COMMENTARY

Literature Commentary by Dr. John G. Bartlett: Viral Infections, January 2008

John G. Bartlett, MD

Disclosures

January 09, 2008

Vaccinia/Smallpox Vaccination

Household transmission of Vaccinia virus from contact with a military smallpox vaccinee -- Illinois and Indiana, 2007. MMWR Morb Mortal Wkly Rep. 2007;56:478-481. The report is the first documented case of eczema vaccinatum reported in the United States since 1988.[3] This is recognized as a life-threatening complication of smallpox vaccination. The sequence of events was as follows:

January 26, 2007: A member of the military received his first-time smallpox vaccination in preparation for deployment. He had a history of childhood atopic dermatitis and household contact with 2 of his children with eczema, both of which are contraindications to vaccination.

February 16-20, 2007: The soldier's deployment was delayed so he visited his family in Indiana. He reported that his vaccination had scabbed over at that time. During the home leave he had extensive contact with his 28-month-old son.

February 24, 2007: The son had fever and then was hospitalized with weeping skin lesions.

March 3, 2007: The child was hospitalized with a generalized papular vesicular rash on the face, neck, and arms. This progressed to cover 50% of the keratinized skin.

March 6, 2007: The mother developed 6 vesicular lesions on the face, these were shown to be vaccinia and she was treated with Vaccinia Immune Globulin Intravenous (Human) (VIGIV). The lesions quickly healed.

March 8, 2007: PCR analysis in the child showed nonvariola orthopoxvirus; the diagnosis of vaccinia was confirmed at the US Centers for Disease Control and Prevention (CDC). The child was treated with VIGIV, but by March 10 the illness progressed to hypothermia and shock requiring vasopressors. Antiviral therapy included cidofovir and an investigational drug, ST-246, under an emergency investigational drug application.

Investigation of 23 family contacts, including 2 siblings and 73 healthcare worker contacts, revealed no additional cases. Multiple swab samples from the home were positive for vaccinia virus DNA by PCR, and culture of 3 items from the home showed viable virus. Disinfection procedures were done with phenolics on household surfaces, and cloth specimens had phenolic presoak followed by hot washes.

The authors note that the mortality rate of eczema vaccinatum was previously reported at 30% to 40%, but this had been reduced to 7% with VIGIV treatment.[4]

Comment: Additional -- and perhaps more colorful -- information on this case was provided in Science magazine.[5] It is noted that the soldier completed a form asking whether he had a history of eczema or household contacts with eczema, which he denied. The pustular rash was impressive, with very characteristic umbilicated circular pustules. The physicians in Chicago began the standard treatment with VIGIV which was brought by a US marshal from the CDC stockpile. However, the child deteriorated, requiring narcotics for pain, blood pressure support, and ventilator support; the condition was considered "grim." This prompted the use of cidofovir, but his condition continued to deteriorate. On March 10, CDC's Inger Damon (Chief, Poxvirus Activity, Division of Viral and Rickettsial Diseases) suggested the experimental smallpox antiviral drug ST-246. The US Food and Drug Administration (FDA) approved emergency use of the drug within hours, and the chief scientific officer of the company that developed it (SIGA Technologies, Inc., Corvallis, Oregon) delivered it to Chicago in a private jet funded by billionaire Ronald Perelman, who is an investor in SIGA. The boy was discharged on April 29 looking "very good." The review finishes with 2 additional notations: (1) the acknowledgement that no one can know which therapy or therapies worked: VIGIV, cidofovir, or ST-246; (2) care was provided with advice from "20 experts on daily conference calls for one month."

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