Clinical Overview

The poxviruses (of the family Poxviridae) are a family of large, enveloped deoxyribonucleic acid (DNA) viruses. The most notorious poxvirus is variola, the causative agent of smallpox. Smallpox was an important cause of morbidity and mortality until recent times. Since the host range of the variola virus is confined to humans, aggressive case identification and contact vaccination were ultimately successful in controlling the disease. The last occurrence of endemic smallpox was in Somalia in 1977 and the last human cases were laboratory-acquired infections in 1978.

The discontinuation of routine vaccination has rendered civilian and military populations more susceptible to a disease that is not only infectious by aerosol, but also infamous for its devastating morbidity and mortality. Since 1983, there have existed two WHO-approved and inspected repositories of variola virus: the CDC in the United States and Vector Laboratories in Russia. Despite the promise of variola virus’ extinction as a biological entity, the prospect of surreptitious weaponization of smallpox remains vexing.

Variola virus is highly stable and retains its infectivity for long periods outside the host. It is infectious by aerosol with an infectivity rate of 30 percent. Variola major carries a fatality rate of 30 percent while variola minor is only 1 percent fatal.

Persons who recovered from smallpox possessed long-lasting immunity, although a second attack could occur in 1 in 1,000.

Clinical Presentation

On natural exposure to aerosolized virus, variola travels from the upper or the lower respiratory tract to regional lymph nodes, where it replicates and gives rise to viremia, which is followed soon thereafter by a rash. The incubation period of smallpox averages 12 days and contacts are quarantined for a minimum of 16 -17 days following exposure. Patients with smallpox are infectious from the time of onset of their eruptive exanthem, most commonly from days 3 through 6 after onset of fever. Clinical manifestations begin acutely with malaise, fever, rigors, vomiting, headache and backache; 15 percent of patients develop delirium.

Two to 3 days later, an enanthem appears concomitantly with a discrete rash about the face, hands and forearms. The rash spreads centrally during the next week to the trunk. Lesions quickly progress from macules to papules and eventually to pustular vesicles. Lesions are more abundant on the extremities and face, and this centrifugal distribution is an important diagnostic feature.

In distinct contrast to the lesions seen in varicella, smallpox lesions on various segments of the body remain generally synchronous in their stage of development. From 8 -14 days after onset, the pustules form scabs, which leave depressed depigmented scars on healing. Patients should be isolated and considered infectious until all scabs separate.


A patient is considered high risk for smallpox when all three of the following features are present: 1. Febrile prodrome (occurring 1- 4 days before rash onset) with fever greater than 102°F and at least one of the following: prostration, headache, backache, chills, vomiting or severe abdominal pain. 2. Classic smallpox lesions: deeply embedded in the dermis, firm/hard, round, well-circumscribed, may be umbilicated, may be discrete, semiconfluent, or confluent lesions in the same stage of development (i.e., all of the lesions on any one area of the body are at the same stage).

The usual method of laboratory diagnosis is demonstration of characteristic virions on electron microscopy of vesicular scrapings. Under light microscopy, aggregations of variola virus particles, called Guarnieri bodies, correspond to B-type poxvirus inclusions. The likelihood of a smallpox diagnosis determines the appropriate laboratory testing and handling of specimens. CDC has developed criteria for determining the risk of smallpox.

Medical Management

Treatment for smallpox largely consists of general supportive measures, including adequate fluid intake, alleviation of pain and fever and keeping the skin lesions clean to prevent bacterial superinfection. No specific antiviral treatment of demonstrated effectiveness was available in the pre-eradication era.

Transmissibility and Infection Control

Smallpox is extremely infectious. Airborne and contact precautions, in addition to standard precautions, should be implemented for patients with suspected smallpox. Place the patient in a private room with negative air-pressure ventilation (minimum 6 air exchanges/hr). Use external air exhaust or high-efficiency particulate air (HEPA) filters if the air is recirculated. Keep the door to the room closed. Place the patient in a private room if available, or cohort patients. Wear gloves when entering the room, change gloves after having contact with infectious material, remove gloves before leaving the room, and immediately wash hands using an antimicrobial agent. Wear a gown when entering the room and remove the gown before leaving the room. Move and transport the patient for essential purposes only. If transport is necessary, a mask should be placed on the patient.

Vaccinia vaccination, delivered within four days of exposure to smallpox has been shown to prevent transmission of the disease or decrease symptoms. The current vaccine is administered by intradermal inoculation with a bifurcated needle, a process that became known as scarification because of the permanent scar that resulted. A vesicle typically appears at the vaccination site 5 to 7 days after the inoculation, with surrounding erythema and induration. The lesion forms a scab and gradually heals over the next 1- 2 week.

Side effects arising from vaccination are relatively uncommon but are nevertheless of enough concern to limit pre-event mass vaccination. Low-grade fever and axillary lymphadenopathy may coincide with the culmination of the cutaneous pox lesion after vaccination. The attendant erythema and induration of the vaccination vesicle is frequently misdiagnosed as bacterial superinfection. Formation of a scar on healing of the vesicle occurs routinely and constitutes a permanent record of a take, or a successful primary vaccination.

Pre-event, the following are contra-indications to vaccinia vaccination: immunosuppressant, human immunodeficiency virus (HIV) infection, either history or evidence of eczema, current household contact, sexual or other close physical contact with a person or persons possessing the conditions listed above, or pregnancy.

Despite the caveats listed above, most authorities state that, with the exception of significant impairment of systemic immunity, there are no absolute contraindications to postexposure vaccination of a person who experiences bona fide exposure to variola virus. However, in such circumstances, concomitant administration of VIG is recommended for pregnant women and individuals with eczema.

All healthcare workers caring for patients with suspected smallpox should be vaccinated immediately.

As with any bioterrorism agent, a case or suspected case of smallpox in someone living or working in the County should be immediately reported by phone to the Anne Arundel County Department of Health at 410-222-7256. To report communicable diseases, click here for instructions.

Patient Handouts

What is Smallpox?
Smallpox is a disease caused by the variola virus. In the United States, routine vaccination against smallpox ended in 1972. Although smallpox was eradicated in 1977, the illness may reappear due to an intentional bioterrorist act.

Anyone exposed to the smallpox virus may get smallpox. Even people who have been vaccinated for smallpox might become ill, because the duration of protection given by the smallpox vaccine is not fully understood.

The smallpox virus can be easily spread from one person to another after coming into close (within 6 feet) contact with a person who has smallpox. The virus is often contained in the droplets that can be coughed or sneezed from a person with smallpox.

Symptoms of smallpox include sudden onset of:
Fever (temperature 101 degrees F or greater), vomiting and occasional abdominal pain, headache and severe backache.

Two to four days after initial symptoms:
Rash on face, arms and legs.

Several days later:
Rash moves to the midsection of the body.

Contact your doctor immediately if you develop these symptoms and if you think that you have been exposed to smallpox.

There is no specific medical treatment for smallpox infection
There is no known treatment for smallpox. The smallpox vaccine is helpful if given within four days of exposure to someone with smallpox. <

Routine smallpox vaccination is not recommended for the general public
If an outbreak of smallpox occurs, doses of the smallpox vaccine will be requested from the national drug stockpile, which is maintained by the Centers for Disease Control. Plans are currently in progress to increase the current stockpile of this vaccine.

Additional information may be obtained from the Centers for Disease Control and Prevention

Trainings/Powerpoint Presentations

The Smallpox Presentation (2003) is available as a PowerPoint or a PDF.

Additional Resources

Essential Reading

Bartlett J, Henderson D, Inglesby T, et a. Smallpox as a Biological Weapon: Medical and Public Health Management. JAMA 1999;281(22):2127-37.

Additional Readings

Centers for Disease Control and Prevention. Smallpox Vaccination and Adverse Reactions: Guidance for Clinicians. Morbidity and Mortality Weekly Report. 2003;52(RR04):1-28.

Damon I, Meltzer MI, LeDuc JW, et al. Modeling Potential Response to Smallpox as a Bioterrorist Weapon. Emerging Infectious Diseases 2001;7(6):959-969.

Recognition of Illness Associated with the Intentional Release of a Biologic Agent. Morbidity and Mortality Weekly Report. 2001;50(41);893-7.

Internet Resources

Centers for Disease Control and Prevention

Center for Infectious Disease Research and Policy of University of Minnesota

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