sábado, 28 de diciembre de 2013

Detection of Infectivity in Blood of Persons with Variant and Sporadic Creutzfeldt-Jakob Disease - Volume 20, Number 1—January 2014 - Emerging Infectious Disease journal - CDC

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Detection of Infectivity in Blood of Persons with Variant and Sporadic Creutzfeldt-Jakob Disease - Volume 20, Number 1—January 2014 - Emerging Infectious Disease journal - CDC

link to Volume 20, Number 1—January 2014

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)


We report the presence of infectivity in erythrocytes, leukocytes, and plasma of 1 person with variant Creutzfeldt-Jakob disease and in the plasma of 2 in 4 persons whose tests were positive for sporadic Creutzfeldt-Jakob disease. The measured infectivity levels were comparable to those reported in various animals with transmissible spongiform encephalopathies.
Among humans, Creutzfeldt-Jakob disease (CJD) is a low incidence disease (≈1 case per million per year) that occurs as either a sporadic (sCJD) or a familial/genetic (fCJD) form. Whereas familial disease forms are linked to a mutation in the prion protein gene (Prnp), no clear epidemiologic risk factors have been identified for sporadic disease forms. sCJD is not a uniform disorder in terms of clinical and neuropathological phenotype. sCJD cases are classified as type 1 or 2 according to the polymorphism at codon 129 of the protease-resistant prion protein (PrP) sequence (methionine/valine) and to the electromobility of the proteinase K–resistant core of the abnormal PrP (PrPres) (1). Type 1 and type 2 isoforms in sCJD are believed to correspond to different transmissible spongiform encephalopathy (TSE) agents
Despite their relative rarity, several hundred iatrogenically transmitted CJD cases were identified during the past 60 years (2). Some data supporting the presence of infectivity in the blood of sCJD-affected patients were reported following the intracerebral inoculation of blood fractions from affected patients into rodents. These observations remain ambiguous because other studies did not confirm them (3,4).
In 1996, a new form of CJD, named variant CJD (vCJD), was identified in humans. Variant CJD was demonstrated to be caused by the agent that causes bovine spongiform encephalopathy in cattle (5). In the United Kingdom, 4 vCJD transmissions (3 clinical cases and 1 asymptomatic infection) were probably caused by the transfusion of non–leuco-depleted erythrocyte concentrates prepared from donors who later had positive test results for vCJD (6). More recently, a presumed additional case of vCJD infection was reported in the United Kingdom in a hemophilic patient who had received fractionated plasma products, including some units linked to a donor who had vCJD diagnosed with vCJD (7). Despite the epidemiologic evidence of bloodborne transmission in vCJD, bioassays performed on conventional rodent models failed to demonstrate the presence of infectivity in the blood (8). The lack of TSE transmission in conventional rodent models could be a consequence of a low infectivity level in blood from vCJD- and sCJD-affected patients (as described in sheep and rodent TSE models) (9) or of the existence of the species barrier phenomenon that limits the transmission of human prions to these animal models. The development during the last decade of transgenic mice models expressing PrP from others species that abrogate the species barrier now offers the potential to detect low level of infectivity (10).
In this study, we used 2 transgenic mouse models that displayed a high sensitivity to the vCJD or sCJD TSE agents to estimate the infectious titer in certain blood fractions from vCJD- and sCJD-affected patients. According to legislation of the United Kingdom, Germany, and France, the experimental protocol, including the use of human samples, was approved by UK National CJD Research & Surveillance Unit tissue bank: REC reference number 2000/4/157-German TSE reference center: Ref Nr 11/11/93, PHRC ref 2004-D50-353 for patient from France.

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