Levels of infectivity in the blood throughout the incubation period of hamsters peripherally injected with scrapie

Casaccia, Patrizia; Ladogana, Anna; Xi, You Geng; Pocchiari, Maurizio

doi:10.1007/bf01313752

Cited by 57 publications

(39 citation statements)

References 21 publications

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“…route into a non-CTA allowed, for a short period of time before the infectious agent was taken up by cells projecting into the CTA, interference in the pathogenesis of the disease. This mechanism differs from that of the anti-scrapie drug amphotericin B (Pocchiari et al, 1987(Pocchiari et al, , 1989, which works also during the transport of the scrapie agent to the CTA (Pocchiari et al, 1991). The anti-scrapie effect of DS500 in i.c.…”

Section: Discussionmentioning

confidence: 81%

Sulphate polyanions prolong the incubation period of scrapie-infected hamsters

Ladogana¹,

Casaccia²,

Ingrosso³

et al. 1992

Journal of General Virology

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124

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The effect of the organic sulphated polyanions, pentosan sulphate (SP54), dextran sulphate 500 (DS500) and suramin, have been tested on golden Syrian hamsters infected with the 263K strain of scrapie by the intraperitoneal (i.p.) or the intracerebral route. SP54 had the greatest effect in prolonging the incubation period of the disease when administered within 2 h of the i.p. inoculum. The same amount of SP54 given 24 h after scrapie inoculation had a potent effect in some animals and no effect in others. This result suggests that SP54 inhibits the uptake of the scrapie agent into the nerve endings and/or carrier cells at the site of the inoculum, i.e. the peritoneum, and that this event occurs in about 24 h. DS500 had a similar although less potent effect (22.4 days delay during the incubation period) than SP54 (54.4 days) when administered within 2 h of scrapie injection by the i.p. route, and suramin had only a minimal effect (10 days). This study suggests that treatment of scrapie and related spongiform encephalopathies of animals and man is possible only before the agent has reached the clinical target areas of the brain.

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Section: Discussionmentioning

confidence: 81%

Sulphate polyanions prolong the incubation period of scrapie-infected hamsters

Ladogana¹,

Casaccia²,

Ingrosso³

et al. 1992

Journal of General Virology

Self Cite

124

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“…Subsequent studies utilizing confocal microscopy confirmed an association between PrP RES and immune cells (FDCs, tingible body macrophages, and B cells) and extended the repertoire of prion diseases with lymphoid involvement to include CWD and vCJD (42,55,60,66,67). B cells have been associated with PrP RES transport and/or deposition within the lymphoid system (9,10,18,22,23,32,43,56,64,66,81). The present study supports this contention in demonstrating that MAb 2-104 ϩ primarily B cells harvested from peripheral blood or retropharyngeal lymph nodes contain sufficient infectious prions to transmit CWD to native or transgenic hosts.…”

Section: Interval To Detection Of Cwd Infection By Tonsil Biopsymentioning

confidence: 99%

B Cells and Platelets Harbor Prion Infectivity in the Blood of Deer Infected with Chronic Wasting Disease

Mathiason

Hayes-Klug

Hays

et al. 2010

J Virol

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Substantial evidence for prion transmission via blood transfusion exists for many transmissible spongiform encephalopathy (TSE) diseases. Determining which cell phenotype(s) is responsible for trafficking infectivity has important implications for our understanding of the dissemination of prions, as well as their detection and elimination from blood products. We used bioassay studies of native white-tailed deer and transgenic cer- Chronic wasting disease (CWD) is an infectious proteinmisfolding disease, or transmissible spongiform encephalopathy (TSE), affecting cervids in North America (59, 76-79) and one Asian country (41,68). CWD is unique among prion diseases in affecting free-ranging wildlife populations (deer, elk, and moose). Early and subsequent observations made by Williams and Miller (58,79) related CWD transmission to direct contact with clinically affected deer, as well as indirect contact with environments previously populated by infected deer (57). Bioassay studies of white-tailed deer have demonstrated that body fluids and excreta (saliva, urine, feces, and blood) contain infectious prions (53, 54). Both clinical and preclinical CWDinfected deer harbored sufficient infectious prions to produce CWD in naïve white-tailed deer following ingestion of saliva or transfusion of whole blood (53, 54).The detection of blood-borne infectious prions has important implications for our understanding of the spread of prions among and within individuals, as well as for the elimination of prions from blood products (13,15,33,45), given the evidence for Creutzfeldt-Jakob disease (CJD) transmission via blood transfusion (16,29,47,50,62,72,73). Identifying the cell phenotype or cell-free protein fractions that harbor prion infectivity would contribute importantly to this understanding and to the development of blood-based assays to detect prion infection. We undertook the present studies to address these issues. MATERIALS AND METHODSBioassay studies of white-tailed deer. White-tailed deer fawns were provided by the Warnell School of Forestry and Natural Resources, University of Georgia, Athens-a region in which CWD has not been detected. The deer fawns were hand raised and human and indoor adapted before overnight transport directly to the Colorado State University (CSU) CWD research indoor isolation facility without contact with the native Colorado environment. The 4-month-old fawns were adapted to the facility housing conditions and diet for 2 months before the study start.Genotyping. All white-tailed deer were genotyped to determine their GG/GS (codon 96) status by the laboratory of Katherine O'Rourke, USDA-ARS, Pullman, WA. Deer were allocated into inoculation cohorts (n ϭ 4) without knowledge of their G96 genotypes.Biocontainment protocols. Protocols to preclude extraneous exposure and cross contamination between cohorts of animals as previously described (53, 54) incorporated protective shower-in requirements, Tyvek clothing, masks, head covers, and footwear while maintaining stringent husbandry. Tonsil biopsy ...

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“…Evidence from laboratory transmission studies indicates that infectivity can sometimes be isolated from blood in TSEs [2]and that infectivity may be present in blood from a relatively early stage in the incubation period well before the onset of clinical disease [3]. The majority of these experiments maximise the chances of successful transmission by inoculating concentrated blood components, for example buffy coat, by the most efficient, intracerebral, route.…”

Section: Laboratory Studiesmentioning

confidence: 99%

“…If infectivity is present in blood, the titre of infectivity is likely to be low [2, 3]. Although the agents of TSEs are notoriously resistant to decontamination, there are procedures such as column chromatography, centrifugation and filtration [16]that are known to reduce infectivity.…”

Section: Risk Reductionmentioning

confidence: 99%

Creutzfeldt–Jakob Disease and the Risk from Blood or Blood Products

Will

Kimberlin²

1998

Vox Sanguinis

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The occurrence of iatrogenic cases of Creutzfeldt–Jakob disease (CJD) and the isolation of infectivity in some laboratory transmission studies in transmissible spongiform encephalopathies raises the possibility that CJD might be accidentally transmissible through blood or blood products. Epidemiological evidence, although not conclusive, does not suggest that classical CJD is transmitted through this route. However, new variant CJD (nvCJD) might pose greater risks of accidental transmission of infection and mechanisms to reduce the theoretical risk are under consideration. The theoretical risks from CJD and nvCJD must be balanced against the established therapeutic benefits of blood and blood products.

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Levels of infectivity in the blood throughout the incubation period of hamsters peripherally injected with scrapie

Cited by 57 publications

References 21 publications

Sulphate polyanions prolong the incubation period of scrapie-infected hamsters

Sulphate polyanions prolong the incubation period of scrapie-infected hamsters

B Cells and Platelets Harbor Prion Infectivity in the Blood of Deer Infected with Chronic Wasting Disease

Creutzfeldt–Jakob Disease and the Risk from Blood or Blood Products

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Levels of infectivity in the blood throughout the incubation period of hamsters peripherally injected with scrapie

Cited by 57 publications

References 21 publications

Sulphate polyanions prolong the incubation period of scrapie-infected hamsters

Sulphate polyanions prolong the incubation period of scrapie-infected hamsters

B Cells and Platelets Harbor Prion Infectivity in the Blood of Deer Infected with Chronic Wasting Disease

Creutzfeldt&ndash;Jakob Disease and the Risk from Blood or Blood Products

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Creutzfeldt–Jakob Disease and the Risk from Blood or Blood Products