Assault with a Chemical Weapon: Its worse out there than just Bioterrorism

2. Assault with a Chemical Weapon: Its worse out there than just Bioterrorism Frank Paloucek DABAT

3. ??? 6th Cent Romans 1346 1800’s WWI 1933-45 Feces-smeared arrows Assyrians poison wells with ergot Animal cadavers into well water Plague-dead corpses catapulted into Kaffa by Tartars British donate smallpox laden blankets Germans use zoonoses against livestock Japan’s “Unit 731” kills 10,000+ Chinese with plague, anthrax, dengue, tularemia Biological warfare in history

4. Lord Jeffrey Amherst, July 1763re: Pontiac’s rebellion

5. In English “You will do well to try to inoculate the Indians by means of blankets, as well as every other method that can serve to extirpate this execrable race…”

6. 1978 1979 1984 1994 2000 G. Markov killed by ricin in umbrella tip Leak of military anthrax spores outside of Sverdlosk – 66+ deaths 751 people poisoned with Salmonella in Dallas OR – salad bars contaminated by local cult Aum Shinrikyu sprays botulism toxin twice and tries anthrax spore cloud 35 anthrax cases reported to FBI in US Recent Biological Accidents or Terrorism

7. ???? 15-1700’s 1979 1994 2001 5th and 6th plagues of Exodus Major livestock disease Europe Leak of military anthrax spores outside of Sverdlosk – 66+ deaths Aum Shinrikyu sprays botulism toxin twice and tries anthrax spore cloud 35 anthrax cases reported to FBI in US, ~10,000 receive 60+ days of prophylaxis Anthrax History

8. Anthrax • Bacillus anthracis (Greek for coal) • Called “Black Bane” in Middle Ages • Major zoonosis – id’ed in 1870 by R. Koch • Id’ed as cause of Woolsorters Disease (specifically for inhalational disease ) • Successful immunization in 1880, Pasteur’s vaccine developed in 1881 • “Wild” prevalent in Africa, Asia and “anthrax belt” of U.S. Midwest/Great Plains

11. Human Infection • Generally due to agricultural or industrial exposure • Three forms • Cutaneous (95%) – 2 in Texas 2001, 1 N.Dakota • Gastrointestinal (<1%) • Inhalational (5%) • 235 cases in U.S from 1955-1994, 20 fatalities. Since 1900, 18 inhalational, last 1978. • Human-to-human transmission is not believed to occur

12. Cutaneous anthrax • Manifests 2-5 days post exposure • Papule that over 1-2 days becomes vesicular, striking edema surrounding • Vesicular fluid noteworthy for lack of neutrophils • Pruritic, but not painful • Ruptures after 5-7 days, the ulcer progress to black eschar that sloughs in 2-4 weeks • Mild systemic symptoms • Fatality if untreated 5-20%

14. Gastrointestinal anthrax • Eating infected meat • Begins 2-5 days later • Severe abdominal pain, melena, ascites, profuse watery diarrhea • Proliferation in mesenteric lymph nodes – edema and hemorrhage usually fatal • Oro-pharyngeal variant also, last outbreak 1982 Thailand from contaminated water buffalo 3/24 deaths.

16. Inhalational Anthrax • 1-6 day incubation • Initial nonspecific “flu-like” syndrome – fever nonproductive cough, myalgias, malaise • Commonly, has transient resolution (while it has migrated and is proliferating in lymph nodes) • “Resumes” with severe respiratory distress, shock and death < 24hours • Meninges frequently involved (50%)

17. Anthrax treatment • “Wild” forms very sensitive to penicillin, ciprofloxacin, doxycycline. Evidence suggest streptomycin increases response to PCN • Cutaneous: treat with oral. GI and Inhalational with intravenous. (Cipro 400 q12 Doxy 100 q 12h and 1 or 2 of following Vanco, PCN, amp) • Vaccine – designed for cutaneous - 92% efficacy, 35% reaction rate • (in monkeys) Vaccination post-lethal aerosol inhalation exposure plus 30 days antibiotics ~ 90%

18. Sverdlosk • Military grade anthrax spore aerosol leak. Cloud over 1.4 million inhabitant city. • Covered-up by military, claimed GI disease. • Post glasnost investigation – 96 confirmed cases and 66+ deaths. • Interesting note- no cases under 24 yrs old. • Cases followed classic air/wind spread and dispersion patterns. • Aum Shinrikyo (1982) used attenuated (non-encapsulated) Tokyo – some pet deaths only.

19. Current U.S. bioterrorist event • 22 cases that have met CDC case definition. • No new cases since 11/7/01. • 12 cutaneous, 10 inhalational – 4 deaths • Source is unknown for one case • All 18 survivors have been treated and discharged. • 32,000 have received prophylaxis. 490 have been surveyed for toxicity – 95 (19%) have reported head/neck swelling, SOB, difficulty breathing.

20. National Pharmaceutical Stockpile • Maintained by CDC • Coordinated with selected metropolitan areas • 12 separate 50 ton 12-hour PUSH Packages – for anthrax, smallpox, plague, tularemia, botulinum toxin, and viral hemorrhagic fevers • Followed by Vendor Managed Inventory materials

21. Pharmacy’s Role • Minimize hysteria • Recognize patterns or outbreaks • Be prepared for unexpected • Antidotes and supportive therapies may be given in unusual doses or routes. Be pharmacovigilant • Coordinate with public health officials • Try to avoid hoarding phenomenon • Check CDC website. Consult and interact with local Boards of Health

22. Chemical Agents • Vesicants • Mustard compounds (WWI) • Cellular Asphyxiants • Cyanide gases • Nerve agents • Phosphoric acid derivative acetylcholinesterase inhibitors (Sarin, tabun, soman, VX) • Organophosphates • Pulmonary irritants – unlikely for chemicoterrorism • Coumarin treated shrapnel in Middle East

23. Nerve agents • None are gases – liquids that vaporize or aerosols • Lethal doses as low as 10 mg for organophosphorus compounds • Death within 15 minutes • Atropine and 2-PAM antidotes • Tokyo subway attack with sarin – most severe patients require <8 mg atropine for systemic symptoms. Many require eye drops for ocular pain • “Blurred vision”, cloud, underwater vision

24. Most Recent ThreatRicin • Most “deadly” plant derived toxin known • From Castor Bean • Cellular poison – no known antidote • Used by Eastern bloc espionage units in “Cold War” • January 2003 – Suspected Algerian terrorist cell arrested in flat (above a pharmacy) where traces of ricin found. Massive hunt for cache now in progress • Food poisoning

25. Bhopal

26. Bhopal • 12/3/84, Union Carbide pesticide plant • Accident – 40 metric tons methyl isocyanate • 2000 deaths, 10,000 injuries 3 hours • Gas dispersed along wind flow • Slightly similar event in 8/85 WV hospitalized 100 people • EPA estimates 17/29 events in U.S. could have been worse

27. Other forms of malicious poisoning • Munchausen Syndrome by Proxy • Child Abuse • Elder Abuse • Criminal Sedation/Disinhibition (Date-Rape) • Homicide • Profit • Toxicomaniacs

28. Munchausen Syndrome by Proxy • Bleeding • Seizures • Respiratory arrest • Sedation • GI • Fever/Infection • Rash

33. Date-Rape • Dis-inhibitors (or Date Rape drugs) • GHB, GBL, 1,4 BD • Ruhypnol - flunitrazepam/ benzodiazepines • Chloral Hydrate (history bar in Chicago) • Scopolamine • Ethanol • Ketamine/PCP • Imidazolines (Visine, Naphcon)