Assault with a Chemical Weapon: Its worse out there

than just Bioterrorism

Frank Paloucek DABAT

Biological warfare in history

??? 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

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

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…”

Recent Biological Accidents or Terrorism

1978 1979

1984

1994

2000

G. Markov killed by ricin in umbrella tipLeak of military anthrax spores outside

of Sverdlosk – 66+ deaths751 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

Anthrax History

????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

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

Table 1. Potential Biological Terrorism Agents Agent

Infective Dose Incubation time (days)

Anthrax 8000-50,000 spores 1-6 Coxiella Burnetti (Q fever) 1-10 organisms 10-20 Brucellosis 10-100 organism 5-60 Plague 100-500 organisms 2-3 Tularemia 10-50 organisms 2-10 Smallpox 10-100 organisms 7-17 Viral encephalitides 10-100 organisms 2-14 Botulinum toxin 0.01 ug/kg 1-5 Staph enterotoxin 0.03-1.7 ug <1

Human Infection Generally due to agricultural or industrial

exposure Three forms

Cutaneous (95%) – 2 in Texas 2001, 1 N.DakotaGastrointestinal (<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

Cutaneous anthraxManifests 2-5 days post exposurePapule that over 1-2 days becomes vesicular,

striking edema surroundingVesicular fluid noteworthy for lack of

neutrophilsPruritic, but not painfulRuptures after 5-7 days, the ulcer progress to

black eschar that sloughs in 2-4 weeksMild systemic symptomsFatality if untreated 5-20%

Gastrointestinal anthrax

Eating infected meatBegins 2-5 days laterSevere abdominal pain, melena, ascites,

profuse watery diarrheaProliferation in mesenteric lymph nodes

– edema and hemorrhage usually fatalOro-pharyngeal variant also, last

outbreak 1982 Thailand from contaminated water buffalo 3/24 deaths.

Inhalational Anthrax

1-6 day incubation Initial nonspecific “flu-like” syndrome – fever

nonproductive cough, myalgias, malaiseCommonly, 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%)

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%

SverdloskMilitary 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.

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.

National Pharmaceutical Stockpile

Maintained by CDCCoordinated with selected metropolitan

areas12 separate 50 ton 12-hour PUSH

Packages – for anthrax, smallpox, plague, tularemia, botulinum toxin, and viral hemorrhagic fevers

Followed by Vendor Managed Inventory materials

Pharmacy’s Role

Minimize hysteriaRecognize patterns or outbreaksBe prepared for unexpectedAntidotes and supportive therapies may be

given in unusual doses or routes. Be pharmacovigilant

Coordinate with public health officialsTry to avoid hoarding phenomenonCheck CDC website. Consult and interact with

local Boards of Health

Chemical Agents

VesicantsMustard compounds (WWI)

Cellular AsphyxiantsCyanide gases

Nerve agentsPhosphoric acid derivative acetylcholinesterase

inhibitors (Sarin, tabun, soman, VX)Organophosphates

Pulmonary irritants – unlikely for chemicoterrorism

Coumarin treated shrapnel in Middle East

Nerve agents

None are gases – liquids that vaporize or aerosols

Lethal doses as low as 10 mg for organophosphorus compounds

Death within 15 minutesAtropine and 2-PAM antidotesTokyo 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

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

Bhopal

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

Other forms of malicious poisoning

• Munchausen Syndrome by Proxy– Child Abuse– Elder Abuse

• Criminal Sedation/Disinhibition (Date-Rape)

• Homicide– Profit– Toxicomaniacs

Munchausen Syndrome by Proxy

• Bleeding• Seizures• Respiratory arrest• Sedation• GI• Fever/Infection• Rash

Date-Rape

• Dis-inhibitors (or Date Rape drugs)GHB, GBL, 1,4 BDRuhypnol - flunitrazepam/ benzodiazepinesChloral Hydrate (history bar in Chicago)ScopolamineEthanolKetamine/PCPImidazolines (Visine, Naphcon)