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Volume 20, Number 1—January 2014

Detection of Infectivity in Blood of Persons with Variant and Sporadic Creutzfeldt-Jakob Disease

Jean Yves Douet, Saima Zafar, Armand Perret-Liaudet, Caroline Lacroux, Séverine Lugan, Naima Aron, Herve Cassard, Claudia Ponto, Fabien Corbière, Juan Maria Torres, Inga Zerr, and Olivier AndreolettiComments to Author 
Author affiliations: Institut National de la Recherche Agronomique/Ecole Nationale Vétérinaire, Toulouse, France (J.Y. Douet, C. Lacroux, S. Lugan, N. Aron, H. Cassard, F. Corbière, O. Andréoletti); National Reference Center for Transmissible Spongiform Encephalopathy, Georg August University, Göttingen, Germany (S. Zafar, C. Ponto, I. Zerr); Hospices Civils de Lyon, France (A. Perret-Liaudet); BioRan, Bron, France (A. Perret-Liaudet); Centro de Investigación en Sanidad Animal, Madrid, Spain (J.M. Torres)

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Table 2

Intracerebral inoculation of blood components collected from 1 vCJD and 4 sCJD cases (MM1) in transgenic mice expressing the bovine or human prion protein gene*†

Mouse model Donor Specimen Inoculated
mice Positive
mice Incubation period, d ID/mL (95%CI)‡
tgBov vCJD Leukocyte 24 3 476, 567, 576 2.23 (0–4.87)
Plasma 24 1 453 2.12 (0–6.52)
Erythrocyte 24 1 433 2.12 (0–6.52)
tgHu sCJD case 1 Plasma 14§ 1 338 3.70 (0–11.65)
Brain 6 6 216 ± 2 NA
sCJD case 2 Plasma 24 0 >700 0 (0- 6.24)
brain 6 6 217 ± 5 NA
sCJD case 3 Plasma 24 1 233 2.12 (0–6.52)
Brain 6 6 205 ± 5 NA
sCJD case 4 Plasma 24 0 >700 0 (0–6.24)
Brain 6 6 207 ± 3 NA
tgHu Control human Plasma 12 0 >650 NA
tgBov Control human Plasma 12 0 >650 NA
tgHu Control human PBS 12 0 >700 NA
tgBov Control human PBS 12 0 >700 NA
tgHu Control human Brain 24 0 >700 NA
tgBov Control human Brain 24 0 >700 NA
tgHu Control human None 24 0 >750 NA
tgBov Control human None 24 0 >750 NA

*vCJD, variant Creutzfeld-Jakob disease; sCJD, sporadic Creutzfeld-Jakob disease; dpi, days postinfection; ID, infectious dose; tgBov, bovine prion protein; tgHu, human prion protein;; PBS, phosphate-buffered saline.
†The leukocyte(s) from a single vCJD case corresponding to a starting volume of 3 mL of blood were suspended in 1 mL of 5% glucose solution. The leukocyte suspension and the crude erythrocytes were homogenized by using a high speed cell disrupter. The leukocyte and erythrocyte homogenates (vCJD case) and crude plasma (vCJD and sCJD cases) were intracerebrally injected into mice (20 µL per mouse). For the 4 sCJD MM1 cases, brain homogenate (10%, temporal cortex) were also inoculated in tgHu. Mice were euthanized when they showed clinical signs of infection or after 650 or 750 dpi. Mice were considered infected when abnormal protease-resistant prion protein; deposition was detected in brain tissue by using Western blot analysis with Sha31 monoclonal antibody: epitope amino acids 145–152 (YEDRYYRE) of the sheep PrP sequence. For samples showing 100% attack rate, incubation periods are reported as mean (± SD). For other samples, individual incubation period of CJD-positive mice are presented; their infectious titers were estimated by using limiting dilution titration method (application of Poisson model) described by Brown et al (13).
‡Leukocyte titer is expressed as ID/mL of the starting whole blood. Plasma and erythrocyte titers are expressed as ID/mL of inoculum.
§24 mice were inoculated; 10 died because of the acute toxicity of the sample.

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