Bioterrorism. Eric S. Toner, MD. National Governors Association July 22, 2009

Transcription

1 Bioterrorism Eric S. Toner, MD National Governors Association July 22, 2009

2 Biological Weapons Have a Long History 14th century: Tartars catapulted bodies of plague victims over siege walls in Crimea 1750 s: British gave smallpox infested blankets to unfriendly Indians in the French and Indian War WWII: Japanese dropped plague infected fleas on Chinese 1972: Order of Rising Sun (American Fascists) dumped Kg of typhoid bacteria into Chicago and St. Louis water supplies

3 Biological Weapons Have a Long History 1986: Rajneeshees poisoned salad bars in Oregon with salmonella 751 sick : Aum Shinrikyo sprayed anthrax and botulinum toxin in Japan 2001: 5 letters (10 gms) mailed to media outlets and Senate 22 cases (11 inhalational, 11 cutaneous) 5 deaths

4 Why Use Biological Weapons? Biggest bang for your buck - highest kill/ dollar ratio also the highest kill/weight ratio 100 kg (220lbs) of anthrax aerosolized over Washington 1-3 million deaths. (Same as 1 megaton hydrogen bomb) (OAT 1993) Compared to nukes: easy to produce easy to hide hard to trace easy to carry out a campaign (reload)

5 Soviet Program After signing the 1972 biological weapons convention, Soviets embarked on massive offensive biological weapons program Produced HUGE quantities Developed multi-drug resistant, vaccine resistant anthrax and plague Genetically engineered new antigens into common bacteria After Soviet breakup: no work for scientists, poor controls over stockpiles

6 Biotechnology and Bioterrorism Rapidly evolving biotechnology increases the threat Any university biology lab can make a biological weapon Tens of thousand of scientists have the skills Many types of factories could be used for large scale production Genetic engineering modified pathogens Synthetic biology make viruses from scratch

7 Existing Biological Weapons Category A: can be aerosolized, developed as weapons, lethal if not treated Bacillus anthracis : Anthrax Variola major : Smallpox Clostridium botulinum toxin: Botulism Yesinia pestis: Plague (pneumonic) Fransicella tularensis :Tularemia Hemorrhagic fever viruses (Ebola/Marburg, Lassa, Rift Valley, Yellow Fever)

8 Category A Agents Plague and Tularemia Both cause pneumonia and are sensitive to common antibiotics (doxycline and cipro) Plague is moderately contagious (by respiratory route) tularemia is not Botulism Neurotoxin of Clostridium botulinum; used medically: BoTox Causes respiratory paralysis, lasts 2-3 months Viral Hemorrhagic Fevers Hard to produce Hard to deliver Limited availability of seed stock In nature cause intense but limited outbreaks rather than huge epidemics

9 Strategic BT threats The preceding four agents could cause tragic loss of life, but not likely to destabilize the country Smallpox and anthrax could, especially if there are multiple releases

10 Smallpox

11 Virus: Variola major Smallpox Killed 300 million in 20 th century Eradicated from nature by WHO in 1977 Only official remaining stocks are at CDC and outside Moscow Illness: Incubation 7-17 days (average 12) Severe illness, high fever, too sick to get out of bed After 3 days pox appears and progress over a week

12 Day 1 Source: CDC

13 Day 2 Source: CDC

14 Day 3 Source: CDC

15 Day 4 Source: CDC

16 Day 5 Source: CDC

17 Day 6 Source: CDC

18 Day 7 Source: CDC

19 Day 8 Source: CDC

20 Day 9 Source: CDC

21 Day 13 Source: CDC

22 No specific treatment 30% die Smallpox Contagious primarily by direct contact Only transmitted by those with rash Post exposure vaccination very effective if done early Approximately 300 million doses of vaccine in SNS With modern travel hard to know who has been exposed Ability to rapidly distribute vaccine to affected population in time is uncertain

23 Possible Societal Effects Enforced isolation of cases Geographic quarantine-unnecessary but likely Travel restrictions-very disruptive of economy International tension over sharing of vaccine Public turmoil over access to vaccine Political pressure for mass vaccination Stigmatization of certain groups Overwhelmed isolation capacity of hospitals Overwhelmed capability of public health

24 Anthrax

25 Bacterium: Bacillus anthracis Spore forming Anthrax

26 Anthrax as a Weapon Nearly ideal as biological weapon: highly lethal environmentally stable can be aerosolized over long distance easy to grow readily available seed stock handlers can be protected easily LD 50 =8,000-10,000 spores (LD 2 = 9 spores)

27 Anthrax as a Weapon Huge stockpiles of weaponized agent were created Soviets developed both supervirulent and antibiotic resistant strains Modeling studies suggest same potential as a nuclear bomb: WHO: 50 Kg aerosolized over city of 5 million 250,000 cases/ 100,000 dead U.S. Office of Technology Assessment:100 kg 130,000-3 million dead

28 Anthrax Spores are the infectious agent Resistant to temperature, UV Can lay dormant in soil for decades Spores are not affected by antibiotics Spores germinate in tissues to cause disease Can take days to months to germinate Bacteria are very antibiotic sensitive post exposure prophylaxis is effective Bacteria produce toxins too much toxin, antibiotics no longer help

29 Three Clinical Syndromes Cutaneous Endemic in much of the world: >20,000 cases per year Case fatality rate <1% with appropriate treatment Gastrointestinal Caused by eating infected meat, not spores Inhalational

30 Inhalational Anthrax Rarely occurs naturally Inhaled spores settle in lungs; carried to lymph nodes where they germinate and release toxins: Incubation is dose dependant (2 to 90 days) Typical clinical course: non-specific initial symptoms lasting 3 to 5 days; may include low grade fever, nausea, cough; followed by chest pain, shortness of breath then rapid development of shock, respiratory failure and multi-organ system failure Case fatality rate without treatment is 100% Case fatality rate with early and aggressive treatment may be ~50%

31 Sverdlovsk Accidental release from a Soviet bioweapons facility in 1979 Estimated 7000 exposed Human cases: 4 km downwind (Animal: 50 km) 79 documented cases, with at least 68 deaths and perhaps several hundred cases Incubation period, mode = 10 days (max 43 days) Many infected were indoors

32 Sverdlovsk Source :FDA

33 Aum Shinrikyo Aum Shinrikyo released liquid suspension of B. anthracis on 8 occasions in 1993 in Tokyo and other cities Had used a non-virulent vaccine strain of B. anthracis Caused no illnesses

34 Vaccine Anthrax Vaccine: licensed 1970 pre-exposure: 5 or 6 doses over 18 months in monkeys, 100% protection from inhalation challenge; immunity drops off after 2 years Yearly boosters post exposure in addition to antibiotics 30% mild local reaction;3.6% moderate local reactions; 1% systemic reactions

35 Treatment Multidrug treatment is needed in most cases Most patient who develop symptoms will need ICU, perhaps for weeks Most patients take months or years fully recover, if at all

36 Post Exposure Prophylaxis 60 days of a first line antibiotic: tetracyclines (doxycycline) flouroquinalones (ciprofloxacin, levofloxacin, etc) Evidence suggests shorter course with concomitant vaccination may be effective as well Must be started before symptoms (may be as short as 2 days) Ability to distribute antibiotics to affected population within 48 hours is uncertain Difficult to know who has been exposed in large scale aerosols release

37 Anthrax National Planning Scenario 330,000 individuals exposed in covert aerosol release in large city (let s say DC) Scenario projects 13,000 cases of inhalational anthrax, most requiring critical care (a much lower number than many other modeling studies)

38 National Capital Region Hospital Surge Capacity ~40 hospitals within 20 miles 30% surge available within 24 hours 3000 beds 400 critical care beds Expected need ~13,000 critical care beds Big triage problem A large proportion of the population will seek medical care No system or rapid diagnostic testing for triage Triage sites outside of hospitals will be necessary Big transportation problem ICU patients too sick to transport No system capable of transporting thousands of people to other cities within a few days

39 Possible Societal Effects Overwhelmed hospitals unable to treat anthrax or other patients Unable to know who has been exposed- would need mass prophylaxis campaign (perhaps millions of people) over few days Difficult compliance with prolonged prophylaxis- few can tolerate 60 days of doxy or cipro Many could die due to lack of ICU care in most cities ICU surge capacity measured in tens rather than thousands of beds The biological Katrina - potentially salvageable patients die because unable to access needed care Affected city shut down due to contamination-large scale decon is impossible

40 Concluding Remarks Bioterrorism is a real and increasing threat WMD commission expects another attack within 5 years Effective response (prophylaxis and treatment) requires early recognition, ability for rapid distribution of countermeasures Most symptoms are initially nonspecific,rapid diagnostic test are not available Overtaxed healthcare system not prepared for surge of this size

41 Information