Orthopoxvirus

Orthopoxvirus is a genus of poxviruses that includes many species isolated from non-human mammals, such as Buffalopox virus, Camelpox virus, Cowpox virus, Monkeypox virus, Rabbitpox virus, Sealpox virus, Volepox virus and Ectromelia virus, which causes mousepox. The most famous member of the genus is Variola vera, which causes smallpox. It was wiped out using another orthopoxvirus, the Vaccinia virus.

Taxonomy
Members of the genus Orthopoxvirus are members of the subfamily Chordopoxvirinae, which is a division of the dsDNA viral family Poxviridae.

Distribution
Orthopox viruses are distributed universally. All mammalian Orthopoxviruses should be considered capable of establishing infections in humans. Zoonoses of many of these mammalian isolates have been reported.

Laboratory transmission
Aerosols of concentrated virus may result in Orthopox infection, especially in non-immunized individuals. Needle sticks, especially with concentrated virus, may result in severe local infection of the skin even in immunized individuals.

Clinical manifestation
They are transmitted primarily by respiratory droplets, though direct contact with bodily fluids or objects contaminated with bodily fluids may also transmit infection. Initial symptoms of Orthopoxvirus infection include fever, malaise, head and body aches, and sometimes vomiting.

Signs and symptoms
The initial symptoms include fever, malaise, head and body aches, and sometimes vomiting. Lesions that developed into crater-like ulcers surrounded by inflammatory tissue and eventually covered by thick black crusts are the characteristic indicators of Orthopox infection. Severe edema and erythema may affect large areas in cases of severe infection. Encephalitis (alteration of mental status and focal neurologic deficits), myelitis (upper- and lower-motor neuron dysfunction, sensory level and bowel and bladder dysfunction), or both may result from Orthooxvirus infection. Rarely, Orthopoxviruses may be detected in cerebrospinal fluid. Some mammalian Orthopox infections are known to result in high instances of mortality.

Treatment
Vaccinia-specific immunoglobulins may be administered to infected individuals. The only product currently available for treatment of complications of Orthopox infection is Vaccinia Immunoglobulin (VIG), which is an isotonic sterile solution of the immunoglobulin fraction of plasma from persons vaccinated with vaccinia vaccine. It is effective for treatment of eczema vaccinatum and certain cases of progressive vaccinia. However, VIG is contraindicated for the treatment of vaccinial keratitis. VIG is recommended for severe generalized vaccinia if the patient is extremely ill or has a serious underlying disease. VIG provides no benefit in the treatment of postvaccinal encephalitis and has no role in the treatment of smallpox. Current supplies of VIG are limited, and its use should be reserved for treatment of vaccine complications with serious clinical manifestations. The recommended dosage of the currently available VIG for treatment of complications is 0.6 ml/kg of body weight. VIG must be administered intramuscularly and should be administered as early as possible after the onset of symptoms. Because therapeutic doses of VIG might be substantial (e.g., 42 ml for a person weighing 70 kg), the product should be administered in divided doses over a 24- to 36-hour period. Doses can be repeated, usually at intervals of 2--3 days, until recovery begins (e.g., no new lesions appear). Future reformulations of VIG might require intravenous administration, and health-care providers should refer to the manufacturer's package insert for correct dosages and route of administration. CDC is currently the only source of VIG for civilians (see Vaccinia Vaccine Availability for contact information). The Food and Drug Administration has not approved the use of any antiviral compound for the treatment of vaccinia virus infections or other Orthopoxvirus infections, including smallpox. Certain antiviral compounds (Siga-246) have been reported to be 100% active against vaccinia virus or other Orthopoxviruses in vitro and among test animals. ST-246 has been granted orphan drug status by the FDA and is currently under study to determine the safety and effectiveness in humans. Questions also remain regarding the effective dose and the timing and length of administration of these antiviral compounds. Insufficient information exists on which to base recommendations for any antiviral compound to treat postvaccination complications or Orthopoxvirus infections, including smallpox. However, additional information could become available, and health-care providers should consult CDC to obtain up-dated information regarding treatment options for smallpox vaccination complications (see Consultation Regarding Complications of Vaccinia Vaccine).