Accuracy of a history of blood donation from surrogate witnesses: data from the UK TMER study.

Look-back studies of blood transfusion in Creutzfeldt-Jakob disease commonly rely on reported history from surrogate witnesses. Data from the UK Transfusion Medicine Epidemiology Review have been analysed to determine the accuracy of the blood donation history provided by the relatives of cases. Our results show that only a small percentage of cases were found to be registered as donors on UK Blood Service (UKBS) databases when there was no family report of blood donation. In contrast, a history of reported donation was less accurate.

Creutzfeldt-Jakob disease and blood transfusion safety.

Transmissible spongiform encephalopathies (TSEs) are untreatable, fatal neurologic diseases affecting mammals. Human disease forms include sporadic, familial and acquired Creutzfeldt-Jakob disease (CJD). While sporadic CJD (sCJD) has been recognized for near on 100 years, variant CJD (vCJD) was first reported in 1996 and is the result of food-borne transmission of the prion of bovine spongiform encephalopathy (BSE, 'mad cow disease'). Currently, 230 vCJD cases have been reported in 12 countries, the majority in the UK (178) and France (27). Animal studies demonstrated highly efficient transmission of natural scrapie and experimental BSE by blood transfusion and fuelled concern that sCJD was potentially transfusion transmissible. No such case has been recorded and case-control evaluations and lookback studies indicate that, if transfusion transmission occurs at all, it is very rare. In contrast, four cases of apparent transfusion transmission of vCJD infectivity have been identified in the UK. Risk minimization strategies in response to the threat of vCJD include leucodepletion, geographically based donor deferrals and deferral of transfusion recipients. A sensitive and specific, high-throughput screening test would provide a potential path to mitigation but despite substantial effort no such test has yet appeared. The initial outbreak of vCJD appears to be over, but concern remains about subsequent waves of disease among those already infected. There is considerable uncertainty about the size of the infected population, and there will be at least a perception of some continuing risk to blood safety. Accordingly, at least some precautionary measures will remain in place and continued surveillance is necessary.

Ten-year follow-up of two cohorts with an increased risk of variant CJD: donors to individuals who later developed variant CJD and other recipients of these at-risk donors.

BACKGROUND: Transmission of variant Creutzfeldt-Jakob disease (vCJD) through blood transfusion is implicated in three deaths and one asymptomatic infection. Based on this evidence, individuals assessed to be at increased risk of vCJD through donating blood transfused to individuals who later developed vCJD, or through being other recipients of such donors, are followed up to further understand the risks of vCJD transmission through blood. OBJECTIVES: To provide a ten-year follow-up of these at-risk cohorts. METHODS: Blood donors to patients who later died from vCJD were identified by the Transfusion Medicine Epidemiological Review (TMER) study. A reverse risk probability assessment quantified the risk of blood transfusion or exposure through diet as the source of vCJD in the recipients. Donors to these recipients, and these donors' other recipients, with a probability risk above 1%, are classified as at increased risk of vCJD for public health purposes. These cohorts are monitored for any vCJD occurrences. RESULTS: A total of 112 donors and 33 other recipients of their donated blood have been classified as at increased risk. After 2397 and 492 vCJD-free years of follow-up, respectively, no deaths in either at-risk cohort were of vCJD-related causes. CONCLUSIONS: The at-risk cohorts have survived disease-free far longer than the estimated incubation time for dietary-acquired vCJD (donors) and transfusion-acquired disease (other recipients). However, due to our still limited understanding of, and a lack of a reliable test for, asymptomatic vCJD infection, public health follow-up is necessary for continued monitoring of at-risk cohorts.

Creutzfeldt-Jakob disease and blood transfusion: updated results of the UK Transfusion Medicine Epidemiology Review Study.

BACKGROUND AND OBJECTIVES: 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. MATERIALS AND METHODS: All vCJD cases of appropriate age and any sporadic CJD (sCJD) or familial CJD (fCJD) cases with a history of blood donation or transfusion are notified to the UKBS. Donation records are sought and the usage of all donations is determined by look back. Death certificates are obtained for all donors to patients with CJD and recipients of transfused components from patients with CJD who are deceased. RESULTS: The study identified 29 sCJD blood donors, of 370 reported, with transfusion to 211 recipients. Five of these recipients were reported to have died with or of dementia, but were not believed to be cases of CJD. The vCJD arm found 18 vCJD blood donors who had donated blood which was issued for clinical usage, of 24 traced donors from 177 UK vCJD cases. To date, 3 cases of vCJD have occurred in 67 recipients identified in this recipient group, and one recipient had post-mortem confirmation of abnormal prion protein deposition in the spleen (all previously reported). CONCLUSION: The results of the ongoing TMER study show no new cases of transfusion-associated vCJD since 2007 and no evidence of transfusion transmission of sCJD.

Notifying blood donors of infection: results of a donor satisfaction survey.

BACKGROUND/OBJECTIVES: When NHS Blood and Transplant (NHSBT) confirms a blood donation to have markers of infection, the donor is contacted by letter to arrange a discussion about the test results and onward care. A survey was carried out to assess the level of satisfaction with this process. MATERIALS/METHODS: A questionnaire was sent to 335 donors who had been notified by NHSBT in 2008 and 2009 that they had tested positive for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV). Ratings were made using Likert scales, where the respondent indicated the level of agreement or satisfaction with statements about the initial notification letter and the subsequent post-test discussion (PTD) with the NHSBT clinician. RESULTS: There was an overall 47.5% (159/335) response rate. Fifty-eight percent (91/157) agreed that they were satisfied with the letter, but 30% (46/152) disagreed that it was easy to stay calm (average score 3.2). Scores for the letter were significantly lower in HIV and HTLV than in hepatitis for several questions. Scores for the discussion were in general higher than the initial letter, with 90% (114/127) satisfied overall, although 2 of 19 HIV positive donors remained dissatisfied. CONCLUSION: Overall, most donors were satisfied with the notification process, although scores were slightly lower for HTLV and HIV. Further audit is planned; in particular to remeasure the satisfaction with, and understanding of, the notification letter for HTLV positive donors and the telephone PTD.

Variant CJD and blood transfusion: are there additional cases?

BACKGROUND AND OBJECTIVES: In this study, we compare variant Creutzfeldt-Jakob disease (vCJD) cases definitely linked to blood transfusion, those with a history of blood transfusion in which no donor has developed vCJD and primary cases with no history of blood transfusion. The aim is to determine whether there are any differences in the demographics or clinical phenotype in these groups that might suggest additional cases of transfusion transmission of vCJD. MATERIALS AND METHODS: All cases of vCJD who are old enough to donate blood (i.e. >17 years old) are notified to the UKBTS at diagnosis, regardless of whether they are known to have a blood donation history. A search is then made for donor records and, if found, all components produced and issued to hospitals are identified and their fate determined. Recipient details are then checked against the NCJDRSU register to establish whether there is a match between these individuals and patients who have been diagnosed with vCJD. In the reverse study, attempts are made to trace the donors to all cases reported to have received a blood transfusion and donors' details are checked against the register to determine if any have developed vCJD. RESULTS: Of the 177 cases of vCJD diagnosed in the UK as of 1 February 2014, the TMER study identified 15 cases reported to have received a blood transfusion. Transfusion records were unavailable for 4 of these cases, all pre-1980, and in one other case there was no transfusion recorded in the medical notes. Transfusion records were found for 10 cases. One case transfused at symptom onset was excluded from this analysis. The mean age at onset of symptoms of the remaining nine transfusion recipients (four female and five male) was 42·9 years; 57·6 years in the three known transfusion-transmitted cases and 35·5 years in the six not linked cases. In one of these cases, details of components transfused were unavailable, and the remaining five cases received a total of 116 donor exposures with 112 donors identified, none of whom is known to have developed clinical vCJD. To date, five of the 112 identified donors have died and none was certified as dying of vCJD or any other neurological disorder. Two of the transfusion-transmitted cases did not fulfil diagnostic criteria for probable vCJD during life but were confirmed at post-mortem. Both cases were in the older age range (68 and 74 years, respectively), and neither had a positive MRI brain scan. The remaining cases all fulfilled the criteria for the diagnosis of vCJD in life, but two of these had atypical features and were older than the expected age at onset for vCJD. CONCLUSION: In conclusion, it is possible that one or more of the vCJD cases that received a blood transfusion derived from an individual not known to have vCJD were infected by the blood transfusion. However, the evidence for this is weak, and the absence of a past history of transfusion in most cases of vCJD excludes a large number of unrecognised transfusion-transmitted cases.

A retrospective case note review of deceased recipients of vCJD-implicated blood transfusions.

BACKGROUND: To date, four instances of probable transfusion-transmission of variant Creutzfeldt-Jakob disease (vCJD) infection have been described, and surviving recipients of vCJD-implicated blood components have been informed that they may be 'at risk' of vCJD. Nearly two-thirds of all recipients of vCJD-implicated blood components are deceased, and many died before the vCJD risk was known. The primary aim of this study was to determine retrospectively whether there was evidence that any of the other deceased recipients of vCJD-implicated blood components had any clinical signs or symptoms suggestive of vCJD in life. In addition, pathological material from recipients, stored at the time of surgery or autopsy, was sought to allow testing for evidence of vCJD infection. A secondary aim of the study was to obtain information on invasive healthcare procedures undertaken on recipients following the transfusion to identify the potential for onward transmission of infection. METHODS: A retrospective review of medical case notes of deceased recipients of vCJD-implicated blood components was carried out, and relevant information was extracted. In cases undergoing post-mortem, details of the findings were obtained. RESULTS: The medical case notes of 33 (83%) deceased recipients of vCJD-implicated blood components, not already known to be infected with vCJD, were reviewed. The median age of recipients was 68 years (interquartile range 57-79 years). Almost half (16) were male. The median time from transfusion to death was 175 days (interquartile range 43-701 days). Most (66%) recipients died in hospital. None of the recipients had documented evidence of clinical signs or symptoms suggestive of vCJD. Only two recipients, both of whom died within a year of transfusion, underwent autopsy examination. Neither brain nor peripheral lymphoreticular tissue was available from either recipient, and pathological material was unavailable from any of the other deceased recipients. Almost half of all recipients underwent at least one invasive healthcare procedure post-transfusion. CONCLUSIONS: A retrospective review of the medical case notes of the deceased recipients of vCJD-implicated blood components found no evidence that any further cases expressed clinical signs or symptoms suggestive of vCJD during life, but only four of the recipients survived for more than 5 years post-transfusion.

HIV screening reactivity due to donor participation in HIV vaccine trials.

We report two instances of human immunodeficiency virus (HIV) serological screening reactivity in blood donations which were subsequently determined to be due to donor participation in HIV vaccine trials. Both donations were screen reactive with atypical patterns on confirmation; no definitive conclusion could be given for either donor. Subsequent questioning identified that both donors had been involved in HIV vaccine trials. In both cases the screening and confirmation identified the presence of HIV antibodies, although vaccine induced. While clinical trials of vaccines are important, the implications of some need careful consideration if they are not to adversely impact other areas of healthcare.

Variant Creutzfeldt-Jakob disease and exposure to fractionated plasma products.

BACKGROUND: The risk to public health of onward transmission of variant Creutzfeldt-Jakob disease (vCJD) via blood transfusion and plasma product administration is of on-going concern, particularly with the recent reported detection of abnormal prion protein in a person with haemophilia. OBJECTIVES: To describe the history of fractionated plasma product exposure in clinical cases of vCJD in the UK. METHODS: Through examination of records held at the National CJD Surveillance Unit (from relatives, general practices and hospitals). RESULTS: Nine out of 168 UK vCJD cases had a history of receipt of fractionated plasma products on 12 different occasions (1 pre-vCJD risk in 1970, the remaining between 1989-1998). According to the UK CJD Incident Panel risk assessment criteria, 11 were low-risk products and one was low or medium risk. CONCLUSION: It is unlikely that any of the UK vCJD clinical cases to date were infected through exposure to fractionated plasma products. However, the possibility that such transmission may result in vCJD cases in the future cannot be excluded.

The introduction of anti-HTLV testing of blood donations and the risk of transfusion-transmitted HTLV, UK: 2002-2006.

The objectives of the study were to describe the introduction of testing blood donations for antibodies to human T-cell lymphotropic virus (anti-HTLV) and to determine the risk of HTLV potentially infectious donations entering the UK blood supply. The rationale for testing was based on (i) evidence of transmission through transfusion in the UK, (ii) the serious nature of HTLV I-associated morbidity and (iii) evidence of infection in UK blood donors. From mid-2002, all blood donations made at UK blood centres were tested in pooled samples using Abbott-Murex HTLV I/II GE 80/81 enzyme immunoassay (EIA). Surveillance data were used to calculate the incidence and prevalence of anti-HTLV and derive estimates of risk. Between August 2002 and December 2006, 106 donations were confirmed positive for anti-HTLV (95 anti-HTLV I and 11 anti-HTLV II). Prevalence was 10-fold higher among donations from new donors than repeat (4.0 and 0.42 per 100 000 donations), and only one repeat donor had evidence of seroconversion. The risk of an HTLV I potentially infectious donation entering the UK blood supply was estimated at 0.11 per million donations (95% confidence interval 0.06 to 0.18). The current very low observed incidence and prevalence among blood donors reflect the very low estimated risk of an HTLV I-positive donation entering the UK blood supply. A change in either the epidemiology of HTLV in UK blood donors or the length of the window period of the test should prompt further review of the risk and a reassessment of anti-HTLV testing in the UK.

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

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. MATERIALS AND METHODS: Sporadic CJD and fCJD cases with a history of blood donation or transfusion are notified to UKBS. All vCJD cases aged > 17 years are notified to UKBS on diagnosis. A search for donation records is instigated and the fate of all donations is identified by lookback. For cases with a history of blood transfusion, hospital and UKBS records are searched to identify blood donors. Details of identified recipients and donors are checked against the NCJDSU register to establish if there are any matches. RESULTS: CJD cases with donation history: 18/31 vCJD, 3/93 sCJD, and 3/5 fCJD cases reported as blood donors were confirmed to have donated labile components transfused to 66, 20, and 11 recipients respectively. Two vCJD recipients have appeared on the NCJDSU register as confirmed and probable vCJD cases. The latter developed symptoms of vCJD 6.5 years and 7.8 years respectively after receiving non-leucodepleted red blood cells (RBCs) from two different donors who developed clinical symptoms approximately 40 and 21 months after donating. A third recipient, given RBC donated by a further vCJD case approximately 18 months before onset of clinical symptoms, had abnormal prion protein in lymphoid tissue at post-mortem (5-years post-transfusion) but had no clinical symptoms of vCJD. CJD cases with history of transfusion: Hospital records for 7/11 vCJD and 7/52 sCJD cases included a history of transfusion of labile blood components donated by 125 and 24 donors respectively. Two recipients who developed vCJD were linked to donors who had already appeared on the NCJDSU register as vCJD cases (see above). No further links were established. CONCLUSION: This study has identified three instances of probable transfusion transmission of vCJD infection, including two confirmed clinical cases and one pre- or sub-clinical infection. This study has not provided evidence, to date, of transmission of sCJD or fCJD by blood transfusion, but data on these forms of diseases are limited.

Documented cases of post-transfusion malaria occurring in England: a review in relation to current and proposed donor-selection guidelines.

BACKGROUND AND OBJECTIVES: Although uncommon, five cases of transfusion-transmitted malaria have been documented in England over the last 20 years. With the reappearance onto the market of high-quality malaria antibody assays, and by utilizing the results of analysis of these five cases, it has been possible to review the donor malaria-deferral guidelines. MATERIALS AND METHODS: Details of the five cases of post-transfusion malaria were reviewed against the proposed new donor-deferral guidelines for malaria. RESULTS: Three of the five cases of post-transfusion malaria were directly attributable to the deferral guidelines, allowing infectious donors to be bled. CONCLUSIONS: The proposed new guidelines will prevent further cases of transmission from semi-immune individuals.

Use of red cells preserved in extended storage media for exchange transfusion in anti-k haemolytic disease of the newborn.

Anti-k is a Kell-related antibody. There is little correlation between the maternal antibody titre and the severity of haemolytic disease of the foetus and newborn, and anaemia is usually associated with low bilirubin levels. Severe erythroblastosis has been reported with a low titre anti-k (IAT 8-16). We report a case of severe haemolytic disease of the newborn (HDN) due to anti-k. HDN was associated with a normal bilirubin level and reticulocytopenia. The foetus was monitored by ultrasound, and delivery by elective caesarean section (CS) was planned. The mother was admitted 1 week before the expected date of delivery, and the infant was delivered by urgent CS. The infant required exchange transfusion. As suitable plasma-reduced (k antigen(-)) red cell units were not readily available, k- SAGM red cell units (preserved in extended storage media: SAGM sodium chloride, adenine, glucose and mannitol) were provided. The post-transfusion Hb remained stable, and the infant did not require further transfusion support. Our findings (reticulocytopenia and normal bilirubin levels) support the hypothesis that the pathogenesis of anaemia and haemolysis in anti-k HDN may be similar to that in anti-K (suppression of erythropoesis and immune destruction of K+ erythroid progenitor cells by macrophages in the foetal liver). The ideal product for exchange transfusion is plasma-reduced RBC, less than 5-days old. We provided a 4-day-old SAGM red cell unit for exchange transfusion in a term infant, and this was uneventful. Caution should be taken, however, and renal function and electrolyte levels should be monitored closely. More information is required regarding the safety of SAGM units for exchange transfusion.

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 unit's 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.

Evidence that anti-HBc but not HBV DNA testing may prevent some HBV transmission by transfusion.

Blood donor screening for antibody to hepatitis B core antigen (anti-HBc) implemented in some countries as a surrogate marker for non-A, non-B hepatitis has been superseded by anti-HCV screening. To assess the value of anti-HBc screening for the detection of hepatitis B surface antigen-negative blood donations that might contain infectious HBV, HBV genomic detection and recipient testing were used. Blood donations were screened and confirmed by multiple anti-HBc assays. Donations containing isolated anti-HBc and those with anti-hepatitis B surface antigen (anti-HBs) level < 0.1 IU/ml were tested for the presence of HBV DNA. Recipients of previous donations from the corresponding donors during the previous 5 years were traced and tested for markers of HBV infection. Of 103 869 donations screened, 586 (0.56%) were anti-HBc positive, two of which contained HBsAg, and 413 (0.4%) had protective (>/= 0.1 IU/ml) levels of anti-HBs. Anti-HBs < 0.1 IU/ml was found in 102 of these donations (0.1%) and isolated anti-HBc in 69 (0.07%). No donations with isolated anti-HBc were HBV DNA confirmed positive. Of 278 recipients of previous donations from 171 donors at risk of HBV carriage, 12 had markers of HBV infection. Six recipients had other identified risk factors. An association with blood transfusion was considered probable in two and possible in four recipients. None of the six corresponding donors had detectable HBV DNA 6-40 months after the implicated donation. The frequency of HBV transmission by chronic carriers negative for hepatitis B surface antigen was estimated in this study to be 1 in 52,000 donations (CI 0.3-7.8/100,000) from HBsAg-negative donors. Such HBV infectious donations may not be detected by DNA amplification.