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Biological Weapons of Mass Destruction

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Title: Biological Weapons of Mass Destruction


1
Biological Weapons of Mass Destruction
  • Stephen Waring, DVM, PhD
  • Associate Director of Research
  • Center for Biosecurity and Public Health
    Preparedness
  • Assistant Professor of Epidemiology and
    Biological Sciences

2
Its an isolated case. There is no terrorism.
Tommy Thompson, Sec of HHS After death of Bob Ste
vens (1st of 4)
3
The gravest danger our Nation faces lies at the
crossroads of radicalism and technology.
History will judge harshly those who saw this co
ming danger but failed to act. In the new world
we have entered, the only path to peace and
security is the path of action.
President Bush The National Security Strategy o
f the United States of America September 17, 2002
4
What is bioterrorism?
  • Intentional or threatened use of viruses,
    bacteria, fungi, or toxins from living organisms
    to produce death or disease in humans, animals,
    or plants

5
How real is the threat?
Threats reported to FBI, 1996-1999
We expect the trend to continue or even increas
e as we get into
the new century.
Through first 4 months
Source FBI
6
Intentional food contamination salmonellosis
  • The Dalles, Oregon in Fall of 1984
  • 751 cases of Salmonella
  • Eating at salad bars in 10 restaurants
  • Criminal investigation identified perpetrators as
    followers of Bhagwan Shree Rajneesh

Source Torok et al. JAMA 1997278389
7
Multistate Outbreak Anthrax, 2001
4 deaths
NY letters
DC letter
Number of cases (all)
October
September
Postmarked data of known contaminated letter
MMWR 200150(43)941-948
8
Considerations
  • Catastrophic public health consequences
  • Mass casualties overwhelm medical systems
  • High morbidity or mortality
  • Contagious
  • Require comprehensive PH preparedness
  • stockpile therapeutics
  • enhanced surveillance or diagnostics
  • response planning
  • Heightened public perception

9
Biological Agents of Greatest Concern
  • Bacillus anthracis (Anthrax)
  • Variola major (Smallpox)
  • Yersinia pestis (Plague)
  • Francisella tularensis (Tularemia)
  • Filo-/Arenavirus (Viral hemorrhagic fevers)
  • Botulinum toxin (Botulism)

10
Why These Agents?
  • Infectious via aerosol
  • Organisms fairly stable in environment
  • Susceptible civilian populations
  • High morbidity and mortality
  • Person-to-person transmission (smallpox, plague,
    VHF)
  • Difficult to diagnose and/or treat
  • Previous development for BW

11
Advantages of using biologicalagents as weapons
  • Easy to obtain
  • Inexpensive to produce
  • Potential for dissemination over large geographic
    area
  • Creates panic
  • Can overwhelm medical services
  • Perpetrators escape easily

12
Epidemiologic Clues for Covert Bioterrorism
Attacks
  • Large numbers of persons with the same illness
  • Uncommon disease agents
  • Geographical, seasonal
  • Increased deaths in animal population
  • Higher incidence than expected from a disease

13
Public Health Response to Bioterrorism
  • CDC recommends 4 areas of preparedness
  • Reinforce PH surveillance systems
  • Increase epidemiologic capacity
  • Enhance PH laboratory capability
  • Develop and enhance communication networks

14
Covert vs. Overt Event

15
Anthrax
  • Human zoonotic disease
  • Woolsorters disease
  • Caused by Bacillus anthracis
  • Soil reservoir
  • Normally humans infected by contact with infected
    animals or byproducts

16
Anthrax as a bioweapon
  • Features of anthrax suitable as BT agent
  • Fairly easy to obtain, produce and store
  • Spores easily dispersed as aerosol
  • Moderately infectious
  • High mortality for inhalational (86-100)

17
Anthrax as a bioweapon
  • Aerosol method of delivery
  • cause primarily inhalational disease
  • Spores on particles of 1-5 µm size
  • Optimal size for deposition into alveoli
  • Form of disease with highest mortality
  • Would infect the largest number of people

18
Anthrax as a bioweapon
  • Sverdlovsk, Russia 1979
  • Accidental release from anthrax drying plant
  • 79 human cases
  • All downwind of plant
  • 68 deaths
  • Some infected with multiples strains

19
Sverdlovsk, Russia Anthrax Incident, 1979
Biopreparat
20
Dispersion of spores
21
Anthrax Cutaneous
  • Most common form (95)
  • Inoculation of spores under skin
  • Incubation hours to 7 days
  • Small papule -- ulcer surrounded by vesicles
  • Painless eschar with edema
  • Death
  • 20 untreated rare if treated

Source www.bt.cdc.gov
22
Anthrax Inhalational
  • Incubation 1 to 43 days
  • Initial symptoms (2-5 d)
  • flu-like
  • Terminal symptoms (1-2d )
  • High fever, dyspnea, cyanosis
  • hemorrhagic mediastinitis/effusion
  • Rapid progression shock/death
  • Mortality 100 despite aggressive Rx

From JAMA 19992811735-1745
23
Anthrax Treatment
  • Antibiotics
  • Penicillin (if PCN susceptible), Doxycycline, or
    Ciprofloxacin
  • Supportive care
  • Standard precautions, no need for quarantine
  • Duration of treatment dependent on form of
    anthrax and/or vaccine use
  • Early treatment improves prognosis

24
Anthrax Post-Exposure Treatment
  • Start oral antibiotics
  • Ciprofloxacin
  • Doxycycline
  • Amoxicillin (if known PCN sensitive)
  • Antibiotics
  • 60 days without vaccine
  • 30 days with 3 doses of vaccine

25
Anthrax Vaccine
  • Current U.S. vaccine (FDA Licensed)
  • Attenuated non-encapsulated strain
  • Protective against cutaneous (human data) and
    possibly inhalational anthrax (animal data)
  • Injections at 0, 2, and 4 weeks, then 6, 12, and
    18 months, yearly boosters
  • 3 dose schedule may be effective
  • 83 serologic response after 3 doses 100 after
    5 doses
  • limited availability

26
Decontamination
  • No person to person transmission
  • Highest risk of infection at initial release
  • Duration of aerosol viability
  • Several hours to one day under optimal
    conditions
  • Covert aerosol long dispersed by recognition 1st
    case
  • Risk of secondary aerosolization is low
  • Heavily contaminated small areas
  • May benefit from decontamination
  • Decontamination may not be feasible for large
    areas

27
Decontamination
  • Skin, clothing
  • Thorough washing with soap and water
  • Avoid bleach on skin
  • Instruments for invasive procedures
  • Sterilize, e.g. 5 hypochlorite solution
  • Sporicidal agents
  • Sodium or calcium hypochlorite (bleach)

28
Decontamination
  • Suspicious letters/packages
  • Do not open or shake
  • Place in plastic bag or leakproof container
  • If visibly contaminated or container unavailable
  • Gently cover paper, clothing, box, trash can
  • Leave room/area, isolate room from others
  • Thoroughly wash hands with soap and water
  • Report to local security / law enforcement
  • List all persons in vicinity

29
Decontamination
  • Opened envelope with suspicious substance
  • Gently cover, avoid all contact
  • Leave room and isolate from others
  • Thoroughly wash hands with soap and water
  • Notify local security / law enforcement
  • Carefully remove outer clothing, put in plastic
  • Shower with soap and water
  • List all persons in area

30
Smallpox Overview
  • Important cause of morbidity and mortality in
    developing world until 1970s
  • up to 30 mortality in unvaccinated
  • 1980 - Global eradication
  • Person-to-person transmission (aerosol/contact)
  • Humans only known reservoir

Variola major
31
Smallpox Clinical Features
  • Prodrome (incubation 7-17 days)
  • Acute onset of fever, malaise, headache,
    backache, vomiting, occasional delirium
  • Transient erythematous rash
  • Exanthem
  • Begins face, hands, forearms
  • Spread to lower extremities then trunk over 7
    days
  • Synchronous progression
  • macules--vesicles--pustules--scabs
  • Lesions on palms /soles
  • Mortality up to 30 for unvaccinated

32
Smallpox vs. Chickenpox
33
Smallpox Vaccination Complications
  • Most common
  • Inadvertent inoculation (skin, eye)
  • Less Common
  • Generalized vaccinia
  • Post-vaccination encephalitis (2.8/million)
  • Fetal vaccinia
  • Eczema vaccinatum (4.5/million)
  • Vaccinia necrosum (0.7/million)
  • Primary vaccination - 1 death/million
  • Revaccination - 0.2 deaths/million

34
Smallpox Vaccination Complications
Eczema vaccinatum
Self-inoculation
Vaccinia necrosum
Courtesy WHO
35
Smallpox Medical Management
  • Strict respiratory/contact isolation of patient
  • Patient infectious until all scabs have
    separated
  • Notify public health authorities immediately for
    suspected case
  • Identification of contacts within 17 days of the
    onset of cases symptoms

36
Plague Overview
  • Rodent flea natural vector
  • Mammalian hosts
  • rodents, squirrels, chipmunks, rabbits, and
    carnivores
  • Enzootic or Epizootic in US
  • About 10-15 cases/year
  • Mainly SW states
  • Bubonic most common form

37
Plague Clinical Forms
  • Bubonic
  • Inguinal, axillary, or cervical LN most common
  • 80 bacteremic
  • 60 mortality untreated
  • Primary or secondary septicemic
  • 100 mortality untreated
  • Pneumonic
  • From aerosol or septicemic spread to lungs
  • Person-to-person transmission by respiratory
    droplet
  • 100 mortality untreated

38
Plague Bubonic
  • Incubation 2-6 days
  • Sudden onset HA, malaise, myalgia, fever, tender
    LNs
  • Regional lymphadenitis (Buboes)
  • Cutaneous findings
  • possible papule, vesicle, or pustule at
    inoculation site
  • Purpuric lesions - late

Source USAMRICD
39
Plague Septicemic
  • Primary or secondary(from bubonic or pneumonic)
  • Severe endotoxemia
  • Systemic inflammatory response syndrome
  • Shock, DIC, ARDS

40
Plague Pneumonic
  • Incubation 1-3 days
  • Sudden onset HA, malaise, fever, myalgia, cough
  • Pneumonia progresses rapidly (24-48h) to dyspnea,
    stridor, cyanosis, hemoptysis
  • Death from respiratory collapse, sepsis

Source USAMRICD
41
Plague Differential Diagnosis
  • Pneumonic
  • Bioterrorism threats
  • Anthrax
  • Tularemia
  • Melioidosis
  • Other pneumonias
  • CAP
  • Influenza
  • HPS
  • SARS
  • Bubonic
  • Staph/streptococcal adenitis
  • Glandular tularemia
  • Cat scratch disease
  • Septicemic
  • gram-negative sepsis
  • Meningococcemia
  • RMSF
  • TTP

42
Plague Medical Management
  • Antibiotic therapy
  • Gentamicin or Streptomycin
  • Tetracyclines
  • Sulfonamides
  • Chloramphenicol (meningitis/pleuritis)
  • Supportive therapy
  • Isolation and droplet precautions for pneumonic
    plague until sputum cultures negative

43
Plague TOPOFF
Aerosol of Y pestis released at Denver Performing
Arts Center
44
Tularemia Overview
  • Disease of Northern Hemisphere
  • Most cases associated with rabbits and hares or
    ticks
  • About 200 cases/year in U.S.
  • most in South central and West
  • majority of cases in summer
  • Low infectious dose
  • 1 to 10 organisms (aerosol or ID)
  • No person-to-person transmission

45
Tularemia Clinical Forms
Lymphoglandular
Ulceroglandular
Oculoglandular
46
Tularemia Pneumonic
  • Incubation 3 to 5 days (range 1-21 days)
  • Abrupt onset fever, chills, headaches, myalgia,
    non-productive cough
  • Segmental/lobar infiltrates, hilar adenopathy,
    effusions
  • Mortality 30 untreated less than 10 treated

47
Pneumonic Tularemia Differential Diagnoses
  • Community acquired pneumonia (CAP)
  • Atypical CAP (Legionella, Mycoplasma)
  • Streptococcal pneumonia, Influenza, H. influenza
  • Other Zoonoses
  • Brucellosis
  • Q Fever
  • Pneumonic plague
  • Histoplasmosis
  • Inhalational Anthrax
  • HPS

48
Viral Hemorrhagic Fevers (VHF) Overview
  • Caused by several different viruses families
  • Filoviruses (Ebola, Marburg)
  • Arenaviruses (Lassa, Junin, Machupo, Sabia,
    Guanarito)
  • Bunyaviruses
  • Flaviviruses
  • Natural vectors - virus dependent
  • rodents, mosquitoes, ticks
  • No natural occurrence in U.S.

49
VHF Clinical Presentation
  • Usual patient history
  • Foreign travel to endemic or epidemic area
  • Rural environments
  • Nosocomial exposure
  • Contact with arthropod or rodent reservoir
  • Domestic animal blood exposure
  • Incubation
  • Typical 5 to 10 days
  • Range 2 to 16 days

50
VHF Clinical Presentation
  • Symptoms
  • Fever, headache, malaise, dizziness
  • Myalgias
  • Nausea/vomiting
  • Initial signs
  • Flushing, conjunctival injection
  • Periorbital edema
  • Positive tourniquet test
  • Hypotension

51
VHF Clinical Presentation
  • Other signs/symptoms
  • Prostration
  • Pharyngeal, chest, or abdominal pain
  • Mucous membrane bleeding, ecchymosis
  • Shock
  • Usually improving or moribund within a week
    (exceptions HFRS, arenaviruses)
  • Bleeding, CNS involvement, marked SGOT elevation
    indicate poor prognosis
  • Mortality agent dependent (10 to 90)

52
VHF Differential Diagnosis
  • Bacterial
  • Typhoid fever, meningococcemia, rickettsioses,
    leptospirosis
  • Protozoa
  • Falciparum malaria
  • Other
  • Vasculitis, TTP, Hemolytic Uremic Syndrome (HUS),
    heat stroke

53
Botulism Overview
  • Caused by toxin from Clostridium botulinum
  • toxin types A, B, E, most commonly associated
    with human disease
  • most potent lethal substance known to man (lethal
    dose 1ng/kg)
  • C. botulinum spores found in soil worldwide
  • 100 reported cases/year in the U.S.
  • infant most common (72)
  • food borne not common
  • No person-to-person transmission

54
Botulism Clinical Forms
  • Foodborne
  • 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
  • not naturally occurring, developed as BW weapon

55
BotulismClinical Presentation
  • Incubation 18 to 36 hours (dose dependent)
  • Afebrile, alert, oriented normal sensory exam
  • early nausea, vomiting, diarrhea
  • Cranial Nerve symptoms
  • ptosis, blurry/double vision, difficulty
    swallowing/talking, decreased salivation
  • Motor symptoms (progressive)
  • bilateral descending flaccid paralysis --
    respiratory paralysis
  • Death 60 untreated

56
BotulismDifferential Diagnoses
  • Neuromuscular disorders
  • Stroke syndrome
  • Myasthenia gravis
  • Guillain-Barre syndrome (Miller-Fisher variant)
  • Tick paralysis
  • Atropine poisoning
  • Paralytic shellfish/puffer fish poisoning
  • Diagnosis based on clinical presentation and
    laboratory confirmation

57
Clinical Summary
58
Summary
59
How will we know?
  • unusual temporal/geographic clustering
  • patients presenting with signs and symptoms that
    suggest an outbreak
  • unusual age distribution for common diseases
    (chickenpox in adults)
  • large number of cases of acute flaccid paralysis
    with prominent bulbar palsies, suggestive of a
    release of botulinum toxin

60
What will we do?
  • Make a plan
  • Know the plan
  • Practice the plan
  • http//www.readygov.com
  • http//www.bt.cdc.gov
  • http//www.tdh.state.tx.us
  • http//www.ci.houston.tx.us


61
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