Smallpox: What You as a Health Care

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Smallpox What You as a Health Care Provider
Should Know Sue Royappa, MD
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After an extensive worldwide eradication program,
the last non-laboratory case of smallpox
occurred in 1977 in Somalia. In 1972, routine
smallpox immunization was discontinued in the
U.S. Since 1983, vaccine production has been
halted. Stockpiled vaccine has been used only
for laboratory researchers. There has however
been recent concern that smallpox virus stocks
may be in the hands of bioterrorists. This
concern was heightened by the terrorist attack on
the World Trade Center and the Pentagon on
September 11, 2001. Since most of the population
is now considered nonimmune, there is
considerable debate as to whether smallpox
vaccination should be resumed.
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Historical significance Smallpox is an acute
contagious disease caused by a variola virus.
The name smallpox is derived from the Latin word
for spotted and refers to the raised bumps that
appear on the face and body of an infected
person. A serious and sometimes fatal
infectious disease. No specific treatment for
smallpox disease, only prevention is
vaccination. Believed to have originated over
3,000 years ago in India or Egypt, is one of the
most devastating diseases known to humanity.
Killed as many as 30 of those infected. Between
6580 of survivors were marked with deep pitted
scars (pockmarks), most prominent on the face.
Blindness was another complication. In 18th
century Europe, a third of all reported cases of
blindness was due to smallpox. In 1898, 95 of
adolescent children in Vietnam were pockmarked
and nine-tenths of all blindness was ascribed to
smallpox. As late as the 18th century,
smallpox killed every 10th child born in Sweden
and France. During the same century, every 7th
child born in Russia died from smallpox.
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In some ancient cultures, smallpox was such a
major killer of infants that custom forbade the
naming of a newborn until the infant had caught
the disease and proved it would survive. In
1798, Edward Jenner's demonstrated that
inoculation with cowpox could protect against
smallpox. In the early 1950s 150 years after
the introduction of vaccination an estimated 50
million cases of smallpox occurred in the world
each year, this fell to around 1015 million by
1967 because of vaccination. The disease is
now eradicated after a successful worldwide
vaccination program. The last case of smallpox in
the United States was in 1949. The last naturally
occurring case in the world was in Somalia in
1977. Immunization stopped in many countries,
such as the US, in 1972. In 1979, the WHO
recommended that vaccination against smallpox be
stopped in all countries, the only exception
being researchers working with smallpox and
related viruses. By 1982, routine vaccination had
been officially discontinued in 149 of the 158
member countries of WHO. By 1986, routine
vaccination had ceased in all countries.
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• Smallpox why fear it now?
• After the events of September, 2001 there is
  considerable concern that smallpox might be used
  as an agent of bioterrorism.
• After the virus was delared to have been
  eradicated in 1980, stocks of smallpox virus
  were retained in the U.S. and the former Soviet
  Union.
• There have been reports that before the
  dissolution of the Soviet Union, smallpox was
  being developed there as a weapon of biological
  warfare.
• Concerns that the virus and the expertise to
  propagate a large amount of virus may have fallen
  into non-Russian hands.
• The current U.S. population essentially nonimmune
  to smallpox.
• An aerosol release of smallpox virus would
  disseminate readily.
• Stable in aerosol form.
• Infectious dose is very small.
• As few as 50-100 cases could generate widespread
  panic.

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Factors that fuel this concern -Historically
feared as one of the most serious of
diseases -High case-fatality rates - 30 in the
past -Physically disfiguring -No
treatment -Communicable from person to
person -Virus able to spread throughout the
population unless checked by vaccination and/or
isolation of patients and their close
contacts How real is the threat? How good of a
biological weapon is smallpox?
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About the virus The causative agent, variola
virus, is a member of the genus Orthopoxvirus.
Other members of the genus include cowpox,
camelpox, and monkeypox. Monkeypox virus has
caused the most serious recent human poxvirus
infections. The entire 186,000 base pair genome
of variola virus has been sequenced. Majority of
the genes of the variola virus are closley
related to the vaccinia virus used to vaccinate
against smallpox. Not been able to identify why
variola has such high virulence compared to
vaccinia. Pathogenesis and Pathology The
oropharynx served as the reservoir for virus
spread. Contacts became infected by inhaling the
virus. Multiplication occurred within lymphoid
organs leading to secondary development of
viremia. Virus localized with small dermal blood
vessels produced endothelial swelling and
intraepidermal vesicles. Extension of infection
into sebaceous glands produced pock marks. Virus
infection stimulated cytotoxic T cells,
antibodies and production of interferons. These
responses restricted viral replication and
induced prolonged immunity in patients who
recovered.
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Forms of the disease Smallpox has two main
forms variola major and variola minor. The two
forms showed similar lesions. The disease
follows a milder course in variola minor, which
had a case fatality rate of less than 1 per cent.
The fatality rate of variola major was around
30. Both were caused by the same virus and
difficult to distinguish in cases of mild variola
major. The main distinguishing feature was the
outcome. The rash in variola minor accelerated
rapidly but without severe sequelae. The
entire genome of variola minor strains have not
been sequenced. The analyzed portions show very
high similarity to variola major. Have not
identified the gene, differential expressionof
genes or viral replication that may account
for the differences in mortality. There were
two rare forms of smallpox hemorrhagic and
malignant. Both were invariably fatal. In the
former, the rash was accompanied by hemorrhage
into the mucous membranes and the
skin. Malignant smallpox was characterized by
lesions that did not develop to the pustular
stage but remain soft and flat.
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Clinical Presentation Incubation Period
(duration 7 to 17 days) Not contagious No
symptoms Initial Symptoms (Prodrome) ( 2 to 4
days) Sometimes contagious fever (101 to 104F),
malaise, headach, myalgia, vomiting Early Rash
(4 days) M ost contagious Starts as small red
spots on the tongue and in mouth. Develop into
sores that break open and spread large amounts of
virus. Then a rash begins on face and spreads to
arms and legs. Spreads to all parts of the body
within 24 hours. Fever usually falls and the
person may start to feel better. On third day
rash becomes raised bumps. On fourth day, the
bumps fill with a thick, opaque fluid and often
have a depression in the center,
umbilicated appearance characteristic of
smallpox. Fever often rises again and remains
high until scabs form.
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Pustular Rash (5 days) ContagiousThe bumps
become pustules bumps feel like BB pellets
embedded in the skin Pustules and Scabs ( 5
days) Contagious Pustules begin to form a crust
and then scab By the end of second week after
rash appears, most sores have scabbed
over Resolving Scabs (6 days) Contagious Scabs
begin to fall off, leaving pitted scars Most
scabs will have fallen off three weeks after the
rash appears The person is contagious to others
until all of the scabs have fallen off Scabs
resolved - Not contagious In the past sometimes
confused with chickenpox, a worldwide infection
of children that is seldom lethal. Chickenpox can
be distinguished from smallpox by its much more
superficial lesions, their presence more on the
trunk than on the face and extremities, the
development of successive crops of lesions in the
same area and by the development of fever
concurrently with the rash. Early infection can
sometimes be difficult to distinguish, although
the difference does become apparent within a few
days.
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Infectivity Persons carrying the virus during
the incubation period cannot infect others.
The frequency of infection is highest after
face-to-face contact with a patient after fever
has begun and during the first week of rash, when
the virus is released via the respiratory tract.
Although patients remain infectious until the
last scabs fall off, the large amounts of virus
shed from the skin are not highly infectious.
Exposure to patients in the late stages of the
disease is much less likely to produce infection
in susceptible contacts.
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Transmission Nonimmunized humans universally
susceptible to infection with smallpox virus. No
animal reservoir. Insects play no role in
transmission. Transmission occurs from person
to person by infected aerosols and air droplets,
especially if symptoms include coughing.
Variola virus is relatively stable in the
natural environment. If aerosolized, it retains
its infectivity for at least several hours if not
exposed to sunlight or ultraviolet light. Can
be transmitted via contaminated clothes and
bedding, risk of infection is much lower.
Patients with variola major bed ridden - spread
limited to close contacts in a small vicinity.
Variola minor was so mild that these patients
remained ambulatory and spread the virus far more
widely. Epidemics developed comparatively
slowly. The interval between each generation of
cases was 23 weeks.
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Treatment Vaccine administered up to 4 days
after exposure to the virus, and before the rash
appears, provides protective immunity and can
prevent infection or ameliorate the severity of
the disease. No effective treatment, other than
the management of symptoms, is currently
available. A number of compounds are under
investigation as chemotherapeutic agents. One of
these, Cidofovir, has produced promising results
in laboratory studies. Control It was noted as
early as the 10th century that accidental
exposure to smallpox by a scratch on the skin
reduced the severity of infection. Led to the
practice of variolation in India and China.
Involved intentional administration of pustular
fluids of scabs to uninfected patients. In 1796,
Edward Jenner showed that innoculation with
cowpox virus protected against smallpox and
carried less risk of illness than variolation.
Subsequently vaccinia virus became the basis for
smallpox vaccine.
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In 1959, WHO adopted the global eradication
program with surveillance and contact
vaccination. It was successful because of the
following - Long incubation period which allows
vaccination to modify the course of disease -
Ease of clinical diagnosis - Does not establish
latent or persistent infection - Lack of
reservoir for variola other than humans In 1980,
the WHO declared that smallpox had been
eradicated successfully. Smallpox vaccine was
last used in the in the general population in the
U.S. in 1971. In 1983, the distribution of the
vaccine to civilian population was disontinued
and vaccination production stopped. Response
teams from CDC with special expertise in smallpox
management were immunized in 2001. President
Bush himself has been vaccinated. It has been
given to adult volunteers specifically for
determining if stockpiled vaccine and diluted
vaccine hve retained immunogenicity.
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• Vaccines
• Dryvax, produced by Wyeth is a live-virus
  preparations of infectious vaccinia virus. It
  does not contain smallpox (variola) virus.
• The seed virus held by the WHO Collaborating
  Center for Smallpox Vaccine in the Netherlands.
  This Center also tests batches of the smallpox
  vaccine for potency every five years. Vaccines
  properly stored for as long as 18 years have not
  lost their potency.
• The vaccine is provided as a freeze-dried powder
  in a 100-dose vial, and contains the antibiotics
  polymyxin B, streptomycin, tetracycline and
  neomycin. The diluent used to reconstitute the
  vaccine is 50 percent glycerin and a small amount
  of phenol as a preservative.
• The vaccine is given as an intradermal
  inoculation into the deltoid area by multiple
  punctures with a bifurcated needle.
• Approximately 140,000 vials of vaccine are in
  storage at the CDC, each with doses for 50-60
  people, and an additional 50-100 million doses
  are estimated to exist worldwide. This stock
  cannot be immediately replenished, since all
  vaccine production facilities were dismantled
  after 1980, and renewed vaccine production is
  estimated to require at least 24-36 months.
• In 2000, CDC awarded a contract to Oravax of
  Cambridge, Massachusetts to produce smallpox
  vaccine. Initially producing 40 million doses,
  Oravax anticipates delivery of the first full
  scale production lots in 2004.

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A "take" is defined as presence of a papule,
vesicle, ulcer, or crusted lesion, surrounded by
an area of induration, on days 6-8 after primary
vaccination or revaccination. In the first week,
the bump becomes a large blister, fills with pus,
and begins to drain. During the second week, the
blister begins to dry up and a scab forms. The
scab falls off in the third week, leaving a small
scar. People who are being vaccinated for the
first time have a stronger reaction than those
who are being revaccinated. More than 95 of
primary vaccinees who experience this reaction
will have a serologic response. "Equivocal
reaction" is the term for other reactions that do
not meet these criteria because of suboptimal
vaccination, suboptimal vaccine, or prior
immunity such a reaction should be interpreted
as a "nontake" and implies inadequate immune
response and the need for revaccination, which
can be done at the time that a reaction
interpreted as being a nontake. Since the
vaccine virus is live, it can spread to other
parts of the body, or to other people. The
vaccinia virus may cause rash, fever, and head
and body aches. In certain groups of people
complications from the vaccinia virus can be
severe.
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Duration of protection following vaccination
Smallpox vaccination provides high-level
immunity for 3 to 5 years and decreasing immunity
thereafter for up to ten years. If a person is
vaccinated again later, immunity lasts even
longer. Historically, the vaccine has been
effective in preventing smallpox infection in 95
of those vaccinated. If symptoms appear, they
are milder and mortality is less in vaccinated
than in non-vaccinated persons. Even when
immunity has waned, vaccinated persons shed less
virus and are less likely to transmit the
disease. One study of smallpox following the
importation of cases into Europe and Canada
(19501971) showed that mortality was 52 in
unvaccinated persons, 1.4 in those vaccinated up
to 10 years before exposure, and only 11 in
those vaccinated over 20 years before exposure.
For the age group of 1049 years, the mortality
rate was 49 in the unvaccinated and 4.3 in
those vaccinated 20 years earlier.
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Contraindications Because the vaccinia virus
used in smallpox vaccine can be spread to others
from the vaccine site of an immunized person, the
contraindications below apply to both potential
vaccinees and their household contacts
(household contacts include persons with
prolonged intimate contact with the potential
vaccinee, including the potential for direct
contact with the vaccination site, e.g., sexual
contacts). Eczema or atopic dermatitis and
other acute, chronic, or exfoliative skin
conditions. Should not be vaccinated, even if the
condition is not currently active. At high risk
of developing eczema vaccinatum, a potentially
severe and sometimes fatal complication. Other
acute, chronic, or exfoliative skin conditions
(e.g., burns, impetigo, chicken pox, contact
dermatitis, shingles, herpes, severe acne, severe
diaper dermatitis with extensive areas of denuded
skin, or psoriasis), are at risk for inadvertent
autoinoculation of the affected skin and should
not be vaccinated until the condition(s)
resolves. Diseases or conditions which cause
immunodeficiency or immunosuppression HIV/AIDS,
solid organ or stem cell transplant, generalized
malignancy, leukemia, lymphoma,
agammaglobulinemia or severe autoimmune
disease. At greater risk of developing a serious
adverse reaction resulting from unchecked
replication of the vaccine virus (progressive
vaccinia). HIV testing should be readily
available to all persons considering smallpox
vaccination.
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Treatments which cause immunodeficiency or
immunosuppression If a potential vaccinee or any
of their household contacts are undergoing
treatment with radiation, high-dose
corticosteroids, chemotherapy agents, or organ
transplant medications, they should not be
vaccinated. Pregnancy At risk of fetal
vaccinia. Although this is a very rare condition
(fewer than 50 cases have ever been reported), it
usually results in stillbirth or death of the
infant shortly after delivery. Women who are
vaccinated should be counseled not to become
pregnant during the 4 weeks after vaccination,
and abstinence or highly effective contraceptive
measures should be recommended to reduce the risk
of pregnancy within four weeks of vaccination.
If a pregnant woman is inadvertently vaccinated
or if she becomes pregnant within 4 weeks after
vaccinia vaccination, she should be counseled
regarding the basis of concern for the fetus.
However, vaccination during pregnancy should not
ordinarily be a reason to terminate pregnancy.
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The following additional contraindications apply
only to potential vaccinees Previous allergic
reaction to smallpox vaccine or any of the
vaccines components. Moderate or severe acute
illness is generally a contraindication to
vaccination. Vaccination should be deferred
until the acute illness has resolved. Smallpox
vaccine is contraindicated for children under 12
months of age. Breastfeeding mothers should
not receive the smallpox vaccine. The close
physical contact that occurs during breastfeeding
increases the chance of inadvertent inoculation.
It is not known whether vaccine virus or
antibodies are excreted in human milk. CDC
recommends that persons with known cardiac
disease such as previous myocardial infarction,
angina, congestive heart failure, or
cardiomyopathy not be vaccinated at this time.
This recommendation follows reports of cardiac
events following smallpox vaccinations including
myocardial infarctions and angina without
myocardial infarction. It is unclear whether or
not there is any association between smallpox
vaccination and these cardiac events. This
exclusion may be removed as more information
becomes available. Contraindications to
Vaccination During a Smallpox Emergency During a
smallpox emergency, all contraindications to
vaccination would be reconsidered in the light of
the risk of smallpox exposure.
30
One analysis concluded that 15 of the US
population will be excluded on the basis of
contraindications. An additional 10 will be
excluded because they regularly come into
household or close contact with persons who have
1 of the contraindications. These groups
combined would total 25 of the US
population. Recent information suggests that 25
may even be an underestimate. The military
vaccination program began on 13 December 2002 of
the first 276 persons screened, 102 (37) were
exempted for medical reasons. Approximately
one-half of them were exempted because of a
contraindication in a household contact.
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Adverse Reactions Following Smallpox
Vaccination Smallpox vaccination (vaccinia) is
generally a safe and effective means of
preventing smallpox. However, in a number of
individuals, smallpox vaccination can produce
adverse reactions. Most are totally benign, but
may be alarming in appearance. Some are serious,
but treatable. A few, which rarely occur, are
serious, life threatening and can be fatal.
Severe adverse reactions are more common in
persons receiving primary vaccination compared to
those being revaccinated. Local
Reactions Primary vaccination can produce
swelling and tenderness of regional lymph nodes
beginning 3 to 10 days after vaccination and in
some cases persisting up to 2 to 4 weeks after
the skin lesion has healed. Other normal local
reactions can include local satellite lesions
(which appear similar to the primary lesion),
considerable local edema, what may be confused
with bacterial cellulitis, but is simply intense
inflammation accompanying the vaccination (viral
cellulitis). In a recent study of adult primary
vaccinees, 36 were sufficiently ill to miss
work, school, or recreational activities or to
have trouble sleeping.
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Systemic Reactions In a recent study, 17 of
adult primary vaccinees experienced fever of at
least 100F within two weeks of vaccination 7
had a fever of 101F or more, and 1.4
experienced a fever of 102F or more. Other
expected systemic reactions include malaise,
soreness at the vaccination site, myalgia, local
lymphadenopathy, and intense erythema ringing the
vaccination site. A variety of erythematous or
urticarial rashes occur approximately 10 days
after primary vaccination in one person per 3700
vaccinated. Vaccinees who develop these rashes
are usually afebrile and the rash resolves
spontaneously within 2 to 4 days. Rarely,
bullous erythema multiforme (or Stevens-Johnson
syndrome) occurs.
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Inadvertent Inoculation Successful vaccination
produces a lesion at the vaccination site.
Beginning about four days after vaccination, the
florid site contains high titers of vaccinia
virus. This surface is easily transferred to the
hands and to fomites, especially since itching is
a common part of the local reaction. Accidental
implantation occurs due to transfer of vaccinia
virus from the primary site to other parts of the
body, or to other individuals. This is the most
frequent complication of smallpox vaccination
(529 per million primary vaccinees), accounting
for approximately half of all complications of
primary vaccination and revaccination. Lesions
of inadvertent inoculation can occur anywhere on
the body, but the most common sites are the face,
eyelid, nose, mouth, genitalia, and rectum.
Lesions in eczematous skin, in disrupted skin and
in the eye pose special hazards, as the infection
can be extensive in skin lesions and a threat to
eyesight. Most lesions heal without specific
treatment.
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Generalized Vaccinia Generalized vaccinia
consists of vesicles or pustules appearing on
normal skin distant from the vaccination site.
In the past, it was estimated to occur in 242
per million primary vaccinees. It is believed to
result from a vaccinia viremia with skin
manifestations. Most rashes labeled as
generalized vaccinia produce only minor illness
with little residual damage. The rash is
generally self-limited and usually requires only
supportive therapy. However, patients with
underlying immunosuppressed illnesses may have a
toxic course and require Vaccinia Immune
Globulin.
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Eczema Vaccinatum Eczema vaccinatum is a
localized or systemic spread of vaccinia virus.
In the past, it was estimated to occur in 10-39
per million primary vaccinees. Transfer of
vaccinia virus can occur from autoinoculation or
from contact with a vaccinee whose lesion is in
the florid stages. Individuals with eczema or
atopic dermatitis are at increased risk. Eczema
vaccinatum can occur regardless of whether the
eczema/atopic dermatitis is active at the time of
vaccination. Virus implanted in disrupted skin
(may be at multiple sites) spreads from cell to
cell producing extensive lesions dependent on
extent of abnormal skin. Treatment should
include hospitalization and urgent treatment with
VIG. Mortality has been prevented in patients
treated promptly and adequately. Severe cases
and fatalities have been observed after contact
of recently vaccinated persons with persons who
have active eczema/atopic dermatitis or a history
of eczema/atopic dermatitis.
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Vaccinia Keratitis Vaccinia keratitis results in
lesions of the cornea due to accidental
implantation of vaccinia virus, and is
potentially threatening to eyesight. Symptoms
appear ten days after transfer of vaccinia virus.
Left untreated, considerable corneal scarring
may result as lesion heals resulting in
significant impairment of vision. Topical
antiviral agents are the treatment of choice
therapy should be determined in immediate
consultation with an experienced ophthalmologist.

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Progressive Vaccinia Progressive vaccinia, also
known as vaccinia necrosum, is a severe,
potentially fatal illness characterized by
progressive necrosis in the area of vaccination,
often with metastatic lesions (e.g., lesions at
places other than the vaccination site). In the
past, it was estimated that progressive vaccinia
occurred in approximately 1 to 2 per million
primary vaccinations, and was almost always fatal
before the introduction of VIG and antiviral
agents. Rare in the past, it may be a greater
threat today, given the larger proportion of
susceptible persons in the population and the
greater number with immunocompromise. Nearly all
instances have been in people with defined
cell-mediated immune defect (T-cell deficiency).
Prompt hospitalization and aggressive use of
VIG are required. Massive doses of VIG are
necessary to control viremia. There is no
proven antiviral therapy. Preliminary studies
with cidofovir show some antiviral effect in
vitro studies in animals are pending.
Immediate consultation with the CDC is
recommended to determine if any experimental
antiviral drugs are available.
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Post-Vaccinial Encephalitis A serious
complication, occurred in two main forms. The
first, seen most often in infants under 2 years
of age, had a violent onset, characterized by
convulsions. Recovery was often incomplete,
leaving the patient with cerebral impairment and
paralysis. The second form, seen most often in
children older than 2 years, had an abrupt onset,
with fever, vomiting, headache, and malaise,
followed by such symptoms as loss of
consciousness, amnesia, confusion, restlessness,
convulsions and coma. Encephalitis or
meningoencephalitis following vaccination has
been reported in about 3 to 12 per million
primary vaccinees how many such cases are
coincidental in time and how many are related to
the vaccination itself is impossible to know.
Most cases are believed to result from autoimmune
or allergic reactions rather than direct viral
invasion of the nervous system. In general,
this is a severe disease with high mortality and
morbidity. Approximately 15-25 percent of
affected vaccinees with this complication die,
and 25 develop permanent neurological sequelae.
There is no specific therapy. Supportive care,
anticonvulsants and hospitalization in intensive
care may be required in individual cases. VIG is
not effective and is not recommended.
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Fetal Vaccinia Fetal vaccinia is a rare
complication of smallpox vaccination. Fewer
than 50 cases of fetal vaccinia infection have
been reported, usually after primary vaccination
of the mother in early pregnancy. Fetal
vaccinia usually results in stillbirth or death
of the infant soon after delivery. Smallpox
vaccine is not known to cause congenital
malformations. Death Death resulting from
smallpox vaccination is rare, in the past
approximately 1 to 2 primary vaccinees died per
million vaccinated. Death is most often the
result of postvaccinial encephalitis or
progressive vaccinia.
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Possible Causal Association Between Smallpox
Vaccination and Myopericarditis Data from
recent smallpox vaccinations have been found to
be consistent with a causal association between
vaccination and myopericarditis, although this is
not proven. Persons receiving smallpox vaccine
should be informed that myopericarditis is a
potential complication of smallpox vaccination
and that they should seek medical attention if
they develop chest pain, shortness of breath, or
other symptoms of cardiac disease after
vaccination.
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Frequency of complications The best estimates of
the frequency of these complications come from a
1968 study conducted by the United States
involving over 14 million vaccinated persons.
Altogether nine deaths occurred. Progressive
vaccinia occurred in 11 persons, with 4 deaths.
Eczema vaccinatum was more common, with 74
cases and no deaths. Sixty additional cases of
eczema vaccinatum occurred in contacts of
vaccinated persons, with one death.
Generalized vaccinia occurred in 143 cases, with
no deaths. Encephalitis was observed in 16
persons, with 4 deaths. On the basis of this
study, it was estimated that approximately one
death per million resulted from complications
following primary vaccination and one death per
four million following revaccination.
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Smallpox and bioterrorism Variola virus as an
agent of bioterrorism has been discussed widely.
Although smallpox was a virulent infection,
transmission was not widespread. Index cases
rarely affected more than five others, usually
individuals sharing living quarters. Transmission
intervals were two or three weeks apart, and
new cases would appear in a community over many
months. The difficulty of introducing the virus
into the population and the limited effects of
doing so, make this virus a less than ideal
weapon for bioterrorism. Most public health
authorities currently feel that the chances of a
smallpox outbreak are very small.
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• Proposed Strategies for Immunization
• The major strategies in the face of a
  bioterrrorism threat include
• mass immunization
• voluntary immunization
• ring vaccination or surveillance and
  containment
• Mass immunizations - most effective in preventing
  spread of disease. Bioterrorist unlikely
• to introduce variola into a well- immunized
  population.
• Known serious adverse effects of the vaccine, the
  large number of
• immunocompromised people in the population,
  limited supply of vaccine and VIG,
• mass vaccination of the public is not recommended
  at present.
• Voluntary immunization - allow each individual to
  weigh pros and cons.
• Much of population not familiar with the
  complications of the vaccine.

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• Ring Vaccination - Surveillance and Containment
• The current CDC recommendation is the ring
  vaccination strategy
• isolate patient
• identify and immunize contacts of infected
  individuals as well as their contacts
• strategy based on knowledge that the vaccination
  can prevent or ameliorate disease
• severity if given within 3 - 4 days of initial
  exposure and decrease symptoms if given
• within the first week
• can control a localized outbreak with minimal
  exposure of vulnerable poulations to the
• complications of immunization
• this was the strategy used by WHO to eradicate
  smallpox in the successful worlwide program
• in the 1960s and 1970s

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Management of an outbreak Emphasis must be
placed on preventing epidemic spread Surveillanc
e of smallpox infection is probably easier than
for any other infectious disease because of the
distinctive rash. Patients diagnosed with
smallpox should be physically isolated. All
persons who have or will come into close contact
with them should be vaccinated. Isolation is
essential to break the chain of transmission.
As hospitals have proven to be sites of epidemic
magnification during smallpox outbreaks, patient
isolation at home is advisable where hospitals do
not have isolation facilities Patients who
developed rash before their isolation should be
asked to recount all recent contacts. Contacts
should be vaccinated. If it is not feasible to
vaccinate contacts, they should be placed on
daily fever watch, which should continue up to 18
days from the last day of contact with the case.
If these contacts have two consecutive readings
of 38 degrees centigrade or above, they should be
isolated.
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Infection control in facilities Health care
providers, even if vaccinated, should wear
gloves, caps, gowns, and surgical masks. All
contaminated instruments, excretions, fluids and
other materials should be decontaminated
chemically, by heat or incineration.
Contaminated clothing and bedding, if not
incinerated, should be autoclaved or washed in
hot water containing bleach. Fumigation of
premises may be done with formaldehyde.
Cadavers should be cremated in a properly
designed facility and all persons coming in
contact with them should be vaccinated or at
least placed on daily fever watch. Laboratory
manipulations with infective materials should be
done in high containment facilities at Biosafety
Level IV, authorized only at two laboratories in
the United States and the Russian Federation.
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The Advisory Committee on Immunization Practices
(ACIP) of the CDC has recommended that health
care institutions have teams that include the
following groups of persons 1. Emergency
department staff, including both physicians and
nurses. 2. Intensive care unit staff,
including physicians, and nurses. 3. General
medical unit staff, including internists,
pediatricians, obstetricians, and family
physicians in institutions where these
individuals are the essential providers of
primary medical care. 4. Primary-care house
staff (i.e., selected medical, pediatric,
obstetric, and family physicians). 5.
Medical subspecialists, including infectious
diseases specialists. 6. Infection-control
professionals. 7. Respiratory therapists.
8. Radiology technicians. 9. Security
personnel. 10. Housekeeping
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The U.S. government plans to have national,
state, and local teams of health
care professionals who have been immunized and
trained in all aspects of smallpox investigation
and care. They will be available to go
immediately to the site of a suspected or proven
caseof smallpox. With teams in every state,
approximately 10 to 20,000 carefully screened
individuals will receive the smallpox
vaccine. For the general poulation, ring
vaccination strategy is recommended for
managing those exposed to smallpox. The
development of safer vaccines or susbstantial
evidence that a terrorist threat is imminent
should lead to reevaluation of the current
recommendations.
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Sheet www.who.int/emc/diseases/smallpox/factsheet.
html 3. UPTODATE www.uptodate.com 4. Center for
Civilian Biodefense Strategies www.hopkins-biodefe
nse.org 5. Smallpox vaccine. Committee on
Infectious Diseases. American Academy of
Pediatrics - Pediatrics - 01-OCT-2002 110(4)
841-5. 6. Smallpox its history and reemergence
as a weapon if biological warfare. Ligon BL -
Semin Pediatr Infect Dis - 2001 Jan 12(1)
71-80 7. Smallpox vaccination in 2003 key
information for clinicians Bartlett J - Clin
Infect Dis - 1-Apr-2003 36(7) 883-902
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8. Smallpox looms large - in life and on the
web. Larkin M - Lancet Infect Dis - 2003 Feb
3(2) 114 9. Adverse events occuring after
smallpox vaccination.Lane J - Semin Pediatr
Infect Dis - 2003 Jul 14(3) 189 10. Smallpox
vaccination and adverse reactions. Guidance for
clinicians. Cono J - MMWR Recomm Rep -
21-Feb-2003 52(RR-4) 1-28 11. Smallpox and
smallpox vaccination Neurological
implications.Booss J - Neurology - 22-APR-2003
60(8) 1241-5