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Download 31. Biological Warfare
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DETECTING AND RESPONDING TO A BIOTERRORIST AGENT INFECTING YOUR PATIENT(S) Panel Discussion 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. NEXT 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 1 5 10 >20 9,500 19,000 500 150 35,000 85,000 125,000 125,000 Tularemia Anthrax >20 >20 30,000 95,000 125,000 125,000 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 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) 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 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 NEXT 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 • 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 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 Transmission Risk Andes virus Undefined Low Anthrax Contact with skin lesions Rare Ebola, Lassa, Marburg, Congo-Crimean, AHF, BHF Smallpox Contact with infective fluid, droplet? Contact, droplet, airborne High Plague (pneumonic) Droplet High Q fever Contact with infected placenta Rare High Airborne Contact Lassa Fever Ebola Marburg virus Smallpox Pneumonic plague Inhalational anthrax Venezuelan equine encephalitis Botulism Brucellosis Cholera Q fever Pulmonary tularemia A A A A C C C C Droplet Standard S S S S S S S S S S S S Precautions D 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 Anthrax** 8,000-50,000 spores 1-6 d Duration Mortality * 3-5 d High Smallpox 1-10 organisms ~12 (7-17d) 4 wks Mod-High Plague** 100-500 organisms 2-3 d 1-6 d High Q fever 1-10 organisms 10-40 d 2-14 d Very low Tularemia 10-50 organisms 3-5d (2-10d) >2 wks Mod 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