DETECTING AND RESPONDING TO A BIOTERRORIST AGENT INFECTING YOUR PATIENT(S) Panel Discussion

1. DETECTING AND RESPONDING TO A BIOTERRORIST AGENT INFECTING YOUR PATIENT(S)Panel Discussion

2. Outline • Brief history of biowarfare • Potential impact and effects of BT • Transmission of BT agents • Clues to BT • “Most likely BW agents” • Rational perspectives • Management • Overview of potential pre-exposure prophylaxis, post-exposure prophylaxis and therapy

3. BIOLOGIC WARFARE: HISTORY • 14TH century, Kaffa: Attacking Tatar force catapulted cadavers of plague victims into city – outbreak of plague led to defeat • 18th century, Fort Pitt, North America: Blankets from smallpox hospital provided to Native Americans – resulted in epidemic of smallpox among tribes in Ohio River valley • 1932-45, Manchuria: Japanese military physicians infected 10,000 prisoners with biological agents (B. anthracis, N. meningitidis, Y. pestis, V. cholerae) – 11 Chinese cities attacked via food/water contamination, spraying via aircraft

4. USE OF BIOLOGICAL AGENTS: US • Site: The Dalles, Oregon, 1984 • Agent: Salmonella typhimurium • Method of transmission: Restaurant salad bars • Number ill: 751 • Responsible party: Members of a religious community had deliberately contaminated the salad bars on multiple occasions (goal to incapacitate voters to prevent them from voting and thus influence the outcome of the election) Torok TJ, et al. JAMA 1997;278:389-395

5. USE OF BIOLOGICAL AGENTS: US • Site: Large medical center, Texas, 1996 • Agent: Shigella dysenteriae • Method of transmission: Ingestion of muffins/doughnuts • Number ill: 12 (27% attack rate) • Responsible party: Disgruntled lab employee? S. dysenteriae identical by PFGE from stock culture stored in laboratory Kolavic S, et al. JAMA 1997;278:396-398.

6. NEXT International Biological Weapons Programs Known Iraq Russia Probable China Iran North Korea Libya Syria Taiwan Possible Cuba Egypt Israel Source: Committee on Armed Services, House of Representatives. Special Inquiry into the Chemical and Biological Threat. Countering the Chemical and Biological Weapons Threat in the Post-Soviet World. Washington, D.C.: U.S. Government Printing Office; 23 Feb 1993. Report to the Congress.

7. BIOTERRORISM: IMPACT • Direct infection: Mortality, morbidity • Indirect infection: Person-to-person transmission, fomite transmission • Environmental impact: Environmental survival, animal infection • Other: Social, political, economic

8. EFFECTS OF A BIOLOGICAL WEAPONS RELEASE Siegrist, Emerging Infectious Diseases 1999

9. BIOLOGICAL WARFARE: IMPACT[release of 50 kg agent by aircraft along a 2 km line upwind of a population center of 500,000 – Christopher et al., JAMA 278;1997:412]

10. TRENDS FAVORING BIOLOGICAL WEAPONS • Biological weapons have an unmatched destructive potential • Technology for dispersing biologic agents is becoming more sophisticated • The lag time between infection and appearance of symptoms generally is longer for biological agents than with chemical exposures • Lethal biological agents can be produced easily and cheaply • Biological agents are easier to produce clandestinely than are either chemical or nuclear weapons

11. TRENDS FAVORING BIOLOGICAL WEAPONS • Global transportation links facilitate the potential for biological terrorist strikes to inflict mass casualties • Urbanization provides terrorists with a wide array of lucrative targets • The Diaspora of Russian scientists has increased the danger that rogue states or terrorist groups will accrue the biological expertise needed to mount catastrophic terrorist attacks • The emergence of global, real-time media coverage increases the likelihood that a major biological incident will induce panic

12. DEVELOPING A RISK ASSESSMENT OF BIOLOGIC WARFARE AGENTS General difficulties in weaponizing a biologic agent • Ability to procure a virulent strain (e.g., anthrax, tularemia) • Ability to culture large amounts of the agent • Ability to process agent into a suitable form (e.g., anthrax spores) • Ability to safely handle and store the agent (may be difficult for hemorrhagic fever viruses)

13. DEVELOPING A RISK ASSESSMENT OF BIOLOGIC WARFARE AGENTS General difficulties in weaponizing a biologic agent • Ability to disseminate the agent as an aerosol • Ability to generate aerosol particles of the proper size (1-10 u) • Ability to assess climatic effects in order to disseminate agent effectively • Different Federal agencies have reached different conclusions regarding the likelihood of an attack using a biologic agent

14. CHARACTERISTICS OF BIOWARFARE • Potential for massive numbers of casualties • Ability to produce lengthy illnesses requiring prolonged and intensive care • Ability of certain agents to spread via contagion • Paucity of adequate detection systems • Diminished role for self-aid and buddy aid, thereby increasing sense of helplessness

15. CHARACTERISTICS OF BIOWARFARE • Presence of an incubation period, enabling victims to disperse widely • Ability to produce non-specific symptoms, complicating diagnosis • Ability to mimic endemic infectious diseases, further complicating diagnosis US Army, Biologic Casualties Handbook, 2001

16. Bioterrorism: Modes of Spread Aerosol Sprays Particle size of agent Stability of agent Wind Speed Wind direction Atmospheric stability Explosives Tend to inactivate biological agents Food and Water Contamination Fairly self-limited

17. Epidemiologic Clues to Bioterrorism • Multiple simultaneous patients with similar clinical syndrome • Severe illness among healthy • Predominantly respiratory symptoms • Unusual (nonendemic) organsims • Unusual antibiotic resistance patterns • Atypical clinical presentation of disease • Unusual patterns of disease such as geographic co-location of victims • Intelligence information • Reports of sick or dead animals or plants

18. NEXT Soviet BW Priorities“Agents Likely to be Used” • Smallpox • Plague • Anthrax • Botulism • VEE • Tularemia • Q Fever • Marburg • Influenza • Melioidosis • Typhus

19. Can be easily disseminated or transmitted person-to-person Cause high mortality, with potential major public health impact Might cause public panic and social disruption Require special action for public health prepardeness Smallpox Anthrax Yersinia pestis Botulism Tularaemia Filoviruses (Ebola and Marburg) Arenaviruses (Lassa and Junin) Category A: Highest Priority

20. Moderately easy to disseminate cause moderate morbidity and low mortality Require specific enhancements of CDC’s diagnostic capacity and enhanced disease surveillance Coxiella burnetti (Q fever) Brucella Burkholderia mallei (glanders) Alphaviruses (Venezuelan encephalomyelitis and Eastern and Western equine) Ricin toxin from Ricinus communis Epsilon toxin of C. perfringes Staph enterotoxin B Salmonella Shigella E. coli O157:H7 Vibrio cholerae Cryptosporidium parvum Category B: Second Highest Priority

21. Pathogens that could be engineered for mass destruction because of availability, ease of production and dissemination and potential for high morbidity and mortality and major health impact Nipah virus Hantavirus Tickborne hemorrhagic fever viruses Tickborne encephalitis viruses Yellow fever MDR TB Category C: Third Highest Priority

22. Major risks Heart disease: 1 in 400 Cancer: 1 in 600 Stroke: 1 in 2,000 Flu & pneumonia: 1 in 3,000 MVA: 1 in 7,000 Being shot by a gun: 1 in 10,000 USA Today: October 16, 2001 Other risks Falling down: 1 in 20,000 Crossing the street: 1 in 60,000 Drowning: 1 in 75,000 House fire: 1 in 100,000 Bike accident:1 in 500,000 Commercial plane crash: 1 in 1 million Lightening strike: 1 in 3 million Shark attack: 1 in 100 million Roller coaster accident: 1 in 300 million RISK OF DYING (US, per year)

23. PERSON-TO-PERSON ACQUISITION

24. Precautions Airborne Contact Droplet Standard Lassa Fever Ebola Marburg virus Smallpox Pneumonic plague Inhalational anthrax Venezuelan equine encephalitis Botulism Brucellosis Cholera Q fever Pulmonary tularemia S A C S A C S A C S A C S D S S S S S S S

25. FOMITE ACQUISITION • Agents acquired from contaminated clothes • Variola major (smallpox) • Bacillus anthracis (anthrax) • Coxiella burnetii (Q fever) • Yersinia pestis (plague) • Management • Remove clothing, have patient shower • Place contaminated clothes in impervious bag, wear PPE • Decontaminate environmental surfaces with EPA approved germicidal agent or 0.5% bleach (1:10 dilution)

26. BW AGENTS CHARACTERISTICS VHF-viral hemorrhagic fevers US Army, Biological Casualties Handbook, 2001 * Untreated, ** Pneumonic form

27. BW AGENT PROPHYLAXIS AND TREATMENT VHF-viral hemorrhagic fevers, PEP-postexposure prophylaxis *Aerosol exposure; **Pneumonic form; ^FDA approved vaccine (not available); #IND +IND BHF, RVF; @ CCHF, Lassa US Army, Biological Casualties Handbook, 2001

28. STEPS IN MANAGEMENT 1. Maintain an index of suspicion 2. Protect thyself 3. Assess the patient 4. Decontaminate as appropriate 5. Establish a diagnosis 6. Render prompt therapy 7. Practice good infection control

29. STEPS IN MANAGEMENT 8. Alert the proper authorities 9. Assist in the epidemiologic investigation 10. Maintain proficiency and spread the gospel US Army, Biologic Casualties Handbook, 2001