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  1. “Preparing Our Communities” Welcome!

  2. Faculty Disclosure • For Continuing Medical Education (CME) purposes as required by the American Medical Association (AMA) and other continuing education credit authorizing organizations: • In order to assure the highest quality of CME programming, the AMA requires that faculty disclose any information relating to a conflict of interest or potential conflict of interest prior to the start of an educational activity. • The teaching faculty for the BDLS course offered today have no relationships / affiliations relating to a possible conflict of interest to disclose. Nor will there be any discussion of off label usage during this course.

  3. Biological Events Chapter 5 3

  4. Objectives Describe the difference between biological events and bioterrorism (BT) Discuss public health BT surveillance Identify the CDC BT Category A agents Identify emerging infectious diseases Compare and contrast BT and other CBRNE WMD utilizing the DISASTER paradigm 4

  5. Biological Events Biological events: Natural vs. Intentional Intentional Natural Release of anthrax in mail Salmonella sprayed on food bar Smallpox infection Aerosolized botulinum toxin Outbreak of monkey pox in pet prairie dogs Avian Flu pandemic Natural occurrence of anthrax Bubonic plague outbreak 5

  6. Bioterrorism Release Types: Overt or Covert Overt Covert Release • Notice of release provided • May contain a threat • Designed to create panic or fear • May be hoax (white powder) or credible threat • No notice or threat • Difficult to detect • Persons seek care at usual medical care facilities • Early symptoms non-specific • so detection may be delayed • Focus: Astute clinician make diagnosis and notify health department (Detection) Covert or Overt ? Covert or Overt ? (1763)Captain Simeon Ecuyer had sent smallpox-infected blankets and handkerchiefs to the Indians surrounding the fort (as a supposed peace offering)-- but actually an early example of biological warfare -- which started an epidemic among the Indians. Letter sent to the New York Post and NBC News: Containing “white powder” 6

  7. Potential Methods of Detection Increased number of patients Increased unexplained deaths Unusual patient age distribution Unusual seasonality Unusual manifestation of disease Animal die-off Notifiable disease reporting by physicians & other providers Automated reporting of laboratory results Number and type of 911 calls Number and type of EMS runs Syndromic surveillance Public Health Surveillance 7

  8. CDC Categories BT Agents Divided into Categories A, B,C based on: Quantity of agent available Ability to disseminate the agent Person-to-person transmission Severity of disease Public response, panic, etc.. Overall risk to national security 8

  9. Category A Agents Anthrax Smallpox Plague Botulinum toxin Tularemia Viral hemorrhagic fevers 9

  10. Category B Agents(examples) Infectious Agents Brucellosis Glanders Bio-toxins Ricin toxin from Ricinus communis (castor beans) Staphylococcal enterotoxin B • Why are these Category B Agents • Less quantity available than Category A • Harder to disseminate • Less person to person transmission- if any • Slightly less severity of disease • Less known to public - therefore less likely to cause panic • Slightly less risk to National Security • Water safety threats • Vibrio cholerae • Food safety threats • Salmonella species • Escherichia coli O157:H7 • Shigella • Viral encephalitis • Venezuelan Equine Encephalitis 10

  11. Category C Emerging infectious diseases as bioterrorism agents Nipah virus Hantavirus Emerging infectious disease that posses a significant public health threat Avian Flu SARS 11

  12. Category A: Anthrax • Endemic in animals worldwide with occasional human cases • Handling infected animal products (especially cattle, sheep, horses, mules and goats) • Spores used for bioattack • Aerosolized directly or sent in mail/packages • Three forms • Cutaneous, Inhalation, GI Anthrax in CSF—US index case 12

  13. Anthrax – Clinical Features Inhalation Incubation: 2-43 days (may be longer) Prodrome Fevers, malaise, dry cough, chest pain, dyspnea, myalgia Abrupt onset of fulminant illness Sudden high fever, respiratory distress, shock Meningitis in ~50% Actual pneumonia uncommon 13

  14. Normal Chest X-Ray Widened mediastinum & pleural effusions Inhalational anthraxUS index case 14

  15. Anthrax – Clinical Features Cutaneous Incubation: 1 to 7days (up to 12 days) Erythematous “itchy” papule  ulcer  characteristic black eschar with surrounding erythema and edema Regional adenopathy and systemic symptoms (e.g., fever, malaise) Most lesions completely resolve 15

  16. Anthrax – Clinical Features Gastrointestinal Incubation period 1-7 days Not likely after a bioattack Presents as febrile illness with bloody diarrhea Eating undercooked infected meat 16

  17. Anthrax Diagnosis Blood cultures Usually positive in < 24h Gram stain pleural fluid or CSF Sputum gram stain/culture is usually NOT positive Inhalational disease Very suggestive if fever and widened mediastinum Cutaneous disease Culture fluid from under eschar Nasal swabs are a poor test 17

  18. Anthrax –Treatment Ciprofloxacin 400 mg IV q12h 10-15 mg/kg for children Other fluoroquinolones probably also effective OR Doxycycline 100 mg IV q12h 2.2 mg/kg for children PLUS 1 or 2 additional antibiotics Clindamycin, rifampin, vancomycin, penicillin, chloramphenicol, imipenem, or clarithromycin 18

  19. Prophylaxis and Infection Control Prophylaxis Ciprofloxacin 500 mg PO BID(Peds:10-15 mg/kg) or Doxycycline 100 mg PO BID (Peds:2.2 mg/kg) Continue for 60 days (? 100 days) Vaccine available for DOD forces Infection Control Standard barrier precautions are needed Not transmitted person-to-person Only immunize / prophylaxis exposed at BT attack 19

  20. Anthrax Vaccination Schedule 6 shots over 18 months, then annual booster Dosing schedule is 0.5 mL subcutaneously at each visit Then yearly boosters 1 2 3 4 5 6 0 4 weeks 2 weeks 6 months 12 months 18 months 20

  21. Botulism Clostridium botulinum A Toxin Producing Obligate, Anaerobic, Spore Forming, Gram Pos. Bacillus 21

  22. Botulism - General Caused by a toxin produced by Clostridium botulinum Sporadic cases and outbreaks caused by tainted foods For bioattack toxin could be delivered as an aerosol or used to contaminate food / water 22

  23. Botulism - Clinical Features 12 to 36 hour “incubation” Range 2 h to 8 days Clinical recognition is key to diagnosis Bulbar palsies: Must be present! Ptosis, blurred vision, dry mouth, dysarthria, trouble swallowing Afebrile,“AAO x 3”, difficulty speaking Descending skeletal muscle paralysis Death: Respiratory muscle paralysis 23

  24. 17 Year-Old with Mild Botulism 24

  25. Botulism - Treatment Supportive care Respiratory failure Prolonged Ventilator support Antitoxin State health department obtained Prevents further damage Does not alter current damage 25

  26. Botulism – Infection Control Prophylaxis No proven prophylaxis at this time Investigational Vaccine Isolation Standard precautions (not P-to-P) Need to contact public health authority immediately:Others may be exposed to contaminated food source or agent 26

  27. Plague Yersinia pestis Yersinia pestis Source: www.cdc.gov Gram Neg., Anaerobic, Rod Shaped Bac. “Safety Pin” Bipolar on Wright Staining 27

  28. Plague - General Endemic in animals throughout the world Prairie dogs in the Southwestern US High potential as a BT agent Endemic form Spread to humans via a flea vector Results in bubonic form of the disease Bioattack Most likely aerosolized Results in pneumonic plague Release of infected fleas Buboes Source: www.cdc.gov 28

  29. Plague – Clinical Features Following Aerosolized Bioattack 1- 6 day incubation Abrupt onset High fever, chills, and malaise Cough with bloody sputum Sepsis Severe rapidly progressive pneumonia Untreated 100% mortality 29

  30. Plague - Diagnosis CXR with patchy infiltrates Culture of blood and sputum Need to inform the laboratory if you suspect plague … special techniques May show characteristic “safety-pin” bipolar staining Sudden # Gm(neg) pneumonia 30

  31. Plague pneumonia Normal Chest X-Ray 31

  32. Plague - Treatment Preferred: Start within first 24 hours for 10 days Streptomycin 1 g IM q12h 15 mg/kg/dose for children Avoid in pregnant women Gentamicin 5 mg /kg IM or IV qd Or 2 mg/kg load the 1.7 mg/kg q8h For children use 2.5 mg/kg q8h Alternative Doxycycline 100 mg IV q12h 2.2 mg/kg/dose q12h for children Ciprofloxacin 400 mg IV q12h Other fluoroquinolones probably effective For children 15 mg/kg/dose q12h 32

  33. Plague - Infection Control Prophylaxis: Treat for 7 days Doxycycline 100 mg PO bid 2.2 mg/kg for children Ciprofloxacin 500 mg PO bid 20 mg/kg for children other fluoroquinolones probably effective Isolation Droplet precautions (Yes, P-to-P) 33

  34. Smallpox Source: www.cdc.gov 34

  35. Smallpox - General One of the deadliest disease Mortality rate of 30% US stopped vaccinating in 1972 Declared eradicated by WHO In 1980, however... Bioattack Aerosolized virus or by exposure to purposefully infected terrorists 35

  36. Smallpox - Clinical Features Incubation period 7-17 day (average 12d), Weaponized 3-5 d Severe prodrome Key difference! 2-3 day of fever, severe myalgias, prostration, occ. n/v, delerium 10% with light facial erythematous rash Distinctive rash Initially on face and extremities Including palms and soles Spreads to trunk 36

  37. Small Pox - Clinical Features Rash Macules  papules  vesicles  pustules Unlike chicken pox, lesions don’t appear in “crops” All lesions in an area are in the same stage of development Lesions are firm, deep, frequently umbilicated Rash scabs over in 1-2 weeks Chickenpox Smallpox 37 Source: www.cdc.gov

  38. Smallpox The main diagnostic tool for smallpox is the history and physical! Source: www.cdc.gov 38

  39. Smallpox - Treatment Vaccination In the early stages of disease Supportive care Penicillinase-resistant antibiotics (for secondary infection) Daily eye rinsing Adequate hydration and nutrition FDA has not approved specific therapy Topical idoxuridine for corneal lesions (Dendrid) Cidofovir ? 39

  40. Smallpox - Infection Control Prophylaxis Vaccine is effective if given within 3 days of exposure Isolation Airborne and contact precautions Febrile illness after potential exposure should prompt isolation before rash starts Immediate contact your hospital epidemiologist and the public health authorities 40

  41. Tularemia Francisella tularensis Source: www.cdc.gov Gram Neg. Coccobacillus 41

  42. Tularemia - General Endemic in North America and Eurasia Sporadic human cases spread by ticks or biting flies Occasionally from direct contact with infected animals (ulceroglandular) Bioattack Aerosolized bacteria Typhoidal tularemia & (+ / - ) pneumonia 42

  43. Tularemia - Clinical Features Bioattack 3-5 day incubation (range 1-14 days) Acute febrile illness with prostration ~80% will have radiographic evidence of pneumonia May have associated conjunctivitis or skin ulcer & regional adenopathy 43

  44. Tularemia - Diagnosis Culture of blood and sputum May take weeks to isolate and ID Gram negative coccobacillus Confirmation may require reference laboratory Potential hazard to laboratory personnel Laboratory must be notified if tularemia is suspected 44

  45. Tularemia - Treatment PreferredTreatment time varies with Abx Streptomycin 1 g IM q12h 15 mg/kg for children Gentamicin 5 mg / kg IM or IB q day for children use 2.5 mg/kg q8h Alternative Doxycycline 100 mg IV q12h 2.2 mg/kg for children Ciprofloxacin 400 mg IV q12h Children 15 mg/kg Other fluoroquinolones probably effective 45

  46. Tularemia - Infection Control Prophylaxis: Treat for 14 days Doxycycline 100 mg PO bid 2.2 mg/kg for children Ciprofloxacin 500 mg PO bid 15-20 mg/kg for children Tetracycline Isolation: Standard precautions (Not P-to-P) 46

  47. Viral Hemorrhagic Fevers Source: www.cdc.gov Ebola virus 47

  48. VHF - General Naturally occurring disease Transmitted to humans by contact with infected animals or arthropod vectors. Sporadic outbreaks in Africa, parts of Asia and Europe (Outside of Africa, likely BT event) VHF viruses as bioterrorism agents Weaponized by several countries Aerosolization Case fatality rates Omsk hemorrhagic fever 0.5% Ebola 90% 48

  49. VHF - Clinical Features Incubation 2 - 21days Depends on virus Initial presentation Nonspecific prodrome (fever, myalgias, headache, abdominal pain, prostration) Exam may show only flushing of face and chest, conjunctival injection, and petechiae Disease progresses to generalized mucous membrane hemorrhage and shock occurs Marburg Disease Bolivian Hemorrhagic Fever 49

  50. VHF - Diagnosis Ancillary testing: Thrombocytopenia, leukopenia, AST elevation common Definitive diagnosis requires detection of antigens or antibodies Testing done at CDC Do not wait to confirm the diagnosis before notifying the local public health authorities 50