Jan Mackenzie

Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion

BACKGROUND Variant Creutzfeldt-Jakob disease (vCJD) is a novel human prion disease caused by infection with the agent of bovine spongiform encephalopathy (BSE). Epidemiological evidence does not suggest that sporadic CJD is transmitted from person to person via blood transfusion, but this evidence may not apply to vCJD. We aimed to identify whether vCJD is transmissible through blood transfusion. METHODS The national CJD surveillance unit reported all cases of probable or definite vCJD to the UK blood services, which searched for donation records at blood centres and hospitals. Information on named recipients and donors was provided to the surveillance unit to establish if any matches existed between recipients or donors and the database of cases of vCJD. Recipients were also flagged at the UK Office of National Statistics to establish date and cause of death. FINDINGS 48 individuals were identified as having received a labile blood component from a total of 15 donors who later became vCJD cases and appeared on the surveillance units register. One of these recipients was identified as developing symptoms of vCJD 6.5 years after receiving a transfusion of red cells donated by an individual 3.5 years before the donor developed symptoms of vCJD. INTERPRETATION Our findings raise the possibility that this infection was transfusion transmitted. Infection in the recipient could have been due to past dietary exposure to the BSE agent. However, the age of the patient was well beyond that of most vCJD cases, and the chance of observing a case of vCJD in a recipient in the absence of transfusion transmitted infection is about 1 in 15000 to 1 in 30000.

Diagnosis of new variant Creutzfeldt-Jakob disease

As of December 31, 1998, 35 deaths had been attributed to new variant Creutzfeldt‐Jakob disease (nvCJD) in the United Kingdom, of which 33 cases had been neuropathologically confirmed and 2 classified as probable nvCJD. Fifteen cases were male and 20 female. The median illness duration was 14 months (range, 8–38 months) and the median age at death was 29 years (range, 18–53 years). The clinical features were consistent with previous descriptions. In nearly all cases, there were early psychiatric symptoms after a median period of 6 months ataxia developed, followed by involuntary movements and cognitive impairment. Electroencephalograms did not show the “typical” appearances found in sporadic CJD, about half the cases tested had a positive 14‐3‐3 immunoassay, and over 70% of cases had bilateral pulvinar high signal on magnetic resonance brain scanning. Prion protein gene analysis showed that all cases were homozygous for methionine at codon 129. Diagnostic criteria for nvCJD have been formulated, which have a high sensitivity and specificity. Ann Neurol 2000;47:575–582

Creutzfeldt–Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiological Review study

This paper reports the results to 31 May 2015 of an ongoing UK study to look for additional cases of variant Creutzfeldt–Jakob disease (vCJD) transmission by blood transfusion, and to seek evidence whether other subtypes of Creutzfeldt–Jakob disease (CJD) may be transmissible via blood components.

Creutzfeldt-Jakob disease and blood transfusion

Background and Objectives  This paper reports the results to 1 March 2006 of an ongoing UK study, the Transfusion Medicine Epidemiological Review (TMER), by the National CJD Surveillance Unit (NCJDSU) and the UK Blood Services (UKBS) to determine whether there is any evidence that Creutzfeldt–Jakob disease (CJD), including sporadic CJD (sCJD), familial CJD (fCJD), and variant CJD (vCJD) is transmissible via blood transfusion.

Iatrogenic Creutzfeldt-Jakob Disease, Final Assessment

The book on iatrogenic Creutzfeldt-Jakob disease (CJD) in humans is almost closed. This form of CJD transmission via medical misadventures was first detected in 1974. Today, only occasional CJD cases with exceptionally long incubation periods still appear. The main sources of the largest outbreaks were tissues from human cadavers with unsuspected CJD that were used for dura mater grafts and growth hormone extracts. A few additional cases resulted from neurosurgical instrument contamination, corneal grafts, gonadotrophic hormone, and secondary infections from blood transfusions. Although the final solution to the problem of iatrogenic CJD is still not available (a laboratory test to identify potential donors who harbor the infectious agent), certain other measures have worked well: applying special sterilization of penetrating surgical instruments, reducing the infectious potential of donor blood and tissue, and excluding donors known to have higher than normal risk for CJD.

Prion protein heterogeneity in sporadic but not variant Creutzfeldt–Jakob disease: U.K. cases 1991–2002

Human prion diseases can occur as an idiopathic disorder (sporadic Creutzfeldt–Jakob disease) or can be acquired, as is the case for variant Creutzfeldt–Jakob disease. These disorders are characterized by the accumulation of a protease‐resistant form of the host‐encoded prion protein termed PrPSc in the brains of affected individuals. PrPSc has been proposed to be the principal, if not sole, component of the infectious agent, with its accumulation in the central nervous system the primary event leading to neurodegeneration. A major question remains as to whether self‐propagating structural differences in PrPSc might account for the clinicopathological diversity evident in Creutzfeldt–Jakob disease and whether different prion protein types underlie the existence of different strains of causative agent. Here, we describe the results of a large‐scale biochemical study of PrPSc from autopsy‐proved cases of variant Creutzfeldt–Jakob disease (n = 59) and compare these with cases of sporadic Creutzfeldt–Jakob disease (n = 170) in the United Kingdom over the period 1991 to 2002. The results show PrPSc in variant Creutzfeldt–Jakob disease to be remarkably stereotyped. In contrast, considerable heterogeneity in PrPSc exists both between and within cases of sporadic Creutzfeldt–Jakob disease. Ann Neurol 2004;55:851–859

The role of cerebrospinal fluid 14-3-3 and other proteins in the diagnosis of sporadic Creutzfeldt–Jakob disease in the UK: a 10-year review

Background It is 10 years since the detection of cerebrospinal fluid (CSF) 14-3-3 was included in the diagnostic criteria for sporadic Creutzfeldt–Jakob disease (sCJD) by the WHO. Since that time, other CSF proteins, such as S100b and tau protein, have been proposed as surrogate markers for sCJD. The authors aimed to investigate the diagnostic value of each of these three proteins. Methods CSF samples collected from patients who were referred to the National CJD Surveillance Unit as suspected cases of sCJD during the period 1997–2007 were analysed for 14-3-3, S100b and tau protein. The sensitivity, specificity, positive predictive value and negative predictive value of each of these markers, either alone or in combination for the diagnosis of sCJD, were assessed. The impact of CSF 14-3-3 analysis on the case classification of sCJD was investigated. Results and discussion CSF 14-3-3 had the greatest sensitivity (86%) when compared with tau protein (81%) and S100b (65%). The combination of a positive CSF 14-3-3 or an elevated tau protein with a raised S100b had the highest positive predictive power for sCJD. During the study period, 100 patients were classified as probable sCJD solely on the basis of the clinical features and a positive CSF 14-3-3. The most sensitive marker for sCJD was a positive CSF 14-3-3. The analysis of CSF 14-3-3 plays a crucial role in the case classification of sCJD.

Validation of diagnostic criteria for variant Creutzfeldt-Jakob disease.

Variant Creutzfeldt–Jakob disease (vCJD), a novel form of human prion disease, was recognized in 1996. The disease affected a younger cohort than sporadic CJD, and the early clinical course was dominated by psychiatric and sensory symptoms. In an attempt to aid diagnosis and establish standardization between surveillance networks, diagnostic criteria were established. These were devised from the features of a small number of cases and modified in 2000 as the clinical phenotype was established. Since then, only minor changes have been introduced; revalidation of the criteria in the current format is overdue.

Variant Creutzfeldt-Jakob disease in France and the United Kingdom: Evidence for the same agent strain.

Variant Creutzfeldt–Jakob disease (vCJD) was first reported in the United Kingdom in 1996. Since then, the majority of cases have been observed in the United Kingdom where there was a major epidemic of bovine spongiform encephalopathy. France was the second country affected. To address the hypothesis of the involvement of a common strain of agent, we have compared clinical, neuropathological, and biochemical data on vCJD patients from both countries.

Three reported cases of variant Creutzfeldt–Jakob disease transmission following transfusion of labile blood components

We were interested to read the article by Sowemimo-Coker et al. [1]. However, we would like to draw attention to an error made when discussing the three probable cases of variant Creutzfeldt–Jakob disease transmission following transfusion of labile blood components [2–4]. The interval between donation and onset of clinical symptoms for the donors of the first [2] and third [4] reported cases (whose recipients were subsequently diagnosed as confirmed and probable vCJD cases within 6–8 years of receiving the transfusion) is given incorrectly as 3 and 2·5 years respectively. The correct intervals are 40 months [2] and 21 months [4] respectively, and 18 months for the second case, who donated to a recipient later diagnosed at post-mortem with preclinical or subclinical vCJD [3]. This data is derived from an ongoing collaborative study (TMER) between the UK National CJD Surveillance Unit (NCJDSU) and the UK Blood Services (UKBS) to determine whether there is any evidence that CJD, including vCJD, is transmissible by blood transfusion [5]. There is a degree of uncertainty surrounding the calculation of the interval from donation to onset of clinical symptoms for vCJD cases; while the donation date is accurately known from UKBS records, the latter is more difficult to ascertain. The clinical onset date is estimated retrospectively by the NCJDSU to the nearest month after interviewing the patient’s relatives and case note review. The mid-month date is then used to calculate the interval from donation to onset of symptoms in the donor, to the nearest month. Details of the three reported cases of vCJD transmission by blood transfusion, including two confirmed cases [2,4] and one preclinical or subclinical infection [3] identified by the TMER study will be published in Vox Sang [5] as part of an update of the TMER results to 1 March 2006 [5]. These three cases involved non-leucodepleted red cell donations from three different donors [5].