SMALLPOX was declared eradicated by the World Health Organization in 1980. However, because of its potential as a biological weapon capable of inflicting mass casualties, Smallpox has again become a concern. A former deputy director of the Soviet Union’s bioweapons program has stated that in the 1980’s and 90’s Russia produced many tons of smallpox virus for use in intercontinental ballistic missiles and bombs and developed more virulent and contagious recombinant strains. The potential for a lethal pandemic following a reintroduction of Smallpox into a world populated by unvaccinated and previously vaccinated but no longer protected persons should not be underestimated: prior to widespread use of smallpox vaccination most individuals worldwide acquired smallpox at some time in their lives.
Smallpox is a DNA virus of the genus orthopoxvirus. The four members of this genus capable of infecting and causing disease in humans are variola (Smallpox virus), monkeypox virus, vaccinia, and cowpox virus. Buffalopox, a fifth orthopoxvirus of uncertain origin that may represent a vaccinia subspecies, can also infect humans. Orthopoxviruses are among the largest (diameter ~ 200 nm) and most complex (186,103 bp: Smallpox strain - Bangladesh 1975) of all known viruses. Prior to eradication of naturally occurring smallpox, two strains of variola virus circulated: variola major, the cause of classical smallpox with a mortality rate of 20% to 50%, and variola minor (alastrim), a milder form with a mortality rate of < 1%. Infection of the respiratory mucosa leads to viral multiplication in regional nodes and an asymptomatic viremia by the third or forth day. Variola multiplication then occurs in the bone marrow, spleen and nodes followed by a second viremia on about the eighth day. The second viremia involves skin and mucosal blood vessels resulting in enanthem, exanthem, and systemic illness.
Following respiratory exposure, the patient enters the incubation period that lasts 12 days (range 7 – 19 days). In about 90 % of patients the onset of symptoms is acute and includes chills, fever, backache, severe abdominal pain, headache, vomiting, and occasionally delirium. Within two to three days, patients develop an enanthem involving the oral cavity. An enanthem typically precedes a maculopapular rash of the face, hands, and forearms that then spreads to the legs and trunk. Over the next 24 to 48 hours, the rash progresses from maculopapular to vesicular to pustular. Pustules are deep in the skin, round and tense. Crusts begin to develop by the eight or ninth day of the rash and leave a scar. With the onset of the enanthem and rash, large amounts of variola are released in the saliva and correlate with the ability of the patient to transmit the infection. Tissues other than the skin, blood, and reticulum cells are usually not involved. Death occurs in 30 %, usually in the second week of illness, and is usually due to toxemia from circulating immune complexes and soluble antigen. Some patients develop a perivascular demyelinating encephalitis, but clinically important secondary bacterial infections are not common. Two other forms of smallpox occur: hemorrhagic (associated with more severe symptoms plus hemorrhages into the skin and mucosa – 100 % fatal) and malignant (the rash develops as soft rather than tense confluent lesions and does not progress to pustules – mortality rate ~ 70 %). .
Diagnosis is based upon clinical presentation (see above) and laboratory confirmation. A recently vaccinated person in gloves and mask should collect specimens for viral identification. Both fluid from lesions, absorbed onto a swab, and scabs can be placed in a plain Vacutainer tube and sealed with tape. Laboratory examination should be in a BL 4 facility. Electron microscopy provides rapid confirmation, but identification requires growth of virus on chorioallantoic egg membranes and characterization by PCR. Therapy is supportive.
Currently there is no specific anti-viral therapy proven effective in clinical smallpox disease.
Vaccinia vaccination by 4th day or intravenous cidofovir by 2nd post exposure day may be of benefit.
One primary case of Smallpox may lead to 20 secondary generation cases and more tertiary cases.
Henderson DA. Et al: Smallpox as a Biological Weapon (Consensus Statement). JAMA. 1999 June 9;281, No. 22: 2127-2137.