BIOLOGICAL TERRORISM Edward L. Goodman, MD, Chief of Infectious Diseases Presbyterian Hospital of Dallas December 14, 2005

Biological Terrorism  Use of biological agents to intentionally produce disease or intoxication in susceptible populations to meet terrorist aims  Has been done in the past on a limited scale  U.S. must be prepared to respond to this threat

History of Biological Warfare  In 1346, Tartar army hurled corpses of plague victims over the walls of Caffa, a seaport on the Crimean coast  In 1718, Russians used same tactic against Sweden  During the Pontiac Rebellion in 1763, the British army provided the Delaware Indians with blankets and handkerchiefs from the “Smallpox Hospital”

History of Biological Warfare

(cont.)

 German program in WWI  Japanese program in WWII  In 1943, the U.S. began research into the offensive use of biological agents: Program stopped by President Nixon in 1969

History of Biological Warfare 

(cont.)

In 1972, U.S. and many other countries signed the Biological Weapons Convention   Former Soviet Union program began massive effort in 1970s Today, term “warfare” is outdated…terrorism of civilian populations major risk: Anthrax in 12 persons 2001

Why There

was

a Belief Bioterrorism in the U.S. Would Not Happen  Biologic weapons seldom used  Their use is morally repugnant to most  Technologically difficult?

 Concept of “nuclear winter” was “unthinkable” and thus dismissed until suicide hijackers and anthrax appeared

The “Coming of Age” and Bioterrorism  Perpetrators  Availability of biological agents  Methods of dissemination

The Spectrum of Terrorists  State-sponsored  Insurgent/rebel  Doomsday/cult-type group  Non-aligned terrorists  Splinter groups  Lone offenders

Sources of Agents for Terrorism Use  World Directory of Collections of Cultures and Microorganisms  453 worldwide repositories in 67 nations  54 ship/sell anthrax  18 ship/sell plague  International black-market sales associated with governmental programs

Methods of Dissemination of Biologic Agents    Postal service: never previously reported Aerosol  Enclosed areas  Community-wide Ingestion   Mass produced food Water supplies

“You have to be lucky all the time. We have to be lucky just once!” – Irish Republican Army

“The only difference between reality and fiction is that fiction has to make sense.” – Tom Clancy

Syndromes Suggesting BT  Encephalitis  Hemorrhagic mediastinitis  Pneumonia with abnormal liver function  Papulopustular rash  Hemorrhagic fever  Descending paralysis  Nausea, vomiting +/- diarrhea

Biological Terrorism: Likely Agents  Bacterial:  Viral:  Toxin: Anthrax Q fever Brucellosis Tularemia Plague Smallpox Viral encephalitides Viral hemorrhagic fever Botulism Ricin Staph, Enterotoxin B

Ideal Characteristics for Potential Biological Terrorism Agent  Inexpensive and easy to produce  Can be aerosolized (1 10µm)  Survives sunlight, drying, heat  Cause lethal or disabling disease  Person-to-person transmission  No effective treatment or prophylaxis

Anthrax  Caused by Bacillus anthracis, a rod shaped, sporulating organism  Is a zoonotic disease in cattle, sheep, and horses  Transmission through scratches or abrasions of skin, wounds, eating insufficiently cooked infected meat, or inhalation of spores

Pathophysiology of Anthrax Dixon, T. C. et al. N Engl J Med 1999;341:815-826

Cutaneous Anthrax Infection of the Hand and Cheek Dixon, T. C. et al. N Engl J Med 1999;341:815-826

Anthrax

(cont.)

  Case fatality in untreated inhalational disease is almost 100%  In recent 2001 occurrence, “only” 3/6 died Incubation 1 – 45 days, most within 21 days  Initial flu-like symptoms are often followed by abrupt development of severe respiratory distress, shock, and death within 24 hours

Anteroposterior Chest Radiograph Obtained on Admission, Showing the Widened Mediastinum That Is Characteristic of Anthrax Bush, L. M. et al. N Engl J Med 2001;345:1607-1610

Cerebrospinal Fluid Specimen Containing Many Polymorphonuclear White Cells and Gram Positive Bacilli (Gram's Stain, x1000) Bush, L. M. et al. N Engl J Med 2001;345:1607-1610

Differential Diagnosis of Clinical Manifestations of Anthrax Dixon, T. C. et al. N Engl J Med 1999;341:815-826

Anthrax

(cont.)

 Medical management must be reserved for those with early symptoms or no symptoms  Use of antibiotics for treatment (penicillin, ciprofloxacin, or IV doxycycline) and prophylaxis and vaccination  No secondary transmission

Recommendations for Postexposure Prophylaxis Swartz, M. N. N Engl J Med 2001;345:1621-1626

Recommendations for Antimicrobial Therapy of Clinical Inhalational Anthrax Swartz, M. N. N Engl J Med 2001;345:1621-1626

Anthrax

(cont.)

 Weaponized by the U.S. in 1950s and 60s  Major emphasis of USSR program  Can be delivered as aerosol

Inhalational Anthrax Sverdlovsk, USSR, 1979

Incubation-Days Cases* Died Days to Death 0-6 7-13 14-20 21-27 28-44 6 28 9 6 11 6 25 7 6 5 4.5

2.5

3.0

4.5

3.5

* 15 additional cases without an exact date of onset; all died.

Shopping Mall Scenario - Denver  Anthrax aerosolized into shopping mall ventilation system; 10,000 people are present and 9,000 people are exposed; terrorist announces attack at 24 hours.

 90% of exposed started on antibiotics by end of day 2, 10% cannot be found initially  Total number hospitalized: 4,950; total requiring ICU care: 2,925; total deaths: 855; total ventilators required: 2601

Shopping Mall Scenario – Denver

(cont.)

 The 13,000 military beds deployed for the Persian Gulf War would STILL not provide enough ICU beds (approximately 1,300)  Even a small biological terrorism event completely overwhelms a city’s medical care resources

Smallpox An even worse scenario

Smallpox  Killed more than 500 million persons in the 20th century despite being eradicated in 1978  Mortality of 30% in susceptible population  Incubation period of 8 to 16 days

Smallpox

(cont.)

 Clinical manifestations begin acutely with fever, rigors, vomiting, headache and backache  Approximately 10% of light-skinned patients exhibit erythematous rash during early phase  Two to three days later, an enanthem appears on face, hands, and forearms

Smallpox

(cont.)

 Transmission begins with rash and lasts throughout convalescence  Ongoing transmission is critical factor  Most in the world are no longer protected by vaccination  Currently vaccine and treatment limited

Date of Onset of Smallpox Cases by Two-Day Intervals Meschede Hospital, 1970 4 3 2 1 Hospital Stay Case 1

13 15 17 19 21 23 25 27 29 31 2 4 6 8 10 12 14 16 18

January February

Plague Not as likely but of concern

Botulism

Challenges in Recognizing a Bioterrorism Attack  Biologic agents with delayed onset  Medical community is unfamiliar with many of these diseases  Current surveillance system may not be adequate to detect attack

Epidemiological Clues to BT Event  Uncommon illness in epidemic form  Explosive point source epidemic curve  Unexplained high mortality  Discordant attack rate: outdoor>indoor  Sentinel illness – even one case of anthrax or smallpox

Syndromes Suggesting BT  Encephalitis  Hemorrhagic mediastinitis  Pneumonia with abnormal liver function  Papulopustular rash  Hemorrhagic fever  Descending paralysis  Nausea, vomiting +/- diarrhea

Ten Commandments Summary 1.

Index of Suspicion 2.Protect Thyself and Thy Patients 3.Assess the Patient 4.Decontaminate 5.Diagnosis

6.Treatment

7.Infection Control 8.Alert 9.Epidemiologic Assessment 10.

Spread the Gospel

Response Planning  Federal government  State and local government  Healthcare systems  Media  Infrastructure support

Impact on Healthcare System  Potential for widespread illness, in unprecedented numbers  Limited therapeutic stockpiles  Need special protective measures for medical care, clinical lab, and autopsy  Panic/terror among the ill, the exposed, and healthcare providers

Other Critical Issues  Legal aspects  Criminal investigation  Controlling civil disorder  Quarantine  Continued public health activities

Planning Responses to Biological Terrorism  Are we ready?

 Should we get ready?

 Is it possible to be effectively prepared?

It’s not a matter of “if,” but when, which agent, and how bad it will be!

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