Biologic Toxins with Bioterrorism Potential

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Biologic Toxins with Bioterrorism Potential
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Acknowledgements

• South Carolina Area Health Education Consortium
  (AHEC)
• Funded by the Health Resources and Services
  Administration.
• Grant number 1T01HP01418-01-00
• P.I. David Garr, MD, Executive Director AHEC
• BT Project Director Beth Kennedy, Associate
  Program Director AHEC
• Core Team
• BT Co-director Ralph Shealy, MD
• BT Project Manager Deborah Stier Carson, PharmD
• BT CME Director William Simpson, MD
• IT Coordinator Liz Riccardone, MHS
• Web Master Mary Mauldin, PhD
• P.R Coordinator Nicole Brundage, MHA
• Evaluation Specialist Yvonne Michel, PhD
• Financial Director Donald Tyner, MBA

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Acknowledgements
This presentation, and the accompanying
instructors manual (current as of 7/02), were
prepared by Jennifer Brennan Braden, MD, MPH, at
the Northwest Center for Public Health Practice
in Seattle, WA, and Jeff Duchin, MD with Public
Health Seattle King County and the Division
of Allergy Infectious Diseases, University of
WA, for the purpose of educating primary care
clinicians in relevant aspects of bioterrorism
preparedness and response. Instructors are
encouraged to freely use all or portions of the
material for its intended purpose. The
following people and organizations provided
information and/or support in the development of
this curriculum. A complete list of resources
can be found in the accompanying instructors
guide.
Jane Koehler, DVM, MPH Communicable Disease
Control, Epidemiology and Immunization section,
Public Health - Seattle King County Ed
Walker, MD University of WA Department of
Psychiatry
Patrick OCarroll, MD, MPH The Centers for
Disease Control and Prevention Project
Coordinator Judith Yarrow Health Policy
Analysis, University of WA Design and Editing
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Biological Toxins of BT Potential Objectives

• List the agents most likely to be used in a
  biological weapons attack and the most likely
  mode of dissemination
• Outline the clinical presentation(s) of the
  biologic toxins and features that may distinguish
  them from more common diseases
• Outline the diagnosis, treatment recommendations,
  infection control, and preventive therapy for
  management of infection with or exposure to
  biologic toxins.

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Biological Agents of Highest ConcernCategory A
Agents

• Easily disseminated, infectious via aerosol
• Susceptible civilian populations
• Cause high morbidity and mortality
• Person-to-person transmission
• Unfamiliar to physicians difficult to
  diagnose/treat
• Cause panic and social disruption
• Previous development for BW

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Biological Toxins of Highest Concern Category A
Agents

• Botulinum toxin (Botulism)
• Report ANY suspected illness due to these agents
  to Public Health immediately.

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Biological Toxins of 2nd Highest
ConcernCategory B Agents

• Ricin toxin from Ricinus communis (castor bean)
• Epsilon toxin from Clostridium perfringens
• Staphlococcus enterotoxin B

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Biologic Toxins

• Category A
• Botulism
• Category B
• Ricin

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Clostridium Botulinum

• C. botulinum spores found in soil worldwide
• Toxin causative agent of botulism
• Types A-G A,BE most commonly associated with
  human disease
• Most potent toxin known (lethal dose 1ng/kg)
• Inactivated by chlorine (20min) and sunlight
  (1-3hrs) destroyed by heat (5min at 85?C)
• Absorbed into circulation via mucosal surface or
  wound, not intact skin
• Interferes with nerve transmission ? paralysis

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Botulism Bioterrorism

• Weaponized by former U.S. and Soviet offensive BW
  programs
• Iran, Iraq, N. Korea, Syria believed to have
  developed/be developing toxin as a weapon
• Therapeutic botox impractical BT weapon
• Licensed vial of type A only 0.3 estimated human
  lethal inhalational dose
• Aerosol use or food supply sabotage most likely

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BotulismClinical Forms

• Food-borne
• Toxin produced anaerobically in improperly
  processed or canned, low-acid foods contaminated
  by spores
• Wound
• Toxin produced by organisms contaminating wound
• Infant
• Toxin produced by organisms in intestinal tract
• Inhalation botulism
• No natural occurrence, developed as BW weapon

• 3 accidental cases in veterinary personnel, W.
  Germany, 1962

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Clostridium BotulinumEpidemiology

• Approximately 100 reported cases botulism/year
  in the U.S.
• Infant most common (72)
• Food-borne not common
• Incubation (food-borne) 12-72 hrs (range 2hr-8d)
• Dose dependent
• Could be less following a BT attack
• No person-to-person transmission
• Death 60 untreated lt5 treated

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Botulism Case Definition

• Ingestion of botulinum toxin results in an
  illness of variable severity. Common symptoms
  are diplopia, blurred vision and bulbar weakness.
  Symmetric paralysis may progress rapidly.
• Laboratory criteria for diagnosis
• Detection of botulinum toxin in serum, stool or
  patients food (food-borne) or other clinical
  specimen (botulism, other) OR
• Isolation of Clostridium botulinum from stool
  (food-borne) or other clinical specimen

MMWR 199746(RR-10)
Assay available at CDC some state public
health labs
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Botulism Case Classification

• Botulism, Food-borne
• Probable Clinically compatible with an
  epidemiologic link
• Confirmed Clinically compatible case that is
  laboratory confirmed or that occurs among persons
  who ate the same food as persons who have
  laboratory-confirmed botulism
• Botulism, Other
• Confirmed Clinically compatible case that is
  laboratory confirmed in a patient ? 1 yr who has
  no history of ingestion of suspect food and has
  no wounds

age parameter may not apply in BT
MMWR 199746(RR-10)
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Clostridium Botulinum Pathogenesis

• Toxin absorbed into circulation via mucosal
  surface or wound, not intact skin
• Binds acetylcholine receptor irreversibly and
  blocks release of acetylcholine into
  neuromuscular junction

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BotulismClinical Presentation

• Acute, afebrile, symmetric descending flaccid
  paralysis
• Always begins in bulbar musculature --gt cranial
  nerve palsies
• Skeletal muscle paralysis follows
• Respiratory failure can occur in as little as24
  hours
• Clear sensorium sensation and mental status
  normal
• Afebrile patient

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BotulismClinical Presentation

• Gastrointestinal symptoms
• May precede neurological symptoms in food-borne
  botulism
• Thought to be secondary to other substances
  contaminating the food
• May not occur in BT attack
• Autonomic effects dry mouth, ileus,
  constipation, urinary retention

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BotulismSymptoms

• Diplopia
• Blurry vision
• Dysphagia
• Dysarthria

• Fatigue
• Dizziness
• Dyspnea
• GI symptoms

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BotulismSigns

• Ptosis
• Gaze paralysis
• Fixed or dilated pupils
• Facial palsies

• Diminished gag reflex
• Tongue weakness
• Arm and leg weakness
• Decreased reflexes

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BotulismDifferential Diagnosis
Source Arnon et al. JAMA 20012851059-1070
Electromyogram
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BotulismDifferential Diagnosis
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BotulismDiagnosis

• Exclusionary tests to rule out other causes
• Normal CSF
• Edrophonium (Tensilon test)
• Reverses paralysis in myasthenia gravis
• May have false positive with botulism
• Normal imaging
• Evaluate for presence of ticks

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BotulismTreatment

• Ventilatory assistance and supportive care
• Recovery depends on regeneration of new motor
  axons and may take weeks to months
• Botulinum antitoxin
• Most effective if given early does not reverse
  action of already-bound toxin
• Trivalent equine product against types A,B, and E
  currently available from CDC
• Heptavalent (A-G) antitoxin - investigational
• Monovalent human anti-serum for infant botulism -
  investigational

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BotulismTreatment

• Botulinum antitoxin
• Single 10ml vial per patient, diluted 110 in
  0.9 saline administered by slow IV infusion
• Screen for hypersensitivity before administering
  equine antitoxin and desensitize if necessary
• Monitor closely during treatment
• Diphenhydramine and epinephrine on hand to treat
  hypersensitivity reactions
• Antibiotics for secondary infection
• Aminoglycosides and clindamycin contraindicated
  exacerbate neuromuscular blockade

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BotulismTreatment

• Ventilatory assistance and supportive care
• Standard precautions
• Botulinum antitoxin
• Most effective if given early does not reverse
  effect of toxin already bound to nerve receptor
• Trivalent equine product against types A,B, and E
  currently available from CDC
• Heptavalent (A-G) antitoxin - investigational
• Monovalent human anti-serum for infant botulism
  -investigational

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BotulismProphylaxis

• Pre-exposure
• Prophylaxis for at-risk lab workers and military
  with investigational vaccine
• No pre-exposure prophylaxis recommended for
  general public
• Post-exposure close monitoring of those exposed
  treat with antitoxin at first signs of illness

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Botulism Decontamination

• Wash exposed surfaces with soap and water.
• Decontaminate environmental surfaces with 0.1
  bleach solution, if necessary.
• Without intervention, toxin will degrade or
  dissipate over hours to days.

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Botulism Summary of Key Points

• Botulism presents as symmetric bilateral weakness
  or paralysis with cranial nerve abnormalities and
  a clear sensorium.
• Inhalational botulism does not occur naturally,
  and any potential cases suggest a deliberate
  source of infection.

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Botulism Summary of Key Points

• Gastrointestinal symptoms may not occur with
  inhalational botulism or with food-borne botulism
  (e.g., resulting from deliberate contamination of
  the food supply).
• A careful dietary and activity/travel history is
  important when evaluating potential botulism
  cases.

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Botulism Summary of Key Points

• An outbreak occurring with a common geographic
  factor, but with no common food exposure, would
  suggest a deliberate aerosol exposure.
• Botulinum antitoxin must be administered as soon
  as possible for optimum results.
• Contact your local health department for any
  suspicion of botulism.

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Ricin

• The castor bean plant, Ricinus communis, is a
  "native of tropical Africa cultivated in several
  varieties for the oil found in its leaves and for
  its bold foliage
• Poisoning by ingestion of the castor bean is due
  to ricin in the bean
• Extracted castor oil does NOT contain ricin
• Perhaps just one milligram of ricin can kill an
  adult.

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Ricin Poisoning

• Accidental exposure to ricin is highly unlikely.
• Exposure
• Inhalation.
• Contamination of water or food.
• Injection
• If injected as little as 500 mg could kill an
  adult.
• A 500-microgram dose of ricin would be about the
  size of the head of a pin.
• Much more needed to kill if inhaled or swallowed
• Not contagious

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Ricin Poisoning

• The symptoms are
• abdominal pain
• vomiting
• diarrhea, sometimes bloody.
• Within several days there is
• severe dehydration,
• a decrease in urine,
• and a decrease in blood pressure.
• If death has not occurred in 3-5 days, the victim
  usually recovers.
• Children are at high risk

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Management of Ricin Poisoning

• Decontamination
• Supportive medical care depending on route of
  exposure
• Ventilation
• Intravenous fluids
• Management of seizure and low blood pressure
• Activated charcoal if the ricin very recently
  ingested
• Flushing eyes if irritated

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Summary - Category A Critical Agents
South Carolina Area Health Education Consortium
infectious dose may be less in certain
circumstances
Modified from USAMRIIDs Medical Management of
Biological Casualties Handbook
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SummaryCategory A Critical Agents

• Decontamination of exposed persons
• Showering or washing thoroughly with soap and
  water adequate for most bleach not necessary
• Infection control
• Standard precautions all cases
• Airborne and contact precautions smallpox and
  viral hemorrhagic fevers
• Droplet precautions pneumonic plague

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