Terri Rebmann, RN, MSN, CIC Infectious Disease Specialist

1. Biological Terrorism Awareness and the Epidemiology of Infectious Agents: Anthrax, Smallpox and Plague Terri Rebmann, RN, MSN, CIC Infectious Disease Specialist 3/02

2. Information contained in this presentation was current as of December, 2001 and was designed for educational purposes only. Medication information should always be researched and verified before initiation of patient treatment. Always review current literature. Please visit our website: http://www.bioterrorism.slu.edu

3. What is Bioterrorism? • Use of disease in a terrorist action to harm or kill an adversary's military forces, population, food, and livestock. This includes any living (or non-living) microorganism or bioactive substance that is produced by a microorganism that can be delivered by military or civilian means.

4. Terrorism VS Bioterrorism • Know the difference • First responders for traditional terrorism • Bioterrorism first responders

5. History of Bioterrorism • 14th Century: Cadavers dropped into wells • 14th Century: Kaffa • 1763: Native Americans given smallpox blankets • Civil War: Animal carcasses • 1925: Geneva Protocol • WWII: Japanese Unit 731

6. History of Bioterrorism • 1969: Nixon ends BW program • 1972: Biological and Toxin Weapons Convention • 1978: Ricin assassination in London • 1984: Contamination of a salad bar in OR • 1995: Aum Shinrikyo subway attack in Tokyo • 2001: Letters containing anthrax spores

7. Changing Goals of Terrorism • Traditional terrorists’ goals: High visibility, low casualty • Current goal of many terrorists: Mass casualties - Biological weapons are ideal From small car bombs to...

8. Why use Biological Weapons? • Large attack area • Detection delayed • Diagnosis delayed • Ease of production

9. Why use Biological Weapons? • Inexpensive • Knowledge easily accessed • Cold War • Equipment accessible • Safe for perpetrators

10. Common Characteristics of Likely BT Agents • Liquid or powder • Aerosolized particles (1- 5 microns) • Line source or point source • Weather

11. Thermal Inversions Normal Conditions:Warm air rises, disperses pollutants, cool air circulates downward Thermal Inversions:Warm air is trapped between cool air layers trapping pollutants at ground level

12. Delivery of BT Agents • Orally • Food • Water • Aerosol

13. CDC’s Categories for Bioterrorism Agents • Category A, B, &C • Based on: • Ease of production • Availability • Ease of dissemination (stability) • Lethality • Infectivity

14. Category A Agents: The Threat • Bacillus anthacis (Anthrax) • Variola major (Smallpox) • Yersinia pestis (Plague) • Botulinum toxin (Botulism) • Francisella tularensis (Tularemia) • Filo and arena viruses (Viral Hemorrhagic Fevers)

15. Epidemiological Clues • Clues from unlikely source • ER or Family Practice Clinic/Office • Pharmacy • Intuition or “hunch” that something is not right • Will require high index of suspicion •  mortality,  severe morbidity, or  respiratory illnesses • Large epidemic of acutely ill patients or multiple, simultaneous epidemics

16. Epidemiological Clues • Unusual or impossible pathogen • Prior or current threat of bioterrorism • Unexplained numbers of dead animals • Will require an astute clinician • Non-specific flu-like illness cluster(s) • High index of suspicion

17. Epidemiological Clues Key: Look for change or trend in your population baseline When you hear hoof beats, think of a horse, but don’t rule out a zebra

18. Anthrax • Bacillus anthracis • One of the most likely agents to be used • Three forms: • Cutaneous: most common in natural cases • GI: Rare, but highly fatal • Inhalational: Most lethal form • Last case > 20 yrs ago (Until Sept 2001) • Probable form to be encountered in BT attack

19. Diagnosis • Prognosis is poor • Prior to Fall 2001, mortality rate: 86-100% • Current mortality rate: ~ 45% • Treat pt ASAP • Presumptive • Base on signs & symptoms and risk of exposure

20. Definitive Diagnosis • Blood culture and Gram stain of smear at your lab • Gram + bacilli should be referred to the state health reference lab for confirmation • Must be coordinated through the local health dept • Alert lab of possible anthrax • Gram positive rods usually labeled “contaminants”  • Sputum cultures are useless (not pneumonic) • Ulcer aspirate (cutaneous disease)  

21. Pathogenesis:Inhalational Anthrax • Incompletely cleared by macrophages • Migrate to mediastinum via lymphatics • Germinate into vegetative bacilli • Causes hemorrhagic necrotizing mediastinitis • Active toxin production • Followed by high-grade bacteremia • Sepsis, multiorgan failure, spread to meninges

22. Clinical Features:Inhalational Anthrax • Incubation period: 1-10 days • 2 stage illness: • Prodromal phase: • Flu-like symptoms • Brief improvement (not seen in recent cases) • Fulminate stage: • High-grade bacteremia • Widened mediastinum without infiltrates

23. Chest radiograph of a 51-year-old laborer with occupational exposure to airborne anthrax spores taken on day 2 of illness. Lobulated mediastinal widening (arrowheads) is present, consistent with lymphadenopathy, with a small parenchymal infiltrate at the left lung base. Photo: JAMA Consensus Article

24. Photo courtesy of CDC PHIL Mediastinal widening on Chest X-Ray in an inhalational anthrax patient

25. Clinical Features:Cutaneous Anthrax • Black eschar • Begins as pruritic macule or papule • Painless ulcer by 2nd day • Contains B. anthracis • Usually progresses to eschar within 5-6 days • Systemic disease may develop • Lymphangitis and lymphadenopathy • If untreated, can progress to sepsis, death

26. Forearm lesion on day 7 of illness shows vesiculation and ulceration of the initial macular or papular anthrax skin lesion. Eschar of the neck on day 15 of illness is typical of the last stage of the lesion before it resolves over 1 to 2 weeks. Photos: JAMA Consensus Article

27. Painless lesion of cutaneous anthrax Painful lesion from spider bite

28. Infection Control • Not transmitted person to person • Standard Precautions

29. Inhalational Anthrax: Treatment Recommendations • Initial multi-drug therapy for adults: • Ciprofloxacin 400mg IV every 12 hours or • Doxycycline 100mg IV every 12 hours • AND one or two of the following: Rifampin, Vancomycin, Imipenem, Chloramphenicol, Penicillin, Ampicillin, Clindamycin, Clarithromycin

30. Inhalational Anthrax Treatment • Initial multi-drug therapy for children: • Ciprofloxacin 20-30 mg/kg/d IV divided q12 ° or • Doxycycline • < 45kg: 2.2 mg/kg IV q12° • > 45kg: adult dose • AND one or two of the following: Rifampin, Vancomycin, Imipenem, Chloramphenicol, Penicillin, Ampicillin, Clindamycin, Clarithromycin

31. Treatment • Switch to PO therapy when clinically appropriate • Ciprofloxacin 500mg twice daily or • Doxycycline 100mg twice daily • All treatment (IV and PO combined) is 60 days • Cutaneous treatment same as inhalational, except use single drug • Treat for 60 days

32. Postexposure Prophylaxis • Antibiotic therapy • Treat ASAP; prompt therapy can improve survival • Contacts do not need it

33. Postexposure Prophylaxis • Same regimen as active treatment • Substituting oral equivalent for IV • Ciprofloxacin 500 mg po bid • Doxycycline 100 mg po bid • Continue for 8 weeks • Vaccine • May be available through CDC

34. Decontamination • Patient decontamination usually not an issue • By the time the pt has developed symptoms or the release is identified, most pts will have showered and changed their clothes

35. Decontamination • Announced attack or release identified within 24 – 48 hrs • Exposed individuals • Shower with soap and water • Bleach not needed • Store clothing in sealed bag • Potential evidence

36. Decontamination • Spores are hardy in the environment • Survive for years in soil • No secondary cases • Sterilize instruments with a sporicidal agent

37. Smallpox • Most devastating infectious disease in history • 500 million vs 320 million • Eradicated from planet in 1970’s • Remains bioterrorism threat Last known person to have smallpox. Somalia 1978 Photo courtesy of CDC PHIL

38. Microbiology • Variola virus • 2 strains • Major and minor • Variola major • Classic smallpox • Predominant form in Asia • Highest mortality (>30%) • Form most likely to be seen

39. Microbiology • Variola minor • Milder disease • Less morbidity/mortality (< 1%) • Less severe prodrome and rash • Predominant form in N. America

40. Diagnosis • Base on signs and symptoms • Notify Local Health Department • Suspicious cases

41. Clinical Features • Incubation period: 12-14 days • Three stages of disease • Incubation • Prodromal (pre-eruptive) • Eruptive Photo courtesy of CDC PHIL

42. Clinical Features • Prodromal Stage • Common symptoms • High fever, prostration, low back myalgias, HA • Occasional symptoms • Vomiting, abdominal pain, delirium • Duration typically 3-5 days • Mucosal lesions appear at end of prodromal stage • Onset of infectiousness

43. Clinical Features • Eruptive Stage (Rash) • Characteristic rash • Centrifugal (in order of appearance & severity) • Lesions all in same stage of maturation • Initially oral mucosa • Head, face • Forearms, hands, palms • Legs, soles, +/- trunk

44. Complications • Disfiguring pock marks • Encephalitis • Secondary bacterial infections • Conjunctivitis or blindness

45. Classic Centrifugal Rash of Smallpox Involving Face and Extremities, Including the Soles. Photo courtesy of National Archives

46. Classic Centrifugal Rash of Smallpox Involving Face and Extremities. Photo courtesy of National Archives

47. Classic Smallpox Rash, Demonstrating Same Development Stage (Pustular) of All Lesions in a Region Photo courtesy of National Archives

48. Progression of Smallpox Lesions in Semiconfluent Case Patient Who Survived. Demonstrates Vesicles, Pustules, Scabs Then Scars.

49. Smallpox VS Chickenpox Photo courtesy of CDC Photo courtesy of CDC PHIL

50. Infection Control • Highly infectious • Droplet, aerosol or clothing • Transmission slower and less likely than with measles or chickenpox • Attack rate 25-40% • 3-4 secondary cases/primary case • 10–20 not uncommon Photo courtesy of National Library of Medicine and WHO