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Bioterrorism: Understanding the Threat and Treatment 20-260223 2 Hours Back to Course Index













The possibility of maliciously created public health emergencies arising in the United States is a growing concern.    In the wake of the September 11th attack on the World Trade Center and Pentagon in 2001 and subsequent acts of terrorism with anthrax and more recent attempted attacks on flights that were thwarted.  The concern is now an ever-present threat level in the back of all of our minds. 


Though some people feel it is impossible to be completely prepared for unexpected events, taking preparedness actions, putting in place procedures and learning about biological weapons will help with disasters much more effectively when they do occur. 


Over recent years, Americans have accepted the realization that terrorists have the knowledge and capability to strike on our soil, against anyone. No longer could we look at terrorism as something that occurs in other countries. With this new reality came the recognition that we as health care workers need to know about the pathogens that are most likely to be used in a future attack and how best to respond if another attack occurs. This course provides a brief history of bioterrorism and identifies the six agents or classes of agents most likely to be used as weapons:


  • Anthrax
  • Smallpox
  • Pneumonic Plague
  • Botulinum Toxin
  • Tularemia
  • Viral Hemorrhagic Fevers


Familiarity with these agents will help health care workers recognize the features that can be used to distinguish an attack from a naturally occurring disease.


The mental health effects of disasters and terror events can be severe and are most effectively characterized as differing stress reactions with psychological consequences. Empirical studies show that addressing these consequences requires a staged approach to care.


After studying the information presented here, you will be able to:


1.  Discuss biological weapons used in the United States.


2.  Identify potential bioterrorist agents and describe methods for dissemination.


3.  Describe how to recognize bioterrorism, the initial patient assessment, and the isolation precautions and decontamination procedures used for each agent.


4.  Discuss anthrax and smallpox, including the signs and symptoms and treatment options.


5.  Discuss additional agents: botulism, plague, tularemia, and viral hemorrhagic fever viruses, including the signs and symptoms and treatment options.




Biological Weapons and the United States


Following the September 2001 terrorist attacks on the World Trade Center and the Pentagon, and the subsequent bioterrorist attacks with anthrax-filled letters sent through the mail, the use of infectious disease as a biological weapon has become one of the most feared possibilities of the 21st century. Yet the deliberate use of infectious disease as a weapon of war or terrorism is not new to the United States. Biological terrorism is the deliberate dissemination of infectious agents through food or water, by an insect vector, or as an aerosol for the purpose of producing disease, death, panic, and social disruption in a civilian population.


In Colonial America during the French and Indian War (1754-1767), the commander-in-chief of British forces, Sir Jeffrey Amherst, suggested that smallpox could be used as a weapon against the Indians hostile to the British. In a letter to Colonel Henry Bouquet, he wrote, Could it not be contrived to send the Small Pox among those disaffected tribes of Indians?   A month earlier, the commander of the local militia at Fort Pitt had considered this same remedy for the Indian problem. He noted in his journal that when some Indians visited the fort, he had given them two blankets and a handkerchief out of the Small Pox Hospital and that he hoped it would have the desired effect.  Whether the subsequent severe epidemic of smallpox among the Indians around Fort Pitt was a result of these gifts or of natural causes is not known.


One hundred years later, in the Civil War, Dr. Luke Blackburn, who later became Kentucky’s governor, tried to infect Union troops by selling them clothing contaminated with both smallpox and yellow fever. The obituary for one Union officer stated that he had died from smallpox due to Dr. Blackburn’s efforts.


By World War I, germ warfare had become more sophisticated. Dr. Anton Dilger, a Johns Hopkins-trained German-American physician working in his Washington, D.C., home, prepared approximately a quart of liquid glanders and anthrax for the use of German agents to inoculate the 3,000 head of horses, mules, and cattle that were being shipped to the Allied forces in France. Several hundred military personnel were secondarily infected from contact with the animals.


Less than 25 years later, during World War II, Americans were among the 10,000 prisoners of war who died after being experimentally infected with anthrax, meningitis, cholera, botulism, and plague in the infamous Japanese Unit 731 that had been set up in occupied China.  Under the direction of Dr. Shiro Ishii, the Japanese were researching the effects of biological weapons on live subjects. After the war, the United States offered protection from prosecution for war crimes to Ishii and other Unit 731 researchers in exchange for their research data and expertise.




Biological Weapons Development


In response to intelligence that other countries were doing it, the United States started developing a biological weapons program in 1943.  After World War II, the program was expanded until the late 1960s. Throughout this 25-year period, the United States developed, weaponized, and stockpiled anthrax, Botulinum toxin, tularemia, brucellosis, Q fever, Staphylococcal enterotoxin B, and Venezuelan equine encephalitis virus as well as many anti-crop agents (plant pathogens that attack agricultural crops such as wheat and rice).


To demonstrate that biological warfare agents could be delivered over massive areas using natural continental air flows, the U.S. government between Sept. 20 and Sept. 27, 1950, released quantities of Serratia marcescens, a bacteria thought to be harmless, in a bacterial fogging of San Francisco.  Following the release, Stanford University Hospital reported an outbreak of 11 cases of urinary tract infections caused by the organism. This led to one case of transient bacteremia and to one death from endocarditis.  Even though the timing was right, the etiologic relationship between the testing and the outbreak was not technically proven, and the military continued covert testing of S. marcescens over cities until 1968.  Two other organisms, both harmless, were also used in testing dispersal methods. Bacillus subtilis was released into the New York subway system, where it was found that such an agent released in a single station could be spread throughout the entire subway system by the movement of the trains.  In addition, large-scale tests with Bacillus globigii took place in Washington, D.C.s, National Airport, and Greyhound Bus Terminal, and again in the New York subway system.




Modern Era


During the 1960s, widespread anti-war, anti-military demonstrations in the United States led to an official ending of the Biological Offensive Weapons Program and led the United States to renounce the use of biological weapons under any circumstances. In 1972, Canada, the United Kingdom, the Soviet Union, and 140 other nations followed suit and agreed to end their own biological weapons programs. Each country signed the Biological and Toxin Weapons Convention, which called for the end to all development, production, and stockpiling of biological and toxin weapons and for the destruction of existing biological weapons stocks.


Despite signing this agreement, at least 10 nations, most notably the Soviet Union and Iraq, continued to research, develop, and stockpile such weapons. According to Ken Alibek, the former deputy chief of research for the biological weapons program of the Soviet Union, between 1972 and 1992 over 60,000 people were involved in the annual production of hundreds of tons of anthrax and dozens of tons of smallpox and plague.  Bombs and intercontinental ballistic missiles loaded with smallpox were developed and stockpiled.  Hybrid designer germs, impervious to vaccines and antibiotics, were developed from Ebola and smallpox.  The Iraqis not only continued developing and stockpiling biological weapons but also openly used them against another country (Iran) and against their own people (the Kurds).  The Iraqis claim to have produced large quantities of Botulinum toxin, Bacillus anthracis, and Clostridium perfringens. From information gathered by inspectors from the United Nations Special Commission on Iraq (UNSCOM), the Iraqis made enough germs and toxins to kill every human being on the planet.




Incidents in the U.S.


In more recent times, bioterrorism has become a growing concern in the United States, not just with biological threats from other nations, but with threats coming from terrorist groups within the country. Until September 2001, the only documented multi-victim bioterrorism events in the United States were related to the deliberate contamination of food.


In 1984, a religious cult led by Bhagwan Shree Rajneesh, trying to influence a local election, contaminated 10 restaurant salad bars in The Dalles, Or., with Salmonella typhimurium.  Although no one died, 751 members of the community developed salmonella gastroenteritis. It took more than a year for authorities to link the outbreak to the religious cult.



In 1996, at St. Paul Medical Center in Dallas, Shigella dysenteriae type 2 was found in the stool cultures of 12 of 45 lab workers who had developed severe gastrointestinal illness.  Each of the infected lab workers, responding to an unsigned e-mail from a supervisor’s computer that invited them to enjoy the pastries left in their break room, had eaten a blueberry muffin or a doughnut. In the following investigation, S. dysenteriae was found in the uneaten pastries.


Further investigation revealed the organism came from the laboratory’s own stock culture. The angry, dissatisfied co-worker who poisoned the pastries was subsequently identified and served jail time.


The third multi-victim biological attack in the United States occurred shortly after the Sept. 11 terrorist attack on the World Trade Center and Pentagon when anthrax-filled letters were sent through the U.S. mail. One of the letters was filled with 2 grams of powder containing approximately 200 billion to 2 trillion anthrax spores.  On Oct. 4, 2001, the index (first) case, a 63-year-old man from Florida, was diagnosed with pulmonary anthrax.  Shortly after diagnosis of the first case, an additional 21 cases (11 inhalational and 11 cutaneous) were identified in residents of seven states along the East Coast (Connecticut, Florida, Maryland, New Jersey, New York, Pennsylvania, and Virginia). Twenty of the victims were mail handlers, who had been exposed at worksites where mail was handled or received.  Only five of the 22 infected patients died, all with inhalational anthrax.


Following the outbreak, more than 10,000 people potentially at risk, were advised to take prophylactic antibiotics, and another 20,000 plus were started on antibiotics until investigation ruled out exposure and treatment was stopped.


For years, anthrax has been at the top of the list of biological warfare agents for every country researching biological weapons. In fact, anthrax sent through the U.S. postal system might have come from our own government’s biological weapons research program. Genetic fingerprinting has shown it to be identical to the stocks of anthrax that have been maintained by the U.S. Army since 1980.


Matching samples of anthrax have been found at five labs: Fort Detrick in Maryland, the Dugway Proving Ground military research facility in Utah, a British military lab called Porton Down, and the microbial depositories at Louisiana State University and Northern Arizona University. Of these, it is known that the Dugway facility has the technology for making the special powdery form of anthrax that can be most easily inhaled the type found in the letters.


Meanwhile, the country remains at risk for future attacks involving anthrax or other infectious pathogens. The reasons are obvious: Pathogenic agents are easy to produce, with instructions readily available on the Internet and in print.


They also are inexpensive. In 2001 NATO prepared cost estimates for weapons that could produce 50 percent human casualties per square kilometer. The estimates were $9,000 for conventional weapons, $3,000 for chemical agents, and less than $5 for biological agents.



Bioterrorism Agents and Methods for Dissemination


Many microorganisms such as bacteria, viruses, fungi, rickettsial agents, and their toxins can be used as biological warfare agents. Those that pose the greatest threats have been categorized by the National Center for Disease Control and Prevention (CDC) and bioterrorism experts in the following ways:


Infectious agents that will cause illness and death for the greatest number of people in the population targeted.


Infectious agents that are stable, easy to mass-produce, and easy to deliver over large population areas; agents with a potential for person-to-person transmission.


Infectious agents that are most likely to cause public fear and potential civil disruption.


Infectious agents that require special public health preparedness needs to be based on stockpile requirements, enhanced surveillance, or diagnostic needs.


The ideal infectious agent will cause a lethal disease with no effective treatment; it can be aerosolized and can survive sunlight, drying, and heat; and it is cheap and easy to produce.







In biological warfare, the most efficient means to infect the greatest number of people is to use a pathogen that can be aerosolized. Each pathogen listed by the CDC under Category A (anthrax, smallpox, plague, Botulinum toxin, hemorrhagic viruses, along with a number of other biological agents) can be dispersed in aerosol particles, droplet nuclei (1-5 microns in size). In certain weather conditions, these infectious particles can remain suspended in the air for hours, and if inhaled, can penetrate deep into the distal bronchioles and terminal alveoli (the gas exchange area) of the victim’s lungs. Unlike larger particles that settle in the upper sections of the respiratory system, these tiny particles cannot be removed from the lungs by coughing or mucociliary clearance.


As we are now well aware, sophisticated technology is not needed to deliver an infectious agent. To distribute a pathogen over greater areas, an infectious aerosol could be dispersed from a crop-dusting airplane flying over a city, through the air conditioning system in a large building, or with a pesticide sprayer in a crowded auditorium.



Ingestion food


While aerosols are the most efficient means of delivering a biological agent to the greatest number of people, the nation’s water supply, crops, and livestock could also be used to distribute infectious material. In fact, in two of the three documented U.S. domestic bioterrorist attacks, food was used to deliver the chosen pathogens (salmonella and Shigella).


In the United States, both food and water are vulnerable to terrorist attacks. The food supply could be targeted in a number of ways. Since food items are imported from countries throughout the world, items could be contaminated before they enter the United States. Inside the country, many chain restaurants and markets have extensive supply systems, and food could be contaminated at major distribution centers. Furthermore, food workers could be a security risk because of their extremely high turnover rates and the fact that the work attracts many people without valid immigration papers.


Fortunately, only a few infectious agents likely to be used for contaminating food will cause severe illness. Rather than targeting a specific food item, it would probably be more effective to attack the food supply itself. Examples would be the use of Xanthomonas oryzae to destroy rice crops and the use of foot-and-mouth disease to destroy livestock.


Ingestion water


While it would be difficult to contaminate a large water reservoir or aqueduct because of the amount of toxin or infectious agent needed, it would be easier for a terrorist to contaminate a storage tank of treated water serving a smaller community. The treated water stored in a tank is usually not filtered again before it reaches the consumer. This leaves only chlorine as a defense against contaminants. While it is known that chlorine will inactivate botulinum toxin, anthrax spores are resistant and can remain stable in chlorinated water for up to two years. The resistance of the plague and brucellosis to chlorine is unknown.


However, if terrorists can infiltrate a water treatment plant and deactivate the chlorination system, infectious agents resistant to chlorine are not needed.


An aerosolized attack with a Category A pathogen is the most efficient method for infecting the greatest number of people and for causing the maximum adverse public health impact. A terrorist attack with Category B agents, which include the foodborne and waterborne agents, is less likely to cause an adverse public health impact, because of the lower morbidity and mortality associated with these agents.



Recognizing a Bioterrorist Attack


Determining if and when a bioterrorism attack has taken place may not always be easy. Unlike the visible attacks on the World Trade Center and the Pentagon, a bioterrorism attack could likely be silent. The infectious agent or toxin could likely be dispersed in its aerosolized form and as such would be odorless and invisible.


The first awareness that an attack may have taken place will occur several days or even a few weeks after the fact when symptomatic patients start showing up at emergency departments and clinics.  Determining whether these patients are victims of a biological warfare agent or have a common respiratory illness would not be easy. The early signs and symptoms of most of the Category A diseases respiratory anthrax, plague, tularemia, and small poxmimic the common flu, with patients presenting with fever and respiratory complaints. To help with this problem, the Association for Professionals in Infection Control and Epidemiology (APIC) and the CDC offer the following guidelines to help determine when to suspect a bioterrorism attack:


  • A rapidly increasing disease incidence (e.g., within hours or days) in a normal healthy population.  
  • An unusual increase in the number of people seeking care, especially with fever, respiratory or GI complaints.  
  • An endemic disease rapidly emerging at an uncharacteristic time or in an unusual pattern.  
  • Clusters of patients arriving from a single locale.  
  • Large numbers of rapidly fatal cases (patients who die within 72 hours after admission to the hospital). 
  • Any patient presenting with a disease that is relatively uncommon and has bioterrorism potential (e.g., pulmonary anthrax, smallpox, plague, tularemia, or viral hemorrhagic disease).  
  • A disease with an unusual geographic distribution (e.g., plague in the Northeast).
  • An unusual number of deaths or illness among animals.



Most health care workers have never seen an actual case of one of the diseases listed in Category A. This lack of experience, even if more than one of the above indicators is present, will make it difficult in many cases to determine whether a bioterrorism attack has actually taken place. Consequently, health care workers need to be especially alert for any increase in unusual patient symptoms presenting at health care centers. With quick recognition of a change in disease patterns and a call to proper authorities, health care workers can help determine the source of the infections and possibly prevent further exposures and deaths.



Initial Patient Assessment


The first casualties from a bioterrorism attack will most likely present with these symptoms:


Inhalational anthrax: Fever, fatigue, a feeling of discomfort, muscular aches, mild chest pain, and a nonproductive cough followed by severe respiratory distress with shortness of breath, sweating, stridor, and cyanosis, with a widened mediastinum and pleural effusions on chest X-ray or CT scan.


Cutaneous anthrax: Skin infection, an itching papule (resembles an insect bite) becomes vesicular with surrounding non-pitting edema, and in two to six days forms a black necrotic center (eschar). Generally found on the head, forearms or hands. Usually not fatal if treated with antibiotics.


Botulism: Drooping eyelids, generalized weakness, dizziness, dry mouth and throat, blurred vision and double vision, difficulty speaking and difficulty swallowing followed by a descending flaccid paralysis, a condition in which paralysis of the arms occurs first, followed by the respiratory muscles, then the legs.


Pneumonic plague: High fever, chills, headache, weakness, and cough with bloody sputum and gram-negative safety pin-shaped organisms; fulminant gram-negative pneumonia with hemoptysis in a previously healthy person.


Tularemia: High fever, chills, weakness, headache, generalized body aches, and elevated white blood cells. A dry cough and chest pain without signs of pneumonia.


Smallpox: A feeling of discomfort, fever, rigors, vomiting, and head and backaches. A rash follows two to three days later with lesions that quickly progress from macules to papules then to oozing pustular vesicles. The vesicles are more abundant on the extremities and face and all develop at the same time (unlike chickenpox, in which vesicles develop in crops). Pustules appear on the palms of hands and soles of feet of patients with smallpox, never in patients with chickenpox.


Viral hemorrhagic fevers: High fever, malaise, body aches, headache, vomiting, and diarrhea. Bleeding from mucous membranes, hemorrhage, shock, and capillary leaks (petechiae).



Isolation Precautions


In the event of infections or casualties from a bioterrorist attack, preventing further transmission of disease will be one of the main goals. Patients with similar symptoms can be cohorted in semi-private or multiple-bed rooms. Special ventilation is not needed for anthrax, botulism, plague, or tularemia.


Standard precautions should be used with all patients regardless of their diagnosis or known infection status. Standard precautions include wearing gloves when touching blood, body fluids, non-intact skin, excretions, secretions, and contaminated items. They include wearing a gown, mask, and eye protection or a face shield during procedures likely to generate splashes of blood or other body fluids. Standard precautions are intended to prevent direct contact with all body fluids, non-intact skin, and mucous membranes. These precautions reduce the risk of transmission from recognized and unrecognized sources. For smallpox, pneumonic plague, and viral hemorrhagic fevers, the following additional precautions, along with standard precautions, are needed to prevent transmission.


Contact and airborne precautions and a negative-pressure room (in which air is exhausted to the outside) should be used for all patients infected with smallpox. Since smallpox can also be transmitted by contact with the patient’s vesicles, lesions, and body fluids, health care workers need to wear personal protective equipment (PPE) for all patient contact and when entering the patient’s environment. Gloves should be worn when in the patient’s room. A gown should be worn if contact with the patient or the patient’s environment is anticipated. Hands should be washed with an antimicrobial agent.


Patient-care equipment such as stethoscopes should be used only for the infected patient or cohort of patients. All linen and waste should be placed in biohazard bags and autoclaved before being laundered or incinerated.


Disinfectants such as bleach and quaternary ammonia are effective for cleaning surfaces contaminated with the viruses. An N-95 mask (used with patients with TB) should be worn when entering the patient’s room.


Airborne precautions, droplet precautions, contact precautions, standard precautions, and a negative pressure room should be used with patients who may have a viral hemorrhagic disease. Contact with all blood-stained materials and contaminated environment must be avoided.





Patients who present to the ED or clinic with symptoms usually will not need to be decontaminated. This is because exposure probably occurred several days, or even weeks earlier, and patients have since showered and changed clothes.


Exceptions to this would include a recent exposure from opening a letter containing a possibly pathogenic agent or a recent exposure to a known release of a bioterrorist agent when patients present with gross contamination. When decontamination is necessary, soap and water are sufficient. Bleach should not be used to decontaminate exposed people. Clothing should be removed and sealed in a plastic bag. Environmental surfaces can be decontaminated with a bleach solution (one-part bleach to nine parts water).


The diseases that can occur from a bioterrorist attack can be misinterpreted as natural occurrences. With heightened awareness, quick recognition of unusual changes in disease patterns, and notification of the health authorities, nurses can help identify a bioterrorism incident in time to take proper precautions and save lives.




Anthrax has been developed as a biological weapon by Japan, Iraq, the United Kingdom, the Soviet Union, and the United States. Because of its ease of production, its stability for decades in spore form, and its ability to cause massive casualties and civil disruption, warfare experts consider it the leading biological warfare threat. Anthrax has been a tool of terror throughout history. The fifth and sixth plagues in the Book of Exodus of the Bible are thought to have been outbreaks of anthrax in livestock and in humans.


Anthrax is a zoonotic disease, usually infecting sheep, cattle, and goats, caused by Bacillus anthracis. This is an aerobic, gram-positive, spore-forming bacillus.


The disease is rarely seen in the United States. Typically, it infects humans only after they come in contact with an infected animal or animal products. The human form of the disease can present in three ways:


  • pulmonary (inhalation of spores)
  • cutaneous (skin contact with spores or spore-contaminated materials) or
  •  gastrointestinal (ingestion of contaminated meat).


Until October 2001, no case of inhalation anthrax had been reported in the United States since 1978.


If anthrax is used as a bioterrorism agent to inflict massive casualties, it most likely will be delivered in an inhalational form as an aerosol. In experimental models of a biological attack using an aerosolized release of anthrax, 220 pounds of anthrax released upwind of Washington, D.C., could cause between 130,000 and 3 million deaths.



Pulmonary Anthrax


Pulmonary anthrax is the most deadly form of the disease. It begins by inhaling anthrax spores into the alveolar spaces of the lung. Until the 2001 U.S. Postal Service anthrax outbreak, it was thought that for an infection to occur at least 8,000 to 50,000 spores had to be inhaled (a bolus of spores smaller than the period at the end of this sentence). However, it now appears that inhaling as few as one to three spores may have been sufficient to cause disease in the two fatal cases from New York City.   Anthrax spores are then transported via the lymphatics to the mediastinal lymph nodes, where germination can occur from two to 60 days later (an average of five days), depending on the dose. Once germination occurs, disease follows rapidly. The bacillus multiplies in the lymph nodes of the mediastinal space. This causes the nodes to swell (thoracic edema) and then bleed into the space between the lungs. A chest X-ray will often show a classic large white area in the center of the chest (mediastinal widening).

Initial symptoms are flu-like with fever, fatigue, cough, and mild chest pains. The initial symptoms are followed by a brief period (several hours to two to three days) of improvement. Two to four days after the first symptoms, the patient has an abrupt onset of respiratory failure and hemodynamic collapse. Fifty percent of the patients develop hemorrhagic meningitis. Death occurs in all untreated patients. Treatment rarely is effective if therapy is started when patients are significantly symptomatic, and fatalities often occur.



Cutaneous Anthrax


Cutaneous anthrax occurs when the anthrax spores enter the skin through an abrasion, cut, or wound. The skin infection starts as a raised itching lesion. In one or two days, the lesion grows into a painless pus-filled vesicle that ruptures to form an ulcer with a characteristic coal-black necrotic area in the center (eschar). Lymph glands in the area of the infection swell and symptoms of fever, malaise, and headache appear. In two to three weeks, the eschar dries and separates from the skin leaving a permanent scar. Without treatment, mortality for cutaneous anthrax victims is about 20 percent, but with appropriate treatment, fatalities are rare.


If a patient has cutaneous anthrax, the skin lesions may be infectious with direct skin contact. Health care providers should wear gloves.



Gastrointestinal Anthrax


No cases of gastrointestinal anthrax have ever occurred in the United States. Symptoms occur two to five days after eating anthrax-contaminated meat. The anthrax spores are thought to germinate predominantly in the terminal ileum or cecum causing edema and necrosis. The patient presents with nausea and vomiting which can rapidly progress to bloody diarrhea and acute abdomen. Massive ascites develop. Death results from intestinal perforation and sepsis.





Vaccination given within three or four days following exposure can prevent, or decrease, the severity of the disease. An antiviral medication used in the treatment of cytomegalovirus may be useful in the event of a smallpox outbreak. Cidofovir (Vistide) has shown effectiveness against poxviridae in animal models.


The following drugs are recommended: oral fluoroquinolones ciprofloxacin (Cipro), levofloxacin (Levaquin), ofloxacin (Floxin).  If fluoroquinolones are not available or are contraindicated, doxycycline (Doxylin) can be used.






Smallpox is considered second to anthrax, of the four top-rated infectious disease agents that are likely to be used in a bioterrorism attack. Both agents are stable in aerosol form, are resistant to destruction, and can be easily grown in large quantities. While anthrax has a higher case fatality rate than does smallpox, smallpox can spread person-to-person throughout the country and the world.


Over the course of human history, smallpox has caused the greatest number of deaths of any infectious disease.  During the 20th century alone, there were over 500 million deaths from smallpox. The virus is thought to have evolved in Africa from an animal poxvirus thousands of years ago.



Symptoms of Smallpox


Smallpox infection is airborne and spreads from person-to-person and by direct contact. Contaminated clothing and bed linens can spread the virus. It takes an aerosol exposure of fewer than 15 minutes to cause infection.


Smallpox symptoms start to like those of other viral illnesses. They include flu-like symptoms of fever, vomiting, headache, and backache. Two to three days later, a rash appears. The rash is most prominent on the face and extremities and spreads to the trunk over the next week. Skin lesions progress from macules to papules, then to oozing pustular vesicles with a foul odor. The lesions appear during a one- to two-day period and evolve at the same rate (with chickenpox, the lesions appear in crops every few days, and lesions of different stages are found on adjacent areas of the skin). Eight to 14 days after smallpox symptoms appear, the vesicles form scabs. Death occurs during the second week after the rash appears in about 30 percent of those infected. There is no antiviral therapy. Antibiotics should be prescribed only for secondary skin infections.


The vaccine for smallpox is nearly 100 percent effective and offers protection for approximately 10 years. If a person has not been vaccinated, vaccination within four days after exposure to smallpox offers some protection against getting the disease and affords significant protection against a fatal outcome.


In December 2002, President Bush announced the formation of a national preparedness program to protect Americans against the use of smallpox as a biological weapon. Part of the plan was to immunize 500,000 civilian hospital-based healthcare workers and emergency first responders, who would then be capable of treating and caring for suspected cases of smallpox without risk of infecting themselves. The hospital-based healthcare teams were to include:


  • Physicians  
  • Nurses who work in emergency rooms, intensive care units, and general medical units with airborne infection isolation rooms  
  • Primary-care house staff  
  • Infectious control professionals  
  • Respiratory therapists  
  • Radiology technicians  
  • Security personnel 
  • Housekeeping staff


The smallpox vaccination program was controversial, and fewer than 40,000 civilian health care and public health workers voluntarily chose to become immunized because of concerns over severe adverse reactions and patient safety issues. One of the concerns was about reports of adverse cardiovascular effects (myocarditis, pericarditis, myocardial infarction, angina) among recipients of the vaccine, including at least two fatalities. These reports led to revised recommendations for vaccine recipients, and in March 2003, the CDC and the U.S. Public Health Service Advisory Committee on Immunization Practices (ACIP) advised that all people with clinician-diagnosed cardiac disease (with or without symptoms) be excluded from the smallpox vaccination programs. This includes people with a history of cardiomyopathy, myocardial infarction, angina, congestive heart failure, or other evidence of coronary artery disease. The CDC and ACIP further suggested that anyone with three or more of the following risk factors for heart disease be excluded from smallpox vaccination:


  • Hypertension  
  • Diabetes mellitus 
  • Hypercholesterolemia  
  • Current smoker  
  • A family history of a mother, father, brother, or sister who had a heart condition before age 50 

Other contraindications for immunization applied to both the person receiving the vaccine and to his or her family members. People should not be vaccinated if they or a member of their family have any of the following conditions:


  • Eczema or atopic dermatitis  
  • Diseases, conditions, or treatments that cause immunodeficiency or immunosuppression  
  • Pregnancy


Patient safety was also a concern for health care workers. The vaccine is a live virus and the person who is vaccinated will shed the vaccinia virus for seven to 10 days. Many health care workers feared, that if vaccinated, they might inadvertently spread the virus to their patients, especially those who are elderly, immunocompromised, or have skin conditions such as eczema.


Our country is vulnerable to a bioterrorist attack with anthrax and with smallpox. An outbreak of disease caused by either agent would cause a widespread public health catastrophe. A single case of smallpox because of its communicability could lead to 10 to 20 other cases. Given that patients with the disease require isolation in a negative-pressure room, an outbreak from an aerosolized attack could easily use up the limited isolation resources of our entire medical system.


With anthrax, the current recommendation for exposed patients is 60 days of antibiotic treatment. The logistics needed to supply the enormous amounts of antibiotics needed post-exposure after an aerosolized attack could be overwhelming. Vaccines have been developed for both agents, and in the case of smallpox, vaccination has been around for centuries. However, the government has not yet made a decision on whether to offer either vaccine to the civilian population.


No single hospital or community could respond to a large-scale public health emergency without outside help. In the U.S., such help is available from the Strategic National Stockpile. The SNS is a national repository of antibiotics, chemical antidotes, antitoxins, life-support medications, IV administration, airway maintenance supplies, and medical/surgical items. First-response packages (12-hour push packages) from the SNS can be delivered anywhere in the country in 12 hours. The push packs contain antibiotics and other medical supplies to treat a wide range of biological and chemical agents.


SMALLPOXCDC photo of a young victim of a past smallpox outbreak.








Botulism  botulism


Botulinum toxin is the most toxic substance known to science. It would take only one aerosolized gram of evenly dispersed, a crystalline toxin to kill more than 1 million people.  In addition to aerosolization, the toxin can also be used to contaminate food or drink.


Clostridium botulinum is a strictly anaerobic, spore-forming, gram-positive, rod-shaped bacteria that can be found in the soil and in water sediments (both fresh and salt) throughout the world. These bacteria produce a toxin that causes a paralytic disease through three natural forms of contact. This includes foodborne, wound, and a special form of intestinal botulism. A fourth, unnatural form of contact is through inhalation of man-made aerosol. Person-to-person transmission of botulism does not occur.


Since 1973, there have been about 100-150 cases of botulism reported each year to the CDC.  Twenty-five percent are foodborne botulism, 70 percent are infant intestinal botulism, and the rest are wound botulism. Seven immunologically distinct forms of neurotoxin (Types A-G) have been identified. Types A and B and E are the most common types responsible for human disease. In foodborne botulism, the severity of the disease is associated with the toxin type. Type A toxin produces a more severe illness than type B toxin, which, in turn, is more severe than type E toxin. The case-fatality rate for type A botulism is twice that of type B. Type C and D toxins occur primarily in birds and mammals.



Inhalation Botulism


The onset of symptoms in inhalation botulism depends on the dose and may vary from 24-36 hours to several days after exposure. Once the toxin is inhaled, it enters the bloodstream and attaches to receptors on the surface of nerve cells. There it blocks the release of chemicals necessary for signal transmission. Patients present with flu-like symptoms (without fever) that steadily increase in severity over 24 to 48 hours to include dizziness, double vision, drooping eyelids, slurred speech, uncontrolled drooling, and nasal drips, inability to swallow, severe muscle weakness, and descending flaccid paralysis.  Progression can be rapid, with complete respiratory failure and death in as little as 24 hours. The mortality for inhalation botulism is not known.




Foodborne/Water Contamination Botulism


Foodborne botulism is caused by eating a preformed toxin produced by C. botulinum in foods that have not been canned or preserved properly. Ninety-four percent of cases occur after eating home-canned vegetables such as asparagus, green beans, and peppers when spores have survived an inadequate cooking and canning process. In the last few decades, other foods have been recognized as possible vehicles for foodborne botulism, including cheese sauce, homemade salsa, and baked potatoes sealed in aluminum foil. Symptoms of foodborne botulism can occur from two hours to eight days after the ingestion of the toxin.  With supportive care, including ventilator assistance, fatalities are less than 5 percent in food-related botulism.




Wound Botulism


In recent years there has been an increase in wound botulism cases in the United States, with most occurring among illegal drug users in California who inject heroin.  Wound botulism occurs when the spores of C.botulinum are inoculated into the subcutaneous tissue and germinate in the wound to produce botulinum toxin. The use of black tar heroin injected subcutaneously (skin-popping) has been associated with an increase in cases.  Wound botulism in California is thought to be related to the availability of cheap black tar heroin grown in Mexico and processed in factories close to the border.  This heroin is believed to be high in impurities.




Intestinal Botulism/Infant Botulism


C. botulinum spores can enter and colonize the gastrointestinal tract of infants, causing infant botulism. This disease most often occurs in those aged 1 week to 11 months (peak susceptibility 2-4 months). The source is unknown in 85 percent of cases; in 15 percent of cases, honey used to sweeten formula is felt to be the cause. Approximately 60 cases of infant botulism are reported each year, with over half of these cases coming from California, for unknown reasons.


Although it is rare, adults who have abdominal surgery that disrupts the natural gastrointestinal flora can contract intestinal botulism.






Treatment for botulism is supportive care and administration of botulinum antitoxin. The antitoxin consists of antibodies for toxin types A, B, and E. As soon as the diagnosis of botulism is made in adult patients (even before laboratory confirmation), the CDC recommends administration of 1 vial of antitoxin to neutralize serum toxin concentrations.  Note that there can be side effects to the antitoxin. Adverse reactions include serum sickness (3.6 percent), hives (2.6 percent), and anaphylaxis (1.9 percent).  The antitoxin is available from the CDC via state and local health departments. No post-exposure prophylaxis is available.


During recovery, botulism patients require ventilatory support and intensive and prolonged nursing care that can continue for several weeks or even months.


Despite the extreme toxicity of botulism, it is of interest to note that purified botulinum toxin is the first bacterial toxin to be licensed as a treatment for problems such as cervical torticollis (stiff neck). It is also used for conditions that include migraine headaches and removing facial wrinkles.




Plague  plauge


Plague, like smallpox, has been one of the most dreaded diseases throughout history. The first plague pandemic in 541 A.D. spread from Egypt to other parts of the world and killed 50-60 percent of the world population.


The second pandemic (1345-1350), described as the Black Death or the Great Pestilence, followed the trade routes from central Asia to Europe, where it became one of the greatest natural disasters in European history. Within two years more than one-third of the population of Europe had died. This pandemic continued for another 130 years.


The third pandemic started in China in 1855, spread throughout the world, and reached San Francisco’s Chinatown in 1900, where it killed 118 people.  As a result of this outbreak and one other U.S. outbreak in 1907, plague became endemic in rodents in the western and southwestern States. Between 1947 and 1996, 84 percent of the reported plague cases in the U.S. were bubonic, 13 percent septicemic, and 2 percent pneumonic.


Plague, the disease caused by the gram-negative bacillus Yersinia pestis, exists in three forms, bubonic, septicemic, and pneumonic. In nature, a plague is a zoonotic disease, with rodents acting as the primary reservoir. Infected humans usually acquire the disease two to eight days after being bitten by a flea (Xenopsylla cheopis) that has taken a blood meal from an infected rodent. After a bite, most people develop the bubonic form of the disease with symptoms of fever, chills, weakness, and the development of an enlarged, painful, swollen lymph node called a bubo in the groin, axilla, or cervical region. Buboes are 1 to 10 cm in diameter with the surrounding area being red-colored and edematous. Sepsis with shock and death can occur two to four days later if the infection is untreated, although 30-50 percent of people with bubonic plague do survive without treatment.  Ten to 12 percent of patients with bubonic plague develop secondary pneumonic plague, and a minority of infected patients develop the septicemic form of disease without a bubo. Bubonic and septicemic plague is not transmitted person-to-person.  The pneumonic form is transmitted person-to-person via droplets.


A bioterrorism-related outbreak of plague is expected to be from aerosolized bacteria, causing the pneumonic form. Two or three days after exposure, patients will present at the emergency department with severe respiratory symptoms including high fever, chills, headache, breathing difficulties, chest pain, cough with production of bloody sputum, and clinical sepsis. Chest X-rays show patchy or consolidated bronchopneumonia. Pneumonic plague victims will not present with buboes. A presumptive diagnosis can be made by the identification of a gram-negative coccobacillus with safety-pin bipolar staining. If treatment is delayed more than 24 hours after the beginning of symptoms, the fatality rate with pneumonic plague is nearly 100 percent.  It is important to note, that in contrast to anthrax, pneumonic plague can lead to secondary cases. Droplet precautions should always be observed when caring for patients with the pneumonic form.


Strict isolation precautions should be taken with the bodies of plague victims. People performing post-mortem procedures that generate aerosols should use a high-efficiency air-filtered mask, and the procedure should take place in a negative pressure room.




Tularemia  tularemia


Tularemia (rabbit fever) is a zoonosis caused by Francisella tularensis. The disease primarily infects wild animals. Humans usually acquire the infection after getting a bite from an infected deerfly, mosquito, or tick or through contact with blood or tissue of infected animals, typically rabbits. One can also become infected through drinking contaminated water, inhaling dust from contaminated soil, or eating inadequately cooked rabbit meat. Most cases of tularemia occur among hunters and other outdoorsmen in rural areas of the south-central and western states (especially Arkansas, Illinois, Missouri, Texas, Oklahoma, South Dakota, Utah, Virginia, and Tennessee). Person-to-person transmission is not known to occur.  During the years 1990 to 2000, a total of 1,368 cases of tularemia were reported to the CDC.


Francisella tularensis, a gram-negative coccobacillus, is one of the most infectious pathogenic bacteria known. Inhaling as few as 10 organisms can cause disease. In fact, the organism is so infective that a lab worker examining an open culture plate can become infected. The organism can survive for weeks at low temperatures in water, moist soil, or animal carcasses. In 1970, the World Health Organization (WHO) reported that 100 pounds of F. tularensis dispersed as an aerosol over a 5 million-person metropolitan area would be expected to cause 250,000 incapacitating casualties, including 19,000 deaths.


After exposure from an infected insect bite, a person usually experiences symptoms of tularemia including fever, chills, headache, body aches, weakness, and fatigue in two to 10 days.  An ulcer, which can last for months, forms at the site of the bite. The infection from the bite wound spreads to regional lymph nodes that enlarge and become necrotic. Once the organism gets into the bloodstream, it can spread the infection throughout the body. In untreated tularemia, the symptoms usually last one to four weeks but can continue for a number of months.


An aerosolized bioterrorism attack would most likely result in tularemic pneumonia with patients presenting with a non-productive cough, shortness of breath, and pleuritic chest pain. Chest X-rays show bilateral patchy infiltrates and scattered cavitary lesions.


There are no known cases of person-to-person transmission of tularemia. The only danger is for laboratory workers. A biological safety cabinet (biological safety level 2 conditions) should be used for all routine examination of cultures in which F. tularensis is suspected.




Viral Hemorrhagic Diseases


Four viral hemorrhagic diseases (VHF) are considered to be potential bioterrorism agents:


  • Ebola virus from the Filovirus family 
  • Marburg virus from the Filovirus family  
  • Lassa (West Africa)  
  • South American hemorrhagic fever viruses from the Arenavirus family.


The South American HFV viruses include the Junin virus (Argentina), the Machupo virus (Bolivia), the Guanarito virus (Venezuela), and the Sabia virus.


The hemorrhagic diseases are RNA viruses (ribonucleic acid) thought to be transmitted to humans from contact with infected animals or arthropod vectors. Each disease is strongly associated with a distinct geographic area of the world and none are presently endemic to the United States.


All VHF viruses can be transmitted person-to-person through unprotected contact with blood, body secretions, and excretions, semen, and tissue specimens from infected patients.


The natural reservoir of both the Ebola virus and the Marburg virus is unknown but is thought to be zoonotic.


The Arenaviruses Junin, Machupo, Guanarito, Sabia, and Lassa viruses are known to be zoonotic diseases. Human infections occur when an individual comes into direct contact with the urine or droppings of the infected rodent host. Infection can also occur by ingesting food or inhaling dust contaminated with rodent excreta. These viruses can be spread from person-to-person by contact with the infected person’s blood or body fluids or by contact with medical equipment contaminated with the viruses. Airborne transmission has also been reported with certain viruses.


When taking care of a patient with viral hemorrhagic fever, the following personal protective equipment (PPE) should be used when entering the patient’s room:


  • Disposable, fluid-resistant N-95 respirator (mask) or powered air-purifying respirators.
  • Disposable face shield, in addition to the N-95 respirator.
  • Disposable, long sleeve, fluid-proof gown or coveralls with a rib or elastic cuffs.
  • Gloves. Gloves should completely cover the cuff of the gown or coverall. For procedures such as phlebotomy, double gloves or reinforced gloves should be worn.
  • Leg, shoe, and head covers should be worn when blood or body fluids soil the floor or when splashing of blood or body fluids might occur.
  • Environmental disinfection with hospital disinfectant or with a dilution of bleach.


Because airborne transmission may occur with the Ebola, Marburg, and Lassa fever viruses, a patient with VHF should be placed in a private room that has monitored negative air pressure in relation to the exterior surrounding areas. The windows and doors to the rooms should remain closed.


During natural outbreaks of VHF in Africa and South America, the use of personal protective equipment, disinfection procedures, and isolation of patients have been sufficient to prevent nosocomial transmission of the viruses.




Public Health Impact


Plague is considered the third most likely pathogen, after anthrax and smallpox, to be used in a bioterrorism attack. Without timely treatment, the pneumonic form of the disease is 100 percent lethal. Tularemia also has a 30 percent to 60 percent fatality rate if untreated. However, effective treatment and post-exposure prophylaxis for both plague and tularemia are available.


The United States has a limited supply of ventilators and intensive care beds. If the botulinum toxin is used in an attack, the number of patients requiring treatment on a ventilator in an intensive care unit would rapidly overwhelm the system. Fortunately, this toxin is not considered an effective biowarfare agent, because of its instability in the environment.


Viral hemorrhagic diseases are highly lethal and require care in an intensive care unit. No prophylaxis or effective treatment is available. Like anthrax, smallpox, and botulism, an attack disseminating these organisms over a large population center would overwhelm the medical system.






For many years, there has been a growing concern that a terrorist group might choose to use a biological weapon on a civilian population. But until the events of September and October 2001, when letters filled with anthrax spores were sent through the postal system, most people believed it would never happen in the United States. Now, we can no longer ignore the possibility of future attacks. Nurses, along with other health care providers, will be the first to see the victims of biological warfare. For this reason, it is critical that they be well-informed about the infectious agents most likely to be used in an attack in order to take the best care of their patients and themselves.