Presentation on theme: "Smallpox Vaccine: Overview for Health Care Response Teams"— Presentation transcript:
1Smallpox Vaccine: Overview for Health Care Response Teams Thomas G. Franck, MD, MPHRegional Physician ConsultantOffice of Emergency Preparedness & ResponseVirginia Department of HealthJanuary 2003
2Objectives To briefly review smallpox disease To gain an in depth understanding of smallpox vaccine, including:history of smallpox vaccinationoverview of vacciniaindicationscontraindicationsnormal responsecomplications1.To briefly review smallpox disease;2.To provide an in depth review of smallpox vaccine, including:brief history of smallpox vaccinationoverview of vacciniavaccinia vaccine indications and contraindicationsnormal response to vaccinia vaccinationadverse events from vaccinia vaccination
3Taxonomy Family: Poxviridae Genus: Orthopoxviruses Smallpox (variola) CowpoxMonkeypoxVacciniaAlthough there are several other members of the genus of viruses called orthopoxviruses, the four listed here represent those that can infect humans.These four viruses have about 93% of their DNA in common, which accounts for their cross-reactivity and the ability to employ one as a vaccination that protects against the others.93% DNA Homology
4Smallpox Caused by Variola virus Unique to humans Person-to-person spreadusually via close contact - dropletscontaminated materials (uncommon)aerosolized droplet nuclei spread (rare)30% case-fatality rate on averageLet’s begin by reviewing some major aspects of smallpox disease.Here is an electron micrograph of variola major virus.It’s a large, enveloped, brick-shaped DNA virus belonging to the family Poxviridae and the genus of Orthopoxviruses.
5Smallpox: Clinical Features Incubation: days (range 7-17)Prodrome: lasts 2-4 daysfever, malaise, headache, backache, vomitingEruptive stage (Rash):Oral cavity/pharynx face, hands, forearms lower extremities trunkSynchronous progression: maculopapules vesicles pustules scabsLesions on palms /solesInfectious stage (especially 1st week)Smallpox disease can be divided into 3 phases: the incubation period, the prodrome, and the eruptive stage.
6This series of photographs demonstrates the typical progression and distribution of smallpox rash.
7Here is a fairly classic presentation of a child with smallpox. This is smallpox due to variola major, ordinary type, which is the most common form.
8Smallpox - Treatment Treatment Prevention/Prophylaxis Supportive care No treatment proven effectiveExperimental treatment with antivirals, e.g., CidofovirPrevention/ProphylaxisVaccination - protective if given within 3 days of exposure
9Smallpox: Why the Concern Now? Last case in US in 1949Last naturally acquired case in 1977Disease declared eliminated by WHO in 1980Stocks of Variola virus held by U.S. & RussiaBio Weapons programs in several countriesRecent Intelligence review: 4 countries may have covert stocks of smallpox virus – Russia, Iraq, North Korea, and France
10Smallpox Vaccine: History 1796: Edward Jenner develops vaccine (cowpox)1805: Use of cows to produce vaccine1940s: Freeze-drying of Vaccinia1965: Licensure of bifurcated needle1972: Routine vaccination stopped in U.S.1983: Vaccine removed from civilian market1990: U.S. Military vaccination stops
11Edward Jenner (1749–l823) the “father” of vaccination. In the background is a dairymaid (or milkmaid) working with some cows.(Courtesy of the Institute of the History of Medicine, The Johns Hopkins University, Baltimore, MD.)
12Jenner transferred “matter” from the hand of an infected dairymaid to 8 year-old James Phipps on 14 May 1796.It turns out this matter was cowpox virus. Jenner demonstrated that a person inoculated and infected with cowpox was protected against smallpox. The procedure, which he called vaccination, represented the first use of a vaccine in the prevention of disease.
14English engraving by James Gillray, 1802 Here we see Jenner vaccinating someone with cowpox.It’s an excellent capture of the anxiety felt by the population at the time, similar to what some of us may be experiencing today.
15Compare the results of variolation with vaccination. (Captain C. Gold, 1801, Courtesy of the Library, London, Wellcome Institute for the History of Medicine.)
16Smallpox 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
17Vaccinia Vaccine “Dryvax” (Wyeth Laboratories) Contains NY City Board of Health strain2.7 million doses licensed (phase 1)*Enough vaccine “to vaccinate every single person in the country in an emergency”**December 2002
18Vaccine Efficacy: Pre-Exposure Reduces chance of getting infected (i.e., decreases secondary attack rate)91%-97% reduction in cases among case contacts with vaccination scarFor those infected, reduces fatality rate and severity of diseaseHow well does the vaccine protect someone if it is given prior to any exposure to smallpox?
19Just to review: The case-fatality rate tells you this: once I am infected and become a case, what are my chances of dying.You can see from the graph that if you have been vaccinated, then you are relatively well-protected compared to those never having been vaccinated. And you are especially well-protected if vaccinated within the last 10 years.Mack, J. Inf Dis, 1972
20Vaccine Efficacy: Post Exposure Generally prevents smallpox, or significantly decreases severity, if given within 3 days of exposureVaccination 4 to 7 days post-exposure still offered protection to many people, but significantly less than vaccination before 4 daysWe have just seen that smallpox vaccination protects us when given in advance, prior to an exposure.But it can also be very effective even after you are directly exposed to smallpox, if given early enough.When estimates for prevention and disease modification are combined, fewer than 5% of all persons vaccinated within 3 days after exposure would be at risk for disease of normal severity
21Vaccine Efficacy: Post Exposure Smallpox AR %29.547.675.096.31.921.8(Madras)(Pakistan)Postexp vaccNever vaccVacc <10 daysVacc <7 daysAnother way to look at post-exposure vaccination efficacy is to examine secondary attack rates.In these 3 studies, the secondary attack rates varied considerably.What these studies demonstrate is that the risk of developing smallpox depended on whether or not you received any vaccination post-exposure.What is not quite so evident from these studies is the important finding that how quickly you received the vaccine after exposure to smallpox is critical to predicting your chances of survival.
22Duration of ImmunityHigh level of protection (95-100%) for 3-5 years following vaccinationImmunity wanes after 5 years, but some residual protection evident at 10 and even 20+ yearsReduction in disease severity with any history of vaccinationHowever, 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.
23Smallpox Vaccine Indications: Non-Emergency Current Indications:Laboratory workers who handle cultures or animals infected with non-highly attenuated vaccinia or other OrthopoxvirusesNew Recommendations:Public health, hospital, and other personnel, generally years of age, who may have to respond to a smallpox case or outbreak
24Smallpox Vaccine Indications: Emergency Situations Ring VaccinationPersons exposed to initial releaseClose contact with confirmed or suspected caseDirect care or transportation of confirmed or suspected caseLaboratory personnelPersons with risk of contact with infectious materials from caseMass Vaccination of entire populations?There are basically 2 major strategies at our disposal when it comes to managing a smallpox outbreak.Some advocate ring vaccination and others advocate mass vaccination.Ultimately, it may depend on the nature of the smallpox outbreak.
25Contraindications: Non-Emergency Situations Eczema/atopic dermatitis (active or history of) or household contact with eczema/atopic dermatitisOther active skin conditions (allergic rash, burns, impetigo, chickenpox, shingles, herpes,psoriasis, severe acne, etc.) or household contact with acitve skin conditionImmunosuppression or household contact with immunosuppressionPregnancy or pregnant household contactBreastfeedingInfants (not advised in children < 18)Severe allergic reaction to prior vaccination or vaccine component
26Contraindications: Immunodeficiency Conditions causing immunodeficiency:HIV, leukemia, lymphoma, other cancers, agammaglobulinemia, certain autoimmune disorders (e.g., SLE), other immune disordersTreatments causing immunodeficiency:Chemotherapy, radiation treatment, antimetabolites, alkyltating agents, organ transplant meds, high-dose corticosteroidsImmunomodulatory medications? UnknownAccording to CDC, cancer chemotherapy or radiation treatment, current or within the past 3 months, is a contraindication.High dose corticosteroids: Equivalent to 2 mgm/kg or greater of oral prednisone daily, or 20 mgm/day, particularly if given for longer than 14 days.For certain immunomodulatory therapies, e.g., DMARDs for Rheumatoid Arthritis, there currently are no specific recommendations. According to the American College of Rheumatology, it may be prudent to avoid vaccination of such patients for now until further information becomes available. For those potential vaccinees with questionable contraindications or possible contraindications, we recommend consultation with a specialist in the appropriate field.
27Contraindications: Eczema/Atopic Dermatitis Eczema: a red, itchy rash that lasts at least two weeks and then comes and goesIt is estimated that at least 15 million people in U.S. have atopic dermatitisThese people are at risk of a serious complication, eczema vaccinatumHere is one definition of eczema, as defined by an experienced group of dermatologists on the American Academy of Dermatology’s Bioterrorism Taskforce.
28Contraindications: Emergency Situations Exposed persons – no contraindicationsUnexposed persons – generally same as non-emergency situations w/ some modifications, depending on situationExample: if there were a smallpox outbreak in the U.S., the category of children 1-17 years old would probably be eliminated as a contraindication.
29Vaccine Administration Surgical needleVaccinostyleRotary lancetJet injectorBifurcated needle**Only administration technique currently in use.
31Invented by Dr. Benjamin A Invented by Dr. Benjamin A. Rubin of Wyeth Laboratories, patented in July Developed in conjunction with Reading Textile Machine Company. Bifurcation holds exactly 1 mg of water, slightly more vaccine because of increased viscosity. WHO procured about 50 million bifurcated needles between 1967 and The 1970 price was about US$5 per 1000.
32This photo demonstrates good vaccination technique.
33Vaccination Site CareRemember – live vaccinia virus is present at site of vaccination until scab falls off on its own, usually 2-3 weeks.DressingHealth care setting: 3 layers of protection – gauze, semipermeable dressing, shirtNon-health care setting: 2 layers of protection – gauze & shirtAvoid salves and ointmentsAvoid touching/scratching site and picking scab
34Post-Vaccination Follow-up Semipermeable dressing: change dressing at least every 3-5 days and as neededGauze 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
35Clinical Response to Vaccination* Sign/symptomPapuleVesiclePustuleMaximum erythemaScabScab separationTime after Vacc3 days5-6 days7-11 days8-12 days14 days21 days*typical response in a nonimmune person
36Clinical Response to Vaccination Major (primary) reactionIndicates viral replication has occurred and vaccination was successfulNo reaction or equivocal reactionNo immunity and vaccination must be repeated
37Let’s look at what the expected response to vaccination should be. Here we see the typical progression of vaccinia.On day 7 we see here a “major reaction”, also known as a “take”.
38Major Reaction* (6-8 days after vaccination) Primary vaccinationVesicular or pustular lesionArea of definite palpable induration surrounding a central crust or ulcerRevaccinationLess pronounced and more rapid progressionPustular lesion or induration surrounding a central crust or ulcer*WHO Expert Committee on Smallpox, 1964
45Smallpox Vaccination: Normal Side Effects Fever: 10% of adultsLocalized 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 sleepingIn a recent study, about one-third of vaccinees felt sick enough to miss work, school, social activity, or have disturbed sleep.In recent clinical trials, only about 5-10% of vaccinees actually missed work.
46Smallpox Vaccination: Adverse Events Contact transmission: spread vaccinia to othersInadvertent autoinoculation: spread to other sites on bodyGeneralized vaccinia: spread throughout bodyEczema vaccinatum: severe skin reactionProgressive vaccinia (vaccinia necrosum)Postvaccinial encephalitisDeath
47Accidental Inoculation Accidental auto-inoculation of cheek with vaccinia virus, approximately 5 days old. Primary take on arm, days old. Photo courtesy of John M. Leedom, MD.
51Eczema Vaccinatum This is a more severe complication. This child had a history of atopic dermatitis when he was vaccinated.
52Eczema VaccinatumAgain, you can see how severe this reaction can be. In fact, it can be fatal.Do not receive smallpox vaccination if you have any history of atopic dermatitis or “eczema.”
53Progressive VacciniaOne of the worst complications is progressive vaccinia, which almost always occurs in someone with immunosuppression, and often this is a defect in cell-mediated immunity.
54Post-Vaccinial Encephalitis Autoimmune processNo predictors of susceptibilitySupportive care; no specific therapyVaccinia Immune Globulin is not effective and is not recommended.15-25% mortality; and25% had permanent neurological sequelaeAny patient with an evolving central nervous system disorder should not receive a vaccination.
55Vaccinia KeratitisThis is caused by Vaccinia virus being deposited onto cornea, which leads to corneal infection or ulceration and subsequent clouding.Treatment – VIG is contraindicated.Combination of a topical antiviral and interferon speeds healing.VidarabineTrifluridineAcyclovir
56Vaccine Adverse Events Complication# per millionHousehold transmission27Accidental autoinoculation25-530Generalized vaccinia23-242Eczema vaccinatum10-39Progressive vaccinia1-1.5Encephalitis3-12Death1-2Looking at the worst case scenario, these rates translate to the following:For generalized vaccinia: 1 per 4,000For eczema vaccinatum: 1 per 26,000For post-vaccinial encephalitis: 1 per 83,000For progressive vaccinia: 1 per 667,000Death: 1 per 1 million primary vaccinations1 per 4 million revaccinations
57Postvaccinal Encephalitis Inadvertent Autoinoculation Complication Rates of Vaccination Rates (per million vaccinations) U.S., 1968 (ten state survey)Complication1081254Total212Postvaccinal Encephalitis31.5Progressive Vaccinia39Eczema Vaccinatum9242Generalized Vaccinia42529Inadvertent AutoinoculationRevaccinationPrimaryVaccinationComplicationPrimaryVaccinationRevaccinationInadvertent Autoinoculation52942Generalized Vaccinia2429Eczema Vaccinatum393Progressive Vaccinia1.53Postvaccinal Encephalitis122Total1254108
58VIG: Vaccinia Immune Globulin Indicated:Eczema vaccinatumProgressive vacciniaGeneralized 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 multiformeEncephalitisContraindicated:Vaccinia keratitisVIG is the Immunoglobulin fraction of plasma from persons vaccinated with vaccinia vaccine.
59Issues for Discussion HIV testing Pregnancy testing Vaccination site care – who, how often?Should healthcare provider continue to work?Liability & workers’ compensationHIV testing – do we recommend or simply offer the test?Pregnancy – do we test?Site care for vaccinated siteGauze +/- semi-permeable bandage?How often to change dressing? Who?Who assesses for a “take” at 7 days?Can healthcare provider continue to work?CDC says “yes”, Wyeth says “no”Options: furlough vs reassignment vs normal duty
60“…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