SMALLPOX

Outline Introduction Immediately report any suspected or

Epidemiology confirmed cases of smallpox to:
Clinical Features SFDPH Communicable Disease Control
Differential Diagnosis (24/7 Tel: 415-554-2830)
Laboratory Diagnosis - By law, health care providers must report suspected
or confirmed cases of smallpox to their local health
Treatment and Prophylaxis
department immediately [within 1 hr].
Complications and Admission Criteria - SFDPH Communicable Disease Control can
Infection Control facilitate specialized testing and will initiate the public
health response as needed.
Pearls and Pitfalls
References
Also notify your:
• Infection Control Professional
• Clinical Laboratory

INTRODUCTION
Smallpox is caused by variola viruses, which are large, enveloped, single-stranded DNA viruses of
the Poxvirus family and the Orthopoxvirus genus. Variola major strains cause three forms of
disease (ordinary, flat type, and hemorrhagic), whereas variola minor strains cause a less severe
form of smallpox. Vaccination with vaccinia virus, another member of the Orthopoxvirus genus,
protects humans against smallpox because of the high antibody cross-neutralization between
orthopoxviruses.1-4

The Working Group for Civilian Biodefense considers smallpox to be a dangerous potential
biological weapon because of “its case-fatality-rate of 30% or more among unvaccinated persons
and the absence of specific therapy.” Of the potential ways in which smallpox could be used as a
biological weapon, an aerosol release is expected to have the most severe medical and public
health outcomes because of the virus’ stability in aerosol form, low infectious dose, and high rate
of secondary transmission. A single case of smallpox would be a public health emergencey.2

EPIDEMIOLOGY
Smallpox as a Biological Weapon

Smallpox has been used as a biological weapon in the distant past. More recently it has been a
focus of bioweapons research. In the 18th century, British troops in North America gave smallpox-
infected blankets to their enemies, who went on to suffer severe outbreaks of smallpox. Defecting
Russian scientists describe covert Russian operations during the 1970s and 1980s that focused on

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 bioweapons research and development including creation of more virulent smallpox strains and
development of missiles and bombs that could release smallpox.2, 4, 5

Aerosol release of virus (such as into a transportation hub) would likely result in a high number of
cases. Other possibilities include use of "human vectors" (i.e., persons who have been deliberately
infected with smallpox) and use of fomites (e.g., contamination of letters sent through the mail).2, 5

Smallpox is of concern as a biological weapon because:2

• much of the population (80%) is susceptible to infection

• the virus has a low infectious dose and carries a high rate of morbidity and mortality
• a vaccine that lacs significant side effects is not yet available for general use
• experience has shown that introduction of the virus creates havoc and panic

An intentional release of smallpox would have the following characteristics:6

• Clustering in time: Multiple similarly presenting cases of fever and rash in mouth and on
face, arms, and legs generally 4 days after release

Naturally Occurring Smallpox

Reservoirs
The natural reservoir for smallpox was humans with disease; there was no chronic carrier state. In
1980, the World Health Organization (WHO) declared smallpox eradicated from the world and
recommended destruction or transfer all remaining stocks to one of two WHO reference labs, the
Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the former Institute of
Virus Preparations (later transferred to the Vector Institute) in Russia. Since eradication, there is
no natural reservoir for smallpox. Presently, smallpox is only officially found in these designated
WHO reference laboratories.2, 5, 6

Mode of Transmission
Historically, humans were able to be infected in a number of ways:1, 2, 6
• Inhalation of droplet nulcei or aerosols originating from the mouth of smallpox-infected
humans
• Direct contact with skin lesions or infected body fluids of smallpox-infected humans
• Direct contact with contaminated clothing or bed linens

Worldwide occurrence
In 1967, a WHO-led international campaign of mass vaccination, surveillance and outbreak
containment was started in order to eradicate smallpox globally. In 1977, the last community-
acquired smallpox case was reported in Somalia, and in 1978, a laboratory accident in England
caused the last human case.3

Occurrence in the United States

The last case of smallpox in the United States occurred in the Rio Grande Valley of Texas in 1949.
The risk of disease was low enough to end routine vaccination of the US population in 1971.3

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 Vaccination is currently required for most military personnel and is recommended for select health
care and emergency workers, described below. Because of the relative frequency and seriousness
of vaccine-related complications and the low risk of smallpox outbreak in the United States, routine
vaccination is not recommended for the vast majority of healthcare workers or for the general U.S.
population.7

In 2002, the CDC recommended pre-event vaccination for local smallpox response teams,
consisting of public health, medical, nursing, and public safety personnel, who would conduct
investigation and management of initial smallpox cases. As of July 31, 2004, 39,608 healthcare
workers and first responders had been vaccinated nationally.6

CLINICAL FEATURES

Historically, smallpox has been divided into variola major and variola minor based on severity of
clinical disease. Variola major was more common and caused more severe disease relative to
variola minor. The case mortality was 15 to 45% for variola major and 1% for variola minor.

The infectious dose for smallpox is a few virions. The virus typically enters the body via respiratory
or oral mucosa and is carried by macrophages to regional lymph nodes from which a primary
asymptomatic viremia develops on the 3rd or 4th day after infection. The reticuloendothelial organs
are invaded and overwhelmed leading to a secondary viremia around the 8th to 12th day after
infection. Toxemia and fever onset follow. Seven to 17 days following infection, fever, malaise,
and extreme exhaustion begin. A maculopapular rash first presents on the face, mouth, pharynx,
and forearms and spreads to the trunks and legs. The rash progresses to a vesicular and pustular
stage (round and deeply embedded). Scabs form on the 8th day of the rash. Scars are formed
from sebaceous gland destruction and granulation tissue shrinking and fibrosis.1-4, 6

Although most data supports communicability with rash onset, some low level of communicablity is
present prior to rash onset because viral shedding from oral lesions occurs during the 1 to 2 days
of fever preceding rash onset. However, secondary transmission peaks 3 to 6 days after fever
onset (1st week after rash onset), and 91.1% of secondary cases occurred by the 9th day after
fever onset.8 The period of communicability ends when all the scabs have fallen off. Scabs are not
very infectious because the tight binding of the fibrin matrix retains the virions; however secondary
cases have been documented through transmission from direct contact with contaminated clothing
and bedding.1-4, 6

Secondary bacterial infection and other organ involvement are uncommon. Encephalitis is a
possible complication. Mortality is most commonly associated with toxemia of circulating immune
complexes and soluble variola antigens and is seen in the second week of illness. Approximately
30 to 80% of unvaccinated close contacts will develop the disease. In addition, 3.5 to 6
transmissions per smallpox case are estimated.6

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 Variola Major

Variola major is associated with the most severe disease, and presents as:
• ordinary (80% or more of cases: mortality is 30% in unvaccinated and 3% in vaccinated
patients)
• flat (4 to 6% of cases: mortality is 95% in unvaccinated and 66% in vaccinated patients)
• hemorrhagic (2 to 3% of cases: mortality is 99% in unvaccinated and 94% in vaccinated
patients)
• modified (13% of cases and low risk of death)
• variola sine eruptione (30 to 50% of vaccinated contacts of smallpox and low risk of death)

CLINICAL FEATURES: ORDINARY VARIOLA MAJOR.1-4, 6

Incubation Period 10-13 days (range 7-19 days)

• Inhalation of droplet nuclei or aerosols originating from the mouths of

smallpox-infected humans
• Direct contact with skin lesions or infected body fluids of smallpox-infected
Transmission humans
• Direct contact with contaminated clothing or bed linens

Prodromal phase
• 2-4 days of fever, chills, headache, backache, and often GI symptoms

Rash phase
• Enanthem (papules, vesicles, then ulcers) of oropharyngeal mucosa beginning
1 day before skin lesions appear
• First skin lesions ("herald spots") are often on the face
• Lesions spread centrifugally: trunk to proximal extremities to distal extremities
• Palms and soles are usually involved, and truncal rash is usually sparse
Signs and Symptoms • Lesion progression: maculopapular (days 1-2), vesicular (days 3-5), pustular
(days 7-14)
• Vesicles and pustules are frequently umbilicated
• Pustules can be like small, embedded hard balls or “shotty”
• Lesions tend to progress at same rate
• Lesions may be discrete, semiconfluent, or confluent
• Lesions are typically painful and cause pitted scars as they heal
• Lesions gradually scab over during days 13-18

• Viral bronchitis or pneumonitis

• Third spacing of fluid with resulting electrolyte and renal abnormalities
• Skin desquamation
• Secondary bacterial infection, particularly skin and pulmonary
Progression and • Spontaneous abortion, stillbirth
Complications • Rarely: blindness, keratitis, corneal ulceration, encephalitis, osteomyelitis or
arthritis, orchitis
• Death may occur during 2nd week of illness, from high-level viremia and
circulating immune complexes

Laboratory Findings • Lymphocytopenia and/or granulocytopenia

GI, gastrointestinal

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 Other forms of smallpox caused by variola major infection include:

Flat-type smallpox (also known as malignant smallpox) occurred in about 4 to 6% of cases

and more frequently in children. It is associated with a late, deficient cellular immune response. It
is characterized by a short incubation period, prostrating prodromal illness, severe systemic toxicity
and high mortality (90-97%). The lesions do not progress to the pustular stage, instead remaining
soft, velvety and flattened. If the patient survives, the lesions will resolve by desquamation
without scabs or scarring.

Hemorrhagic smallpox occurred in about 2 to 3% of cases. Pregnant women are highly

susceptible. Similar to flat-type smallpox, it is associated with a defective immune response. It is
characterized by a short incubation period, prostrating prodromal illness, severe systemic toxicity,
and high mortality (96%). The rash begins as a dusky erythema, followed by extensive petechiae,
mucosal hemorrhage, and intense toxemia. Thrombocytopenia and coagulopathy may be present.
These patients usually died during week 1 of illness, often before the development of the typical
pox lesions.

Modified smallpox occurred in about 13% of cases. It occurred in persons with some immunity.
The pre-eruptive illness is typical in duration and severity as ordinary smallpox; however, during
the eruption, fever is absent and the skin lesions are superficial, pleomorphic, fewer in number,
and evolve rapidly.

Variola sine eruption occurred in about 30 to 50% of vaccinated contacts of smallpox cases. It is
characterized by a sudden onset of fever, headache, occasional backache which resolves within 48
hours, influenza-like symptoms and no rash.

Variola Minor

Variola minor, caused by different strains of variola, is a milder form of smallpox. Compared with
variola major, there are milder constitutional symptoms, discrete lesions that evolve a bit more
rapidly, lower rates of hemorrhagic disease, and only rare fatal outcomes (<1%). The illness may
be difficult to distinguish clinically from modified smallpox and variola without eruption. In the
1890s, variola minor spread from South Africa to Florida. In the early 1900s, variola minor
became prevalent in the United States, Latin America, and Europe.

DIFFERENTIAL DIAGNOSIS

The characteristic features of smallpox need to be differentiated from other illnesses that present
with vesicular or pustular rash. One disease that could be confused with smallpox is chickenpox.
These may be differentiated clinically, as follows:

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 CLINICAL DIFFERENTIATION OF VARIOLA VS. VARICELLA9
Feature Variola Varicella

• Duration: 2-4 days • Commonly does not occur

Prodrome • Fever, chills, headache, backache, often • If present, mild symptoms and duration
GI symptoms of 1 day

• Centrifugal: more dense on face and • Centripetal: more dense on trunk

Rash distal extremities • Spares palms and soles
Distribution • Frequently involves palms and soles • Back and abdomen equally involved
• More involvement of back than abdomen

• Usually appear on oropharyngeal mucosa • Lesions appear in crops

first, then all over within 1-2 days • At any point in time, crops of lesions are
• Progress at same rate; at any point in at different stages of evolution
Lesion time, lesions are at same stage of • Lesions progress quickly (1-2 days) from
Evolution evolution macules to papules to vesicles to scabs
• Lesions progress slowly (7-14 days) from
macules to papules to vesicles to
pustules to scabs

• May be semiconfluent or confluent • Usually discrete

Lesion • Deep • Superficial
Attributes • May be umbilicated • Rarely found of palms and soles
• Often painful; pruritic only as scabs • Do not umbilicate or dimple
• Typically painless; intensely pruritic
GI, gastrointestinal

Monkeypox is another disease that could be confused with smallpox. In 2003, an outbreak of
monkeypox, associated with prarie dog contact, took place in the midwestern United States.
Monkeypox in humans presents similarly to ordinary smallpox. However, monkeypox is milder and
has prominent lymphadenopathy and a shorter duration of rash.

The CDC has outlined criteria for determining the risk of smallpox when evaluating patients with
generalized vesicular or pustular rash:9, 10

Risk of Smallpox in Patients with Generalized Vesicular or Pustular Rash

All three major criteria present:

a) Febrile prodrome 1-4 days before rash onset, with fever >101°F, plus 1 or more of the
following: prostration, headache, backache, chills, vomiting, severe abdominal pain

High b) Classic smallpox lesions present (vesicles or pustules that are deep-seated, firm or hard,
round, and well-circumscribed; sharply raised and feel like BB pellets under the skin; may
become umbilicated or confluent as they evolve)

c) Lesions on any one part of the body are in the same stage of development

Moderate Febrile prodrome as in (a) above, plus either (b) or (c) above

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 OR

Febrile prodrome as in (a) above, plus at least four of the following minor criteria:
• Centrifugal distribution
• First lesions appeared on the oral mucosa/palate, face, or forearms
• Patient appears toxic or moribund
• Slow evolution of lesions from macules to papules to pustules over several days
• Lesions on the palms and soles

No viral prodrome
Low OR
Febrile prodrome as in (a) above, plus < 4 minor criteria above

Additional considerations in the differential diagnosis of smallpox include:

Macular/papular stage

• measles • rubella
• scarlet fever

Vesicular/pustular stage:
• disseminated herpes zoster • bullous pemphigoid
• disseminated herpes simplex • impetigo (Streptococcus, Staphylococcus)
• Mmolluscum contagiosum • human monkey pox

Either stage:
• erythema multiforme major • chickenpox
- (Stevens-Johnson syndrome) • contact dermatitis
• miscellaneous drug eruptions • generalized vaccinia
• secondary syphilis • acne
• enteroviral infection (hand, foot & • scabies/insect bites
mouth disease)

Hemorrhagic smallpox may resemble:

• meningococcemia
• rickettsial infections
• Gram-negative septicemia

Flat-type smallpox may resemble:

• hemorrhagic chickenpox

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LABORATORY DIAGNOSIS
The diagnosis of smallpox requires a high index of
If you are testing or considering testing for
suspicion because the disease has been eradicated
smallpox, you should:
and its clinical presentation is similar to other pox
viruses. Routine laboratory findings for specific ƒ IMMEDIATELY notify
clinical presentations of smallpox are listed in the SFDPH Communicable Disease Control
clinical features table. Radiographic findings do (24/7 Tel: 415-554-2830).
not assist in identification of smallpox. SFDPH can authorize and facilitate testing, and
will initiate the public health response as needed.

Diagnosis of smallpox will be clinical initially, but ƒ Inform your lab that smallpox is under
followed by laboratory confirmation. Once suspicion.
smallpox has been confirmed in a geographic
area, additional cases can be diagnosed clinically, and specimen testing can be reserved for specific
cases in which the clinical presentation is unclear or to assist with law enforcement activities.

Clinicians should use the CDC-developed tools to assess the likelihood that patients with acute
generalized vesicular or pustular rash illnesses have smallpox.9 CDC has also developed algorithms for
laboratory evaluation of suspect smallpox cases based on the likelihood of disease.10 If a patient is
determined to be at high risk for smallpox, clinicians should call their local public health authorities
immediately and obtain photos of the patient. Public health will provide guidance on specimen
collection and packaging and will facilitate transport of specimens to the appropriate public health
laboratory.

Multiple tests will be used to evaluate for smallpox. Polymerase chain reaction (PCR) testing will be an
important method; however, other methods will also be used including: electron microscopic
examination of vesicular or pustular fluid or scabs, direct examination of vesicular or pustular material
looking for inclusion bodies (Guarnieri’s bodies), culture on egg chorioallantoic membrane, tissue
culture, strain analysis with a restriction fragment length polymorphism assay, and serology.
Definitive laboratory identification and characterization of the variola virus requires several days.

TREATMENT AND PROPHYLAXIS

These recommendations are current as of this document date. SFDPH will provide periodic updates as needed
and situational guidance in response to events (www.sfcdcp.org).

Treatment
The management of confirmed or suspected cases of smallpox consists of supportive care, with careful
attention to electrolyte and volume status, and ventilatory and hemodynamic support. General
supportive measures include ensuring adequate fluid intake (difficult because of the enanthem),
1-4, 6
alleviation of pain and fever, and keeping skin lesions clean to prevent bacterial superinfection.

Currently there are no FDA approved antiviral agents with proven activity against smallpox in humans.

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Antiviral agents that have shown some activity in vitro against poxviruses may be available from the
CDC under an investigational protocol. ST-246 is a novel agent that is currently undergoing safety and
efficacy testing.6, 11 Additionally, cidofovir, a nucleoside analogue DNA polymerase inhibitor, might be
useful if administered within 1-2 days after exposure; however, there is no evidence that it would be
more effective than vaccination, and it has to be administered intravenously and causes renal toxicity.

Immunity from prior vaccination

Protection from smallpox is estimated to last between 11.7 to 28.4 years after primary vaccination
and longer for variola minor than for variola major. Those who were previously vaccinated may retain
some protection that could decrease the severity of the disease and allow for greater mobility thereby
complicating public health response.12

Postexposure prophylaxis
Postexposure prophylaxis for smallpox is the administration of vaccinia vaccine after suspected
exposure to smallpox has occurred but before symptoms are present. Immunity generally develops
within 8 to 11 days after vaccination with vaccinia virus. Because the incubation period for smallpox
averages about 12 days, vaccination within 4 days may confer some immunity to exposed persons and
reduce the likelihood of a fatal outcome. Postexposure vaccination may be particularly important for
those vaccinated in the past, provided that revaccination is able to boost the anamnestic immune
response. In addition to vaccination, exposed persons should be monitored for symptoms.
Temperature should be checked once a day, preferably in evening, for 17 days after exposure for
fever (over 38°C).2-4, 6, 7

If a case or cases of smallpox occur, public health authorities will conduct surveillance and implement
containment strategies. Ring vaccination will be important and includes identification of contacts of
cases and provision of prophylaxis and guidance on monitoring for symptoms. Large-scale voluntary
vaccination may be offered to low-risk populations to supplement and address public concerns.

Vaccine Supply, Administration, and Efficacy

The smallpox vaccine used in the United States (formerly Dryvax, now ACAM2000) is a lyophilized
(freeze-dried) preparation of live attenuated vaccinia virus, an Orthopoxvirus closely related to
cowpox that induces antibodies that are protective against smallpox. The ACAM2000 uses vaccinia
virus derived from the Dryvax vaccine via plaque purification cloning. The virus is then grown in
African green monkey (Vero) cells. The ACAM2000 preparation also contains HEPES, human serum
albumin, mannitol and trace amounts of neomycin and polymixin B. The diluent contains glycerin and
a phenol preservative.13

Production of the Dryvax vaccine stopped in the 1980s. Acambis currently makes the ACAM2000
vaccine which received FDA approval in September 2007. By that time 192.5 million doses of
ACAM2000 were already in the United States stockpile. All lots of Dryvax vaccine expired February 20,
2008, and were destroyed by March 31, 2008.6, 14

Technique. The Dryvax vaccine should be administered by trained, vaccinated personnel using a
bifurcated needle that is stroked against the skin until blood appears. Vaccinees are instructed to

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keep the site dry and covered, to avoid touching the site, and to thoroughly launder or carefully
discard any materials that come into contact with the site. Should smallpox vaccination be
deemed necessary, it will be coordinated by local, state and federal health agencies. For
additional information on vaccine administration, see
7
http://www.bt.cdc.gov/agent/smallpox/vaccination.

Vaccine Contraindications and Complications

The ACAM2000 and Dryvax vaccines have similar safety profiles.14 Both have serious complications.
Likelihood of adverse effects is 3 to 4-fold higher in infants and in primary recipients. Based on the
U.S. Vaccine Adverse Events Reporting System of recently vaccinated people, there was a rate of 26.4
deaths per 10,000 vaccinees. Adverse events included the following: 33% cardiac, 25% nonspecific
chest pain, 21% neurological, 14% infection, 3% malignancy, 3% pulmonary (noninfectious), and 1%
normal vaccination response.13, 15, 16

Vaccination during the pre-exposure period is contraindicated for certain persons. During a
smallpox emergency, however, all contraindications would be reviewed in the context of
the risk of smallpox exposure, and updated recommendations would be issued by public
health authorities. Current contraindications to vaccination are as follows (see
www.bt.cdc.gov/agent/smallpox/vaccination for further description):7, 13

• past or present eczema or atopic dermatitis (risk of eczema vaccinatum)

• other acute or chronic exfoliative skin conditions (e.g. burns, impetigo, chicken pox,
contact dermatitis, shingles, herpes, severe acne, psoriasis), until the condition resolves
• immunodeficiency states, due to disease or treatment of disease
• pregnancy (vaccination may offer partial protection for mother, but increases risk of fetal
vaccinia)
• breastfeeding
• hypersensitivity to vaccine components
• under 18 years of age in nonemergency situations
• having a household contact who is immunodeficient, who has past or present eczema or
atopic dermatitis, or who has an acute, chronic, or exfoliative skin condition
• physician-diagnosed cardiac disease, or 3 or more major risk factors for cardiac disease

Well-documented adverse reactions to vaccination are listed below:1, 2, 7, 13

• tenderness, erythema, or other localized reactions at the injection site

• systemic symptoms of fever, malaise, myalgias, local lymphadenopathy
• dermatologic reactions, including erythema multiforme and Stevens-Johnson syndrome,
urticaria, exanthems, contact dermatitis, and erythematous papules
• secondary bacterial infections at injection site
• focal and generalized suppurative folliculitis (without evidence of viral infection; may be
mistaken for generalized vaccinia)
• inadvertent autoinoculation of another body site (most common sites are face, eyelid,
nose, mouth, genitalia, rectum)
• generalized vaccinia: vesicles or pustules appearing distant from the vaccination site

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 • eczema vaccinatum: localized or dissemination of vaccinia virus; usually mild but may be
severe and fatal
• vaccinia keratitis
• progressive vaccinia: progressive necrosis in vaccination area, often with metastatic sites;
can be severe and fatal
• postvaccinial encephalitis
• fetal vaccinia: occurs when mother is vaccinated during during pregnancy; usually results
in premature birth or miscarriage
• myopericarditis, identified among military personnel vaccinated between December 2002
and December 2003
• death: 1.1 deaths per 1 million primary vaccine recipients
• contact vaccinia: transmission of vaccinia virus from newly vaccinated persons to
susceptible unvaccinated contacts

The primary therapy for adverse reactions to smallpox vaccination is vaccinia immunoglobulin
(VIG).7 However VIG is contraindicated in vaccinia keratitis and provides no benefit in
postvaccinial encephalitis. VIG is manufactured from the plasma of persons vaccinated with
vaccinia vaccine. An intravenous preparation (VIGIV) was recently licensed by the FDA.17 Cidofovir
and topical ophthalmic antiviral agents are also recommended by some experts.7 Cidofovir use
requires an Investigational New Drug (IND) protocol, and topical ophthalmic agent use is off-label.

COMPLICATIONS AND ADMISSION CRITERIA

Before smallpox was eradicated worldwide, viral bronchitis and pneumonitis were the most
frequent complications of ordinary-type smallpox. Cutaneous complications included
desquamation, massive subcutaneous fluid accumulation with electrolyte abnormalities and renal
failure, or, less commonly, secondary bacterial infection of smallpox lesions. Infrequently,
smallpox patients experienced encephalitis, osteomyelitis, corneal ulceration, or ocular keratitis.
Ordinary-type smallpox with confluent lesions, rather than discrete lesions, carried a much higher
risk of massive exfoliation, tissue destruction, bacterial sepsis, and death. Hemorrhagic-type and
flat-type smallpox were nearly always fatal.1-4, 6

Many patients do not require hospitalization. Those with discrete lesions, nonhemorrhagic and non-
flat-type, are less likely to become critically ill or require much supportive care and can be more
easily managed outside the hospital. These people should be isolated and monitored at home or in
a nonhospital facility, and smallpox vaccination should be provided to caregivers and household
members. Patients with evidence of severe disease or presentations that suggest progression to
severe disease is likely should be considered for admission to a negative-pressure environment
with strict maintenance of Airborne Precautions.2, 6

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INFECTION CONTROL
These recommendations are current as of this document date. SFDPH will provide periodic updates as needed
and situational guidance in response to events (www.sfcdcp.org).

Clinicians should notify local public health authorities, their institution’s infection control
professional, and their laboratory of any suspected smallpox cases. Public health authorities may
conduct epidemiological investigations and will implement disease control interventions to protect
the public. Infection control professionals will implement infection control precautions within the
healthcare setting. Laboratory personnel should take appropriate safety precautions.

Smallpox is transmissible from person to person by exposure to respiratory secretions and by

direct contact with pox lesions and fomites. Airborne and Contact Precautions in addition to
Standard Precautions should be implemented for patients with suspected smallpox and until all
scabs have separated. Healthcare workers caring for patients with suspected smallpox should be
vaccinated immediately.18, 19

Decontamination
Survival of the virus in the environment is inversely proportional to temperature and humidity. All
bedding and clothing of smallpox patients should be minimally handled to prevent re-aerosolization
and autoclaved or laundered in hot water with bleach. Standard disinfection and sterilization
methods are deemed to be adequate for medical equipment used with smallpox patients and
cleaning surfaces and rooms potentially contaminated with the virus. Airspace decontamination
(fumigation) is not required.2, 19

PEARLS AND PITFALLS

1. The CDC has developed a number of clinical diagnostic tools to assist with the visual
recognition, differential diagnosis, and initial management of suspected smallpox.
20
These resources are available at: http://www.bt.cdc.gov/agent/smallpox/index.asp.

2. Hemorrhagic smallpox is rare but can be confused with invasive meningococcal

disease, rickettsial infections, or gram-negative sepsis because of the patient’s ill
appearance, petechial and purpuric lesions, and hemorrhagic manifestations.

3. Smallpox is most often transmitted through direct contact with respiratory droplets as
a result of close (within 2 meters) or face-to-face contact. Viruses can also travel over
greater distances as airborne particles, particularly in cases with coughing.
Transmission has occasionally been linked to fomites carried on clothing or bedding
that has been contaminated by dried respiratory secretions or draining skin lesions.

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 4. Since 2003, many health departments have established smallpox preparedness teams
consisting of providers who have been pre-vaccinated against smallpox who can
asssist with the response to a suspected case of smallpox.

REFERENCES

1. Damon I. Orthopoxviruses: Vaccinia (Smallpox Vaccine), Variola (Smallpox),

Monkeypox, and Cowpox. In: Mandel GL, Bennett JE, Dolin R, eds. Principles and
practice of infectious diseases. 6 ed. New York: Churchill Livingstone; 2005:1742-1751.
2. Henderson DA, Inglesby TV, Bartlett JG, et al. Smallpox as a biological weapon:
medical and public health management. Working Group on Civilian Biodefense. Jama.
Jun 9 1999;281(22):2127-2137.
3. Breman JG, Henderson DA. Diagnosis and management of smallpox. N Engl J Med. Apr
25 2002;346(17):1300-1308.
4. Moore ZS, Seward JF, Lane JM. Smallpox. Lancet. Feb 4 2006;367(9508):425-435.
5. Rotz LD, Cono J, Damon I. History of Smallpox and Bioterrorism. In: Mandel GL,
Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. 6 ed. New York:
Churchill Livingstone; 2005:3612-3617.
6. CIDRAP. Smallpox: Current, comprehensive information on pathogenesis, microbiology,
epidemiology, diagnosis, treatment, and prophylaxis. Center for Infectious Disease
Research and Policy, University of Minnesota. Available at:
http://www.cidrap.umn.edu/cidrap/content/bt/smallpox/biofacts/smllpx-summary.html.
7. CDC. Smallpox Vaccination, Information for Health Professionals. Centers for Disease
Control and Prevention. Available at: www.bt.cdc.gov/agent/smallpox/vaccination.
8. Nishiura H, Eichner M. Infectiousness of smallpox relative to disease age: estimates
based on transmission network and incubation period. Epidemiol Infect. Oct
2007;135(7):1145-1150.
9. CDC. Smallpox: Diagnosis/Evaluation. Centers for Disease Control and Prevention.
Available at: http://www.bt.cdc.gov/agent/smallpox/diagnosis/.
10. CDC. Acute, Generalized Vesicular or Pustular Rash Illness Testing Protocol in the
United States. Centers for Disease Control and Prevention. November 14. Available at:
http://emergency.cdc.gov/agent/smallpox/diagnosis/pdf/poxalgorithm11-14-07.pdf.
11. Jordan R, Tien D, Bolken TC, et al. Single-dose safety and pharmacokinetics of ST-246,
a novel orthopoxvirus egress inhibitor. Antimicrob Agents Chemother. May
2008;52(5):1721-1727.
12. Nishiura H, Schwehm M, Eichner M. Still protected against smallpox? Estimation of the
duration of vaccine-induced immunity against smallpox. Epidemiology. Sep
2006;17(5):576-581.
13. FDA. Produce Approval Information: Smallpox (Vaccinia) vaccine. U.S. Food and Drug
Administration. August 31. Available at:
http://www.fda.gov/cber/products/acam2000.htm.
14. CDC. Notice to Readers: Newly Licensed Smallpox Vaccine to Replace Old Smallpox
Vaccine. MMWR. February 29 2008;57(08):207-208.

S.F. Dept Public Health – Infectious Disease Emergencies SMALLPOX, July 2008 Page 13/14
15. Casey CG, Iskander JK, Roper MH, et al. Adverse events associated with smallpox
vaccination in the United States, January-October 2003. Jama. Dec 7 2005;294(21):2734-
2743.
16. Sejvar JJ, Labutta RJ, Chapman LE, Grabenstein JD, Iskander J, Lane JM. Neurologic
adverse events associated with smallpox vaccination in the United States, 2002-2004.
Jama. Dec 7 2005;294(21):2744-2750.
17. FDA. FDA approves new plasma-derived product to treat complications of smallpox
vaccination. U.S. Food and Drug Administration. February 18. Available at:
http://www.fda.gov/bbs/topics/ANSWERS/2005/ANS01341.html.
18. CDC. Guide F: Environmental Control of Smallpox Virus, Smallpox Response Plan.
Centers for Control and Prevention. March 20. Available at:
www.bt.cdc.gov/agent/smallpox/response-plan/files/guide-f.doc.
19. Siegel JD, Rhinehart E, Jackson M, Chiarello L, HICPAC. Guideline for Isolation
Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings, 2007.
Centers for Disease Control and Prevention. Available at:
http://www.cdc.gov/ncidod/dhqp/gl_isolation.html.
20. CDC. Smallpox. Centers for Disease Control and Preventino. Available at:
http://www.bt.cdc.gov/agent/smallpox/index.asp.

S.F. Dept Public Health – Infectious Disease Emergencies SMALLPOX, July 2008 Page 14/14