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

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

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

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

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.

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.

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

EFFECTS OF A BIOLOGICAL WEAPONS RELEASE

Siegrist, Emerging Infectious Diseases 1999

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] Agent Downwind No. dead No. reach, km incapacitated Rift Valley fever 1 400 35,000 Tick-borne encephalitis Typhus Brucellosis Q fever Tularemia Anthrax 1 5 10 >20 >20 >20 9,500 19,000 500 150 30,000 95,000 35,000 85,000 125,000 125,000 125,000 125,000

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

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

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)

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

DEVELOPING A RISK ASSESSMENT OF BIOLOGIC WARFARE AGENTS

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

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

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

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

Soviet BW Priorities Agents Likely to be Used

Smallpox Plague Anthrax Botulism VEE Tularemia Q Fever Marburg Influenza Melioidosis Typhus

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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)

Category B: Second Highest Priority

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

Moderately easy to disseminate cause moderate morbidity and low mortality Require specific enhancements of CDCs diagnostic capacity and enhanced disease surveillance

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

RISK OF DYING (US, per year)

Other risks

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

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

PERSON-TO-PERSON ACQUISITION
Disease Andes virus
Anthrax Ebola, Lassa, Marburg, Congo-Crimean, AHF, BHF Smallpox Plague (pneumonic) Q fever

Transmission Undefined
Contact with skin lesions Contact with infective fluid, droplet? Contact, droplet, airborne Droplet Contact with infected placenta

Risk Low
Rare High High High Rare

Contact

Lassa Fever Ebola Marburg virus Smallpox Pneumonic plague Inhalational anthrax Venezuelan equine encephalitis Botulism Brucellosis Cholera Q fever Pulmonary tularemia

S S S S S S S S S S S S

A A A A

C C C C D

Droplet

Precautions

Standard

Airborne

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)

BW AGENTS CHARACTERISTICS
Disease ID Incubation Duration Mortality * 3-5 d High 4 wks 1-6 d Mod-High High Very low Mod

Anthrax** 8,000-50,000 spores 1-6 d Smallpox Plague** Q fever Tularemia 1-10 organisms 100-500 organisms 1-10 organisms 10-50 organisms ~12 (7-17d) 2-3 d

10-40 d 2-14 d 3-5d (2-10d) >2 wks

VHF-viral hemorrhagic fevers US Army, Biological Casualties 2001 VHF 1-10 organisms 4-21 d 7-16Handbook, d Mod-High * Untreated, ** Pneumonic form

BW AGENT PROPHYLAXIS AND TREATMENT

Disease Anthrax**^ Smallpox Plague**^ Q fever# Tularemia# VHF+ Vaccine Efficacy* Effective, 1,000 LD50 monkeys Effective, high dose primates Ineffective, 118 LD50 monkeys 94%, 3500 LD50 guinea 80%,1-10 LD50 No vaccine PEP Antibiotics Vaccine, VIG Antibiotics Antibiotics Antibiotics None Treatment Antibiotics Cidofovir? Antibiotics Antibiotics Antibiotics Ribavirin@

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

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

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