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