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Profiles for Health Care Workers (Fact Sheets) - "A" Agents

  • Health Care Providers: If you suspect a patient has been exposed to a biological or chemical agent please call the Office of Infectious Disease Services at (602) 364-4562
    On-call staff are available 24 hours a day, 7 days a week.

Anthrax | Botulism | Plague | Smallpox | Tularemia | Viral Hemorrhagic Fevers


Causative Agent:
Smallpox is an acute viral illness caused by variola, one of the orthopox viruses. There are two different strains of the virus, variola major and variola minor. Variola major causes a more severe illness. No cases of smallpox have been observed in the world since 1978. The World Heath Organization declared the world free smallpox free in 1980.

Routes of Exposure:
Inhalation or contact with skin lesions or secretions

Infective Dose:
The infectious dose is unknown, but it is believed to be 10-100 virions.

Incubation Period:
The incubation period of ranges from 7-17 days, with an average of 12 days.

Clinical Effects:
The illness begins with a prodrome lasting 2-3 days, with generalized severe malaise, fever, rigors, headache, and backache. Abdominal pain and delirium are sometimes present. These symptoms are followed by a rash that progresses over 7 to 10 days. Lesions develop at the same stage, starting first as macules, and then changing to papules, then to vesicles, then to pustules and finally to scabs. The lesions are most concentrated on the face and extremities, and they are least dense on the trunk. The lesions are firm and deep-seated.

Approximately 10% of cases will have an atypical type of rash described as either flat smallpox or hemorrhagic smallpox. These patients also have a prostrating febrile prodrome. In the flat form, the skin lesions never fully organize; instead they remain soft, flattened and velvety to the touch. In the hemorrhagic form there is bleeding under the skin and overwhelming DIC without the development of characteristic pox lesions.

The mortality rate of smallpox is 20-50% in unvaccinated individuals. Hemorrhagic and malignant cases are 95-100% fatal.

Smallpox is not contagious during the incubation period. Persons with smallpox become infectious at the onset of the rash, and remain infectious until all of the scabs have fallen off. Person-to-person transmission occurs by droplet exposure to oropharyngeal secretions, and by contact with skin lesions. Close, face-to-face contact is usually required for transmission, although airborne transmission in a hospital may have occurred in one outbreak.

Primary contamination & Methods of Dissemination:
Any case of smallpox would be considered an act of terrorism. Smallpox virus could be delivered via aerosol, or by means of an intentionally infected individual.

Secondary Transmission & Persistence of organism:
Humans are the only for host for smallpox. People have been infected by contact with smallpox patients’ linen, presumably by fomite transmission. However, smallpox has only been found to spread when there is an identifiable patient with active infection.

Decontamination & Isolation:

  • Patients – Airborne and contact precautions should be observed in addition to standard precautions.
  • Equipment, clothing & other objects – Contaminated clothing and bed linens can spread the virus. Laundry should be bagged with minimal agitation to prevent contamination of air, surfaces, or people. Only immunized workers using proper PPE should handle contaminated laundry. Laundering should be done using hot water to which bleach has been added. Disinfectants that are used for standard hospital control, such as hypochlorite or quaternary ammonia, are effective for cleaning surfaces possibly contaminated with virus. Waste should be placed in biohazard bags and discarded according to medical waste regulations.

Outbreak control:
Control of smallpox is based upon vaccination with the vaccinia virus and isolation of cases. A suspect case of smallpox should be considered a public health emergency. Local, tribal and state health departments should be notified immediately. As soon as the diagnosis of smallpox is made, all suspected smallpox cases should be isolated. Additionally, all household and face-to-face contacts should be vaccinated as soon as possible. The smallpox vaccine does not confer lifelong immunity.

Laboratory testing:
Smallpox virus can be found in vesicular or pustular fluid by PCR or by culture. Electron microscopy can identify an orthopox virus, but cannot differentiate between variola, vaccinia, or monkeypox. Smallpox virus testing is currently only available through the CDC.

Local and state health departments should be contacted immediately if smallpox is a consideration.

People who collect samples to test for smallpox should wear proper personal protective equipment and have received a recent smallpox vaccine. Smallpox evaluation is done by sampling skin lesions, drawing blood, and doing throat swabs for testing by culture, EM, PCR, and serology.

Therapeutic Treatment:
There is no proven effective anti-viral treatment for smallpox. Cidofovir has in vitro activity against smallpox and could be available by an investigational new drug protocol.

Prophylactic Treatment:
A highly effective smallpox vaccine exists using vaccinia virus, another orthopox virus. It is being used by the military and for public health preparedness. It is not being offered to the general public since as of July 2004 there is no one in the world with smallpox infection. There is enough vaccine available to vaccinate everyone in the United States, if there were a smallpox outbreak. Vaccination within 3 days of exposure will prevent or significantly modify smallpox in the vast majority of persons. Vaccination 4 to 7 days protects against death, but will not prevent infection.

Differential Diagnosis:
The differential diagnosis of a generalized vesicular rash should include varicella (chickenpox) and monkey pox. The lesions of varicella arise in crops, are superficial, and are almost never found on the palms or soles. In contrast, the rash associated with smallpox does not appear in crops: all lesions on one part of the body will be at the same stage of development. Smallpox lesions are deep and firm, and are most concentrated on the face and extremities, including palms and soles. Monkey pox, a naturally occurring relative of smallpox, occurs in Africa. The lesions are clinically indistinguishable from smallpox, they are fewer in number and the patients are less toxic. Smallpox cases that present in the hemorrhagic form can be misdiagnosed as meningococcemia or severe acute leukemia. The CDC website has an algorithm to assess the risk of a rash for smallpox.


  • Chin J. Control of Communicable Diseases Manual, Seventeenth Edition, American Public Health Association; 2000.
  • Henderson DA, Inglesby TV, Bartlett JG, et al. Smallpox as a Biological Weapon: Medical and Public Health Management. JAMA. 1999; 281: 2127-2137.
  • Kortepeter M, Christopher G, Cieslak T, et al. Medical Management of Biological Casualties Handbook, U.S. Army Medical Research Institute of Infectious Diseases, U.S. Department of Defense; 2001:44-48
  • McClain DJ. Smallpox. In: Zajtchuk R, Bellamy RF, eds. Medical Aspects of Chemical and Biological Warfare. Washington, DC: Office of the Surgeon General, U.S. Department of the Army; 1997: 539-559.

Find the PDF version of this Fact Sheet in the Zebra Manual.