Prion infection surveillance project

Dr Anna Molesworth

Prion diseases are associated with a naturally occurring protein (the prion protein) that has changed into an abnormal form. Most cases have no known cause, but one type of prion disease called variant Creutzfeldt-Jakob Disease (vCJD), usually linked to having eaten contaminated beef in the past, may also be spread from person to person by blood donation from someone who themselves may later develop vCJD.

The prion surveillance project was started by the Primary Immunodeficiency Association (PiA) and the UK Primary Immunodeficiency Network in 2006 with the aim to see if any evidence could be found of prion infection in antibody deficient patients who received certain UK-sourced immunoglobulin products between December 1996 and December 2000. Patients who had received these products had previously been informed of their potential exposure to prion disease in 2004 as part of a national patient notification and risk assessment process. Following the 2004 notification, the prion surveillance study would be done by following these patients over several years, with consent, and testing any available tissue (for example, the tissue left over from routine biopsies) and blood for the abnormal prion protein that causes prion disease. Participants could also agree to donate tissues obtained from a post-mortem.

Results and transfer of study from Manchester to Edinburgh

The prion surveillance study began in July 2006 and was led by Dr Matthew Helbert, Consultant Immunologist, and Research Nurse Cathy Bangs, working with NHS Trusts throughout the UK in collaboration with the National CJD Research & Surveillance Unit (NCJDRSU) in Edinburgh, and under sponsorship of Central Manchester University Hospitals NHS Foundation Trust. The results to date have now been published in the journal Vox Sanguinis. Dr Helbert, lead author on the paper, comments: ‘We found that surveillance of 75 immunodeficiency patients exposed to UK-sourced immunoglobulin, including batches derived from donors who went on to develop vCJD, has not detected any clinical cases of vCJD, or of asymptomatic infection in 15 patients who had available tissue samples of sufficient quality for testing. These results have been very reassuring but it is very important that we continue to monitor patients over the long term as we know that prion disease may take many decades to develop after exposure.'

Following the retirement of Dr Helbert in 2015, Dr Anna Molesworth at the NCJDRSU in Edinburgh will now take the lead for the study, with continued funding from the UK Department of Health Policy Research Programme. The NCJDRSU brings together doctors, scientists and nurses with a special interest in prion disease surveillance, epidemiology and clinical and laboratory research. As part of this study, Dr Molesworth and her team will undertake the recruitment and long-term follow-up of participants over the next several years, continuing the NCJDRSU’s long-term commitment to this project and other public health research involving prion disease. Among her other work, Dr Molesworth contributes to the clinical surveillance of CJD in the UK and its related public health activities, including enhanced surveillance of patients exposed to CJD in the medical setting, working closely with the UK national public health agencies as part of her role.

'Our unit provides doctors with information about prion disease, and advice on how to look after their patients, as well as undertaking research into the causes of prion disease’, said Dr Molesworth. ‘With renewed funding from the Department of Health Policy Research Programme we have been able to appoint a dedicated research nurse to help with outreach to the immunology centres. By working with immunology teams and patients throughout the UK, we hope to understand more about the causes of prion disease, particularly about the long-term risks that may be associated with past treatment with blood products in patients with primary immunodeficiencies.’

What it means to patients and how will they now be involved?

‘With transfer of the study to the unit in Edinburgh, we have made some changes to the protocol, with the intention of simplifying the research process’, explains Dr Molesworth. ‘The changes include developing a questionnaire for recording a patient’s immunoglobulin treatment, past medical history of blood transfusion products and any surgery. We would also like to ask participants where they have lived, their type of work and if there is any family history of dementia. This information may help to identify the most likely cause of prion infection, if ever we have a positive finding.’

There is still no blood test for prion infection that can reliably tell us if someone is infected with vCJD before they develop symptoms of the disease, however, scientists continue to work on this.

‘Going forward we will continue to collect blood samples but only once every two years instead of once a year, with an annual telephone call in between, and samples will now be sent to the CJD Resource Centre at the National Institute for Biological Standards and Control (NIBSC) in Hertfordshire for storage and future testing (when a suitable blood test becomes available), instead of Manchester where they have previously been stored. Most importantly we will continue to seek consent in life from all participants for post-mortem examination and tissue investigation for evidence of CJD. Collecting tissue at post-mortem is the best way to get the type of samples that will help us confidently state whether prion infection has taken place. Understandably, it is a very difficult subject to discuss. But we strongly encourage participants to consider making a gift of tissue after their death and to discuss this fully with their family member’, said Dr Helbert.

The project’s steering committee and patient representation

The project’s steering committee meets regularly and Rae McNairney, who is the patient representative on the committee and a member of PID UK’s patient panel, has been helping with the ethics application and developing patient and family material. ‘I’ve been involved since this project started, when as part of the board of the PiA the decision was taken to support this study, and I worked with Dr Helbert to produce patient information leaflets. Although the study will not provide an individual with a personal result, it may result in information that will help others in the future, and advances in healthcare just wouldn’t be possible without people who are willing to take part. It’s really important to raise awareness of the study among people with PID and their clinicians so that we can start to obtain tissue samples.’

The study has recently appointed Kudzai Karekwaivanane, a nurse with clinical experience gained from working in the UK and Zimbabwe who will be contacting immunology centres and hopes to start meeting patients this year. In the meantime, if you are already part of this study, or if you would like to find out more, please contact your local immunology team or Kudzai at the NCJDRSU on 0131 537 2128 or 07464 677118.

Publication reference:

Helbert MR, Bangs C, Bishop M, Molesworth A, Ironside J (2015). No evidence of asymptomatic variant CJD infection in immunodeficiency patients treated with UK-sourced immunoglobulin. Vox Sanguinis. 2015 Nov 3. doi: 10.1111/vox.12358. [Epub ahead of print; see]

Posted August 2016