Smallpox VaccinationMark Upfal, MD, MPHDetroit Medical Center

Emergency Medicine Grand Rounds

Detroit Receiving Hospital

February 13, 2003

Collaborators: Kay Cadwell, Pat Goins, Kathy Reilly

Topics

Smallpox vaccination & history

Vaccine effectiveness

Administration/Outcomes

Revaccination

Topics

Adverse Reactions

Treatment

Contraindications

Topics

Smallpox & Vaccination History

Smallpox

Smallpox on trunk

Pustules scabs scars

Jenner 1798 Treatise on Vaccination

Historic Timetable1796 Dr. Jenner infects James Phipps w/ cowpox

1805 Use of cows to produce vaccine

1940s Freeze-drying technology

1949 Last US case of smallpox

1965 Licensure of bifurcated needle

1971 Routine vaccination stopped in US

1975 Last case of V. major in Bangladesh

1977 Last case of V. minor in Somalia

1983 Vaccine withdrawn from civilian market

Topics

Smallpox vaccination & history

Vaccine effectiveness

Protects against orthopox viruses

ATB’s w/in 10 days

Post-exposure – effective if given w/in 4-5 days

Topics

Smallpox vaccination & history

Vaccine effectiveness

Administration/Outcomes

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

Vaccine Administration

Method of Administration

Applied to the upper arm using a multiple-puncture technique with a bifurcated needle.

Semipermeable Adhesive Dressing

Infection control procedures

Normal Vaccination Reaction Time

0 Vaccination

3-4 Papule

5-6 Vesicle with surrounding erythema → vesicle with depressed center

8-9 Well-formed pustule

12+ Pustule crusts over → scab

17-21 Scab detaches revealing scar

Major reaction

Vesicular or pustular lesion or palpable induration surrounding a central crust or ulcerIndicates success

Equivocal reactionMay be technique failure & no immunity

Repeat vaccination

Expected Outcome

Papules 3-5 days Pustular lesion6-12 days

Scab 13-21 days

CDC recommends daily checksfor HCWs

Topics

Smallpox vaccination & history

Vaccine effectiveness

Administration/Outcomes

Revaccination

Revaccination

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

Topics

Adverse Events

Smallpox Vaccination and Adverse Reactions

Guidance for Clinicians

January 24, 2003 / 52(Dispatch);1-29

Common Side Effects

Local pain (30%), itching (80%) & erythema

Malaise

Low grade fever

Regional lymphadenopathy

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

Autoinnoculation

Autoinnoculation

Autoinnoculation

Autoinnoculation

Generalized Vaccinia

Generalized vesicular skin lesions w/o eczema Hx or other preexisting skin dz

Believed 2o to viremia w/ dermal seeding

Usually minor; Few signif. sequelae

Generalized Vaccinia

Generalized Vaccinia

Generalized Vaccinia

Generalized vaccinia

Child recovered without sequela

Generalized Vaccinia

Eczema Vaccinatum

Patients w/ h/o eczema

Generalized dermal spread

Rarely mild cases present only scattered individual lesions

Eczema Vaccinatum

Can occur w/ inactive eczema

More severe in contacts

Contact almost always in household

Pre-Tx Eczema Vaccinatum

Post-Tx Eczema Vaccinatum

Eczema vaccinatum

Eczema Vaccinatum in a 27 yo

Eczema Vaccinatum in a 22 yo

Eczema vaccinatum

Eczema Vaccinatum

Eczema vaccinatum

Eczema vaccinatum from contact w/ recently vaccinated child

Patient recovered without sequelae or permanent ocular damage

Vaccinia necrosum (progressive vaccinia)

Immunocompromised individuals

Severe local spread w/ necrosis

Can be fatal

Progressive Vaccinia in a child with hypogammaglobulinemia

Progressive vaccinia (vaccinia necrosum)seen w/ cell-mediated immunodeficiency

Fatal in a child with immunodeficiency

Progressive vaccinia

Progressive vaccinia in lymphosarcoma

Severe Progressive Vaccinia in a child with SCID

Vaccinial keratitis

VIG is contraindicated

Vaccinial Keratitis

Encephalitis

VIG not useful

Fetal Vaccinia (28 week birth)

Strep Infection @ vaccine site

Staph Infection @ vaccine site

Infant with Post-Vaccination Erythema Multiforme

Adverse Reactions – U.S., 1968

Complication Rate per Million doses

Rate

Autoinoculation 529 1/1,890

Generalized vaccinia

242 1/4,132

Eczema vaccinatum

39 1/25,641

Progressive vaccinia 1.5 1/666,666

Encephalitis 12 1/83,333

Total 1254 1/797

Lane JM, et al. J Infect Dis 1970;122:303-9.

What’s different today?

Many more immunocompromised

Better administration technique & follow-up

Better screening for contraindications

Better medical care for side effects

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

Topics

Adverse Reactions

Treatment

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

Cidofivir Indications

Failure of VIG treatment

Patient is near death

VIG supplies exhausted

5 mg/kg IV over 60 min. (see package insert!)

Cidofivir Side Effects

Severe renal toxicity

Administer with IV hydration & probenicid

Neutropenia, proteinuria, ocular toxicity, metabolic acidosis

? Carcinogenicity, teratogenicity, hypospermia

Ocular treatment

VIG only if no keratitis

Trifluridine

Vidarabine (no longer manufactured)

Topics

Adverse Reactions

Treatment

Contraindications

Contraindications

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

Pregnant or planning pregnancy

Household contacts with these conditions

Serious, life-threatening allergies to ATBs - polymyxin B, streptomycin, tetracycline, or neomycin

Contraindications

Contraindications today

Solid organ transplant patients

184,000

Cancer patients/survivors 8,500,000

HIV positive 550,000 known; 300,000 unknown

Atopic dermatitis 28,000,000

Q & A

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