Smallpox Vaccine: Overview for Health Care Response Teams

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Smallpox VaccineOverview for Health Care
Response Teams

• Thomas G. Franck, MD, MPH
• Regional Physician Consultant
• Office of Emergency Preparedness Response
• Virginia Department of Health
• January 2003

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Objectives

• To briefly review smallpox disease
• To gain an in depth understanding of smallpox
  vaccine, including
• history of smallpox vaccination
• overview of vaccinia
• indications
• contraindications
• normal response
• complications

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Taxonomy

• Family Poxviridae
• Genus Orthopoxviruses
• Smallpox (variola)
• Cowpox
• Monkeypox
• Vaccinia

93 DNA Homology
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Smallpox

• Caused by Variola virus
• Unique to humans
• Person-to-person spread
• usually via close contact - droplets
• contaminated materials (uncommon)
• aerosolized droplet nuclei spread (rare)
• 30 case-fatality rate on average

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Smallpox Clinical Features

• Incubation 12-14 days (range 7-17)
• Prodrome lasts 2-4 days
• fever, malaise, headache, backache, vomiting
• Eruptive stage (Rash)
• Oral cavity/pharynx ? face, hands, forearms ?
  lower extremities ? trunk
• Synchronous progression maculopapules ? vesicles
  ? pustules ? scabs
• Lesions on palms /soles
• Infectious stage (especially 1st week)

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Smallpox - Treatment

• Treatment
• Supportive care
• No treatment proven effective
• Experimental treatment with antivirals, e.g.,
  Cidofovir
• Prevention/Prophylaxis
• Vaccination - protective if given within 3 days
  of exposure

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SmallpoxWhy the Concern Now?

• Last case in US in 1949
• Last naturally acquired case in 1977
• Disease declared eliminated by WHO in 1980
• Stocks of Variola virus held by U.S. Russia
• Bio Weapons programs in several countries
• Recent Intelligence review 4 countries may have
  covert stocks of smallpox virus Russia, Iraq,
  North Korea, and France

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Smallpox Vaccine History

• 1796 Edward Jenner develops vaccine (cowpox)
• 1805 Use of cows to produce vaccine
• 1940s Freeze-drying of Vaccinia
• 1965 Licensure of bifurcated needle
• 1972 Routine vaccination stopped in U.S.
• 1983 Vaccine removed from civilian market
• 1990 U.S. Military vaccination stops

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Smallpox Vaccine

• Live virus called Vaccinia
• An orthopoxvirus, genetically distinct from other
  orthopoxviruses such as cowpox, monkeypox, and
  variola (cause of smallpox)
• Origin unknown May be a virus now extinct in
  nature

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Vaccinia Vaccine

• Dryvax (Wyeth Laboratories)
• Contains NY City Board of Health strain
• 2.7 million doses licensed (phase 1)
• Enough vaccine to vaccinate every single person
  in the country in an emergency

December 2002
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Vaccine EfficacyPre-Exposure

• Reduces chance of getting infected (i.e.,
  decreases secondary attack rate)
• 91-97 reduction in cases among case contacts
  with vaccination scar
• For those infected, reduces fatality rate and
  severity of disease

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Mack, J. Inf Dis, 1972
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Vaccine EfficacyPost Exposure

• Generally prevents smallpox, or significantly
  decreases severity, if given within 3 days of
  exposure
• Vaccination 4 to 7 days post-exposurestill
  offered protection to many people, but
  significantly less than vaccination before 4 days

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Vaccine EfficacyPost Exposure
Smallpox AR 29.5 47.6 75.0 96.3 1.9 21.8
Postexp vacc Never vacc Vacc lt10 days Never
vacc Vacc lt7 days Never vacc
(Madras) (Pakistan) (Pakistan)
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Duration of Immunity

• High level of protection (95-100) for 3-5 years
  following vaccination
• Immunity wanes after 5 years, but some residual
  protection evident at 10 and even 20 years
• Reduction in disease severity with any history of
  vaccination
• However, best protection if vaccinated lt3-5 yrs
  ago we cannot rely on previous vaccinations to
  protect our population and we should consider the
  population to lack immunity to smallpox.

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Smallpox Vaccine IndicationsNon-Emergency

• Current Indications
• Laboratory workers who handle cultures or animals
  infected with non-highly attenuated vaccinia or
  other Orthopoxviruses
• New Recommendations
• Public health, hospital, and other personnel,
  generally 18-65 years of age, who may have to
  respond to a smallpox case or outbreak

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Smallpox Vaccine Indications Emergency Situations

• Ring Vaccination
• 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
• Mass Vaccination of entire populations?

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ContraindicationsNon-Emergency Situations

• Eczema/atopic dermatitis (active or history of)
  or household contact with eczema/atopic
  dermatitis
• Other active skin conditions (allergic rash,
  burns, impetigo, chickenpox, shingles,
  herpes,psoriasis, severe acne, etc.) or household
  contact with acitve skin condition
• Immunosuppression or household contact with
  immunosuppression
• Pregnancy or pregnant household contact
• Breastfeeding
• Infants (not advised in children lt 18)
• Severe allergic reaction to prior vaccination or
  vaccine component

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ContraindicationsImmunodeficiency

• Conditions causing immunodeficiency
• HIV, leukemia, lymphoma, other cancers,
  agammaglobulinemia, certain autoimmune disorders
  (e.g., SLE), other immune disorders
• Treatments causing immunodeficiency
• Chemotherapy, radiation treatment,
  antimetabolites, alkyltating agents, organ
  transplant meds, high-dose corticosteroids
• Immunomodulatory medications? Unknown

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Contraindications Eczema/Atopic Dermatitis

• Eczema a red, itchy rash that lasts at least two
  weeks and then comes and goes
• It is estimated that at least 15 million people
  in U.S. have atopic dermatitis
• These people are at risk of a serious
  complication, eczema vaccinatum

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ContraindicationsEmergency Situations

• Exposed persons no contraindications
• Unexposed persons generally same as
  non-emergency situations w/ some modifications,
  depending on situation

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Vaccine Administration

• Surgical needle
• Vaccinostyle
• Rotary lancet
• Jet injector
• Bifurcated needle

Only administration technique currently in use.
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Vaccination Technique
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Vaccination Site Care

• Remember live vaccinia virus is present at site
  of vaccination until scab falls off on its own,
  usually 2-3 weeks.
• Dressing
• Health care setting 3 layers of protection
  gauze, semipermeable dressing, shirt
• Non-health care setting 2 layers of protection
  gauze shirt
• Avoid salves and ointments
• Avoid touching/scratching site and picking scab

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Post-Vaccination Follow-up

• Semipermeable dressing change dressing at least
  every 3-5 days and as needed
• Gauze dressing secured by tape change dressing
  every 1-3 days and as needed
• Take evaluation 7 days after vaccination (/-
  1 day)
• If significant side effects or adverse event,
  follow-up with designated health care provider

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Clinical Response to Vaccination
Sign/symptom 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
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Clinical Response to Vaccination

• Major (primary) reaction
• Indicates viral replication has occurred and
  vaccination was successful
• No reaction or equivocal reaction
• No immunity and vaccination must be repeated

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Major Reaction(6-8 days after vaccination)

• Primary vaccination
• Vesicular or pustular lesion
• Area of definite palpable induration surrounding
  a central crust or ulcer
• Revaccination
• Less pronounced and more rapid progression
• Pustular lesion or induration surrounding a
  central crust or ulcer

WHO Expert Committee on Smallpox, 1964
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Primary
Revaccination
Day 3
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Primary
Revaccination
Day 7
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Primary
Revaccination
Day 10
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Revaccination
Primary
Day 14
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Normal VariantsSatellite Lesions
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Normal VariantsCellulitis Lymphangitis
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Smallpox VaccinationNormal Side Effects

• Fever 10 of adults
• Localized soreness 35-47
• Headache/muscle aches 40-50
• Redness/swelling gt 3 inches 15
• 1/3 may feel bad enough to miss work, school,
  activity, or have trouble sleeping

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Smallpox VaccinationAdverse Events

• Contact transmission spread vaccinia to others
• Inadvertent autoinoculation spread to other
  sites on body
• Generalized vaccinia spread throughout body
• Eczema vaccinatum severe skin reaction
• Progressive vaccinia (vaccinia necrosum)
• Postvaccinial encephalitis
• Death

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Accidental Inoculation
Accidental auto-inoculation of cheek with
vaccinia virus, approximately 5 days old. Primary
take on arm, 10-12 days old. Photo courtesy of
John M. Leedom, MD.
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Accidental Inoculation
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Generalized Vaccinia
Generalized vaccinia in an apparently normal
child. Recovered without sequelae. Photo courtesy
of John M. Leedom, M.D.
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Generalized Vaccinia
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Eczema Vaccinatum
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Eczema Vaccinatum
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Progressive Vaccinia
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Post-Vaccinial Encephalitis

• Autoimmune process
• No predictors of susceptibility
• Supportive care no specific therapy
• Vaccinia Immune Globulin is not effective and is
  not recommended.
• 15-25 mortality and
• 25 had permanent neurological sequelae

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Vaccinia Keratitis
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Vaccine Adverse Events
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Complication Rates of VaccinationRates (per
million vaccinations)U.S., 1968 (ten state
survey)
Revaccination
Primary Vaccination
Complication
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529
Inadvertent Autoinoculation
9
242
Generalized Vaccinia
3
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Eczema Vaccinatum
3
1.5
Progressive Vaccinia
2
12
Postvaccinal Encephalitis
108
1254
Total
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VIGVaccinia Immune Globulin

• Indicated
• Eczema vaccinatum
• Progressive vaccinia
• Generalized vaccinia (if severe or recurrent)
• Accidental implantation (ocular or extensive
  lesions)
• Not Recommended
• Accidental implantation (mild instances)
• Generalized vaccinia (mild or limited - most
  instances)
• Erythema multiforme
• Encephalitis
• Contraindicated
• Vaccinia keratitis

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Issues for Discussion

• HIV testing
• Pregnancy testing
• Vaccination site care who, how often?
• Should healthcare provider continue to work?
• Liability workers compensation

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• 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