for first responders and medical professionals. Although contrary to the natural responses of most in the first responder community, the most important first action to take upon recognition of a weapon or mass destruction release is to protect the first responder. Though it is difficult, one must focus upon the community under attack rather than the individual. For the community of victims to survive, medical assets will have to be brought to bear upon the victims. If the medical assets, namely the first responders, have contaminated themselves in the rush to help, they have added themselves as victims rather than preserved their ability to help. The three women in the photo are rushing to help victims of the Oklahoma City bombing. Had a chemical, biological or nuclear device been used in conjunction with this attack, these well meaning first responders would have been casualties. Instead of constructing a set of rules to govern every possible situation, it is of probably greater utility to teach principles and allow the first responder to choose his or her own path. Toward that end, this manual will elaborate the elements of cross contamination and the basics of personal protective equipment (PPE).

All of the chemical and biological agents have different characteristics and affect the victim in different ways but all have in common extreme toxicity. When approaching an unknown situation, one must assume the worst and prepare against the common methodologies of cross-contamination from the victim or the scene. To minimize the possibility of air and water borne contaminates seeping into the staging or treatment area, always locate up hill, up wind, and up stream from any WMD scene. Cross-contamination is the process by which a first responder becomes a victim. The routes of cross-contamination are:

Respiratory protection is achieved by a variety of mask type appliances that are applied over the head, and/or nose and mouth. There are three basic types of respiratory protection. The first type is the use of an air filtration system like a HEPA (high efficiency particulate air) filter. This type of filter is common in medical facilities and is used whenever a contagious patient is treated. The HEPA filter is very good protection against biological agents and radiological fallout, but has very little activity against chemical agents. An air-purifying respirator is the next type of filter and it utilizes a resin made of typically of charcoal to inactivate chemicals in the air. A typical configuration is depicted on the right. When combined with a HEPA type filter, this mask becomes very effective against both chemical and biological unknowns. The disadvantage of an air-purifying respirator is that it increases the work of breathing and therefore limits other work. Charcoal filtration units can also be overcome by high concentrations of chemicals. In essence, they can be used up. A hasty source of charcoal filtration protection is the paint vapor masks sold in most hardware stores. The best type of respiratory protection is a supplied air respirator or self-contained breathing apparatus (SCBA). This type of appliance is either attached to an air source or an air tank (SCBA) from which clear filtered air is supplied to a regulator type apparatus. The supplied air respirator ensures the first responders air source and is considered superior to the filtration type masks. The disadvantage to a supplied air respirator is that it is dependent upon the air source. Because air tanks are difficult to carry, and a continuous air source requires bulky equipment, the supply is limited due to practical considerations.

Contact protection is achieved through disposable barrier clothing. Biological weapons are easily fended off by the use of standard latex gloves, and disposable plastic aprons. These items are cheap, plentiful, and readily available in almost every medical setting. Unfortunately, latex offers little protection against chemical weapons. Some chemical weapons require a significantly greater level of protective gear, made from fabrics not commonly available. The concept of total encapsulation is used whenever working with the most toxic of substances. Total encapsulation requires the rescuer to don a vapor tight bulky suit with a supplied air respirator. The resultant apparel is cumbersome and retains heat quite efficiently. Thick butyl rubber gloves, required for protection, limit the fine tactile skills required to do many common medical tasks. While it is possible to attain some skills with intensive training, total encapsulation degrades the ability of the rescuer to below 50% of his or her normal capacity. The degree of encapsulation is commonly termed Protective Level of which there are four levels:

It would be nice to think that we all had the time to train regularly and be fitted properly for the highest levels of PPE protection. In reality, only those individuals, whos job it is to train and prepare for toxic exposures will possess Level A or B protection. The development of the Metropolitan Medical Strike Team concept is just this type of unit. The MMST issue aside, it is the opinion of this program that every rescuer must have basic familiarity with and access to Level C PPE. Level C PPE, while insufficient protection for sustained exposure, would afford the most rescuers, the most adequate protection during the initial stages of recognition of the WMD event. Level C is the standard military issue level of PPE to soldiers at risk of exposure to chemical weapons.

Biological weapons are typically associated with a latent period, or prodrome, prior to the onset of lethal disease. Biological weapons are odorless, tasteless and in the prodromal phase are rarely detectable by patient evaluation. Because of these factors, it is difficult to conceive of the situation when a first responder could protect him or herself from the initial dissemination. As in the care of any patient with a communicable disease, blood and body fluid precautions are the rule. Because biological weapons are spread as aerosols, a victims cough containing an aerosol of bacterial or viral droplets can act as a method of secondary spread. A HEPA filter mask, and latex barriers are all that is needed to protect oneself from the risks of a biological weapon cross-contamination

Decontamination is the process by which potential lethal contamination is removed from the surfaces of a victim in order to allow better medical access and to protect medical personnel from the dangers of cross contamination. Never before has cleanliness been so close to godliness. Decontamination may only be performed by personnel dressed in personal protective equipment (PPE). Federal standards dictate that Level A as the only acceptable level of PPE for individuals involved with sustained exposure to potentially high levels of an unknown chemical. Although this is clearly the best possible option, it will be little help to those first responders during the initial stages of a WMD event. Toward that end, several methods of hasty decontamination will be discussed. Formal training in decontamination is required to conform to federal standards. This level of training is best concentrated upon the metropolitan medical strike team (MMST). It is the opinion of this manual that hasty decontamination techniques should be taught to every first responder.

After recognition and protection phases, the first responders at the scene, in maximum PPE available, should identify a site for victim collection and hasty decontamination. The site must be uphill, upstream and upwind from the WMD event. The site must be divided into a dirty side termed the hot zone, and a clean side termed the cold zone. The cold zone must be uphill, upstream, and upwind from the hot zone. Once established, the victims must be collected in the hot zone. It is important for the hot zone to be physically marked and the victims contain themselves in the hot zone. If victims are allowed to wander about, the clean side of the decontamination area will become contaminated thereby negating any benefit. The first step of decontamination is containment.

Once contained, the victims should disrobe, and physically remove any observable contamination from the skin. Clothing must be accumulated deposited on the downhill, downstream, and downwind portion of the hot zone to prevent off-gassing. Off-gassing is the continued exposure of victims from vapors contained upon their clothing. Simply disrobing victims is 85-90% effective at removing a vapor exposure. Victims may typically be left in their undergarments. Physical removal of chemicals from the skin must utilize non-contaminated fabric or paper. Avoid use of contaminated articles of clothing.

The skin and most importantly the hair must be washed with a decontamination solution or absorbing powder. Decontamination solutions and powders may take several forms. The following list of solutions may be readily available and effective:

Which solution a rescuer should choose depends upon availability and environmental conditions. Obviously hosing down half-naked people exposed to winter conditions may be effective against the contaminate, but potentially lethal to the victim. Prima non nocere, or first do no harm is a guiding medical principal since the time of Galen, and it applies to decontamination methodology. When selecting a decontamination method, remember that victims continue to absorb the toxic contamination from their skin as long as the substance remains in contact with the victim. Time is of the essence. A perfect decontamination solution will do no good if applied after a lethal contamination has been absorbed. The guiding principle here is to gain the greatest amount of decontamination in the shortest amount of time possible.

Probably the best hasty decontamination solution is 0.5% hypochlorite solution. Sodium Hypochlorite is common household bleach. Household bleach is concentrated at 5%, therefore a proper decontamination solution would 10 parts water to one part household bleach. Along with Level C protection, access to bleach and water should be part of every first responders armamentarium. Hypochlorite works equally well for many chemicals and biological weapons. A word of caution, application of hypochlorite solution to a riot control agent exposure will cause the victim to blister. Soap and water is the recommended solution for riot control agents.

Chemical weapons are compounds that, because of their great toxicity, are considered among the most toxic of poisons. Chemicals may be absorbed through the skin or through the air in aerosols (suspended particles like a mist) or vapors. Chemical weapons are classified by their basic action on man. The basic groups are summarized in the following table:

Type of chemical weapon Onset of action Duration of action

Please note the short mnemonic to remember the types of chemical agents would be CLOBR

Because of the advent of chemical weapons in World War I and during the buildup to World War II, the technical knowledge required for the synthesis of chemical weapons is now commonplace in industry and institutions of higher learning. Many chemical weapons are no more than useful industrial compounds. Others require specific synthesis. The organophosphate nerve poisons are closely related to useful pesticides, and could be made in the same factories as Malathion, Parathion, or other useful chemicals. Many nations are known to be engaging in the synthesis of chemical weapons. Unfortunately, several of these nations are known to sponsor international terrorist groups. Among these are Russia, North Korea, Iran, Iraq, China, and the Sudan. Well-organized and well-funded terrorist groups are equally capable of synthesizing, and using chemical weapons in quite sophisticated ways. Previously considered inhuman, and indecent, the use of these weapons has been justified by national or religious ideology. Terrorism from within our borders is also a risk. The Atlanta, and Birmingham abortion clinic bombings, along with the Oklahoma City tragedy demonstrate the ease Americans will kill Americans to foment their ideology. Racial, religious, political, and anti-Federal ideologies have been used as justification for spilled American blood.

Cyanide is a common industrial chemical and is used in industries such as printing, electroplating, photography, and agricultural chemicals. In the United States, annual production of cyanide (for peaceful purposes) exceeds 300,000 tons. Cyanide is shipped around the country in 33,000-gallon rail cars that largely go unguarded. For these reasons, it is not difficult to obtain cyanide for clandestine purposes. A white separatist group, The Covenant, managed to obtain a 33 gallons of cyanide of the mid-1980s, for what purpose, we do not know. The Tylenol poisonings of the same time period are a testament to the ease of acquisition and use of cyanide as a weapon of terror. The most recent event involving cyanide was the alleged use of cyanide in the 1993 World Trade Center bombing. Hydrogen cyanide, (the active ingredient in gas chamber executions) was alleged to have been produced in an attempt to contaminate the routes of egress from the building. Because of the volatility (lighter than air) of hydrogen cyanide, the attack of a structure combining an explosion and cyanide contamination of the routes of escape demonstrates a significant degree of sophistication on the part of the terrorist.

The mechanism of cyanide is that it binds to ferric (Fe+++) iron. Iron is used to carry the oxygen used in energy production on the molecular level. Examples of iron containing molecules include hemoglobin, myoglobin, and cytochrome oxidase. Iron itself exists in two basic forms called valance states. Understanding valance states is admittedly a bit tedious but, the valance state of iron will become important in understanding the treatment for cyanide. Ferric Iron (Fe+++) is found on cytochrome oxidase. Cytochrome oxidase is part of the metabolic engine of each cell and is vital to the production of energy. Ferrous iron (Fe++) is the form used in hemoglobin and myoglobin to transiently store oxygen. The basic mechanism of toxicity is for the Cyanide molecule to bind to the ferric iron (Fe+++) present in the cytochrome oxidase enzyme, rendering the enzyme useless in the production of energy. If a lethal dose of cyanide is given, the sudden loss of energy causes immediate cessation of cardiovascular and central nervous system function. Death can occur in minutes.

Cyanide poisoning is difficult to detect because, in sub-lethal doses, it produces non-specific symptoms. Because of the interference with oxygen metabolism, these symptoms would include non-specific agitation or obtundation. These findings are indicative of the brain losing energy, and are similar to a patient with low oxygen level. Please note; the oxygen level will be normal! Because the cytochrome oxidase enzyme has been poisoned, it is the cell that cannot use the oxygen present in the blood and suffocates in the midst of plenty. Because little oxygen will be extracted in higher doses of cyanide exposure, a cherry red color to the body has been described. This is due to the oxyhemoglobin (red blood) present in the veins and capillaries. Unfortunately, cherry red coloration is an inconsistent finding, and not clinically useful. The most reliable assessment is the presence of unexplained metabolic acidosis in a number of patients, some of whom may have collapsed, from the same site of exposure. Carbon Monoxide would also present in a similar manner but would be detectable by co-oximetry available in most hospitals, and suspected by the setting in which the exposure occurred. A bitter almond odor is associated with hydrogen cyanide gas, but up to 40% of the population cannot detect this odor. Cyanide levels are not readily available in most hospital laboratories.

Suspected victims of a cyanide exposure are triaged into two categories. Immediate casualties are those individuals who have collapsed. Delayed casualties are those who are still ambulatory. The main treatment of cyanide exposure is removal from the source. For the severely exposed victims, the medical treatment of cyanide involves manipulation of the elemental iron present in the hemoglobin molecule through the use of a cyanide kit. The first step in the use of the cyanide kit is to create methemoglobin which converts ferric iron (Fe+++) to ferrous iron (Fe++). Inhaled amyl nitrite and intravenous sodium nitrite are capable of rapid methemoglobin formation. It is important to understand that methemoglobin does not carry oxygen and is potentially lethal, particularly if an adult dose is given to a child. As dangerous as methemoglobin may be, a collapsed patient will succumb to cyanide poisoning unless intervention occurs. It is the ferrous iron (Fe++) of methemoglobin that will bind the cyanide molecule from the cytochrome oxidase enzyme and create cyanomethemoglobin. Once cyanide has been removed from the cytochrome enzyme, the second agent, sodium thiosulfate is administered. The sodium thiosulfate will provide additional sulfur to the aid in the detoxification of this cyanomethemoglobin by the liver enzyme rhodanese. A cyanide treatment kit contains instructions and includes the following ingredients:

Recognition: Characteristic odors, respiratory symptoms

Lung irritants or pulmonary edema formers are a group of common industrial compounds that are known to produce significant lung injury. The compounds included in this class of weapon include Chlorine gas, Phosgene gas, and Anhydrous Ammonia. All the chemicals in this class are detectable by odor and therefore avoidable unless released in very large amounts. Unfortunately, these chemicals are manufactured in vast amounts and shipped, unguarded, across country in trucks and by rail. Clearly, their ready availability represents a significant threat to the populace. For example, the 1984 Bhopal India disaster involved the reaction between isocyanate and phosgene to create methy-isocyanate. In the Bhopal tragedy, 50,000 pounds of reagent was accidentally allowed to escape from a reaction chamber and 150,000 casualties were produced downhill from the Union Carbide facility. By intentionally damaging a chemical plant, a population center may be threatened through industrial sabotage of its resident industry. All three compounds are amenable to this type of action. Indeed, every community in America with a water treatment plant has a large tank of chlorine within easy access of a determined saboteur. Chlorine and Phosgene were significant chemical agents in World War I. Both are heavier than air and collect in the trenches causing the unfortunate soldier to choose between death by suffocation or death by gunfire. Neither prospect being of particular appeal, the threat of the use of this weapon terrorized the troops of both sides and energized the development of the defensive masks and suits we use today.

When inhaled by the victim, these compounds set about a chain of physiologic events that result in the accumulation of excess lung water. Because it is the least irritating agent, phosgene is thought to have the greatest lethality and will be discussed in detail. Upon contact with mucous membranes, phosgene reacts with water to form hydrochloric acid. This acid exposure causes the initial symptoms of cough and pharyngeal irritation. Phosgene is about 4 times heavier than air and is widely used in chemical synthesis because of its ability to donate single carbon groups. It is this donation of carbonyl groups that causes the true toxicity of the compound. When absorbed into the lower respiratory tract, phosgene goes to work adding carbon groups onto the working cell constituents. The ultimate death of the cell, the liberation of mediators of inflammation, and the formation of resultant non-cardiogenic pulmonary edema is the pathophysiology of concern. The formation of non-cardiogenic pulmonary edema therefore lags behind the time of exposure. Do not be fooled by the resolution of initial respiratory symptoms. A phosgene exposure must be observed for 24 hours. Onset of pulmonary edema within 6 hours of exposure is a poor prognostic sign and indicative of a lethal exposure.

Initially, a phosgene casualty should be removed from the source, disrobed, and washed with soap and water to prevent continued exposure of the patient and the health care workers. Treatment of a phosgene casualty includes supplemental oxygen and assisted ventilation. A peculiarity of phosgene is that exercise will increase the rate of pulmonary edema formation. For these reasons, the victim must be encouraged to remain restive. It is important to realize that, because pulmonary edema fluid will be taken from the rest of the body fluid, the phosgene casualty will likely be volume depleted despite the formation of pulmonary edema. For these reasons, resist the temptation to treat lung edema with a diuretic. An asymptomatic but definitely exposed patient should be triaged as Delayed. Victims with signs and symptoms of pulmonary edema and those with associated health risks should be triaged as Immediate.

Anhydrous ammonia exposure causes immediate symptoms in the victim because of the very alkaline pH and the caustic nature of the compound. Mucous membrane irritation is severe with only a minimal exposure. Prolonged exposure to anhydrous ammonia is lethal. The mechanism by which death occurs is a direct result of the highly alkaline nature of anhydrous ammonia. Cells and biological compounds, when exposed to highly alkaline substances undergo liquifaction necrosis. Liquifaction necrosis involves the reduction of complex molecules and cellular structures into their respective monomers. In essence, the cell is turned into sauce. Tissue destruction and the resultant pulmonary edema formation are the common causes of death. Rescuers should be wary of the contact risk involved with caring for these victims. Treatment of the victim begins with removal from the source, disrobing, and washing. Prolonged irrigation is required for complete decontamination. A pH test paper (nitrazine paper) can be used to verify continued areas contamination. Immediate casualties are those with respiratory symptoms. Minimal casualties are those without respiratory involvement.

Chlorine exposure also causes immediate symptoms as hydrochloric acid is rapidly produced when the chlorine gas contacts water in the nasal passages. Formation of hydrochloric acid in the lower respiratory tract quickly causes lung damage due to coagulation necrosis. Coagulation necrosis refers to the process of welding cells and biological compounds together into a single mass. The frying of an egg is an example of thermal coagulation. The sudden loss of respiratory surface area along with the resultant tissue injury quickly produces death in significant exposures. Treatment of the victim begins with the removal from the source, disrobing, and washing of the patient. Again, pH paper (nitrazine paper) is of significant utility in the detection of contaminated surface areas. Immediate casualties are those with respiratory involvement. Delayed casualties are those individuals without respiratory compromise.

Severity	Vapor-onset in 1-2 minutes	Liquid-onset in several minutes
Mild	Miosis, Rhinorrhea, Dim Vision,	Local fasciculations, Local sweating
Moderate	All above with Nausea, Vomiting	All above with Nausea, Vomiting
Severe	Convulsions, Apnea, Death	Convulsions, Apnea, Death

Severity	Vapor	Liquid
Mild	Observation only	2mg atropine, 600mg 2-PAM, Observation
Moderate	2 mg atropine, 600 mg 2-PAM, Observation	2-4 mg atropine,600-1200 mg 20PAM Observation
Severe	6 mg atropine, 1800 mg 2-PAM, 10 mg Diazepam	6 mg atropine, 1800 mg 2-PAM, 10 mg, Diazepam

The now infamous Sarin gas belongs to group of super toxic organophosphate compounds, termed nerve agents. Included in this group are the following compounds: Tabun (designated GA), Sarin (designated GB), Soman (designated GD), and VX. The nerve agent compounds are odorless and tasteless, and are readily absorbed through the skin, or by inhalation. They are highly toxic by either route. When inhaled, toxicity is determined by a concentration time product in which the milligram concentration per cubic meter is multiplied by the time of contact. Sarin, for example, has a LCt50 of 100 mg-min/m3. This means that 50% mortality is achieved when adult subjects are exposed to 100 mg total exposure. It is important to recognize that the cumulative dose may be achieved by inspiring a low concentration for a longer period of time. It is this feature of nerve agent toxicity that mandates decontamination. In the Tokyo example, a significant number of health personnel were overcome by breathing the vapor contained on victims clothing. Simply disrobing the patients, and setting up a triage post in open air would have alleviated a number of casualties.

Nerve agents are liquids at room temperature and have relatively low vapor pressures. Sarin (GB) is the most volatile at 2 mm. Hg, which is similar to waters vapor pressure. The photo to the left demonstrates the physical appearance of common chemical weapons. Note that the compound is an oily brownish liquid. When heated, as in the Matsumoto incident, Sarin will come out of solution at a faster rate and produce a highly toxic concentration of agent. The nerve agents are also about 4 times heavier than air so they collect in low-lying areas. The Tokyo subway attack utilized this property by allowing the unheated vapor to accumulate in the lower reaches of the subway with obvious lethal consequences. The other G nerve agents are less volatile than Sarin and the agent VX is only considered a contact risk. It is important to note that some of the victims of the Subway attack include individuals who attempted to pick up the packets of agent and sustained a subsequent liquid exposure. Liquid exposure presents its own problems in management as the agent VX could be laid down at a location prior to occupation by the intended victims. An understanding of the effect route of exposure has on the presentation of the clinical toxidrome is critical to the management of the victim.

The toxic effects of nerve agent compounds are achieved through the inhibition of acetylcholinesterase, and the subsequent over-stimulation of the acetylcholine receptor. Muscarinic, Nicotinic, and CNS subtypes of receptors are affected. Muscarinic receptors, when stimulated, increase the activity of salivary glands, lacrimal glands, smooth muscle, and pupillary constriction (miosis). The muscarinic syndrome is best remembered by the SLUDGE acronym; S (salivation), L (lacrimation), U (urination), D (diarrhea/diaphoresis), G (general weakness), E (emesis). Of specific concern for medical personnel is the effect upon bronchial smooth muscle and bronchial mucous glands. Nicotinic receptors are found primarily on skeletal muscle as well as certain ganglia, most significantly, the adrenal medulla. Stimulation of nicotinic receptors results in fasciculation and ultimate paralysis of the affected skeletal muscle. The CNS effects of these compounds are sedation, seizure, apnea, and ultimate death.

Nerve agent toxidromes are described on the basis of both route and amount of exposure. The following table depicts toxidromes of vapor and liquid exposures:

Severity	Vapor-onset in 1-2 minutes	Liquid-onset in several minutes
Mild	Miosis, Rhinorrhea, Dim Vision,	Local fasciculations, Local sweating
Moderate	All above with Nausea, Vomiting	All above with Nausea, Vomiting
Severe	Convulsions, Apnea, Death	Convulsions, Apnea, Death

Please note that the symptoms produced by the same agent will vary with portal of entry. In both Aum Shinrikyo attacks, almost all the exposures, both primary and secondary, were by vapor. Because the nerve agents are not particularly volatile, a large number of people were affected with a relatively low concentration. The most severely injured victims had the longest times of exposure or were closest to the munition. One should not make that same assumption in a liquid or aerosol exposure. Because of slower rates of percutaneous absorption, the need for surface decontamination, and the persistence of agents on clothing, the risk of delayed symptoms and progression to lethal dose exposures is greater with liquid exposures. Aerosol exposures have components of both vapor and liquid because an aerosol is composed of small droplets of liquid agent, which may be inhaled, or may settle on the skin or other objects. An aerosol is easily created by common industrial or agricultural spraying devices.

Treatment of nerve agent victims consists of the opposition of the cholinergic crisis with several medications. Atropine directly opposes the binding of acetylcholine at muscarinic receptors and will serve to relieve bronchospasm, and decrease secretions. Atropine does not have activity at nicotinic sites, does not cross the blood brain barrier, and therefore will not relieve paralysis or convulsions. Oximes are a class of compounds that bind with organophosphates preferentially to many other compounds including the acetylcholinesterase enzyme. It is this preferential binding that will remove the offending agent from the acetylcholinesterase enzyme. Pralidoxime chloride (2-PAM) is the most commonly used oxime for this purpose. Although organophosphate binding to acetylcholinesterase is considered irreversible, permanent inactivation of the enzyme is by the transfer of the phosphate moiety. This process is agent and time dependent and is referred to as aging. Pralidoxime does not work once this process has occurred. In addition, oximes do not cross the blood brain barrier, and will not decrease convulsions. Diazepam has proven to be effective in animal studies to both reduce mortality and improve morphological brain lesions, and is currently recommended for severe exposures.

Atropine and pralidoxime are contained in autoinjectors commonly known in the military as a Mark I kit. The Mark I kit is simple to use and contains 2 mg. of atropine in one autoinjector and 600 mg. pralidoxime in a second autoinjector, paired in a safety base. These dosages are considered initial treatment doses and are given in multiple doses based upon therapeutic response. The medications may be given IV with the following considerations. Intravenous atropine will induce Torsade de Pointes (intractable V-fib) when given to hypoxic patients so the IM route is suggested. Pralidoxime will induce significant hypertension if given IV push, therefore an infusion of one gram over 30-60 minutes is the current recommendation. Nerve agent therapy differs from other organophosphate therapy in that the maximum dosages required for treatment are less. The maximum dosage needed to resuscitate a single Tokyo subway casualty was 20 mg. This may favorably compare to reports of 1-2 grams of atropine required for a more common organophosphate intoxication. The following table contains current treatment recommendations, based upon presentation:

Severity	Vapor	Liquid
Mild	Observation only	2mg atropine, 600mg 2-PAM, Observation
Moderate	2 mg atropine, 600 mg 2-PAM, Observation	2-4 mg atropine,600-1200 mg 20PAM Observation
Severe	6 mg atropine, 1800 mg 2-PAM, 10 mg Diazepam	6 mg atropine, 1800 mg 2-PAM, 10 mg, Diazepam

In judging therapeutic response of atropine, the endpoint is the easing of bronchospasm and a drying of secretions. Atropine will oppose the action of nerve agents only at the muscarinic sites. The use of miosis, or heart rate is not useful. Observation is a key component of the treatment algorithm. Because liquid agents will provide a slower but greater total absorption of agent, further treatment may be needed, despite a good initial response.

Decontamination of the nerve agent casualty depends on the type of exposure. Similar to cigarette smoke, nerve agent vapor clings to clothing. Disrobing the vapor casualty is estimated to provide 80-90% effective decontamination with exposed skin and hair cleansing responsible for the remainder. Off-vapors from clothing were the primary cause of secondary injury to health care workers. In the Tokyo experience, 13 of 15 treating physicians at Keio University Hospital were overcome within 40 minutes by off-vapors. Simply disrobing the patients outside would have saved health professionals from exposure. As noted in the photo to the right, little effort was taken in Tokyo to prevent this exposure risk. Liquid contamination remains persistent on surfaces including patients and fomites, and therefore, becomes a risk for treating professionals. Liquid agent exposure requires physical removal or washing. Nerve agents are deactivated by hydrolysis which may be facilitated by the addition of 0.5% hypochlorite. A 0.5% hypochlorite solution is a 10:1 dilution of household bleach. Because of the extreme toxicity of these agents, health care professionals are at significant risk for secondary contamination. Every hospital likely to receive patients of this sort must have the capability to decontaminate patients.

Triage of organophosphate nerve agent casulties relates to their triage category and response to therapy. Because of the rapid onset of symptoms, field treatment is mandated for these casualties. Immediate category casualties are those with severe exposures, followed by moderate exposures. Following successful field treatment, a casualty may be down-graded to Delayed and monitored for recurrence of symptoms. Minimal category casualties may decontaminated and observed in the field. Expectant category casualties would include those severely exposed casualties for whom field treatment is unavailable.

The prototype blister agent is Mustard Gas. Mustard is actually not related to table mustard, nor is it typically a gas. Mustard is a thick oily liquid that freezes at 57 degrees F. The odor of the substance is that of horseradish, onions, garlic or mustard, hence its moniker. Mustard is the chemical weapon most frequently used in warfare since its synthesis in 1917, and proved the most effective chemical weapon in WWI. In addition, mustard is probably the weapon most easily synthesized by terrorists. Mustard was recently used by Iraq in the Iran-Iraq war. Interestingly, mustard is not highly lethal but an incapacitating agent. In the military setting, an incapacitating agent is often more useful than a rapidly lethal agent because of the resources required to care for casualties individuals and the distracting concern of fellow soldiers for their buddies. For the terrorist, the main advantage of mustard is its persistence. There are structures in France that still contain detectable mustard absorbed in the wood and other building material. Persistence allows the terrorist to lay down the vesicant agent prior to the occupation of the space by the intended victim. Mustard is painless when absorbed but exerts its action within 1-2 minutes. Unfortunately, the identifiable effects develop in 4-24 hours.

Mustard is a DNA alkylation agent, which is its primary mode of action. DNA alkylation refers to the action of mustard to stop DNA synthesis and therefore kill growing cells. For this reason, the less toxid nitrogen mustard is actually one of the first chemotherapeutic agents, and it is still in use today. Sulfur or distilled mustards are considered the likely weaponized form of the compound. The initial signs of mustard exposure are erythema and the formation of vesicles that occurs within the first 8 hours. These effects form at the site of exposure, so if heated mustard vapor or a mustard aerosol is used, the eyes, nose and airway will be most effected. This was the primary mode of exposure for the majority of WWI casualties. Airway management, therefore, is the critical issue for airborne mustard exposures. After the airway risks, the ultimate cause of death from mustard exposure is the DNA akylation of rapidly dividing cells in the immune system. Similar to radiation, death from this process takes some time. Because mustard is absorbed from the skin, the LD50 for mustard is related to the body surface area involved. The LD50 for mustard is 20% BSA (about 7.5 grams). It is important to understand that mustard burns do not require the same fluid volumes that are associated with thermal burns. Additionally, there are reports of survivors from mustard up to 90% BSA, however, for triage purposes, a 50% BSA burn is considered expectant.

Other vesicants include Lewisite, various industrial corrosives, and electromagnetic radiation. Mustard may be suspected by odor, delayed presentation, and confirmed by various testing devices. Lewisite has the odor of geraniums, and is immediately active upon application to the skin. Lewisite contains arsenic, but is somewhat less toxic than mustard. The heavy metal chealator BAL (British Anti-Lewisite) may be used for absorbed arsenic. Because of the immediate onset of symptoms, cross-contamination is more avoidable than in mustard casualties. The decontamination for either type of vesicant is the physcial removal of the compound from body surfaces. It should be noted that the decontamination run-off will contain active compound therefore, it should be closely contained. Again 0.5% hypochlorite is the solution of choice to aid in hydrolysis. In the Iran-Iraq war, Iranian mustard casualties were sent to European hospitals and contaminated several health care workers and facilities. This highlights the persistence threat from mustard. Although mustard may be transferred by fomites, the blister fluid from the casualty contains no active compound.

Triage of mustard casualties is somewhat problematic because of the delay of symptom onset. Immediate category casualties would include all those with airway compromise. Delayed category casualties would include all other exposures. Because casualties have survived with upwards of 90% body surface area contamination, no casualty should be classed as Expectant, although in cases of finite resources, one should bear in mind the LD50 for body surface area exposure is 20%.

E. Riot Control Agents

Riot control agents consist of a group of compounds known for their intense mucosal irritant properties. Commonly sold as personal protective devices, these agents are familiar and available anyone. Although considered non-lethal, if present in very high concentrations and in enclosed spaces, deaths have been reported. The most probable use of these compounds is as a hoax agent. Significant panic in the lay public could be induced by the application of these agents under the threat of a more lethal agent. Bear in mind that, while Cyanide, Organophosphate Nerve agents are rapidly acting, they are typically non-irritating. In addition, organophosphate nerve agents will produce characteristic symptoms of miosis, sweating and fasciculation. Mustard may produce intense blistering of the exposed skin surface while riot control agents only work upon mucosa. Lung irritants may be most easily confused with riot control agents but their characteristic odors will aid in their discrimination. Treatment of a riot control casualty is largely supportive with removal from the source and disrobing typically all that is necessary. Although not dermally active, it is important to note that the application of hypochlorite with riot control agents will produce intense skin irritation and blister formation. For this reason, soap and water only is used as a decontamination solution. Individuals with pulmonary diseases or cardiovascular risks may develop exacerbations of their disease states in response to these agents. Triage all individuals with mucosal symptoms only as Minimal. Individuals with secondary exacerbations of pre-existent disease should be triaged according to their disease and acuity.

Once the domain of the military physician, the intentional spread of infectious disease with the use of modern technology affords the terrorist with a cheap, stealthy, and highly lethal modality to foment their organizational ideology. Biological weapons, because they naturally occur, are available to anyone with knowledge and a small amount of equipment, as demonstrated by Larry Wayne Harriss ability to obtain both plague and anthrax. A home-brewers kit is a fermentation vehicle built for yeast culture. Very little modification is needed to make a bacterial fermenter. Viral agents may be cultured in a fertilized egg under the proper conditions. There are over 400 potential or actualized etiological agents amenable for biological weapons construction. Progress in the area of gene splicing and molecular biology makes it possible to custom design a variety of pathological characteristics as well as antibiotic resistance capabilities into a chosen pathogen. For this reason it is less important understand each disease process. One should direct ones energies to the recognition of an atypical epidemic in a potential target population. The commonality of symptoms and site of exposure are the keys to detection of a bio-weapon. It should be noted, a devastating crop disease may ultimately produce more harm to the nation than the loss of a population segment

To infect a large section of the population, the distribution of a biological weapon would be by aerosol, that is, the suspension of infective particles in air. A biological aerosol is odorless, tasteless, and invisible. The particle size for optimum pulmonary transmission is 1-5 microns. The technology used to create this particle size us non-proprietary, and in common use. As scene in the figure to the left, a hand-held military aerosol generator is in use. In addition, many bacilli are 1-5 microns in their natural state. A large number of organisms can easily be produced by the geometric propagation of biological progeny. With the use of an airplane equipped with a crop-dusting aerosol generator, an entire city may be exposed. It is estimated that 50 kg of anthrax spores, aerosolized in the proper conditions over a city of 500,000, would produce a lethal form of pneumonia in 24,000 people. It is this capability that earns the biological weapons reputation as a weapon of mass destruction.

The stealth quality of the biological weapon comes from the incubation period for disease presentation. Once exposed to the pathogen, the development of disease may take 2-14 days, allowing the assailant to escape prior to the recognition of the bio-weapon. Individuals exposed will also develop their symptoms at different times and present to various health care facilities. This will further complicate the recognition of the intentional epidemic. Many of the agents are treatable, but only if recognized early. The EMS and public health system are the best early warning systems currently available. Naturally occuring epidemics are part of the medical experience. Differentiation of a naturally occuring epidemic from a biological weapon is therefore the critical feature of management. The key to the recognition of a biological weapon is:

The prototype bacterial agent is anthrax. Bacillus Anthracis causes a fatal disease in herbivores, and is responsible for Woolsorters Disease in man. Anthrax is a common soil bacteria, and typically enters the skin through a cut or scratch. In the US, 5-10 cases per year of cutaneous anthrax occur in individuals who come in contact with slaughtered animals. In the Middle East, 100-300,000 cases occur each year, and in 95-99% of cases the form of the disease is cutaneous. The bacterium causes an abscess in a local lymph node with a typical blackened eschar as noted int the picture to the right. The disease progresses to fatal septicemia in about 20% of cases without treatment. With treatment the mortality is essentially 0. This hardy bacterium is capable of forming a spore that can remain viable without nutrients for up to 40 years. It is this ability to sporulate that gives anthrax its reputation as a formidable biological weapon. Because the organism, once weaponized, requires no ongoing care, considerably less care must be taken to ensure a viable and infective organism. Anthrax is a found in Michigan soil.

The weaponized form of anthrax is an aerosol of bacterial spores. Because of the aerosol distribution, an unusual respiratory form of the disease will occur. The anthrax bacteria enter through the respiratory tract and no visable eschar is formed, rather a chest cold like syndrome is produced. Although respiratory symptoms occur, chest X-ray findings are non-specific. Initially, the flu-like syndrome will show improvement in 2-6 days. However, in the 4-6 day period, the terminal septic phase develops and maximal antibiotic treatment will not prevent death. There are rapid ELISA tests for anthrax antigens but these are not commonly available. An occasional finding in the septic phase is the fulminate overgrowth of bacteria visible on gram stain of the blood. Should the septic phase develop, death typically occurs within 24 hours. Antibiotic treatment, initiated prior to the onset of the terminal septic phase, can be life-saving for those exposed to anthrax. For this reason, it is critical to recognize this disease and treat the community at the earliest moment.

Antibiotic	Treatment	Prophylaxis
Ciprofloxacin	400 mg IV q 8-12	500mg po BID for 4 weeks
Doxycycline	100 mg IV q 12	100 mg po BID for 4 weeks

There is an approved vaccine for this agent available from the Michigan Department of Public Health.

Although little known in the United States, we are currently experiencing the worlds 4th modern pandemic of plague. The epicenter of this outbreak is China and India. Approximately 3,000 new cases of plague are diagnosed worldwide with 8-10 cases occurring in the US. The plague is responsible for the Black Death epidemic in which 25 million people were killed during the Middle Ages. The terror potential of spreading the Black Death is not to be underestimated. Because of the inexperience of American health professionals with this agent, a significant delay in initial diagnosis and treatment can be expected

Plague is a disease of rodents, historically the rat, and is caused by the organism Yersinia Pestis. In the US, ground squirrels and prairie dogs provide the reservoir. It is not the rodent, however, that spreads the disease, it is the flea, as seen on the right. In its naturally occuring state, the plague has two forms, bubonic and pneumonic. Bubonic plague is the most common form of the disease and typically precedes the pneumonic form. The disease is transmitted to the flea feeding upon an infected rodent. The Yersinia Pestis bacteria then reproduce within the flea and eventually obstruct the foregut of the flea. The starving, plague laden fleas, in a frantic effort to survive, abandon the rodent and bite the human victim. The flea bite introduces the bacteria into the lymphatic system. In the lymph node, an abscess with a blackened eschar is termed a Bubo. Because fleas most commonly bite the lower extremities, the most common site for buboe formation is the inguinal lymph nodes as noted in the picture above. Bubonic plague takes its name from this finding. The death rate from bubonic plague is about 50% without treatment, and falls to 5% with proper antibiotics. In those fatal cases, the disease progresses to the septicemic form in which the lungs are involved.

Once the lungs are infected, respiratory droplets containing the Yersinia Pestis bacteria are spread by coughing. Pneumonic plague occurs when these droplets are inspired and a plague-pneumonia is formed. A useful diagnostic tip is that pneumonic plague will present with bloody sputum in a large number of people. Typically, a lymph node aspirate is used for gram stain and culture, but sputum, and/or blood must be used for pneumonic plague diagnosis. When visualized on gram stain, the bacterium exhibits a characteristic Safety Pin gram negative pattern as shown in the figure to the right. Pneumonic plague is 100% fatal without treatment but, like anthrax, mortality from pneumonic plague can be reduced to 8-10% with early antibiotic therapy. For this reason, it is critical to recognize this disease and treat the community at the earliest moment. The characteristics of a biological attack would include, pneumonic plague with no bubonic form will occur and the disease will not be found in the rodent population. Treatment is summarized in the following table.

Antibiotic	Treatment			Prophylaxis
Ciprofloxacin		400 IV q12 x10 days	500mg po BID x10 days
Doxycycline		100mg q12 x 10 days	100 mg po BID x 10 days
Streptomycin		30mg/kg/day divided q12 x10 days IM

There is an approved vaccine for against Yertsinia Pestis that has proven efficacy against the bubonic form only.

Tularemia is normally a disease of rabbits, transmitted by biting insects to man. The normal form of the disease is termed ulceroglandular fever, commonly known as rabbit fever. The organism propagates in a lymph node and there it forms an abscess with a small ulceration. The lesion can be easily confused with a spider envenomation. The disease in uncomfortable, but not serious. Like anthrax and plague, the weaponized, the form of disease is pneumonia because of the respiratory mode of transmission. Tularemia pneumonia is typically not fatal with or without antibiotics but the organism is difficult to grow on standard culture media. Because tularemia does not normally cause pneumonia, and is difficult to detect, a significant delay in diagnosis can be expected. The characteristic that makes tularemia an effective biological weapon is its extreme infectivity. As few as 10 organisms are required to be effective. Although a mortality rate of only 4% has been reported, if a large number of victims are infected, the end result would be a significant number of casualties. High rates of infectivity and difficulty in detection make tularemia an effective terror weapon. An investigational vaccine is currently being evaluated.

Cholera is a form of bacterial enteritis common in many parts of the world, and is caused by the organism Vibrio Cholerae. It is not commonly seen in the United States because of our water and sewage treatment. The disease is characterized by profuse rice water diarrhea up to 15 liters per day. Typically, the victim is incapacitated by this amount of diarrhea. The weaponized form of the disease is primarily a water or food-borne risk. Cholera causes a secretory diarrhea. Secretory diarrhea induces the loss of electrolytes and fluids. The disease is only lethal in those unable to rehydrate by oral means in areas without IV therapy. Most cholera patients are treated with oral rehydration as the degree of nausea is insignificant. The World Health Organization oral rehydration formula is 20 grams glucose, 3.5 grams NaCl, and 2.5 grams NaHCO3, and 1.5 grams KCl per liter of fluid. There exists no vaccine. Antibiotic therapy may shorten the disease marginally.

Viral hemorrhagic fevers are endemic in discreet locations. These diseases have very specific hosts and the disease is limited by the range of the animal or insect hosts. Because of the limited and remote range of the host, this group of diseases is ever increasing in number as they are discovered. Common characteristics of viral hemorrhagic fevers are abnormal bleeding and fever. Although common in many parts of the world, viral hemorrhagic fevers are uncommon in the United States. The hantavirus (see picture on right) outbreak in the four-corners region of the desert southwest in May of 1993 is an example of this disease type, and the difficulty in management. The host for hantavirus is various species of mouse found in the southwest. The method of transmission is through aerosolizaton of mouse feces. The disease causes the onset of non-cardiogenic pulmonary edema and has a high mortality. Significant delays in recognition of the viral etiology as well as effective methods of treatment caused serious concern on the part of the medical community. Hantavirus positive patients have been demonstrated throughout the United States prior to the outbreak in the southwest indicating that this disease has been present for some time prior to its recognition. Diseases of this type are termed emerging and if intentionally spread, would cause significant confusion in the medical system.

Ebola is the most lethal viral hemorrhagic disease yet discovered. Initially, the disease was reported in Zaire, but the most current outbreak is in Gabon. The characteristics include abnormal bleeding, purpura, petichia, renal failure, obtundation, and death. The mortality rate is around 88% for the Zairian strain and around 53% for the Gabon. The host is considered to be primates, and the mode of dissemination is thought to be aerosol. In addition to the African experience, an outbreak of a viral hemorrhagic fever occurred in Marburg Germany in the late 1980s. The outbreak was limited to animal care workers with contact to a shipment of African Green monkeys. The mortality of the Marburg strain was 26%. The virus was again detected in 1989 in Reston, VA, and 1990 in Alice TX. The hosts were from Philippine macaques, and although the disease was fatal in the primate, the virus did not cause fulminate disease in humans. In all cases, the virus appears as the shepherds crook, as depicted above, and is morphologically identical. DNA sequencing reveals minor mutation between all the strains. No reservoir has been found for Ebola Gabon or Zaire, but it is suspected to be another primate. There is no treatment or vaccine.

Smallpox, caused by the Variola virus, is a cutaneous disease related to chicken-pox. The presentation of the disease is a vescular eruption most heavily on the face. Due to the diligent work of health care workers, and active vaccination programs, smallpox was declared eradicated in 1980, and the US stopped vaccination in 1981. Small reserves remain however, at the CDC in the US and at Vektor in present day Russia. It is suspected that knowledge and perhaps the agent itself was distributed within the old USSR and is now in the possession of terrorist sponsoring nations. Because of the 1981 cessation of the vaccination program in the US, we are a population at risk. Transmission is typically by contact with infected individuals. No data exists on respiratory transmission. The rash may be discriminated from chicken pox by the heavy crop of vesicles on the face, and the lack of vesicles in various states of healing. Thirty percent of exposed victims will develop the disease, and thirty percent of those with the disease will die. There is no treatment, but a vaccine exists.

Venezuelan Equine Encephalitis is caused by an arbovirus (see micrograph on right) common to horses and responsible for large outbreaks in South America. It is spread to humans by a biting insect and has a high rate of infectivity. The disease produced manifests with fever, prostration and viral meningitis. A very high rate of infectivity is noted, in fact, only ten organisms are needed to create the disease. Although not highly lethal, morbidity is widely experienced, and this disease only retrospectively diagnosed by serologic testing. There is some controversy over the effects of an aerosolized agent. Some argue that, because of the proximity of the olfactory bulb, the respiratory route would induce an higher rate of meningitis and therefore a higher mortality rate. There remains no published data on the subject. The characteristics of a biological attack would the potential high rate of viral meningitis and the absence of pre-existent disease in the equine population. There is no specific treatment but an investigational vaccine does exist.

C. Toxicological Weapons

Toxicological weapons are substances derived from living organisms and therefore represent a hybrid between chemical and biological weapons. Toxin as a group are much more toxic milligram per milligram than are chemical weapons. Unlike biological weapons, they require no growth media and are typically stable for storage. Toxins are typically odorless and tasteless and produce no symptoms upon exposure. The recognition of a toxidrome, or group of symptoms, is seminal to the detection of the attack.

Botulinum toxin is produced by the bacterium Clostridium Botulinum and has the distinction of being the most toxic substance known to man. The lethal dose in man for botulinum toxin is 0.001 ug/kg or 1 nanogram per kilogram of body weight. This toxicity is 15,000 times more lethal than VX, the most lethal of the chemical agents. A single milligram of pure toxin contains 200 lethal doses for the average size man. Clostridium Botulinum is found in the soil and the toxin is active in an impure state. In a naturally occurring outbreak, a contaminated foodstuff is the source of the agent. The typical scenario is improperly canned food or perhaps food that is left in a warmed exposed condition for significant amounts of time. A natural outbreak will be traceable to a common food source consumed within the past 24-36 hours. In a biological terrorist attack, the agent may be aerosolized and inhaled, or spread upon a food source. Whether inhaled or consumed, the toxin will exert the same effect.

The onset of symptoms occurs within 24-36 hours and typically presents with ptosis or droopy eye lids. The paralysis proceeds from the head downward over the body, ultimately causing a cessation of respiration. Botulinum toxin exerts its effect by binding with the motor end-plate, that is where the nerve plugs into the muscle. A destruction of this end-plate structure occurs and the muscle is unable to take voluntary commands. Once destroyed, 6-8 weeks are required to reconstruct the end-plate. Should ventilatory failure occur, the victim would remain dependent on the ventilator for 1-2 months.

If an exposure to botulinum toxic is suspected, one may treat the patient with an antitoxin. The antitoxin consists of equine derived Fab (antibodies) antitoxin fragments that work well for unbound, toxin in the circulation. Once the toxin has bound to the end-plate, the antitoxin is of little use, therefore, one would give the antitoxin on the basis of exposure, rather than the onset of symptoms. A vaccine is investigational and not commonly available.

Staphylococcal Enterotoxin B is another food borne toxin that commonly causes outbreaks of food poisoning. It is derived from the bacterium Staphylococcu Aureous. Staphylococcus Aureous is a common skin organism. A natural outbreak would include the onset of nausea, vomiting, fever, prostration, and diarrhea within 6-12 hours of the consumption of the contaminated foodstuff. The most common type of foodstuff is mayonnaise or creamy salads. All victims can be traced back to the common source, and the symptoms subside with the expulsion of the toxin from the gastrointestinal tract.

This toxin may be weaponized as an aerosol and, in this form, the symptoms include fever, prostration, and cough without the same degree of gastrointestinal symptoms. Although benign and self-limiting, the toxidrome is indistinguishable from more virulent forms of biological weapons, hence its use as a terror weapon. As a military weapon, it is used to temporarily render an opponents forces incapable of action, or used in conjunction with a more lethal agent. For the terrorist, non-lethal retribution against a target population is considered a likely scenario. Since all that is needed to form staphylococcal enterotoxin B is potato salad and a warm day, this toxin is highly accessible to amateurs and pranksters.

Ricin is a plant toxin derived from castor beans. Ricin is active by ingestion or inhalation, and is a potent inhibitor of protein synthesis. If ingested, ricin causes gastrointestinal hemorrhage, and the necrosis of the liver, spleen and kidney. If inhaled, ricin causes necrotizing pulmonary lesions, pulmonary edema, and respiratory failure. In either case, death occurs by day 3. An interesting use of ricin involved the 1978 assassination of Bulgarian KGB defector Georgi Markov. It happened that a KGB loyalist used a spring-loaded umbrella to fire a small hollow pellet containing ricin into Mr. Markovs calf while he waited at a bus stop. Mr. Markov shortly became quite ill with a mysterious illness. Not until the small pellet was recovered from the leg of Mr. Markov was his illness confirmed as a toxicological assassination. Mr. Markov ultimately succumbed to the effects of the toxin.

Castor beans are processed into castor oil in many parts of the world for manufacture of products such as hydraulic and brake fluids. Ricin is contained in the waste mash or water soluable component of processing. The worlds annual production of waste mash is around 1 million tons. This waste mash is 5-10% ricin. The separation process is simple and compound is stable. Diagnosis of ricin exposure is difficult to detect initially, as it requires recovery of the toxin and chemical analysis. There are no available treatments, and no vaccine.

Mycotoxins are derived from the Fusaria species of grain mold. There are about 6 species of Fusaria capable of making a heterogenous group of 40 compounds we know as mycotoxins. During periods of deprivation, the disease toxic alimentary aleukia occurs when fusaria are ingested in significant amounts. Mycotoxins are potent inhibitors of both protein and DNA synthesis. In addition, mycotoxins are the only known biological agent toxic by contact route. When ingested, inhaled, or absorbed, the syndrome includes emesis, hemorrhage, and immune compromise. Lethal amounts are known to cause death within 24 hours. Diagnosis of mycotoxin exposure requires recovery of the toxin and chemical analysis. There is no known method of treatment, or vaccination.

American civil defense owes much to the threat of nuclear exchange with the former Soviet Union. There is a great deal of awareness of nuclear weapons and a great deal of appropriate fear of their discharge. The de-novo construction and successful detonation of a nuclear device is, however, a difficult task. To create such a weapon, significant amounts of high grade fissionable material must be stolen or manufactured, ultra-precise bomb mechanics must be machined and tested, high grade containment facilities must be used to avoid detection during manufacture of the weapon, and a necessary understanding of nuclear physics at the highest level must supervise design and construction. Although fissionable material is available on the black market, these significant resources are typically only possessed by nations. It is this level of resource expenditure that makes the terrorist detonation of a nuclear device less likely.

While an actual nuclear device may be difficult to achieve, possession of radioactive material is not. Radioactive sources are in use in many industries as well as available for purchase from unscrupulous vendors. The combination of a radioactive source with a conventional explosive device presents a particular problem for first responders. Therefore, an understanding of radiation effects on the human body and safe levels of radiation exposure is necessary for the safe management of this contingency. To aid in our discussion, radiation devices are divided into the following categories:

Whatever the device, it is important to understand the difference between irradiation, and contamination. Irradiation of a victim refers to the exposure of that victim to an amount of ionizing radiation such as X or gamma rays. We are exposed to small amounts of electromagnetic irradiation from the sun, hospital X-ray machines, and microwave ovens on a continuous basis. Unless the victim is exposed to large doses of high-energy gamma rays, the irradiated victim is not radioactive and no protective equipment is required to care for the victim. A simple radiological device will produce such victims. Like the X-ray machine at the hospital, the simple radiological device delivers a fairly constant amount of radiation per unit of time. This amount of radiation is measurable by radiation dosimeters, and just like the X-ray machine, safe amounts of exposure are well known. Safety at the scene and the ultimate survival of the victims will be based upon the level of irradiation present, and the time of exposure.

Contamination with radiological material is more important to consider. Contamination refers to radioactive fallout or radioactive dust that can be inspired, ingested or retained on the skin. Both Radiological Dispersal Devices and Improvised Nuclear Devices create fallout contamination in addition to the risk of irradiation. With advance knowledge, the first responder can easily protect him or herself from fallout contamination with appropriate disposable clothing, and HEPA filter respiratory protection. As mentioned in the preceding paragraph, safe working times in a given level of exposure are well established. Without knowledge of potential radiological contamination, the first responder is likely to unknowingly contaminate him or herself

The recognition of a radiological event is clearly evident in the case of an Improvised Nuclear Device. Federal level assets will be brought to bear on the crisis and what remains of the local authorities will be incorporated into the ongoing management efforts. In the case of a Radiation Dispersion Device, potential contamination must be suspected by the managing authority. Confirmation of a radioactive component to the explosion must be confirmed by a radiation-measuring device such as a dose rate meter or Geiger-Mueller Counter. The use of a Simple Nuclear Device or radiation source may be suspected on radiation sickness encountered in workers or inhabitants of a given locale. Radiation sickness is a constellation of symptoms that will be described in a later paragraph. Confirmation of a radioactive source is again dependent on the use of radiation measuring device. Radiation measuring devices must be available to all first responders at the scene of a potential terrorist event.

Protection of first responders in a radiological event is composed of two distinct goals:

As mentioned, irradiation may be measured in a given area and safe times of exposure may then be calculated. The safe level of radiation for man varies with a persons age and reproductive status, but 40-50,000 milli-REM (40-50 REM) is considered safe for a single exposure in a year. This is the same amount of radiation exposure given to a patient during a cardiac catheterization. Therefore, if the level of irradiation in a given area is100 milli-REM per minute, it would take 400 minutes or about 6.5 hours to achieve the maximum level. A time-dosage calculation must be done for every first responder involved. Because of the risk of fallout contamination, skin and respiratory protection must be given to each provider.

As one moves away from the radiological source, the level of irradiation falls. Specifically, the level of radiation will decrease by a factor of 4 (the square root) if the distance is doubled. Distance is therefore the best and most readily attainable method of reducing exposure to victims and first responders. It should be noted that in the case of a Simple Radiological Device, the level of irradiation obeys the inverse square rule. That is, the level of irradiation will increase by a factor of four, each time the distance to the source is halved. For this reason, never directly contact a radiological source.

Radiation is composed of either particles or electromagnetic radiation. Particulate radiation may take the form of alpha, beta, or neutron particles. Each type of particle possesses different characteristics of tissue penetrance and ionization. Several types of radioactive particles are shielded by personal protective equipment. Alpha and Beta particles for example require only ordinary work clothing for shielding. Neutrons however penetrate more effectively and more effective shielding is required. Electromagnetic radiation exists in waves of energy, similar to radio or microwaves. The difference is in the level of energy, and therefore the degree of penetrance. The higher the frequency of the wave, the higher the energy the wave will possess. High-level gamma radiation, for example, requires many inches of lead for protection and therefore, shielding becomes somewhat impractical. Standard, disposable level C suits, in combination with time-dosage calculations, and respect for the effects of distance from the source are adequate protection for first responders.

Radiation effects on man are related to DNA damage caused by ionization. Because rapidly dividing cells are most susceptable to DNA damage, the gastrointestinal and hematopoetic cells are typically the first, and most severly effected. Data from past nuclear experience indicates the lethal dose of irradiation in man to be about 350-450,000 milli-REM. It is important to note that while 50% of those victims exposed to this level of radiation will die, it may take up to 60 days. Radiation sickness will progress according to the following stages: