1. Biologic Disasters Bruce Friedberg, MD Department of Emergency Medicine, John Muir Medical Center- Concord Campus Disaster Preparedness Committee

2. Objectives • Review of most likely agents • Clinical signs and symptoms • Management review • Treatments • Infection control • Post-exposure prophylaxis • Vaccinations available

3. Four AM in the ED • 36 year old male presents with fevers and chills, non-productive cough and nausea • Physical exam reveals a well developed male in a Rolling Stones tee shirt • VSS except for a fever of 100.4°, physical exam is otherwise normal • CBC shows mild elevation in WBC, Electrolytes are normal • Patient is hydrated with one liter of NS and discharged with a DX of “Viral Syndrome”

4. Four AM in the ED • While getting ready to discharge the patient, the nurse finds he is now SOB, with a fever of 104° • Upon returning from this CXR he now has hemoptosis • Rapid progression into shock and is declared dead at 7 am. • The nurse tells you that 25 new patients are in triage with viral symptoms

5. Is this a Bioterrorism attack?

6. Epidemiology • Clues suggesting a bioweapon release • Large numbers present at once (epidemic) • Previously healthy persons affected • High morbidity and mortality • Unusual syndrome or pathogen for region or season • Recent terrorist claims or activity • Unexplained epizootic of dead, sick animals

7. Bioterrorism: Defined • The intentional or threatened use of bacteria, viruses, fungi or toxins to create panic, death or disease. • Purpose • Creating fear • Illness • Death • Disruption of social and economic infrastructure

8. Our Role • High level of suspicion • Hoofbeats could be a zebra • Disease Surveillance • hospitals will likely be the 1st with the ability to recognize an attack- We are the first line of defense • Recognize typical BT disease syndromes • Know treatment/prophylaxis of BT agents • Know how to report suspected BT cases • Help protect your facility from contamination • Will often require a decontamination washing. • “Code Orange” used for multiple patients.

9. Why Bioterrorism Agents? • Inexpensive $ • $2000 typical conventional weapon • $1 biologic agent (50% casualties/km2) • Many casualties with minimal planning • Invisible, mimic several common illnesses • Long incubation periods allow escape time for perpetrators • Easily procured

10. CDC Threat Classification • Class A agents: most severe potential for widespread illness and death • Easily disseminated or transmitted from person to person • High mortality rates • Easily weaponized • Class B agents: less potential • Class C agents: future threats

11. Terrorist Dissemination Methods • Aerosol likely route for most agents • Easiest to disperse • Highest number of people exposed • Most contagious route of infection • Food / Waterborne less likely • Only effective for some agents

12. Category A Diseases • Anthrax (Bacillus anthracis) • Smallpox (variola virus) • Plague (Yersinia pestis) • Tularemia (Francisella tularensis) • Botulism (botulinum toxin) • Viral Hemorrhagic Fever

13. Anthrax Bacillus anthracis

14. Anthrax • 2001(fall)- anthrax mailings • NBC news, Sen. Tom Daschle • 22 total cases/ 11 inhalation/ 5 deaths

16. Anthrax: info • Cutaneous • Gastrointestinal (rare) • Inhalation • Spores are Odorless/Invisible • Likely dissemination route: Aerosolization

17. Cutaneous anthrax • 2000 cases annually (worldwide) • Transmitted from Herbivores • Skin is exposed to spores • Painless, pruritic papule develops • “Painless” black eschar follows • 1-14 day latent period • Mortality: 20%, if untreated • Readily responds to Ciprofloxacin

18. Inhalation anthrax: clinical • 18 cases in US between 1900-1976 • Follows inhalation of spores • Possible sixty day delay in symptoms • Estimated 3 million deaths from 100 kg release (spores can travel airborne for 60 miles) • During fall 2001 “mailings” • 45% mortality • 4 day latent period

19. Inhalation anthrax: clinical • Initial sxs (hours to days): • Malaise, drenching sweats • Low-grade fever • Non-productive cough • Nausea/ vomiting • Terminal sxs (usually hours) • abrupt dyspnea, stridor, cyanosis • Rapid progression to shock and death

20. Inhalational anthrax: clinical • CXR (10/11 in 2001 mailings were abnormal): • Hemorrhagic mediastinitis with widened mediastinum on CXR • Peripheral Blood smear shows Gram-positive bacilli • Aerobic Blood culture shows growth of large, gram-positive bacilli

21. Anthrax: treatment • Infection Control • Standard precautions • If cutaneous wear gloves • Not transmitted from person to person • Give Antibiotics Early • Ciprofloxacin • Doxycycline

22. Anthrax: treatment • All post-exposure contacts should be treated for 60 days • Ciprofloxacin • Alternate: doxycycline • Vaccine (developed in 1970s) • Used by military

23. Smallpox Orthopoxvirus (variola species)

24. Smallpox: info • One of highest-threat bioterrorism agents • High case fatality rate • Lack of specific therapy • Routine US vaccines stopped in 1972 • Herd immunity no longer present • Likely dissemination route: Aerosolization or human carriers

25. Small pox: info • 12- 14 day incubation period • Most infective during initial rash period • Less infective after crusting of lesions

26. Smallpox vs Varicella 14-21 day incubation Minimal prodromal Rapid development of rash Centripetal: seldom on soles and plams Asynchronous lesions- successive crops • 12-14 day incubation • Prodromal symptoms • Slow development of rash • Centrifugal: greatest concentration of lesions on face and extremities • Synchronous lesions

27. Smallpox vs Varicella

28. Smallpox: treatment • Supportive only • Infection control • Pt isolation • Standard, Contact & Airborne precautions (N-95 mask recommended) • Immunized individuals should be protected • Antiviral agents not currently recommended

29. Smallpox: Prophylaxis • Vaccine within 4 days of exposure can lessen severity of infection • Contraindicated in immunocompromised and pts with eczema • “there is enough smallpox vaccine to vaccinate every person in the United States in the event of a smallpox emergency” • Vaccinia immune globulin (VIG) • Within 2-3 days of exposure • Consider for those with contraindications to the vaccine

30. Botulinum Toxin Clostridium botulinum

31. Botulism toxin: info • Most poisonous substance known • Occurs naturally in soil (odorless, colorless, tasteless) • Most cases from contaminated undercooked meat (inactivated if >85 C for 5 minutes) • Toxin has neuroparalytic effects • Toxin irreversibly binds to acetylcholine receptors • Likely dissemination route: • Contamination of food or Aerosolization

32. Botulism: info • Mortality: • Treated = < 5% • Untreated = up to 60% • Diagnosis is CLINICAL • Incubation of 2 hours to 8 days • Many casualties will require long term respiratory support • Confirmatory testing is slow (only at CDC and 20 other public health sites)

33. Botulism: clinical • Afebrile • Descending flaccid paralysis • Bulbar deficits initially • Four “D’s” • Diplopia • Dysarthria • Dilated pupils • Dysphagia

34. Botulism: treatment • Supportive care • Respiratory support could be for months • new motor axons must grow to paralyzed areas • Antitoxin (available only from CDC) • May prevent spread of paralysis, BUT does not reverse paralysis • Infection Control • Standard precautions

35. Botulism: prevention • No effective post exposure prophylaxis • +/- Antitoxin • Vaccine • DOD pentavalent toxoid is available • Used for last 30 years in lab workers

36. Plague Yersinia pestis

37. Plague: info • The “Black Death” has caused more fear and terror than perhaps any other infectious disease in history • It has laid claim to at least 200 million lives • Most human cases are from bites from infected fleas who have had a blood feed from an infected rodent • Human to human transmission occurs only in pneumonic plague from direct inhalation • Likely dissemination route: Aerosolization

38. Plague • Bubonic • Septicemic • Pneumonic

39. Plague: clinical • Usually present 2-8 days after exposure • Sudden onset of fever, chills, weakness +/-acutely swollen painful lymph nodes • Swollen lymph nodes = “Buboes” • possibly suppurative

40. Bubonic and septicemic plague: clinical Symptoms + Buboes present Bubonic plague Symptoms without Buboes Septicemic plague -gram-negative sepsis -DIC

41. Pneumonic Plague: clinical • Approaches 100% fatality rate (untreated) • Highly contagious • Within 24 hours of exposure: • High fever • Vomiting and abdominal pain • Cough with bloody sputum • DIC

42. Pneumonic Plague: clinical • DX with sputum secretions/ Gram stain & culture

43. Plague: treatment • Infection Control • Standard and droplet precautions (if pneumonic plague suspected) • Antibiotics recommended (for 10 days) • Start treatment prior to ID (delay can decrease survival) • Streptomycin (reduces mortality to 5-14%) • Gentamicin, Ciprofloxacin,Doxycycline, Chloramphenicol

44. Plague: prevention • Post exposure prophylaxis: • Treat with antibiotics for seven days • No vaccine is currently available (previously used in military)

45. Tularemia Francisella tularensis

46. Tularemia: info • Infection occurs naturally from bites by infected arthropods, handling infectious animal tissues, contact with or ingestion of contaminated food, water, or soil and inhalation of infective aerosols • No person to person transmission • Survives for weeks in water, moist soil, straw, and decaying animal carcasses • The signs and symptoms people develop depend on how they are exposed to tularemia

47. Tularemia- clinical forms • Ulceroglandular • Pleuropneumonitis • Oropharyngeal • Oculoglandular • Septicemic

48. Tularemia: clinical • 1-14 day incubation • If inhaled, symptoms can include abrupt onset of fever, chills, headache, muscle aches, joint pain, dry cough, and progressive weakness • One of the most infectious pathogenic bacteria known. • Inhalation of as few as 10 organisms can cause disease. • Likely dissemination route: Aerosolization

49. Tularemia- treatment • Infection Control • Contact and Airborne Precautions • Use Antibiotics (14-21 days) • Streptomycin • Gentamicin • Ciprofloxacin

50. Tularemia- prevention • Post-exposure prophylaxis • Doxycycline • Ciprofloxacin • Tetracycline • Vaccine available • Live attenuated vaccine (under FDA review)