Warfare Terrorism Carstairs - ACMT · 2014-09-29 · Biological Warfare" Ricin! • Ricinus...

8/11/14

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Warfare/Terrorism/HAZMAT CDR Shaun D. Carstairs

Department of Emergency Medicine Naval Medical Center San Diego

San Diego, CA

Warfare/Terrorism/HAZMAT

•  Chemical

•  Nuclear

•  Biological

•  Hazardous Materials

Disclosure

•  The views expressed herein are solely those of the speaker and in no way reflect the official policy, position, or doctrine of the U.S. Navy, Department of Defense, or the U.S. Government.

•  The contents of this presentation are not endorsed in any way by the U.S. Navy, Department of Defense, or the U.S. Government.

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Thank You…

•  …to COL J. Dave Barry for his work on previous versions of these slides

The Core Content of Medical Toxicology

3% of the content.

Chemical Agents

•  Nerve agents

•  Blister agents

•  Incapacitating agents

•  Riot control agents

•  Pulmonary agents

•  Blood agents (cyanogens)

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Chemical Agents��Nerve Agents

•  History •  1930’s: Nazis synthesize “G” agents during WWII

•  Never used in battle •  Tested in concentration camps

•  1940’s: Soviet Union begins production after capturing German munitions

•  1950’s: U.S. begins production •  1990’s: Aum Shinrikyo cult (Matsumoto ‘94, Tokyo ’95), Iraq

against Kurdish minority


C

T

L

S

ne

ne

Autonomic Nervous System parasympathetic sympathetic

N

N

N

N

N

M

M

M

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C

T

L

S

N

N

N

N

M

M

N

ne

ne

Sympathetic Parasympathetic (cholinergic)

M mio

sec

sec

hr

sec

mot

mict

sec

agit

Sz

Fasic

paraly

hr vasoconstr

rr

Property Tabun (GA) Sarin (GB) Soman (GD) VX Volatility (mg/m3) 610 22000 3900 10.5

Persistency on soil 1-1.5 d 2-24 h Relatively persistent 2-6 days

LCt50 in humans (mg min per m3) 400 100 50 10

LD50 in humans (mg per 70 kg human) 1000 1700 350 6-10

Aging half-life >14 h 3 h 2-6 min 48 h

http://www.atsdr.cdc.gov/csem/csem.asp?csem=11&po=23



•  Personal Protection

•  Respiratory

•  Skin

•  Decontamination

•  Soap/water

•  Alkaline solutions (diluted sodium hypochlorite)

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•  Treatment

•  Atropine – combat excess

muscarinic ACh

•  Goal – dry respiratory secretions

•  Diazepam – combat excess nicotinic Ach

•  Oximes (e.g., 2-PAM) – combat “aging”


• Pretreatment

•  Pyridostigmine

•  Carbamate (reversible) – protects small % of AChE from irreversible OP aging

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Chemical Agents��Blister Agents

•  Mustards

•  Sulfur mustard (HD)

•  Nitrogen mustard (HN)

•  Lewisite (L)

•  Phosgene oxime (CX)


• History

•  1917 – WWI, Ypres

•  1930’s – Italians in Ethiopia

•  1940’s – WWII

•  Japanese vs. Chinese

•  German/Japanese conc. camps

•  1960’s Egypt vs. Yemen (alleged)

•  1980’s Iraq vs. Iran

•  2014 Syria

High casualty rate, low mortality (>20:1)


Agent Form Color Odor Pain Tissue Damage Blister Persistence

Sulfur mustard (HD)

Liquid Pale yellow

to dark brown

Garlic, onion, or mustard

Hours later

Immediate, but effects delayed till hours later

Fluid-filled

2 weeks-3 years

Lewisite (L) Liquid

Colorless to amber or black

Geranium-like Immediate Seconds to

minutes Fluid-filled Days

Phosgene oxime (CX)

Solid or liquid

Colorless as solid,

brown as liquid

Irritating Immediate Seconds Solid wheal 2 hours

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Chemical Agents��Mustard

• Mechanism •  Alkylating agent

•  “Cyclization” à reactive sulfonium ion

•  Alkylates sulfhydryl (-SH) and amino (-NH2) groups

•  Depletes glutathione •  Increased oxidative stress


• Clinical effects

•  Vapor or liquid exposure

•  Cellular damage within 1-2 min

•  Clinical effects 2-48 hrs (usually 4-8 hrs)


•  Skin: erythema à vesicles à blisters/bullae

•  Eyes: mild à severe conjunctivitis

•  Blindness possible

•  Airways: bronchospasm, pulmonary edema, obstruction/hemorrhage in severe cases

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•  GI: Nausea/vomiting, GI bleed

•  Systemic:

•  BM suppression & immunosuppression (high doses)

•  IARC Group I – respiratory cancer


• Diagnosis •  M8, M9 paper, etc.

•  Thiodiglycol (urine, blood)

• Treatment •  Decontamination

•  Supportive/symptomatic care

•  No antidote


• Decontamination

•  Remove large globs or liquid

•  Soap/water, diluted hypochlorite

•  Military self-decontamination kits

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Chemical Agents��Lewisite

• History •  Less persistent alternative to

mustard agents •  No confirmed battlefield use

• Mechanism unclear •  Similar to other arsenicals? •  Inhibition of pyruvate

dehydrogenase/other enzymes

Chemical Agents��Lewisite

• Clinical effects •  Immediate (unlike mustard) •  Skin: erythema, vesicles,

blisters •  Eyes: conjunctivitis •  Airways: MM irritation,

pulmonary edema

• Treatment •  Same as mustard •  BAL (British anti-Lewisite)

(dimercaprol) •  Topical/systemic

Chemical Agents��Phosgene Oxime

• Background •  No battlefield use •  Penetrates garments more

quickly than other agents •  Rapid onset, severe and

prolonged effects

• Mechanism •  Unclear •  Not a true vesicant •  Irritant or “nettle” agent

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Chemical Agents��Phosgene Oxime

• Clinical effects •  Immediate, severe tissue

damage •  Skin: erythema, wheals,

urticaria •  Eyes: conjunctivitis •  Airways: pulmonary edema

• Treatment •  Supportive •  No antidote

Chemical Agents��Incapacitating Agents

•  U.S. experimented with multiple agents •  Antimuscarinics felt to be most promising

•  BZ (3-quinuclidinyl benzilate) •  Physostigmine is potential antidote

•  Opioids •  Kolokol-1 (fentanyl analogue)

•  2002 Chechen Moscow theater siege

Chemical Agents��Riot Control Agents

•  CN (chloracetophenone) – Mace ®

•  CS (O-chlorobenzilidene malenonitrile)

•  Capsaicin (“pepper spray”)

•  Chloropicrin (trichloronitromethane)

•  Adamsite (DM) – vomiting agent

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Chemical Agents��Riot Control Agents

• OC – Capsaicin (“pepper spray”)

•  Better safety margin/more potent

•  Release of Substance P à “neurogenic inflammation”

Chemical Agents��Pulmonary Agents

•  Phosgene (CG)

•  Diphosgene (DP)

•  Chlorine (Cl)

•  Nitrogen oxides (NOx)

•  Perfluoroisobutylene (PFIB)

Chemical Agents��Pulmonary Agents

Agent Color Physical State Odor Water Solubility

Timing of Effects

Chlorine (Cl) Yellow-green

Gas; with pressure and cooling can be

liquid Strong bleach Intermediate

Immediate irritation,

pulmonary edema 2-24

hrs later

Phosgene (CG)

Colorless or white to pale-yellow liquid

Gas; with pressure and cooling can be

liquid

Freshly mown hay, green corn Poor

Delayed up to 48 hrs

(usually 2-6 hrs)

Diphosgene (DP) Colorless Gas Freshly mown

hay, green corn Poor

Delayed up to 48 hrs

(usually 2-6 hrs)

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Chemical Agents��Perfluoroisobutylene (PFIB)

•  Similar toxicity to phosgene

•  10x as potent

•  Delayed pulmonary toxicity

•  Formed from pyrolysis of PTFE

Nuclear/Radiological

•  Atomic radiation primer

•  Measurement

•  Acute radiation syndrome/dosimetry

•  Treatment of radiation injuries

•  Scenarios

•  Specific radionuclides

Nuclear/Radiological��Atomic Radiation Primer

• Nonionizing radiation •  Doesn’t have enough energy

to disrupt atoms or molecules •  Ionizing radiation

•  Radiation with enough energy to disrupt an atom or molecule that it hits

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•  Ionizing radiation effects •  DNA effects

•  Repairable damage

•  Mutations

•  Cell death


•  Ionizing radiation effects •  Free radical formation

•  Hydroxyl free radicals


•  Ionizing radiation effects •  Dose absorbed depends

upon:

•  Time

•  Distance (1/r2)

•  Shielding

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Nuclear/Radiological��Measurement

Gamma Spectroscopy

Nuclear/Radiological��Acute Radiation Syndrome

Nuclear/Radiological��Acute Radiation Syndrome

•  Four stages •  Prodromal: nausea/vomiting, diarrhea, anorexia; occurs minutes to

days following exposure •  Latent: relatively asymptomatic for hours to days •  Manifest (clinical) illness:

•  Hematologic syndrome (>0.7 Gy, >70 rad) •  Gastrointestinal syndrome (>10 Gy, >1000 rad) •  CNS syndrome (>50 Gy, >5000 rad)

•  Recovery or death

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Nuclear/Radiological��Dosimetry

• Lymphocyte reduction

•  Drop in lymphocytes q6 hours

•  Dose proportional to rate of decline of lymphocytes

Nuclear/Radiological��Dosimetry

• Chromosomal cytogenetics

•  # of aberrations proportional to dose

Nuclear/Radiological��Treatment

• Treat conventional (life-threatening) injuries first! • Decontaminate (if necessary)

•  External decon (remove clothes, decontaminate wounds first) •  Internal decon

• Dosimetry screen •  CBC w/diff q6 hrs •  Absolute lymphocyte count (ALC)

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•  Internal decontamination

•  Antacid: decrease absorption, precipitate to insoluble salt

•  Saturate critical organ with stable isotope; e.g. KI for 131I exposure

•  Chelation: DTPA (239Pu), Prussian blue (137Cs), BAL, etc.

•  Catharsis (decrease residence time)


• Supportive care

•  Antimicrobials, antiemetics, antidiarrheals, anxiolytics

•  IV fluids, electrolytes, analgesics, burn therapy, psychosocial care

•  Surgical intervention in first 36 hrs

•  Stimulation of hematopoietic system (cytokines, CSF’s)

Nuclear/Radiological��Sources/Scenarios

• Simple radiological device

• Radiological dispersal device

• Reactor accident – “meltdown”

•  Improvised nuclear device

• Nuclear weapon

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Nuclear/Radiological��Specific Radionuclides

•  Iodine (131I) •  t1/2 = 8.03 days, emits beta/gamma radiation

•  Low levels in hospital nuclear medicine departments

•  Nuclear reactor accidental releases/nuclear weapons

•  Accumulates in thyroid tissue

•  If incorporated à thyroid damage

•  Prophylactic treatment with potassium iodide (KI)


• Depleted uranium (238U) •  t1/2 = 4.5 billion years, emits alpha/beta/gamma radiation

•  0.7x as radioactive as natural uranium


• Depleted uranium (238U) •  Low risk radiation hazard

•  Internal contamination (inhalation) is controversial

•  Primarily a chemical toxicity (renal toxicity)

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• Thorotrast (232ThO2) •  Angiographic contrast agent

used in 1930’s •  Long t1/2 (400 yrs?); internal

alpha radiation •  Inc. incidence of malignancies

•  Liver CA, leukemia, angiosarcoma

•  IARC 1

Biological Warfare

• Toxins

• Bacteria

• Viruses

Biological Warfare��Toxins

• Botulinum toxin

• Ricin

• Staphylococcal enterotoxin B (SEB)

• T-2 mycotoxins

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Biological Warfare��Botulinum Toxin

• Produced by Clostridium botulinum •  7 antigenic types: A-G

• Military relevance •  Most potent toxin known, easily produced •  Weaponized by several countries/entities

•  Soviet Union, Iran, Iraq, N. Korea, Syria •  U.S. (1960’s) – known as Agent X •  Terrorists – Aum Shinrikyō (1990’s)

Arnon SS et al. JAMA 2001; 285:1059-1070


• Foodborne: toxin ingestion after production by bacteria in (canned) food

•  Infant: intestinal colonization • Wound: colonization •  Inhalational: weaponized agents • All have similar clinical picture

•  Progressive descending flaccid paralysis •  Always starts with cranial nerve/bulbar involvement

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• Diagnosis •  Mouse neutralization assay •  ELISA •  Wound or stool culture


• Treatment •  Supportive care •  Antitoxin

•  Bivalent (A, B) – BabyBIG ® – human-derived •  Trivalent (A, B, E) –equine-derived whole Ab •  Heptavalent (A-G) – equine-derived Fab2

•  Vaccine (investigational)

Biological Warfare��Ricin

• Ricinus communis (castor bean) •  Attractive as a biological weapon since it is widely available,

cheap, and has heat-stable toxin •  History

•  Compound W (WWII) •  Georgi Markov (1978)

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• Mechanism: inhibits protein synthesis •  B chain – binds to cell surface, undergoes endocytosis to enter

cell •  A chain – binds to and inhibits 60S ribosome, inhibiting protein

synthesis


• Symptoms •  Vary based upon route of exposure •  Oral – N/V/D, vascular collapse, shock •  Intramuscular – local pain, regional painful swollen lymph nodes,

multi-organ failure •  Inhalational – pulmonary edema, pneumonia, mediastinal

lymphadenitis, multi-organ failure


• Diagnosis •  ELISA assay of nasal swab, blood, or other body fluids

• Treatment •  Supportive care

•  AC may bind orally ingested toxin •  No antidote

• Prophylaxis •  Vaccine being investigated

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Biological Warfare��Staphylococcal Enterotoxin B

• Military relevance •  Potent compared to chemical agents •  Incapacitating (usually not lethal) •  Studied by U.S. in 1960’s as biological incapacitant


•  “Superantigens” à profound activation of immune system •  Bind monocytes (MHC Class II molecules) à stimulation of

helper T-cells à massive release of cytokines (interferon gamma, IL-6, TNF-α) à intense inflammatory response


• Gastrointestinal syndrome •  Identical to staphylococcal food poisoning

• Pulmonary syndrome •  Inhalation of weaponized toxin

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Biological Warfare��T-2 Mycotoxin

• Byproduct of Fusarium spp. • Alimentary toxic aleukia (ALA) •  “Yellow rain” – Laos/Kampuchea • Purported cause of Gulf War Syndrome

Biological Warfare��Bacteria

• Anthrax

• Plague

• Tularemia

• Brucellosis

• Q Fever

Biological Warfare��Anthrax

• Bacillus anthracis •  Gram-positive, encapsulated, spore-forming bacillus

• Virulence factors •  Antiphagocytic capsule •  Lethal toxin •  Edema toxin

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• Virulence factors •  Antiphagocytic capsule – no virulence without this capsule •  Lethal toxin

•  Zinc metalloproteinase – stimulates macrophages to release TNF and IL-6

•  Edema toxin •  Calmodulin-dependent adenylate cyclase – increased cAMP

leads to massive edema and impaired neutrophil function


• Pathophysiology •  Spores exist worldwide in soil •  Spores enter body, are ingested by macrophages and germinate

•  Incubation period 1-6 days •  Bacteria multiply in local lymph nodes leading to:

•  Edema •  Hemorrhage •  Tissue necrosis


• Cutaneous anthrax •  95% of cases, 2000 annually

worldwide •  Vesicle à painless necrotic

ulcer à lymphadenitis à black eschar à scar

•  Septicemia rare

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•  Inhalational anthrax •  Woolsorter’s disease •  Aerosolized release as a

biological weapon •  Fever, malaise, myalgia, fatigue •  Chest pain, respiratory

distress •  Widened mediastinum •  Mortality approaches 100%


• Gastrointestinal anthrax •  Rare but high mortality (25-60%) •  Ingestion of poorly cooked, contaminated meat •  N/V/D, abdominal pain à ascites, hematemesis à toxemia, shock,

death


• Treatment •  Ciprofloxacin •  Doxycycline •  Penicillin •  Raxibacumab – monoclonal Ab against lethal toxin of B. anthracis

•  Inhalational anthrax

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•  Immunization •  Cell-free vaccine

•  Attenuated, unencapsulated strain •  Main ingredient is “protective antigen” •  FDA approved for “at-risk populations” •  Series of 6 shots with annual booster


• Prophylaxis

Bartlett JG et al. Clin Inf Dis 2002; 35:851-8

Biological Warfare��Plague

• Siege of Caffa, 1346 •  Corpses of plague victims catapulted into city

Bartlett JG et al. Clin Inf Dis 2002; 35:851-8

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• World War II •  Japanese Army Unit 731 dropped plague-infected fleas over

China • Soviet Union, 1970s-1980s

•  Reported to have genetically engineered, dry, antibiotic-resistant form of plague


• Yersinia pestis •  Gram-negative bacillus •  Transmission

•  Flea vectors from rodent hosts •  Respiratory droplets from infected animals/humans

•  Very effective BW agent •  Can be aerosolized •  No effective vaccine


• Bubonic plague •  Incubation period 2-10 days •  85-90% of cases historically •  Fever, malaise, enlarged lymph

nodes •  Secondary septicemia occurs

in ~25% of patients •  Distal gangrene – “Black

Death”

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• Pneumonic plague •  Infection of lungs with Y.

pestis

•  Incubation period 2-3 days •  5-15% of cases historically •  Fever, malaise, cough,

hemoptysis •  Bilateral alveolar infiltrates •  Almost universally fatal


• Treatment •  Streptomycin or gentamicin •  Alternatives: Ciprofloxacin, doxycycline, chloramphenicol •  Isolation to prevent secondary cases

• Postexposure prophylaxis •  Ciprofloxacin •  Doxycycline •  Chloramphenicol


• Vaccination •  Killed whole-cell vaccine •  Effective against bubonic plague •  Does not reliably protect against pneumonic plague

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Biological Warfare��Tularemia

• Francisella tularensis •  Gram-negative coccus

•  Different presentations •  Ulceroglandular (most common) – skin ulcer/lymphadenopathy •  Glandular •  Oculoglandular •  Oropharyngeal •  Pneumonic (most serious) – likely with weaponization – cough,

chest pain, SOB

Biological Warfare��Tularemia

•  Ideal bioweapon •  Easily aerosolized •  Highly infective (10-50 bacteria needed) •  Highly incapacitating

• Treatment •  Doxycycline •  Gentamicin

Biological Warfare��Brucellosis

• Brucella spp. •  Gram-negative cocci •  Typically contracted from unpasteurized milk or contaminated

meat •  Nonspecific symptoms (fever, chills, malaise) •  High morbidity, low mortality •  Treatment

•  Doxycycline + rifampin

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Biological Warfare��Q Fever

• Coxiella burnetii •  Rickettsia-like organism •  Can cause disease from inhalation of single organism! •  Nonspecific symptoms

•  Fever, headache, fatigue, myalgias •  Pulmonary infiltrates in 50% of patients •  Treatment

•  Doxycycline or tetracycline

Biological Warfare��Viruses

• Smallpox

• Equine encephalitis

• Viral hemorrhagic fevers (VHF)

Biological Warfare��Smallpox

• Variola virus (poxvirus) •  Large enveloped DNA virus •  Certified by WHO as eradicated in 1977

•  Military relevance •  Infectious as aerosol •  Increasingly naïve (unimmunized) population •  Easy large-scale production, stable virus

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•  Incubation – not contagious (7-17 d) • Prodrome – viral syndrome (2-4 d) • Rash – highly contagious

•  Vesicular à pustular à umbilicated à scab •  Scabs form 10-14 d after onset of rash

•  Recovery – immunity •  No longer contagious once all scabs separate •  14-28 d after rash onset


• Rash •  Centrifugal •  Synchronous (all in same

stage) • Highly contagious by

aerosol • 30% mortality in

unvaccinated population


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• Laboratory diagnosis •  Virus isolation from pharyngeal swab or scab material (PCR,

ELISA) • Treatment

•  Supportive care •  Isolation (and vaccination) of patient and all contacts for 17 d •  Vaccination (within 4 d) •  VIG (within 1 week) •  Cidofovir


• Vaccination •  Vaccinia – poxvirus related to

cowpox •  Scarification with bifurcated

needle •  Contraindicated in:

immunosuppressed, HIV, eczema, pregnancy, children <18 months

Biological Warfare��Equine Encephalitis

• Venezuelan Equine Encephalitis • Weaponized during Cold War • Symptoms

•  Fever, headache, myalgias • Low mortality

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Biological Warfare��Viral Hemorrhagic Fevers

• Filoviridae •  Ebola/Marburg viruses

• Arenaviridae •  Lassa fever

• Bunyaviridae •  Rift Valley fever

• Flaviviridae •  Yellow fever, Omsk hemorrhagic fever, Kyasanur forest disease

Biological Warfare��Viral Hemorrhagic Fevers

• Symptoms •  Fever •  Headache •  Bleeding/DIC (Ebola, Marburg, Lassa) •  Rash

• Mortality up to 90% with Ebola/Marburg (others 0-20%) • Treatment: supportive

Hazardous Materials

• Treaties

•  Incident Command System, Site Safety

• National Pharmaceutical Stockpile

• Regulatory/Legal Acts

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Hazardous Materials

http://www.globalsecurity.org/security/library/policy/army/fm/3-11-21/appc.htm

Hazardous Materials

Warfare/Terrorism/HAZMAT

•  Chemical

•  Nuclear

•  Biological

•  Hazardous Materials

Warfare Terrorism Carstairs - ACMT · 2014-09-29 · Biological Warfare" Ricin! • Ricinus...

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Transcript of Warfare Terrorism Carstairs - ACMT · 2014-09-29 · Biological Warfare" Ricin! • Ricinus...