1. DPT 8.0 The Biologic Incident Management of Biological Casualties

2. DPT 8.0 Hospital Management of Biological Casualties

3. DPT 8.0 Biological Warfare Agents Terminal Objective Be able to describe the various types of biological warfare agents and recognize the signs and symptoms of exposure. Be able to describe how to properly manage and treat infectious victims Know which agents are a risk for secondary transmission and how to protect against this spread using personal protective equipment (PPE) and isolation measures.

4. DPT 8.0 Biological Warfare (BW) Agents - History Oldest of the NBC triad of agents Used for > 2,000 years – Sieges of middle ages – Smallpox blankets given to Native Americans – Germany in World War I – Japan in World War II

5. DPT 8.0 Aerosol / Infectivity Relationship 18-20 15-18 7-12 4-6 (bronchioles) 1-5 (alveoli) Infection Severity Particle Size (Micron, Mass Median Diameter) The ideal aerosol contains a homogeneous population of 2 or 3 micron particulates that contain one or more viable organisms Maximum human respiratory infection is a particle that falls within the 1 to 5 micron size Less Severe More Severe

6. DPT 8.0 BW - Epidemiologic Clues Large epidemic with high illness and death rate HIV(+) individuals may have first susceptibility Respiratory symptoms predominate Infection non-endemic for region Multiple, simultaneous outbreaks Multi-drug-resistant pathogens Sick or dead animals Delivery vehicle or intelligence information

7. DPT 8.0 BW - Epidemiological Information Travel history Infectious contacts Employment history Activities over the preceding 3 to 5 days

8. DPT 8.0 Biological Agents - Types and Characteristics Bacteria Viruses Toxins

9. DPT 8.0 Bacteria as Biological Agents Bacteria – Single celled microorganism – Invade tissue; cause inflammatory reaction or produce toxins – May form spores Anthrax Plague Tularemia Q Fever

10. DPT 8.0 Anthrax - Microbiology Bacillus anthracis - gram +, spore-forming bacillus Endemic infection in animals Humans develop infection naturally from handling contaminated fluids or hides (“Woolsorters Disease”)

11. DPT 8.0 Anthrax - Pathogenesis Inoculation, ingestion, or inhalation of spores which may travel to the regional lymph nodes Vegetative bacteria produce edema factor and lethal factor (toxins) Inhalation route has highest mortality and is most likely route to be used by terrorists Inhaled anthrax causes a mediastinitis rather than a pneumonia Untreated skin infection - 21% mortality if septicemia develops (treated 1%)

12. DPT 8.0 Cutaneous Anthrax

13. DPT 8.0 Gastrointestinal Anthrax

14. DPT 8.0 Inhalational Anthrax 2 to 6-day incubation period followed by fever, myalgias, cough, and fatigue Initial improvement followed by abrupt onset of respiratory distress, shock, and death in 24 to 36 hours Physical findings are nonspecific, pneumonia is rare Chest x-ray - may show widened mediastinum with or without a bloody pleural effusion 50 % of cases have associated hemorrhagic meningitis

15. DPT 8.0 Prevention of Secondary Anthrax Transmission No documented cases of person-to-person transmission of inhalational anthrax has ever occurred Cutaneous transmissions are possible Universal precautions required

16. DPT 8.0 Anthrax - Soviet Incident An accident at a Soviet military compound in Sverdlovsk (microbiology facility) in 1979 resulted in an estimated 66 deaths downwind. Biological Warfare research, production and storage facility Path of airborne Anthrax MOSCOW Sverdlovs k

17. DPT 8.0 Inhalational Anthrax - Sverdlovsk

18. DPT 8.0 Inhalational Anthrax Post Mortem - Sverdlovsk

19. DPT 8.0 BW Anthrax - Diagnosis Clinical picture of sudden onset of respiratory distress with mediastinal widening on x-ray A small number of patients may present with GI or cutaneous anthrax Gram stain of blood and blood cultures - but these may be late findings in the course of the illness ELISA and immunohistology testing may confirm diagnosis but samples must go to reference laboratory

20. DPT 8.0 Anthrax - Treatment Acute Treatment Usually futile in severe mediastinitis patients who inhaled or ingested spores Ciprofloxacin - 400 mg IV q 8 to 12 hr Doxycycline - 100 mg IV q 12 hr X 4 wks Vaccination begins at the start of drug therapy Post-exposure Oral prophylaxis – Ciprofloxacin (500 mg po q 12 h) X 4 wks until 3 doses of vaccine – Doxycycline (100 mg po q 12 h) X 4 wks until 3 doses of vaccine FDA licensed vaccine

21. DPT 8.0 Anthrax - Pediatric Treatment Prophylaxis Penicillin Doxycycline IV Therapy Penicillin Doxycycline

22. DPT 8.0 Anthrax Disease Complex Summary GI Papule Õ vesicle edema + eschar Resolve Toxic shock and Death Hemorrhagic Meningitis Cutaneous Inhalational Tracheobronchial Lymphadenitis Mediastinitis, cyanosis, stridor, pulmonary edema 1 - 6 days ABRUPT ONSET 50% 20% 24 - 36 hours

23. DPT 8.0 Plague - Microbiology Yersinia pestis - gram(-), non- motile, non-spore forming bacillus Fleas living on infected rodents spread infection to humans Recovery offers temporary immunity

24. DPT 8.0 Plague - Pathogenesis Produces disease by being consumed by macrophages and transported to regional lymph nodes, causing regional adenitis Bacteremia - spread to other organs (lungs, spleen, liver, and brain)

25. DPT 8.0 Plague Transmission PNEUMONIC BUBONIC and SEPTICEMIC SECONDARY PNEUMONIC and OROPHARYNGEAL Fleas (active or dormant) Rodent Aerosol Surface contact

26. DPT 8.0 Pneumonic Plague Prevention of Secondary Infection Secondary transmission is possible and likely Standard, contact, and aerosol precautions for at least 48 hrs until sputum cultures are negative or pneumonic plague is excluded

27. DPT 8.0 Plague Endemic Counties Counties with Plague-Positive Samples 1970 - 1994

28. DPT 8.0 Inhalational (Pneumonic) Plague Signs and Symptoms 2 to 3 day incubation period followed by high fever, myalgias, chills, HA, and cough with bloody sputum In contrast to anthrax, pneumonia and sepsis develop acutely and may be fulminant with patients developing dyspnea, stridor, cyanosis, and circulatory collapse Patchy infiltrates or consolidation seen on chest x-ray

29. DPT 8.0 Bubonic Plague Signs and Symptoms Erythema, fever, rigors Bubo formation in regional lymph nodes Bubo aspiration and gram stain is diagnostic – Differentiate from Tularemia Cat-scratch fever Staph-strep lymphadenitis

30. DPT 8.0 Acral Gangrene Acral gangrene may be a late complication of pneumonic or septicemic plague, and may occur in the finger, toes, earlobes, nose, and penis.

31. DPT 8.0 Plague - Acral Gangrene

32. DPT 8.0 Plague - Diagnosis Gram stain and culture of lymph node aspirates, sputum, or CSF samples Bipolar staining “Safety Pin” may be present Immunoassays are also available

33. DPT 8.0 Plague - Treatment Care is otherwise supportive Vaccine effective only for bubonic plague Prophylaxis - tetracycline or doxycycline Antibiotics must be started within 24 hours of symptoms to impact survival Streptomycin (30 mg/kg/day IM divided BID for 10 days) Doxycycline (100 mg IV BID for 10 days) Chloramphenicol for plague meningitis Respiratory isolation mandatory for at least the first 48 hours of treatment

34. DPT 8.0 Plague - Pediatric Treatment Prophylaxis Doxycycline Trimethoprim/Sulfamethoxazole IV Therapy Streptomycin (over 1 year of age) Gentamicin Chloramphenicol

35. DPT 8.0 Plague Disease Complex Inhalational Systemic Toxicity Respiratory failure & circulatory collapse Liver enzymes  6% late meningitis Fulminant Pneumonia Fever, URI syndrome Sudden onset Leukemoid reaction Gram - ve rods in sputum Fever/rigors Erythema Tender bubo 1 - 10 cm  APTT ecchymosis DIC Stridor, cyanosis, productive cough, bilateral infiltrates Pharyngitis 2 -3 days 2 - 10 days 24 hrs 9%

36. DPT 8.0 Viruses as Biological Agents Smallpox Viral Hemorrhagic Fevers (VHF) Venezuelan Equine Encephalitis (VEE)

37. DPT 8.0 Viruses - General Characteristics RNA or DNA within a protein coat Require a host to function and survive Many viruses attack a specific type of cell causing disease or cancer

38. DPT 8.0 Viruses - General Characteristics May cause disease through direct cytopathic effect, immune complex deposition and other effects May result in end-organ system failure, vascular damage Few antiviral medications available Vaccination is the most effective means of preventing infection

39. DPT 8.0 Smallpox - Microbiology Variola (Var-ï-óla) virus, an Orthopox virus, both minor and major forms of smallpox exist Structure is a large DNA virus Declared eradicated in 1980 and the U.S. stopped its civilian vaccination in 1981, U.S. military stopped in 1985

40. DPT 8.0 Smallpox - Pathogenesis

41. DPT 8.0 Smallpox - Case Study In 1963, en route by air from Australia to Sweden, a seaman stops in Djakarta, Singapore, Rangoon, Calcutta, Karachi, Teheran, Damascus, and Zurich Fifteen days later he develops a fever and rash Diagnosed with smallpox; 19 cases identified More than 300,000 vaccinated worldwide

42. DPT 8.0 Smallpox - Diagnosis & Treatment DIAGNOSIS Clinical presentation Demonstrate virus from vesicular sampling via electron microscopy Confirmation by tissue culture TREATMENT Supportive Vaccine still available from CDC Immune globulin may also be available from CDC

43. DPT 8.0 Smallpox - Prevention of Secondary Infection Contagious All contacts are quarantined for at least 17 days Infectious until all scabs are healed over

44. DPT 8.0 Monkeypox Virus

45. DPT 8.0 Smallpox / Monkeypox - Clinical Course Summary Inhalational Replication in regional node of airways 12 day incubation Viremia Acute malaise, fever, rigors, headache Exanthema on face, arms, hands Macules  papules  pustular vesicles Scabs separate + pt non-infective Flat Smallpox Hemorrhagic Smallpox rapid death before typical lesions 8 - 10 days 2 - 3 days variants + mental status changes

46. DPT 8.0 Viral Hemorrhagic Fevers (VHF) - Microbiology RNA viruses causing high fevers and generalized vascular damage Human infections by insect bites or by contact with blood and body fluids

47. DPT 8.0 VHF Pathogenesis Fever, myalgias, prostration Cases evolve into shock and generalized mucous membrane hemorrhage Conjunctival injection, petechial hemorrhage, and hypotension Abnormal renal and LFT - poor prognosis Mortality varies; 50 - 80% Ebola Zaire Disease severity and survival depends on various host factors; target organ is the vascular bed.

48. DPT 8.0 VHF Treatment Hemodynamic resuscitation and monitoring – Invasive Swan Gantz catheter as feasible Careful fluid management – use of colloid Vasopressors and cardiotonic drugs Cautious sedation and analgesia No anti-platelet drugs or IM injections Coagulation studies and replacement of clotting factors / platelet transfusions

49. DPT 8.0 Prevention of Secondary VHF Transmission No vaccine is available at this time Single room w/ adjoining anteroom as only entrance – handwashing facility with decontamination solution Negative air pressure if possible Strict barrier precautions – gloves, gown, mask. shoe covers, protective eyeware/faceshield – consider HEPA respirator for prominent hemorrhage, vomiting, diarrhea, cough

50. DPT 8.0 Prevention of Secondary VHF Transmission Chemical toilet All body fluids disinfected Disposable equipment/sharps into rigid containers and autoclaved/incinerated Double-bag refuse-outside bag disinfected Electronic/mechanical equipment can be paraformaldehyde disinfected

51. DPT 8.0 Prevention of Secondary VHF Transmission Wash / irrigate wound site immediately Mucous membranes (eye, mouth, nose) – Continuous irrigation with rapidly flowing water or sterile saline for >15 minutes Skin – Scrub for >15 minutes while copiously soaking the wound with detergent solution – Germicidal solution (Dilute 1 part laundry bleach with 9 parts tap water)

52. DPT 8.0 The VHF RNA Viruses Acute onset febrile illness High fever, myalgia, GI disturbances Severe systemic illness coagulation abnormalities Rapid progression into shock and death Renal failure Pulmonary Syndrome Major organ necrosis Four Corners Agent Ebola Marburg Hantaan Oropharangeal lesions Severe bleeding ecchymosis Jaundice Syndrome Lassa Machupo Congo fever Yellow fever Dengue (2x) Rift Valley 7 days

53. DPT 8.0 April 5, 1995 - Zaire laboratory worker - fever and bloody diarrhea May 17 - 93 cases - 92% fatality - most cases were in health care providers June 25 - 296 cases Ebola Case Study When institutional barrier precautions were implemented by WHO/CDC - the infection rate among health care workers dramatically decreased.

54. DPT 8.0 Toxins as Biological Agents Botulinum Ricin Staphylococcal Enterotoxin B (SEB)

55. DPT 8.0 Toxins General Characteristics Naturally produced poisons More toxic per weight than manmade chemical agents Non-volatile Minimal absorption in intact skin Not prone to person-to-person transmission

56. DPT 8.0 Botulinum Toxin - Characteristics Neurotoxin produced by Clostridium botulinum - Botulism Most lethal compound per weight (15,000 times more toxic than the nerve agent VX) Different toxicity if inhaled or ingested HcHc HcHc HNHN HNHN light chain neutralizing epitopes neutralizing epitopes Bot A Toxin

57. DPT 8.0 Botulism - Pathogenesis Blocks the release of ACh at 3 places in the presynaptic terminal of the neuromuscular junction and autonomic nervous system Bulbar palsies and skeletal muscle weakness MUSCLE NERVE

58. DPT 8.0 Botulism - Signs & Symptoms Descending paralysis Bulbar palsies – blurred vision – mydriasis – diplopia – ptosis – photophobia – dysphagia – dysarthria “Floppy” baby flaccid paralysis

59. DPT 8.0 Botulism - Diagnosis and Treatment Clinical diagnosis - bulbar palsy with descending paralysis Mouse neutralization assay can confirm diagnosis Treatment is supportive – Long-term mechanical ventilation Antitoxins are available; must be administered early CDC vaccine protective for A and B toxins

60. DPT 8.0 Ricin - Characteristics Toxic by multiple routes of exposure Can be dispersed as an aerosol Effective orally, by injection, or inhalation

61. DPT 8.0 Ricin - Pathogenesis

62. DPT 8.0 Ricin - Signs & Symptoms Fever, chest tightness, cough, SOB, nausea, and joint pain 4 to 8 hours after inhalation Airway necrosis and edema leads to death in 36 to 72 hours Ingestion causes N,V, severe diarrhea, GI hemorrhage, and necrosis of the liver, spleen, and kidneys - shock and death within 3 days Injection causes marked necrosis of muscles and lymph nodes with multiple organ failure leading to death

63. DPT 8.0 Ricin - Diagnosis & Treatment DIAGNOSIS Difficult Routine labs are nonspecific ELISA of blood Immunohistochemical tests may confirm TREATMENT Supportive - oxygenation and hydration No antitoxin or vaccine available

64. DPT 8.0 Teaching Points BW EXPOSURE: WET OR DRY AGENT AEROSOLS BACTERIAL AGENTS – LETHAL: Anthrax, Tularemia, Plague – NON-LETHAL: Q Fever VIRAL AGENTS – LETHAL: Smallpox / Monkeypox, Viral Hemorrhagic Fevers – NON-LETHAL: Venezuelan Equine Encephalitis TOXINS – LETHAL: Ricin, Botulinum Toxin A – NON-LETHAL: Staphyloccal Enterotoxin B SECONDARY INFECTION IS POSSIBLE WITH – Plague, Smallpox/Monkeypox, and VHF

65. DPT 8.0 Biological Agents Case Study Emergency departments always seem busier during a full moon despite evidence to the contrary. Tonight was no exception. Over a 6-hour period, it seemed that almost half of the patients presented with similar complaints of high fever, cough, shortness of breath, and generalized ill feeling. Five young, previously healthy individuals required intubation and mechanical ventilation for severe respiratory distress. Strangely, most of the patients knew each other from work and none of their family members were suffering similar symptoms. At 11 p.m., the only other community hospital in the area went on diversion because all of their intensive care unit (ICU) beds were full and their need for mechanical ventilators was at a critical level. The public health officer on call was not aware of any recent infectious outbreak.

66. DPT 8.0 Biological Agents What might the causative agent be? How could you identify common factors which might relate the patients to each other? How long ago might the attack have occurred? If you are suspicious that patient illnesses could be the result of a biological attack, whom should you notify? What precautions should you and other healthcare providers take?