1. DETECTING AND RESPONDING TO A BIOTERRORIST AGENT INFECTING YOUR PATIENT(S) Panel Discussion Leland S. Rickman, M.D. Associate Clinical Professor of Medicine Division of Infectious Diseases Director, Epidemiology Unit UCSD Medical Center UC San Diego

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 14 TH century, Kaffa: Attacking Tatar force catapulted cadavers of plague victims into city – outbreak of plague led to defeat 18 th 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. 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. International Biological Weapons Programs NEXT

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] AgentDownwind reach, km No. deadNo. incapacitated Rift Valley fever 1 400 35,000 Tick-borne encephalitis 1 9,500 35,000 Typhus 519,000 85,000 Brucellosis 10 500125,000 Q fever>20 150125,000 Tularemia>2030,000125,000 Anthrax>2095,000125,000

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. SYNDROMIC CLUES TO BIOTERRORISM Respiratory casualties –Rapid onset: Nerve agents, cyanide, mustard, lewisite, phosgene, SEB inhalation –Delayed onset: Inhalational anthrax, pneumonic plague, pneumonic tularemia, Q fever, SEB inhalation, ricin inhalation, mustard, lewisite, phosgene Neurologic casualties –Rapid onset: Nerve agents, cyanide –Delayed onset: Botulism-peripheral symptoms, VEE- CNS symptoms US Army, Biologic Casualties Handbook, 2001

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

20. Category A: Highest Priority 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)

21. Category B: Second Highest Priority 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

22. Category C: Third Highest Priority 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

24. RISK OF DYING (US, per year) 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

25. PERSON-TO-PERSON ACQUISITION DiseaseTransmissionRisk Andes virusUndefinedLow AnthraxContact with skin lesionsRare Ebola, Lassa, Marburg, Congo-Crimean, AHF, BHF Contact with infective fluid, droplet? High SmallpoxContact, droplet, airborneHigh Plague (pneumonic)DropletHigh Q feverContact with infected placentaRare

26. Precautions SAC SAC SAC SAC SD S S S S S S S Lassa Fever Ebola Marburg virus Smallpox Pneumonic plague Inhalational anthrax Venezuelan equine encephalitis Botulism Brucellosis Cholera Q fever Pulmonary tularemia Airborne Contact Standard Droplet

27. 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)

28. BW AGENTS CHARACTERISTICS DiseaseIDIncubationDurationMortality * Anthrax**8,000-50,000 spores1-6 d3-5 dHigh Smallpox1-10 organisms~12 (7-17d)4 wksMod-High Plague**100-500 organisms2-3 d1-6 dHigh Q fever1-10 organisms10-40 d2-14 dVery low Tularemia10-50 organisms3-5d (2-10d)>2 wksMod VHF1-10 organisms4-21 d7-16 dMod-High VHF-viral hemorrhagic fevers * Untreated, ** Pneumonic form US Army, Biological Casualties Handbook, 2001

29. BW AGENT PROPHYLAXIS AND TREATMENT DiseaseVaccine Efficacy*PEPTreatment Anthrax**^Effective, 1,000 LD 50 monkeys Antibiotics SmallpoxEffective, high dose primates Vaccine, VIGCidofovir? Plague**^Ineffective, 118 LD 50 monkeys Antibiotics Q fever # 94%, 3500 LD 50 guinea Antibiotics Tularemia # 80%,1-10 LD 50 Antibiotics VHF + No vaccineNoneRibavirin @ VHF-viral hemorrhagic fevers, PEP-postexposure prophylaxis *Aerosol exposure; **Pneumonic form; ^FDA approved vaccine (not available); # IND US Army, Biological Casualties Handbook, 2001 + IND BHF, RVF; @ CCHF, Lassa

30. 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

31. 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