Overview of Chemical and Biological Weapons/Terrorism Tucker Greene, MD, FAAEM, ACMT Cape Coral, FL

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

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

Introduction Persistent v. Non-Persistent Biological: Persistent v. Non-Persistent Biological: –Persistent: Anthrax –Non-Persistent: Viruses Persistent v. Non-Persistent Persistent v. Non-Persistent –Persistent: Mustard, VX –Non Persistent: Phosgene, CN

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

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

(brief) History Definitions Definitions –Kill: Soman, VX –Injure: Phosgene –Incapacitate: CS, BZ Countermeasures Countermeasures –Until WWI, US not concerned or interested

(brief) History Pre-WWI Developments Pre-WWI Developments Ancient: hellebore, mandrake in water b.c Ancient: hellebore, mandrake in water b.c Recent: Recent: – : Chlorine, Mustard (dichloroehtylsulfide), chloropicrin –Civil War: Dougherty: Chlorine, 3 qts in shell

(brief) History Biological: Biological: –Mongols in Caffa 1346, bubonic plague bodies –Spanish v French 1495, Leprosy Blood in Naples against French

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

Protection, Control WWI Chemical WWI Chemical –German Wilhelm: Gas cloud due to lack of shells –Allies: Chlorine response Biological: Biological: –Both sides attempting to use anthrax and glanders

US Chemical Warfare Service (CWS) and New Age Chemical Agents placed in Artillery Shells Chemical Agents placed in Artillery Shells –Cl2, Choropicrin, Mustard, Phosgene Biological Agents Biological Agents –Ricin –Brucellosis

US Chemical Warfare Service (CWS) and New Age Detection, Alarms, Treatment Detection, Alarms, Treatment –Human and Animal –Treatment »Inhalation Vomiting Vomiting Venesection Venesection KI KI Steam Tents Steam Tents »Skin: ZnO, Starch, Boric Acid, Calamine

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

US Chemical Warfare Service (CWS) and New Age Near ending of CWS: Near ending of CWS: –Binary weapons –Disposal at Sea –Disseminated Danger of lesser nations? –Johnston Atoll Destruction program

US Chemical Warfare Service (CWS) and New Age Gulf War Gulf War –Iraq with known biological and chemical weapons –MARK I Kit »2-PAM, atropine, valium –Pryidostigmine Bromide –Kamisiyah arsenal detonation »Mustard »sarin

US Chemical Warfare Service (CWS) and New Age Aum Shinrikyo Cult Aum Shinrikyo Cult –Experiments with botulinum and anthrax in subways yields no impact –Later sarin attack kills 50 but injures 5000

DEFENSE (WWI) Mask against Chemical Agents Mask against Chemical Agents Plume identification Plume identification Mobile Decontamination Mobile Decontamination –5% of Division strength Psychological aspect of persistence: mustard (low volatility, low dose effect, still used) Psychological aspect of persistence: mustard (low volatility, low dose effect, still used) –“Gas Mania”

DEFENSE (WWI) Mustard 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

DEFENSE (WWII) Germans thought US possessed secret gases beyond GA< GB< GD and feared reprisal Germans thought US possessed secret gases beyond GA< GB< GD and feared reprisal Continued Vigilance Continued Vigilance –Walt Disney example

Chemical Warfare and the HealthCare Provider

National Warfare Capability

Chemical Warfare Agents

Nerve Agents

Organophoshates History History –Ethanol + Phosphoric Acid –Tabun - GA –Sarin - GB –Soman- GD –VX

Organophosphates Examples Examples

Organophosphates Absorption Absorption –inhalation –dermal –oral Activation Activation –ie parathion Metabolism Metabolism –cholinesterase

Mechanism of Toxicity Mechanism of Toxicity Organophosphates

Organophosphates Clinical Effects Clinical Effects

–Muscarinic (postganglionic parasympathetic) »“SLUDGE” »miosis, bronchorrhea, bradycardia –Nicotinic (neuromuscular junction) –Nicotinic (autonomic ganglion ) Organophosphates

Organophosphates Management/Treatment Management/Treatment –Decontamination –Stabilization –Antidotes »Atropine »Pralidoxime Pralidoxime

Organophosphates Delayed Toxicity Delayed Toxicity –Intermediate Syndrome –Peripheral Neuropathy »Tri -o-cresyl phosphate (TOCP) »Tri -o-cresyl {tolyl} phosphate TOTP »Neurotoxic Esterase

Organophosphates Delayed Toxicity Delayed Toxicity –Intermediate Syndrome –Peripheral Neuropathy »Tri -o-cresyl phosphate (TOCP) »Tri -o-cresyl {tolyl} phosphate TOTP »Neurotoxic Esterase

Organophosphates Laboratory Laboratory –Don’t Need To Treat!!! –Cholinesterase Levels »RBC v Plasma »Variation from Baseline

Pretreatment Pyridostigmine (carbamate) Pyridostigmine (carbamate) Used in Gulf War Used in Gulf War

Vesicants

Sulfur Mustard

Phosgene

Lewisite

Inhalational Agents

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

Inhalational Agents

Cyanide Treatment Cyanide Treatment –Nitrites –Thiosulfate –Hydroxycobalamin –Hyperbaric O2

Incapacitating Agents

Anticholinergics Anticholinergics LSD, other Indoles LSD, other Indoles Opiates Opiates

Riot Control Agents Rapid Onset, Upper Airway and GI Symptoms Rapid Onset, Upper Airway and GI Symptoms CS (o-Chlorobenzylidene) CS (o-Chlorobenzylidene) CN (1-Chloroacetophenone) CN (1-Chloroacetophenone) Other Other –DM (Diphenylaminearsine) –CR (Dibenzo(b,f)-1:4oxazepine –CA (Bromobenzylcyanide)

Riot Control Agents CS 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

Riot Control Agents Treatment Treatment –Alkaline decon of skin; no hypochlorite –Topical steroids for skin –Local anesthetics for eyes

Field Management of Chemical Casualties Hot Zones Hot Zones Clean v Decontamination areas Clean v Decontamination areas Counter-current or Reverse Airflow for Decontamination Areas Counter-current or Reverse Airflow for Decontamination Areas Triage Triage –Potential ID –Look for Combined Agents/Injuries –Difficult to Treat Combinations

Decontamination Chemical Chemical –Desirable Traits for Dermal Decon –Physical Removal –Aqueous –Adsorbent Biological –Dermal not as Important (T-2 is exception) –Hypochlorite –Environmental UV

BIOLOGICALS

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

Use of Biological Weapons Requirements Requirements –Ease of Production –Lethality/Incapacitation –Particle size –Ease of Dispersion –Stability Methods of Delivery –Food –Water –Air

Use of Biological Weapons Advantage/Disadvantage Advantage/Disadvantage –Predominantly concerns of the pathogen occurring in aggressors –Persistence –Insidious, low cost, minimal detection Tactical Concerns –Hard to Trace or Fingerprint –Terrorism as we now have known the anthrax cases

Biological Agents Anthrax Anthrax Plague Plague Tularemia Tularemia Brucellosis Brucellosis Q Fever Q Fever Smallpox Viral Encephalitides Viral Hemorrhagic Fevers Toxins –Plants –Animals –Mycotoxins

Anthrax History History –Bacillus anthracis –Zoonotic:goats sheep, cattle, swine, horses –5 th and 6 th 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

Anthrax Epidemiology Epidemiology –1958: ,000 cases worldwide –Since 1970 one case/decade –Woolsorter’s Disease Pathogenesis –Antiphagocytic Capsule –Lethal Toxin –Edema Toxin –Mechanism by cell binding and then active toxin

Anthrax Clinical Disease Clinical Disease –Cutaneous –Inhalational –Gastointestinal –Meningeal Diagnosis –CLINICAL SUSPICION OF EXPOSURE

Anthrax Treatment Treatment –Pen G –Doxycycline –Ciprofloxacin –Many other possibly effective Recombinants may possess resistance as the native vegetative state has lactamases

Plague History History –Pandemics of the 6 th, 14 th, 20 th century –24 Million died from –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

Plague Epidemiology 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

Plague Clinical Features 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

Plague Diagnosis Diagnosis –Differential »Cat Scratch »Tularemia »LGV »Chancroid »TB »Streptococccal »Rickettsiae Lab Confirm –Aspiration of Bubo –Wright-Giemsa, Gram Stain

Plague Treatment 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

Tularemia History 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

Tularemia Epidemiology 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

Tularemia Clinical Features Clinical Features –Incubation 3-6 day –Ulceroglandular 75% »Skin or mucous membranes, nodes >1cm –Typhoidal 25% »Smaller nodes »Non-mucous membranes Multiple Const/Syst complaints –Fever –HA –Chills –Abdominal pain –Fluctuant Lymph nodes (drainage)

Tularemia Diagnosis Diagnosis –Difficult serology and growth medium procedures –ELISA most reliable Treatment –Streptomycin –Aminoglycosides –Chloramphenicol –Tetracyclines Prophylaxis –Doxycycline

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

Brucellosis Epidemiology 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 bacteria/gram

Brucellosis Clinical Features Clinical Features –diverse, variability –3d to weeks incubation –Neuropsychiatric along with fever, cough, arthritis –Mild lab abnormalities Diagnosis –Serum agglutination –PCR –IgG

Brucellosis Treatment Treatment –Doxycycline –Streptomycin –Aminoglycosides Prophylaxis Prophylaxis –Prevention (no-vaccine) –Doxycycline

Q Fever History 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

Q Fever Epidemiology 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

Q Fever Clinical Features Clinical Features –Incubation days –Asymptomatic seroconversion –Acute Disease: »Chill,rigors,retroorbital HA »Fever, myalgias –Chronic: endocarditis Diagnosis –Serological »Comp Fixation »Indir Flour Ab »ELISA

Q Fever Treatment Treatment –Tetracyclines –Macrolides –Quinolones in chronic disease Prophylaxis Prophylaxis –Vaccine –Doxycycline

Smallpox Variola – ds-DNA, Orthopox Virus 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 Possible to recover Smallpox from preserved cadavers or recombinant with monkeypox

Smallpox Pathogenesis and Clinical Features 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

Smallpox Diagnosis and Treatment 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

Viral Encephalitides

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

Viral Hemorrhagic Fevers

Toxins

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