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. Anthrax Plague Tularemia Smallpox Brucellosis Q fever Cholera Venezuelan equine encephalitis Ebola, Lassa, Marburg Botulinum toxin Staphylococcal enterotoxin B etc... Bioterrorism Threats

3. Anthrax Plague Tularemia Smallpox Brucellosis Q fever Cholera Venezuelan equine encephalitis Ebola, Lassa, Marburg Botulinum toxin Staphylococcal enterotoxin B etc… Bioterrorism Threats

4. Anthrax as a Bioterrorism Agent—Theory • 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

5. Anthrax as a Bioterrorism Agent—The 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.

6. 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 ABCNEWS.com October 30, 2001

7. Anthrax ‘Hot Spots’ • New York • CBS News headquarters • NBC News headquarters • The New York Post • Morgan postal facility • Gov. George Pataki’s New York City offices ABCNEWS.com October 30, 2001

8. 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 Anthrax ‘Hot Spots’ Washington, D.C. ABCNEWS.com October 30, 2001

9. Bacillus anthracis Texas Department of Health

10. Anthrax Cutaneous Lesion, day 1 Texas Department of Health

11. Anthrax Cutaneous Lesion, day 2 Texas Department of Health

12. CDC

13. Mediastinal Widening of Anthrax Texas Department of Health

14. 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

15. 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

16. University of KentuckyAnthrax Algorithm—1 Referred by Fire Department with credible threat for exposure to possible source (e.g. powder in envelope), <24 hours • The ED Charge Nurse will notify: 1. Lab and Hospital Safety officer if >5 pts @ 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*

17. University of KentuckyAnthrax Algorithm—2 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♣ • WBCw/ diff • CXR (CT?) if respiratory symptoms • Blood cultures X2 • Rapid influenza test • Give antibiotics***

18. University of KentuckyAnthrax Algorithm—3 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***

19. University of KentuckyAnthrax Algorithm—4 No symptoms**, and no identifiable source • Reassurance • Written educationalmaterials

20. University of KentuckyAnthrax Algorithm—Notes • *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

21. Bacillus anthracis on Culture • Grows overnight on agar • Colonies are non-pigmented, non-mucoid, with a ground-glass appearance • Colonies may have comma-shaped projections—the “Medusa Head” • Non-hemolytic, and non-motile

22. Bacillus anthracis on Sheep Blood Agar Texas Department of Health

23. 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

24. University of KentuckyAnthrax Algorithm Only StandardPrecautions are needed for anthrax after decontamination†‡

25. Susceptible Ciprofloxacin Doxycycline Chloramphenicol Clindamycin Rifampin Vancomycin Imipenem Clarithromycin Questionable Cephalosporins Penicillins Erythromycin Azithromycin Antibiotic Susceptibility Testing of Bioterrorism Anthrax Isolates

26. 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)

27. 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

28. Treatment of Cutaneous Anthrax • Ciprofloxacin 400mg q12h or doxycycline 100mg q12h • Give orally for 60 days

29. Anthrax Post-exposure Chemoprophylaxis • Adults • Doxycycline 100mg po bid for 60 days ($4.80) -or- • Ciprofloxacin 400mg po bid for 60 days ($480.00) • Children—same • Pregnant women—same MMWR October 19, 2001

30. Anthrax Prophylaxis—Vaccine • 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

31. 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)

32. Differential Diagnosis of Cutaneous Anthrax • Spider bite • Ecthyma gangrenosum • Ulceroglandular tularemia • Plague • Staphylococcal or streptococcal cellulitis

33. Plague

34. Gram stain of Yersinia pestis TDH

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

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

37. Plague—Infection 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

38. Tularemia

39. 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

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

41. Tularemia—Infection 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

42. 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)

43. 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

44. 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 Alibek’s 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

45. 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)

46. Four Clinical Forms of Variola Major

47. Chickenpox Erythema multiforme Allergic dermatitis Drug rash Syphilis Scabies Psoriasis Vaccinia Herpes Measles Rubella Molluscum contagiosum Septicemia (meningococcemia) Differential Diagnosis of Smallpox

48. Chickenpox TDH

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

50. Management of Smallpox • No therapy available (cidofovir?) • Supportive care • Public health measures