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

2. 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

4. 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”

5. 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

6. 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the Biological Weapons Convention Former Soviet Union program began massive effort in 1970s Today, term “warfare” is outdated…terrorism of civilian populations major risk: Anthrax in 12 persons 2001

7. 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

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

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

10. 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

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

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

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

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

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

17. 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

19. 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

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

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

22. 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

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

26. 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)

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

28. 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

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

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

32. Anthrax (cont.) Weaponized by the U.S. in 1950s and 60s Major emphasis of USSR program Can be delivered as aerosol

35. Incubation-Days 0-6 7-13 14-20 21-27 28-44 Cases* 6 28 9 6 11 Died 6 25 7 6 5 Days to Death 4.5 2.5 3.0 4.5 3.5 * 15 additional cases without an exact date of onset; all died. Inhalational Anthrax Sverdlovsk, USSR, 1979

38. 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

39. 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

40. Smallpox An even worse scenario

41. 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

42. 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

43. 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

49. JanuaryFebruary 43214321 Cases 13 15 17 19 21 23 25 27 29 31 2 4 6 8 10 12 14 16 18 Hospital Stay Case 1 Date of Onset of Smallpox Cases by Two-Day Intervals Meschede Hospital, 1970

51. Plague Not as likely but of concern

56. Botulism

60. 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

61. 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

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

63. 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

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

65. 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

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

67. Planning Responses to Biological Terrorism Are we ready? Should we get ready? Is it possible to be effectively prepared?

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

69. World Trade Center

70. New York City