Smallpox Vaccination
History of Vaccination in the US
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Before 1972, smallpox vaccination
required for all children at age 1 year
Most states required smallpox
vaccination before school entry
Vaccine
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DryVax©, a lyophilized, live vaccinia virus
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Store at -17oC to -20oC (-4 to - 1oF)
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Re-constituted store 30 days at 2–8oC (36 – 46oF)
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Contains
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polymyxin B sulfate
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dihydrostreptomycin sulfate
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chlortetracycline hydrochloride
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neomycin sulfate
Aventis vaccine kept for emergencies
Supply of Vaccine
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(12/5/2002)
Existing Supply:

Dryvax: 15 million doses (2.7 million doses

Aventis Pasteur: 85 million doses
are approved for distribution as a licensed
vaccine)
In Production:
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Acam 1000: 54 million doses
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Acam 2000: 155 million doses
Strains of Vaccinia
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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
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Neutralizing and HI antibodies appear about 10
days after vaccination
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>95% of primary vaccinees have antibody titres
≥ 1:10
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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
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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

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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
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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
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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
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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
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Day 12 +
Pustules break down
and crust over
This is a major
reaction – a POSITIVE
TAKE
Normal Primary Vaccination
Day 14
Normal Primary Vaccination
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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%
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Swelling of regional lymph nodes 25 -50%
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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
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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
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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 revaccinees
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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
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Small area of erythema
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Possibly a small pustule
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Should be re-vaccinated
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After 2 unsuccessful re-vaccinations seek
consultation
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Could result from
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residual immunity or
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reaction to vaccine components rather than a
viral replication –
but cannot distinguish between the two
Equivocal reaction - Allergic
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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
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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
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Usually occur about 7 days after
vaccination
These are not the normal reactions to a
smallpox vaccination
Can be minimised by careful screening of
vaccinees for contraindications
Serious Adverse Events
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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 ►
◄ Accidential 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
† Excludes contact cases
All
doses
Primary
doses
1.1
0.8
8.9
13.6
0.6
2.9
0.9
10.4
25.4
1.1
†† Source: From N. Engl J Med, 1969; 281: 1201-1208
Treatment for Serious Adverse
Reactions
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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
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Contains thimerosal
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Dosage:
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Usual dosage 0.6ml/kg IM dose may be divided
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For severe cases 1 – 10 ml/kg
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700 doses of IM VIG are available now
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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
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Inadvertent inoculation of other body sites
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— 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
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Eczema vaccinatum—Indicated for severe cases
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Progressive vaccinia—Indicated for severe cases
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Postvaccinial encephalitis — Not effective
Contraindications to Vaccine in
the Absence of Exposure or
Potential Exposure to Smallpox
Contraindications: Pre-Event
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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]
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Eye disease of the cornea or conjunctiva,
especially if pruritic or inflammatory
Contraindications: Pre-Event
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Immunosuppression (organ transplants,
HIV and cancer): 10 million individuals
(3.6 percent) may be at increased risk for
progressive vaccinia
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≥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
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Breast feeding because of risk of
inadvertent inoculation
Hypersensitivity to any of the vaccine
components
Hypersensitivity to thimerosal
Contraindications: Post Event
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None if a person is exposed or
at potential exposure
Risk of Transmission to Contacts
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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
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Lister strain, considered to have fewer side effects
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Total full reaction among vaccinated – 76 % ( n= 929 )
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Side Effects:
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Fever - 5 %
Muscle pain - 18 %
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Fatigue and weakness - 31 %
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Other - 13 % .
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Headaches - 28 %
Nausea - 12 %
Shivering - 9 %
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
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" 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
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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
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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
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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 vaccines
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 non-take, reimmunize 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. RR-10.
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 Cofirmed
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 SMALLPOXCRITERIA
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: Collect at least 3 good specimens from each patient
 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