Vaccinia progressive

Progressive vaccinia, also known as vaccinia necrosum, occurs when the vaccinial lesion fails to heal and instead progresses to involve adjacent skin with tissue necrosis (Fig. 2.11 see color plate 2.11). The lesion can spread metastatically to other parts of the skin, to bones and to viscera (26). Although progressive vaccinia occurs 

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During the US pre-event smallpox vaccination program, there were no reports of eczema vaccinatum, progressive Vaccinia, or fetal Vaccinia (19,20). 

Fig. 2.11 (See color plate) Severe progressive vaccinia. From Fulginiti, V. Smallpox vaccination adverse reaction. CDC Smallpox, http //www.bt.cdc.gov/training/smallpoxvaccine/reactions/ adverse.html...

Vaccinia immune globulin IV is a vaccinia-specific immunoglobulin G (IgG), which directly neutralizes vaccinia virus. It is indicated in treatment and/or modification of aberrant infections induced by vaccinia virus (including accidental implantation in eyes, mouth, or other areas where vaccinia infection would constitute a special hazard), eczema vaccinatum, progressive vaccinia, severe generalized vaccinia, and vaccinia infections in individuals who have skin conditions such as bums, impetigo, varicella-zoster, or poison ivy, or in individuals with eczematous skin lesions. Treat complications that include vaccinia keratitis with caution. 

More severe complications of vaccinia vaccination include eczema vaccinatum, progressive vaccinia, and postvaccinial encephalitis. These complications are rare, but occur at least 10 times more often among primary vaccinees than among revaccinees. Eczema vaccinatum is a localized or systemic dissemination of vaccinia virus among persons who have eczema (Figure 27-7). Although usually mild and self-limited, this complication could be severe or even fatal in up to 10% of cases. 

Progressive vaccinia (vaccinia necrosum) is a progressive necrosis in the area of vaccination, often with metastatic lesions (Figure 27-8). This complication occurred almost exclusively in persons with cellular immunodeficiency,93 with a case fatality rate of higher than 75%.94... 

Vaccinia-immune globulin (VIG) is of value in the treatment of progressive vaccinia, eczema vaccinatum,97 and perhaps ocular vaccinia (VIG is discussed below in the section titled Passive Immunoprophylaxis). Topical idoxuridine may benefit vaccinia keratitis.98 99... 

Fig. 27-8. Progressive vaccinia or vaccinia necrosum. As seen in this child, progressive viral replication at the inoculation site in an immunocompromised individual leads to inexorable local tissue destruction. Reprinted with permission from Fenner F, Henderson DA, Arita I, Jezek Z, Ladnyi ID. Smallpox and Its Eradication. Geneva, Switzerland World Health Organization 1988 298. Photograph by C. H. Kempe.

Although clinical trials128 129 showed no therapeutic efficacy of thiosemicarbazones against smallpox, anecdotal reports130131 suggest some usefulness of methisazone in treating progressive vaccinia. 

Fulginiti VA, Kempe CH, Hathaway WE, et al. Progressive vaccinia in immunologically deficient individuals. Birth Defects. 1968 4 129-145. 

Progressive vaccinia (or vaccinia necrosum). Ongoing infection of skin with tissue destruction frequently leading to death. 

Early animal experiments have underlined the potential of vaccinia-based vector vaccines. Vaccinia virus-housing genes from HIV have clearly been found to elicit both humoral and cell-mediated immune responses in monkeys. Similar responses in other animals have been reported when surface polypeptides from a variety of additional pathogens have been expressed in recombinant vaccinia systems (Table 10.16). Human clinical trials are now in progress. 

The response just described is a major reaction, indicating that the vaccinia virus replicated in the skin, resulting in a successful vaccination. People previously vaccinated people should develop a major reaction just like primary vaccinees, except that the lesion progresses faster. Any vaccine recipient developing a major reaction should be considered protected. 

The first viral vector systems were developed more than 25 years ago [9], and since then viral gene therapy strategies has been progressively developed [10]. A variety of virus vectors has been employed and modified to deliver genes to cells to provide either transient, such as adenovirus [11-13], poxviruses (vaccinia) [14], or herpes virus [15], or permanent, such as retroviruses (lentivirus) [16-18] and adeno-associated virus [19], transgene expression each approach has its characteristic advantages and disadvantages. 

TroVax is Oxford BioMedica s therapeutic cancer vaccine, consisting of the 5T4 antigen [104] encoded by a modified vaccinia Ankara (MVA) virus. Early phase clinical trials reported potent CD4 + T cell and antibody responses in colorectal and prostate cancer patients [105, 106]. Time to progression was significantly longer in patients who developed 5T4-specific cellular responses compared with those who did not (5.6 vs. 2.3 months, respectively). However, there were no objective clinical responses. 

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