BIOLOGICAL AGENTS AS WEAPONS: MEDICAL IMPLICATIONS
BY KEN MILLER
The effectiveness of an attack involving biological agents rests heavily on the method used to disseminate them. Human exposure to biological agents could be respiratory, gastrointestinal, cutaneous (through the skin), or through live vectors (as mosquitoes or other insects) or person to person. Of these, the respiratory route is the most important. The cutaneous route is the least likely mode of exposure for causing serious disease.
For maximum effectiveness, a biological agent must be delivered as an aerosol. But not just any aerosol will work. To penetrate the lungs deeply enough to cause serious infection, the aerosol particles must be between one and five microns in diameter (one micron is one one-thousandth of a millimeter). Larger particles are filtered by the upper respiratory tract; smaller particles are unstable in ambient environmental conditions.
As you would expect, weather conditions at the target site are also important. High winds and turbulence break up an aerosol cloud. Optimal conditions would be calm air, inversion conditions (allowing the aerosol to stay low to the ground and follow the terrain), and low ultraviolet light (which may inactivate the aerosol). In other words, late night and early morning would be the optimal times for an aerosol attack.
This aerosol could be delivered from a line source such as an airplane, a helicopter, or a boat traveling upwind from the target or from a point source such as a stationary sprayer or airburst of bombsites from a missile. Apparently, the particles sprayed from agricultural sprayers are too large for maximally effective biological agent dissemination. The spray would have to be modified to be effective–delivered through a finer nozzle and at a higher driving pressure. Of course, an indoor release would allow the aerosol to persist and would increase inhalational exposure.
Probably one of the most important areas for distinguishing biological warfare from biological terrorism is the efficiency of the means of delivery. The technology and equipment for military strikes are known and are available. Military use of biological agents, though discouraged as a battleground tactic by the world community, would be expected to be very efficient. Use of biological agents by a terrorist, however, may be by unconventional and perhaps less efficient means (at least, we hope the means will be less efficient). The tactics employed and the purity of the agent could vary widely.
Also, multiple agents or a combination of biological and chemical agents may be tried. The deployment of a biological agent in a terrorist attack should be less of a threat to life if the agent is not aerosolized. For example, there have been several recent news reports of letters sent to targeted individuals stating the contents contained anthrax. Even if there was a dried anthrax culture on the paper, the risk is less than in aerosolized delivery. Nonetheless, the terrorist threat is still psychologically effective.
Other means of dissemination may cause agent-specific illness, but inhalation is the route most likely to cause a fatal form of the disease. This is where the most misinformation was reported during the news coverage of the anthrax incident in Las Vegas. Most media sources I saw during the coverage of the incident failed to understand that the lethality of a biological agent greatly depends on the method of dissemination. The potential risk to the general public was overstated.
RECOGNITION OF THE AGENT
Recognizing the type of agent used in the attack is the real problem. Although the military has developed means to identify many chemical and biological agents on the battlefield, this technology would not be immediately available at a civilian incident. By the time it becomes available, many individuals and emergency responders could have been exposed. But, that is not the least of it.
A well-deployed biological agent will produce no symptoms or signs for hours in the case of toxins and for days in the case of bacteria or viruses. Unless there is a salient event, such as a bomb blast, to disperse the agent, we would not even know that we have an emergency on our hands until patients start showing up at hospital emergency departments a few days later. Victims could include on- and off-duty emergency responders.
A biological weapon attack could easily be over before it is detected. If the agent chosen occurs naturally in the area–as would be the case with salmonella (a common food poisoning bacterium)–there would be an increase in the number of sick individuals above background cases. There could be both civilian and emergency services casualties. A large geographical region could be affected by bacteria or viruses deployed upwind; a small tactically important area could be affected by toxins. Casualties may be co-located at a common site or aligned with wind direction or food consumption from a specific source. You would expect an abrupt increase in casualties evolving over hours to days.
Recognition may lie in the epidemiology of the cases and the type of agent that is eventually identified as the cause of the sickness in individuals. Unlike a natural epidemic, the incidence of a disease caused by a biological agent terrorist attack may present with a compressed epidemic curve (number of new cases of disease over time). Cases will show up at health care sites over hours to days and peak within a few days instead of over days to weeks. Since epidemiology will be so important, it is essential that the local health department become involved as soon as an unusual number of cases start showing up at hospitals.
An agency`s public information officer will also be critical here. Collecting medical intelligence on the disease and keeping the public and the victims informed will be essential. Remember that there may be victims who as yet have no symptoms but who have been told they may have been exposed to something bad. The medical community, which usually is a resource to the fire service on medical issues, may also be in an information vacuum. There may not be a consensus on the means of postexposure prophylaxis. Conflicting opinions will only add to victims` and the public`s anxiety and will fuel speculation by the media. A hazardous materials response team with a good database may become a resource to the medical community.
Our experience during the December 1997 influenza epidemic in southern California might be similar to what we would experience during a biological agent attack–only the symptoms of disease might be unusual for the area. The death rate might also be unusually high, and cases may be tracked back to a common source. Initially, the number of cases being treated in emergency departments increased. These cases included health care personnel, which compounded the problem. The number of patients then steadily increased; the number plateaued over several weeks and eventually returned to background case incidence level. The influenza epidemic was regionwide and slower to evolve. A biological terrorist attack most likely would be more localized and may follow geographical contours, weather patterns, or a water or food source.
Identifying the weaknesses in our EMS and health care infrastructure brought out by this influenza epidemic will not only prepare us for the next natural infectious disease episode but will also heighten awareness of what might be expected in a biological agent release.
DIRECTION
As mentioned above, a biological weapon attack can be over long before patients start showing up with symptoms. Unless the terrorist decides to declare his work early (and assuming the information given is correct), the most likely detection method in a civilian event might be epidemiological surveillance. Identification of the organism may be by conventional microbiology laboratory methods or presumptively by the clinical presentation of the resulting illness (its symptoms and signs) and then systematically tracing back where and how each case became infected.
In the meantime, patients would be treated based on the laboratory tests, if available, or the most likely possibilities, given the symptoms and signs. The bacterial agents historically used as biological weapons may be cultured by standard microbiology methods and referenced when trying to design empirical treatment until more is known. However, since clinical and industrial microbiology laboratories do not commonly look for these agents, it may be helpful to suggest to them what you might be looking for. Special culture techniques may be needed to aid in the identification.
Other more specific methods of detection include mass spectrometry for toxins, antibody and antigen tests, DNA probes, and detection of metabolic products. Some of these tests will require a reference laboratory and will take time.
COUNTERMEASURES
Preattack
A few preattack countermeasures may be possible: protection of food and water sources and control of rodents and insects, which may transmit some of the biological agents, for example. Protection of food and water is more practical in a military contingency than in a civilian one. Truly effective defense against terrorism would mean restricting common freedoms: This presents significant problems for emergency planners and is one reason terrorists continue to be effective.
Postattack
Among the postattack countermeasures are the following.
Hygiene and sanitation. They will prevent further spread of the agent from contaminated areas.
Collective protection. This term is used for holding people in shelters with filtered positive-pressure ventilation and is a military tactic, but it has been reported that the HEPA (high-efficiency particulate air) filters in HVAC (heating, ventilation, and air-conditioning) units of commercial buildings could effectively protect occupants from an aerosol attack if other sites of air entry are blocked.
Shelter-in-place. The population is specifically instructed to stay indoors as a temporary measure of protection. It is most effective for a fast-moving toxic cloud, when people near the release point have insufficient time to evacuate, or when there is a finite duration exposure. Shelter-in-place may be harmful for long-term or continued release of a toxic agent if the outcome of the release cannot be reasonably predicted, if the cloud is prevented from dispersing, or if the agent is flammable or highly reactive. It should be concluded as soon as the cloud or aerosol passes (this is verified by monitoring and is more readily done in chemical than biological agent releases). The structures should be opened and ventilated and the population evacuated. The international news media showed examples of this during Operation Desert Storm in reference to protecting Israeli civilians from potential chemical or biological attack from Iraqi SCUD missiles.
Vaccines. Some are now available to protect from infection by selected biological agents. However, they must be administered well in advance of exposure and require periodic revaccination. They are practical only for military personnel based on an anticipated threat. Some can be used postexposure.
Antibiotics. They can also be effective if administered orally after exposure but before symptoms occur. Intravenous antibiotics, with supportive therapy of the individual, are therapeutic once infection has occurred. However, some of the more aggressive biological agents cause a fast-moving disease, so early treatment is essential. Once multisystem illness occurs, fatalities remain high even with treatment. Should a biological agent attack be carried out effectively, a larger number of people could be exposed. Some fraction (large or small) will become ill. This could potentially overwhelm the supply of common antibiotics used prophylactically or therapeutically. During the influenza epidemic in southern California, I received several phone calls late at night (in the emergency department) from pharmacists asking if they could substitute another antibiotic for the one prescribed for respiratory complications because of a temporary shortage of a specific drug. This could also be a problem when antibiotics are used for prophylaxis of large numbers of people.
Personal protective equipment (PPE). The military issues PPE called “the battledress overgarment” (BDO). It consists of a hood, a full face mask with air-purifying respirator, butyl rubber gloves and booties, and a carbon-infiltrated overgarment. The BDO is designed to protect the soldier from chemical and biological agents. The carbon in the BDO adsorbs chemical agents. During the decontamination of casualties, the military adds a butyl rubber apron over the BDO for the decon team. Comparable PPE in the fire service would be Levels A (vapor and splash), B (splash), and C (protective equipment).
Since the inhalational route of exposure presents the greatest risk of fatal disease from biological agents, respiratory protection is critical while the aerosol is still present. Once the aerosol has dissipated, contaminated surfaces may still present an infectious risk but not necessarily one as great as inhalation.
If a biological terrorist attack is immediately identified, Level A and Level B protection will allow for rescue of victims and their collection for decontamination. Level A protection would provide maximum safety during the rescue of nonambulatory victims from a con-taminated environment. Unlike chemical agents, where off-gassing of vapor is still a hazard after the agent has dispersed, the respiratory protection of Level B could still be adequate when only a biological agent is suspected. However, it is unlikely that the agent(s) would be identified at the scene; therefore Level A protection would be the safer choice.
The BDO seems to be an enhanced Level C protection system; it incorporates full skin protection with a full face air-purifying respirator (instead of SCBA) using a HEPA filter filtering one- to 1.5-micron-size particles as well as a canister to filter chemical agents.
When you are caring for decontaminated victims out of the hot zone, universal precautions should be sufficient. If you are caring for symptomatic victims days after the attack, universal precautions with HEPA or N95 masks will be effective. Only two biological agents used historically cause disease that can be transmitted person to person: pneumonic plague and smallpox. Both are transmitted by respiratory aerosol from coughing or respiratory secretions [suctioning, bag-valve-mask (BVM) ventilation, intubation], so respiratory protection with a well-fitted HEPA or N95 mask or HEPA air-purifying respirator and universal precautions will be effective protection.
Drainage from lesions produced by brucellosis, an-thrax, and viral hemorrhagic fevers can potentially transmit disease person to person, but universal precautions are sufficient. In all cases, a good washing of the hands and exposed skin and decontamination or disposal of equipment after patient care will reduce the risk of rescuer infection.
DECONTAMINATION
Biological agents may be encountered in several forms: aerosols, slurry mix, thick droplets, dry powder, spores, and vectors (infected insects or rodents that then infect people). Casualties may present in several ways: (1) exposed and contaminated (some ambulatory, some nonambulatory); (2) exposed, unaware, and no symptoms (during the incubation period); and (3) infected. The actions rescuers will take will depend on the presentations.
Chemical and biological terrorism present two potentially major complicating realities not commonly encountered in industrial and transportation hazardous materials incidents–the large number of people who may be contaminated and the fact that some of them will self-triage and self-transport to local hospitals. Also, some chemical agents require that respiratory support and specific antidotes be administered during and immediately following decon (a situation requiring coordination between haz mat and EMS). The problem with the self-triaged contaminated victims is that they may contaminate and disable close-by emergency departments, making subsequent triage and transport decisions at the incident more difficult.
The challenge of mass decon can also contribute to the chances of victims` self-transporting. The longer it takes to set up and operate mass decon, the greater the probability that ambulatory victims will seek their own care. Probably the most practical and rapid approach to mass decon is to set up sequential (two to three) elevated master streams, deck guns, or 112- to 134-inch handlines operated on a fog pattern and low pressure and walk the ambulatory victims through the water curtain while still clothed. Ladder pipes with a 212-inch gated wye with two 212-inch nozzles attached operated at hydrant pressure (or up to 50 psi at the nozzle) seems to work. At the end of this decon corridor, tarps could be set up for privacy. Ambulatory victims may then undress and wash with soap and water and then dry and redress in large trash bags with holes cut out for the head and arms. (See “Mass Casualty Decon for Terrorist Incidents” by William M. Moultrie, December 1998, p. 77.)
Since a suspected terrorist incident constitutes a crime scene, all clothing removed from victims will be evidence. This means that the clothing needs to be bagged, tagged for later victim identification (like triage bags), and set aside in a secure location until the Federal Bureau of Investigation (FBI)–the lead law enforcement agency–determines its disposition. Such mass decon tactics will work for biological agents and toxins and for many, but not all, chemical agents.
The consensus seems to be that the dilution of any biological agent by the method described above is so great that it is not necessary to contain runoff. Rescuers working in this decon corridor would be protected in Level B personal protective equipment (which for many departments is considered equivalent to structural turnout gear with SCBA).
Nonambulatory Victims
In the case of a biological agent release, nonambulatory victims would have to have been incapacitated by the dispersing mechanism, such as a bomb or secondary event, since the resulting disease takes time to develop and incapacitate. Unlike chemical agents, symptoms are not immediate.
If there are nonambulatory victims, rescue may require personnel in Level A protection. Contaminated victims would then be taken to the decon corridor or where personnel in Level B or Level C (if appropriate air-purifying respirator canisters are available) protection can perform decon by systematic clothing removal and containment, soap and water (or just lots of water), wash-down (probably in two stages), drying, and covering. Sodium or calcium hypochlorite in dilute solution (0.5 percent in the military manuals) may be used as an oxidant for chemical and as a disinfectant for biological agent decon in the initial step but is not essential. It is better to proceed with water or soap and water decon than to wait for the availability of hypochlorite. Don`t forget: Opened wounds will have to be irrigated with sterile saline at each stage of decon as well.
What about the biological agent release when victims may not know they have been exposed? This is entirely likely if a terrorist uses a biological agent dispersed with a nondestructive aerosol mechanism. Victims won`t know they are victims until they start getting sick hours to days later. The key here is that once the aerosol (or any other dispersal form) has dissipated, these victims are no more a hazard to rescuers than any other patient with an infectious disease. Most likely, they will have been self-decontaminated through the use of their usual hygiene. Contaminated clothing may still have the organism on it, but its threat is greatly reduced if it is not reaerosolized. As already mentioned, only pneumonic plague and smallpox can be transmitted person to person through respiratory secretions. In general, universal precautions with respiratory protection will be adequate protection if these two diseases are suspected or if pulmonary symptoms are the predominant problem. n
References
Medical Management of Biological Casualties, U.S. Army Medical Research Institute of Infectious Diseases, second edition, Aug. 1996.
NATO Handbook on the Medical Aspects of NBC Defensive Operations, Part II–Biological, Departments of the Army, Navy and Air Force, Feb. 1996.
Franz, DR, et al, “Clinical Recognition and Management of Patients Exposed to Biological Warfare Agents,” JAMA, 278(5):399-411, 1997.
Metropolitan Medical Strike Team Field Operations Guide, U.S. Department of Health and Human Services, Office of Public Health and Science, undated.
Proceedings, National Disaster Medical System Annual Conference, Denver, Mar. 1998.
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Selected Specific Biological Agents
Anthrax
The usual exposure of humans to anthrax is in the cattle, animal hide, and wood industry. This bacterium exists in a spore form that can survive adverse environmental conditions for years and then revert to the infectious bacterial form. Human disease may be contracted through cutaneous (skin ulcers), gastrointestinal, or inhalational exposure. Contact with the spores through minor skin lesions can cause skin infections and ulcerations, but this is not the potentially fatal form of the disease.
Inhalational anthrax results from inhaling aerosolized spores or bacterial forms. The resulting infection occurs in the lymph nodes next to the heart and lungs. This goes on to form a necrotizing hemorrhagic mediastinitis, a progressive destructive infection of the structures around the heart and lungs. The incubation period is one to five days after exposure. Initial symptoms are nonspecific and are quite common for the early stages of various diseases: fever, fatigue, nonproductive cough, and chest discomfort. After two to three days of vague symptoms, there is an abrupt onset of respiratory distress, dyspnea, stridor, and cyanosis leading to respiratory failure and septic shock. At this stage of the disease, treatment is usually not effective, and death occurs within 24 to 36 hours. The one characteristic diagnostic finding is on the chest X ray: a widened mediastinum with pleural effusions (widening of the shadow of the structures next to the heart and large vessels and the shadow of fluid accumulating outside of the base of the lungs).
In the early stages of the infection, intravenous antibiotics such as penicillin, ciprofloxacin, and doxycycline can be effective. Otherwise, bag-valve-mask ventilation, intubation, respiratory support, IV fluids, and dopamine may be needed for septic shock. When exposure to anthrax is suspected, and before symptoms appear, prophylaxis can be attempted with oral antibiotics such as ciprofloxacin or doxycycline for four weeks. A vaccine is available, but in the civilian exposure scenario discussed here, mass vaccinations of the population at large before any exposure are not practical. The vaccine has been recommended for postexposure prophylaxis in addition to the oral antibiotics, but the availability of and access to sufficient quantities for a widespread civilian exposure has been questioned.
Plague
This disease is transmitted to people in nature by fleas on rodents. The forms of the disease are bubonic, septicemic, and pneumonic. Bubonic plague is a necrotizing lymphadenitis (progressive ulcerating lymph node infection) leading to septic shock. This sounds bad enough, but a bomb full of fleas just doesn`t seem like an effective weapon. Like anthrax, weaponized plague will be most effective when dispersed as an aerosol. And, like inhalational anthrax, pneumonic plague is the rapidly fatal form of the disease.
The incubation period is two to three days, followed by a rapidly progressive pneumonia leading to respiratory failure. Respiratory secretions can transmit the disease from one person to another, so respiratory isolation and protection of the rescuers will be necessary. Intravenous antibiotics such as streptomycin and doxycycline can be effective if started early enough (usually within 24 hours of symptom onset). Prophylaxis of exposure to plague before symptom onset can be tried with one week of oral antibiotics such as tetracycline or doxycycline. As with anthrax, there is a vaccine for plague. Mass vaccinations of civilian populations are not practical, however, and the vaccine may not be effective against the pneumonic form of the disease.
Botulinum Toxin
Botulism can occur in several forms: gastrointestinal, infantile, and wound. Gastrointestinal botulism results from improper home canning of foods (insufficient heat to kill the botulism spores). Infantile botulism is rare and has been attributed to toxin in honey. Wound botulism is also unusual but is encountered in areas with widespread drug abuse. Injection sites or ulcers from skin popping can become infected with the organism that produces the toxin.
The toxin from this organism is a group of neurotoxins that block the release of the neurotransmitter acetylcholine at neuromuscular receptor sites (the junction between a muscle and the nerve that stimulates the muscle). The clinical syndrome is that of muscular weakness and bulbar paralysis with anticholinergic signs. Bulbar paralysis presents as eye muscle weakness and abnormal extraocular muscle movement, double vision, photophobia, and difficulty speaking and swallowing. It progresses to skeletal muscle weakness, and death occurs from respiratory muscle paralysis.
Anticholinergic signs are dry mouth and mucous membranes, dry eyes, dilated pupils, blurred vision, urinary retention, confusion, and tachycardia. It is important to distinguish these symptoms from those resulting from overatropinization when treating nerve agent toxicity.
Botulinum toxin could be dispersed as an aerosol but could also be used in food or water sabotage. Symptom onset is from 24 to 36 hours after inhalation or up to several days after ingestion. The toxin is not absorbed through the skin. Initial treatment is respiratory support, BVM ventilation, or intubation, if the respiratory muscles are affected. An antitoxin is available from the Centers for Disease Control and Prevention, but it must be given early in the disease`s progression to be effective.
Ricin
Ricin is produced from castor beans and, like botulinum toxin, is dangerous in extremely small doses. Apparently, it is fairly easy to synthesize and therefore is potentially widely available. Ricin can be effective by inhalation, injection, and ingestion but is not absorbed across intact skin. So aerosol or food or water sabotage could be expected.
Ricin works by inhibiting protein synthesis by cells. This shuts down many metabolic pathways essential for cellular and organ function and survival. Inhalation symptoms–fever, cough, dyspnea, and chest pain–develop and progress over 24 to 72 hours and lead to pneumonia, pulmonary edema, shock, and death. Ingesting the toxin leads to gastrointestinal bleeding and liver, spleen, and kidney damage progressing to shock but with less or no pulmonary symptoms. Treatment can only be directed at the symptoms encountered; there is no specific therapy.
Our discussion here really reviews the principles of hazardous materials mitigation. Virtually all of the haz mat training we rely on for industrial and transportation incidents applies to the management of biological and chemical terrorism casualties. Besides understanding the toxicology and biology of the historical agents, the two aspects of chemical and biological terrorism that are different from our daily haz mat thinking are the possibility of contending with mass decon and the need for field application of selected antidotes for specific agents. The real challenge here is to be prepared for the unexpected.
We have focused on the “usual” agents employed in biological warfare. When it comes to terrorism, all bets are off on the mode of deployment of an agent, its purity, and its composition. There is also the potential for multiple or unusual agents. However, understanding the general principles discussed here will allow us to approach any unknown agent safely and effectively. n
n KEN MILLER, M.D., Ph.D., is medical director of the Orange County (CA) Fire Authority, medical team manager of USAR CA TF-5, and unit commander of DMAT CA-1. He is also an assistant professor of emergency medicine at the University of California-Irvine Medical Center. He formerly spent 13 years as an EMT-B and paramedic for the Exeter Township (PA) Ambulance Association, Hershey (PA) Fire Department, Mercy Ambulance (Las Vegas), and San Diego City Paramedic Services. He has a B.S. in chemistry and a Ph.D. in pharmacology and is a board-certified emergency physician.
