Medication Summary
VIG is the only drug available for amelioration of some vaccinia-related complications. VIG is produced from pooled human sera taken from vaccinia-immunized individuals and is available only from the CDC. VIG has been effective when administered early in cases of vaccinia necrosum and eczema vaccinatum. VIG has not been effective in cases of encephalopathy. The use of VIG for generalized vaccinia reactions is usually unnecessary. Vaccinia immune globulin, intravenous (VIGIV) has recently been approved by the US Food and Drug Administration.
Cidofovir (Vistide, Gilead Sciences, Foster City, Calif), a nucleotide analogue of cytosine, has demonstrated antiviral activity against certain orthopoxviruses in cell-based in vitro and animal model studies. The CDC proposes an investigational use of cidofovir in the treatment of vaccinia-related complications, which has not been studied among humans; thus, the benefits are uncertain.
Immune globulins
Class Summary
These agents are used for passive immunity. Therapy consists of administration of immunoglobulin pooled from serum of immunized subjects.
Vaccinia immune globulin intravenous (VIG)
Produced from the pooled sera of vaccinia-immunized individuals. Preparation contains antibodies targeted against vaccinia virus. Indicated for the treatment of vaccinia necrosum and eczema vaccinatum.
Vaccinia immune globulin intravenous
Derived from human plasma and manufactured from pooled plasma donors who received booster immunizations with smallpox vaccine (Dryvax). Contains increased antibody levels against vaccinia virus. Indicated to treat rare adverse reactions and aberrant infections caused by vaccinia virus, including aberrant infections (eg, accidental implantation in the eyes, mouth, other potentially hazardous areas), eczema vaccinatum, progressive vaccinia, severe generalized vaccinia, and vaccinia infections in immunocompromised individuals.
Antiviral Agent
Class Summary
Cidofovir will be released for civilian use by the CDC and for military use by the Department of Defense if the patient meets the following criteria: (1) VIG treatment fails to elicit a response, (2) a patient is near death, or (3) all inventories of VIG have been exhausted. This proposed use of cidofovir is investigational, and its effectiveness in the treatment of vaccinia-related complications among humans is unknown.
Cidofovir (Vistide)
Not licensed for use as a treatment for smallpox. Currently approved for treatment of CMV retinitis in AIDS. Cidofovir is the first member of a group of antivirals known as acyclic phosphonate nucleotide analogs. Cidofovir diphosphate, the active intracellular metabolite of cidofovir, inhibits herpes virus polymerases at concentrations that are 8- to 600-fold lower than those needed to inhibit human cellular DNA polymerases alpha, beta, and gamma. Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis. Adefovir, cidofovir, and ribavirin are under investigation for smallpox. Ribavirin as an aerosol treatment for pediatric respiratory syncytial virus is under investigation.
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| Complication | Number of cases from 450,293 vaccinations administered between 12/13/2002 and 5/28/2003 | Department of Defense rate per million vaccinees (95% confidence interval) | Historical number of cases from 1950s and 1960s |
| Death | 0 | 0 (0-3.7) | Age 1 y at first vaccination - 5 per 1 million primary vaccinees |
| Age 1-4 y at first vaccination - 0.5 per 1 million primary vaccinees | |||
| Age 5-19 y at first vaccination - 0.5 per 1 million primary vaccinees | |||
| Age ≥ 20 y at first vaccination - No data | |||
| Encephalitis | 1 | 2.2 (0.6-7.2) | 3 per 1 million primary vaccinees |
| Vaccinia necrosum/progressive vaccinia | 0 | 0 (0-3.7) | Approximately 1 patient per million during primary or revaccination |
| Usually fatal over a period of several months | |||
| Eczema vaccinatum | 0 | 0 (0-3.7) | 1 per 100,000 primary vaccinees |
| 1 per 1 million revaccinees | |||
| Generalized vaccinia | 36 | 80 (63-100) | Occasional occurrence in immunocompetent individuals |
| 3 per 100,000 primary vaccinees | |||
| 1 per 1 million revaccinees | |||
| Accidental vaccinia | 48 | 107 (88-129) | 3 per 100,000 to 1 million vaccinees |
| Erythematous rash | 36 | 80 (63-100) | Approximately 1 per 100,000 primary vaccinees* |
| Acute myopericarditis | 37 | 82 (65-102) | 100 per 1 million vaccinees |
| *Incidence was slightly higher when vaccination occurred before age 1 year. | |||

