Smallpox and smallpox vaccination

Booss, John; Davis, Larry E.

doi:10.1212/01.wnl.0000063319.64515.6b

Cited by 41 publications

(28 citation statements)

References 30 publications

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“…Historically the most frequent precipitants were the childhood exanthemata and smallpox vaccination; around 1 per 1000 cases of measles typically is complicated by ADEM [45]. Primary smallpox vaccination is less frequently complicated by ADEM but still the most recent figures from the USA suggest an incidence in adults of 3.5 cases per 1,000,000 vaccinations [9]. In resource rich countries measles, mumps and rubella are now rare due to vaccination and routine smallpox vaccination has largely been abandoned.…”

Section: Acute Parainfectious Inflammatory Encephalopathies ■ Patholomentioning

confidence: 99%

Infection–associated encephalopathies—their investigation, diagnosis, and treatment

2006

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Reduced level of consciousness is a common clinical finding in acutely sick patients. In the majority of cases a cause for the encephalopathy is readily identifiable,whilst in a minority the aetiology is more difficult to ascertain. Frequently the onset of encephalopathy is associated with, or follows, infection. The mechanisms through which infection leads to encephalopathy are diverse. They range from direct microbial invasion of the brain or its supporting structures, to remote, infection-triggered mechanisms such as acute disseminated encephalomyelitis. Most common however, is the encephalopathy caused through a remote effect of systemic sepsis-septic encephalopathy. This article discusses the clinical presentation and underlying pathogeneses of the acute encephalopathies associated with infection, aiming to aid both their recognition and treatment.

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Section: Acute Parainfectious Inflammatory Encephalopathies ■ Patholomentioning

confidence: 99%

Infection–associated encephalopathies—their investigation, diagnosis, and treatment

2006

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“…However, replication-competent poxvirus vectors pose serious health risks because of their welldocumented capacity to disseminate in immunosuppressed individuals (7,9,31,41,43). These risks have increased in recent years due to a rising proportion of the population living with immunosuppression resulting from human immunodeficiency virus (HIV) infection, organ transplantation, or cancer therapies.…”

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confidence: 99%

Role of Genes That Modulate Host Immune Responses in the Immunogenicity and Pathogenicity of Vaccinia Virus

Jackson

Ilyinskii²,

Philippon³

et al. 2005

J Virol

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Poxvirus vaccine vectors, although capable of eliciting potent immune responses, pose serious health risks in immunosuppressed individuals. We therefore constructed five novel recombinant vaccinia virus vectors which contained overlapping deletions of coding regions for the B5R, B8R, B12R, B13R, B14R, B16R, B18R, and B19R immunomodulatory gene products and assessed them for both immunogenicity and pathogenicity. All five of these novel vectors elicited both cellular and humoral immunity to the inserted HIV-BH10 env comparable to that induced by the parental Wyeth strain vaccinia virus. However, deletion of these immunomodulatory genes did not increase the immunogenicity of these vectors compared with the parental vaccinia virus. Furthermore, four of these vectors were slightly less virulent and one was slightly more virulent than the Wyeth strain virus in neonatal mice. Attenuated poxviruses have potential use as safer alternatives to current replication-competent vaccinia virus. Improved vaccinia virus vectors can be generated by deleting additional genes to achieve a more significant viral attenuation.

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“…Although vaccination is now being offered to some healthcare workers and other "first responders," there are valid concerns about potential vaccine risks (3,9). Vaccination is not recommended for those with eczema and other exfoliative skin disorders or those with immunodeficiencies or for pregnant women.…”

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confidence: 99%

Inhibitory Activity of Alkoxyalkyl and Alkyl Esters of Cidofovir and Cyclic Cidofovir against Orthopoxvirus Replication In Vitro

Keith

Wan

Ciesla

et al. 2004

Antimicrob Agents Chemother

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A new series of ether lipid esters of cidofovir (CDV) were evaluated against vaccinia and cowpox viruses. Activity was dependent on number of atoms in the alkyl or alkoxyalkyl chain, the linker moiety, and the presence of a double bond in the alkoxyalkyl chains linked to the phosphonate moiety of CDV.The threat of an intentional or unintentional spread of poxvirus infections to a vulnerable population has led to increased efforts to find safe, rapidly deployable treatments against such infections. Although vaccination is now being offered to some healthcare workers and other "first responders," there are valid concerns about potential vaccine risks (3, 9). Vaccination is not recommended for those with eczema and other exfoliative skin disorders or those with immunodeficiencies or for pregnant women. Therefore, the use of antiviral therapy in the event of a poxvirus outbreak or in the treatment of vaccination complications against smallpox virus (4) points to the continued need to examine available antiviral therapies as well as to develop new and more efficient treatment.Cidofovir (CDV) and cyclic CDV (cCDV) have been shown to be potent inhibitors of poxvirus replication in vitro (1,7,8,13) and in animal model studies (5, 10, 12); however, these compounds are inactive when given orally.Previous in vitro studies have shown that multiple-log increases in antiviral activity against orthopoxvirus replication (8), as well as enhanced inhibition of cytomegalovirus and herpesvirus replication by these esters (2), were observed with hexadecyloxypropyl (HDP) and octadecyloxyethyl (ODE) derivatives of CDV and cCDV (HDP-CDV, HDP-cCDV, ODE-CDV, and ODE-cCDV) compared to the results seen with the parent compounds. HDP-CDV, ODE-CDV, and oleyloxypropyl-CDV (OLP-CDV) have oral bioavailabilities of 88 to 93% in mice (6) and have oral activity against vaccinia virus (VV) and cowpox virus (CV) infections in mice (11).In this study, the unmodified acyclic nucleoside phosphonates CDV and cCDV (along with a new series of analogs synthesized by esterification of these compounds with an alkyl chain with or without the propoxy-or ethoxy-linker moieties) were evaluated (using methodologies described previously) (7) for activity (plaque reduction assay) against VV and CV and for cytotoxicity (neutral red uptake assay) in human foreskin fibroblast (HFF) cells. To determine efficacy, briefly, HFF cells seeded in 6-well plates 2 days prior to use were infected with either VV or CV by the addition of 20 to 30 PFU per well. After a 1-h incubation period, various concentrations of drug were added to triplicate wells and plates were incubated at 37°C for 3 days. Toxicity was evaluated using HFF cells seeded in 96-well plates incubated with various concentrations of drug for 7 days at 37°C. After incubation, cell monolayers were stained with a 0.01% solution of neutral red. The compounds were synthesized as reported previously (8).As presented in Table 1, the most active ether lipid esters of CDV were OLE-CDV, ODBG-CDV, TDP-CDV, OLP-CDV, and ODP-...

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Smallpox and smallpox vaccination

Cited by 41 publications

References 30 publications

Infection–associated encephalopathies—their investigation, diagnosis, and treatment

Infection–associated encephalopathies—their investigation, diagnosis, and treatment

Role of Genes That Modulate Host Immune Responses in the Immunogenicity and Pathogenicity of Vaccinia Virus

Inhibitory Activity of Alkoxyalkyl and Alkyl Esters of Cidofovir and Cyclic Cidofovir against Orthopoxvirus Replication In Vitro

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