Lecture Notes: Bioterrorism
Last revised: Monday, November 19, 2001           Copyright 2001. Thomas M. Terry
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How likely is it that we will see more attacks with biological weapons?

Possible biological agents that bioterrorists might use

Select Agents: Criteria for inclusion:

Bacteria or bacterial toxins

Anthrax

  • Caused by Bacillus anthracis, gram+ bacterium, endospore former. See gram stain.
  • B. anthracis normally found in lower vertebrates, including cattle, camels, goats, sheep, other herbivores. Can infect humans.
  • What are endospores? Almost all bacteria become dormant when starved, start to grow again very quickly once nutrients are available. Can survive dehydration (like freeze-dried coffee), return to life when water is available.
    Some bacteria, including anthrax bacteria, have specialized dormancy structure, the endospore. Endospores can survive boiling for up to several hours, can be revived after decades of dormancy. One recent report suggests that dormant endospores were revived from insect gut trapped in million year old amber. Endospores are durable, hardy, and highly resistant to heat, drying, etc.
  • Disease symptoms: 3 types
    1. Cutaneous: 95% of anthrax infections are due to entry or bacteria through cut or other abrasion in skin. After a few deays, leads to painful swelling with black center filled with dead tissue. If untreated, 1 in 5 cases are fatal. See picture of necrotic anthrax infection.
    2. Inhalation: when substantial numbers of endospores (8000 or more) are inhaled in an aerosol, can infect lung. Early symptoms of inhalational anthrax mimic flu and include malaise, fever, cough and chest discomfort. Virulence factors include "lethal toxin", attacks many cells in body, produces serious breathing problems, shock. After a brief period of recovery, patients with inhalation anthrax will develop severe respiratory distress. Inhalational anthrax is usually fatal, even with aggressive antimicrobial therapy. An accidental release in 1979 from a military biologic facility in the city of Sverdlovsk in the former Soviet Union caused many infections, and about 80% mortality of infected civilian victims downwind from the facility. Ref: Meselson M, Guillemin J, Hugh-Jones M, et al. The Sverdlovsk anthrax outbreak of 1979. (1994) Science 266:1202-8.
    3. Intestinal: eating contaminated meat can cause acute inflammation of intestinal tract, nausea, vomiting (including vomiting blood), severe diarrhea. If untreated, 50% or more cases are fatal.
  • View chart showing how anthrax can infect body
  • Anthrax was developed as potential weapon by scientists in Soviet Union. Iraq, Russia and as many as ten nations have the capability to load anthrax spores into weapons. Several other countries are known to be developing biologic weapons programs.
  • Since anthrax is readily available and can be easily and cheaply manufactured and weaponized, it has great appeal to terrorists.
  • It is estimated that an attack on a major US city could cost up to $26.2 billion per 100,000 victims to mitigate.
  • Vaccine has been developed, but not fully tested or used. U.S. tried to vaccinate soldiers during Gulf War, but many refused.
  • Inhalation anthrax is extremely rare under normal circumstances. You need to be exposed to a lot of endospores in a very finely dispersed state. Amateur microbiologists could grow anthrax bacilli and produce endospores, but they would be clumped, not a fine powder, and would not easily be infectious. The recent anthrax mailings contained very finely dispersed endospores, most likely produced using techniques developed by military bioweapons manufacture (the process is called "weaponizing"). Where did they come from? $64,000 question!
  • How do you detect anthrax? Current procedures used federal government are as follows:
    1. Tier 1 - An ImmunoAssay Screen is conducted which checks for the presence of generic Bacillus species, which is an extremely common type of bacteria that does not itself indicate the presence of the anthrax bacillus. These results are either negative, indicating that there are no Bacillus spp. (including Anthrax) present, and no further testing is conducted, OR the result is "not negative" and requires further testing.
    2. Tier 2 - A "PCR" test is conducted to look for three DNA markers specific to Anthrax. If all three Anthrax DNA markers are found, the test is positive for Anthrax. If one or two of the markers are found, the test is "not negative" and would proceed to the next tier.
    3. Tier 3 - The samples are cultured. Culturing normally takes 48 hours; however, if the samples are dilute, they will have to try to enhance growth until an identifiable colony of bacteria is grown. Dilute samples can take anywhere from four to seven days to grow an identifiable colony.
  • For further reading visit CDC fact sheet on Anthrax

Botulin Toxin

  • Botulin toxin, a neurotoxin (attacks nervous system).
  • Derived from Clostridium botulinum, anerobic soil bacterium, endospore former.
  • Botulism is a fairly rare disease. Most cases result from improper home canning. When botulin endospores are present, they may withstand boiling. Once food is sealed, spores can germinate in anaerobic environment. Bacteria produce gas leading to bulged cans, a telltale giveaway
  • Bacteria produce a protein, botulin toxin= most potent toxin known. 1 gram could theoretically kill 10million people.
  • Toxin interferes with synaptic transmission at nerve-muscle junctions flaccid paralysis.
  • View movie showing botulin toxin activity (requires free Shockwave plug-in)
  • Could bioterrorists exploit the botulin toxin? It is heat sensitive, like most proteins, so it is unclear how long it would remain active if added to water system, the most likely scenario for attempting mass murder. Once people were alerted, boiling water would inactivate the toxin.
  • See CDC fact sheet on botulism

Bubonic Plague

  • 1894, French scientist Yersin discovered cause = bacterium Yersinia pestis. Normally found in rodents, transmitted by fleas.
  • Bacterium binds to macrophages, uses Type III secretory system to inject toxic molecules (YOPs = Yersinia Outer Proteins) into cell. Macrophages die in great numbers.
  • View animation of Y. pestis infecting a macrophage (by Tom Terry)
  • Name comes from large, painful swellings ("buboes") in lymph nodes of neck, groin, or armpit. 3 days later, high fever, delirious, black splotches due to hemorrhaging under skin. Often buboes would burst, agonizing frenzy for victims.
  • 1346-1352: "The Great Pestilence", killed one out four people in Europe, N. Africa & Middle East. 70-80% of those who got it died within 5 days.

  • Fleas that ingest bacteria get bacterial growth in gut, blocks food flow. Fleas become ravenously hungry, go on feeding frenzy, repeatedly biting victim, spreading disease. When too few rodents to infect, will spread to other warm-blooded hosts (e.g. humans).
  • If humans have lung infections, can spread person-to-person by droplets, extremely rapid spread possible. Otherwise only by flea bites.
  • Note: plague still around, occurs regularly in Africa, S. America, and SW U.S. (10 cases reported in 1986).

    But never likely to approach epidemic status since we know how it spreads, how to treat cases as they occur. Bacteria can be killed by antibiotics if treatement is started in time.
  • How could terrorists use plague? Probably as an aerosol.
    • Military biological weapons programs of U.S. and U.S.S.R. developed capacity to transmit by aerosols. Bacteria would remain viable as aerosol for 1 hour
    • If 50 kg (110 lbs) of Y. pestis were released as an aerosol over a city of 5 million, pneumonic plague could occur in as many as 150,000 persons. 36,000 would be expected to die.
    • Sudden appearance of a large number of previously healthy people 1-6 days after exposure, with fever, cough, shortness of breath, chest pain, and a fulminant course leading to death should immediately suggest the possibility of pneumonic plague or inhalational anthrax.
    • The presence of hemoptysis, the coughing up of blood, in this setting would strongly suggest plague.
  • Prevention and treatment
    • Disease can be controlled by antibiotics, but only if correctly administered prophylactically or at first appearance of symptoms.
    • Vaccine production was discontinued in 1999, no longer available. Was effective against bubonic, but ineffective against pneumonic plague.
  • Visit "Plague and Public Health in Renaissance Europe", including narrative accounts of the great plague epidemic of 1348 in several European cities.
  • See CDC fact sheet on Plague

Tularemia

  • Tularemia (also known as rabbit fever or deerfly fever) is an infectious disease in ticks and rabbits caused by the bacterium Francisella tularensis.
  • Name comes from description in 1911 of a plague-like illness in ground squirrels in Tulare county, California.
  • Francisella tularensis is found worldwide in over a hundred species of wild animals, birds and insects. Disease in humans is relatively uncommon: about 150-300 cases annually in U. S., mostly from tick bites.

  • Humans normally contact tularemia from bite of infected vector (mosquito, tick, deerfly), or when broken skin comes in contact with infected animal carcass (e.g. rabbit). See image showing sore caused by tularemia.
  • Terrorists might try to spread Francisella tularensis through drinking water or aerosol. As few as 5-10 bacteria can result in disease. Human-to-human transmission of tularemia is uncommon.
  • Clinical symptoms depend on route of infection. Inhalation of bacteria, though rare in the normal worl, can produce sudden chills, fever, weight loss, abdominal pains, tiredness, and headaches. Patients with this form of tularemia may develop an unusual pneumonia that can be fatal.
  • Tularemia can be successfully treated with antibiotics such as streptomycin, gentamicin, and tobramycin. Diagnosis is difficult, because symptoms are common to many diseases.
  • See CDC fact sheet on Tularemia

Rickettsia

  • The rickettsia are obligate intracellular parasites. They are considered a separate group of bacteria because they have the common feature of being spread by arthropod vectors (lice, fleas, mites and ticks).They cause some very serious diseases such as typhus fever.
  • View Rickettsia growing inside human cells.
  • Symptoms are variable, but often come on suddenly as headache, chills, fever, prostration, and general pains; macular eruption on the 5 and 6th day on upper trunk and spreading to entire body; pronounced toxemia.
  • Disease terminates approximately 2 weeks after onset of fever; case fatality rate from 10-40% in absence of treatment
  • Rickettsial diseases are more challenging to treat than many other diseases. The drugs of choice for treatment of rickettsial diseases are chloramphenicol and tetracycline. Each of these is highly toxic, especially in children, and must be used with care.

Viruses

Smallpox (Variola) Virus

  • Infectious agent is Variola major virus. Highly infectious -- only 10-100 particles can cause infection.

  • The infectiousness of the virus was seen in 1970, when a German electrician returned from Pakistan, having contracted the virus. He was hospitalised, and though he never left his room, he infected 4 patients on the floor he was staying, 8 on the floor above, and 9 two floors above. One person infected was simply a visitor to the hospital, and was never closer than 30 feet to the patients room
  • Virus has been officially eradicated as a result of successful worldwide vaccination and quarantine measures -- last known case occurred in 1970's, except for an infected lab worker since. However, known stocks survive in Center for Disease Control and Prevention (CDC) in Atlanta, US, and in the Research Institute for Viral Preparation in Moscow, Russia. Possible that other stockpiles exist.
  • Variola is highly infectious as aerosol. Incubation period is 7-17 days, during which virus multiplies in respiratory tract, then spreads to blood and lymph. Causes characteristic inflammations over surface of skin (pox).
     

    Other symptoms include high fever, vomiting, headache, general malaise, and abdominal and back pain. 15% of patients develop delirium, and the disease has a 30% mortality rate in unvaccinated.

Ebola and other hemorrhagic fever viruses

  • Among the most newsworthy viruses are those that cause rupture of capillaries, internal bleeding = "Hemorrhagic Fever" viruses: Ebola, Lassa fever virus, Marburg virus, South American Haemorrhagic fever viruses, etc.
  • Ebola virus named for river in Democratic Republic of the Congo (formerly Zaire) where outbreak was first recognized.
      

  • Symptoms of infection begin with fever, headache, diarrhea, stomach pains -- symptoms that could be due to many infections. Within a week, most victims also develop chest pain. Some some go blind, bleed from the nose, eyes, and other orifices. Bleeding results from the virus blocking blood clotting as well as stimulating leakage of blood vessels. Disease is very lethal: 70-90% of infected people die
  • Even though this is a scary disease, it seems highly unlikely it would be a potential terrorist weapon. The virus is so lethal that it is classified as a type IV agent, and requires maximum protective features (sealed body suits, totally contained laboratory environments) to protect those studying it. Other agents are much easier to grow and safer for those interacting with them.
  • See CDC fact sheet on viral hemorrhagic fevers
Table showing effectiveness of selected biological agents, from "Need to know Newsletter, Jan. 6, 2000"
AGENT SYMPTOMS INFECTION VACCINE
Tularemia Usually within 3-5 days after exposure, but as long as 2 weeks; ulcers, swollen lymph nodes, fever and pneumonia appear. In its most severe forms, it is fatal in about 35% of untreated cases within days or weeks.
 The military has a vaccine, but treatment with antibiotics can be effective, even when administered after days or weeks.
Smallpox About 12 days after exposure, high fever, fatigue, back aches begin, followed in 2-3 days by a rash and lesions on face, arms and legs. As many as 30% of those infected may die, usually during the first two weeks of illness.
 Routine vaccinations ceased in 1972, but about 15 million does are still available and more are in production.
Plague Symptoms start 1-6 days after exposure, starting with high fever, chills, headache and progressing quickly to severe breathing difficulty, coughing blood.
 Death follows within 2-4 days.
 There is a vaccine for bubonic plague (carried by fleas) but it's not effective against the aerosolized form of the disease. Antibiotic treatment started within 24 hours of symptoms can improve the chance of survival.
Anthrax Begin within 6 days of exposure, with fever, fatigue, cough and chest discomfort at first, followed by severe breathing difficulty, sweating and turning blue.
 Death follows 24-36 hours after severe symptoms begin.

 Vaccines must be given 18 months prior to exposure to be fully effective, though there is evidence of some protection after the first three doses (given over 4 weeks.)
Viral
Hemorrhagic
Fever
 Depending on the virus, (Ebola, Marburg, etc.) symptoms such as high fever, muscle aches, chills and diarrhea begin within a few days, followed by severe chest pain, shock and bleeding.
 These diseases do not always result in death, but Ebola has been up to 90% fatal in some outbreaks, with death occurring a week after infection.
 No vaccines exist for hemorrhagic fevers, except for yellow fever and Argentine hemorrhagic fever.
Botulism
 Symptoms begins 12 -36 hours after eating tainted food, including double or blurred vision, slurred speech, difficulty swelling and progressive weakness that descends the body, starting at the shoulders.
 Victims who ingest small doses may survive, but larger does can cause paralysis of breathing muscles and death within 24 hours unless patient is put on a ventilator.
 The CDC keeps a national supply of anti-toxin, which must be given quickly.

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