1. Smallpox Vaccination Mark Upfal, MD, MPH Detroit Medical Center Emergency Medicine Grand Rounds Detroit Receiving Hospital February 13, 2003 Collaborators: Kay Cadwell, Pat Goins, Kathy Reilly

2. Topics Smallpox vaccination & history Vaccine effectiveness Administration/Outcomes Revaccination

3. Topics Adverse Reactions Treatment Contraindications

4. Topics Smallpox & Vaccination History

5. Smallpox

6. Smallpox on trunk

7. Pustules scabs scars

8. Jenner 1798 Treatise on Vaccination

9. Historic Timetable 1796Dr. Jenner infects James Phipps w/ cowpox 1805Use of cows to produce vaccine 1940sFreeze-drying technology 1949Last US case of smallpox 1965Licensure of bifurcated needle 1971Routine vaccination stopped in US 1975Last case of V. major in Bangladesh 1977Last case of V. minor in Somalia 1983Vaccine withdrawn from civilian market

10. Topics Smallpox vaccination & history Vaccine effectiveness

12. Protects against orthopox viruses ATB’s w/in 10 days Post-exposure – effective if given w/in 4-5 days

13. Topics Smallpox vaccination & history Vaccine effectiveness Administration/Outcomes

14. No alcohol or prep Dip into vial & pick up droplet btwn needle prongs Never vaccinated: 3 rapid punctures perpendicular to skin, induces trace blood after 15-20” Previously vaccinated: 3 rapid punctures perpendicular to skin, induces trace blood after 15- 20” Wipe off w/ gauze; dispose waste as biohazard Administration

15. Vaccine Administration

16. Method of Administration Applied to the upper arm using a multiple-puncture technique with a bifurcated needle.

18. Semipermeable Adhesive Dressing

19. Infection control procedures

20. Normal Vaccination Reaction Time 0Vaccination 3-4Papule 5-6Vesicle with surrounding erythema → vesicle with depressed center 8-9Well-formed pustule 12+Pustule crusts over → scab 17-21Scab detaches revealing scar

21. Major reaction Vesicular or pustular lesion or palpable induration surrounding a central crust or ulcer Indicates success Equivocal reaction May be technique failure & no immunity Repeat vaccination

22. Expected Outcome Papules 3-5 days Pustular lesion 6-12 days Scab 13-21 days CDC recommends daily checks for HCWs

26. Topics Smallpox vaccination & history Vaccine effectiveness Administration/Outcomes Revaccination

27. Those vaccinated in 1970’s may not be protected May have fewer adverse reactions Revaccinate researchers every 10 yrs if still working with the virus

28. Topics Adverse Events

29. Smallpox Vaccination and Adverse Reactions Guidance for Clinicians January 24, 2003 / 52(Dispatch);1-29

31. Common Side Effects Local pain (30%), itching (80%) & erythema Malaise Low grade fever Regional lymphadenopathy

32. Adverse Events (1/800) Autoinnoculation 529 per million Generalized Vaccinia 242 per million Eczema Vaccinatum 39 per million Vaccinia necrosum 1.5 per million Vaccinial Encephalitis 12 per million

33. Autoinnoculation

38. Generalized Vaccinia Generalized vesicular skin lesions w/o eczema Hx or other preexisting skin dz Believed 2 o to viremia w/ dermal seeding Usually minor; Few signif. sequelae

39. Generalized Vaccinia

42. Generalized vaccinia Child recovered without sequela

43. Generalized Vaccinia

44. Eczema Vaccinatum Patients w/ h/o eczema Generalized dermal spread Rarely mild cases present only scattered individual lesions

45. Eczema Vaccinatum Can occur w/ inactive eczema More severe in contacts Contact almost always in household

46. Pre-Tx Eczema Vaccinatum

47. Post-Tx Eczema Vaccinatum

48. Eczema vaccinatum

49. Eczema Vaccinatum in a 27 yo

50. Eczema Vaccinatum in a 22 yo

51. Eczema vaccinatum

52. Eczema Vaccinatum

53. Eczema vaccinatum

54. Eczema vaccinatum from contact w/ recently vaccinated child Patient recovered without sequelae or permanent ocular damage

55. Vaccinia necrosum (progressive vaccinia) Immunocompromised individuals Severe local spread w/ necrosis Can be fatal

56. Progressive Vaccinia in a child with hypogammaglobulinemia

57. Progressive vaccinia (vaccinia necrosum) seen w/ cell-mediated immunodeficiency Fatal in a child with immunodeficiency

58. Progressive vaccinia

59. Progressive vaccinia in lymphosarcoma

60. Severe Progressive Vaccinia in a child with SCID

61. Vaccinial keratitis VIG is contraindicated

62. Vaccinial Keratitis

63. Encephalitis VIG not useful

64. Fetal Vaccinia (28 week birth)

65. Strep Infection @ vaccine site

66. Staph Infection @ vaccine site

67. Infant with Post-Vaccination Erythema Multiforme

68. Adverse Reactions – U.S., 1968 ComplicationRate per Million doses Rate Autoinoculation 5291/1,890 Generalized vaccinia 2421/4,132 Eczema vaccinatum 391/25,641 Progressive vaccinia 1.51/666,666 Encephalitis 121/83,333 Total12541/797 Lane JM, et al. J Infect Dis 1970;122:303-9.

69. What’s different today? Many more immunocompromised Better administration technique & follow-up Better screening for contraindications Better medical care for side effects

70. Precautions Potentially infectious from papule (2-5d) to scab separation (14-21d) Opsite dressing Proper waste disposal Personal hygiene, universal precautions Wash clothing hot (detergent/bleach) Per CDC, no need to furlough HCWs

71. Topics Adverse Reactions Treatment

72. Vaccinia Immune Globulin (VIG) Ig from vaccinees Used for eczema vaccinatum, progressive vaccinia, severe generalized vaccinia & ocular vaccinia Not effective in postvaccinial encephalitis Contraindicated in vaccinial keratitis Now available both IM & IV

73. Cidofivir Indications Failure of VIG treatment Patient is near death VIG supplies exhausted 5 mg/kg IV over 60 min. (see package insert!)

74. Cidofivir Side Effects Severe renal toxicity Administer with IV hydration & probenicid Neutropenia, proteinuria, ocular toxicity, metabolic acidosis ? Carcinogenicity, teratogenicity, hypospermia

75. Ocular treatment VIG only if no keratitis Trifluridine Vidarabine (no longer manufactured)

76. Topics Adverse Reactions Treatment Contraindications

77. Eczema Hx (incl mild or remitted) Other acute or chronic skin conditions if active (burns, impetigo, zoster, psoriasis) Immunodeficiency HIV, CA, Steroids (>20 mg, >2 wks in past 3 mo.), Organ transplant

78. Pregnant or planning pregnancy Household contacts with these conditions Serious, life-threatening allergies to ATBs - polymyxin B, streptomycin, tetracycline, or neomycin Contraindications

79. Contraindications today Solid organ transplant patients 184,000 Cancer patients/survivors8,500,000 HIV positive550,000 known; 300,000 unknown Atopic dermatitis28,000,000

80. Q & A *Special thanks to Dr. William Atkinson, CDC National Immunization program, for his kind contribution of slides to this presentation.