Variant Creutzfeldt–Jakob disease and its transmission by blood

Abstract

Summary. Variant Creutzfeldt–Jakob disease (vCJD) is a novel acquired human prion disease resulting from human exposure to the agent causing bovine spongiform encephalopathy (BSE). vCJD differs from all other human prion diseases in that the disease‐associated form of the prion protein and infectivity are present in lymphoid tissues throughout the body. Lymphoid tissues and lymphocytes are implicated in the peripheral pathogenesis of prion diseases (where infectivity may be detected during the preclinical phase of the illness), giving rise to concerns that blood and blood products may also contain infectivity, thus representing a possible source of iatrogenic spread of vCJD. These concerns have been reinforced by the recent transmission of BSE in an experimental sheep model by blood transfusion from an infected animal in the preclinical phase of the illness. Studies in other animal models suggest that most infectivity in blood may be cell‐associated, with lower levels in the plasma, and there is evidence to indicate that any infectivity present may be reduced during the process of plasma fractionation. At present, the attempts to detect disease‐associated prion protein and infectivity in buffy coat from vCJD patients have been negative, but these studies have been limited in size and in the sensitivity of the detection systems employed. Further studies are required to develop more sensitive means of detection of disease‐associated prion protein in blood; such techniques could also be employed for screening purposes, both individually and to help ascertain more precisely the likely numbers of future cases of vCJD.

Misfolded protein aggregates: Mechanisms, structures and potential for disease transmission

“…Transmission of BSE, variant CJD, and scrapie by blood has been proved in several animal models [85]. Epidemiological data indicates that human vCJD blood is infectious during both incubation period and clinical phase and can be transmitted through transfusion route [86]. To our knowledge, besides of prion diseases and systemic amyloidosis, no others PMDs has been reported to be transmissible host-to-host by oral, vertical, blood transfusion or any other natural route, till now.…”

The effects of leukodepletion on the generation and removal of microvesicles and prion protein in blood components

“…Variant Creutzfeldt‐Jakob disease (vCJD) was first described in 1996, 1 and the causative agent is thought to be the same strain of prion disease that causes bovine spongiform encephalopathy 2 . The transmission of the disease across species from cattle to human is most likely via dietary exposure 3 but infectivity has also been shown in the peripheral blood of animals experimentally infected with a variety of prion diseases, 4 and transmission of passaged vCJD and bovine spongiform encephalopathy by blood transfusion has been shown in mouse and sheep models, respectively 5,6 . Recently the national surveillance system in the United Kingdom has identified two probable cases of transmission of the vCJD prion by blood transfusion, both via nonleukodepleted units of red cells (RBCs) 7,8 …”

Variante Creutzfeldt-Jakob-Krankheit

“…Wäh-rend in der "All ge mein be völ ke rung" zwischen 40 und 50 he tero zy got sind (Met/ Val), sinkt der An teil der He tero zy go ten auf 10-15 bei Per so nen mit TSE-Er krankun gen, vgl. Ta bel le 5 [30,31,32,33,34].…”

“…Wel che Be deu tung der Nach weis die ses Pro te ins bei noch nicht Er krank ten für den zeit lichen Ver lauf der In fek ti on hat, ist ebenso un be kannt wie der Zeit punkt nach Infek ti on, ab wann der Nach weis von PrP Sc in Ge we ben von vCJK-in fi zier ten Per sonen mög lich ist. Prin zi pi ell lässt sich der [30], Al péro vitch et al [31], Kretz schmar [32], Iron si de und Head [33], Bran del et al [34], Nur mi et al [63]. Die Pro zent zah len va ri ieren in den ver schie de nen Pub li ka ti o nen.…”

“…Die Über tra gung der vCJK durch Blut ist in Über ein stim mung mit Er geb nis sen in Tierver su chen, in de nen der Er re ger in lym phati schen Ge we ben wie bei der vCJK nach gewie sen wer den kann. Als Bei spiel ist hier vor al lem die Über tra gung von TSE bei Scha fen durch Blut trans fu si on zu nen nen [52]; Über sicht bei Iron si de und Head [33]. Pa ti en ten mit sCJK ha ben über die Blutspen de kei ne Er kran kung über tra gen [53].…”