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Smallpox is an illness caused by the variola virus. This virus belongs to the orthopoxvirus family of viruses. When smallpox was circulating in the environment, there were several forms of the disease, with some more severe and life-threatening than others. The various forms included Variola Major, modified-type smallpox, hemorrhagic smallpox, malignant (flat-type) smallpox, and Variola Minor. Variola Major was the most common form of the illness when smallpox was circulating in the environment.
Variola Major
According to the Centers for Disease Control (CDC), Variola Major was the most common form of the illness when smallpox was circulating. The incubation period of Variola Major ranged from seven to 19 days, but most frequently lasted between 10 and 14 days. Persons infected with the virus were not contagious and had no symptoms of illness during this period.
The first symptoms of illness occurred in the prodrome period, which began immediately following the incubation period, and lasted approximately four days. Symptoms included:
- Anorexia
- Vomiting
- Malaise
- High fever (between 101°F to 105°F)
- Chills
- Headache
- Backache
- Severe abdominal pain
- Pharyngitis
- Extreme exhaustion
- A rash, mostly seen in light-skinned individuals.
When the fever resolved, rash lesions would begin to develop and appear in the back of the mouth, behind the oral cavity (oropharynx), followed by the face, arms, legs, and then would have spread to the torso, palms and soles. Rash lesions would develop evenly during the illness and progress from macules (distinct, flat, discolored skin) to papules (raised red or pink itchy bumps) to vesicles (fluid-filled blisters) within four to five days. In another one or two days, the vesicles would evolve to pustules that were round, firm, and found deep in the dermis. Crusting and scabbing of the lesions usually began on the ninth day and the crusts generally began to fall off about 2 weeks after the onset of the rash.
Complications of smallpox included severe bacterial infections of the skin and organs, sepsis, pneumonia, encephalitis, and keratitis.
The most common long-term health consequence of smallpox was scarring which occurred all over the body but most often on the face. Additional sequelae included stillbirths and spontaneous abortions, infertility in males, osteomyelitis, encephalitis, and blindness. Persons who recovered from smallpox illness developed long-term immunity.
Historically, Variola Major was fatal in approximately 30 percent of cases.
Modified-type Smallpox
When the vaccine failed to prevent illness, previously vaccinated individuals would develop a condition known as modified-type smallpox. Symptoms of illness were usually the same as in persons who developed Variola Major; however, the rash generally resolved within 10 days, instead of 2 weeks, and fever was not always present. There were usually fewer lesions, and lesions were often superficial. Modified-type smallpox infections were rarely fatal.
Hemorrhagic Smallpox
Hemorrhagic smallpox usually occurred in adults but could still develop in children. Additionally, pregnant women were also more at risk of developing this particular form of the disease. Symptoms of hemorrhagic smallpox were similar to Variola Major except that the incubation period was shorter and prodromal symptoms were usually more severe. Additionally, after the onset of illness, skin redness would occur and progress to a petechial rash (small pinpoint purple or red rash) and hemorrhaging of the skin and mucous membranes. Hemorrhagic smallpox was usually fatal by the fifth or sixth day after rash onset, and frequently as a result of multi-system organ failure due to toxemia. Vaccination was ineffective against hemorrhagic smallpox.
Malignant (Flat-type) Smallpox
Most common among children, flat-type smallpox was rare and identified by skin lesions that developed slowly, merged together, and became soft and flat. Most cases of flat-type smallpox were fatal due to toxemia, however, if a patient survived, the rash would heal without scabbing. This type of smallpox was fatal in approximately 97 percent of cases.
Variola Minor (Alastrim)
Variola Minor was a less severe form of illness and was rarely fatal. Death occurred in less than one percent of cases. This form was most common in the U.S. by the early part of the 20th Century. By the 1930s and until smallpox was eliminated from the U.S., variola minor, the mildest form of smallpox, had emerged as the predominant strain.
Additional Orthopoxvirus Diseases
Monkeypox (Mpox)
Monkeypox (Mpox) is an infection caused by the mpox virus and like smallpox is also a member of the Orthopoxvirus family. The incubation period of mpox is usually between 7 and 14 days. Symptoms of mpox are similar to smallpox but are generally milder. Individuals infected with mpox usually present with headache, backache, fever, chills, muscle aches, extreme fatigue and exhaustion. Swelling of the lymph nodes also occurs, which is a symptom not present with smallpox infection.
A rash, which usually appears on the face, begins within one to three days of fever, and spreads throughout the body. The lesions of the rash progress from macules to papules to vesicles before erupting as pustules and scab over. Most individuals recover from mpox within two to four weeks.
Mpox is rare and is generally found in Africa, although cases and outbreaks have occurred globally. The virus was first identified among monkeys involved in research in 1958. While the main species that harbors the virus remains unknown, health officials believe that African rodents, monkeys, and other primates likely harbor and transmit the virus. The first known case of human infection was documented in the Democratic Republic of the Congo (DRC) in 1970. Transmission of mpox virus is thought to occur through the respiratory tract, breaks in the skin, or mucous membranes.
Complications of mpox illness include sepsis, encephalitis, eye infections that may result in blindness, bronchopneumonia, myocarditis, and other secondary infections that may lead to death.
There are three clades (types) of mpox that have been identified: Clade I, Clade IIa and Clade IIb. Clade I is found in the Congo Basin of Africa and is reported to have a mortality rate of 10 percent. It is also more easily transmissible and associated with higher rates of mortality. Historically, those most at risk have been individuals who hunt, kill, and eat bushmeat (meat from wildlife).
Clade IIa is typically found in West Africa and is rarely fatal, with a mortality rate of less than one percent. Clade IIb is the strain associated with the 2022 global outbreak, and is rarely fatal in immunocompetent individuals. Unlike Clade I and Clade IIa, which generally spreads from animals to humans, Clade IIb is easily transmitted from human to human.
IMPORTANT NOTE: NVIC encourages you to become fully informed about smallpox/monkeypox (Mpox) and the smallpox/monkeypox (Mpox) vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself. This information is for educational purposes only and is not intended as medical advice.