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Beyond the Usual Suspects: Biological Agents
In the wake of the 9/11 attacks, Americans were gripped by a fear that other attacks would soon follow. This fear also included the potential for an attack with a biological warfare agent. Then, in September and October of that year, a series of letters containing militarized anthrax spores was sent to various government and news agencies. Experts believed the anthrax was "militarized," or military-grade, material produced in a sophisticated laboratory, like a government facility, and not a "homegrown" variety that might come from a foreign terrorist group.
Biological agents are considered the "poor mans' atomic bomb" because they can be produced relatively cheaply, with laboratory equipment that is easy to obtain and by technicians without a great deal of expertise. The phrase poor man's atomic bomb was originally used in 1988 before the Iranian Parliament by Speaker Hashemi Rafsanjani, who was comparing biological agents to nuclear weapons. It has since been echoed by U.S. news agencies and members of Congress.1
Concern about attacks with biological agents usually centers around organisms like anthrax, smallpox, the Ebola virus or toxins like botulinum toxin-that is, the usual suspects. But there are many other organisms that could be used.
Beyond the Usual Suspects
The Centers for Disease Control and Prevention has defined three levels of agents with potential as bioterrorist weapons: Categories A, B and C.2 Category A includes anthrax, smallpox, botulinum toxin and viruses, like Ebola, that cause viral hemorrhagic fevers (VHFs). It also contains plague (Yersinia pestis) and tularemia (Francisella tularensis).
Category B includes a list of 47 agents containing bacteria that cause brucellosis (Brucella species), Q fever (Coxiella burnetii), typhus (Rickettsia bacteria, particularly Rickettsia prowazekii) and a variety of viral encephalitis diseases. Also in Category B are toxins like ricin (castor beans), epsilon toxin (Clostridium perfringens) and Staphylococcal enterotoxin B. The incubation time and symptoms for these agents are included in Table 1.
The harm these agents can cause is impacted by a variety of factors, including environmental conditions like temperature, rain, humidity and wind. A full discussion of these environmental factors is beyond the scope of this article, but see reference No. 3 (Eitzen) for more details.
Regardless of what agent is used in an attack, bioagents all share one characteristic that is not found in other weapons of mass destruction: incubation period, or the length of time between exposure and the start of symptoms.4 With biological agents, exposure does not necessarily mean infection. Infection depends on the dose of agent received, the host's natural immunological resistance and the overall health of the exposed individual.
Individuals may be exposed to an agent at an indoor sporting event, large mall or other area. When leaving the area, they won't yet be contagious and won't immediately begin to spread the disease to others. Keep in mind, however, that exposed people can transfer some infectious agents to others through contact with their contaminated clothing, hair or items they might be carrying. The ability to infect others does not occur until after the incubation period; depending on the agent, this could take from several days to as long as three weeks. This lag can make it almost impossible to immediately determine that an attack has taken place. Only when multiple victims exhibiting similar signs and symptoms begin showing up at clinics and hospitals and activating EMS through 9-1-1 will a pattern suggesting common exposure begin to emerge. Medical investigators and law enforcement will have to develop a backward timeline to determine where infected individuals had been over the preceding days and weeks. Identifying a common location will help them deduce the place, date and time of the attack.
Since the exposed will become sick around the same time, there may be many calls to EMS within a short period. It is important that EMS personnel be familiar with the signs, symptoms and transport consideratons of patients exposed to various biological agents.
Plague
Plague is caused by the bacteria Yersinia pestis and was responsible for millions of deaths in Europe in the Middle Ages. A number of cases occur naturally in the U.S. each year, primarily in the southwestern states.5 Patients usually have fever, weakness and rapidly developing pneumonia with shortness of breath, chest pain, cough and, sometimes, bloody or watery sputum. Nausea, vomiting and abdominal pain may also occur. Without early treatment, pneumonic plague usually leads to respiratory failure, shock and rapid death.6 The CDC has developed an online training module on plague that is available to EMS.7
Tularemia
A Category A agent sometimes overlooked is Francisella tularensis, which causes the disease tularemia. Inhaling F. tularensis causes an abrupt onset of an acute, nonspecific febrile illness beginning 3-5 days after exposure, with pleuropneumonitis developing in a substantial number of cases during subsequent days.8 The incubation period can be as long as 14 days from inhalation exposure. Infection can also occur in the eyes and broken skin.
Brucellosis
Brucellosis, also called undulant fever and Malta fever, can be caused by any one of four bacterial species that are infectious in humans. They are commonly transmitted naturally through abrasions of the skin from handling infected animals like goats, cattle or dogs. Many cases occur from the ingestion of unpasteurized milk from infected cows. Brucellosis is highly infective when inhaled, with as few as 10-100 bacteria being sufficient to cause disease in humans.9 This requires that it be handled in the laboratory under biosafety Level 3 conditions. This is the next-to-highest level of containment and requires use of biohazard hoods and appropriate personal protection of laboratory workers.
Brucella species are very stable to environmental conditions and can survive for long periods in wet ground or on food. These features make them agents of prime consideration for bioterrorists. The disease is relatively prolonged, incapacitating and disabling in its natural form, although mortality rates (5% of untreated cases) are low, with most deaths caused by complicating endocarditis or meningitis. In 1954, brucellosis became the first biological agent weaponized by the U.S. military. Brucellosis infection, while low in mortality, can often lead to a chronic infection, causing depression, chronic fatigue and arthritis. This has made it a renewed candidate as a terrorist agent.9
Typhus
Epidemic typhus is caused by the coccobacilli Rickettsia prowazekii and is related to the Coxiella organism that causes Q fever. The round bacterial cells are about two microns in diameter and replicate in the cytoplasm and nucleus of the cells they infect. Typhus is transmitted by the bites of fleas or lice that reside on rats and flying squirrels. Although rare in the U.S., it has become prevalent in recent years among homeless populations. It has an incubation period of 6-14 days, but once symptoms develop, they progress rapidly. They can include high fever, chills, headaches, skin rashes and generalized pain that can last for 2-3 weeks. The rash may become extensive and in some cases extend over the majority of the body. Fevers can run as high as 104°F in adults and 106°F in children. Cardiac and circulatory problems such as tachycardia, low blood pressure and thrombosis often develop. In addition, there may be neurological manifestations, including agitation, spasticity, stupor and coma.10
Q Fever
Q fever, caused by Coxiella burnetii, presents as an atypical pneumonialike illness with high fever, usually starting 2-14 days after exposure (depending on the dose to which the individual is exposed). Coxiella is highly infectious by inhalation: As little as a single inhaled bacterium can cause illness.11 Used as a bioterrorist agent, the organism would produce high levels of incapacitating disease. The bacteria are resistant to heat, drying and some common disinfectants, and can persist in the environment for extended periods.
Coxiella belong to the Rickettsia family of bacteria. They are very small coccobacilli, round in shape, that, unlike most bacteria, reproduce intracellularly (within the cell), rather than in the intercellular fluid outside of cells. Coxiella is even more unique in that it reproduces within intracellular structures called phagolysosomes.12 These structures are usually responsible for destroying other forms of bacteria during an infection.
Equine Encephalitis
A number of equine encephalitis viruses are on the Category B list. These include western equine encephalitis (WEE), eastern equine encephalitis (EEE) and Venezuelan equine encephalitis (VEE). They all belong to the viral family Togaviridae. Unlike most infectious agents, these viruses have RNA, not DNA, as their genetic material. In this regard they are similar to the Category A hemorrhagic fever viruses like Ebola and Marburg. When an RNA virus infects the cells of the nervous system, it hijacks the cells' normal replication mechanisms and diverts them into producing copies of itself. Eventually, the cell ruptures and releases hundreds of new viral particles, which circulate and infect additional cells. Signs of infection occur within 1-6 days of infection with a sudden onset of severe flulike symptoms, including headache, chills, fever, pain behind the eyes, nausea and vomiting. Mild cases persist for 3-5 days, but in severe cases the virus invades the central nervous system, causing encephalitis, disorientation, convulsion and paralysis. Children are more susceptible than adults, and the death rate in children is 2-3 times higher.13
Equine encephalitis is transmitted to humans by the bite of infected mosquitoes, which acquire it from rodents and horses. As bioweapons, these viruses are highly infectious by the aerosol route, with as little as a single particle capable of producing disease. They are also stable in aerosols and relatively easy to grow artificially in large quantities. They can be weaponized and are stable enough to withstand long-term storage.14
Staphylococcal Enterotoxin B
Staphylococcus aureus and Staphylococcus pyrogenes are both capable of producing a very stable low-molecular-weight protein toxin that can produce a severe food poisoning episode. While it's generally not fatal, exposure to high levels of this toxin, such as in an aerosol attack, can lead to septic shock and death. Symptoms occur within 3-12 hours of exposure and are similar to those of colds or respiratory infections. The toxin reacts with components of the immune system and causes release of cytokines, small molecules that mediate the cells' immune response.15
Staphylococcal enterotoxin B is a very robust protein, easily aerosolized and stable for extended periods of time. Military tests showed that an aerosol could be distributed from a single aircraft that would cover an area twice the size of metropolitan Los Angeles, with about 30% of the population becoming casualties.
Transport and PPE
Transport of infected individuals will require the same precautions as transport of any patient with an infectious disease, such as TB or flu. When notice of a biological attack has been given or if a patient is suspected of being exposed to an agent and is showing signs of a fever and rash before the cause is known, additional precautions should be taken. EMS should use standard PPE against patients with infectious diseases. A fit-tested N95 (or higher) respirator should be worn, as well as appropriate gloves and clothing to provide adequate dermal contact protection. Unless their respiratory conditions prohibit it, patients with an active cough should wear a surgical mask or oxygen mask with oxygen.16 A more detailed description of PPE requirements for EMS can be found in previous issues of EMS and Advanced Rescue Technology magazines.17,18
What Is the Strategic National Stockpile?
The CDC's Strategic National Stockpile (SNS) program sets aside large quantities of medicine and supplies to protect the American public if there's a public-health emergency such as a terrorist attack, large flu outbreak or natural disaster severe enough to cause local supplies to run out. Once federal and local authorities agree that the SNS is needed, medicines will be delivered to any state in the U.S. within 12 hours or less. Each state has plans to receive and distribute SNS materials to local communities as quickly as possible.19 The SNS has antibiotics and vaccines for use against biological agents and protocols for their administration. EMS personnel should be familiar with the SNS program and the means for utilizing it.
Responding to An Attack
Since it likely won't be known that an event has occurred until the end of the incubation period, it's important for EMS to understand what might occur upon notification that an attack has taken place. Once a diagnosis has been confirmed in a number of patients and interviews and reports establish that an attack has occurred, there will be a public notification for those who were in the same area at the estimated time of infection to report for evaluation and treatment.20 This may create a general panic, resulting in large numbers of people showing up at emergency departments and clinics and calling 9-1-1 at about the same time, overwhelming EMS and medical staffs. In addition, situations at hospitals or for EMS teams could become unruly. Law enforcement and medical staffs would be faced with trying to contain crowds of people, some genuinely exposed and others fearing they were. Finding a way to keep such crowds contained until provision for treatment is made-and, at the same time, trying not to become contaminated-will be a great challenge.1
The recent outbreak of Marburg virus in Angola, which had a death rate greater than 85%, is an example of what can happen. Because of lack of education about the virus and measures needed to stop its spread, frightened citizens hid sick family members to keep World Health Organization medical teams from taking them away for treatment and isolation. In some cases people even stoned health workers in full protective suits and gear to keep them away from their houses.21
It would be easy to say, "Well, this was an isolated case in Africa, where these things are not understood." However, imagine the scene at several city hospitals a week after an attack, when dozens of people start showing up with a contagious disease. Dozens of others arrive, thinking they too are sick, and begin mixing with those who are contagious. Soon the crowd spills out into the street. News coverage spreads the word that a contagious disease is loose in the city, and as a result, dozens more people crowd the hospitals. Soon fighting breaks out as people try to get treatment. EMS arrives, transporting additional contagious individuals. People panic as they see hospital workers dressed in "moon suits" isolating patients in an attempt to stop the spread of the disease.
Despite all of our advanced education and knowledge, a real biological attack may cause panic and chaos in our population. EMS personnel need to have a game plan ready so that they're prepared to cope with this situation-and not become victims of it.
References
Doug Hanson writes extensively for EMS, law enforcement and first responder publications. In addition to writing for many trade journals, he has also written hundreds of technical papers and presented testimony before Congress. He writes a monthly column for the website Officer.com. He can be reached at dougmh@comcast.net.
