This document discusses bioterrorism and various biological agents that could potentially be used as bioweapons. It defines bioterrorism and describes biological weapons as microbes or their toxins. Various microorganisms are discussed in detail, including anthrax, plague, smallpox, viral hemorrhagic fevers like Ebola, and biological toxins such as botulinum toxin. For each agent, the document covers characteristics, potential use as a bioweapon, symptoms, diagnosis, treatment and other relevant details.

1. BIOTERRORISM
Dr Gurpreet Singh

2. Definition of Bioterrorism
 Premeditated threat or actual use of biological
weapons to produce disease or death in people,
animals, or plants.
 Biological weapons: microbes or their toxins.

3. Biological Weapons

4. Bioterrorism Overview
 Microorganisms or their toxins can be in liquid or
powder form.
 Various delivery methods are possible:
 aerosol
 envelope or package
 food or water contamination
 Exposure can be isolated to a single area or can be
more widespread.

5. Bioterrorism
Microorganisms as biologic weapons would
most likely result in illness occurring days to
weeks after attack and would affect persons
dispersed from the site.

6. Biological Agents:
Types and Characteristics
Bacteria
Viruses
Biological Toxins

7. CDC Categories
 Category A:
 easily disseminated OR transmitted person to
person
 susceptible population
 potential for panic / disruption
 requires special action for treatment
 high morbidity and mortality
 examples: anthrax, smallpox, plague, botulism,
viral hemorrhagic fevers, tularemia

8. CDC Categories
 Category B:
 moderately easy to disseminate
 moderate morbidity, low mortality
 examples: Q fever, brucellosis, glanders, some
toxins
 Category C:
 emerging pathogens that could be engineered for
mass dissemination in the future
 potential for high morbidity and mortality
 examples: hantavirus, tickborne viruses, MDR TB

9. Isolation Precautions
 Standard (“blood and body fluid”):
 gloves
 mask with face shield
 gown
 Airborne:
 standard plus negative pressure room and N95 mask
(“duckbill mask”)
 Handwashing

10.  Gram positive bacillus that forms
spores
 Spores found in soil worldwide
 Humans usually infected by contact
with infected animals or contaminated
animal products
No person-to-person
transmission of inhalation
anthrax
Anthrax: Overview

11. Anthrax: Cutaneous
 Most common form (95%)
 Inoculation of spores in skin
 Incubation: hours to days
 Progression:
1. small papule
2. ulcer surrounded by vesicles
3. painless eschar with edema
 Death:
• untreated – 20%
• treated – rare

17. Anthrax: Gastrointestinal
 Ingestion of contaminated meat
 Fever, vomiting, bloody diarrhea
 Intestinal eschar similar to
cutaneous anthrax lesion
 Progression to general toxemia
 Mortality 50% despite treatment

18. Inhalational Anthrax
Pathogenesis
• 1-5 micron Anthrax spore size is optimal for deposition
into alveoli
• Inhaled spores are ingested by alveolar macrophages
and transported to mediastinal and peribronchial lymph
nodes, spores germinating en route
• Anthrax bacilli multiply in lymph nodes, causing
hemorrhagic mediastinitis, and spread throughout the
body in the blood

19. Inhalational Anthrax
Clinical Presentation
• 10 days to 6 weeks after inhalation of spores, infected
patients develop fever, non-productive cough, myalgia
and malaise
• Early in the course of the disease, chest radiographs
show a widened mediastinum, which is evidence of
hemorrhagic mediastinitis, and marked pleural effusions
• After 1-3 days, the disease takes a fulminant course
with dyspnea, strident cough, and chills, culminating in
hypotension, shock, and death

20. Anthrax: Inhalational

21. Inhaltional Anthrax: Diagnosis
 Chest X-ray—widened mediastinum, pleural
effusions, infiltrates, pulmonary congestion
 Affected tissue biopsy for
immunohistochemistry
 Any available sterile site fluid for Gram stain,
PCR, or culture
 Pleural fluid cell block for
immunohistochemistry

22. Anthrax Testing
 Nasal Swab:
 A tool for epidemiology, not diagnosis
 Limitations:
 positive test indicates exposure, not infection
 false positives have been seen
 negative test does not rule out anthrax infection
 Serologic tests:
 Available at special labs but not used for routine screening
 Blood cultures:
 Probably best test for symptomatic individual at risk

23. ANTHRAX: Treatment
 Inhalation anthrax or cutaneous anthrax with
systemic involvement:
 ciprofloxacin (400mg, IV, q12h) or doxycycline
(100 mg, IV, q12h)
 combine with one of the following:
 rifampin, vancomycin, penicillin, ampicillin,
clindamycin, clarithromycin
 Treat for 60 days

24. Anthrax: Other Treatment
 Uncomplicated cutaneous anthrax:
 Cipro (500 mg, po, bid) or doxycycline (100 mg,
po, bid)
 Prophylaxis for exposure:
 Cipro (500 mg, po, bid) or doxycycline (100 mg,
po, bid)
 Children or breastfeeding mothers: amoxicillin
 Levoquin- adults 18 and older
 Treat for 60 days

25. Plague: Overview
 Yersinia pestis (gram-negative
coccobacillus)
 About 10 U.S. cases/yr (SW)
 Two major forms
 Very contagious via respiratory
droplets

26. Plague Epidemics
3 major recorded epidemics:
 550, 1350 (Black Death), 1850 (China)
 30% - 60% mortality in infected
continents

27. Plague
 GOOD NEWS:
 future epidemics unlikely due to sanitation,
public health practices, and antibiotics.
 BAD NEWS:
 US and Russia and other countries have
developed techniques to aerosolize plague,
eliminating need for fleas to spread the
infection.

28. Plague as a Bioweapon
 Infected fleas could spread bubonic form
(less likely scenario)
 Aerosolized organisms would spread
pneumonic form (more likely scenario)

29. Plague: Bubonic
 Bite from infected flea
 Sudden onset flu-like syndrome
 Buboes:
 tender, enlarged lymph nodes
(inguinal, axillary, cervical)
 Can spread to lungs (hematogenous)
 Can also lead to endotoxic septicemic
phase

30. Plague: Pneumonic
 Inhalation of organisms (aerosol)
 Incubation: 1-3 days
 Sudden onset flu-like syndrome
 Pneumonia progresses rapidly to
hypoxemia, cyanosis, hemoptysis
 Endotoxin: septic shock with
DIC, ARDS, death

31. Plague Disease Complex
ARDS DIC
Fulminant
Pneumonia
Flu-like
Syndrome
Sudden
onset
2 -3
days
24 hrs
Inhalational of plague
organisms
Endotoxemia
Respiratory failure
Circulatory collapse
Flu-like syndrome
Tender buboes
2 - 10 days

32. Plague:
Diagnostic Tests
 No widely available rapid tests
 Gram stain of body fluids or lymph node aspirate
may reveal gram-negative organisms
 Blood cultures should be positive within 2 days.
 Confirmatory testing via government labs (antigen
detection, immunoassays, and PCR)

33. Pneumonic Plague:
Isolation precautions
 SECONDARY
TRANSMISSION IS
POSSIBLE - EASILY
 USE STANDARD AND
AIRBORNE PRECAUTIONS

34. Management / Prophylaxis
 Antibiotic therapy
 IV amino glycoside and IV doxycycline
 Ciprofloxacin
 Antibiotic resistant strains exist
 Supportive measures
 Prophylaxis for respiratory droplet exposure:
 oral doxycycline or oral ciprofloxacin for 7-10 days
 vaccine - no longer manufactured in U.S.

35. Viruses as Bioweapons
 Viral Hemorrhagic
Fevers:
 Ebola
 Lassa
 Marburg
 Smallpox

36. Viral Hemorrhagic Fevers
 Group of illnesses caused by several RNA
viruses
 All can be used as bioweapons
 Examples: Ebola, Marburg, Lassa
 Mortality can be very high (90% for Ebola)

37. VHF: Occurrence
 Naturally occurring infections can occur via
transmission from infected rodents and arthropods
 Readily transmissible from person to person via body
fluids:
 great risk for healthcare workers
 usually travelers to endemic areas

38. CURRENT OUTBREAK
 Current outbreak in Africa
 80-89% MORTALITY

39. VHF: Pathophysiology
 Variable incubation (2-21 days)
 Flu-like symptoms with high fever
 Increased vascular permeability causes:
 hemorrhage in GI tract and mucous membranes
 petechial or ecchymotic rash
 edema
 hypotension
 Rapid progression to shock and death

40. VHF: Lab Testing
 No widely available rapid tests
 Government labs can provide nucleic acid assays
 Routine labs reveal clotting abnormalities:
 elevated PT and PTT, decreased platelets

41. VHF: Treatment
 Supportive treatment
 IV ribavirin used occasionally for Lassa
fever.
 Vaccines under development
 Postexposure prophylaxis with oral ribavirin
may be useful
 Contact and respiratory precautions
necessary

42. Smallpox
 Variola virus
 Characteristic skin lesions
 About 30% mortality in unvaccinated
 Last known natural case: Somalia in 1977
 Global eradication 1980

44. Smallpox as a Bioweapon
 Can be aerosolized
 Highly contagious
 No effective treatment
 Vaccination ceased in 70’s
 Stable in the environment (contamination for
months)

45. Smallpox: Pathophysiology
 Virus inhaled or deposited on mucous
membranes
 Goes to lymph nodes, incubates for 7-17 days
 Release into blood causes flu-like symptoms
 Rash begins 2-3 days later
 Death due to toxemia of viral antigens and
circulating immune complexes

46. Smallpox: Skin lesions
 Macular (flat, red) rash 2-3 days after flu
symptoms
 Starts on face, forearms, hands (+ palms and
soles)
 Rash evolves synchronously in an area
 Evolves into tense vesicles
 Scabs form in 7-10 days if patient lives
 Infectious until all scabs are shed.

50. Day 3 Day 5 Day 7

51. Chickenpox with characteristic
rose-colored macules, papules,
vesicles, pustules, necrotic
pustules, and crusted lesions
occurring simultaneously.

52. Herpes zoster (varicella virus) with
characteristic grouping of vesicles
Herpes zoster showing dermatomal
distribution of lesions

53. Prodrome yes minimal or none
Distribution out to in in to out
Lesions painful / deep pruritic / superficial
Progression synchronous asynchronous
Palms / Soles yes no
Smallpox vs. Chickenpox
Smallpox Chickenpox

54. Smallpox vs. Chickenpox

55. Smallpox: Diagnosis
 CLINICAL PRESENTATION AND PATIENT
HISTORY IS THE KEY TO DIAGNOSIS
 No widely available rapid test
 Electron microscopy to confirm presence of
variola virus particles

56. Smallpox:
Treatment and Prophylaxis
 No effective treatment
 Animal trials with cidofovir are promising
 Vaccinia immune globulin may be useful
 Vaccination within 3-4 days of ALL potential contacts
may prevent or lessen disease

57. Smallpox: Precautions
 Airborne and Contact Isolation
 Airborne Isolation:
 negative pressure room
 anteroom
 closed ventilation system
 N95 mask (Duckbill mask)
 Contact Isolation:
 strict use of PPE and handwashing

58. Smallpox: Precautions
 Patients may be cohorted
 Laundry kept separate and in Red Bag
 Limit number of personnel in contact
 Mask patient if in-hospital transport
 Contacts placed under 18 day fever
surveillance (>100.5 reportable)

59. Smallpox Vaccine
 Vaccination in U.S. ended in 1972 except military
personnel
 Not known if previous vaccination is protective
now
 Not a benign vaccine: side effects and
fatalities
 Possibly MANY deaths if given to all in US

60. Smallpox Vaccine
 Vaccine is for vaccinia, a closely related and more benign
virus
 Vaccine contraindicated in some, unless exposure has
occurred:
 Immunosuppressed (hiv / cancer/transplant patients
 chronic steroid usage (eyedrops)
 eczema or chronic exfoliative skin disorders
 pregnancy
 age under 18
 CARDIAC DISEASE- Mi’s / Myopathy / Angina

61. Smallpox Vaccine
 Virus sheds from vaccine site for up to 6
weeks
 Shedding can infect household contacts
with vaccinia
 Some serious vaccine reactions:
 encephalitis, severe vaccinia, anaphylaxis,
Stevens-Johnson
 Auto-inoculation of orifices can occur

62. BIOLOGICAL TOXINS

63.  BOTULINUM – BO-TOX
 RICIN
 STAPHYLOOCCAL ENTEROTOXIN B (not reviewed)
 T-2 MYCOTOXINS (not reviewed)

64. Botulinum Toxin
 7 neurotoxins produced by Clostridium botulinum
 Among the most toxic substances known
 May be found in naturally contaminated food
 As a bioweapon, likely to be delivered by aerosol
 No person-to-person transmission
 Multiple cases without common food source
suggests bioterrorism

65. Botulinum Toxin:
Mechanism of Action
 Site: neuromuscular junction (pre-synaptic)
 Action: binds at acetylcholine release sites to prevent
release
 Effect: muscle weakness (skeletal and cranial nerve
distribution)
 Does not cross the blood-brain barrier:
 patients remain alert and afebrile

66. Botulinum Toxin:
Clinical Findings
 Botulism onset: about 1-3 days
 Cranial nerve palsies early:
 Eye: blurred vision, photophobia, diplopia, ptosis
 Throat: dysarthria, dysphagia
 Skeletal muscle weakness later:
 symmetrical, descending, progressive
 abrupt respiratory failure

67. Botulinum Toxin:
Differential Diagnosis
 Differential Diagnosis:
 tetanus, myasthenia gravis, Guillain-Barre
 Botulism differentiated by:
 more cranial nerve involvement
 facial muscles more involved than below
neck
 lack of sensory changes

68. Botulinum Toxin: Lab
 Laboratory testing:
 generally not helpful
 detection of toxin in serum is possible

69. Botulinum Toxin: Treatment
 Do not wait for lab confirmation
 Administer antitoxin:
 available from CDC but very limited supplies
 only binds to circulating toxin to prevent progression
 will not reverse symptoms already present
 anaphylaxis and serum sickness may result
 do not prophylax exposed but asymptomatic patients
 Respiratory support necessary
 Recovery takes weeks to months

70. RICIN

71. Ricin
 Potent protein toxin derived from castor beans
 Easily produced / Recently found in France
 Inhibits protein synthesis
 Causes necrotizing airway lesions:
 tracheitis
 bronchitis and bronchiolitis
 interstitial pneumonia with ARDS

72. Ricin
 Inhalation as an aerosol produces severe
respiratory symptoms:
 day 1: cough, fever, dyspnea
 day 2-3: pulmonary edema, resp failure, death
 Specific serum test is available
 No treatment available other than supportive

73. Agent Type
Minimum
Dose
Incubation
period
Initial
Symptoms
Duration
of illness Lethality
Animal
Indicator
Anthrax Bacteria
8,000
(spores) 1-6 days Flu-like 3-5 days High 90% Yes
Plague Bacteria
100
organisms 2-3 days
Pneumonia /
Flu-like 1-6 days High 90-100% Yes
Tuleramia Bacteria 10 organisms
2-10 days
(avg. 3-5) Flu-like >=2 w eeks
Moderate
5-30% Yes
Brucellosis Bacteria 10 organisms 5-60 days Flu-like
Weeks to
months Low 2-10% Yes
Q Fever Rickettsia 1 organisms 10-40 days Flu-like 2-14 days Low 4% Yes
Smallpox Virus 10 organisms
7-17 days
(avg. 12) Flu-like 4 w eeks High 30%
Animal
Varients
Encephalitides
VEE, EEE, WEE Virus 10 organisms 2-6 days Flu-like
days to
w eeks low Yes
Hemorrhagic
Fevers
Ebola, Marburg Virus 1 organism 4-21days Flu-like 7-16 days
High
Marburg 25%
Ebola 50-90% Yes
Botulinum Toxin 100 ng 1-5 days
muscle
w eakness 24-72 hours High 30% Yes
Characteristics of BT Agents
Chotani, 2003

74. Thankyou