Transcript Smallpox Vaccination - Office of Public Health Practice

Smallpox Vaccination
History of Vaccination in the US
• Before 1972, smallpox vaccination
required for all children at age 1
year
• Most states required smallpox
vaccination before school entry
Vaccine
• DryVax©, a lyophilized, live vaccinia virus
• Store at -17oC to -20oC (-4 to - 1oF)
• Re-constituted store 30 days at 2–8oC (36 – 46oF)
• Contains
•
•
•
•
polymyxin B sulfate
dihydrostreptomycin sulfate
chlortetracycline hydrochloride
neomycin sulfate
• Aventis vaccine kept for emergencies
Supply of Vaccine (12/5/2002)
• Existing Supply:
• Dryvax: 15 million doses (2.7 million doses
are approved for distribution as a licensed
vaccine)
• Aventis Pasteur: 85 million doses
• In Production:
• Acam 1000: 54 million doses
• Acam 2000: 155 million doses
Strains of Vaccinia
• New York City Board of Health
(NYCBOH) used in the DryVax and
Aventis vaccine
• Lister strain used by many Europeans
and the Israelis
• Both were used by the WHO
Immune Response
• Neutralizing and HI antibodies appear about 10
days after vaccination
• >95% of primary vaccinees have antibody titres
≥ 1:10
• Cell mediated response (DTH) can be detected
as early as 2 days after vaccination
• Antibody response is about 4 – 8 days earlier
than with natural variola infection, therefore vx
after exposure can modify infection
Source: Henderson & Moss. In Vaccines Eds Plotkin & Orenstein 3rd Ed 1999
Duration of Immunity
• Neutralizing antibodies (NA) can be
detected > 20 years after Vx
• Anamnestic (memory) response seen
upon re-vaccination, with significant
elevation in NA by day 7
Source: Henderson & Moss. In Vaccines Eds Plotkin & Orenstein 3rd Ed 1999
Smallpox vaccination
•Administered using a
bifurcated needle and 15
punctures delivered into the
skin
•Positive “take” can be seen
after about 7 days
Bifurcated needle with and without
the vaccine dose
Vaccination site immediately
after vaccination
•Note: small amount
of blood which
should appear at the
site if punctures were
sufficiently deep into
the skin
Vaccination Site Management
• Blot excess vaccine off the site
• Cover with non-occlusive bandage –
this is to prevent maceration of the
site
• If patient contact use gauze covered
by a semi-occlusive bandage – to
prevent transmission to others
• Site should be examined every day
Normal Primary Vaccination
•Vaccinia virus
proliferates in the basal
cells of the epidermis
•By day 3….. Papule
•Day 5-6 Vesicle with
surrounding erythema
– so called Jennerian
pustule
Normal Primary Vaccination
•Day 8 – 9 Well formed
pustule
•This is a major
reaction – a POSITIVE
TAKE
Normal Primary Vaccination
◄ Normal
reactions - 5 days
Normal reaction 8 days 
Normal Primary Vaccination
•Day 12 +
•Pustules break down
and crust over
•This is a major
reaction – a POSITIVE
TAKE
Normal Primary Vaccination
Day 14
Normal Primary Vaccination
•Day 16
•Scabs begin to dry
completely and
then fall off by day
21 leaving a visible
circular scar
•This is a major
reaction – a
POSITIVE TAKE
Normal Vaccine Reactions
Among Primary Vaccinees
• Low grade fever > 37.7oC
2 – 16%
• Swelling of regional lymph nodes 25 -50%
• Myalgia, chills, headache, fatigue 0.3-37%
&/or nausea
These are normal and should not be considered as
adverse events
They occur usually about 3-10 days after vaccination
Vaccine reactions
among re-vaccinees
• Among those for whom 25 years or
more has elapsed since last
vaccination, essentially all should
experience a "major reaction"
Vaccine reactions
among re-vaccinees
• Level of response depends upon level of
immunity
• Persons with some residual CMI can
develop an erythema and even a pustule,
BUT there may not be sufficient immunity to
inhibit viral replication
• Those with substantial immunity may
experience no more than a minor DTH
reaction
Reactions in re-vaccinees
Day 3: Note small vesicles
have already formed
Accelerated reaction –
major reaction.
Note the position next to an
old smallpox vaccination
scar.
Source: CDC web page
http://www.bt.cdc.gov/training/smallpoxvaccine/reactions/normal_accelerated.html#
Vaccine reactions among re-vaccinees
• It is impossible to distinguish clinically
between an equivocal reaction which
is due to residual immunity and one
which is due to an allergic reaction
• Therefore all reactions, other than a
major reaction, should be read as a
no-take and repeated using a different
batch of vaccine
ReVaccination
Primary
Primary
Types of
reaction at
the
vaccination
site
Note: it is impossible to distinguish clinically between a re-vaccination reaction
due to residual immunity and one due to a hypersensitivity reaction
After Burdon KL. Textbook of Microbiology 1948
Equivocal Reaction
•
•
•
•
Small area of erythema
Possibly a small pustule
Should be re-vaccinated
After two unsuccessful re-vaccinations seek
consultation
• Could result from
• residual immunity or
• reaction to vaccine components rather than a
viral replication –
but cannot distinguish between the two
Equivocal reaction - Allergic
• Erythema and a small, evanescent papule
are present within several days
• Symptoms resolve quickly
• These are “sensitivity” reactions that can
be evoked with vaccine virus that is no
longer viable.
• Revaccination is indicated.
Equivocal reaction – No Reaction
• In some individuals, no take is seen after
revaccination, even at long intervals after a
primary vaccination.
• Usually this is due to poor technique, low
potency vaccine, or inactivation of the virus
at the skin site (e.g. if alcohol is used to
prepare the site).
• Revaccination is indicated using vaccine of
assured potency.
Normal Variant Satellite Lesions
The frequency of satellite lesions varies from study to study
and ranges from 2.4 to 6.6 %.
No treatment other than symptomatic relief
Lymphangitis and cellulitis
Normal Variant Cellulitis
Serious Adverse Reactions
• Usually occur about 7 days after
vaccination
• These are not the normal reactions to
a smallpox vaccination
• Can be minimized by careful
screening of vaccinees for
contraindications
Serious Adverse Events
• Potential adverse events should be referred
to the designated Hospital Assigned
Physician who can evaluate adverse events
• All adverse events should be reported to
both the state health department and to the
Vaccine Adverse Events Reporting System
(VAERS)
• Do NOT report normal reactions to
smallpox vaccination
Smallpox Vaccination: Complications
▲
Eczema vaccinatum ►
◄ Generalized vaccinia
Erythema multiforme ►
◄ Accidental transfer from
mother to 2-year old
Rates of Complications of
Smallpox Vaccination Per Million
Doses, USA, 1968†, ††
Post-Vaccinal Encephalitis
Progressive Vaccinia
Eczema Vaccinatum
Accidental Infection
Death
All
doses
Primary
doses
1.1
0.8
8.9
13.6
0.6
2.9
0.9
10.4
25.4
1.1
† Excludes contact cases
†† Source: From N. Engl J Med, 1969; 281: 1201-1208
Treatment for Serious Adverse
Reactions
• VIG and cidofovir available only from
CDC via state health departments
• Cidofovir (Vistide) may be used under
an Investigational New Drug (IND)
protocol to treat serious smallpox
vaccine
Vaccinia Immune Globulin
• Contains thimerosal
• Dosage:
• Usual dosage 0.6ml/kg IM dose may be divided
• For severe cases 1 – 10 ml/kg
• 700 doses of IM VIG are available now
• Approximately 3300 doses of the new IV
VIG will be available by the end of
December 2002.
Indications for Use of Vaccinia Immunoglobulin
(VIG) for Treatment of Adverse Reactions
Associated With Smallpox Vaccination
• Inadvertent inoculation of other body sites
• — Usually not required
— Indicated for inoculation of eye or eyelid
— BUT contraindicated for vaccinial keratitis
because increased scarring can occur
• Generalized vaccinia—Indicated if patient is
toxic or if patient has serious underlying illness
Source: Vaccinia (smallpox) vaccine: recommendations of the Advisory
Committee on Immunization Practices (ACIP), 2001. MMWR
2001;50(RR10):1-25
Indications for Use of Vaccinia Immunoglobulin
(VIG) for Treatment of Adverse Reactions
Associated With Smallpox Vaccination - II
• Eczema vaccinatum—Indicated for severe
cases
• Progressive vaccinia—Indicated for severe
cases
• Postvaccinial encephalitis — Not effective
Contraindications to Vaccine in
the Absence of Exposure or
Potential Exposure to Smallpox
Contraindications: Pre-Event
• Eczema and atopic dermatitis and other
chronic skin conditions: 28 million in the US
at risk for eczema vaccinatum
[Has the patient had an itchy, scaly rash that lasts
more than 2 weeks and which comes and goes? –
this should be considered as atopic dermatitis]
• Eye disease of the cornea or conjunctiva,
especially if pruritic or inflammatory
Contraindications: Pre-Event
• Immunosuppression (organ transplants,
HIV and cancer): 10 million individuals
(3.6 percent) may be at increased risk for
progressive vaccinia
• ≥2mgm/kg/ day prednisone or
≥20mgm/day for 14 or more days
• Pregnancy
• Any of the previous conditions in a
member of the household
Contraindications: Pre-Event
• Breast feeding because of risk of
inadvertent inoculation
• Hypersensitivity to any of the vaccine
components
• Hypersensitivity to thimerosal
Contraindications: Post Event
• None if a person is exposed
or at potential exposure
Risk of Transmission to Contacts
• Transmission in virtually all cases from
persons who were primary vaccinees
• 16.8 – 20 cases of contact EV per 106
primary vaccinations
• 62% of contacts cases in children < 5
years
• 1.8% of contact cases in persons > 20
years
Source: Neff et al. Contact Vaccinia – Transmission of Vaccinia From
Smallpox Vaccination. JAMA 288;(15) 1901-1905. Oct 16, 2002
Recent Israeli Experience
• Lister strain, considered to have fewer side effects
• Total full reaction among vaccinated – 76 % ( n= 929 )
• Side Effects:
• Fever - 5 %
• Headaches - 28 %
• Muscle pain - 18 %
• Nausea - 12 %
• Fatigue and weakness - 31 % • Shivering - 9 %
• Other - 13 %
• There was one case of suspected encephalitis. The
physicians in that case wanted to do a spinal tap, though
the patient refused
(Israeli Ministry of Health records, 2002)
Efficacy of Post-Exposure Vaccination
• " Vaccination within 3 days of exposure will
completely prevent or significantly modify smallpox
in the vast majority of persons
• Overall, 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.
• Vaccination 4 to 7 days post-exposure still offered
protection to many people, but significantly less
than vaccination before 4 days."
Source: Ray Strikas, MD, CDC. Dec 13, 2002
Q & A: Vaccine and Pregnancy
Q. What if a woman is vaccinated and
then finds out that she is pregnant?
A. Vaccination during pregnancy does
not appear to increase the risk of
miscarriage or stillbirth. Fetal
vaccinia is rare. (Plotkin & Orenstein
p. 85). VIG may be indicated,
contact the HAP.
Q & A: VIG and Immunity
Q. If VIG is administered for a severe
reaction, will this affect my immunity?
A. No, the fact that there is a severe
reaction indicates that there has
been a strong immune response.
The VIG will have no impact on the
immune system and its memory.
Q & A: Steroids
Q. A person who is on steroids should not receive
the vaccine in a pre-event situation because of
immunosuppression. What is the dose of steroid
that should be the cutoff for deciding
immunosuppression or not?
A. 20mg/day prednisone for 14 days
2mg/kg/day prednisone
These are similar to the levels of steroid that are
used for the cutoff for other live virus vaccine such
as MMR or varicella.
Q & A: Re-Vaccination
Q. What is the recommended timeframe
for revaccination on non-takers?
A. If their vaccination site is looked at
on Day 7 -12 & found to be a nontake, re- immunize immediately or
any time thereafter. (Note the patient
receives a new PVN number)
Q & A: Swimming Pools
Q. Can I swim in the pool before the
vaccination scab has dropped off?
A. No, even with a dressing, this is
probably an inappropriate activity
References
Henderson & Moss.Vaccines 3rd Ed. Eds Plotkin &
Orenstein 3rd Ed 1999
CDC. Vaccinia (Smallpox) Vaccine
Recommendations of the Advisory Committee
on Immunization Practices. MMWR 50 No. RR10. June 22, 2001
Neff et al. Contact Vaccinia – Transmission of
Vaccinia From Smallpox Vaccination. JAMA
288;(15) 1901-1905. Oct 16, 2002
www.bt.cdc.gov/agent/smallpox/index.asp
Supplemental
Slides
Generalized Vesicular or Pustular Rash Illness Protocol
Patient with
Acute, Generalized
Vesicular or Pustular Rash Illness
Institute Airborne & Contact Precautions
Alert Infection Control on Admission
Low Risk for Smallpox
(see criteria below)
History and Exam
Highly Suggestive
of Varicella
Diagnosis
Uncertain
Varicella Testing
Optional
Test for VZV
and Other Conditions
as Indicated
Moderate Risk of Smallpox
(see criteria below)
ID and/or Derm Consultation
VZV +/- Other Lab Testing
as indicated
Non-Smallpox
Diagnosis Confirmed
Report Results to Infx Control
High Risk for Smallpox
(see criteria below)
ID and/or Derm Consultation
Alert Infx Control &
Local and State Health Depts
No Diagnosis Made
Ensure Adequacy of Specimen
ID or Derm Consultant
Re-evaluates Patient
Response Team Advises
on Management &
Specimen Collection
Cannot R/O Smallpox
Contact Local/State Health Dept
Testing at CDC
NOT Smallpox
Further Testing
SMALLPOX
Criteria for Determining Risk of Smallpox
High Risk for Smallpox  report immediately
1.Febrile prodrome (see below) AND
2.Classic smallpox lesions (see below and photo at right) AND
3.Lesions in same stage of development (see below)
Moderate Risk for Smallpox  urgent evaluation
1.Febrile prodrome (see below) AND
2.One MAJOR smallpox criterion (see below)
OR
1.Febrile prodrome (see below) AND
2. >4 MINOR smallpox criteria (see below)
Low Risk for Smallpox  manage as clinically indicated
1.No viral prodrome OR
2.Febrile prodrome and <4 MINOR smallpox criteria (no major criteria)
(see below)
Major Smallpox Criteria
FEBRILE PRODROME: occurring 1-4 days before rash onset: fever >102°F and at
least one of the following: prostration, headache, backache, chills, vomiting or
severe abdominal pain. All smallpox patients have a febrile prodrome. The fever may
drop with rash onset.
CLASSIC SMALLPOX LESIONS: deep, firm/hard, round, well-circumscribed; may be
umbilicated or confluent
LESIONS IN SAME STAGE OF DEVELOPMENT: on any one part of the body (e.g.,
the face, or arm) all the lesions are in the same stage of development (i.e. all are
vesicles, or all are pustules)
Minor Smallpox Criteria
Centrifugal distribution: greatest concentration of lesions on face and distal extremities
First lesions on the oral mucosa/palate, face, forearms
Patient appears toxic or moribund
Slow evolution: lesions evolve from macules to papulespustules over days
Lesions on the palms and soles (majority of cases)
Condition
Clinical Clues
Varicella (primary infection with
varicella-zoster virus)
Most common in children <10 years; children usually do not
have a viral prodrome
Disseminated herpes zoster
Prior history of chickenpox; immunocompromised hosts
Impetigo (Streptococcus pyogenes,
Staphylococcus aureus)
Honey-colored crusted plaques with bullae are classic but
may begin as vesicles; regional not disseminated
Drug eruptions and contact dermatitis
Exposure to medications; contact with possible allergens
Erythema multiforme (incl. Stevens
Johnson Sd)
Major form involves mucous membranes and conjunctivae
Enteroviruses incl. Hand, Foot and
Mouth disease
Summer and fall; fever and mild pharyngitis at same time as
rash; distribution of small vesicles on hands, feet and mouth
or disseminated
Disseminated herpes simplex
Lesions indistinguishable from varicella;
immunocompromised host
Scabies; insect bites (incl. fleas)
Pruritis; in scabies, look for burrows (vesicles and nodules
also occur); flea bites are pruritic, patient usually unaware of
flea exposure
Molluscum contagiosum
Healthy afebrile children; HIV+ individuals
Bullous Pemphigoid
Bullous lesions. Positive Nikolski sign.
Secondary syphilis
Rash can mimic many diseases; rash may involve palms and
soles; 95% maculo-papular, may be pustular. Sexually active
persons
Conditions With Vesicular or Pustular Rashes
Laboratory Testing for Varicella:
at least 3 good specimens from each patient
Collect




Direct fluorescent antibody (DFA)—rapid, depends on adequate specimen (see below)
Indirect fluorescent antibody (IFA) —rapid, depends on adequate specimen (see below)
Polymerase chain reaction (PCR)--available in research labs, some tertiary care centers
Serologic testing: an IgG (collected at time of rash) provides evidence of prior varicella, and
makes acute varicella infection unlikely but does not rule out herpes zoster in persons at risk
of dissemination. IgM is not useful for diagnosis.
 VZV culture—results delayed, useful only if processed in-house
 EM (electron microscopy)—can identify herpes viruses
How to Collect a Specimen for DFA or IFA Testing
1.
2.
3.
4.
5.
6.
Unroof (open) vesicle or pustule with a sterile lancet
Swab base of vesicle vigorously with a sterile swab
Smear swab onto 3 areas (or wells) of a microscope slide
Allow slide to air dry
Transport to lab for immediate fixing and staining
VZV positive specimens are seen with varicella (chickenpox) and herpes zoster (shingles)
The hospital lab performs _________________ test
For DFA/IFA , call ________________ (specimen is tested at outside lab)
A suspected case of smallpox is a
public health and medical emergency!
Clinical case definition of smallpox:
an illness with acute onset of fever >101°F followed
by a rash characterized by vesicles or firm pustules in
the same stage of evolution without other apparent
cause.
Report ALL suspected cases (without waiting for lab results) to:
1. Hospital Infection Control ( ) ___-____ or ( ) ___-____ Pager
2. (Local) health department ( ) ___-____ or ( ) ___-____ Pager
3. (State) health department (517) 335-9030 or (517)335-8024
Questions? Centers for Disease Control and Prevention:
(404)639-3532 days; Nights/weekends/holidays: (770) 488-7100