Bioterrorism: A Review for Physicians

1
Bioterrorism A Review for Physicians

• Martin E. Evans, M.D.
• Professor of Infectious Diseases
• University of Kentucky
• October 30, 2001

2
Bioterrorism Threats

• Anthrax
• Plague
• Tularemia
• Smallpox
• Brucellosis
• Q fever
• Cholera

• Venezuelan equine encephalitis
• Ebola, Lassa, Marburg
• Botulinum toxin
• Staphylococcal enterotoxin B
• etc...

3
Bioterrorism Threats

• Anthrax
• Plague
• Tularemia
• Smallpox
• Brucellosis
• Q fever
• Cholera

• Venezuelan equine encephalitis
• Ebola, Lassa, Marburg
• Botulinum toxin
• Staphylococcal enterotoxin B
• etc

4
Anthrax as a Bioterrorism AgentTheory

• 1970 WHO report predicted
• 50kg released from an aircraft over a city of 5
  million would result in 250,000 casualties
  (100,000 deaths)
• 1993 US Congressional Office of Technology
  Assessment report predicted
• 100kg released over Washington, DC would result
  in 130,000 to 3 million deaths

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Anthrax as a Bioterrorism AgentThe Reality

• As of October 24, CDC has identified 11 confirmed
  and 4 suspected cases
• Seven were inhalational, and 8 were cutaneous
  anthrax
• Six of the inhalational cases occurred in persons
  handling mail. There have been 3 deaths.
• Eight case were consistent with exposures along
  the postal route of letters known to be
  contaminated with B. anthracis spores.

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Anthrax Hot Spots

• Florida
• American Media Inc, Boca Raton
• Two Boca Raton postal facilities
• Lake Worth postal facility
• New Jersey
• Hamilton Township postal facility
• Princeton postal facility

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Anthrax Hot Spots

• New York
• CBS News headquarters
• NBC News headquarters
• The New York Post
• Morgan postal facility
• Gov. George Patakis New York City offices

8
Anthrax Hot Spots Washington, D.C.

• Dirksen Senate Office Building
• Hart Senate Office Building
• Ford House Office Building
• Longworth House Office Building
• Off-site Capitol Hill mail facility
• Off-site White House mail facility
• Off-site Justice Department mail facility
• Off-site State Department mail facility

• Off-site Supreme Court mail facility
• CIA mail facility
• Supreme Court Building
• State Department
• State Department Annex
• Wilbur J. Cohen Federal Office Building
• Brentwood postal facility
• Southwest Washington postal facility

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Bacillus anthracis
Texas Department of Health
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Anthrax Cutaneous Lesion, day 1
Texas Department of Health
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Anthrax Cutaneous Lesion, day 2
Texas Department of Health
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CDC
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Mediastinal Widening of Anthrax
Texas Department of Health
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Gastrointestinal Anthrax

• Develops after ingestion of contaminated meat
• May present as fever with oropharyngeal
  ulcerations and cervical lymphadenopathy
• May present as abdominal distress with fever,
  hematemesis, hematochezia, and sepsis

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Diagnosis of Anthrax

• Culture of vesicular fluid, exudate, eschar,or
  biopsy of skin lesion
• Characteristic chest radiograph
• Sputum of little value
• Blood culture
• Stool culture
• PCR, immunofluorescence and immunohistochemistry

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University of KentuckyAnthrax Algorithm1
Referred by Fire Department with credible threat
for exposure to possible source (e.g. powder in
envelope),

The ED Charge Nurse will notify

1. Lab and Hospital Safety officer if 5 pts _at_
one time

2. Infection Control if additional resources are
needed

Decontaminate (at source, or shower In ED)

Culture possible source

Culture nose?

No antibiotics (unless anthrax in the community)

IC to give patients culture results within 72
hours

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University of KentuckyAnthrax Algorithm2
Referred by Fire Department with credible threat
for exposure to possible source (e.g. powder in
envelope), ?24 hours

• No symptoms
• Decontaminate (at source, or shower in ED)
• Culture possible source
• Culture nose?
• No antibiotics (unless anthrax in the community)
• IC to give patients culture results within 72
  hours

• Symptoms
• Decontaminate (at source, or shower in ED)
• Culture possible source
• Culture nose?
• WBC w/ diff
• CXR (CT?) if respiratory symptoms
• Blood cultures X2
• Rapid influenza test
• Give antibiotics

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University of KentuckyAnthrax Algorithm3
Symptoms, but no identifiable source

• No known anthrax in the community
• Routine work-up for symptoms
• Anthrax nose culture at discretion of ER MD
• No antibiotics for anthrax
• Follow-up on positive lab results by ED personnel
  as per usual protocol

• Anthrax in the community
• Decontaminate (at source, or shower in ED)
• Culture nose?
• WBC w/ diff
• CXR (CT?)
• Blood cultures X2
• Rapid influenza test
• Give antibiotics

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University of KentuckyAnthrax Algorithm4
No symptoms, and no identifiable source

• Reassurance
• Written educational materials

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University of KentuckyAnthrax AlgorithmNotes

• Laboratory will immediately notify Infectious
  Diseases Consultant, Infection Control Hospital
  Administration if lab results are positive.
• ?Done for epidemiological reasons (to detect
  exposed individuals). Swab moistened in saline.
  Same swab introduced 3-4cm into right and left
  nostrils.
• 2-5 days of fever and one or more of the
  following drenching sweats, sore throat,
  headache, myalgias, malaise, malaise, cough,
  chest pain, SOB, nausea, vomiting, abdominal
  pain, diarrhea.
• Call ID Consult, doxycycline drug of choice
  for prophylaxis.
• If pneumonia on CXR, consider plague and place
  patient in Droplet Isolation, call Infection
  Control and ID Consult.
• If unusual skin rash consistent with smallpox,
  place patient in Airborne/Contact Isolation using
  N95 respirator, call Infection Control and ID
  Consult.
• Centers for Disease Control hotline (770)
  488-7100

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Bacillus anthracis on Culture

• Grows overnight on agar
• Colonies are non-pigmented, non-mucoid, with a
  ground-glass appearance
• Colonies may have comma-shaped projectionsthe
  Medusa Head
• Non-hemolytic, and non-motile

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Bacillus anthracis on Sheep Blood Agar
Texas Department of Health
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Anthrax Infection Control

• Decontaminate surfaces with bleach
• No need to decontaminate the environment for fear
  of secondary aerosolization
• Anthrax is NOT spread from person to person
• No need to give prophylaxis or treatment to
  contacts of infected patients or exposed persons

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University of KentuckyAnthrax Algorithm
Only Standard Precautions are needed for anthrax
after decontamination
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Antibiotic Susceptibility Testing of Bioterrorism
Anthrax Isolates

• Susceptible
• Ciprofloxacin
• Doxycycline
• Chloramphenicol
• Clindamycin
• Rifampin
• Vancomycin
• Imipenem
• Clarithromycin

• Questionable
• Cephalosporins
• Penicillins
• Erythromycin
• Azithromycin

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Treatment of Inhalational Anthrax

• Ciprofloxacin 400mg iv q12h or doxycycline 100mg
  iv q12h
• Plus one or two others (rifampin, imipenem,
  vancomycin, chloramphenicol, clindamycin,
  clarithromycin, or penicillin)

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Treatment of Inhalational Anthrax

• Clindamycin and clarithromycin have poor CSF
  penetration (up to 50 of patients have
  hemorrhagic meningitis)
• Penicillins may be hydrolyzed by b-lactamases (B.
  anthracis has an inducible b-lactamase)
• Consider use of steroids
• Switch to oral therapy when stable and continue
  for a total of 60 days

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Treatment of Cutaneous Anthrax

• Ciprofloxacin 400mg q12h or doxycycline 100mg
  q12h
• Give orally for 60 days

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Anthrax Post-exposure Chemoprophylaxis

• Adults
• Doxycycline 100mg po bid for 60 days (4.80)
• -or-
• Ciprofloxacin 400mg po bid for 60 days (480.00)
• Childrensame
• Pregnant womensame

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Anthrax ProphylaxisVaccine

• Licensed by Bioport Corporation but not readily
  available
• More efficacious if given before exposure
• Administered as 0.5ml SC doses at 0, 2, 4 weeks
  and then 6, 12, and 18 months
• Boosters must be given yearly

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Differential Diagnosis of Cutaneous Anthrax

• Dissecting aortic aneurysm (no fever)
• Community acquired pneumonia (pleural effusion)
• Tularemia or plague pneumonia (pleural effusion)
• Hantavirus pulmonary syndrome
• Mediastinitis (bacterial, fungal)

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Differential Diagnosis of Cutaneous Anthrax

• Spider bite
• Ecthyma gangrenosum
• Ulceroglandular tularemia
• Plague
• Staphylococcal or streptococcal cellulitis

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Plague
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Gram stain of Yersinia pestis
TDH
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Plague

• Incubation period 1-6 days
• Pneumonia most likely
• Diagnosis by blood cultures, sputum cultures and
  stain
• Treatment is SM, GM, doxycycline, FQ,
  chloramphenicol

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Plague Exposure

• Wash skin, hair, clothes, get prophylaxis
• No vaccine available
• Prophylax with doxycycline, FQ, or chloramphenicol

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PlagueInfection Control

• Patient-to-patient transmission occurs with
  pneumonic plague
• Droplet Precautions for first 72h of Rx
• Prophylax patient contacts
• Disinfect environment with bleach
• No need for decontamination for secondary
  aerosolization after 1h

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Tularemia
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Tularemia

• Incubation period 1-14 days
• Pneumonia or pharyngitis most likely
• Diagnosis by blood cultures, sputum cultures and
  stain, serology
• Treatment is SM, GM, doxycycline, chloramphenicol

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Tularemia Exposure

• Wash skin, hair, clothes, get prophylaxis
• No vaccine available
• Prophylax with doxycycline or chloramphenicol

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TularemiaInfection Control

• Patient-to-patient transmission does not occur
• Standard Precautions
• No need to prophylax patient contacts
• Disinfect environment with bleach
• Not known if need to decontaminate for secondary
  aerosolization

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Smallpox

• When the Spanish landed in Mexico in April, 1520
  there was a single African slave with smallpox in
  their entourage.
• Over the next 10 years, smallpox reduced the
  Aztec population from 25 to 17 million.
• French and Indian Wars (1754-1767)

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Smallpox

• An epidemic in Iceland in 1707 killed 36 of the
  population (then 50,000)
• During the Boston epidemic of 1752 a total of
  5,545 persons (38 of the population) contracted
  smallpox
• Edward Jenner, 1796
• WHO campaign begun in 1967

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Smallpox as Bioterrorism Agent

• In 1980 WHO recommended stopping vaccination and
  destroying all smallpox stock except at the CDC
  and Institute of Virus Preparations in Moscow
• Ken Alibeks allegations in Biohazard, 1999,
  Random House
• Beginning in 1980, the Soviet government began to
  produce smallpox in large quantities
• Ongoing program to develop more virulent and
  contagious recombinant strains

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Clinical Course of Smallpox

• Incubation period of 7-17 days
• Prodrome of high fever and intense frontal
  headache, agonizing lumbar pains, and vomiting
• After 3-4 days, the rash begins as spots on the
  forehead and wrists with rapid spread over the
  face and extremities (looks like measles)

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Four Clinical Forms of Variola Major
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Differential Diagnosis of Smallpox

• Chickenpox
• Erythema multiforme
• Allergic dermatitis
• Drug rash
• Syphilis
• Scabies
• Psoriasis

• Vaccinia
• Herpes
• Measles
• Rubella
• Molluscum contagiosum
• Septicemia (meningococcemia)

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Chickenpox
TDH
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Diagnosis of Smallpox

• Culture the virus (but should only be handled in
  a Biosafety Level 4 laboratorydo NOT submit
  cultures to your hospital laboratory!)
• Send material from vesicles, pustules, or scabs
  for electronmicroscopy

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Management of Smallpox

• No therapy available (cidofovir?)
• Supportive care
• Public health measures

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Communicability

• Spread from person to person
• Respiratory aerosols or droplet nuclei
• Contaminated clothing or bed linens
• Direct contact (variolation)
• Transmission does not occur until onset of the
  rash and is most infectious through the 7-10th
  day of rash
• Scabs are probably not infectious
• Typically, there are 10-20 secondary cases for
  each primary case

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Secondary Attack Rates Among Household Contacts
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Smallpox Infection Control

• In the hospital, isolate with Airborne/Contact
  Precautions using an N-95 or HEPA filtered
  respirator
• Vaccinate all healthcare workers, emergency
  medical responders, and mortuary staff
• Send patients home ASAP or to smallpox hospital

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Containment of Smallpox in Bangladesh
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Attributes of Smallpox that Facilitate its
Eradication

• It is a socially acceptable disease
• There is no animal reservoir
• It has a relatively long incubation period
• The patient is not infectious during incubation
• There are no chronic carriers or sub-clinical
  cases

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Attributes of Smallpox that Facilitate its
Eradication

• Infected patients are easily recognized
• The smallpox virus is immunologically stable
• It produces long lasting immunity
• An efficient vaccine is available

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Effect of Vaccination on Smallpox Mortality
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Effect of Vaccination in Infancy on Smallpox
Mortality
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The Cowpock by James Gilray, 1802
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Complications of Smallpox Vaccination in 14
Million Persons
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Risk of Dying Each Year in the United States
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Smallpox Outbreak, Meschede Hospital, Germany,
1970
Wehrle PF, Bull WHO 197043669
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Meschede Hospital Outbreak
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Defense Against Smallpox

• Recognize cases
• Isolate cases
• Quarantine laws
• Smallpox hospital
• Vaccinate contacts
• Initially healthcare workers and other essential
  personnel (fire, police, politicians)
• General population

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References

• Dixon TC, et al. Anthrax. NEJM 1999341815-826
• Inglesby TV, et al. Anthrax as a biological
  weapon. JAMA 19992811735
• CDC. Anthrax Guideline for antimicrobial
  therapy. MMWR 200150909-919

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References

• Henderson DA, et al. Smallpox as a biological
  weapon. JAMA 19992812127
• Inglesby TV, et al. Plague as a biological
  weapon. JAMA 20002832281
• Dennis DT, et al. Tularemia as a biological
  weapon. JAMA 20012852763
• Arnon SS, et al. Botulinum toxin as a biological
  weapon. JAMA 20012851059