Clinical Features

The incubation period of smallpox averages 12 days, although it could range from 7-19 days following exposure. Clinical symptoms begin acutely with malaise, fever, rigors, vomiting, headache, and backache; 15% of patients develop delirium.

Approximately 10% of light-skinned patients exhibit a rash during this phase. After two to three days small bumps erupt concurrently with a discrete rash about the face, hands and forearms.

Following eruptions on the lower extremities, the rash spreads centrally to the trunk over the next week. Lesions quickly progress from rash to red bumps, and eventually to pus-filled sores. Lesions are more abundant on the extremities and face, and this centrifugal distribution is an important diagnostic feature. In distinct contrast to varicella, lesions on various segments of the body remain generally synchronous in their stages of development.

From 8 to 14 days after onset, the pustules form scabs that leave depressed depigmented scars upon healing. Although variola concentrations in the throat, eyes, and urine diminish with time, virus can be readily transmitted from scabs during convalescence. Therefore, patients should be isolated and considered infectious until all scabs separate.

For the past century, two distinct types of smallpox were recognized. Variola minor was distinguished by milder systemic toxicity and more diminutive pox lesions, and caused 1% mortality in unvaccinated victims.

Variola major caused mortality of 3% and 30% in the vaccinated and unvaccinated, respectively. Other clinical forms associated with variola major, flat-type and hemorrhagic type smallpox, are notable for high death rate. A naturally occurring relative of variola, monkeypox, occurs in Africa, and is clinically indistinguishable from smallpox with the exception of a lower case fatality rate and notable enlargement of lymph nodes.

Diagnosis

Smallpox must be distinguished from other similar diseases, such as chickenpox, cowpox, or allergic contact dermatitis. Particularly problematic to infection control measures would be the failure to recognize relatively mild cases of smallpox in persons with partial immunity. An additional threat to effective quarantine is the fact that exposed persons may spread the virus from a throat infection without ever manifesting the disease. Therefore, quarantine and initiation of medical countermeasures should be promptly followed by an accurate diagnosis so as to avert panic.

The usual method of diagnosis is demonstration of characteristic virions on electron microscopy of vesicular scraping. Under light microscopy, aggregations of variola virus particles, called Guarnieri bodies are found. Another rapid but relatively insensitive test for Guarnieri bodies in vesicular scrapings is Gispen's modified silver stain, in which cytoplasmic inclusions appear black.

None of the above laboratory tests are capable of discriminating variola from vaccinia, monkeypox or cowpox. This differentiation classically required isolation of the virus and characterization of its growth on chorioallantoic membrane. The development of polymerase chain reaction diagnostic techniques promises a more accurate and less cumbersome method of discriminating between variola and other Orthopoxviruses.

Medical Management

Medical personnel must be prepared to recognize a skin eruption in possible bioterrorism theaters as potentially variola, and to initiate appropriate countermeasures. Any confirmed case of smallpox should be considered an international emergency with immediate report made to public health authorities. Precautions against both airborne and bodily fluid contaminate infection must be in place for a minimum of 17 days following exposure for all persons in direct contact with the index case, especially the unvaccinated.

Strict quarantine of exposure contacts may prove to be impractical and impossible to enforce. A reasonable alternative would be to require contacts to check their temperatures daily. Any fever above 38 C (101 F) during the 17-day period following exposure to a confirmed case would suggest the development of smallpox.

The contact should be isolated immediately, preferably at home, until smallpox is either confirmed or ruled out and remain in isolation until all scabs separate. Patients should be considered infectious until all scabs separate. Immediate vaccination or revaccination should also be undertaken for all personnel exposed to either weaponized variola virus or a clinical case of smallpox.

The potential for airborne spread to other than close contacts is controversial. In general, close person-to-person contact is required for transmission to reliably occur. Nevertheless, variola's potential in low relative humidity for airborne dissemination was alarming in two hospital outbreaks. Smallpox patients were infectious from the time of onset of their eruptive skin sores, most commonly from days 3-6 after onset of fever. Infectivity was markedly enhanced if the patient manifested a cough. Indirect transmission via contaminated bedding or other materials was infrequent. Some close contacts harbored virus in their throats without developing disease, and hence might have served as a means of secondary transmission.

Vaccination with a verified clinical "take" (vesicle with scar formation) within the past 3 years is considered to render a person immune to smallpox. However, given the time since mass vaccination of the population, re-vaccination of all potentially exposed personnel would seem prudent if there existed a significant prospect of smallpox exposure.

Preventative Measures

Smallpox vaccine (vaccinia virus) before exposure and infection is the recommended procedure. Vaccination after exposure to smallpox may prevent or reduce the effects of the disease if given as soon as possible and preferably within 7 days after exposure.

A serum-filled blister typically appears at the vaccination site 5-7 days post-inoculation. The lesion forms a scab and gradually heals over the next 1-2 weeks.

Side effects include low-grade fever and swollen lymph glands. The attendant redness and hardening of the vaccination site is frequently misdiagnosed as bacterial infection. More severe first-time vaccine reactions include secondary spreading of the virus to other sites such as the face, eyelid, or other persons (6 in 10,000 vaccinations) and the usually mild, skin and sometimes systemic reaction in individuals who have been inoculated with smallpox vaccine. This is a systemic spread of the virus which produces lesions away from the primary vaccination site (3 in 10,000 vaccinations).

Vaccination is not recommended in the following conditions:

• Suppressed immune systems.
• HIV infection.
• History or evidence of non-contagious skin lesions.
• Current sexual, or other close physical contact with person(s) possessing one of these conditions.
• Vaccination should not be given during pregnancy.

Most authorities state that, with the exception of significant impairment of the immune system, there are no absolute contraindications to post- exposure vaccination of a person who has been exposed to variola.

Passive Prevention

Vaccinia Immune Globulin (VIG) is generally indicated for treatment of complications to the smallpox (vaccinia) vaccine, and should be available when administering vaccine. Limited data suggests that vaccinia immune globulin may be of value in post-exposure treatment of smallpox when given within the first week following exposure, and concurrently with vaccination. Vaccination alone is recommended for those without contraindications to the vaccine. If greater than one week has elapsed after exposure, administration of both products, if available, is reasonable.