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Last updated Aug. 14, 2019

Approved by: Maulik P. Purohit MD MPH

CDC/Dr. N.S. Deodakar

Victim of smallpox (1965 image) displaying characteristic maculopapular rashes.

What are the other Names for this Condition? (Also known as/Synonyms)

  • Small Pox Viral Infection
  • Variola Virus Infection

What is Smallpox? (Definition/Background Information)

  • Smallpox is a highly contagious viral infection caused by variola virus. It was eradicated from the world in 1980
  • The virus can survive in the environment only for a short period and is most stable at low temperatures and low humidity. It can effectively spread through air and may be inhaled. Less commonly Smallpox may also be transmitted through exposure to skin lesion discharge material
  • Variola virus is a brick-shaped DNA virus, which is a member of Orthopoxvirus genus. Unlike other DNA viruses, this virus replicates in the cells' cytoplasm, while other DNA viruses multiply in the cells' nucleus. There are 2 types of variola - variola major and variola minor

Variola major Smallpox has 4 subtypes:

  • Ordinary Smallpox: It is the most common form of Smallpox and a majority of the cases belonging to this category (over 90%)
  • Modified Smallpox: When Smallpox develops in previously vaccinated individuals. It is a mild condition
  • Flat Smallpox (Malignant Smallpox): A severe form in which the lesions do not project above the skin surface
  • Hemorrhagic Smallpox (Fulminant Smallpox): It is a deadly variety of Smallpox that is rare, causing severe bleeding in the skin and mucosal membranes

Variola minor Smallpox is less common and much less virulent; it was previously found mainly in South Africa, South America, Europe, and Australia.

  • Other very rare forms of Smallpox are pulmonary form of Smallpox (in low immunity individuals), pharyngeal form affecting the throat and causing influenza-like symptoms, rarely result in skin rashes
  • The signs and symptoms associated with this infectious condition include fever with chills , headache, backache, followed by the appearance of skin rashes
  • Common complications of Smallpox are secondary bacterial infection of the skin lesions, infection of the eyes, bones, and lungs
  • The treatment of Smallpox is aimed at managing the symptoms of the disease. Smallpox is a deadly infection and the mortality rate for untreated cases may be as high as 30% or higher
  • The infection can be prevented in someone exposed to the virus by administering Small Pox vaccine within 4 days of exposure

Who gets Smallpox? (Age and Sex Distribution)

  • Any individual exposed to the Variola virus is susceptible to Smallpox
  • Both males and females are at risk
  • The last endemic case of variola major was reported in Bangladesh in 1975 and an endemic of variola minor in Somalia in 1977

What are the Risk Factors for Smallpox? (Predisposing Factors)

The risk factor associated with Smallpox is close contact with an infected individual.

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Smallpox? (Etiology)

Smallpox is caused by a DNA virus called variola virus.

  • The variola virus is transmitted by close contact with an infected individual. The virus spreads through respiratory route as droplets. Even a few virions (complete virus particles) are enough to cause the disease
  • The infected individual has the potential to transmit the disease, until the last Smallpox scab separates or drops. The infectivity and virus shedding is very high during the first 10 days of the disease
  • The incubation period (time between the entry of virus into the body and appearance of rash) is 7-17 days

What are the Signs and Symptoms of Smallpox?

Signs and symptoms associated with Smallpox include:

  • Prodromal phase lasting 2-4 days
    • Fever (38.8-40°C or 101-104°F)
    • Severe headache
    • Backache
    • Pharyngitis (sore throat)
    • Nausea          
    • Vomiting (in rare cases)
    • Prostration (tiredness or fatigue)
    • Exanthema on the mucous membranes of the tongue and the oropharynx
  • Skin rashes: The appearance of small, red macules (change in skin color) that are first noticed on the face. It the spreads to the arms and legs and the trunk. After 2 days, the macules form firm skin eruptions (about 2-3 mm), which then evolve into 2-5 mm vesicles (fluid-filled eruptions)
  • Neuropsychiatric symptoms such as hallucinations, delirium, depression, and psychosis
  • Conjunctivitis after 5 days of onset of rash
  • Osteomyelitis (bone infection) due to viral infiltration of the bone, which is common in children

How is Smallpox Diagnosed?

A complete evaluation of medical history and a thorough physical exam may be undertaken by the healthcare provider.

The major criteria for diagnosis of Smallpox include:

  • Febrile prodrome (fever before the onset of rash, seen within 4 days) and any one of the following symptom - prostration, pain in the back, chills, vomiting, abdominal pain that may be severe
  • The presence of classic Smallpox lesions that may be defined and well-circumscribed
  • The lesions are present on any body part and are observed to have the same development stage

The minor criteria for diagnosis of Smallpox include:

  • The rashes appear on the body and spread outwardly to the arms and legs
  • The lesions may first appear on the mouth and cheek (oral mucosa), face and then forearms
  • The health of the patient gradually wanes and he/she appears “toxic”
  • The rashes evolve slowly (over several days) from change in skin color (macule) to papules or bumps to vesicles (fluid-filled blisters)
  • Appearance of lesions on even the palms and soles

Other methods of diagnosis may include:

  • Viral swab from the throat and skin lesions that are subject to electron microscopy and PCR technique
  • Tzanck preparations
  • Direct fluorescent antibody testing for  variola viruses
  • Blood tests
  • Skin biopsy
  • Lumbar puncture

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Smallpox?

Dermatologic (skin) complications of Smallpox include the following:

  • Formation of furuncles and/or abscesses secondary to bacterial infection
  • Sepsis
  • Pockmarks on the skin

Ophthalmologic (eye) complications of Smallpox include the following:

  • Inflammation of the eye lids (blepharitis)
  • Conjunctivitis
  • Corneal ulceration
  • Keratitis (infection of the cornea)
  • Blindness (rarely)

Orthopedic (bone & joint) complications include the following:

  • Arthritis: Pain in the joints secondary to joint inflammation
  • Osteomyelitis variolosa (infection of the bone)
  • Symmetrical elbow joint involvement

Respiratory complications include the following:

  • Pulmonary edema (fluid accumulation in the lungs)
  • Pneumonitis (infection of the lung parenchyma)
  • Bronchopneumonia (infection of the lung parenchyma)

How is Smallpox Treated?

  • The treatment for Smallpox is supportive, such as managing fever, pain, protecting the skin from bacterial infections, correcting electrolyte imbalances, and treating corneal infection (using idoxuridine)
  • Patients should be kept in isolation for 3-4 weeks until the last blister heals

How can Smallpox be Prevented?

  • Smallpox can be prevented through vaccination, if an exposed individual is administered Smallpox vaccine within 4 days of exposure
  • The disease severity is moderate when the vaccine is given from 4-7 days of exposure

What is the Prognosis of Smallpox? (Outcomes/Resolutions)

  • Smallpox is a viral infection that can be fatal if left untreated; the death rate may be as high as 30% or even higher
  • Severe forms of Smallpox are usually fatal and these include the hemorrhagic and malignant forms

Additional and Relevant Useful Information for Smallpox:

The following DoveMed website link is a useful resource for additional information:


What are some Useful Resources for Additional Information?

References and Information Sources used for the Article:

Helpful Peer-Reviewed Medical Articles:

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Aug. 4, 2015
Last updated: Aug. 14, 2019