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Stevan Cordas DO Incapacitants1 Incapacitants Stevan Cordas DO MPH.

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Presentation on theme: "Stevan Cordas DO Incapacitants1 Incapacitants Stevan Cordas DO MPH."— Presentation transcript:

1 Stevan Cordas DO Incapacitants1 Incapacitants Stevan Cordas DO MPH

2 Stevan Cordas DO Incapacitants2 Definition Under the Department of Defense definition, an incapacitant is an agent that produces temporary physiological or mental effects, or both, which will render individuals incapable of concerted effort in the performance of their assigned duties.

3 Stevan Cordas DO Incapacitants3 History 600 BC – Solon used hellebore to cause diarrhea in enemy. 184 BC – Hannibal used belladonna to create disorientation AD – Hashish used by Muslims AD - Bishop of Muenster proposed belladonna grenades – Natives in Africa and Vietnam used indigenous plant to cause disorientation in occupying troops.

4 Stevan Cordas DO Incapacitants4 History Following WWII the CIA and the DoD began to explore various substances to act as incapacitants quinuclidinyl benzilate termed BZ (NATO) was the only one weaponized Department of Defense joint non-lethal weapons program (JNLWP).

5 Stevan Cordas DO Incapacitants5 Types of Psychoactive Incapacitants Central nervous system stimulants – amphetamines, cocaine etc. Central nervous depressants – antipsychotics, barbiturates, opioids, benzodiazepines. Psychedelics –LSD –25, PCP, MDMA etc. Delerients – scopolamine, BZ, atropine etc.

6 Stevan Cordas DO Incapacitants6 Epidemiology Psychoactive drugs and plants readily available worldwide. BZ is commercially available as QNB. Hard to make in a home lab. Sudden delirium in a previously healthy person or group of persons should raise suspicion.

7 Stevan Cordas DO Incapacitants7 Epidemiology Anticholinergics are readily found in plants such as belladonna (Atropa belladonna), mandrake root, Black henbane (Hyoscyamus niger), the thornapple or Jimson weed (Datura stramonium) and woody nightshade (Solanum dulcamara) and Jerusalem cherry (Solanum pseudocapsicum), all members of the Solanaceae botanical family (along with tobacco coincidentally) British report that Iraq had stockpiled Agent 15, a glycolic acid ester, an agent similar to BZ.

8 Stevan Cordas DO Incapacitants8 Pathophysiology BZ is an anticholinergic. This is a class of drugs that blocks, as a competitive inhibitor of acetylcholine, the post synaptic and postjunctional muscarinic receptor sites on the peripheral and/or the central nervous system. The nicotinic receptors in the skeletal muscle are not affected.

9 Stevan Cordas DO Incapacitants9 Pathophysiology Anticholinergics, such as BZ and Agent 15, work the direct opposite of nerve gas agents and cause an understimulation of muscarinic exocrine gland, central and peripheral nervous system and smooth muscle receptors.

10 Stevan Cordas DO Incapacitants10 Differential Diagnosis Lead, mercury. Solvents. Alcohol. Anxiety states. Recreational drug abuse. Medical disease –hepatic failure, renal failure, hypothyroidism.

11 Stevan Cordas DO Incapacitants11 Toxicology of BZ A stable crystalline solid. Not soluble in water but in DMSO and solvents. Can be aerosolized. Formula C 21 H 23 NO 3. MW is ; melting 167° C; Boiling point 320° C. Safety margin 30. ID50 is 6.2 g/kg. Less than 1 mg will cause delirium in a 70 kg man.

12 Stevan Cordas DO Incapacitants12 Clinical Manifestations of BZ Ocular –Mydriasis, loss of near vision, dry eyes. Oral – Xerostomia. Cardiac - unpredictable – usually tachycardia lasting one to two days. Skin – Dry, flushed, hyperthermic. GU – Bladder distended, decreased force.

13 Stevan Cordas DO Incapacitants13 Clinical Manifestations of BZ Dose dependent central effects. Level of consciousness –drowsy, sedated, stupor to coma. Perceptual – mad as a hatter, hallucinations, illusions. Attention and memory impairment. Disturbances in insight and judgment – Vulgarity, confabulation.

14 Stevan Cordas DO Incapacitants14 Clinical Manifestations of BZ Deficits in expression and comprehension. – Slurred speech, flat voice, preserveration, semiautomatic speech, handwriting deteriorates, cannot converse. Disorientation – time and place, picking behaviors, mumbling, vulgarity. Sharing of illusions and hallucinations. Paranoia – especially as other symptoms resolve.

15 Stevan Cordas DO Incapacitants15 Laboratory Testing There are no laboratory tests for BZ and no field detection equipment.

16 Stevan Cordas DO Incapacitants16 Treatment Evacuate. Restrain if necessary. Treat hyperthermia if it is severe. Watch for cardiac arrhythmias, destructive behavior and general status. Give specific antidote IM or IV – Physostigmine. Not effective in the first four hours however.

17 Stevan Cordas DO Incapacitants17 Physostigmine IM 2 to 4 mg every one to 4 hours for 4 or 5 doses. IV, if restrained, 30 g/kg slowly. A fast bolus IV may cause a fatal cardiac arrhythmia or convulsions. Available as Antilirium or Eserine. Other similar agents do not cross the blood brain barrier.

18 Stevan Cordas DO Incapacitants18 Prophylaxis If pre-warned, military protective gear will prevent the effects of anticholinergics. No preventive therapy available for civilians. Evacuate area as BZ persists especially in water, soil and moist surfaces.

19 Stevan Cordas DO Incapacitants19 Reporting There are currently no formal reporting requirement for incapacitants. All unusual circumstances that are suspected of being related to terrorist actions must be reported to law enforcement officials. It is also advisable to report such actions voluntarily to local health departments.

20 Stevan Cordas DO Incapacitants20 Ricin Toxin Stevan Cordas DO MPH

21 Stevan Cordas DO Incapacitants21 Ricin Ricin is a glycoprotein toxin derived from castor plant beans. It can be produced relatively easily and inexpensively in large quantities in a fairly low technology setting. Ricin can be prepared in liquid, crystalline or powder form.

22 Stevan Cordas DO Incapacitants22 Ricinus Communis (Castor Plant)

23 Stevan Cordas DO Incapacitants23 Ricin - A 66 Kilodalton Heterodimer With an A and B Chains

24 Stevan Cordas DO Incapacitants24 History of Ricin Since antiquity, it is known that the oil is helpful but the plant is poisonous. Ricin, mainly in the seeds, first named Ehrlich discovered the basic principle of antibody production using ricin – the beginning of immunology – Named compound W after WWI – developed by both U.S. And Great Britain into weapons.

25 Stevan Cordas DO Incapacitants25 History of Ricin Allies developed a W bomb in WWII but did not use it. Increased production and weaponization by both allies and others starting in United states ceased biological warfare production in 1969 and destroyed supplies. Iraq and others produced ricin weaponry as part of their inventory.

26 Stevan Cordas DO Incapacitants26 History of Ricin First shown to inhibit tumors in Modern use as research tool developed in 1972 by Sharon and Lis. Chimeric toxins use is currently being studied – native ricin is conjugated to tumor specific monoclonal antibody. Used by Bulgarian secret police to assassinate a defector in 1978.

27 Stevan Cordas DO Incapacitants27 Epidemiology World wide distribution of plant. Readily separated and concentrated. Widespread availability. Implicated with several domestic terrorist incidents. A cluster of cases in the same locality with severe pulmonary distress must include in differential diagnosis.

28 Stevan Cordas DO Incapacitants28

29 Stevan Cordas DO Incapacitants29 Pathophysiology B chain has lectin properties - permit binding to galactosides on cell wall and permitting endocytic uptake of the protein. Once in cell, the A chain acts as an enzyme after a latent period of 8-24 hours in vivo, cell death occurs by cleaving the 28A subunit of RNA. Protein synthesis ceases. Multiple areas of multifocal ulcerations and hemorrhage. Nephritis, liver necrosis.

30 Stevan Cordas DO Incapacitants30 Toxicology Ricin composes about 5% of the Castor plant. Especially in beans and seeds. Both chains are glycoproteins 32 kd each. It has been purified and crystallized. 100 fold variation in toxicity for various animals. Toxicity varies by route of administration and is 100 times more lethal by injection than orally.

31 Stevan Cordas DO Incapacitants31 Toxicology Low oral toxicity is due to poor absorption of toxin. Target cell receptors are widespread over the body but macrophages and monocytes are the only white cells to contain galactose in cell membrane. LD50 is 20 mg/kg(100 hours) orally. 4 g/kg by inhalation and intravenously. (Mice).

32 Stevan Cordas DO Incapacitants32 Clinical Manifestations - Oral Oral – Rauber et el – 751 cases. 14 fatalities. Death rate in general said to be 6%. Often just nausea, vomiting, diarrhea sometimes bloody and abdominal cramps with prostration. Also burning eyes noted. More severe cases also had dilated pupils, shock, anuria, sore throat, fever, vascular collapse, shock and possibly death.

33 Stevan Cordas DO Incapacitants33 Clinical Manifestations - Injection Low doses g/kg in cancer patients could be tolerated with fatigue and flu like symptoms. Vascular leak syndrome seen. Lasted 1-2 days after a latent period of 4 to 6 hours.

34 Stevan Cordas DO Incapacitants34 Clinical Manifestations - Injection Markov was assassinated in London by the Bulgarian KGB with 500 g. Immediate local pain hours later high fever, nausea, vomiting. 36 hours later localized lymphadenopathy,then suddenly hypotensive, cardiac rate 160 then complete AV block, GI bleeding, anuria, shock and death. Death 3-5 days.

35 Stevan Cordas DO Incapacitants35 Clinical Manifestations - Inhalation Allergic reaction to castor beans in workers rhinitis, asthma and conjunctivitis seen. Inhalation of ricin would produce same picture as by subcutaneous except that experimentally a diffuse necrotizing pneumonitis occurs with alveolar flooding. An 8 hour latent period is noted. Dose dependent. Tracheitis and mediastinal purulent lymphadenitis also seen.

36 Stevan Cordas DO Incapacitants36 Differential Diagnosis of Ricin Aerosol Staphylococcus B enterotoxin Organofluorine polymers Phosgene Oxides of nitrogen Paraquat - Naphthylthiourea (ANTU)

37 Stevan Cordas DO Incapacitants37 Laboratory Diagnosis ELISA analysis of swab of nasal mucosa if obtained within 24 hours of exposure. Survivors after about 2 weeks develop antibodies. Identification in body fluids is difficult as it is bound rapidly and metabolized. Immunohistochemical means on autopsy or tissue.

38 Stevan Cordas DO Incapacitants38 Field Testing Field screening testing is now possible using tests such as the RAMP Ricin field test. This is a 15 minutes immunochromatographic test. See ctsbiodefense1c.htm for more details ctsbiodefense1c.htm

39 Stevan Cordas DO Incapacitants39 Treatment No vaccine or immunization is available for humans. Toxoid has been submitted to the FDA for an IND. Experimentally inhalation of protective antibody (passive protection) is highly effective after exposure. For oral – super activated charcoal and IV fluids.

40 Stevan Cordas DO Incapacitants40 Treatment For aerosol – supportive measures -positive end expiratory ventilatory pressure, iv fluids, anti- inflammatory drugs and analgesics. Research drugs to block enzymatic action of A protein. Detoxify (decontaminate) using water or dilute bleach. Wear N95 mask if inhalation source.

41 Stevan Cordas DO Incapacitants41 Prophylaxis No prophylaxis is currently possible though it is possible with animal experiments using a vaccination.

42 Stevan Cordas DO Incapacitants42 Reporting Ricin is a putative bioterrorism weapon. Report to your local or state health department immediately.

43 Stevan Cordas DO Incapacitants43 Castor Beans

44 Stevan Cordas DO Incapacitants44 T2 and Other Mycotoxins Stevan Cordas DO MPH Consultant Texas Department of Health

45 Stevan Cordas DO Incapacitants45 Fungi Over 100,000 species of fungi found in four phyla. Consists of mushrooms, lichens, corals, molds and others. Just as mushrooms can be used beneficially but some can be fatal, molds also can be viewed in this manner.

46 Stevan Cordas DO Incapacitants46 Molds 75% of fungi belong to the family Ascomycota which produce the sexual spores internally in a structure called the ascus. These fungi are molds that can produce products that are fatal to plants, animals and humans. One product is called T2.

47 Stevan Cordas DO Incapacitants47

48 Stevan Cordas DO Incapacitants48 T2 (3",4$,8")-12,13,-Epoxytrichothec-9-ene-3,4,8,15-tetrol 4,15- diacetate 8-(3-methylbutanoate); 3" -hydroxy -4$, 15- diacetyloxy-8"-(3-methylbutyryloxy)-12,13-epoxy -) 9 - tricothecene

49 Stevan Cordas DO Incapacitants49 T2 T2 is a mycotoxin. It was the only such toxin to be weaponized until Sadam Hussein weaponized aflatoxin. It is the only biologic agent that can kill by transdermal absorption. Oral ingestion probably caused ATA (alimentary toxic aleukia).

50 Stevan Cordas DO Incapacitants50 History of T2 Evidence of T2 use as yellow rain in Laos, Cambodia and Afghanistan by Soviets and their surrogates. May have been used in the Iran- Iraq war. No conclusive human case from a biological attack of T2 has been documented.

51 Stevan Cordas DO Incapacitants51 Iraq United nations inspectors reported in 1995 that Iraq weaponized a number of biologic agents including anthrax, clostridia botulinum and a mycotoxin, aflatoxin. Aflatoxin is one of the most potent mutagens and carcinogens known.

52 Stevan Cordas DO Incapacitants52 Toxicology of T2 Maintained as crystalline powders or liquids. Non volatile. Can extract from fungal cultures with organic acids. Cytotoxic to most eukaryotic cells by inhibiting protein synthesis. LD 50 varies with species. In monkey it is 0.8 mg/kg.

53 Stevan Cordas DO Incapacitants53 Toxicology Inhibits protein and DNA metabolism. Rapidly crosses pulmonary and intestinal mucosa. Slowly absorbs across skin unless a penetrant is added. Liver is main organ for metabolism of T2. Metabolites can be detected up to 28 days.

54 Stevan Cordas DO Incapacitants54 Clinical Effects Acute – gastric and intestinal lesions. Hematopoetic and immunological effects are radiomimetic. CNS –lassitude, anorexia, nausea.

55 Stevan Cordas DO Incapacitants55 Clinical Effects Vascular effects with shock and possibly death. Reproduction organ function suppressed. Weakness, cough, chest pain, diarrhea often bloody. Dermal effects – if that route was used – inflammation and necrosis, vesicles. Bloody ooze from nose and mouth.

56 Stevan Cordas DO Incapacitants56 Chronic Effects of T2 ATA – immediate phase of GI effects, weakness, and dizziness followed by leucopoenia primarily granulocytes. If exposure continues a dark red rash with ulcers and gangrenous areas – larynx gets involved with death by strangulation. If they survive it takes months to recover.

57 Stevan Cordas DO Incapacitants57 Chronic Effects Since it is a potent inhibitor of replication and is most toxic to rapidly proliferating cells. A phase I and II Cancer trial was done with a similar mycotoxin (anguidine or DAS) given IV 3 mg/m3 daily for 5 days. Life threatening toxicity and severe hypotension occurred. Effects included confusion, ataxia, chills, vomiting diarrhea and burning erythema.

58 Stevan Cordas DO Incapacitants58 Differential Diagnosis A sudden attack on a otherwise healthy cohort with irritant polysystemic symptoms including skin burning in the absence of miosis after being exposed to a vapor with yellow or reddish color. Staph B does not affect the skin. Other vesicants have an odor this does not.

59 Stevan Cordas DO Incapacitants59 Laboratory Diagnosis Requires a high index of suspicion. No detector to warn one ahead of time. Obtain samples for presumptive testing by liquid - gas chromatography then mass spectroscopy for confirmatory testing. Screening testing is becoming available. White count takes about 48 hours to drop.

60 Stevan Cordas DO Incapacitants60 Treatment In the military a protective suit and M40 or later mask is used. Or N95 mask. Remove from area. Decontaminate after removing clothing with soap and water. No specific therapy is known. Superactive charcoal may trap some of the T2.

61 Stevan Cordas DO Incapacitants61 General Therapeutic Protocol in Animals Supercharcoal Magnesium sulfate Metoclorpramide Dexamethasone Sodium bicarbonate Normal saline

62 Stevan Cordas DO Incapacitants62 Prophylaxis No vaccine is available though several are in research with some efficacy in animals. If protective garment and mask is available use it.

63 Stevan Cordas DO Incapacitants63 Reporting T2 is a putative bioterrorist agent and must be reported to the local or state health department and law enforcement immediately on suspicion.

64 Stevan Cordas DO Incapacitants64 Always Contact Local Public Health Department Tarrant County Public Health 1101 S. Main Street Fort Worth, Texas Dallas County Department of Health & Human Services 2377 N. Stemmons Freeway Dallas, Texas

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