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Clinical Manifestation of<br />

Smallpox<br />

Exposure to the virus is followed by an incubation<br />

period during which people do not have any symptoms<br />

and may feel fine. The incubation period averages<br />

about 12 to 14 days with a range from 7 to 17 days.<br />

During this time people are not contagious and cannot<br />

spread the virus to others. Typically, a two stage illness<br />

will follow. First is the Prodrome stage, lasting from<br />

2 to 4 days. During this stage the person will present<br />

with “flu-like” symptoms including fever, malaise,<br />

head and body aches, and sometimes vomiting. The<br />

fever is usually high, in the range of 101 to 104 degrees<br />

Fahrenheit. During this stage the person is sometimes<br />

contagious. They then move to the next stage of the<br />

disease, the Eruptive stage. A rash emerges first as<br />

small red spots on the tongue and in the mouth.<br />

These spots develop into sores that break open and<br />

spread large amounts of the virus into the mouth and<br />

4, 7 throat.<br />

This is the most contagious time. At this time, a rash<br />

will also appear on the skin, starting on the face and<br />

spreading to the arms and legs and then to the hands<br />

and feet. The rash will usually spread to all parts of<br />

the body within 24 hours. The fever usually breaks<br />

as the skin rash appears and the person may feel<br />

better. Around the third day of the skin rash, the rash<br />

becomes raised bumps. By the fourth day, the bumps<br />

fill with thick, opaque fluid and have a depression<br />

in the center that looks like a bellybutton. (This is<br />

a major distinguishing characteristic of smallpox).<br />

Fever will rise again and stay high until scabs form<br />

over the bumps. The bumps will become pustules,<br />

raised, round and firm to the touch. The pustules then<br />

begin to form a crust and then scab over. The pustules<br />

and scab portion takes approximately 5 days, and the<br />

person remains very contagious during this time. At<br />

this time the scabs begin to fall off, leaving pitted scars.<br />

This takes another 6 to 7 days, and the person remains<br />

contagious. About three weeks after the rash first<br />

appeared the scabs fall off and the person is no longer<br />

contagious.<br />

Transmission<br />

Humans are the only natural reservoirs of Variola<br />

virus. Person-to-person transmission of smallpox<br />

occurs by aerosol droplets expelled from the<br />

oropharynx of infected persons, or by direct contact<br />

with an infected person. The virus can also be spread<br />

through contaminated bedding and clothing. Smallpox<br />

can also be spread through direct contact with infected<br />

bodily fluids. It is not known to be transmitted by<br />

insects or animals.<br />

Diagnosis<br />

Smallpox is most frequently misdiagnosed as varicella,<br />

or chickenpox, which is caused by the herpes virus.<br />

The most effective criteria for distinguishing the<br />

two infections is an examination of the following<br />

characteristics of the lesions:<br />

Time and pattern of appearance<br />

The most obvious distinction between smallpox<br />

and chickenpox is the manner in which the skin<br />

lesions appear. In chickenpox, the lesions occur in<br />

successive “crops.” It is possible to determine several<br />

different stages of lesion maturation and development<br />

at the same time. In smallpox, the lesions appear<br />

simultaneously. All lesions have the same maturation.<br />

Density and location<br />

Chickenpox lesions tend to be denser over the trunk,<br />

while smallpox lesions are denser on the face and<br />

extremities. Smallpox are almost always seen on the<br />

palms and soles of the feet, which is unusual for<br />

chickenpox.<br />

Smallpox can be confirmed in the laboratory by<br />

electron microscopic examination of vesicular<br />

or pustule liquid or scabs. Definitive laboratory<br />

identification and characterization involves growth<br />

of the virus in the cell culture, and characterization<br />

of strains by use of biologic assays, including<br />

polymerase chain reaction, restriction fragment-length<br />

polymorphism analysis and ELISA. Confirmation<br />

using these methods can be accomplished in a few<br />

hours. Notification of the local and state health<br />

department is necessary.<br />

Treatment<br />

Currently there are no known effective antivirals.<br />

Give the person supportive care and antibiotics for<br />

secondary infections.<br />

The discovery of a single suspected case of smallpox<br />

must be treated as an international health emergency<br />

and immediately brought to the attention of national<br />

officials through local and state health authorities.<br />

Post Exposure<br />

Prophylaxis<br />

All contacts must be vaccinated within three to five<br />

days. Contacts include all household members,<br />

patients, staff and visitors to the hospital at the same<br />

time as the smallpox case. 9<br />

Monitor all patient contacts for 17 days, and if one<br />

of the contacts starts showing signs of a fever, they<br />

should be isolated as soon as possible. Patients<br />

become infectious the day before the rash, so conduct<br />

a thorough history of all contacts the day before they<br />

broke out, and monitor all of those contacts.

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