Overview of Chemical and Biological WeaponsTerrorism

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Overview of Chemical and Biological
Weapons/Terrorism

• Tucker Greene, MD, FAAEM, ACMT
• Cape Coral, FL

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Introduction

• Long History of humans using both agents
• Precedents
• Ancient
• Middle Ages - Anthrax contaminated livestock
• Recent
• Southeast Asia Tricothecenes
• Iran/Iraq Sarin
• Arum Shryinko Tokyo subway attack

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Introduction

• Agent Progression
• Chemical
• Industrial process
• Biological
• Agents, offspring
• toxins
• Different Results than predicted for both

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Introduction

• Persistent v. Non-Persistent Biological
• Persistent Anthrax
• Non-Persistent Viruses
• Persistent v. Non-Persistent
• Persistent Mustard, VX
• Non Persistent Phosgene, CN

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Introduction

• Stability or Infectivity
• Anthrax Spores stable, reasonably infective,
  lethal?
• Tularemia, Q-Fever, Brucellosis unstable, very
  infective, non-lethal

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Introduction

• Biological Agents
• Mimic other natural diseases
• Usually incapacitating
• Chemical Agents
• Exaggerate or Isolate a particular clinical
  feature of chemical agents in general
• I.e organophosphates and nerve agents
• KEY Mechanism of Intoxication
• Dermal, Inhalation, Ingestion

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(brief) History

• Definitions
• Kill Soman, VX
• Injure Phosgene
• Incapacitate CS, BZ
• Countermeasures
• Until WWI, US not concerned or interested

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(brief) History

• Pre-WWI Developments
• Ancient hellebore, mandrake in water 1000-200
  b.c
• Recent
• 1700-1850 Chlorine, Mustard (dichloroehtylsulfid
  e), chloropicrin
• Civil War Dougherty Chlorine, 3 qts in shell

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(brief) History

• Biological
• Mongols in Caffa 1346, bubonic plague bodies
• Spanish v French 1495, Leprosy Blood in Naples
  against French

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Protection, Control

• US Civil War agreed but not adhered to
• Hoffman Respirator in 1866
• Archduke Francis murder in 1914, control among
  WWI participants

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Protection, Control

• WWI Chemical
• German Wilhelm Gas cloud due to lack of shells
• Allies Chlorine response
• Biological
• Both sides attempting to use anthrax and
  glanders

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US Chemical Warfare Service (CWS) and New Age

• Chemical Agents placed in Artillery Shells
• Cl2, Choropicrin, Mustard, Phosgene
• Biological Agents
• Ricin
• Brucellosis

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US Chemical Warfare Service (CWS) and New Age

• Detection, Alarms, Treatment
• Human and Animal
• Treatment
• Inhalation
• Vomiting
• Venesection
• KI
• Steam Tents
• Skin ZnO, Starch, Boric Acid, Calamine

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US Chemical Warfare Service (CWS) and New Age

• Biologicals get new start in late 1930s after
  skepticism
• Nuclear Age comes and biologicals take a back
  seat (where someone was sitting)
• Chemical Warfare takes second Priority
• Edgewood (Aberdeen), MD
• McClellan, AL
• Rocky Mountain, CO

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US Chemical Warfare Service (CWS) and New Age

• Near ending of CWS
• Binary weapons
• Disposal at Sea
• Disseminated Danger of lesser nations?
• Johnston Atoll Destruction program

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US Chemical Warfare Service (CWS) and New Age

• Gulf War
• Iraq with known biological and chemical weapons
• MARK I Kit
• 2-PAM, atropine, valium
• Pryidostigmine Bromide
• Kamisiyah arsenal detonation
• Mustard
• sarin

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US Chemical Warfare Service (CWS) and New Age

• Aum Shinrikyo Cult
• Experiments with botulinum and anthrax in subways
  yields no impact
• Later sarin attack kills 50 but injures 5000

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DEFENSE (WWI)

• Mask against Chemical Agents
• Plume identification
• Mobile Decontamination
• 5 of Division strength
• Psychological aspect of persistence mustard (low
  volatility, low dose effect, still used)
• Gas Mania

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DEFENSE (WWI)

• Mustard
• Conjunctivitis
• Skin burns
• Inhalation (worse than phosgene and chlorine)
• Accounted for up to 30 of casualties but 1500
  deaths/52,900 US AEF Force deaths

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DEFENSE (WWII)

• Germans thought US possessed secret gases beyond
  GAlt GBlt GD and feared reprisal
• Continued Vigilance
• Walt Disney example

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Chemical Warfare and the HealthCare Provider
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National Warfare Capability
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Chemical Warfare Agents
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Nerve Agents
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Organophoshates

• History
• Ethanol Phosphoric Acid
• Tabun - GA
• Sarin - GB
• Soman- GD
• VX

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Organophosphates

• Examples

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Organophosphates

• Absorption
• inhalation
• dermal
• oral
• Activation
• ie parathion
• Metabolism
• cholinesterase

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Organophosphates

• Mechanism of Toxicity

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Organophosphates

• Clinical Effects

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Organophosphates

• Clinical Effects
• Muscarinic (postganglionic parasympathetic)
• SLUDGE
• miosis, bronchorrhea, bradycardia
• Nicotinic (neuromuscular junction)
• Nicotinic (autonomic ganglion)

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Organophosphates

• Management/Treatment
• Decontamination
• Stabilization
• Antidotes
• Atropine
• Pralidoxime

Pralidoxime
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Organophosphates

• Delayed Toxicity
• Intermediate Syndrome
• Peripheral Neuropathy
• Tri -o-cresyl phosphate (TOCP)
• Tri -o-cresyl tolyl phosphate TOTP
• Neurotoxic Esterase

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Organophosphates

• Delayed Toxicity
• Intermediate Syndrome
• Peripheral Neuropathy
• Tri -o-cresyl phosphate (TOCP)
• Tri -o-cresyl tolyl phosphate TOTP
• Neurotoxic Esterase

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Organophosphates

• Laboratory
• Dont Need To Treat!!!
• Cholinesterase Levels
• RBC v Plasma
• Variation from Baseline

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Pretreatment

• Pyridostigmine (carbamate)
• Used in Gulf War

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Vesicants
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Sulfur Mustard
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Phosgene
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Lewisite
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Inhalational Agents
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Inhalational Agents

• Upper Airway
• Water soluble
• Middle Airway
• Alveolar
• Non-soluble in water
• Cellular Asphyxiants

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Inhalational Agents
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Inhalational Agents

• Cyanide Treatment
• Nitrites
• Thiosulfate
• Hydroxycobalamin
• Hyperbaric O2

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Incapacitating Agents
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Incapacitating Agents

• Anticholinergics
• LSD, other Indoles
• Opiates

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Riot Control Agents

• Rapid Onset, Upper Airway and GI Symptoms
• CS (o-Chlorobenzylidene)
• CN (1-Chloroacetophenone)
• Other
• DM (Diphenylaminearsine)
• CR (Dibenzo(b,f)-14oxazepine
• CA (Bromobenzylcyanide)

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Riot Control Agents

• CS
• Solid, low Vp
• Tear Gas
• Airway irritation
• Conjunctival tearing
• Dermal effects can cause blistering
• IV/Oral can liberate cyanide moeities

• CN
• Solid powder
• Same symptoms as CS
• Highly sensitizing to skin with deaths reported
  with large exposures

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Riot Control Agents

• Treatment
• Alkaline decon of skin no hypochlorite
• Topical steroids for skin
• Local anesthetics for eyes

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Field Management of Chemical Casualties

• Hot Zones
• Clean v Decontamination areas
• Counter-current or Reverse Airflow for
  Decontamination Areas
• Triage
• Potential ID
• Look for Combined Agents/Injuries
• Difficult to Treat Combinations

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Decontamination

• Chemical
• Desirable Traits for Dermal Decon
• Physical Removal
• Aqueous
• Adsorbent

• Biological
• Dermal not as Important (T-2 is exception)
• Hypochlorite
• Environmental UV

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BIOLOGICALS
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History

• Secret US Weapons Program
• Response to Japan during WWII
• Stockpiling 400 kg anthrax bombs
• Experiments
• San Francisco (Serratia marcenscens)
• New York Subway (B. subtilis)
• African Americans exposed to Aspergillus f.

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Use of Biological Weapons

• Methods of Delivery
• Food
• Water
• Air

• Requirements
• Ease of Production
• Lethality/Incapacitation
• Particle size
• Ease of Dispersion
• Stability

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Use of Biological Weapons

• Tactical Concerns
• Hard to Trace or Fingerprint
• Terrorism as we now have known the anthrax cases

• Advantage/Disadvantage
• Predominantly concerns of the pathogen occurring
  in aggressors
• Persistence
• Insidious, low cost, minimal detection

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Biological Agents

• Anthrax
• Plague
• Tularemia
• Brucellosis
• Q Fever

• Smallpox
• Viral Encephalitides
• Viral Hemorrhagic Fevers
• Toxins
• Plants
• Animals
• Mycotoxins

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Anthrax

• History
• Bacillus anthracis
• Zoonoticgoats sheep, cattle, swine, horses
• 5th and 6th plagues of Exodus
• Isolated 1876 Koch
• Vaccine 1881 Pasteur

• Organism
• 1-5 mic x 5-10 mic
• Capsule forms in presence of CO2, HCO3
• Sporulation occurs in dead tissue exposed to
  oxygen

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Anthrax

• Epidemiology
• 1958 20-100,000 cases worldwide
• Since 1970 one case/decade
• Woolsorters Disease

• Pathogenesis
• Antiphagocytic Capsule
• Lethal Toxin
• Edema Toxin
• Mechanism by cell binding and then active toxin

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Anthrax

• Clinical Disease
• Cutaneous
• Inhalational
• Gastointestinal
• Meningeal

• Diagnosis
• CLINICAL SUSPICION OF EXPOSURE

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Anthrax

• Treatment
• Pen G
• Doxycycline
• Ciprofloxacin
• Many other possibly effective

• Recombinants may possess resistance as the native
  vegetative state has lactamases

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Plague

• History
• Pandemics of the 6th, 14th, 20th century
• 24 Million died from 1346-1352
• Endemic throughout history
• Zoonotic
• Enzoontic
• Epizootic

• Infectious Agent
• Yersinia pestis
• Gram-neg, non-sporulating, coccobacillus
• pH 6 antigen induced at low pH for virulence
• Antiphagocytic capsule
• Complex interspecies toxins

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Plague

• Epidemiology
• Oriental rat flea most common vector
• Multiple animals serve as vectors
• US rat squirrel fleas
• Endemic in Western US

• Pathogenesis
• 1-10 organism can infect via bites
• Multiple Virulence factors
• Spread via lymph
• Sepsis occurs when untreated to all organs

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Plague

• Clinical Features
• 80 as bubonic form
• 10 as sepsis
• 10 as pulmonary
• As warfare agent presentation would be bubonic
  and pulmonary

• Generally present as gram negative infection with
  plague specific features

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Plague

• Diagnosis
• Differential
• Cat Scratch
• Tularemia
• LGV
• Chancroid
• TB
• Streptococccal
• Rickettsiae

• Lab Confirm
• Aspiration of Bubo
• Wright-Giemsa, Gram Stain

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Plague

• Treatment
• Isolation for first 48 hrs of treatment
• Streptomycin, ceftriaxone, chloramphenical,
• Doxycyclcine all acceptable
• If treated early, buboes do not require drainage
• Postexposure Prophylaxis Doxycycline
• Immunization high risk individuals

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Tularemia

• History
• Discovered in 1911 in Tulare County, California
  by McCoy
• Edward Francis discovered deer fly transmission
• High infectivity after aerosolization

• Agent
• Francisella tularensis
• Obligate aerobe, coccobacillus
• Two biovars US isolate highly virulent for
  rabbits, humans

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Tularemia

• Epidemiology
• Principle reservoir is the tick in the US
• Abdominal Pain, Pharyngitis, from contaminated
  water in areas where water mammals live (non-US)

• Pathogenesis
• Possibly capsular
• Unclear, no toxins
• Spreads through skin, mucous membranes, GI
• 5-10 organisms
• Humoral response by MHC II mediated T-cell
  immunity

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Tularemia

• Clinical Features
• Incubation 3-6 day
• Ulceroglandular 75
• Skin or mucous membranes, nodes gt1cm
• Typhoidal 25
• Smaller nodes
• Non-mucous membranes

• Multiple Const/Syst complaints
• Fever
• HA
• Chills
• Abdominal pain
• Fluctuant Lymph nodes (drainage)

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Tularemia

• Diagnosis
• Difficult serology and growth medium procedures
• ELISA most reliable

• Treatment
• Streptomycin
• Aminoglycosides
• Chloramphenicol
• Tetracyclines
• Prophylaxis
• Doxycycline

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Brucellosis

• Agent
• Non-toxic, nonsporulating,aerobic, Gram-neg,
  coccobacilli
• 6 species with several biovars
• Unusual LPS component of cell membrane

• History
• Zoonotic infection
• Domestic
• Wild
• Animal Products, contact with infected animals,
  aerosols
• Relapsing Fever, associated with ruminant
  abortion
• US actively developed warfare agent with Brucella

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Brucellosis

• Epidemiology
• Transmission at abortion, slaughter, and milk
• Highly infectious in lab workers who work with
  the Brucella
• Fewer than 200 fatal cases/yr in US

• Pathogenesis
• Enter thru skin, GI, mucous membranes
• Phagocytized by WBC but carried to lymph nodes
• Placenta may carry 1010 bacteria/gram

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Brucellosis

• Clinical Features
• diverse, variability
• 3d to weeks incubation
• Neuropsychiatric along with fever, cough,
  arthritis
• Mild lab abnormalities

• Diagnosis
• Serum agglutination
• PCR
• IgG

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Brucellosis

• Treatment
• Doxycycline
• Streptomycin
• Aminoglycosides
• Prophylaxis
• Prevention (no-vaccine)
• Doxycycline

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Q Fever

• History
• 1937 discovery
• Zoonotic
• Coxiella Burnetii
• 50 g of dried powder equal to casualty rate of
  anthrax or tularemia
• Multiple wars with soldiers infected from living
  in barns, near livestock

• Agent
• Close relative of Legionella, not true
  rickettsiae
• Obligate intracellular pathogen
• Spore-like formation
• Phase I/II

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Q Fever

• Epidemiology
• Extremely infectious
• Single organism capable of disease
• Multiple hosts, arthropod to human
• Human infection from livestock same as
  Brucellosis but also shed in urine
• Urine persistence can infect from objects such as
  straw

• Pathogenesis
• Inhalation of aerosols
• Phagocytosis with eventual lysis and release

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Q Fever

• Clinical Features
• Incubation 10-40 days
• Asymptomatic seroconversion
• Acute Disease
• Chill,rigors,retroorbital HA
• Fever, myalgias
• Chronic endocarditis

• Diagnosis
• Serological
• Comp Fixation
• Indir Flour Ab
• ELISA

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Q Fever

• Treatment
• Tetracyclines
• Macrolides
• Quinolones in chronic disease
• Prophylaxis
• Vaccine
• Doxycycline

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Smallpox

• Variola ds-DNA, Orthopox Virus
• Major 30 mortality, Asia, Africa
• Minor 1 mortality, Europe, South America
• Possible to recover Smallpox from preserved
  cadavers or recombinant with monkeypox

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Smallpox

• Pathogenesis and Clinical Features
• Highly stable and infective for long periods
  outside of host
• Fever, followed by rash 3-6 days later
• Rash period is infective, lymphoid dissemination
• Head to toe spread
• Incubation avg 12 days
• Sx fever, delerium, backache, cough (aerosol)
• Hemorrhagic and Flat-type higher mortality

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Smallpox

• Diagnosis and Treatment
• Dx Guarnieri bodies viral aggregation
• Distinguish subclinical Smallpox from Varicella
• Quarantine for 3 days for rash development post
  exposure
• Vaccines
• Vaccinia
• VIG within 7 days of disease care if recently
  vaccinated

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Viral Encephalitides
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Viral Encephalitides

• Zoonotic viruses
• Aerosolization transmission as well as insect
  route of biological warfare agent a source of
  concern
• Each VE has distinct but similar incubation,
  symptoms and mortality
• Vaccines key to management of VEE, WEE, EEE

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Viral Hemorrhagic Fevers
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Toxins
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Toxins

• General Discussion and Overview
• Mechanism of Toxicity
• Diagnosis/Recognition
• Treatments/Antidotes