Preparing for and Responding to Bioterrorism: Information for Primary Care Clinicians

1. Preparing for and Responding to Bioterrorism: Information for Primary Care Clinicians

2. Acknowledgements This presentation, and the accompanying instructor’s manual (current as of 12/02), were prepared by Jennifer Brennan Braden, MD, MPH, at the Northwest Center for Public Health Practice in Seattle, Washington, and Jeff Duchin, MD with Public Health – Seattle & King County, and the Division of Allergy & Infectious Diseases, University of Washington, for the purpose of educating primary care clinicians in relevant 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. Jane Koehler, DVM, MPH Communicable Disease Control, Epidemiology and Immunization section, Public Health - Seattle & King County Ed Walker, MD; University of WA Department of Psychiatry Patrick O’Carroll, MD, MPH The Centers for Disease Control & Prevention Project Coordinator Judith Yarrow Health Policy & Analysis, University of WA Design and Editing

3. Diseases of Bioterrorist Potential Smallpox CDC, AFIP

4. Diseases of BT Potential Learning Objectives • Be familiar with the agents most likely to be used in a biological weapons attack and the most likely mode of dissemination • Know the clinical presentation(s) of the Category A agents and features that may distinguish them from more common diseases • Be familiar with diagnosis, treatment recommendations, infection control, and preventive therapy for management of infection with or exposure to Category A agents.

5. Biological Agents of Highest ConcernCategory A Agents • Easily disseminated, infectious via aerosol • Susceptible civilian populations • Cause high morbidity and mortality • Person-to-person transmission • Unfamiliar to physicians – difficult to diagnose/treat • Cause panic and social disruption • Previous development for BW

6. Biological Agents of Highest ConcernCategory A Agents • Variola major (Smallpox) • Bacillus anthracis (Anthrax) • Yersinia pestis (Plague) • Francisella tularensis (Tularemia) • Botulinum toxin (Botulism) • Filoviruses & Arenaviruses (Viral hemorrhagic fevers) • Report ANY suspected illness due to these agents to Public Health immediately.

7. Biological Agents of 2nd Highest ConcernCategory B Agents • Coxiella burnetti (Q-fever) • Brucella species (brucellosis) • Burkholderia mallei (glanders) • Alphaviruses (Venezuelan, Western and Eastern encephalomyelitis viruses) • Ricin toxin from Ricinus communis (castor bean) • Epsilon toxin from Clostridium perfringens • Staphlococcus enterotoxin B

8. Biological Agents of 2nd Highest ConcernFood- or Water-borne Category B Agents • Salmonella species • Shigella dysenteriae • Escherichia coli 0157:H7 • Vibrio cholera • Cryptosporidium parvum

9. Biological Agents of 3rd Highest ConcernCategory C Agents • Emerging pathogens that could be engineered for mass dissemination in the future • Nipah virus • Hantaviruses • Tick-borne hemorrhagic fever viruses • Tickborne encephalitis viruses • Yellow fever • Multidrug-resistant tuberculosis

10. Smallpox Overview • Two strains: variola major and variola minor • Variola minor – milder disease with case fatality typically 1% or less • Variola major – more severe disease with average 30% mortality in unvaccinated • Person-to-person transmission

11. SmallpoxOverview • Killed approximately 300,000,000 persons in 20th century • Routine smallpox vaccination in the U.S. stopped in 1972 • WHO declared smallpox eradicated in 1980 • Vaccine has significant adverse effects • No effective treatment

12. SmallpoxOverview • Person-to-person transmission • Average 30% mortality from variola major in unvaccinated • A single case is considered a global public health emergency

13. Smallpox Pathogenesis • Virus implants on oropharynx or respiratory mucosa and is transported to regional lymph nodes • Day 3-4: asymptomatic viremia followed by viral multiplication in spleen, bone marrow, lymph nodes, lung • Day 8: secondary viremia leads to fever and toxemia on day 12-14

14. Smallpox Pathogenesis • Virus localizes in small blood vessels of respiratory and pharyngeal mucosa, then dermis = characteristic rash and case communicability • Toxemia: circulating immune complexes and variola antigens

15. Smallpox Transmission • Infectious dose extremely low • Spread primarily by droplet nuclei >aerosols > direct contact • Maintains infectivity for prolonged periods out of host • Contaminated clothing and bedding can be infectious

16. Smallpox Transmission • Transmission does not usually occur until after febrile prodrome • Coincident with onset of rash • Slower spread through the population than chickenpox or measles • Large outbreaks in schools were uncommon • Less transmissible than measles, chickenpox, influenza

17. SmallpoxTransmission • Secondary cases primarily household, hospital, and other close contacts • Secondary attack rate 37-87% among unvaccinated contacts • Patients with severe disease or cough at highest risk for transmission • Greatest infectivity from rash onset to day 7-10 of rash • Infectivity decreases with scab formation and ceases with separation of scabs

18. SmallpoxClinical Features • Prodrome (incubation 7-19 days) • Acute onset of fever, malaise, headache, backache, vomiting, occasional delirium • Transient erythematous rash • Exanthem(2-3 days later) • Preceded by enanthem on oropharyngeal mucosa • Begins on face, hands, forearms • Spread to lower extremities then trunk over ~ 7 days CDC • Synchronous progression: macules  vesicles  pustules  scabs • Lesions most abundant on face and extremities, including palms/soles

19. SmallpoxClinical Course WHO

20. SmallpoxClinical Presentation CDC

21. SmallpoxClinical Presentation WHO This link will take you away from the educational site

22. SmallpoxClinical Presentation WHO

23. SmallpoxClinical Progression WHO

24. SmallpoxClinical Progression Day 10 Day 14 Day 21 Thomas, D.

25. SmallpoxClinical Progression

26. SmallpoxClinical Types • Ordinary smallpox: 90% of cases • Case-fatality average 30% • Occurs in non-immunized persons • Modified smallpox • Milder, rarely fatal • Occurs in 25% of previously immunized persons and 2% of non-immunized persons • Fewer, smaller,more superficial lesions that evolve more rapidly

27. SmallpoxClinical Types • Hemorrhagic smallpox: <3% of cases • Immunocompromised persons and pregnant women at risk • Shortened incubation period, severe prodrome • Extensive viral multiplication, coagulopathy • Dusky erythema followed by petechiae and hemorrhages into skin and mucous membranes • Almost uniformly fatal within 7 days

28. SmallpoxClinical Types • Malignant, or flat-type smallpox: 7% of cases • Slowly evolving lesions that coalesce without forming pustules • Associated with cell-mediated immune deficiency • Usually fatal • Variola sine eruptione • Occurs in previously vaccinated persons or infants with maternal antibodies • Asymptomatic or mild illness • Transmission from these cases has not been documented

29. Malignant Smallpox Thomas, D.

30. SmallpoxComplications • Encephalitis • 1 in 500 cases Variola major • 1 in 2,000 cases Variola minor • Keratitis, corneal ulceration • Blindness in 1% of cases • Infection in pregnancy • High perinatal fatality rate • Congenital infection

31. CDC Major Smallpox Criteria • Febrile prodrome Occurring 1-4 days before rash onset: fever >102°F and at least one of the following: prostration, headache, backache, chills, vomiting or severe abdominal pain • Classic smallpox lesions Deep, firm/hard, round, well-circumscribed; may be umbilicated or confluent • Lesions insame stage of development on any one part of the body (e.g., face or arm) More on CDC's response plan... This link will take you away from the educational site

32. CDC Minor Smallpox Criteria • Centrifugal distribution: greatest concentration of lesions on face and distal extremities • First lesions on oral mucosa or palate, face, forearms • Patient appears toxic or moribund • Slow evolution: lesions evolve from macules to papules to pustules over days • Lesions on palms and soles (majority of cases)

33. CDC Criteria for Determining Risk of Smallpox • High risk: report immediately All three major criteria • Moderate risk: urgent evaluation Febrile prodrome and 1 major or 4 minor criteria • Low risk: manage as clinically indicated No viral prodrome or Febrile prodrome and <4 minor criteria (no major criteria)

34. CDC Recommended Evaluation of Patients at High Risk of Smallpox • Contact and airborne precautions • Notify infection control • Infectious disease and/or dermatology consult • Notify local/state health dept immediately Response team advises on management and specimen collection • Specimen testing at CDC

35. CDC Recommended Evaluation of Patients at Moderate Risk of Smallpox • Contact and airborne precautions • Notify infection control • Infectious disease and/or Dermatology consult • VZV and/or other lab tests as indicated • If cannot rule out smallpox, contact local/state health dept. immediately

36. CDC Recommended Evaluation of Patients at Low Risk of Smallpox • Contact and airborne precautions • Notify infection control • Evaluate clinically for VZV • Test for VZV and other conditions, as indicated

37. Differential Diagnosis of SmallpoxVariola vs. Varicella Source: CDC

38. Differential Diagnosis of SmallpoxVariola vs. Varicella Source: CDC

39. Variola vs. VaricellaLesion Distribution Chickenpox Smallpox WHO This link will take you away from the educational site

40. Variola vs. VaricellaLesion Distribution Smallpox Chickenpox WHO

41. Varicella Disseminated herpes zoster Drug eruptions and contact dermatitis Disseminated herpes simplex Impetigo Erythema multiforme Scabies, insect bites Bullous pemphigoid Secondary syphillis Molluscum contagiosum Enterovirus exanthem Differential Diagnosis of Smallpox

42. SmallpoxDiagnosis • Clinical diagnosis = public health emergency • Laboratory confirmation: vesicular or pustular fluid on swab or biopsy • Seal in vacutainer and overpack - transport to state public health laboratory • Culture (BSL-4 Lab) followed by PCR and RFLP

43. SmallpoxDiagnosis • EM: characteristic “brick shaped” morphology distinct from HSV and VZV • Light microscopy: Giemsa stain  aggregations of viral particles (Guarnieri bodies) • Gel diffusion test: vesicular fluid + hyperimmune globulin

44. SmallpoxSpecimen Collection • Specimen collection by trained teams • Only recently, successfully vaccinated personnel (within 3yrs) wearing appropriate barrier protection should be involved in specimen collection • Respiratory and contact precautions • Testing done by CDC; contact local HD before collecting clinical specimens More on CDC's response plan... This link will take you away from the educational site

45. SmallpoxSpecimen Collection • If necessary, unvaccinated personnel without contraindications to vaccination may collect specimens • If smallpox confirmed, will need immediate vaccination

46. SmallpoxMedical Management • Respiratory and contact isolation for hospitalized cases • Negative pressure room; HEPA-filtered exhaust • All health care workers employ aerosol and contact precautions regardless of immunization status • No specific therapy available • Supportive care: fluid and electrolyte, skin, nutritional

47. SmallpoxMedical Management • Antibiotics for secondary infection • Antiviral drugs under evaluation • Notify Public Health and hospital epidemiology immediately for suspected case

48. SmallpoxOutbreakManagement • Case identification, isolation, and immunization • Rapid identification of contacts • Immediate vaccination or boosting of ALL potential contacts including health care workers • Vaccination within 4 days of exposure may prevent or lessen disease • Isolation with monitoring for fever or rash • 18 days from last contact with case • Respiratory isolation if possible for febrile contacts • Passive immunization (VIG) • Potential use for contacts at high risk for vaccine complications

49. SmallpoxOutbreakManagement • Strategy for outbreak containment: Ring vaccination • Isolation of confirmed & suspected smallpox cases • Tracing, vaccination & close surveillance of contacts • Vaccination of contacts of contacts

50. Isolation CDC Smallpox Response Plan • Facility Categories • Type C – Contagious • Confirmed and probable cases • Type X – Uncertain diagnosis • Vaccinated febrile contacts without rash • Type R – Asymptomatic • Non-febrile contacts