Preparing for and Responding to Bioterrorism: Information for the Public Health Workforce

1. Preparing for and Responding to Bioterrorism: Information for the Public Health Workforce

2. Acknowledgements This presentation, and the accompanying instructor’s manual, were prepared by Jennifer Brennan Braden, MD, MPH, at the Northwest Center for Public Health Practice in Seattle, WA, for the purpose of educating public health employees in the general aspects of bioterrorism preparedness and response. Instructors are encouraged to freely use all or portions of the material for its intended purpose. The following people and organizations provided information and/or support in the development of this curriculum. A complete list of resources can be found in the accompanying instructor’s guide. Patrick O’Carroll, MD, MPH Project Coordinator Centers for Disease Control and Prevention Judith Yarrow Design and Editing Health Policy and Analysis; University of WA Washington State Department of Health Jeff Duchin, MD Jane Koehler, DVM, MPH Communicable Disease Control, Epidemiology and Immunization Section Public Health - Seattle and King County Ed Walker, MD; University of WA Department of Psychiatry

3. Diseases of Bioterrorist Potential: Tularemia & Viral Hemorrhagic Fevers CDC, AFIP

4. Diseases of Bioterrorist PotentialLearning Objectives • Describe the epidemiology, mode of transmission, and presenting symptoms of disease caused by the CDC-defined Category A agents • Identify the infection control and prophylactic measures to implement in the event of a suspected or confirmed Category A case or outbreak

5. Francisella Tularensis • Causative agent of tularemia • Non-motile, non-spore-forming gram negative cocco-bacillus found in diverse animal hosts • Studied by U.S. and others as potential BW weapon • Resistant to freezing temperatures, sensitive to heat and disinfectants

6. Francisella TularensisEpidemiology • Humans infected by various modes: • Handling contaminated animal tissues or fluids • Bite of infective deer flies, mosquitoes, or ticks • Direct contact with or ingestion of contaminated water, food, or soil • Inhalation of infective aerosols (most likely BT route) • About 200 cases of tularemia/year in U.S. • Most in South-central and Western states • Most in rural areas • Majority of cases in summer

7. Francisella TularensisEpidemiology • Low infectious dose: 10-50 organisms produce disease • Incubation period: probably 3-5 days following aerosol exposure (range 1-21 days) • Case fatality rate • Treated: <1-3% • Untreated: 30-60% (pneumonic), 5% (ulceroglandular) • Recovery followed by permanent immunity • No person-to-person transmission

8. Tularemia: Case Definition • An illness characterized by several distinct forms, including the following • Ulceroglandular (cutaneous ulcer with regional lymphadenopathy) • Glandular (regional lymphadenopathy with no ulcer) • Oculoglandular (conjunctivitis with preauricular lymphadenopathy) • Oropharyngeal (stomatitis or pharyngitis or tonsillitis & cervical adenopath) MMWR 1997;46(RR-10)

9. Tularemia: Case definition, cont. • An illness characterized by several distinct forms, including the following • Intestinal (intestinal pain, vomiting, diarrhea) • Pneumonic* (primary pleuropulmonary disease) • Typhoidal (febrile illness w/o early localizing signs & symptoms • Clinical diagnosis supported by evidence or history of a tick or deerfly bite, exposure to tissues of a mammalian host of F. tularensis, or exposure to potentially contaminated water. MMWR 1997;46(RR-10) *most likely BT presentation

10. Tularemia: Case Definition, cont. • Laboratory criteria for diagnosis • Presumptive: • Elevated serum antibody titer(s) to F. tularensis antigen (w/o documented 4-fold or greater change) in a patient with no history of tularemia vaccination OR • Detection of F. tularensis in a clinical specimen by fluorescent assay • Confirmatory: • Isolation of F. tularensis in a clinical specimen OR • 4-fold or greater change in serum antibody titer to F. tularensis antigen MMWR 1997;46(RR-10)

11. Tularemia: Case Classification • Probable: Clinically compatible with lab results indicative of a presumptive infection • Confirmed: Clinically compatible with confirmatory lab results MMWR 1997;46(RR-10)

12. Ulceroglandular TularemiaClinical Features • 75-85% of naturally occurring cases • General symptoms – high fever, malaise, muscle aches, headache, chills & rigors, sore throat • Cutaneous papule appears at inoculation site concurrent with generalized symptoms • Papule --> pustule --> tender indolent ulcer with or without eschar • Tender regional lymphadenopathy

13. Ulceroglandular Tularemia

14. Pneumonic TularemiaClinical Features • Initial clinical picture: systemic illness with prominent signs of respiratory disease • Abrupt onset fever, chills, headaches, muscle aches, non-productive cough, sore throat • Nausea, vomiting, diarrhea in some cases • Mortality 30% untreated; < 10% treated

15. Tularemia Treatment & Prophylaxis • Vaccine: live attenuated vaccine under FDA review – availability uncertain • For known aerosol exposures, 14d oral antibiotics recommended • If covert attack, observe for development of fever for 14 days and treat with antibiotics if febrile • Post-exposure antibiotics – most effective when given w/in 24 hours of exposure

16. TularemiaInfection Control • Standard precautions • No patient isolation necessary due to lack of human-to-human transmission • Alert lab of suspicion for tularemia

17. TularemiaSummary of Key Points • In naturally occurring tularemia, infection virtually always occurs in a rural setting. Infection in an urban setting with no known risk factors or contact with infected animals suggests a possible deliberate source. • Tularemia is not transmitted person to person.

18. TularemiaSummary of Key Points • The most likely presentations of tularemia in a BT attack are pneumonic and typhoidal disease, as opposed to cutaneous disease in naturally occurring cases. • Tularemia can be treated and prevented with antibiotics.

19. Viral Hemorrhagic Fevers • Diverse group of illnesses caused by RNA viruses from 4 families: • Arenaviridae, Bunyaviridae, Filoviridae, Flaviridae • Differ by geographic occurrence and vector/reservoir • Share certain clinical and pathogenic features • Potential for aerosol dissemination, with human infection via respiratory route (except dengue) • Target organ: vascular bed • Mortality 0.5 - 90%, depending on agent

20. Viral Hemorrhagic Fevers • Category A agents • Filoviruses • Arenaviruses • Category C agents • Hantaviruses • Tick-borne hemorrhagic fever viruses • Yellow fever

21. Viral Hemorrhagic Fevers Transmission • Zoonotic diseases • Rodents and arthropods main reservoir • Humans infected via bite of infected arthropod, inhalation of rodent excreta, or contact with infected animal carcasses • Person-to-person transmission possible with several agents • Primarily via blood or bodily fluid exposure • Rare instances of airborne transmission with arenaviruses and filoviruses • Rift Valley fever has potential to infect domestic animals following a biological attack

22. Viral Hemorrhagic FeversSummary of Agents

23. Viral Hemorrhagic FeversSummary of Agents

24. Viral Hemorrhagic FeversClinical Presentation • Clinical manifestations nonspecific, vary by agent • Incubation period 2-21 days, depending on agent • Onset typically abrupt with filoviruses, flaviviruses, and Rift Valley fever • Onset more insidious with arenaviruses

25. High fever Headache Malaise Weakness Exhaustion Dizziness Muscle aches Joint pain Nausea Non-bloody diarrhea Viral Hemorrhagic FeversInitialSymptoms Prodromal illness lasting < 1 week may include:

26. Flushing, conjunctival injection (“red eye”) Pharyngitis Rash Edema Hypotension Shock Mucous membrane bleeding Viral Hemorrhagic FeversClinical Signs

27. VHF Surveillance: Clinical Identification of Suspected Cases • Clinical criteria: • Temperature 101F(38.3C) for <3 weeks • Severe illness and no predisposing factors for hemorrhagic manifestations • 2 or more of the following: • Hemorrhagic or purple rash • Epistaxis • Hematemesis • Hemoptysis • Blood in stools • Other hemorrhagic symptoms • No established alternative diagnosis JAMA 2002;287 Adapted from WHO

28. Viral Hemorrhagic FeversTreatment • Supportive care • Correct coagulopathies as needed • No antiplatelet drugs or IM injections • Investigational treatments, available under protocol: • Ribavirin x 10 days for arenaviridae and bunyaviridae • Convalescent plasma w/in 8d of onset for AHF

29. Viral Hemorrhagic Fevers Management of Exposed Persons • Medical surveillance for all potentially exposed persons, close contacts, and high-risk contacts (i.e., mucous membrane or percutaneous exposure) x 21 days • Report hemorrhagic symptoms (slide 47) • Record fever 2x/day • Report temperatures  101F(38.3C) • Initiate presumptive ribavirin therapy • Percutaneous/mucocutaneous exposure to blood or body fluids of infected: • Wash thoroughly with soap and water, irrigate mucous membranes with water or saline

30. Viral Hemorrhagic FeversManagement of Exposed Persons • Patients convalescing should refrain from sexual activity for 3 months post-recovery (arenavirus or filovirus infection) • Only licensed vaccine: Yellow Fever • Investigational vaccines: AHF, RV, HV • Possible use of ribavirin to high risk contacts of CCHF and LF patients

31. Viral Hemorrhagic FeversInfection Control • Airborne & contact precautions for health care, environmental, and laboratory workers • Negative pressure room, if available • 6-12 air changes/hour • Exhausted outdoors or through HEPA filter • Personal protective equipment • Double gloves • Impermeable gowns, leg and shoe coverings • Face shields and eye protection • N-95 mask or PAPR

32. Viral Hemorrhagic FeversInfection Control • Dedicated medical equipment for patients • If available, point-of-care analyzers for routine laboratory analyses • If unavailable, pretreat serum w/Triton X-100 • Lab samples double-bagged & hand-carried to lab • Prompt burial or cremation of deceased with minimal handling • Autopsies performed only by trained personnel with PPE

33. Viral Hemorrhagic FeversSummary of Key Points • A thorough travel and exposure history is key to distinguishing naturally occurring from intentional viral hemorrhagic fever cases. • Viral hemorrhagic fevers can be transmitted via exposure to blood and bodily fluids.

34. Viral Hemorrhagic FeversSummary of Key Points • Contact and airborne precautions are recommended for health care workers caring for infected patients. • Post-exposure management consists of surveillance for fever and hemorrhagic symptoms, and possibly ribavirin therapy for symptomatic individuals.

35. Case Reports • Tularemia • Viral Hemorrhagic Fevers MMWR Morb Mortal Wkly Rep 2001;50(33) MMWR Morb Mortal Wkly Rep 2001;50(5)

36. Resources http://www.bt.cdc.gov/ • Centers for Disease Control & Prevention • Bioterrorism Web page: • CDC Office of Health and Safety Information System (personal protective equipment) • USAMRIID -- includes link to on-line version of Medical Management of Biological Casualties Handbook • Johns Hopkins Center for Civilian Biodefense Studies http://www.cdc.gov/od/ohs/ http://www.usamriid.army.mil/ http://www.hopkins-biodefense.org

37. Resources • Office of the Surgeon General: Medical Nuclear, Biological and Chemical Information • St. Louis University Center for the Study of Bioterrorism and Emerging Infections • Public Health - Seattle & King County http://www.nbc-med.org http://bioterrorism.slu.edu http://www.metrokc.gov/health

38. Resources http://www.doh.wa.gov • Washington State Department of Health • Communicable Disease Epidemiology • (206) 361-2914 OR • (877) 539-4344 (24 hour emergency) • Association for Professionals in Infection Control • MMWR Rec & Rep. Case definitions under public health surveillance. http://www.apic.org/bioterror 1997;46(RR-10):1-55