Smallpox Vaccine: Overview for Health Care Response Teams Thomas G. Franck, MD, MPH Regional...
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Transcript of Smallpox Vaccine: Overview for Health Care Response Teams Thomas G. Franck, MD, MPH Regional...
Smallpox Vaccine:Smallpox Vaccine:
Overview for Health Care Overview for Health Care Response TeamsResponse Teams
Thomas G. Franck, MD, MPHThomas G. Franck, MD, MPHRegional Physician ConsultantRegional Physician Consultant
Office of Emergency Preparedness & ResponseOffice of Emergency Preparedness & Response
Virginia Department of HealthVirginia Department of Health
January 2003January 2003
ObjectivesObjectives
To briefly review smallpox diseaseTo briefly review smallpox disease To gain an in depth understanding To gain an in depth understanding
of smallpox vaccine, including:of smallpox vaccine, including:– history of smallpox vaccinationhistory of smallpox vaccination– overview of vacciniaoverview of vaccinia– indicationsindications– contraindicationscontraindications– normal responsenormal response– complicationscomplications
TaxonomyTaxonomy
Family: PoxviridaeFamily: Poxviridae
Genus: OrthopoxvirusesGenus: Orthopoxviruses
Smallpox (variola)Smallpox (variola) CowpoxCowpox MonkeypoxMonkeypox VacciniaVaccinia
93% DNA Homology
SmallpoxSmallpox
Caused by Variola virusCaused by Variola virus Unique to humansUnique to humans Person-to-person spreadPerson-to-person spread
– usually via close contact - dropletsusually via close contact - droplets– contaminated materials (uncommon)contaminated materials (uncommon)– aerosolized droplet nuclei spread (rare)aerosolized droplet nuclei spread (rare)
30% case-fatality rate on average30% case-fatality rate on average
Smallpox: Clinical Smallpox: Clinical FeaturesFeatures
Incubation:Incubation: 12-14 days (range 7-17) 12-14 days (range 7-17) Prodrome:Prodrome: lasts 2-4 days lasts 2-4 days
– fever, malaise, headache, backache, fever, malaise, headache, backache, vomitingvomiting
Eruptive stageEruptive stage (Rash): (Rash):– Oral cavity/pharynx Oral cavity/pharynx face, hands, face, hands,
forearms forearms lower extremities lower extremities trunk trunk– Synchronous progression: maculopapules Synchronous progression: maculopapules
vesicles vesicles pustules pustules scabs scabs– Lesions on palms /solesLesions on palms /soles– Infectious stage (especially 1Infectious stage (especially 1stst week) week)
Smallpox - TreatmentSmallpox - Treatment
TreatmentTreatment– Supportive careSupportive care– No treatment proven effectiveNo treatment proven effective– Experimental treatment with Experimental treatment with
antivirals, e.g., Cidofovirantivirals, e.g., Cidofovir Prevention/ProphylaxisPrevention/Prophylaxis
– Vaccination - protective if given Vaccination - protective if given within 3 days of exposurewithin 3 days of exposure
Smallpox:Smallpox:Why the Concern Now? Why the Concern Now?
Last case in US in 1949Last case in US in 1949 Last naturally acquired case in 1977Last naturally acquired case in 1977 Disease declared eliminated by WHO in 1980Disease declared eliminated by WHO in 1980 Stocks of Variola virus held by U.S. & RussiaStocks of Variola virus held by U.S. & Russia Bio Weapons programs in several countries Bio Weapons programs in several countries Recent Intelligence review: 4 countries may Recent Intelligence review: 4 countries may
have covert stocks of smallpox virus – Russia, have covert stocks of smallpox virus – Russia, Iraq, North Korea, and FranceIraq, North Korea, and France
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
Smallpox Vaccine: Smallpox Vaccine: HistoryHistory
Smallpox VaccineSmallpox Vaccine
Live virus called “Vaccinia”Live virus called “Vaccinia”
An orthopoxvirus, genetically distinct An orthopoxvirus, genetically distinct from other orthopoxviruses such as from other orthopoxviruses such as cowpox, monkeypox, and variola (cause cowpox, monkeypox, and variola (cause of smallpox)of smallpox)
Origin unknown: May be a virus now Origin unknown: May be a virus now extinct in natureextinct in nature
Vaccinia VaccineVaccinia Vaccine ““Dryvax” (Wyeth Laboratories)Dryvax” (Wyeth Laboratories)
Contains NY City Board of Health strainContains NY City Board of Health strain
2.7 million doses licensed (phase 1)*2.7 million doses licensed (phase 1)*
Enough vaccine “to vaccinate every single Enough vaccine “to vaccinate every single person in the country in an emergency”*person in the country in an emergency”*
*December 2002
Vaccine Efficacy:Vaccine Efficacy:Pre-ExposurePre-Exposure
Reduces chance of getting infected Reduces chance of getting infected (i.e., decreases secondary attack (i.e., decreases secondary attack rate)rate) 91%-97% reduction in cases among 91%-97% reduction in cases among
case contacts with vaccination scarcase contacts with vaccination scar
For those infected, reduces fatality For those infected, reduces fatality rate and severity of diseaserate and severity of disease
Mack, J. Inf Dis, 1972
Vaccine Efficacy:Vaccine Efficacy:Post Exposure Post Exposure
Generally prevents smallpox, or Generally prevents smallpox, or significantly decreases severity, significantly decreases severity, if if given within 3 days of exposuregiven within 3 days of exposure
Vaccination 4 to 7 days post-Vaccination 4 to 7 days post-exposureexposurestill offered protection to many still offered protection to many people, but significantly less than people, but significantly less than vaccination before 4 daysvaccination before 4 days
Vaccine Efficacy:Vaccine Efficacy:Post ExposurePost Exposure
Postexp vaccNever vacc
Vacc <10 daysNever vacc
Vacc <7 daysNever vacc
Smallpox AR %29.547.6
75.096.3
1.921.8
(Madras)
(Pakistan)
(Pakistan)
Duration of ImmunityDuration of Immunity
High level of protection (95-100%) for 3-5 High level of protection (95-100%) for 3-5 years following vaccinationyears following vaccination
Immunity wanes after 5 years, but some Immunity wanes after 5 years, but some residual protection evident at 10 and even residual protection evident at 10 and even 20+ years20+ years
Reduction in disease severity with any Reduction in disease severity with any history of vaccinationhistory of vaccination
However, best protection if vaccinated <3-5 However, best protection if vaccinated <3-5 yrs ago; yrs ago; we cannot rely on previous we cannot rely on previous vaccinations to protect our population and vaccinations to protect our population and we should consider the population to lack we should consider the population to lack immunity to smallpox.immunity to smallpox.
Smallpox Vaccine Indications:Smallpox Vaccine Indications:Non-EmergencyNon-Emergency
Current Indications:Current Indications:– Laboratory workers who handle cultures or Laboratory workers who handle cultures or
animals infected with non-highly attenuated animals infected with non-highly attenuated vaccinia or other Orthopoxvirusesvaccinia or other Orthopoxviruses
New Recommendations:New Recommendations:– Public health, hospital, and other personnel, Public health, hospital, and other personnel,
generally 18-65 years of age, who may have generally 18-65 years of age, who may have to respond to a smallpox case or outbreakto respond to a smallpox case or outbreak
Smallpox Vaccine Indications: Smallpox Vaccine Indications: Emergency SituationsEmergency Situations
Ring VaccinationRing Vaccination– Persons exposed to initial releasePersons exposed to initial release– Close contact with confirmed or suspected Close contact with confirmed or suspected
casecase– Direct care or transportation of confirmed or Direct care or transportation of confirmed or
suspected casesuspected case– Laboratory personnelLaboratory personnel– Persons with risk of contact with infectious Persons with risk of contact with infectious
materials from casematerials from case Mass Vaccination of entire populations?Mass Vaccination of entire populations?
Contraindications:Contraindications:Non-Emergency Non-Emergency SituationsSituations
Eczema/atopic dermatitis (active or history of) or Eczema/atopic dermatitis (active or history of) or household contact with eczema/atopic dermatitishousehold contact with eczema/atopic dermatitis
Other active skin conditions (allergic rash, burns, Other active skin conditions (allergic rash, burns, impetigo, chickenpox, shingles, herpes,psoriasis, impetigo, chickenpox, shingles, herpes,psoriasis, severe acne, etc.) or household contact with acitve severe acne, etc.) or household contact with acitve skin conditionskin condition
Immunosuppression or household contact with Immunosuppression or household contact with immunosuppressionimmunosuppression
Pregnancy or pregnant household contactPregnancy or pregnant household contact
BreastfeedingBreastfeeding Infants (not advised in children < 18)Infants (not advised in children < 18) Severe allergic reaction to prior vaccination or Severe allergic reaction to prior vaccination or
vaccine componentvaccine component
Contraindications:Contraindications:ImmunodeficiencyImmunodeficiency
Conditions causing immunodeficiency:Conditions causing immunodeficiency:– HIV, leukemia, lymphoma, other cancers, HIV, leukemia, lymphoma, other cancers,
agammaglobulinemia, certain autoimmune agammaglobulinemia, certain autoimmune disorders (e.g., SLE), other immune disorders (e.g., SLE), other immune disordersdisorders
Treatments causing immunodeficiency:Treatments causing immunodeficiency:– Chemotherapy, radiation treatment, Chemotherapy, radiation treatment,
antimetabolites, alkyltating agents, organ antimetabolites, alkyltating agents, organ transplant meds, high-dose corticosteroidstransplant meds, high-dose corticosteroids
– Immunomodulatory medications? UnknownImmunomodulatory medications? Unknown
Contraindications: Contraindications: Eczema/Atopic Eczema/Atopic DermatitisDermatitis Eczema:Eczema: a red, itchy rash that lasts a red, itchy rash that lasts
at least two weeks and then comes at least two weeks and then comes and goesand goes
It is estimated that at least 15 It is estimated that at least 15 million people in U.S. have atopic million people in U.S. have atopic dermatitisdermatitis
These people are at risk of a serious These people are at risk of a serious complication, eczema vaccinatumcomplication, eczema vaccinatum
Contraindications:Contraindications:Emergency SituationsEmergency Situations
Exposed persons – no Exposed persons – no contraindicationscontraindications
Unexposed persons – generally same Unexposed persons – generally same as non-emergency situations w/ some as non-emergency situations w/ some modifications, depending on situationmodifications, depending on situation
Vaccine Vaccine AdministrationAdministration
Surgical needleSurgical needle VaccinostyleVaccinostyle Rotary lancetRotary lancet Jet injectorJet injector Bifurcated needle*Bifurcated needle*
*Only administration technique currently in use.
Vaccination Vaccination TechniqueTechnique
Vaccination Site CareVaccination Site Care
Remember – Remember – live vaccinia viruslive vaccinia virus is is present at site of vaccination until present at site of vaccination until scab falls off on its own, usually 2-3 scab falls off on its own, usually 2-3 weeks.weeks.
DressingDressingHealth care setting: 3 layers of protection Health care setting: 3 layers of protection
– gauze, semipermeable dressing, shirt– gauze, semipermeable dressing, shirtNon-health care setting: 2 layers of Non-health care setting: 2 layers of
protection – gauze & shirtprotection – gauze & shirt Avoid salves and ointmentsAvoid salves and ointments Avoid touching/scratching site and Avoid touching/scratching site and
picking scabpicking scab
Post-Vaccination Follow-Post-Vaccination Follow-upup
Semipermeable dressing: change Semipermeable dressing: change dressing at least every 3-5 days and as dressing at least every 3-5 days and as neededneeded
Gauze dressing secured by tape: change Gauze dressing secured by tape: change dressing every 1-3 days and as neededdressing every 1-3 days and as needed
““Take” evaluation: 7 days after Take” evaluation: 7 days after vaccination (+/- 1 day)vaccination (+/- 1 day)
If significant side effects or adverse If significant side effects or adverse event, follow-up with designated health event, follow-up with designated health care providercare provider
Clinical Response to Clinical Response to Vaccination* Vaccination*
Sign/symptomPapuleVesiclePustule
Maximum erythemaScab
Scab separation
Time after Vacc3 days
5-6 days7-11 days8-12 days14 days21 days
*typical response in a nonimmune person
Clinical Response to Clinical Response to Vaccination Vaccination
Major (primary) reactionMajor (primary) reaction– Indicates viral replication has Indicates viral replication has
occurred and vaccination was occurred and vaccination was successfulsuccessful
No reaction or equivocal reactionNo reaction or equivocal reaction– No immunity and vaccination must be No immunity and vaccination must be
repeatedrepeated
Major Reaction*Major Reaction*(6-8 days after (6-8 days after vaccination) vaccination)
Primary vaccinationPrimary vaccination– Vesicular or pustular lesionVesicular or pustular lesion– Area of definite palpable induration Area of definite palpable induration
surrounding a central crust or ulcersurrounding a central crust or ulcer RevaccinationRevaccination
– Less pronounced and more rapid Less pronounced and more rapid progressionprogression
– Pustular lesion or induration surrounding Pustular lesion or induration surrounding a central crust or ulcera central crust or ulcer*WHO Expert Committee on Smallpox,
1964
Day 3
Primary Revaccination
Day 7
Primary Revaccination
Day 10
Primary Revaccination
Day 14
Primary Revaccination
Normal Variants:Normal Variants:Satellite LesionsSatellite Lesions
Normal Variants:Normal Variants:Cellulitis & Cellulitis & LymphangitisLymphangitis
Smallpox Vaccination:Smallpox Vaccination:Normal Side EffectsNormal Side Effects
Fever: 10% of adultsFever: 10% of adults Localized soreness: 35-47%Localized soreness: 35-47% Headache/muscle aches: 40-50%Headache/muscle aches: 40-50% Redness/swelling > 3 inches: 15% Redness/swelling > 3 inches: 15% 1/3 may feel bad enough to miss 1/3 may feel bad enough to miss
work, school, activity, or have work, school, activity, or have trouble sleepingtrouble sleeping
Smallpox Vaccination:Smallpox Vaccination:Adverse EventsAdverse Events
Contact transmission: spread vaccinia to others Contact transmission: spread vaccinia to others Inadvertent autoinoculation: spread to other Inadvertent autoinoculation: spread to other
sites on bodysites on body Generalized vaccinia: spread throughout bodyGeneralized vaccinia: spread throughout body Eczema vaccinatum: severe skin reactionEczema vaccinatum: severe skin reaction Progressive vaccinia (vaccinia necrosum)Progressive vaccinia (vaccinia necrosum) Postvaccinial encephalitisPostvaccinial encephalitis DeathDeath
Accidental InoculationAccidental 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.
Accidental InoculationAccidental Inoculation
Generalized VacciniaGeneralized Vaccinia
Generalized vaccinia in an apparently normal child. Recovered without sequelae. Photo courtesy of John M. Leedom, M.D.
Generalized VacciniaGeneralized Vaccinia
Eczema VaccinatumEczema Vaccinatum
Eczema VaccinatumEczema Vaccinatum
Progressive VacciniaProgressive Vaccinia
Post-Vaccinial Post-Vaccinial EncephalitisEncephalitis Autoimmune process Autoimmune process No predictors of susceptibility No predictors of susceptibility Supportive care; no specific therapy Supportive care; no specific therapy Vaccinia Immune Globulin is not Vaccinia Immune Globulin is not
effective and is effective and is not recommendednot recommended. . 15-25% mortality; and 25% had permanent neurological
sequelae
Vaccinia Keratitis
Vaccine Adverse Vaccine Adverse EventsEvents
ComplicationComplication # per # per millionmillion
Household transmissionHousehold transmission 2727
Accidental autoinoculationAccidental autoinoculation 25-53025-530
Generalized vacciniaGeneralized vaccinia 23-24223-242
Eczema vaccinatumEczema vaccinatum 10-3910-39
Progressive vacciniaProgressive vaccinia 1-1.51-1.5
EncephalitisEncephalitis 3-123-12
DeathDeath 1-21-2
Complication Rates of Complication Rates of VaccinationVaccination
Rates (per million vaccinations)Rates (per million vaccinations)U.S., 1968 (ten state survey)U.S., 1968 (ten state survey)
10810812541254TotalTotal
221212Postvaccinal Postvaccinal EncephalitisEncephalitis
331.51.5Progressive Progressive VacciniaVaccinia
333939Eczema Eczema VaccinatumVaccinatum
99242242Generalized Generalized VacciniaVaccinia
4242529529Inadvertent Inadvertent AutoinoculationAutoinoculation
RevaccinationRevaccinationPrimaryPrimary
VaccinationVaccinationComplicationComplication
10810812541254TotalTotal
221212Postvaccinal Postvaccinal EncephalitisEncephalitis
331.51.5Progressive Progressive VacciniaVaccinia
333939Eczema Eczema VaccinatumVaccinatum
99242242Generalized Generalized VacciniaVaccinia
4242529529Inadvertent Inadvertent AutoinoculationAutoinoculation
RevaccinationRevaccinationPrimaryPrimary
VaccinationVaccinationComplicationComplication
VIG:VIG:Vaccinia Immune Vaccinia Immune GlobulinGlobulin
Indicated:Indicated:– Eczema vaccinatumEczema vaccinatum– Progressive vacciniaProgressive vaccinia– Generalized vaccinia (if severe or recurrent)Generalized vaccinia (if severe or recurrent)– Accidental implantation (ocular or extensive Accidental implantation (ocular or extensive
lesions)lesions) Not Recommended:Not Recommended:
– Accidental implantation (mild instances)Accidental implantation (mild instances)– Generalized vaccinia (mild or limited - most Generalized vaccinia (mild or limited - most
instances)instances)– Erythema multiformeErythema multiforme– EncephalitisEncephalitis
Contraindicated:Contraindicated:– Vaccinia keratitisVaccinia keratitis
IssuesIssues for Discussion for Discussion
HIV testingHIV testing
Pregnancy testingPregnancy testing
Vaccination site care – who, how often?Vaccination site care – who, how often?
Should healthcare provider continue to Should healthcare provider continue to work?work?
Liability & workers’ compensationLiability & workers’ compensation
“…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