Smallpox Vaccine and Use Sources: Bill Atkinson, Mike Lane, Walt Orenstein, and Joanne Cono, CDC

1. Smallpox Vaccine and UseSources: Bill Atkinson, Mike Lane, Walt Orenstein, and Joanne Cono, CDC Joel Ackelsberg, MD, MPH New York City Department of Public Health Communicable Disease Program jackelsb@health.nyc.gov

2. Variolation • “Artificial” infection of susceptible person with variola virus • Practiced in China and probably India in the 9th century • Infection by different routes

3. Variolation • Cutaneous inoculation resulted in severe local lesions, usually with many satellite pustules • Usually caused a generalized rash and severe constitutional symptoms • Could be fatal, and could be transmitted to contacts

5. Smallpox – Boston, 1752 Variolation 2,124 30 (1.4) Smallpox* 5,545 537 (9.7) Cases Deaths *28% of smallpox cases caused by variolation

6. Protection from Smallpox • Folklore in Europe that milkmaids rarely pockmarked • Belief that protection from smallpox resulted from infection acquired from cows • Jenner observed that some with history of cowpox “resisted” variolation

8. Jenner’s Experiment • Transferred “matter” from the hand of an infected dairymaid to 8 year-old James Phipps on 14 May 1796 • Variolation unsuccessful on 1 July 1796 • Phipps did not respond to variolation 5 years after original vaccination

10. Vaccination • Jenner’s observations soon reproduced by others • Practice quickly spread throughout Europe • Benjamin Waterhouse performed first vaccinations in U.S. in Boston, 1800

12. Smallpox Vaccine • Until the mid-19th century vaccine was generally transferred from arm-to-arm • Also distributed dried using threads, ivory points, or glass slides • Cows first used in Italy in early 19th century

13. “…it now becomes too manifest to admit of controversy, that the annihilation of the Small Pox, the most dreadful scourge of the human species, must be the final result of this practice.” -Edward Jenner, 1801

14. Smallpox Vaccine • Original material used by Jenner was probably cowpox • Vaccine constituent changed from cowpox to vaccinia during the 19th century

15. Vaccinia Virus • Origin of vaccinia virus unknown • Genetically distinct from cowpox and variola • May be a virus now extinct in nature

16. Vaccinia Virus • Multiple strains with different levels of virulence for humans and animals • U.S. vaccine (Dryvax, Wyeth Laboratories) contains New York City Board of Health strain

17. Vaccine Production • Virus grown on skin of calves, sheep, and water buffalo • Material from lesions harvested before crusting to maximize viral titer • Pulp ground and originally mixed with 40%-60% glycerol and distributed in glass capillary tubes

18. Smallpox (Vaccinia) Vaccine • 15 million doses now in stock • 100-dose vials • Contract for additional 54 million doses produced on cell culture media

19. Response to Vaccination • Neutralizing antibody: • 10 days after primary vaccination • 7 days after revaccination • Considered fully protected after a successful response demonstrated at vaccination site

20. Vaccine Efficacy • Clinical efficacy estimated in household contact studies • 91%-97% reduction in cases among contacts with vaccination scar • Studies did not consider time since vaccination or potency of vaccine

21. Post Exposure Vaccine Efficacy • Clinical efficacy estimated in household contact studies • SAR 2%-75%, varied by time since exposure • Disease generally less severe (modified type) in those with post exposure vaccination

22. Post Exposure Vaccine Efficacy % with smallpox 29.5 47.6 75.0 96.3 1.9 21.8 Postexp vacc Never vacc Vacc <10 days Never vacc Vacc <7 days Never vacc Madras Pakistan Pakistan

23. Duration of Immunity • High level of protection (~100%) for 3 years following vaccination • Substantial but waning immunity for >10 years • Reduction in disease severity

24. CFR by Vaccination Status, Europe, 1950-1971 Mack TM. J Infect Dis 1972;125:161-9.

25. Duration of Protection† †From Outbreak in Liverpool, England, 1902-1903 In Fenner F et al. Smallpox and its Eradication, pp53

26. Antibody Persistence • Level of antibody that protects against smallpox infection unknown • Neutralizing antibody >1:10 persists up to 30 years following 3 doses

27. Antibody Persistence Following Second Revaccination Baruch El-Ad, et al J Infect Dis 1990;161:446-8.

28. Vaccine Administration • Surgical needle • Vaccinostyle • Rotary lancet • Jet injector • Bifurcated needle* *Only administration technique currently in use.

31. Clinical Response to Vaccination* Symptom/sign Papule Vesicle Pustule Maximum erythema Scab Scab separation Time after Vacc 3 days 5-6 days 7-11 days 8-12 days 14 days 21 days *Typical response in a nonimmune person

32. Evolution of Smallpox Vaccine Recommendations • 1971 Discontinue routine vaccination • 1976 Discontinue vaccination of HCWs • 1980 Vaccine recommended for lab workers • 1991 “Vaccinia vaccine” • 1991 Consider vaccine for HCWs exposed to recombinant vaccinia • 2001 Bioterrorism guidelines

34. Smallpox (Vaccinia) VaccineIndications in Nonemergency Situations • Laboratory workers who handle cultures or animals infected with nonhighly attenuated vaccinia • Consider for other health care workers with contact with contaminated material • (first response teams)

35. Smallpox (Vaccinia) VaccineIndications in Emergency Situations • Persons exposed to initial release • Close contact with confirmed or suspected case • Direct care or transportation of confirmed or suspected case • Laboratory personnel • Persons with risk of contact with infectious materials from case

36. Transmission of Vaccinia • Vaccinia virus may be recovered from the site of vaccination from development of papule (2-5 days) until scab separates from the skin • Household contacts at highest risk of contact transmission

37. Major Complications of Smallpox Vaccination • Inadvertent autoinoculation • Eczema vaccinatum • Generalized vaccinia • Progressive vaccinia (vaccinia necrosum) • Postvaccinal encephalitis • Other dermatologic conditions

38. Contraindications and PrecautionsNonemergency Situations • Severe allergic reaction to prior dose or vaccine component • Eczema, history of eczema, or household contact with eczema or history of exzema • Other skin conditions • Immunosuppression or immuno-suppressed household contact • Pregnancy • Age <18 years

39. Contraindications and PrecautionsEmergency (post-release) Situations • Exposed persons – no contraindications • Unexposed persons – same as nonemergency situations

40. Vaccinia Immune Globulin • Immunoglobulin fraction of plasma from persons vaccinated with vaccinia vaccine • Effective for treatment of eczema vaccinatum, progressive vaccinia, severe generalized vaccinia, and ocular vaccinia • Not effective in postvaccinial encephalitis • Contraindicated in vaccinial keratitis

41. Adverse Reaction Rates* *Adapted from CDC.. MMWR 2001;50(RR-10)

42. Risk Factors • Eczema (contact too) • Age less than 1 yr • Anaphylaxis • Neomycin, Streptomycin, Tetracycline • Immunosuppression • Cancer (disease or therapy) • HIV • Iatrogenic (transplant)

43. Bilateral Ocular autoinocuation in primary vaccinee 43

44. Eczema Vaccinatum 44

45. Eczema Vaccinatum (contact) 45

46. Progressive Vaccinia 46

47. Progressive Vaccinia 47

48. Public Health Factors in Choosing a Vaccination Strategy • Vaccine Supply • Extent of Outbreak • Risk and acceptability of vaccine-related adverse events 48

49. Key Containment Strategies 49

50. Eradication Strategy of the 1970s • Vaccination of close contacts of cases • Occasionally supplemented with broader campaigns • Vaccine was readily available 50