Chemical and Biological Warfare Agents

Chemical and Biological Warfare Agents

Charles Stewart MD FACEP

Thinking Out of The BoxThinking Out of The Box

Unrestricted warfare Unrestricted warfare

“With technological developments being in the process of striving to increase the types of weapons, a breakthrough in our thinking can open up the domain of the weapons kingdom at one stroke.”

Unrestricted Warfare is a Way of Thinking Out of the Box…

Unrestricted Warfare is a Way of Thinking Out of the Box…

Unrestricted warfare Unrestricted warfare

“The new concept of weapons will cause ordinary people and military men alike to be greatly astonished at the fact that commonplace things that are close to them can also become weapons with which to engage in war. We believe that some morning people will awake to discover with surprise that quite a few gentle and kind things have begun to have offensive and lethal characteristics.”

Unrestricted warfare Unrestricted warfare “It means that all weapons and technology can be superimposed at will, it means that all the boundaries lying between the two worlds of war and non-war, of military and non-military, will be totally destroyed.”

Unrestricted Warfare Qiao Liang and Wang Xiangsui

Beijing: PLA Literature and Arts Publishing House, February 1999

Unrestricted Warfare Qiao Liang and Wang Xiangsui

Beijing: PLA Literature and Arts Publishing House, February 1999

Realism in Theater Realism in Theater Are we sufficiently prepared for

the Right Threats? Some other possible problems

NIH. –Not invented here Media “guidance“ does not actually

define a real threat. Politicians often “react” and nay not

properly plan for real threats “Security” may make us less secure Simple solutions don’t always solve

complex problems.

What Should We Really Plan For? What Should We Really Plan For?

Explosives Flammable agents Chemical agents Biological Agents Radiological dispersion weapons Nuclear weapons Snipers?

All of them are possible threats !All of them are possible threats !

Bombings are still the single most common form of terrorism

Bombings are still the single most common form of terrorism Conventional explosives are easy

to get and easy to use. Look for new ways to make and

deliver them.

Types of terror attacks?Think Bombs!

Types of terror attacks?Think Bombs!

8 7 %

6 %

4 %

3 %

B o m b in g s K id n a p p in g s S h o o t in g s A l l o t h e r s

Terrorist threat of explosives Terrorist threat of explosives Readily available

PredictableFamiliar effects

Abundant training available

Abundant information available

No difficulty with delivery

Asymmetric Warfare Asymmetric Warfare Them:

4 small crews100% “ martyrs”

Us: More than 4000 direct casualties 100’s of millions of $$ in damages Massive damage to tourism and

transportation industries

Law of unintended consequences Law of unintended consequences

Lessons learned Big missions can cause big consequences

but provoke large responses Little missions can cause big consequences

with minimal risks Anthrax or sniper model attacks

Does this mean that new incidents will be small in scope with maximum media impact?

Possibly

Law of unintended consequencesLaw of unintended consequences

“Pearl Harbor” syndrome fully activated

Secondary losses Loss of safe haven

Afghanistan Iraq?

System degradation Financial support degradation

Potential Terrorist TargetsPotential Terrorist Targets Critical facilities and infrastructure

CongressPresidential staffSupreme Court

Enclosed spaces Large crowds (high profile events) Facilities of interest to terrorists’

cause

In 2001, They Planned for at Least 3 and Possibly 4 Targets

In 2001, They Planned for at Least 3 and Possibly 4 Targets

?

In 2003, They Chose 3 Targets in Saudi Arabia In 2003, They Chose 3 Targets in Saudi Arabia

Terrorist threat of snipers Terrorist threat of snipers Weapons are

readily available in almost all countries PredictableEffects familiar to

EMS Absolutely no

difficulty with delivery

High media impact

Terrorist threat of snipersTerrorist threat of snipers Look at how two poorly trained and

poorly equipped snipers affected 3 states in 2002 10 dead,3 injured Think about how two or three teams

of well trained snipers would be able to hurt us.

Has your EMS unit discussed/gamed/planned how to handle this type of terrorism?

Terrorist Threat of Chemical and Biological Agents

Terrorist Threat of Chemical and Biological Agents Ideal weapons of terrorism

Easily and cheaply madeEasily deliveredRapidly manufacturedTechnical information not “hot” Political effects far beyond local

casualties

Terrorist Threat of Incendiary Agents Terrorist Threat of Incendiary Agents

Readily available PredictableFamiliar effects

Abundant training available

Abundant information available

No difficulty delivering

Terrorist Threat of Nuclear Weapons Terrorist Threat of Nuclear Weapons Not easily available

Fairly predictable Great difficulty with

delivery?? Unfamiliar effects to most

EMS Abundant training

available Abundant information

available

Readily detected ?Closely controlled

Terrorist Threat of Radiological Weapons Terrorist Threat of Radiological Weapons Moderately available

Fairly predictableUnfamiliar effects to

most EMS Abundant training

available Abundant information

available No difficulty with delivery

Readily detected This is the easiest type of

terrorism to detect! Media hype expected

Radiologic Dispersal Weapons Radiologic Dispersal Weapons

Great media hype Probably a small number of actual

casualties A quantity of sufficiently radioactive

agent to cause real damage must: Be set up as a fine particle (ground) Transported to the area where it is to be

used Shielded from detection

This is not an easy set of tasks

Chemical and biological weapons are simply tools of unrestricted warfare

Chemical and biological weapons are simply tools of unrestricted warfare

Terrorist Threat of Chemical Weapons Terrorist Threat of Chemical Weapons

Moderately available Fairly predictableUnfamiliar effects to

most EMS ? Abundant training

available Abundant information

available Readily detected ??

No difficulty with delivery

Simplistic solutions? Simplistic solutions? Decontamination –wash them all

down with water?Simple, easily implemented solution Particularly effective for Sarin

Simplistic solutions?Simplistic solutions? Neglects fact that hydrolysis is not

always effective or beneficial Water is not particularly effective for Vx

and other oily or thickened Agents? – Thickened Soman was in Russian inventory.

Vx is hydrolyzed to EA2192 – Water actually makes VX into a far more toxic

and longer lasting substance

EA2192 = Diethyl methylphosphonate, 2 diisopropylaminoethyl mercaptan, ethyl hydrogen methyl-phosphonate, bis(ethylmethylphosphonic)anhydride, bis S- (2-diisopropylaminoethyl) methylphosphononodithiote.

Simplistic solutions?Simplistic solutions? Bleach is bad ?

GRAS – generally recognized as safe! Theoretically could consume 4 oz with no

ill effects. Hundreds of children have done so.

Bleach is a better decontamination agent than water

Much more rapid than water Known activity against mustard, Soman,

and VX-(military evidence in 50’s)

Simplistic solutions?Simplistic solutions? Water is not particularly effective

for mustardEuropeans found bleach and sodium

thiosufate to be more effective No experience at all with water

decontamination of “dusty” agentsDusty mustard Dusty Soman and Sarin

Decon Shower Decon Shower

Simplistic solutions?Simplistic solutions? Water will dilute and render safe

this substance by lowering the concentration so that no significant downstream damage will occur? Sarin – probably -volatile and non

persistent VX-???-long lived toxic hydrolysis

products Soman-???Mustard -???

Downstream safety Downstream safety

?

Dusty Agents Dusty Agents Combination of a chemical warfare

agent with a very finely divided silica or talc powder to make a particulate aerosol

Civilian technology Ortho Ant-Stop is an

organophosphate in an inert carrier

Dusty mustardDusty mustard Enhanced penetration of protective

equipment Goes under MOPP gear “May” penetrate Level A PPE

Insufficient data exists to substantiate this statement

More rapid and enhanced pulmonary effect of mustard on unprotected

Dusty VX –Sarin –Soman Dusty VX –Sarin –Soman Enhanced penetration of protective

equipment Goes under MOPP gear “May” penetrate Level A PPE*

More rapid and enhanced pulmonary absorption of VX on unprotected “May” give a picture more like Sarin*

“May” make Sarin or Soman less volatile*

*Insufficient data exists to substantiate this statement

Dusty AgentsDusty Agents Original Solution

”WHILE EMPHASIZING THAT THERE IS NO EVIDENCE THAT IRAQ HAS DEVELOPED A DUSTY V-AGENT, FATALITIES RANGING FROM 3 TO 38 PERCENT ARE PROJECTED FOR THE SAME CONCENTRATIONS CITED ABOVE FOR TROOPS IN FULL MOPP IF SUCH AN AGENT WERE USED. USE OF THE PONCHO OVER THE MOPP GEAR IS EXPECTED TO REDUCE THESE PROJECTED CASUALTIES TO NEAR ZERO EVEN FOR A DUSTY NERVE AGENT. “

Dusty AgentsDusty Agents One senses that the prior

recommendation was a desperate attempt to offer reassurance and a temporary “solution” for the troops.

Certainty, an open flapping poncho would offer no substantial improvement in chemical threat protection

SERPACWASERPACWA Better solution took

8 years to develop Skin Exposure

Reduction Paste Against Chemical Warfare Agents

Paste contains a perfluoroalkylpolyether (PFAPE) oil as a base polymer and polytetrafluoroethylene (Teflon polymer) dispersed within the base oil

ATSP soon to come

Simplistic solutions?Simplistic solutions? Everybody needs to be in Level A-

B-C gear for personal protection Governmental recommendations?

OSHA? OPP gear is, at best, level C protection

– Splash-Resistant over suit – Purified air (Negative Pressure) Protective

mask Turn-out gear +SCBA = 30 minutes

protection? I don’t know the “ Right” answer to this question.

MOPPMOPP

Chemical Threats –NIH Problem Chemical Threats –NIH Problem What is best cyanide antidote?

? Lilly cyanide kit? Expensive Awkward to use Dangerous to peds

Chemical Threats –NIH Problem Chemical Threats –NIH Problem

Hydroxycobalamin NlH? Vitamin B12 Widely available and quite cheap Not FDA approved for this

Kelocyanor? NIH? Available and widely used in Europe Pricy?

Terrorist Threat of Biowar AgentsTerrorist Threat of Biowar Agents

We were assured that biological agents were poor weapons of terrorism??Unpredictable

Weather Lifespan (survivability) ? Few good studies on effectiveness

StigmaDifficulty with delivery ??

Terrorist Threat of Biowar AgentsTerrorist Threat of Biowar Agents We were assured that biological

agents were poor weapons of terrorism??Unpredictable

Weather Lifespan (survivability) ? Few good studies on effectiveness

StigmaDifficulty with delivery ??

We Were Expecting “ The Big One”...We Were Expecting “ The Big One”...

We Got …We Got …

Historically most episodes of terrorism are rather small affairs…This is a principle

of asymmetric warfare…

Think about the confusion generated by …

Why Bioweapons? - Other AdvantagesWhy Bioweapons? - Other Advantages Undetectable by usual means Remote effect (time-lag)

Perpetrator can leave scene Widespread effect before discovery

FlexibleCovert vs OvertSmall scale vs large scale

Small amounts can inspire significant terror

Real Threat…or Fancy Fiction

Real Threat…or Fancy Fiction

Delivery will be a problem???

Real Threat…or Fancy FictionReal Threat…or Fancy Fiction

Terrorists need more expertise than they’ve got???

Larry Wayne Harris

Larry Wayne Harris

Real Threat…or Fancy Fiction

Real Threat…or Fancy Fiction

You just can’t get these bugs anymore….(we have controls,

you know)???

Endemic source of plague in western USA Endemic source of plague in western USA

Real Threat…or Fancy FictionReal Threat…or Fancy Fiction High lethality does not mean a

large number of deaths???

Remains to be proven. Remains to be proven.

Biowarfare Agent SourcesBiowarfare Agent Sources Home production Laboratory / commercial

production Industrial facilities Foreign military sources Medical / university research

facilities

HistoryHistory Romans

Used dead animals to foul water supply

MongolsCatapulted plague victims into Kaffa

EnglishGave smallpox infested blankets to

Indians during French-English war in colonies.

History: German Agents in WWIHistory: German Agents in WWI

Dr. Alton Dilger in Washington DCAnthrax and

GlandersAbout 3500

horses infectedMore people died

than from the 2001 anthrax

History - TerroristHistory - Terrorist 1915 Dr. A Dilger (German-

American) produces anthrax and glanders

1972 ‘Order of the Rising Sun’ prepares 30 kg of typhoid bacteria cultures

1978 Giorgi Markov assassinated with ricin

History - Unit 731History - Unit 731 1918 - Unit 731 established in

Japan Unit 731 deploys in Manchuria in

WWII Investigates multiple organisms

including plague

1941 Bubonic plague sprayed in China by Japanese

1942 Bacterial “bombs” used by Japanese

History - USA ExperimentsHistory - USA Experiments 1950-1969 Off coast USA –

Experiments with Serratia US Army and Navy for several cities including San Francisco and LA

1966 Bacillus subtilis via subway route in NYC

US Army

1966 Pentagon ‘bombed’ by Chemical Corps

History: A Salad Bar in OregonHistory: A Salad Bar in Oregon 1984 Rajneesh

cult seeds salad bars in Oregon with typhoid to influence an election

AnthraxAnthrax Known experience with this agent Sverdlovsk (Ekatrinburg) Russia

1979Accidental military releaseWe will talk about this later.

History History 1983 2 brothers in Northeastern

USA produce 1 ounce of pure ricin 1984 Red Army Faction found with

botulinum toxin in Paris

History History 1991 Iraq bioweapons program

uncovered during Gulf War 1992 Ken Alibek defects to USA

and exposes the Soviet program

Ladies and gentlemen… we have a real problem.

History History 2001 Anthrax

used via postal delivery methods…. Osma Bin Laden suspected.

History History Sort of puts the lie to anybody who

thinks this ain’t gonna happen here …

Asymmetric Warfare Asymmetric Warfare We need to be prepared for the

next phase… and we don’t know what that phase is or when it will occur.We aren’t ready for a lot of these

problems

Possible Biologic AgentsPossible Biologic Agentsanthrax, cryptococcosis, escherichia coli, haemophilus influenzae, brucellosis (undulant fever), coccidioidomycosis (San Joaquin Valley or desert fever), psittacosis (parrot fever), yersina pestis (the Black Death of the 14th Century), tularemia (rabbit fever), malaria, cholera, typhoid, bubonic plague, cobra venom, shellfish toxin, botulinal toxin, saxitoxin, ricin, smallpox, shigella flexneri, s. dysenteriae (Shiga bacillus), salmonella, staphylococcus enterotoxin B, hemorrhagic fever, Venezuelan equine encephalitis, histoplasma capsulatum, pneumonic plague, West Nile fever, Rocky Mountain spotted fever, dengue fever, Rift Valley fever, diptheria, melioidosis, glanders, tuberculosis, infectious hepatitus, encephalitides, blastomycosis, nocardiosis, yellow fever, typhus, tricothecene mycotoxin, aflatoxin, and Q fever.

Who knows?

Possible Biologic AgentsPossible Biologic Agents The CDC “master list”

A compromise between A limited budget Public /media fears Agents known to hove been developed as

warfare agents

Does not cover all threats! A growing threat New and emerging diseases not listed

Detection of OutbreakDetection of Outbreak Epidemiologic investigation Syndrome Based

Inhalation anthrax

BW - Epidemiologic CluesBW - Epidemiologic Clues Large epidemic with high illness

and death rate Infection non-endemic for region Multiple, simultaneous outbreaks Multi-drug-resistant pathogens Sick or dead animals

BW - Epidemiologic Clues…BW - Epidemiologic Clues… Delivery vehicle or vector found Intelligence of possible event

BW - Epidemiological Information

BW - Epidemiological Information

Travel history Infectious contacts Employment history Activities over the

preceding 3 to 5 days

Aerosol SpreadAerosol Spread Ideal aerosol is a homogeneous

population of 2 or 3 micron particulatesThis is the best “suspension” of

particles for RESPIRATORY spreadPlease note that other sizes may well

be infective also. Maximum human respiratory

infection is a particle within 1 to 5 micron size

Infection Severity

Aerosol / Infectivity RelationshipAerosol / Infectivity Relationship

Particle Size

18-20

15-18

7-12

4-6(bronchioles)

1-5 (alveoli)

Less Severe

More Severe

Delivery SystemsDelivery Systems Airborne

Biological Agents - Types and CharacteristicsBiological Agents - Types and Characteristics

Live Agents Biotoxins

These are more like chemical warfare agents

Possible Live Biowarfare AgentsPossible Live Biowarfare Agents Viruses Rickettsia Bacteria Fungi ?? Prions ?? (mad cow disease)

AnthraxAnthrax

AnthraxAnthrax

Anthrax is an acute infectious disease of animals caused by Bacillus anthracis.

Gram positive rods

Spore forming

May persist in soil for over 50 years!

Anthrax Anthrax Humans can

develop infection from handling contaminated fluids or hides (“Woolsorters

Disease”)

AnthraxAnthrax Spores can be

produced in a dry form for biological warfare

may be stored and ground into particles.

When inhaled by humans, these particles cause respiratory failure and death within a week.

AnthraxAnthrax

It is rare to find infected animals in the United States..

Most United States cases are in Texas, Louisiana, Mississippi, Oklahoma and South Dakota.

AnthraxAnthrax Anthrax is most

common in under-developed agricultural regions

South and Central America

Southern and Eastern Europe

Asia, Africa,

the Caribbean

the Middle East.

AnthraxAnthrax 3 forms of Anthrax infection

cutaneous (skin) - most commoninhalationgastrointestinal

Anthrax - Pathogenesis Anthrax - Pathogenesis Virulent bacteria produce toxins

edema factor lethal factor

Spores are ingested by WBC’s and travel to the regional lymph nodes

Cutaneous AnthraxCutaneous Anthrax Cutaneous

VesicleUlcerates with black necrotic centerRegional lymphadenopathy

Untreated skin infection - 20% mortality if septicemia develops (treated 1%)

Cutaneous AnthraxCutaneous Anthrax

Inhalation AnthraxInhalation Anthrax

Initial symptoms like a viral syndrome1 to 6-day incubation period followed by

fever, myalgias, cough, and fatigue

Often get better for short time

Initial improvement is followed by abrupt onset of respiratory distress, shock, and death in 24 to 36 hours

Inhalation AnthraxInhalation Anthrax

Chest x-ray shows a widened mediastinum with or without a bloody pleural effusion

Inhalation AnthraxInhalation Anthrax Inhaled anthrax causes

mediastinitisGerminated bacteria travel to

regional lymph nodes 50 % of cases have associated

hemorrhagic meningitis

Anthrax MeningitisAnthrax Meningitis

Intestinal AnthraxIntestinal Anthrax

Consumption of contaminated meat

Inflammation of the intestinal tract

Nausea, loss of appetite, vomiting, fever

Abdominal pain, bloody vomit, and diarrhea

Death in 25% to 60% of cases

AnthraxAnthrax Biowarfare agent

Does not spread person to personSpores may be spread with multiple

types of equipmentProphylaxis is possibleCheap and easy to produceReadily available

Anthrax TransmissionAnthrax Transmission No documented person-to-person

transmission of inhalation anthrax has ever occurred

Cutaneous transmission is possibleUniversal precautions required

Inhalation Anthrax - DiagnosisInhalation Anthrax - Diagnosis

Nonspecific symptomsFever, headache, malaise

Substernal chest pain Sudden onset of respiratory distress

Widened mediastinum on chest x-rayHemorrhagic mediastinitis

Some patients may present with GI or cutaneous anthrax

Inhalation Anthrax - DiagnosisInhalation Anthrax - Diagnosis

Emergency physicians are “first responders” in this disease.

This is contrary to usual EMS thinking But the “ first response “ for patients

with initial complaints of malaise, fever, headache probably won’t occur in the field.

The first Anthrax diagnosis was made by emergency physicians

Anthrax -diagnosisAnthrax -diagnosis Nasal swabs

Poor way to check asymptomatic folks

Gram stain of bloodOften too late for inhalation disease

ELISA and immunohistology testing may confirm diagnosis but samples must go to reference laboratory for cultures

Anthrax - ProphylaxisAnthrax - Prophylaxis Anthrax vaccine

Cell free filtrateProven for cutaneousNot proven for inhalation or massive

exposures.Requires 6 injectionsRequires yearly booster

Anthrax - ProphylaxisAnthrax - Prophylaxis Unimmunized persons

Cipro 500 bid PO No reason why another quinolone would

not be effective.

Doxycycline 100 bid PO?? PenicillinContinue antibiotics for 4 weeks at a

minimumVaccinate!

Anthrax - TherapyAnthrax - Therapy Penicillin

Resistance is easy to achieve Cipro Chloramphenicol Doxycycline

Tetracycline Erythromycin

Anthrax - Pediatric TreatmentAnthrax - Pediatric Treatment Prophylaxis

PenicillinDoxycycline? Cipro

IV TherapyPenicillin? CiproDoxycycline

AnthraxAnthrax Known experience with this agent Sverdlovsk (Ekatrinburg) Russia

1979 Accidental military release

Sverdlovsk = EkaterinburgSverdlovsk = Ekaterinburg

Anthrax - SverdlovskAnthrax - Sverdlovsk

This accident resulted in over 66 deaths downwind.

Biological Warfare research, production and

storage facility

Biological Warfare research, production and

storage facility

Path of airborne Anthrax – over 20

kilometers downwind

Path of airborne Anthrax – over 20

kilometers downwind

Inhalation Anthrax is a slow infectionInhalation Anthrax is a slow infection

Exposure

01

23

45

67

89

1011

1213

14 16 18 20 22 24 26 28 30 32 38 4034 36 4243

Each represents one death

1979 Sverdlovsk deaths… per day after exposure

Current experience

Current experience

We still don’t know who did this.

The technology could still be re-used???

PlaguePlague Yersinia (Pasturella) pestis

The Black Death - Bubonic plagueFlea bite

Found worldwide Prairie dogs in Rocky Mountain areas

Bipolar gram-negative rod

PlaguePlague 3 Presentations

BubonicSepticRespiratory

Plague - bubonicPlague - bubonic Usual natural transmission form Localized abscess at site of

infection Regional lymph glands form large

abscesses Incubation 2-10 days

Plague Disease ComplexPlague Disease Complex

Inhalational

SystemicToxicity

Respiratory failure & circulatory collapse

Liverenzymes

6% latemeningitis

Fulminant Pneumonia

Fever, URI syndrome

Sudden onset

Leukemoidreaction

Gram negativerods in sputum

Fever/rigors Erythema

Tender bubo1 - 10 cm

APTTecchymosis

DIC

Stridor, cyanosis,productive cough,bilateral infiltrates

Pharyngitis2 -3 days 2 - 10 days

24 hrs

9%

Bubonic PlagueBubonic Plague Erythema, fever, rigors Bubo formation in

regional lymph nodes Bubo aspiration and

gram stain is diagnostic

Plague - pneumonicPlague - pneumonic Aerosol transmission Highly lethal Rapid infection (1-2 days)

Plague - pneumonicPlague - pneumonic 2 to 3 day incubation period

followed by high fever, myalgias, chills, headache, and cough with bloody sputum

Pneumonia and sepsis develop acutely and may be fulminant Patients develop dyspnea, stridor,

cyanosis, and circulatory collapse

Plague – pneumonicPlague – pneumonic Patchy infiltrates or consolidation

seen on chest x-ray

Plague - septicPlague - septic Blood-borne spread from other

sites to lungs, CNS and other sitesHighly lethalOften has features of pneumonic but

slower onset

Acral GangreneAcral Gangrene Late complication

of pneumonic or septicemic plague

May occur in the fingers, toes, earlobes, nose, or penis.

Plague - diagnosisPlague - diagnosis Clinical suspicion Lymph node aspirate

Gram stain Check sputum and CSF too…. Culture of the aspirate, sputum,

CSF, or blood

PlaguePlague Therapy must be started rapidly! Streptomycin (30 mg/kg/day IM

divided BID for 10 days) Doxycycline (100 mg IV BID for 10

days) Chloramphenicol for plague

meningitis

Plague - Pediatric TreatmentPlague - Pediatric Treatment Prophylaxis

Doxycycline Trimethoprim/Sulfamethoxazole

IV TherapyStreptomycin (over 1 year of age)GentamicinChloramphenicol

Plague - prophylaxisPlague - prophylaxis Vaccine is available… but it won’t

protect against aerosol spread… Vaccine effective only for

bubonic plague Prophylactic doxycycline will

‘probably’ be effective if started prior to exposure...

Plague - ProphylaxisPlague - Prophylaxis Secondary

transmission is possible and likely

Universal and aerosol precautions until sputum cultures are

negative pneumonic plague is

excluded

Plague - prophylaxisPlague - prophylaxis Strict isolation is important for

plague victims…Respiratory isolation is mandatory for

the first 48 hours of treatment Violent coughing easily spreads

infected sputum Vector control is important to

prevent infection of local fleas and rodents.

PlaguePlague This agent is not an ideal war

bug...but it is readily available, has limited spread, and is relatively hardy. It would cause substantial casualties.

It has the potential of infecting local fleas and rodents as a persistent agent.It was used in WWII as a warfare agent

TularemiaTularemia Incubation 2-10 days Oculoglandular Typhoidal Treatment: gentamicin Prophylaxis: vaccine

(experimental) or 2 weeks of tetracycline

SmallpoxSmallpox Variola virus Extinct?

2 ‘legal’ repositories known US and Russia Russia developed military stocks of

smallpox

Monkeypox, cowpox, and ‘chickenpox’ are quite similar

May lend to genetic manipulation Or just selection of a specific variant

SmallpoxSmallpox

Last known natural smallpox victim

Ali Maalim Somalia 1977

Smallpox - presentationSmallpox - presentation Incubation period 12-14 days Prodromal period Skin lesions

Uniform progression of the lesionsRash looks like chickenpox lesions only

uniform Healing in 1-2 weeks Fatal in 30% of cases (Variola

major)

Smallpox …comes in more thon one

variant Smallpox …comes in more thon one

variant Variola major …30% mortality Variola minor …5% mortality Variola “hemorrhagic variant”

mortality unknown …probably >70% Variola “flat variant “

mortality unknown …probably >50%

SmallpoxSmallpox Diagnosis by clinical examination Electron microscopy Viral culture

SmallpoxSmallpox Therapy is supportive Would antiviral drugs…work?

There are some drugs that appear to have appropriate effect in animal studies, but these are in short supply

CDC/Cheryl Tryon

Child with Smallpox rashChild with Smallpox rash

SmallpoxSmallpox Prophylaxis

Vaccine is available and very effective.

Jenner

Vaccinia immune globulin Role is unclear Used for treatment of vaccina reactions

CDC/James Hicks, 1973

Smallpox rash close-up Smallpox rash close-up

SmallpoxSmallpox All material used in patient care

should be burned or autoclaved Considerable potential for person-

to-person spread

Smallpox - prophylaxisSmallpox - prophylaxis Quarantined all

contacts for at least 17 days

Infectious until all scabs are healed over

SmallpoxSmallpox Has already been used in warfare

British use of smallpox infested blankets for Indians

CDC

Last child with SmallpoxLast child with Smallpox

Smallpox Smallpox Current plan is to

encircle an outbreak of small pox with a ring of immunization so that the infection can’t spread any further .

Smallpox Smallpox Ring system requires

A group of health care providers who are already immunized .

Rapid identification of cases

Isolation of the suspected cases

Smallpox ring system requires Smallpox ring system requires Contact tracing Massive

immunizations Isolated outbreak Effective

immunization (prevents disease)

Smallpox Smallpox Ring system

assumes Folks will not refuse

vaccination Resources are not

exhausted Quarantine will be

observed. 1:3-1:5 infectivity

What about O’ Hara ?What about O’ Hara ? Any major airport

Agent release or infected person

High travel season

Widespread infection Infection date may

not be known Contact tracing

difficult Look at SARS

Smallpox Smallpox Ring system

assumes that immunization will be effective both in decreasing mortality of the disease in those who have been exposed and effective in preventing further spread of disease

But… will it be “ blackpox “But… will it be “ blackpox “ The smallpox variant developed by

the Russians was a hemorrhagic smallpox

(This type of smallpox is sometimes called” blackpox” because of the massive subcutaneous

hemorrhage found in these patients ) Vozozhdeniye Island in Aral Sea was

site of a presumed accidental release in 1971

Patient #

Age Sex Date of onset

Type of Rash Prior Vacc

Dead vs live

1 24 F 8/17 Classic Yes Rec

2 9 M 8/27 Classic Yes Rec

3 23 F 9/10 Hemorrhagic No †

4 36 F 9/10 Classic Yes Rec

5 5.5 M 9/18 Classic Yes Rec

6 38 M 9/24 Mild Yes Rec

7 0.8 M 9/26 Hemorrhagic No †

8 60 F 9/26 Mild Yes x3 Rec

9 33 M 9/28 Mild Yes Rec

10 0.33 F 10/2 Hemorrhagic No †

The Aralsk smallpox epidemic in 1971 was a presumed weapon release from

Vozozhdeniye Island in the Aral Sea.

Aralsk smallpox outbreak Aralsk smallpox outbreak

Smallpox –blackpox variant Smallpox –blackpox variant Ring Strategy would not stop spread of this

form of disease It was not protective against getting the

disease. Vaccination is protective against death in

black pox Massive immunization would decrease

mortality100% mortality in unimmunized.

Note: Data about this variant of smallpox is scanty and may well

not be this grim

What about the Toronto model ?What about the Toronto model ? SARS

Health care system devastated

Resources exhausted

EMS shut down This is for a

disease with 10% mortality

Monkeypox VirusMonkeypox Virus

Viral hemorrhagic feverViral hemorrhagic fever

Fever, myalgias, prostration Target organ is the vascular

bed.Conjunctival injection, petechial

hemorrhage, and hypotensionFollowed by shock and

generalized hemorrhage

Ebola virusEbola virus Viral

Hemorrhagic fever

No known therapySome antisera

may…be effective

No known prophylaxis

VHFVHF Mortality varies

50 - 80% Ebola Zaire Abnormal renal and liver

function tests - poor prognosis Disease severity and survival

depends on various host factors

VHF TreatmentVHF Treatment Hemodynamic resuscitation and

monitoringInvasive Swan Gantz catheter as

feasible Careful fluid management

use of colloid Vasopressors and cardiotonic

drugs

VHF TreatmentVHF Treatment Cautious sedation and analgesia No anti-platelet drugs or IM

injections Coagulation studies and

replacement of clotting factors / platelet transfusions

Prevention of VHFPrevention of VHF Single room w/ adjoining anteroom

as only entrancehandwashing facility with

decontamination solution Negative air pressure if possible

Prevention of VHFPrevention of VHF Strict barrier precautions

gloves, gown, mask. shoe covers, protective eyeware/faceshield

consider HEPA respirator for prominent hemorrhage, vomiting, diarrhea, cough

There is no effective vaccine at this time.

Ebola Case Study 1995Ebola Case Study 1995 April 5 - Zaire laboratory worker

fever and bloody diarrhea May 17 - 93 cases - 92% fatality

most cases were in health care providers

June 25 - 296 cases When institutional barrier precautions

were implemented by WHO/CDC - the infection rate among health care workers dramatically decreased.

Possible biotoxinsPossible biotoxins Botulinum Clostridia Ricin Saxitoxin Tetrodotoxin Staphylococcal enterotoxin Tricothecene mycotoxins

Botulinum toxinsBotulinum toxins Seven species (A-G) Anaerobic spore forming bacterium

Canned foodsGI tractWounds

Aerosol of toxinLethal toxin

Botulinum toxinsBotulinum toxins

Clostridum botulinum

Botulinum toxinsBotulinum toxins Signs and symptoms

PtosisDiplopiaDysphagiaDysphoniaFlaccid paralysisRespiratory failure

Botulinum toxinsBotulinum toxins Diagnosis

No available rapid laboratory diagnosis

Assay exists… but is only good for confirmation

Takes a while to return the results….

Suspect if numerous casualties develop bulbar paralysis, muscle weakness, and respiratory failure

Botulinum toxinsBotulinum toxins Treatment

Supportive care Intubation Ventilation

Trivalent antitoxin (A,B,E) Horse serum Must be given as soon as possible

Heptavalent USAMRIID antitoxin Investigational horse serum

Botulinum toxinsBotulinum toxins Prophylaxis

Toxoid (A,B, C, D, E) Investigational product 3x injections with yearly booster High risk of exposure

Botulinum toxinsBotulinum toxins Decontamination

Was with bleach or soap and waterPressure cook all foodsToxin does not go through skin

BotulinumBotulinum Outbreak control

Immediate release Rapidly decontaminated

Late contamination Boil for 10 minutes

Ok… Why haven’t we seen...Ok… Why haven’t we seen... Unpredictable

Collateral damageMoral qualms???

Personal safety Severe response

Damage causeOut of control?? Deny responsibility

Why haven’t we seen..Why haven’t we seen.. Higher authority says no... Present day tactics are successful Lack of precedent Can’t get credit for the...

Delivery Systems – ImprovDelivery Systems – Improv The ‘experts’ have constantly

pointed out that biowarfare can’t be used by “unsophisticated” folks.You need a lot of training to

effectively use biowarfareYou need a lot of equipment to make

biowarfare agents effectiveAum Shin tried it and failed (before

sarin).

BioterrorismBioterrorism Obviously this line of reasoning

didn’t stop the current terrorists from using anthrax

Delivery system

… crude, but very effective for terrorism… and not very expensive

Delivery system

… crude, but very effective for terrorism… and not very expensive

Delivery Systems - ImprovDelivery Systems - Improv It depends on just what you want

to accomplish…English with smallpox and blankets

during French & Indian WarLetter ‘biobombs’Other improv devices

Terrorism is changingTerrorism is changing Increased security about other

means Increase in spectacular and/or high

casualty eventsNYC and Pentagon

Increase in state sponsorship Increase in religious sponsorship

`Everybody who doesn’t worship my way deserves to die!”

And biotechnology is changing...And biotechnology is changing... Dual use technology is burgeoning Gene sequences are becoming

public knowledge Increased availability of

information Private hire of former Soviet

scientists

Foreign Outlook on the US is changingForeign Outlook on the US is changing

The “last” superpower Jealousy of our freedom and

lifestyle The great Satan

Imposing ‘Our’ view and religionsA fickle bully A place where

TV makes the decisions and is constantly present

The soft and decadent live in the US

The Changing Role of the USThe Changing Role of the US

Decrease in international stability leads to increase use of US forces as police

Retribution / Retaliation cycle of current ‘wars’ in Afghanistan and Iraq

In Topoff II, we trained at 2 major places…In Topoff II, we trained at 2 major places…

Topoff IITopoff II Pre-arranged

Date and location known Compressed time format

Limited scope Limited # of patients No significant disruption of normal

medical services

What if every yellow spot were a biological release .... What if every yellow spot were a biological release ....

Please remember Please remember Sophisticated planning of

simultaneous attacks on multiple targetsDetailed knowledge of system

weaknessesUnderstand and employ media to best

effect Use of unusual “tools” to achieve high

casualties and shock effect Self-sacrifice (martyr) can be expected

Who?Who? Undefined constituency and/or

vague objectives Prior pattern of high casualty

incidentsSophisticated planning of simultaneous

attacks on multiple targets Demonstration of sophistication Willing to take risks ?? State sponsorship

OBL?OBL?

Who elseWho else OBL or a successor? Palestine

PLF-GCAbu Nidal

Saddam or a successor ? United States Aryan Nations

Neo-Nazi groups? Japanese Red Army Hizbollah Sikh

Who will reap the whirlwind???Who will reap the whirlwind???