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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. 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. Smallpox was finally pushed back to the horn of Africa and then to a single last natural case, which occurred in Somalia in 1977.
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.
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.
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. The disease can also be transmitted by contaminated clothes and bedding.Epidemics develop comparatively slowly. The interval between each generation of cases is 2–3 weeks.
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.
Management of an outbreak
Emphasis must be placed on preventing epidemic spread. In doing so, it should be kept in mind that smallpox patients are not infectious during the early stage of the disease but become so from the first appearance of fever and remain so, though to a lesser degree, until all scabs have separated. Also, immunity develops rapidly after vaccination against smallpox (see above). Surveillance of smallpox infection is probably easier than for any other infectious disease. A distinctive rash is produced (see above) which is wholly characteristic in the great majority of cases. The rash is most dense over the face and hands – unclothed and readily visible portions of the body. Experiences from the eradication campaign indicate that, in the presence of a strong surveillance system sensitive to smallpox cases and backed by an adequate infrastructure, small but rapid and thorough containment actions can break the transmission chain and halt a smallpox outbreak within a relatively short time. Containment involves efficient detection of cases and identification and vaccination of contacts. Patients diagnosed with smallpox should be physically isolated. All persons who have or will come into close contact with them should be vaccinated. As hospitals have proven to be sites of epidemic magnification during smallpox outbreaks, patient isolation at home is advisable where hospitals do not have isolation facilities. Whatever the policy, isolation is essential to break the chain of transmission. Patients who developed rash before their isolation should be asked to recount all recent contacts. Contacts should be vaccinated. If it is not feasible to vaccinate contacts, they should be placed on daily fever watch, which should continue up to 18 days from the last day of contact with the case. If these contacts have two consecutive readings of 38 degrees centigrade or above, they should be isolated. All specimen collectors, care givers and attendants coming into close contact with patients should be vaccinated as soon as smallpox is diagnosed as the cause of an outbreak. In the case of a widespread outbreak, people should be advised to avoid crowded places and follow public health advice on precautions for personal protection.
Smallpox vaccine contains live vaccinia virus, a virus in the orthopoxvirus family and closely related to variola virus, the agent that causes smallpox. Immunity resulting from immunization with vaccinia virus (vaccination) protects against smallpox. Most existing vaccine stocks and the vaccine used in the WHO eradication campaign consist of pulp scraped from vaccinia-infected animal skin, mainly calf or sheep, with phenol added to a concentration sufficient to kill bacteria but not so high as to inactivate the vaccinia virus. The vaccine is then freeze dried and sealed in ampoules for later re-suspension in sterile buffer and subsequent intradermal inoculation by multiple puncture with a bifurcated needle.
About the virus
The causative agent, variola virus, is a member of the genus Orthopoxvirus, subfamily Chordopoxvirinae of the family Poxviridae. Other members of the genus include cowpox, camelpox, and monkeypox. Monkeypox virus has caused the most serious recent human poxvirus infections. Variola virus is relatively stable in the natural environment. If aerosolized, it probably retains its infectivity for at least several hours if not exposed to sunlight or ultraviolet light. The variola virus measures 260 by 150 nanometers and contains a molecule of double-stranded DNA putatively coding for some 200 different proteins, one of the largest viral genomes known. The size of the genome makes it especially difficult to create a synthetic copy of the virus.


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