Smallpox Vaccine:

Overview for Health Care Response Teams

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

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

Taxonomy

 Family: Poxviridae  Genus: Orthopoxviruses     Smallpox (variola) Cowpox Monkeypox Vaccinia 93% DNA Homology

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

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  lower extremities  – Synchronous progression: maculopapules vesicles   pustules  face, hands, forearms trunk scabs  – Lesions on palms /soles – Infectious stage (especially 1 st week)

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

Smallpox: Why 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

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

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

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

Vaccine Efficacy: Pre-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

Mack, J. Inf Dis, 1972

Vaccine Efficacy: Post Exposure

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

Vaccine Efficacy: Post Exposure

(Madras) Postexp vacc Smallpox AR % 29.5

Never vacc 47.6

(Pakistan) Vacc <10 days Never vacc 75.0

96.3

(Pakistan) Vacc <7 days Never vacc 1.9

21.8

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 <3-5 yrs ago; we cannot rely on previous vaccinations to protect our population and we should consider the population to lack immunity to smallpox.

Smallpox Vaccine Indications: Non-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

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?

Contraindications: Non-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 < 18) Severe allergic reaction to prior vaccination or vaccine component

Contraindications: Immunodeficiency

 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

Contraindications: Eczema/Atopic Dermatitis

   Eczema: least two weeks and then comes and goes a red, itchy rash that lasts at 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

Contraindications: Emergency Situations

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

Vaccine Administration

     Surgical needle Vaccinostyle Rotary lancet Jet injector Bifurcated needle*

*Only administration technique currently in use.

Vaccination Technique

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

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

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

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

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

Primary Revaccination Day 3

Primary Revaccination Day 7

Primary Revaccination Day 10

Primary Revaccination Day 14

Normal Variants: Satellite Lesions

Normal Variants: Cellulitis & Lymphangitis

Smallpox Vaccination: Normal Side Effects

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

Smallpox Vaccination: Adverse 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

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.

Accidental Inoculation

Generalized Vaccinia

Generalized vaccinia in an apparently normal child. Recovered without sequelae. Photo courtesy of John M. Leedom, M.D.

Generalized Vaccinia

Eczema Vaccinatum

Eczema Vaccinatum

Progressive Vaccinia

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

Vaccinia Keratitis

Vaccine Adverse Events Complication

Household transmission Accidental autoinoculation Generalized vaccinia Eczema vaccinatum Progressive vaccinia Encephalitis Death

# per million

27 25-530 23-242 10-39 1-1.5

3-12 1-2

Complication Rates of Vaccination Rates (per million vaccinations) U.S., 1968 (ten state survey) Inadvertent Autoinoculation Generalized Vaccinia Eczema Vaccinatum Progressive Vaccinia Postvaccinal Encephalitis

VIG: Vaccinia 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

Issues

for Discussion

 HIV testing  Pregnancy testing  Vaccination site care – who, how often?

 Should healthcare provider continue to work?

 Liability & 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