Contact transmission of vaccinia virus from smallpox vaccinees in the United States, 2003–2011

Wertheimer, Ellen; Olive, D; Brundage, John F.; Clark, Leslie L.

doi:10.1016/j.vaccine.2011.12.049

Cited by 15 publications

(10 citation statements)

References 14 publications

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“…The exposure of naïve individuals to the vaccine virus through contact with shedding vaccinees is a challenge in the ongoing polio eradication campaign and is a recognized risk of the smallpox vaccine (33,34). While a safe and efficient inactivated polio vaccine is available, efforts to develop an inactivated MV vaccine ceased in the 1960s, after a formalin-inactivated formulation was associated with more severe disease (35).…”

Section: Discussionmentioning

confidence: 99%

Nectin-4-Dependent Measles Virus Spread to the Cynomolgus Monkey Tracheal Epithelium: Role of Infected Immune Cells Infiltrating the Lamina Propria

Frenzke

Sawatsky

Wong

et al. 2013

J Virol

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cAfter the contagion measles virus (MV) crosses the respiratory epithelium within myeloid cells that express the primary receptor signaling lymphocytic activation molecule (SLAM), it replicates briskly in SLAM-expressing cells in lymphatic organs. Later, the infection spreads to epithelia expressing nectin-4, an adherens junction protein expressed preferentially in the trachea, but how it gets there is not understood. To characterize the mechanisms of spread, we infected groups of 5 or 6 cynomolgus monkeys (Macaca fascicularis) with either a wild-type MV or its "N4-blind" derivative, which is unable to enter nectin-4-expressing cells because of the targeted mutation of two hemagglutinin residues. As expected, both viruses caused similar levels of immunosup-

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Section: Discussionmentioning

confidence: 99%

Nectin-4-Dependent Measles Virus Spread to the Cynomolgus Monkey Tracheal Epithelium: Role of Infected Immune Cells Infiltrating the Lamina Propria

Frenzke

Sawatsky

Wong

et al. 2013

J Virol

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“…The number of percutaneous punctures used to administer ACAM2000 to persons receiving their first smallpox vaccination (15) is greater than had been used for Dryvax (3). [16][17][18] A recent study 19 summarized contact vaccinia transmission events from December 2002 to March 2011, a period when both Dryvax ® and ACAM2000 ® were used. Additional case reports and investigations of sporadic contact transmission events associated with ACAM2000 ® have been described.…”

Section: Introductionmentioning

confidence: 99%

Unintentional transfer of vaccinia virus associated with smallpox vaccines

Tack

Karem

Montgomery

et al. 2013

Human Vaccines & Immunotherapeutics

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“…The treatment of progressive vaccinia infections in patients with compromised immune systems has been a daunting challenge (2)(3)(4)(5). As the number of individuals who have been successfully treated has increased, greater understanding has been gained regarding the use of combination chemotherapy involving antiviral compounds plus VIG.…”

Section: Discussionmentioning

confidence: 99%

“…erious, life-threatening, progressive vaccinia infections have arisen in individuals after receipt of a smallpox vaccination, usually in military personnel or their household contacts, such as young children (1)(2)(3). A primary component of the treatment of such infections is vaccinia immune globulin (VIG) (4,5).…”

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confidence: 99%

“…Vaccinia infections in SCID mice are difficult to treat due to the profound immunosuppressive state of the mice, and a cure is not generally possible unless treatment is initiated very early postexposure (13). The delayed-treatment SCID mouse model may be a good representation of the treatment of vaccinia infections in immunocompromised humans, who require aggressive antiviral/ VIG therapy (3)(4)(5). In an alternative mouse model, we developed a progressive vaccinia virus cutaneous infection model in normal hairless mice (SHK-1 strain) that were immunosuppressed with cyclophosphamide (15).…”

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confidence: 99%

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Enhanced Efficacy of Cidofovir Combined with Vaccinia Immune Globulin in Treating Progressive Cutaneous Vaccinia Virus Infections in Immunosuppressed Hairless Mice

Smee

Dagley

Downs

et al. 2015

Antimicrob Agents Chemother

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The treatment of progressive vaccinia in individuals has involved antiviral drugs, such as cidofovir (CDV), brincidofovir, and/or tecovirimat, combined with vaccinia immune globulin (VIG). VIG is costly, and its supply is limited, so sparing the use of VIG during treatment is an important objective. VIG sparing was modeled in immunosuppressed mice by maximizing the treatment benefits of CDV combined with VIG to determine the effective treatments that delayed the time to death, reduced cutaneous lesion severity, and/or decreased tissue viral titers. SKH-1 hairless mice immunosuppressed with cyclophosphamide and hairless SCID mice (SHO strain) were infected cutaneously with vaccinia virus. Monotherapy, dual combinations (CDV plus VIG), or triple therapy (topical CDV, parenteral CDV, and VIG) were initiated 2 days postinfection and were given every 3 to 4 days through day 11. The efficacy assessment included survival rate, cutaneous lesion severity, and viral titers. Delays in the time to death and the reduction in lesion severity occurred in the following order of efficacy: triple therapy had greater efficacy than double combinations (CDV plus VIG or topical plus parenteral CDV), which had greater efficacy than VIG alone. Parenteral administration of CDV or VIG was necessary to suppress virus titers in internal organs (liver, lung, and spleen). The skin viral titers were significantly reduced by triple therapy only. The greatest efficacy was achieved by triple therapy. In humans, this regimen should translate to a faster cure rate, thus sparing the amount of VIG used for treatment. Serious, life-threatening, progressive vaccinia infections have arisen in individuals after receipt of a smallpox vaccination, usually in military personnel or their household contacts, such as young children (1-3). A primary component of the treatment of such infections is vaccinia immune globulin (VIG) (4, 5). VIG is expensive and difficult to produce in large quantities. The U.S. government maintains a small stockpile of the material that can be severely depleted, even by just one treated individual. As an example, in 2012, the case of an immunosuppressed military vaccinee with a severe progressive vaccinia infection was reported. The individual was successfully treated, but treatment required 341 vials of VIG over the course of 75 days in addition to oral and topical treatments with tecovirimat (ST-246) and brincidofovir (CMX001, an orally active prodrug of cidofovir [CDV]) (4).Many animal models exist for studying the treatment of infections with vaccinia virus, including those using mice, prairie dogs, rabbits, and nonhuman primates (6-8). Mice are most often used because of their availability in large numbers and relatively low cost. Several studies in mice have reported VIG as a single treatment for severe vaccinia virus infections (9-12). Two reports addressed the use of CDV in combination with VIG to treat progressive vaccinia infections in severe combined immunodeficient (SCID) mice (13,14). These investigations were performe...

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Contact transmission of vaccinia virus from smallpox vaccinees in the United States, 2003–2011

Cited by 15 publications

References 14 publications

Nectin-4-Dependent Measles Virus Spread to the Cynomolgus Monkey Tracheal Epithelium: Role of Infected Immune Cells Infiltrating the Lamina Propria

Nectin-4-Dependent Measles Virus Spread to the Cynomolgus Monkey Tracheal Epithelium: Role of Infected Immune Cells Infiltrating the Lamina Propria

Unintentional transfer of vaccinia virus associated with smallpox vaccines

Enhanced Efficacy of Cidofovir Combined with Vaccinia Immune Globulin in Treating Progressive Cutaneous Vaccinia Virus Infections in Immunosuppressed Hairless Mice

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