Transcript No Slide Title

Smallpox: What You as a Health Care
Provider Should Know
Sue Royappa, MD
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.
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 65–80% 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.
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 10–15 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.
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.
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?
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.
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.
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.
Pustular Rash (5 days) Contagious
The 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.
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.
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 2–3 weeks.
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.
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.
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.
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.
Day(s) after
vaccination
Event and/or lesion
0
Vaccination
3 4
Papule
5 6
Vesicle with or without erythema
8 9
Pustule
12
Crust forms and becomes a scab
17 21
Scab detaches and leaves a scar
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 (1950–
1971) 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 10–49 years, the mortality rate was 49% in the unvaccinated
and 4.3% in those vaccinated 20 years earlier.
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.
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.
The following additional contraindications apply only to potential vaccinees:
Previous allergic reaction to smallpox vaccine or any of the vaccine’s 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.
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.
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.
Systemic Reactions
In a recent study, 17% of adult primary vaccinees experienced fever of at least 100°F within
two weeks of vaccination; 7% had a fever of 101°F or more, and 1.4% experienced a fever
of 102°F 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
Management of an outbreak

Emphasis must be placed on preventing epidemic spread

Surveillance 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.
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.
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
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.
Group to be vaccinated
Selected members of the armed
forces and personnel who serve in
high-risk parts of the world
Approximate
no. of
persons
500,000
Selected personnel from the US State
Department who serve overseas
Public health response and health
care teams
Other medical care providers and first
responders
General public
Status of
vaccination
Mandatory
Time of
vaccination
Program
phase
Initiated 13 Dec
2002
I
Voluntary
440,000
Voluntary
10,000,000
Voluntary
Not recommended at present; would
be administered under oversight of a
clinical trial
I
Late January
2003
I
II
Possibly in late
2003 or 2004
III
References
1. CDC Smallpox Home
www.bt.cdc.gov/agent/smallpox/index.asp
2. WHO Smallpox Fact Sheet
www.who.int/emc/diseases/smallpox/factsheet.html
3. UPTODATE
www.uptodate.com
4. Center for Civilian Biodefense Strategies
www.hopkins-biodefense.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
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