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Epidemiology and Pathology

The smallpox virus is filterable, and grows on the chorioallantoic membranes of hen's eggs. It is visible on electron microscopy; it replicates entirely within the cell cytoplasm.

Despite the centuries during which smallpox has afflicted mankind, it is still not certain how it is spread. It is probable that the ancient Chinese idea that it was "inhaled" is correct. Either infected droplets from a patient or dust containing virus particles may be inhaled and incubate in tonsillar and cervical lymphoid tissue. It is probable that handto-hand contact is another important route of transmission, because the corpses of victims are as infectious as patients. Skin crusts which have dried may remain infectious for 2 or more years. Outbreaks have been recorded amongst laundry workers handling the soiled linen of patients, and in dock workers unloading contaminated bales of cotton originating in endemic areas. In the past, continuing into the present century, smallpox spread in vast, devastating epidemics across the world.

After inoculation, probably in the tonsillar tissue with subsequent spread to cervical lymph nodes, the virus spreads to the reticuloendothelial system, where it multiplies until it is released. This transient viremia causes no clinical reaction and the viruses are reabsorbed by the reticuloendothelial system to multiply further, and then cause a severe and overwhelming second viremia. It is at this stage that the clinical illness usually begins, although some patients have died within 48 hours of infection from an overwhelming toxemia with little or no clinical evidence of smallpox.

Transplacental infection is known to occur, and causes abortion in the first 3 months of pregnancy. The fetus may be born with the scars of smallpox when infection occurs later during pregnancy, may be entirely normal, may be born dead, or may have evidence of an active infection at birth. At all ages the skin, mucous membranes, and testicles are the most commonly affected organs, and the lungs usually escape the infection. Microscopically, it is difficult to separate the disease from other viral infections. At first, the vesicles are sharply demarcated, but fusion occurs later and secondary infection of the vesicles is very common, particularly in the tropics. This confuses the histopathological features.


Bone and joint infection occurs only in children; smallpox osteomyelitis has never been recorded in an adult. Osteomyelitis and arthritis were described as long ago as 1873 and have been recorded wherever smallpox has occurred. There are no race or sex differences and bone and joint involvement will be found in 2% to 5% of children who have clinical smallpox. If a radiological search is made for bone infection, osteomyelitis will be demonstrated even when there are no clinical findings; the incidence may rise as high as 20%. It should be emphasized that this is a true viral infection. Variola bodies can be identified in otherwise sterile joint effusions, and there may be viral inclusions in the bone marrow as well. The whole clinical course of the bone and joint infection is totally different from that of pyogenic or other bacterial osteomyelitis. There is no response to any antibiotic or chemotherapeutic regimen and the radiological appearances are unlike those of any bacterial or fungal osteomyelitis or arthritis; many detailed investigations have failed to demonstrate any other organism in the smallpox cases.

Laboratory Diagnosis

Laboratory studies can be of considerable significance in patients who have died with little clinical evidence of the disease, or in some children with a "strange" osteomyelitis in which the previous smallpox infection has not been clinically recognized. Unfortunately, all available laboratory tests require specific expertise and careful interpretation. There is a complement fixation test and another for soluble antigens; both are reliable. Direct examination of the smears from vesicles may demonstrate elementary bodies; recognition of the virus by electron microscopy is possible. It should be reemphasized that the techniques are difficult and that laboratory identification is not easy. Cultures are more certain and may be obtained on the chorioallantoic membrane of developing chick embryos. Colonies are produced in 3 days; those of variola are pinpoint, whereas the vaccinia cultures are confluent and varicella fails to grow. Unfortunately, it is not always possible to culture variola virus, so that failure to produce a colony does not necessarily mean that the virus is varicella.

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Copyright: Palmer and Reeder