1. New Jersey Preparedness Training Consortium Continuing Education for health care professionals “modulebiov1” Bioterrorism

2. Bioterrorism:Who are 1st Responders? • Primary Care Personnel • Hospital ER Staff • EMS Personnel • Public Health Professionals • Other Emergency Preparedness Personnel • Laboratory Personnel • Law Enforcement

3. Indicators of BT Events • Increasing Frequency of Cases • Rare or Non-endemic Disease • Trouble Identifying Cause of Symptoms

4. Scenarios • Overt Event • Announced • Patients Fall ill or Die (Increased Morbidity and Mortality) • Microorganisms Unconfirmed • Hoaxes Assumed to be Real

5. Scenarios • Covert Event • No Prior Warning - Unannounced • Patients Fall ill or Die from Causes of Unknown or Unusual Origin • Unusual Cluster(s) of Cases - May be Geographically Distributed • Undetermined Causative Agent

6. Potential Bioterrorism Agents • Bacterial Agents • Anthrax • Brucellosis • Cholera • Plague, Pneumonic • Tularemia • Q Fever Source: U.S. A.M.R.I.I.D. • Viruses • Smallpox • VEE • VHF • Biological Toxins • Botulinum • Staph Entero-B • Ricin • T-2 Mycotoxins

7. Important Report ALL suspected or confirmed illness due to these agents to health authorities immediately In New Jersey: • Local city/county LINCS agency • NJDHSS • 609-588-7500 • 609-392-2020 (after hours)

8. Advantages of Biologics as Weapons • Easy to obtain • Inexpensive to produce • Potential dissemination over large geographic area • Creates panic • Can overwhelm medical services • Susceptible civilian populations • High morbidity and mortality • Difficult to diagnose and/or treat • Some are transmitted person-to-person via aerosol

9. Routes of Infection • Skin (cuts, abrasions, mucosal membranes) • Gastrointestinal • Food • Potentially significant route of delivery • Secondary to either purposeful or accidental exposure to aerosol • Water • Capacity to affect large numbers of people • Dilution factor • Water treatment may be effective in removal of agents • Respiratory • Inhalation of spores, droplets & aerosols • Aerosols most effective delivery method • 1-5F droplet most effective

10. Medical Response • Pre-exposure • active immunization • prophylaxis • identification of threat/use • Incubation period • detection and diagnosis • active and passive immunization • antimicrobial or supportive therapy • Overt disease • diagnosis • treatment • may not be available • may overwhelm system • may be less effective • direct patient care will predominate

11. Biological Agents of Highest Concern • Francisella tularensis(Tularemia) • Yersinia pestis(Plague) • Filoviruses and Arenaviruses (Viral hemorrhagic fevers) • Botulinum toxin (Botulism) • Bacillus anthracis(Anthrax) • Variola major (Smallpox)

12. Francisella tularensis Tularemia

13. Tularemia: Overview • Disease of Northern Hemisphere • In U.S., most cases associated with rabbits/hares (winter) and ticks (summer) • About 200 cases/year in U.S. • most in South central and Western states • majority of cases in summer (tick exposure)

14. Tularemia: Clinical Forms • Ulceroglandular • Ulcer with regional adenopathy • Glandular • Regional adenopathy without skin lesion • Oculoglandular • Painful purulent conjunctivitis with adenopathy

15. Reported Cases of Tularemia - 1990-1998

16. Tularemia • Contagious --- no person to person transmission • Infective dose --- 10-50 organisms • Incubation period --- 1-21 days (average=3-5 days) • Duration of illness --- ~2 weeks • Mortality --- treated : low untreated: moderate • Persistence of organism ---months in moist soil • Vaccine efficacy --- good, ~80%

17. Yersinia pestis Plague

18. Plague: Overview • Natural vector - rodent flea • Mammalian hosts • rats, squirrels, chipmunks, rabbits, and carnivores • Enzootic or Epizootic CDC: Wayson’s Stain of Y. pestis showing bipolar staining

19. Plague Epidemiology • Three Clinical Types: • bubonic (infected lymph nodes) • septicemic (blood-borne organisms) • pneumonic (transmissible by aerosol; deadliest)

20. Plague Epidemiology • U.S. averages 13 cases/yr • Bubonic most common form • Pneumonic, only 1-2 cases/yr • 30% of cases are in Native Americans in the Southwest. 15% case fatality rate • Most cases occur in summer

21. Plague: Prophylaxis • Bubonic contacts • If common exposure, consider oral Doxycycline, Tetracycline, or TMP/SMX for 7 days • Other close contacts, fever watch for 7 days (treat if febrile)

22. Plague: Prophylaxis(continued) • Pneumonic contacts(respiratory/droplet exposure) • Consider oral Doxycycline, Tetracycline, or TMP/SMX • Continue for 7 days after last exposure • Vaccine no longer manufactured in U.S. • Not protective against pneumonic plague

23. Plague:Medical Management • Supportive therapy • Isolation with droplet precautions for pneumonic plague until sputum cultures negative • Antibiotic resistant strains have been documented

24. Plague:Medical Management • Antibiotic therapy • Gentamicin or Streptomycin • Tetracyclines • Sulfonamides • Chloramphenicol (meningitis/pleuritis)

25. Plague: Septicemic • Primary or secondary • Secondary from bubonic or pneumonic forms • 100% mortality if untreated • Severe endotoxemia • Systemic inflammatory response syndrome • Shock, Disseminated intravascular coagulopathy (DIC) • Adult Respiratory Distress Syndrome (ARDS)

26. Differential Diagnosis(cont) • Septicemic • Other gram-negative sepsis • Meningococcemia • Rocky Mountain Spotted Fever (RMSF) • Thrombotic Thrombocytopenic Purpura (TTP)

27. Bubonic Staph/streptococcal adenitis Glandular tularemia Cat scratch disease Pneumonic Other bioterrorism threats Anthrax Tularemia Melioidosis Other pneumonias (CAP, influenza, HPS) Hemorrhagic leptospirosis Plague: Differential Diagnosis

28. Plague: Pneumonic • Pneumonic • From aerosol or septicemic spread to lungs • Person-to-person transmission by respiratory droplet • 100% mortality untreated

29. Plague: Pneumonic(cont) • Incubation: 1-3 days • Sudden onset headache, malaise, fever, myalgia, cough • Pneumonia progresses rapidly to dyspnea, cyanosis, hemoptysis • Death from respiratory collapse/sepsis USAMRICD: Pneumonic infiltrate of pneumonic plague

30. Plague: Clinical FormsBubonic • Bubonic • Inguinal, axillary, or cervical lymph nodes most common • 80% can become bacteremic • 60% mortality if untreated

31. Plague: Bubonic • Incubation: 2-6 days • Sudden onset headache, malaise, myalgia, fever, tender lymph nodes • Regional lymphadenitis (Buboes) • Cutaneous findings • possible papule, vesicle, or pustule at inoculation site • Purpuric lesions - late USAMRICD: Inguinal/femoral buboes

32. Yersinia pestisSpecimen Selection • Specimen selection is important • Bubonic - bubo - lymph node aspirate • Septicemic - blood - Obtain three sets 10-30 minutes apart • Pneumonic • Sputum/throat • Bronchial washings

33. Hemorrhagic Fever Viruses • Families Responsible for VHF: • Arenaviridae • Bunyaviridae • Filoviridae • Flaviviridae

34. Hemorrhagic Fever Viruses • Arenaviruses • Argentine Hemorrhagic Fever • Bolivian Hemorrhagic Fever • Sabia Associated Hemorrhagic Fever • Lassa Fever

35. Hemorrhagic Fever Viruses • Bunyaviruses • Crimean-Congo Hemorrhagic Fever • Rift Valley Fever • Hantavirus Pulmonary Syndrome Hemorrhagic Fever

36. Hemorrhagic Fever Viruses • Filoviruses • Ebola Hemorrhagic Fever • Marburg Hemorrhagic Fever

37. Hemorrhagic Fever Viruses Marburg Ebola

38. Hemorrhagic Fever Viruses • Flaviviruses • Tick-borne Encephalitis • Kyasanur Forest Disease • Omsk Hemorrhagic Fever

39. Viral Hemorrhagic Fevers • Contagious --- Moderate • Infective dose --- 1-10 particles • Incubation period --- 4-21 days • Duration of illness --- 7-16 days • Mortality ---variable • Persistence of organism --- unstable • Non-endemic in U.S. • No vaccine

40. Clostridium botulinum Botulism

41. FOODBORNE BOTULISM • Infective dose: 0.001 g/kg • Incubation period: 18 - 36 hours • Dry mouth, double vision, droopy eyelids, dilated pupils • Progressive descending bilateral muscle weakness & paralysis • Respiratory failure and death • Mortality 5-10%, up to 25%

42. FOODBORNE BOTULISM • Among 309 persons with clinically diagnosed botulism reported to CDC from 1975 to 1988: • Stool cultures for C. botulinum: 51% + • Serum botulinum toxin testing: 37% + • Stool botulinum toxin testing: 23% + • Overall, at least one of the above tests was positive for 65% of all patients

43. Level A Proceduresfor Botulism Event • Properly collected specimens are to be referred to designated testing laboratories • Prior to the shipment of any botulism-associated specimen, the designated laboratory must be notified and approved by the State Health Department

44. Level A Proceduresfor Botulism Event • Clinical specimens to be collected: 1. Serum 2. Gastric contents or vomitus 3. Feces or return from sterile water enema 4. Wound tissue

45. Bacillus anthracis Anthrax

47. Caused by the spore-forming bacterium, Bacillus anthracis • Zoonotic disease in herbivores (e.g., sheep, goats, cattle) follows ingestion of spores in soil • Human infection typically acquired through contact with anthrax-infected animals or animal products or atypically through intentional exposure • Three clinical forms • Cutaneous • Inhalational • Gastrointestinal Anthrax: Basics

48. Animal (Stern's) vaccination started in 1957, after OK enzootic. Recommended for use in animals in endemic areas thereafter. Cases of Anthrax in the U.S., 1951–2000* (N = 409) 2000w *Only 18 of these cases were inhalational; the remainder were cutaneous. wOne cultured case (cutaneous) reported in 2000 from North Dakota.

49. Anthrax: Current Issues in the U.S. • Anthrax remains an endemic public health threat through annual epizootics. • B. anthracis is one of the most important pathogens on the list of bioterrorism threats • Aerosolized stable spore form • Human LD50 8,000 to 40,000 spores, or one deep breath at site of release

50. Anthrax Bioterrorism Issues (1) • Surveillance for cutaneous and inhalational disease to identify attack • Targeting prevention strategies • Rapidly identify exposed populations • Conduct epidemiologic investigation with environmental testing • Supply postexposure prophylaxis • Trace route of vehicle of exposure