CONFIDENTIAL

Virtual Drug Development, Inc.

Dr. R. Stephen PorterPresident, CEO, and Chairman

Brentwood, TN

www.virtualdrugdevelopment.com

CONFIDENTIAL

Bioterrorism

• History• The Threat• The Organisms• Counter-bioterrorism

• Deterrence• Detection• Response

• VDDI

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Common Misconceptions

• Large scale bioterrorism will not occur

• Bioterrorism is similar to other WMD events (i.e.. Chemical radiation)

• The federal Government is equipped to deal with Bioterrorism;Local Governments are not

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History

• Tartars attack on Caffa (1346)• Plague

• French and Indian Wars (1763)• Small Pox Blankets (Sir Jeffery Amherst

• WWI-Germans infected horses and Cattle B. Anthracis (Anton Dilger JHU)

• 3500 horses infected• 1925 Geneva Protocol

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Plague• According to a traditional story, the plague came to Europe from the town of

Caffa, a Crimean port on the Black Sea where Italian merchants from Genoa maintained a thriving trade center. The Crimea was inhabited by Tartars, a people of the steppe, a dry, treeless region of central Asia. When the plague struck the area in 1346, tens of thousands of Tartars died. Perhaps superstition caused the Muslim Tartars to blame their misfortune on the Christian Genoese. Or perhaps a Christian and Muslim had become involved in a street brawl in Caffa, and the Tartars wanted revenge. In any case, the Tartars sent an army to attack Caffa, where the Genoese had fortified themselves. As the Tartars laid siege to Caffa, plague struck their army and many died. The Tartars decided to share their suffering with the Genoese. They used huge catapults to lob the infected corpses of plague victims over the walls of Caffa. As the Tartars had intended, the rotting corpses littered the streets, and the plague quickly spread throughout the besieged city. The Genoese decided they must flee; they boarded their galleys and set sail for Italy, carrying rats, fleas, and the Black Death with them."

(Corzine, 1997)

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History

• WWII-Modern Era of BW

• Japanese Unit 731 in Manchuria (1932-1945)

• 11 Chinese cities attacked-plague in Chusien

• U.S. offensive program (1942)• S. Marcescens “attack” on SF (1950)

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History

• Korean War (1950s)• US offensive program “officially

Terminated” (1969)• Biological Weapons and Toxic

Convention (1972)-103 nations including Iraq

• Stop development, stockpiling• Yearly Reports to UN

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History

• Russian Offensive Program• Sverdlovsk (1979)• Biopreparat program• 55K workers in 6 Labs ands 5

production plants• 1992 Yeltsen admitted to program after

Ken Alibek defected

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History

• Recent Events• Rajneesh attack Oregon (1984)• Larry Wayne Harris (1995) Bought

plague • American Type Culture Collection

(ATCC)• Shipped Anthrax to Iraq

• Abortion Clinics TN, KY OH, IN (1998)

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Biopreparat•All-Union Production Association Biopreparat, created in 1973 by the Central Committee of the CPSU and the USSR Council of Ministers, some 40 research and development (R&D) and production facilities.• Biopreparat actively involved in military BW programs.•Leading Biopreparat facilities included the State Scientific Center of Applied Microbiology in Obolensk, the Institute of Immunological Studies in Lyubuchany, the State Scientific Center of Virology and Biotechnology (known as Vector) near Novosibirsk, the State Scientific Institute of Ultrapure Biological Preparations in Leningrad, and the Scientific Experimental and Production Base in Stepnogorsk, Kazakhstan. The 15th Directorate of the MOD supervised the work of the Biopreparat facilities and coordinated their activities with those of the MOD’s military biotechnological centers. As the Kazakhstani example will show, in addition to being run by the same upper echelon of the MOD, the military and Biopreparat BW systems shared some technologies and personnel.

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Renaissance Island

• Vozrozhdeniye Island open-air test site in the Aral Sea

• tons of powdered anthrax

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THE THREAT

• Why use bioweapons?• Cheap- 800x than nuclear weapon• Easy to acquire-dual use• High fatality –1993 OTA Report

• 100 Kg anthrax could kill more (3 million) than H bomb (1.9M)

• High fear/panic factor

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THE THREAT

• Why have bioweapons not been used?• Unpredictability• Reprisals/Accountability• Superpower stability• Conventional weapons work

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THE THREAT

• Bioterrorist Profile (Simon 1989:OTA)• Not concerned about response to

attack• History of large scale violence with

high causalities• Sophistication in weaponry and tactics• State Sponsorship• Willingness to take risk

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THE THREAT

• Likely Perpetrators• Japanese RED Army (JRA)

• World revolution

• Aum Shinrikyo cult- Shoko Asahara• World revolution

• Neo-Nazi/Militia in US and Europe

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THE THREAT

• Likely Perpetrators Cont…• Islamic extremist-Hezbollah, Ramsi

Yousef• Sikh extremists in India• Animal rights grps. In US• State Sponsored- Libya, Iran, Iraq,

N.Korea, Cuba

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THE ORGANISM

• Ideal organisms• Easy to obtain• Easy to cultivate• Highly Infectious• Stable in Environment• Contagious

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THE ORGANISMS

• Means of Delivery• Food and Water Supply

• Chlorination and cooking kill agents• Requires huge amounts

• Aerosolization-sprayers• Mechanical stress kills agents• Particle size .5 to 5 Microns• Metrological conditions

• Zoonotic delivery

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Anthrax

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Anthrax as a WMD

Inhalational Anthrax• Requires 8k-50k spores• Biphasic illness-incubation 2-43 days• Necrotizing mediastinitis; meningitis• Diagnosis difficult-sputum cultures; blood

cultures are too late• Treatment with IV PCN, TCN, Cipro for 4-8 wks • Side effects• Resistant Strains

• AVIP: Vaccination X 6 doses over 18 months

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Life Cycle Stages for Intervention

NAD Synthetase

X

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B. Anthracis; USAMRIID Data

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B. Anthracis InfectionsEfficacy Assay

Dixon TC, Meselson M, Guillemin J, Hanna, PC. Anthrax. 341(11) N. Engl J. Med. 1999;341:815-26.

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SMALL POX

• “..the most terrible of all ministries of death”

• Marcus Aurelius 180 AD), Tsar Peter II (1730)

• Hapsburg dynasty (18th Century)• Last case in Somalia in 1977• Declared eradicated in 1980• Last vaccination in 1972

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SMALL POX

• Good bioweapon• Highly infective 10-100 organisms• Stable in environment• Contagious

• Infection• Constitutional sxs follow in 3 days by

typical rash• 30% mortality

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SMALL POX

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SMALL POX

• Dx clinical . PCP, cx from lesions

• Treatment (cidofovir, Vistide)• Isolate close contacts for 17 days

• Vaccine-Vaccina

• Small pox only survives at CDC and in Moscow Virologic Institute.

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Plague

• Yersenia pestis

• The Oriental Rat Flea: Xenopsylla cheopis

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Plague• According to a traditional story, the plague came to Europe from the town of

Caffa, a Crimean port on the Black Sea where Italian merchants from Genoa maintained a thriving trade center. The Crimea was inhabited by Tartars, a people of the steppe, a dry, treeless region of central Asia. When the plague struck the area in 1346, tens of thousands of Tartars died. Perhaps superstition caused the Muslim Tartars to blame their misfortune on the Christian Genoese. Or perhaps a Christian and Muslim had become involved in a street brawl in Caffa, and the Tartars wanted revenge. In any case, the Tartars sent an army to attack Caffa, where the Genoese had fortified themselves. As the Tartars laid siege to Caffa, plague struck their army and many died. The Tartars decided to share their suffering with the Genoese. They used huge catapults to lob the infected corpses of plague victims over the walls of Caffa. As the Tartars had intended, the rotting corpses littered the streets, and the plague quickly spread throughout the besieged city. The Genoese decided they must flee; they boarded their galleys and set sail for Italy, carrying rats, fleas, and the Black Death with them."

(Corzine, 1997)

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PLAGUE

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PLAGUE• Pneumonic plague

Least common (< 14% of all cases), but most severe form characterized by fulminant pneumonia • termed primary pneumonic plague if acquired via respiratory tract and hematogenous spread to lungs • overall mortality: 57% • The form most likely to be seen in a bioterrorism setting

• Bubonic plagueMost common form (75-97% of all cases) • characterized by painful lymphadenitis (buboes) • contracted through the bite of an infected flea or handling infected animals • overall mortality: 15% • This form is unlikely to occur in a bioterrorism setting

• Septicemic plagueLess common form (< 20% of all cases) • systemic infection characterized by high-grade bacteremia and sepsis • termed primary septicemic plague if no buboes are detected or secondary septicemic plague if developed as a complication of bubonic • overall mortality: 22-50%

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PLAGUE

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PLAGUE

• According to Dr. Matt Luther, Vanderbilt University Medical Center "The plague often caused DIC in severe forms, and DIC can be fatal. The picture above demonstrates what DIC can look like. In its most deadly form DIC can cause a victims skin to turn dark purple. The black death got its name from the deep purple, almost black discoloration." Victims usually died the same day symptoms appeared. In some cities, as many as 800 people died every day.

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PLAGUE• Adults• streptomycin 1 g IM q 12 hrs (should be avoided in pregnant

or lactating women) or• gentamicin 2 mg/kg IV/IM load dose then 1–1.75 mg/kg

IV/IM q 8 hrs per renal function• Children• streptomycin 15 mg/kg/day IM q 12 hrs (not to exceed

2g/day) or• gentamicin 2.5 mg/kg IV/IM q 8 hrs (q 12 hrs for < 1 wk old

or premature infants)• Alternative therapies include: doxycycline, tetracycline,

ciprofloxacin, and chloramphenicol

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COUNTER-BIOTERRORISM

• Cost of an attack (Kaufman, 1997)

• Human toll of anthrax attack (100K)• 50K infected• 33K dead

• Economic toll of anthrax attack (pop100K)

• $26 billion

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COUNTER-BIOTERRORISM

• Deterrence• Enforce existing laws

• Prevent use• Threat of reprisals and condemnation• Immunization• Intelligence (HUMIT)

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COUNTER-BIOTERRORISM

• Detection of an Attack• Clinical detection need trained local

health• Explosion of ill patients• Animals• Weather conditions• Antimicrobial resistance patterns

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COUNTER-BIOTERRORISM

• Detection (cont..)• Canary chips/biosensors• Particle detectors-subways• MALDI-TOF

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COUNTER-BIOTERRORISM

• Response to an attack• Treat victims/exposed and protect others• Abx and immunizations • Housing and transporting ill• Quarantine, placement of deceased

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COUNTER-BIOTERRORISM

• Response Cont..)• Protect unexposed

• HEPA filters +pressure aerosol disinfectants in buildings

• Protect water and food

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Conclusions

• Bioterrorist attacks will occur in the future

• We must prepare for this as a public health event

• Communication at State and Local level, business government pull together