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Clinical and Translational Research

Investigation of Variant Creutzfeldt-Jakob Disease Implicated Organ or Tissue Transplantation in the United Kingdom

Molesworth, Anna1,6; Yates, Philip2; Hewitt, Patricia E.3; Mackenzie, Jan1; Ironside, James W.1; Galea, George4; Ward, Hester J.T.5

Author Information
doi: 10.1097/TP.0000000000000105
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Abstract

Variant Creutzfeldt-Jakob disease (vCJD) is a rare illness, with a total of 177 cases having been reported in the United Kingdom (UK) since the first case was reported in 1996. Although consumption of bovine spongiform encephalopathy (BSE) contaminated meat products remains the most likely route by which humans became infected (1), human-to-human transmission of vCJD has occurred through blood transfusion (2) and could also theoretically occur as a result of the transplantation of organs or tissues (here defined as including cellular therapy products) from sub-clinically infected individuals if the donor were infected with vCJD (3, 4). Factors believed to affect this risk include the relative infectivity of the tissue (resulting from the intrinsic infectivity of the tissue itself (5) or contamination with residual blood), the mass of the tissue, and the site of transplant (4).

In the UK, donors of blood components to, and recipients of blood from, vCJD cases are traced by the UK blood services in collaboration with the UK National CJD Research and Surveillance Unit (NCJDRSU), to minimize the risk of onward vCJD transmissions (6). In view of the potential for transplant-associated vCJD transmission, a medical “look-back” study was undertaken by the NCJDRSU in collaboration with the UK blood and transplant services. This was done as part of efforts to ensure traceability for organs and tissues as is already the case for blood components and plasma products in the UK, and thus enhance the ascertainment of transplant-associated vCJD. This study aimed to investigate whether UK cases could have contracted vCJD by receiving an organ or tissue transplant, or could have transmitted vCJD to others by this route. The use of bone and dura mater in dentistry were previously investigated in a case-control study of dental risk factors for vCJD (7) and are not considered further here.

RESULTS

Review of Medical Histories

Medical histories were reviewed for all 177 UK vCJD cases. Of these, 173 had primary care general practice (GP) records available and for a further three cases the medical histories were reported by the families. For the remaining one vCJD case, for whom there was no GP or family record, the medical history was provided by the consultant clinician responsible for the patient’s care.

A total of 138 cases had a history of surgical procedures across a wide range of specialties; of these cases, 35 had undergone procedures where the receipt or donation of organs or tissues might have occurred. Procedures of interest are presented in Table 1. The outcome of the review is summarized in Table 2. Further investigations of the medical notes for the 35 cases confirmed one patient as having undergone organ (liver) transplantation approximately 20 years previously, for whom a look-back was undertaken. Despite rigorous scrutiny of the medical records for the vCJD cases, no other situations were identified where the receipt or donation of an organ or tissue occurred.

T1-18
TABLE 1:
Opportunities for in-life allogeneic donation and receipt of organs and tissuesa
T2-18
TABLE 2:
Outcome of investigations

Transplantation

It was possible to confirm the identity of the liver donor, the date of death, and place of donation, and that there were four other organ or tissue recipients (of two kidneys and two corneas). It was also possible to confirm that the heart had also been donated and sent to the regional tissue bank for processing into heart valves. Two heart valves had subsequently been requested and issued to different operating theaters on separate occasions. Details of the donation and receiving theaters were held by the regional tissue bank. No other organs or tissues had been taken from the donor. The liver donor had died of causes unrelated to CJD. The liver recipient had additionally received red cells from 103 donors in transfusions before and after the liver transplant operation. None of the blood donors to the liver recipient have subsequently been reported as vCJD cases.

Public Health Implications

The estimated risk to the blood donors to the vCJD case and other recipients of blood from these same blood donors had previously been assessed and, as a result, the implicated blood donors had been asked to take public health precautions to minimize the risk of onward vCJD transmissions; the risk to the other recipients of blood from the same donors was not considered sufficient to warrant notification (8). Had the liver transplantation involved a living donor transplant, the donor would have been similarly informed of their increased vCJD risk; any implicated tissues still in stock would have been discarded. Expert advice was sought from the UK CJD Incidents Panel regarding the recipients of the six other organs or tissue from the liver donor and, in view of the earlier decisions relating to the blood donors, the other transplant recipients were not considered to have an increased vCJD risk (CJD Incidents Panel, personal communication March 15, 2012).

DISCUSSION

We investigated all 177 UK vCJD cases and identified one situation where an organ (liver) recipient had subsequently developed vCJD. No other situations were identified where the receipt or donation of organs or tissues occurred from, or to, people who went on to develop vCJD. The liver recipient had lived in the UK throughout life, and although transfusion- or transplantation-associated infection cannot be ruled out, the patient could also have contracted vCJD by dietary exposure to BSE as for the majority of vCJD cases in the UK (9).

The study was not without its limitations. The review of the medical notes was as thorough as possible, but inaccurate or incomplete, or both, surgical histories, together with assumptions made, as part of the initial screening of medical histories, about the types of operation where the receipt or donation of organs and tissues were likely, may mean that some potential scenarios might have been missed. Nonetheless, we feel that for the majority of vCJD cases any relevant procedures, which are significant and relatively uncommon interventions, are unlikely to have gone unrecorded.

With regard to traceability, tracing the liver donor and the four other organ recipients from the same donor was relatively straightforward as the recipient details were held by the UK blood and transplant services. The heart valves could be traced through the respective tissue banks to theater issue although we did not confirm if the individual recipients could be identified as there was no public health justification to do so. We recommend the long-term retention of theater records to aid future public health investigations should the need arise.

How will transplant-associated vCJD be captured in the future? Currently, direct links between vCJD cases may be detected through existing clinical surveillance mechanisms or through enhanced surveillance of vCJD in individuals “at-risk” of CJD. The former mechanism relies on collecting full and detailed information regarding the time and place of medical interventions, and as part of national surveillance activities we will continue to give a high profile into the future to asking about known transplants and other medical procedures. Enhanced surveillance additionally requires identification and registration of “at-risk” individuals and their ongoing investigation for evidence of vCJD. However, neither the routine nor the enhanced surveillance processes are without their limitations, and both may be incomplete; as a result, transplant-associated vCJD may be missed. We suggest, therefore, that a greater emphasis should be placed on the use of donation and transplant registries, specifically a structured approach to reconciliation of known vCJD cases against such registries, as is currently the situation in the UK for blood components and plasma products (6), with a view to detecting potential receipt or donation of organs and tissues and thus enhance the ascertainment of transplant-associated vCJD.

MATERIALS AND METHODS

Participants

All cases of confirmed or probable vCJD (standard diagnostic criteria) who had been ascertained as resident in UK at onset of clinical symptoms and who had ever been referred to the NCJDRSU (May 1995 to December 2013; n=177) were considered eligible for inclusion in the study.

Review of Medical Notes

As part of routine surveillance activities at NCJDRSU, for each vCJD case the GP medical records were requested after the patient’s death with consent of a close family member and, together with information given by the relative at around the time of the patient’s diagnosis, reviewed to derive a medical history. Specific questions were asked to elicit the possibility of organ or tissue receipt or donation. These included the history of any operations or other nonsurgical hospital admission, a specific question on whether, where, and when the patient had undergone an organ or tissue transplant and, finally, any history of fertility treatment or of treatment involving a course of injections which might, for example, include immunotherapy with hematopoietic stem cells (HSC).

Information for all cases was anonymized and then screened by a medical specialist consultant (Scottish National Blood Transfusion Service Tissues and Cells Directorate) to identify possible scenarios where allogeneic organ or tissue donations and transplants could potentially have occurred. We focused on the time period from 1980, before which time exposure to BSE agent is thought unlikely to have occurred, until death (for donation) or onset of symptoms (receipt). Opportunities for the receipt and donation of organs and tissues are summarized in Table 1. For each operation a patient underwent, an assessment was done as to whether or not this was a procedure where an organ or tissue could have been received or donated. If a possible scenario was identified, the hospital records for that operation were then reviewed by NCJDRSU in an attempt to confirm whether or not a transplant or donation actually took place. As part of this process, we also checked the use of donated eggs or sperm to achieve a pregnancy, identified by attendance at a fertility clinic and, for childbirth to a female vCJD patient, whether there could have been a cord blood or amnion donation. We excluded autologous procedures and transplants received within a year of onset of vCJD symptoms as not relevant.

If the receipt or donation of an organ or tissue was confirmed or thought to be highly likely, anonymity was broken and a “look-back” was then performed to identify the establishment that had handled the implicated organ or tissue (normally registered with the UK Organ Donation and Transplantation directorate or with the tissue bank) and hence establish to what extent the respective donors or recipients could be traced. Finally, we sought to establish how many other organs and tissues from the same donor were involved and whether they had been transplanted, discarded, or banked. Subsequent public health actions would then be taken in line with UK guidance on the management of incidents where patients may have been exposed to CJD through medical procedures (10).

ACKNOWLEDGMENTS

The authors thank their patients and their family members for their help in the collection of data. CJD Surveillance, including this look-back study, is independent work commissioned and funded by the Department of Health Policy Research Programme (National CJD Research & Surveillance Unit; 007/0190) and the Scottish Government Health Department. The views expressed in this publication are those of the authors and not necessarily those of the funding bodies.

REFERENCES

1. Ward HJT, Everington D, Cousens SN, et al. Risk factors for variant Creutzfeldt-Jakob disease: a case-control study. Ann Neurol 2006; 59: 111.
2. Llewelyn CA, Hewitt PE, Knight RSG, et al. Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 2004; 363: 417.
3. Gill ON, Spencer Y, Richard-Loendt A, et al. Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. BMJ 2013; 347: f5675.
4. Standards and Quality Analytical Team. Risk Assessments for vCJD Transmission via Donated Bone or Tissues. London: Department of Health, UK; 2006.
5. World Health Organisation (WHO). WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies. Geneva: WHO; 2010, report no. WHO/EMP/QSM/2010.1.
6. Hewitt PE, Llewelyn CA, Mackenzie J, et al. Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiological Review study. Vox Sang 2006; 91: 221.
7. Molesworth AM, Smith AJ, Everington D, et al. Risk factors for variant Creutzfeldt-Jakob disease in dental practice: a case-control study. Br Dent J 2012; 213: E19.
8. Standards and Quality Analytical Team. Assessing the Implications for Blood Donors if Recipients are Infected With vCJD. London: Department of Health, UK; 2004.
9. Molesworth AM, Cousens SN, Gill ON, et al. Variant Creutzfeldt-Jakob disease in the United Kingdom: a country-wide or local risk? J Epidemiol Community Health 2010; 64: 616.
10. 10. Public Health England & Health Protection Scotland. Public health actions to be taken following a report of a new case of CJD or a person at increased risk of CJD. Colindale (London), 2013 available at http://www.hpa.org.uk/web/HPAweb&HPAwebStandard/HPAweb_C/1225960588712. Accessed March 11, 2014.
Keywords:

Organ; Tissue; Transplantation; Donation; Public health; vCJD

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