Smallpox

Bacteriology at UW-Madison

The Microbial World

Lectures in Microbiology by Kenneth Todar PhD University of Wisconsin-Madison Department of Bacteriology

Smallpox

Smallpox

Smallpox disease has been known throughout recorded history and has occurred in epidemics many times. Before vaccination about 95% of the population contracted 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 is a laboratory 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.

Variola 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.

The 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 varicella (chickenpox), the disease most frequently confused with smallpox, new lesions appear in crops every few days, and lesions at different 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.

Epidemiology

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 a few virus particles. In the 1960’s and 1970’s in Europe, during a very limited 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 fever (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.

Treatment and Prevention

There is no proven treatment for smallpox. Patients with smallpox may be helped by intravenous fluids, medicine to control fever or pain, and antibiotics for any secondary bacterial infections that may occur.

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.

Immunity

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. The origin of 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. Immunity that 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.

Before 1972, smallpox vaccination was recommended for all U.S. children beginning at 1 year of age. Most states required that children be vaccinated before entry into school. Routine vaccination in the U.S. stopped in 1972, and since then, very few people under 33 years of age have been vaccinated. The immune status of those who were vaccinated before smallpox vaccination ceased is not clear, as the length of protective immunity has never been satisfactorily measured. Neutralizing antibodies are known to decline substantially 5 to 10 years post vaccination. In any case, those 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.

Currently, 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 weapon 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.

Currently, deliberate 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 the world.

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 smallpox 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 again.

Smallpox and vaccination on the web
CDC Smallpox Home
Vaccinia (Smallpox) Vaccine
NIP: Smallpox/home page
HHS - Smallpox
Smallpox Information
Latest ACIP Smallpox Recommendation
RNCEUS: Smallpox