Smallpox
Historical significance
Smallpox is an acute contagious disease caused by variola virus, a member of the orthopoxvirus family.
Smallpox, which is believed to have originated over 3,000 years ago in India or Egypt, is one of the most devastating diseases known to humanity. For centuries, repeated epidemics swept across continents, decimating populations and changing the course of history.
In some ancient cultures, smallpox was such a major killer of infants that custom forbade the naming of a newborn until the infant had caught the disease and proved it would survive.
Smallpox killed Queen Mary II of England, Emperor Joseph I of Austria, King Luis I of Spain, Tsar Peter II of Russia, Queen Ulrika Elenora of Sweden, and King Louis XV of France.
The disease, for which no effective treatment was ever developed, killed as many as 30% of those infected. Between 65–80% of survivors were marked with deep pitted scars (pockmarks), most prominent on the face.
Blindness was another complication. In 18th century Europe, a third of all reported cases of blindness was due to smallpox. In a survey conducted in Viet Nam in 1898, 95% of adolescent children were pockmarked and nine-tenths of all blindness was ascribed to smallpox.
As late as the 18th century, smallpox killed every 10th child born in Sweden and France. During the same century, every 7th child born in Russia died from smallpox.
Edward Jenner's demonstration, in 1798, that inoculation with cowpox could protect against smallpox brought the first hope that the disease could be controlled.
In the early 1950s – 150 years after the introduction of vaccination – an estimated 50 million cases of smallpox occurred in the world each year, a figure which fell to around 10–15 million by 1967 because of vaccination.
In 1967, when WHO launched an intensified plan to eradicate smallpox, the "ancient scourge" threatened 60% of the world's population, killed every fourth victim, scarred or blinded most survivors, and eluded any form of treatment.
Through the success of the global eradication campaign, smallpox was finally pushed back to the horn of Africa and then to a single last natural case, which occurred in Somalia in 1977. A fatal laboratory-acquired case occurred in the United Kingdom in 1978. The global eradication of smallpox was certified, based on intense verification activities in countries, by a commission of eminent scientists in December 1979 and subsequently endorsed by the World Health Assembly in 1980.
Forms of the disease
Smallpox had two main forms: variola major and variola minor. The two forms showed similar lesions. The disease followed a milder course in variola minor, which had a case-fatality rate of less than 1 per cent. The fatality rate of variola major was around 30%.
There are two rare forms of smallpox: haemorrhagic and malignant. In the former, invariably fatal, the rash was accompanied by haemorrhage into the mucous membranes and the skin. Malignant smallpox was characterized by lesions that did not develop to the pustular stage but remained soft and flat. It was almost invariably fatal.
Clinical features
The incubation period of smallpox is usually 12–14 days (range 7–17) during which there is no evidence of viral shedding. During this period, the person looks and feels healthy and cannot infect others.
The incubation period is followed by the sudden onset of influenza-like symptoms including fever, malaise, headache, prostration, severe back pain and, less often, abdominal pain and vomiting. Two to three days later, the temperature falls and the patient feels somewhat better, at which time the characteristic rash appears, first on the face, hands and forearms and then after a few days progressing to the trunk. Lesions also develop in the mucous membranes of the nose and mouth, and ulcerate very soon after their formation, releasing large amounts of virus into the mouth and throat.
The centrifugal distribution of lesions, more prominent on the face and extremities than on the trunk, is a distinctive diagnostic feature of smallpox and gives the trained eye cause to suspect the disease. Lesions progress from macules to papules to vesicles to pustules. All lesions in a given area progress together through these stages. From 8 to 14 days after the onset of symptoms, the pustules form scabs which leave depressed depigmented scars upon healing.
In the past, smallpox was sometimes confused with chickenpox, a worldwide infection of children that is seldom lethal. Chickenpox can be distinguished from smallpox by its much more superficial lesions, their presence more on the trunk than on the face and extremities, and by the development of successive crops of lesions in the same area.
Smallpox is a disease which can be easily diagnosed by trained health workers without the need for laboratory support. During the eradication campaign, WHO produced training materials designed to help health staff recognize smallpox, distinguish it from chickenpox, and avoid common diagnostic errors. These materials are now available electronically.
Infectivity
Persons carrying the virus during the incubation period cannot infect others.
The frequency of infection is highest after face-to-face contact with a patient after fever has begun and during the first week of rash, when the virus is released via the respiratory tract.
Although patients remain infectious until the last scabs fall off, the large amounts of virus shed from the skin are not highly infectious. Exposure to patients in the late stages of the disease is much less likely to produce infection in susceptible contacts.
As a precaution, WHO isolation policy during the eradication campaign required that patients remain in isolation, in hospital or at home, until the last scab had separated.
Transmission
In the absence of immunity induced by vaccination, human beings appear to be universally susceptible to infection with the smallpox virus.
There is no animal reservoir. Insects play no role in transmission.
Smallpox is transmitted from person to person by infected aerosols and air droplets spread in face-to-face contact with an infected person after fever has begun, especially if symptoms include coughing. The disease can also be transmitted by contaminated clothes and bedding, though the risk of infection from this source is much lower.
In the past, patients suffering from variola major (the more severe form of the disease) became bedridden early (in the phase before the eruption of rash) and remained so throughout the illness. Spread of infection was limited to close contacts in a small vicinity. Variola minor, however, was so mild that patients infected with this form frequently remained ambulatory during the infectious phase of their illness and thus spread the virus far more widely.
During the eradication campaign, investigations of outbreaks caused by importations of cases into industrialized countries in temperate areas showed that, in a closed environment, airborne virus could sometimes spread within buildings via the ventilation system and infect persons in other rooms or on other floors in distant and apparently unconnected spaces. This mode of transmission is not important in those tropical areas where houses and hospitals do not use ventilation systems.
Epidemics develop comparatively slowly. The interval between each generation of cases is 2–3 weeks.
When natural outbreaks occurred, the initial, or "index", case rarely infected as many as 5 other persons, even during the peak transmission season. On some occasions, such as the outbreak that followed importation of a case into Yugoslavia in 1972, index cases infected more than a dozen people.
Unfortunately, historical data are available only from periods with substantial population immunity either from vaccination or from having survived natural infection. In the absence of natural disease and vaccination, the global population is significantly more susceptible. Some experts have estimated today's rate of transmission to be more on the order of 10 new infections per infected person.
Treatment
Vaccine administered up to 4 days after exposure to the virus, and before the rash appears, provides protective immunity and can prevent infection or ameliorate the severity of the disease.
No effective treatment, other than the management of symptoms, is currently available.
A number of compounds are under investigation as chemotherapeutic agents. One of these, Cidofovir, has produced promising results in laboratory studies.