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Fall 2012

Friday October 19th 2012.



2Fall 2012



Scenario

You are working an Emergency Medicine Residency in a large urban

hospital. A massive explosion has just happened in your city, causing

a six-story office building to collapse.

The building was constructed in the 1960s: Asbestos may (or may

not… have been used in the construction

Early evidence points to a deliberate cause, probably a bomb. As yet,

no person or group has claimed responsibility. Rescue operations

, .

Some ambulatory and a few non-ambulatory patients are beginning to

arrive in your ER, having been transported by private vehicles. Many

o these casualties are covered with a ine white dust.

Do you need any special precautions or procedures? Or do you

merel treat these casualties for their obvious in uries?

3Fall 2012



Possibilities1. The dust is only gypsum from dry wall material and

harmless

2. The dust contains Asbestos and presents a longterm dan er

3. The dust contains varying amounts of a weapons-

grade chemical toxin.

radioactive material

5. The dust contains weapons-grade biological

4Fall 2012



FBI Definition

errorist Incident

“….a violent act or an act dan erous to human

life, in violation of the criminal laws of the

United States, or of any state, to intimidate or coerce a government, the civilian population, or

any segment thereof, in furtherance of political

”.

5Fall 2012



Biological Vs. Chemical Agents

Organic or inorganic compounds which have atoxic effect on livin thin s, the a lication of

which may have military utility

Biological Agents Living organisms and/or Viruses (Self-Replicating

Organisms) which have an adverse effect on

v ng ngs, e app ca on o w c as m aryutility

6Fall 2012



7Fall 2012



Terminology Some Common Acronyms

=

WME = Weapons of Mass Effect (not quite

NBC (or CBN) = Chemical, Biological &

BNICE = Biological, Nuclear, Incendiary,

8Fall 2012



NBC WeaponsNuclear, Biological, Chemical

(terrorist) attack. All have overwhelmingdisadvanta es to use as “conventional”

weapons

Availability, Storage, transportation

Dis ersal or a lication

Overt/Covert?

First detected

9Fall 2012



Nuclear Weapons:

Three T es “ Big Bang” - The “Suitcase” atomic (Fission)

bomb: Conventional trauma plus short and long term radiation

exposure

“ Little Ban ” - The “Dirt Bomb”: Conventional explosive used to disperse radioactive

material. May not be immediately distinguished from a

conventional IED Same type of casualties as #1, but fewer in number and

more localized

“ No Bang” - Non-Explosive Radiation

release: May not be immediately noticed

10Fall 2012



Nuclear Weapons

All victims will require Decontamination

v u or es o ce, re, , e c.are almost always the “First

Responders”

May not be the case with a “no bang” non-explosive release of radioactive material

Immediate effects same as an

explosive attack, plus short- and long-

11Fall 2012



Chemical Weapons

Ma or ma not be covert

A vapor cloud, spray or “sticky” coating may be observed.Sometimes an odor is present as well.

Symptoms of exposure will appear in minutes to

hours

term radiation damage

Police, fire and EMT personnel usually become the

“first responders” All but long-term (chronic) victims will require

econ am na on

12Fall 2012



Improvised Chemical Weapons The FBI “Top Ten” List

non-governmental organizations (terrorists)

All are shipped and stored around the nation

Security on many of these is minimal

13Fall 2012



The FBI Top Ten All are commonly available Commercial Chemicals and also very

low-tech

1. Ammonia 6. Methyl.

3. Chlorine 7. Phosgene4. Cyanide 8. Phosphine

. Sulfide.

10. Fluorine

14Fall 2012



Battlefield Chemical Weapons

Vesicants – Blister agents – Mustards

.

Also severely damage eyes, lungs GI tractand other or ans

Sulfur Mustard ( H )

Distilled Mustard HD

Nitrogen Mustard ( HN-1, HN-2 and HN-3 )

Lewisite L

Phosgene Oxime ( CX )

15Fall 2012



Battlefield Chemical Weapons

Nerve Agents

Most toxic of Chemicals, but hard tomanufacture

G Agents

Tabun ( GA )

Sarin ( GB )

Soman ( GD )

V Agents: Only one - VX

16Fall 2012



Riot Control AgentsNon-lethal Chemicals

In this case ou will et Self-referred atients

They will sit in your waiting room and out-gas Cumulative effect can cause actual spread of symptoms!

“ ” – – membranes (and Skin to a lesser extent). Material is asublimating nonpersistent solid, dispersed as a smoke or

solution spray

OC - Oleoresin Capiscum – “Pepper Spray” Natural origin. Apersistent liquid. Has both irritating and inflammatory effect .Causes bletharospasm as well as dyspnea.

a o oran s n om s ew ese ave no recphysical effects at all. Goal is to disperse crowds withoutdamaging their ability to navigate. Compounds chosen so thatthe do not cause olfactor fati ue. – rofoundl obnoxious odor persists!

17Fall 2012



Persistent vs Non-PersistentChemical Weapons

Non ersistent: Persistent: Remain in

Disappear fromenvironment in less

environment and onexposed persons for 24

an ours en o

be gases or volatile

ours or more. en o

be viscous liquids

Phosgene Oxime ( CX )

Tabun ( GA )

,

Lewisite ( L )

Oleoresin Capiscum ( OC )

Sarin ( GB ) Soman ( GD )

18Fall 2012



Mamagement Scenarios

,

teams will be put in the field close to thescene

A concentric set of “Response Zone”

release site

, ,

the release event may have been at an

unknown initiall location and ma have

taken place days or weeks previously.19Fall 2012



Zones for Defense

Cold ZoneDecontamination

WIND

Corridor

Hot Zone

Warm Zone Original Release

Point

20Fall 2012



Biological Weapons

Much more difficult to re are trans ort and

disperse than radiologic or chemical weapons Some have “multiplication effect” – they are

transmitted from man to man after initial release

Final number of casualties exceeds initial contacts ymp oms appear ays o wee s a er exposure.

The actual release will almost certainly be covert.

,

environment, therefore become the “ first

responders”

21Fall 2012



The CDC Categories

Categories are ranked in order of .

terms of availability, ease of use, andne r s o e genera popu a on

Category A

Category B

Cate or C

22Fall 2012



Category ABiological Agents

,

Security because organism:

easily disseminated

Causes hi h mortalit with ma or ublic healthimpact

May cause panic and social disruption

Requires special action for public healthpreparedness

23Fall 2012



Category ABiological Agents

-

Clostridium botulinum toxin

-

variola major - Smallpox Francisiella tularensis - Tularemia

viral hemorrhagic fevers

Ebola, Marburg, etc.

24Fall 2012



Category BBiological Agents

-

Are moderately easy to disseminate

Require significant enhancements of CDC’s

ca abilit and enhanced disease surveillance

25Fall 2012



Category B

List of Biological Agents

-

Clostridium perfringens epsilon toxin

-

Coxiella burnetti - Q fever Ricinus communis toxin - Ricin

Staph aureus - Enterotoxin B

26Fall 2012



Category CBiological Agents

.

pathogens that could be engineered for massdissemination in the future because of

Availability

Ease of Production and Dissemination

Potential for High morbidity, High mortality and

major Public Health impact

27Fall 2012



Category C

List of Biological Agents

Multi - Drug Resistant Tuberculosis

Tickbourne Encephalitis virus Tickbourne Hemorrhagic Fever viruses

Yellow Fever

( My Suggestions: recombinant Influenza Virus or Haemophilus ducreyi )

28Fall 2012



Biosafety

“

combinations of laboratory

pract ce an proce ure,

laborator facilities, andsafety equipment when

infectious microorganisms.”

29Fall 2012



Principles:Biosafety Levels

-

disease.-

disease.

-

associated with human disease and with

.

BSL4 - dangerous/exotic agents of life

.

30Fall 2012



BSL-1Introduction

“ Suitable for work involving wellcharacterized agents not known to cause

minimal potential hazard to laboratory

ersonnel and the environment.” Examples:

Bacillus subtilis

Naegleria gruberiInfectious canine hepatitis virus

E. coli (non-toxigenic strains)

31Fall 2012



BSL-2Introduction

“ Suitable for work involving agents of moderate potential hazard to personnel

”.

Examples * :

Salmonellae

.

Hepatitis B virus

* Note that Immunization or antibiotic treatment isavailable for all of these

32Fall 2012



BSL-2Key Difference

BSL-2 differs primarily from the lower level in itsemphasis on protection from Blood borne

pathogens

Strict control and disposal of sharps Strict “needle stick” procedures

PPE includes e e and hand rotection

33Fall 2012



BSL-2 Application

Virtually all primary samples from Humansourced clinical materials may be handled

under BSL-2 conditions.

However, some specific agents (mostly thosewith the potential for airborne spread) , once

identified or even suspected, should then be

an e un er - or even rare y -conditions. (Example: MDR TB = BSL-3 )

BSL-2 is adequate for Bloodborne pathogens

34Fall 2012



OSHA Requirements

SGU Students are now required to be

certified as trained prior to entry into any

-

In short they must know how to preventand if necessary, deal with hazards due to:

• Sharps

• Splashes

•

• Sticks

• and , of course, Sex.

All of which are the ways in whichbloodborne pathogens are spread.

Such is the essence of BSL-2

35

Fall 2012



PPE for BSL-2 & BSL-3

ersona ro ec ve

Equipment

™

with full hood and PAPR

(Powered Air Purifyingesp rator

Protects against liquids,

What is wrong with the PPE

36Fall 2012



BSL-3Introduction

“

which may cause serious or potentially

the inhalation route.”

aerosol. Infection are serious, possibly lethal)

Some Exam les:

M. tuberculosis St. Louis encephalitis virus

Coxiella burnetii

37Fall 2012



BSL-3Key Difference

BSL-3 differs primarily from lower levels in itsemphasis on protection from Airborne

(Respiratory) pathogens

Negative pressure rooms Double airtight doors

HEPA filter on exhaust ventilation

HEPA = High Efficiency Particulate Air

-

38Fall 2012



A BSL-3 Fashion Show

39Fall 2012



BSL-4Introduction

“ Suitable for work with dangerous andexo c agen s a pose a g n v ua

risk of aerosol transmitted laboratoryinfections and life-threatenin disease.”

Exposure potential to pathogens spread bytransmission Infection possibly lethal

Exam les: Ebola Zaire Sin Nombre virus

Rift Valle Fever

40Fall 2012



BSL-4Key Difference

BSL-4 differs primarily from lower levels in itsemphasis on maximum protection from

unknown transmission routes

Dedicated air supply and HEPA filtered

Entrance through change room: Shower onexit.

PPE requires that full body air supply positivepressure suits worn at all times within facility 41Fall 2012



PPE for BSL-4

42Fall 2012



Weapon-izationof

Natural Infectious Diseases Requires sophisticated biological engineering

to:

Grow the infectious agent to very large volumes

and high concentrations without loss of virulence

n ance or a eas ma n a n v ru ence

Stabilize the infectious agent so that it may be

Interface the infectious agent with the delivery

s stem

43Fall 2012



Weapon-izationof

Natural Infectious Diseases

Not an easy matter. Natural agents usually:

Are unstable outside of their natural

host/reservoir

sensitive to slight environmental changes Sensitive to drying, shock, UV radiation

Require a vector

Require a very high minimum infectious dose

44Fall 2012



Example:

Weapon-ization of Bacillus anthracis

.

2. Reduce spore size.

lungs

. 1. Freeze-dry the washed, isolated spores

.

1. Mix with Bentonite or Silica: This enhances

surfaces and other particles45Fall 2012



Dispersal

of Biologic Agents

attempts (Aum Shinrikyo) were total failures

Must release as dust or nebulized liquid spray if

aerosolization is the goal May become difficult to remain clandestine

Cannot use explosive dispersal

Alternately, must release as contaminant of foodor water

46Fall 2012

Th



The

um nr yo Attempts -

period, (1991 - 1996) the well-financed

Japanese doomsday cult Aum Shinryokotried to inflict mass casualties by spreading

. u oun er

Shoko Ashahara

• In one such incident, Anthrax spores were sprayed from the top of a

building in downtown Tokyo for four hours.

• In another, the exhaust of an automobile was modified to serve as a s ra er

of the spores, and the car driven around the city.

• All attempts ended in failure: No anthrax cases resulted.

• In frustration, the cult dropped its use of Anthrax and switched to using the

nerve gas Sarin

47Fall 2012



Actual U.S. Incidents

Strange local epidemic of salmonella

Sharply focused region

2001 eastern US

-

48Fall 2012



Bar

1984 - the Dalles, central Oregon

Large religious commune “Rajneeshpuram”

Followers of the grandly-titled guru, ShriBhagwan Rajneesh attempted to influence

local county elections.

o owers spraye cu ures o . yp mur um

(from ATCC) over salad bars in 10 local

restaurants

Resulted in 751 cases, no deaths49Fall 2012

I Al R l d i A d



It Also Resulted in Arrests and

Convictions...’ -

Sheela was convicted for this but served lessthan four ears of her 20 ear sentence

Upon release she fled to Switzerland

Presumabl still there Anand Puja also sentenced

50Fall 2012

“Y ’ G M il!”



“You’ve Got Mail!”October/November, 2001

Total of seven letters so far known Two sent to Florida

Three to New York

Two to Washington, D.C.

Each letter contained ± 2 grams of weapons-

grade spores: (Perhaps one Trillion spores!)

as 3080 LD50s

51Fall 2012



Continued Events of

October/November, 2001

- ,

Minimum of 5,100 persons exposed, countingostal handlers and office workers.

Tens of thousands of letters may potentially have

been contaminated 22 cases of anthrax

11 Inhalational (all confirmed)

u aneous con rme

5 deaths (all from Inhalational)

52Fall 2012

C Cl d ?



Case Closed … ?

The Final Suspect

Died by suicide on July 29,

….Hours (or days?) before

the filin of a FederalIndictment charging him with

having created and mailed the

Bruce Edwards Ivins

1946 - 200853Fall 2012

Bi l i l Att k



Biological Attack

The Physicians Will See It First

“With a covert biological agent attack, the most

increased number of patients showing up at

disseminated disease agent.”

Couch, Dick. 2003 “U.S. Armed Forces

Nuclear, Biological and Chemical Survival

anua apter . age as c

Books, New York, NY

54Fall 2012

Epidemiologic Clues



Epidemiologic Clues

Presence of a large epidemic

of a Biologic Attack

Unusually severe disease or unusual routes of exposure

Unusual geographic area, unusual season, or absence of normal vector

Multiple simultaneous epidemics of di fferent diseases

Unusual strains of organisms or antimicrobial-resistance patterns

Credible threat, as determined by authorities, of biologic attack

rec ev ence o o og c a achttp://www.medscape.com/viewarticle/448589_print

55Fall 2012

Generalized “Flu like” Symptoms



Generalized Flu-like Symptoms

Symptoms include: Fever, Malaise, Chills, Muscle& Joint Pain, L m hadeno ath , Headache

Many also include respiratory symptoms

Chest Pain Cou h Lun or Nasal Con estion Breathing Difficulty

Biolo ic Toxins Botulinum, Ricin, T2

Mycotoxin) produce variable symptoms

56Fall 2012

Simulated Terrorist Incidents



Simulated Terrorist Incidents

Done at various levels by some governmental. .

Only the two have so far been made public

“Dark winter” June 2001

“ ”-

“Atlantic storm” January 2005 (details never fully

ublished

57Fall 2012

“Dark Winter”



Dark Winter

June 2001

S onsored b the Johns Ho kins center for Biodefense strategies

First such senior-level U.S. President andnational security council) exercise

Simulated a deliberate covert smallpox attackon three simultaneous locations (Oklahoma,Pennsylvania and Georgia)

mu a on covere an ypo e ca wo weeperiod in December 2002

58Fall 2012

Assumptions



Assumptions

Parameters were based on an actual smallpoxoutbreak that took place in Yugoslavia in 1972 Infection rate set at 1:10 – meaning that each confirmed

case passed the disease on to 10 susceptible personse ore e ng e ec e .

Mean incubation period of 7 days before overt symptoms

Disease becomes contagious after 3 days

ree na ona secur y counc mee ngs weresimulated December 9, 2002

December 15, 2002 December 22, 2002

59Fall 2012

December 9 2002



December 9, 2002

”Dark Winter” Simulation

The Oklahoma alert: 12 confirmed and 14 suspected cases detected. Suspect casesalso in Georgia and Pennsylvania, but notconfirmed

12 million smallpox vaccine doses availablen e . . n m on wor w e

Council adopted “ring” method of vaccination ar w nvo ve ea care wor ers an

general population closest to infected individuals

Work wa out from there

60Fall 2012

December 15 2002



December 15, 2002

“Dark Winter” Simulation

300 deaths nationwide. 2000 confirmed cases in 15 states

Smallpox spreas to Canada Mexico and the U.K. Canada and Mexico areasking for vaccinations.

. ,Universities and Sporting events closed.

Russia offers 4 million doses of vaccine to the US

Healthcare system in affected areas breaks down. 20 hospitals closed ina oma. ecur y mus e prov e y na ona guar

Federal Government prepares to invoke martial law nationwide, suspendHabeas Corpus,

Governor of Texas closes border with Olkahoma and ur es other overnorsto do likewise

Public Health officials trace infections to three Shopping Malls, one each inthe three original states. No perpetrators yet found

61Fall 2012

December 22 2002



December 22, 2002


1 000 deaths 16 000 cases nationwide. Disease

found in 28 states and 10 foreign countries

Businesses in Atlanta, Philadelphia and Oklahoma

City are mostly closed. Nationwide economy greatly

diminished.

o ence con nues o esca a e across e coun ry

In the past 48 hours there were 14,000 new cases.

,

Domestic vaccine supply is exhausted. No new

roduct will be read for another 4 weeks

62Fall 2012

After December 22, 2002



After December 22, 2002

”Dark Winter” Simulation US economy collapses with major food shortages

Mass exodus from affected cities

Predict that 2nd generation of cases will hit first week, ,

deaths.

3rd generation hits on January 20 with 300,000,

4th generation predicted February with 3 millioninfected and 1 million dead.

Russia, France and Germany all demand USprovide them with vaccination

Cuba offers to sell the vaccine

63Fall 2012

Lessons Learned



Lessons Learned


Such an attack is a ma or threat ca able of inflictin

catastrophic national damage

The nation is (as of June 2001) woefully unprepared

Governmental organization is not well suited for

management of a BW attack

systems

Information management is a crucial element

New ethical, political, cultural, operational and legal

challenges emerge

64Fall 2012

Blue Advance -02



Blue Advance 02

,

Staff

As a military simulation, parts of the results

never been released, and remain classified.

“ ”

been detailed

65Fall 2012

The Scenario



Blue Advance -02

Intentional release of Small ox aboard a cruise shi

before it docked at San Juan, Puerto Rico.

Unsuspecting passengers carried the disease to the

wider Puerto Rican population.

Initial number of cases was 950

San Juan hospital capacity was exceeded

Emergency assets were fully depleted

declaration Fatality rate projected at 30%

66Fall 2012

Do it Yourself!Universit of Pittsbur h Center for Biosecurit



Universit of Pittsbur h Center for Biosecurit

Offers “Atlantic Storm” as an interactive exercise Online!http://www.atlantic-storm.org/index.html

Fall 2011

Consistent Problems



of Dealing With a BW Attack

1. Reco nizin the breakin events as bein theearly signs of an attack

1. BW agents tend to be exotic zoonoses (Smallpox being,

alarm

2. First cases may not appear in the same hospital and at

.venues is needed

3. Surveillance Systems are coming on line:

-. . .

2. International Society for Infectious Diseases<http://www.isid.org>

- < >. .

68Fall 2012

Consistent Problems




2. Civilian healthcare s stems lack sufficient surge capacity: Hospitals and healthcarepersonnel are quickly swamped andexhausted

1. Extra help must be made available on very

1. Logistical and Medico-legal problems soon emerge

3. Public Affairs and Information Mana ement

become crucial1. “Holding press conferences does not distract

rom cr s s managemen : s cr s smanagement!.”

69Fall 2012

Consistent Problems




.

fragile and soon break down..

Posse Comitatus and suspend Habeas Corpus

must be taken promptly.

2. Military help in the form of emergency medical

support as well as security and law enforcement

70Fall 2012

Consistent Problems




Onl the first of these, earl detection of an attack,admits to a technological solution. The second and

third problems are economic and political deployment of a BW agent and its effects (theincubation period – usually several days) mostresearch has focused on the development of rapidfield detection of Chemical and/or Radiologica ents

Field Detection of Biologic Agents lags far behind inpriority and current state of development. No

-

71Fall 2012

Biologic Weapons



Point Sensors

1 ol merase chain reactions PCR to am lif row

the suspect DNA which is then subsequently

detected by fluorescence tagged antigens (high

sens v y an spec c y u s ow n spee o

preparation),

- - -sensitivity

3 new research in B-cell reactions to the bio a ent

directly without the need to detect the antigen (verysensitive and specific but difficult as of yet to keep

e ce cu ures a ve .

72Fall 2012

Novel Detection Systems



y

“Lab-on-a-chip”: Total Analysis Systems (mTAS) have thepotential to

(1) Isolate specific cells or viruses of interest

(2) Amplify the information if necessary(3) Accurately measure a specific indicator of the cell or virus

(4) Deliver a quantitative result

Example:

“ ” -separated and identified by their response to an alternatingcurrent at Radio Frequencies. Each genus and species seemsto have a uni ue “harmonic” in this art of the electroma neticspectrum. This phenomenon is being investigated for its value asa real-time point detection system.

73Fall 2012

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