Bacteriology at UW-Madison
The Microbial World
Lectures in Microbiology by Kenneth Todar PhD University of Wisconsin-Madison Department of Bacteriology
© 2009 Kenneth Todar PhD
Smallpox disease has been known throughout recorded history and has
occurred in epidemics many times. Before vaccination about 95% of
some form of disease, one-quarter died, and
many were left blind or disfigured.
Smallpox (variola) is caused by
variola virus, a member of the
Poxviridae family. Poxviruses
are all large,
ovoid, dsDNA viruses, just barely visible in the light
microscope. Poxviruses are capable of causing skin lesions in a
variety of animals including humans. Vaccinia
strain of the virus used for vaccination against smallpox.
The variola virus emerged in human populations thousands of years ago.
Except for laboratory stockpiles, the variola virus has been
eliminated. However, in the aftermath of the events of September and
October, 2001, there is heightened concern that the variola virus might
be used as an agent of bioterrorism.
virus, the agent of human smallpox. The virus emerged
in human populations thousands of years ago, and has produced
devastating epidemics throughout recorded history. http://microbes.historique.net/smallpox.html
Pathogenesis of Smallpox
The incubation period for smallpox is 1-12 days before the symptoms of
fever, headache and rash appear.
The virus enters through the respiratory tract, grows on mucous
membranes, and spreads to regional lymph nodes where it multiplies
before entering the bloodstream. Fever and other symptoms appear at
this time. The virus invades internal organs, (heart, liver, kidney)
and skin, producing the typical smallpox lesions. Death may result due
to hemorrhage and generalized toxemia.
majority of smallpox cases present with a characteristic rash that
is most dense on the face and extremities. The lesions appear over a 1
to 2 day period and develop at the same rate. On any given part of the
body, the lesions are generally in the same stage of development. In
(chickenpox), the disease most frequently confused with smallpox, new
lesions appear in crops every few days, and lesions at
stages of maturation are found next to each other. Varicella lesions
are much more superficial and are almost never found on the palms or
soles. Chickenpox also has a much greater concentration of lesions on
the trunk than on the face and extremities than smallpox.
Variola occurs in
two predominant strains – variola
major, which has a 30% or
greater mortality rate, and variola
minor, with a 1% mortality rate.
Before the introduction of smallpox
vaccination, almost everyone eventually developed smallpox, and either
died of it or developed lifelong immunity. Smallpox is highly
contagious. The infectious dose is unknown, but is believed to be only
few virus particles. In the 1960’s and 1970’s in Europe, during a very
smallpox outbreak, individuals with the infection transmitted smallpox
to as many as 10 to 20 other people.
Generally, direct and fairly prolonged face-to-face contact is
required to spread smallpox from one person to another. Smallpox also
can be spread through direct contact with infected bodily fluids or
contaminated objects such as bedding or clothing. Rarely, smallpox has
been spread by virus carried in the air in enclosed settings such as
buildings, buses, and trains. Humans are the only natural hosts of
variola. Smallpox is not known to be transmitted by insects or animals.
A person with smallpox is sometimes contagious with onset of
(prodrome phase), but the person becomes most contagious with the onset
of rash. At this stage the infected person is usually very sick and not
able to move around in the community. The infected person is contagious
until the last smallpox scab falls off.
There is no proven treatment for smallpox.
smallpox may be helped by intravenous fluids, medicine to control fever
or pain, and antibiotics for any secondary bacterial infections that
One of the best ways to prevent
smallpox is through vaccination.
If given to a person before exposure to smallpox, the vaccine can
completely protect them. Vaccination within 3 days after exposure will
prevent or greatly lessen the severity of smallpox in most people.
Vaccination 4 to 7 days after exposure likely offers some protection
from disease or may decrease the severity of disease. Vaccination will
not protect smallpox patients who already have a rash.
In 1798, Edward Jenner reported his observations on cowpox, noting the clinical
similarity between smallpox and cowpox. He noted that milk maids were
immune to smallpox without having the disease. Jenner tried his
"experiment in nature" which was, of course, a landmark in the control
of infectious disease.
Jenner found that artificial inoculation of cowpox material conferred
immunity to smallpox. An organism with little or no virulence could
confer immunity against a related dangerous pathogen. Artificial
inoculation of people with cowpox became widespread and was highly
effective in controlling smallpox.
Today, "vaccination" against smallpox uses a different virus - vaccinia - the origin of which is
not known. Vaccinia is more closely related to variola than cowpox and
confers better immunity.
vaccinia virus is not known. Present day vaccination
against smallpox utilizes this virus, inoculation with which confers
immunity to infection by variola. Dr Milan V. Nermut
Immunity to smallpox acquired from active infection is lifelong.
results from vaccination is probably only complete for 3-5 years. After
this period, smallpox
infection can occur but it is less severe. Maternal antibody provides
infants with passive protection for 3-5 months following birth.
Smallpox outbreaks have occurred from time to time for thousands of
years, but the disease is now eradicated after a successful worldwide
vaccination program. The last case of smallpox in the United States was
in 1949. The last naturally occurring case in the world was in Somalia
in 1977. After the disease was eliminated from the world, routine
vaccination against smallpox among the general public was stopped
because it was no longer necessary for prevention.
smallpox vaccination was recommended for all U.S. children beginning at
year of age. Most states required that children be vaccinated before
entry into school. Routine vaccination in the U.S. stopped in 1972, and
very few people under 33 years of age have been vaccinated. The immune
those who were vaccinated before smallpox
vaccination ceased is not clear, as the length of protective immunity
been satisfactorily measured. Neutralizing antibodies are known
to decline substantially 5 to 10 years post vaccination. In any case,
who received the recommended single dose vaccination as children do not
have lifelong immunity, and it must be
assumed that the population at large is highly susceptible to infection.
the smallpox vaccine is not widely available to the general public.
However, according to CDC, there is enough smallpox vaccine to
vaccinate every person in
the United States in the event of a smallpox emergency.
Potential as a Bioweapon
British soldiers in North America first used smallpox as a biological
during the French and Indian Wars. Soldiers gave blankets that had been
used by smallpox patients to Native American Indians with the intent of
infecting them with smallpox. As a result, smallpox epidemics wiped out
more than 50% of the affected tribes.
reintroduction of smallpox into the human population would be a
horrific event. Smallpox is a significant threat as a bioweapon due to
its mortality rate of 30% or more among unvaccinated persons, and
the fact that there is no specific treatment other than supportive
care. Although smallpox has long been regarded as the most devastating
of all infectious diseases known to man, its potential for devastation
is far greater now than at any time in history. Smallpox vaccination
stopped in the U.S. more than 25 years ago. In a now highly
susceptible, mobile population, smallpox would be a true international
emergency, with potential to spread quickly and widely throughout
Today, the smallpox virus is kept in two approved labs in the U.S. and
Russia. However, credible concern exists that the virus was made into a
weapon by some countries and that terrorists may have obtained it.
Because smallpox is a serious, deadly disease, CDC calls it a “Category
A” agent. Category A agents are believed to present the greatest
potential threat for harming public health.
CDC has a detailed plan to protect Americans against the use of
as a biological weapon. This plan includes the creation and use of
special teams of health care and public health workers. If a smallpox
case is found, these teams will take steps immediately to control the
spread of the disease. Smallpox was wiped out through specific public
health actions, including vaccination, and these actions will be used
vaccination on the web
HHS - Smallpox
Latest ACIP Smallpox Recommendation
Written and Edited by Kenneth Todar. All rights
Return to The Microbial World Homepage