Smallpox

Smallpox, because of its high case-fatality rates and transmissibility, now represents one of the most serious bioterrorist threats to the civilian population.

Over the centuries, naturally occurring smallpox, with its case-fatality rate of 30 percent or more and its ability to spread in any climate and season, has been universally feared as the most devastating of all the infectious diseases.

Smallpox was once worldwide in scope; before vaccination was practiced almost everyone eventually contracted the disease. In 1980, the World Health Assembly announced that smallpox had been eradicated and recommended that all countries cease vaccination. That same year, the Soviet government embarked on an ambitious program to grow smallpox in large quantities and adapt it for use in bombs and intercontinental ballistic missiles. That initiative succeeded. Russia still possesses an industrial facility that is capable of producing tons of smallpox virus annually and also maintains a research program that is thought to be seeking to produce more virulent and contagious strains.

An aerosol release of smallpox virus would disseminate readily given its considerable stability in aerosol form and epidemiological evidence suggesting the infectious dose is very small. Even as few as 50-100 cases would likely generate widespread concern or panic and a need to invoke large-scale, perhaps national emergency control measures.

Several factors fuel the concern: the disease has historically been feared as one of the most serious of all pestilential diseases; it is physically disfiguring; it bears a 30 percent case-fatality rate; there is no treatment; it is communicable from person to person; and no one in the U.S. has been vaccinated during the past 25 years. Vaccination ceased in this country in 1972, and vaccination immunity acquired before that time has undoubtedly waned.

Approximately 140,000 vials of vaccine are in storage at the Centers for Disease Control and Prevention, each with doses for 50-60 people, and an additional 50-100 million doses are estimated to exist worldwide. This stock cannot be immediately replenished, since all vaccine production facilities were dismantled after 1980, and renewed vaccine production is estimated to require at least 24-36 months.

In 2000, CDC awarded a contract to Oravax of Cambridge, Massachusetts to produce smallpox vaccine. Initially producing 40 million doses, Oravax anticipates delivery of the first full scale production lots in 2004.

Recommendations of the Working Group include testing and ultimate consideration for FDA approval of a vaccinia strain grown in tissue culture rather than on calves, finding a rapid diagnostic test for smallpox virus in the asymptomatic early stages, and developing a more attenuated strain of vaccine.

The Disease

Transmission:Smallpox spreads directly from person to person, primarily by droplet nuclei expelled from the oropharynx of the infected person or by aerosol. Natural infection occurs following implantation of the virus on the oropharyngeal or respiratory mucosa.

A smallpox outbreak poses difficult problems because of the ability of the virus to continue to spread throughout the population unless checked by vaccination and/or isolation of patients and their close contacts.

Between the time of an aerosol release of smallpox and diagnosis of the first cases, an interval of as much as two weeks is apt to occur. This is because there is an average incubation period of 12 to 14 days.

Signs and Symptoms: After the incubation period, clinical manifestations begin acutely as the patient experiences high fever, malaise, rigors, vomiting, and prostration with headache and backache. Severe abdominal pain and delirium are sometimes present. A mascopapular rash then appears, first on the mucosa of the mouth and pharynx. Within one or two days, lesions first appear face and forearms, spreading to the trunk and legs as the rash becomes vesicular and later pustular quickly progressing from macules to papules (red spots) and eventually to pustular vesicles (blisters). They are more abundant on the upper extremities and face. The pustules are characteristically round, tense and deeply embedded in the dermis; crusts begin to form about the eighth or ninth day. When the scabs separate, pigment-free skin remains, and eventually pitted scars form.

Diagnosis: Neither electron nor light microscopy are capable of discriminating variola from vaccinia, monkeypox or cowpox. The new PCR diagnostic techniques may be more accurate in discriminating between variola and other Orthopoxviruses.

Treatment: At present there is no effective chemotherapy, and treatment of clinical cases of smallpox is limited to supportive therapy and antibiotics as required for treating secondary bacterial infections. There are no proven antiviral agents effective in treating smallpox.

Prophylaxis (Prevention): Immediate vaccination or revaccination should be undertaken for all personnel exposed.

Isolation and Decontamination: Droplet and airborne precautions for a minimum of 17 days following exposure for all contacts. Patients should be considered infectious until all scabs separate, and they quarantined during this period. In the civilian setting, strict quarantine of asymptomatic contacts may prove to be impractical and impossible to enforce. A reasonable alternative would be to require contacts to check their temperatures daily and to remain at home.

Contaminated clothing or bed linen could also spread the virus. All bed linens and objects in contact with the infected person should be handled carefully [latex gloves, surgical masks] so as not to spread the virus and special precautions need to be taken to insure that all bedding and clothing of patients are autoclaved.Disinfection of clothing, dishes and utensils with hypochlorite [bleach] should be carefully performed.

Any fever above 38 degrees C (101 F) during the 17-day period following exposure to a confirmed case would suggest the development of smallpox. The contact should then be isolated immediately, preferably at home, until smallpox is either confirmed or ruled out, and remain in isolation until all scabs separate. Although the fully developed cutaneous eruption of smallpox is unique, earlier stages of the rash could be mistaken for varicella (chicken pox). The smallpox blisters tend to all be at the same stage and size, whereas in chickenpox they are in different sizes and stages.

Secondary spread of infection constitutes a nosocomial hazard [spread by medical personnel in the hospital] from the time of onset of a smallpox patient's exanthem [rash] until scabs have separated. Quarantine with respiratory isolation should be applied to secondary contacts for 17 days post-exposure. Vaccinia vaccination, with the attenuated [weakened] virus early in the disease, and vaccinia immune globulin both possess some efficacy in post-exposure prophylaxis.

References:

1. USAMRIID Manual of Biological Warfare.

2. "Biohazard," Dr. Ken Alibek, former Deputy Commander of the Soviet Biopreparat for Research on Biological Weapons.

3. Col. Byron Weeks, MD, ret.