1. Agents of Bioterrorism 4th Intermountain Hazardous Materials Conference May 20-22, 2003 Kim Christensen Utah Department of Health Laboratory

2. Objectives • Public Health’s Role in BT • LRN • Bioterrorism Agents • Specimen selection • Specimen packaging • Shipping/Transport • Training Opportunities • Contact Information

3. UDOH Lab’s Core Functions • Disease Identification and Outbreak Investigation • Reference Services • Specialized Testing • Direct Services • Environmental Testing

4. UDOH Lab’s Core Functions • Rapid Testing • Laboratory Improvement • Applied Research • Support of Surveillance and Epidemiology Investigations • Emergency Preparedness and Response

5. Newborn Screening Rabies Influenza HIV STDs TB Arbovirus Surveillance Foodborne Organism Identification OME Molecular Biology UDOH Lab Testing

6. Why is the UDOH LabInvolved with BT? • Mandate by Congress • Experience with Biological Agents of Concern and Outbreak Investigations • Link between Local Laboratory Level and CDC/Federal Agencies

7. Laboratory Response NetworkLRN • Test According to Consensus Protocols • Timely and Accurate Testing and Reporting • Linked with Local, State and Federal Agencies

8. LRN Laboratory Levels • LEVEL A – Clinical Labs • LEVEL B – Public Health Labs • LEVEL C – Typing Labs, Public Health Labs • LEVEL D – CDC

9. Agents of Bioterrorism

10. Agents of Highest ConcernCategory A • Bacillus anthracis (Anthrax) • Francisella tularensis (Tularemia) • Yersinia pestis (Plague) • Clostridium botulinum (Botulism) • Variola major (Smallpox) • Viral Hemorrhagic Fevers

11. Other possible agentsCategory B • Brucella species (Brucellosis) • Burkholderia mallei (Glanders) • Burkholderia pseudomallei (Melioidiosis) • Coxiella burnetti (Q-fever) • Arboviruses • Mycotoxins • Ricin toxin (castor beans) • SEB (Staphylococcus Enterotoxin B)

12. Why these Organisms? • Can cause disease via aerosol route • Fairly stable in aerosolized form • Susceptible civilian population • High morbidity and mortality rates • Difficult to diagnose and/or treat • Some can be transmitted person-to-person

13. Orthopox virus DNA virus Brick-shaped structure 200 nm in diameter Incubation 8-16 days Mortality 30% Clinical symptoms Acute Fever Headache Vomiting Backache SmallpoxVariola major

14. Smallpox • Spread by infected droplets • Most infectious after onset of rash • Contagious until the last scab falls off • Vaccine given within 4 days of exposure can prevent disease or lessen symptoms • 70% recovery rate • Chicken pox vs. Smallpox

15. Smallpox • Disease Progression • Incubation Period • Initial Symptoms – Prodrome • Rash Development & Distribution

16. Rash Begins on face, hands, forearms & spreads to lower extremities within 7 days Lesions on palms & soles of feet Smallpox - Rash

17. Rash Synchronous progression: maculesvesicles pustules scabs Smallpox - Rash

18. SmallpoxUDOH Testing • Vaccinia virus • Rule-out for Smallpox • Varicella zoster virus • Rule-out for Smallpox • Variola major virus • Smallpox beta testing lab

19. Smallpox Specimen Selection • Tissue biopsy • Scabs • Vesicular fluid • Swab • Dried on slide (touch prep)

20. Utah Smallpox Immunization Program

26. Bacillus anthracis – Gram-positive, spore-forming bacillus (rod) AnthraxBacillus anthracis

27. AnthraxBacillus anthracis • Three forms of human anthrax occur: • Cutaneous • Gastrointestinal • Oropharyngeal • Abdominal • Inhalation

28. Cutaneous Exposure- A skin lesion evolving during a period of 2-6 days from a papule, through a vesicular stage, to a depressed black eschar. AnthraxBacillus anthracis

29. Anthrax Lesion on Neck

30. Cutaneous Anthrax • Intense itching • Painless skin sore • Incubation 1-5 days (up to 60) • 20% fatality if untreated (may spread to blood) • Direct contact with skin lesion may result in cutaneous infection

31. Inhalation Anthrax • Inhalation Anthrax- • A brief prodrome resembling a viral respiratory illness with radiograph evidence of mediastinal widening

32. Inhalation Anthrax • Flu-like symptoms – • Fever, fatigue, muscle aches, difficulty breathing, headache, chest pain & non-productive cough • 1-2 day improvement followed by respiratory failure, meningitis may develop • No person-to-person spread

33. Inhalational Sputum Blood Gastrointestinal Blood Stool Cutaneous Vesicles Eschars Swabs Environmental Powder Evidentiary Anthrax Specimens

34. TularemiaFrancisella tularensis • Plague-like disease in rodents (California) • Deer-fly fever (Utah) • Glandular tick fever (Idaho and Montana) • Market men’s disease (Washington, DC) • Rabbit fever (Central States) • O’Hara’s disease (Japan) • Water-rat trappers disease (Russia)

35. Tularemia • Person-to-person transmission = NO • Infective dose = 10-50 organisms • Incubation period = 1-21 days (avg. 3-5) • Duration of Illness = ~ 2 weeks • Mortality – low (treated), moderate (untreated) • Persistence of organism – months in moist soil • Vaccine efficacy – good ~80%

36. Pneumonic- Incubation 3-5 days Flu-like symptoms Mortality – 30% untreated <10% treated Ulceroglandular Ulcer w/adenopathy Glandular Adenopathy w/o lesion Oculoglandular Painful, purulent conjunctivitis Typhoidal Possible presentation for BT Septicemia TularemiaClinical Presentations

37. Tularemia Specimen Selection • Blood • Tissue • Lesion aspirate, swab • Sputum • Serum • Environmental samples

38. PlagueYersinia pestis • Distribution • Highest in 4 corners area – Western states • Prairie dog population

39. PlagueYersinia pestis • Transmission – • Inhalation • Direct contact • Fleas

40. Plague • Clinical presentations • Bubonic • Infected lymph nodes • Septicemic • Blood-borne organisms • Pneumonic • Transmissible by aerosol; deadliest

41. Bubonic Flu-like with painful buboes (lymph nodes) Septicemic Similar to bubonic No swelling of lymph nodes Plague

42. Pneumonic Highest mortality Rapid transmission Fever Hemoptosis Lymphadenopathy Cough Plague

43. Specimen selection is Important!! Bubonic Bubo, lymph node aspirate Septecemic Blood Pneumonic Sputum Bronchial washings/tracheal aspirate Environmental Fleas powder Plague Specimen selection

44. BotulismClostridium botulinum • A neuroparalytic illness • Action of a potent toxin • 7 types of botulinum toxin • Types A, B, E and F (humans) • Types C and D (birds & mammals) • Type G (not yet confirmed as cause)

45. Botulism • Foodborne • Diplopia (double vision), blurred vision, flaccid, symmetric paralysis (rapid progression) • Infant • Constipation, poor-feeding, “failure to thrive”, weakness, impaired respiration and death • Wound • Same symptoms as foodborne w/infection through a wound • Other • Non-infant patient with no suspect food or wound

46. Foodborne Incubation: 18-36 hours Most likely presentation for BT event Mortality Currently 5-10% Previously 60% Wound Mortality 15% Emerging problem of drug users Injecting Black Tar Heroin Botulism

47. BotulismSpecimen Selection • Clinical specimens – • Serum • Gastric contents or vomitus • Stool or sterile water enema return • Food samples • Autopsy specimens – • Serum • Gastric and intestinal contents

48. BotulismSpecimen Selection • Bioterrorism – Intentional Release • Serum • Stool • Enema fluid • Gastric aspirate • Nasal swab • Food samples • Environmental samples

49. BrucellosisBrucella species • Transmission • Unpasteurized dairy products • Most common mode • Direct skin contact • Occupational hazard for farmers, butchers, veterinarians, & lab personnel • Aerosols • Highly infectious

50. BrucellosisBrucella species • Infective dose = 10 -100 organisms • Incubation period = 5 days - > 6 months • Duration of illness = weeks to months • Fever, profuse sweating, malaise, headache and muscle/back pain. • Person to person transmission = no • Mortality = <5% • Persistence of organism = very stable