CLINICAL DESCRIPTION

Smallpox is a systemic viral disease which presents with a characteristic eruptive rash. The onset of smallpox is sudden, with a prodrome characterized by fever, malaise, headache, severe backache, prostration, and occasionally abdominal pain. After 2-4 days the temperature falls and a rash appears.

The rash progresses through successive stages of macules, papules, vesicles, pustules, and finally scabs that fall off at the end of the 3rd – 4th week of illness; the lesions are at the same stage of development in any given area. The fever frequently rises as the rash progresses to the pustular stage. The lesions first appear on the face and subsequently on the body and extremities, are more abundant on the face and extremities than on the trunk (centrifugal distribution), and are abundant over prominences and extensor surfaces. In previously vaccinated persons, the rash may be significantly modified to the extent that systemic symptoms are mild to nil and only a few highly atypical lesions are seen which sometimes do not pass through the usual successive stages of rash.

Two principal clinical-epidemiologic varieties of smallpox are recognized: variola minor (alastrim) with a case-fatality ratio of less than 1%, and variola major (classical smallpox) with a case-fatality ratio among the unvaccinated of 15 – 40%. Death occurs as early as the 3rd – 4th day of development of rash but more usually during the 2nd week. Approximately 3% of hospitalized variola major cases experience a fulminating disease characterized by a severe prodrome, prostration and bleeding into the skin and mucous membranes, uterus and genital tract, especially in pregnant women; such hemorrhagic cases are rapidly fatal. In some instances when the usual rash does not appear, disease was confused with severe acute leukemia, meningococcemia or idiopathic thrombocytopenic purpura.

In the highly lethal “flat” variety, observed in about 5% of cases, the focal lesions are slow to develop, and the vesicles contain very little fluid and tend to project only slightly above the surrounding skin and are soft and velvety to the touch. In the few patients with this type who survived, the lesions sometimes resolve without the usual pustulation and crusting.
Variola minor is associated with the rash similar to that observed in variola major; however, the patient generally experiences less severe systemic reactions and “hemorraghic” and “flat” types were virtually unknown.

Smallpox is usually distinguished by the clear-cut prodromal illness, the centrifugal distribution of the rash, the appearance of all lesions more or less simultaneously, the similarity in appearance of all lesions in a given area, and its more deeply seated lesions. The disease most commonly confused with smallpox is chickenpox.

Laboratory diagnosis is based on identification of virus by direct electron microscopy, immunohistochemistry, and polymerase chain reaction (PCR). Isolation of virus on live-cell cultures, followed by nucleic acid identification, or growth on chorioallantois, is confirmatory. The serologic testing does not differentiate among orthopoxvirus species, and paired serum samples are required to distinguish recent infection from vaccination in the remote past. Testing can be performed at Level C or D laboratories only.

CASE CLASSIFICATION

1. CONFIRMED
   
   A clinically compatible illness, AND
   • Isolation of smallpox (variola) virus from a clinical specimen (Level D* laboratory only), OR
   • Polymerase chain reaction (PCR) identification of variola DNA in a clinical specimen, OR
   • Negative stain electron microscopy (EM) identification of variola virus in a clinical specimen (Level D* laboratory or approved Level C** laboratory).

   * CDC and USAMRIID
   ** The NJ Public Health and Environmental Laboratories, NJDHSS, and others that have required safety and containment facilities.

2. PROBABLE
   
   A clinically compatible illness that is not laboratory confirmed, but has an epidemiological link to another confirmed or probable case.
   
   
3. POSSIBLE

   Either

   • A clinically compatible illness that is not laboratory confirmed and does not have an epidemiological link to a confirmed or probable case of smallpox, OR
   • A case that has an atypical presentation that is not laboratory confirmed but has an epidemiological link to a confirmed or probable case of smallpox. Atypical presentations of smallpox include a) hemorrhagic lesions or b) flat, velvety lesions not appearing as typical vesicle nor progressing to pustules.

   NOTE:
   1. The case definitions above (which are identical to CDC’s) may require revision by public health personnel conducting the epidemiological investigation depending upon the specifics of the epidemic.
   2. Report any suspicion of smallpox called to your attention by a healthcare provider or any positive laboratory result pertaining to smallpox.
   3. Report any other communications received from anonymous sources which might be smallpox caused by bioterrorism.

   Initial confirmation of a smallpox outbreak requires testing in a Level D laboratory (CDC and USAMRIID). Level C laboratories will assist with testing of clinical specimens following initial confirmation of an outbreak by CDC.