Familiar to all who work on the front line of clinical transplantation, is the phone call about donor medical suitability in which you are told the potential donor has a history of an eponymously named syndrome or disease, the details of which you are only vaguely, or not at all, aware of. Can it be transmitted by donation? That problem is usually resolved by consulting the literature, or a relevant specialist colleague, or the physician looking after the donor, but the data are often limited and one has to work from first principles. The traditional search of MEDLINE may discover a relevant report, but the unique aspects of a published case can still leave one wondering about the correct course of action with any particular donor. Surely there has to be a better answer to this very frequent problem?
Medical Products of Human Origin (MPHO) have been known to be associated with transmission of disease for as long as transplantation of organs, cells, and tissues has been undertaken.1 The term “MPHO” is now used to designate the increasingly complex landscape of such human “products,” which extends from the familiar territory of blood transfusion, corneal transplants, and solid organ transplantation, to now include many assisted human reproductive therapies and a variety of single cell constructs in proven and unproven treatments.
Transmission of disease really came to the attention of the general community in the context of both blood transfusion and the blood products used in the treatment of hemophilia, when hepatitis and then HIV were transmitted. Such is the global frequency of blood transfusion, and the universal penetration into the hemophiliac community due to the practice of pooling, that public notice turned into public outcry and the demand for heads to roll.2
Shining a light on this problem is not enough to solve it. The components of reducing the risk of disease transmission include effective and reliable screening protocols based on medical history, physical examination and screening blood tests. The 4 areas of potential disease transmission that need routine consideration in every donor, are infections including prions, malignancies, genetic conditions and a variety of transferrable diseases such as allergies and “auto” immune disorders.
A burgeoning nomenclature has been built up across the regulatory and clinical frameworks to help distinguish, define, and classify the problems we may face. Certainty is not a feature of much of the literature, unfortunately, and we have had to rely on graded definitions of the donor origin of “adverse reactions” such as an infection or a cancer in the recipient, as “possible, likely/probable, or definite/certain/proven” depending upon the data available. Many of these events have been collated and investigated only because of the initial suspicion of a clinician including the recent identification of a new Arena virus with 3 deaths as a consequence of an unusual early posttransplant encephalitis linked to one donor and a novel virus discovered, after detailed research, turning “probable” into “proven.”3 This is one area of medical practice where there will never be a randomized controlled trial and we will forever be constrained to observational and epidemiological data.
The work of the Organization(WHO) in organ, cell, and tissue donation and transplantation, that began in 2003 with a resolution of the WHO Executive Board, has spawned several projects and enduring processes. These include: revision of the WHO Guiding Principles adopted in 20104; the Global Observatory of Donation and Transplantation run on behalf of the WHO by the Spanish Organization Nacional Trasplante5; and the project Notify run as a collaborating center of the WHO, by the Italian National Transplant Centre (CNT). The details of the ongoing “Project Notify” are now published in this issue of Transplantation.6
The Notify Library is an open access, searchable database of systematically identified reports of disease transmission and other adverse occurrences arising from the donation and clinical application of MPHO. It is built from inclusion of reliably documented events reported in a published article or official vigilance reporting system, which have instructive value for the fields of transfusion, transplantation, or assisted reproduction. The selection and review of included references for publication is carried out by international experts who collaborate in 5 topic specific editorial groups: infection and malignancy transmission, living donor reactions, process-related incidents, and clinical complications.
The Notify Library7 now has 1733 records and 2632 references involving organ transplantation (~40%), blood and blood components (~20%), hematopoietic progenitor cells (~16%), tissues (~15%) with the remaining ~5% coming from reproductive tissues and cells and miscellaneous other MPHO. It has been designed to be easy to search both by professionals in the field and the general public, to provide a quick and reliable mechanism to access known data on a particular issue or problem.
The library relies upon a constant stream of new information coming from the literature, but that literature is obsessed with “novelty” and editors, like myself, are not predisposed to publish the second case of disease transmission without a particular new message not conveyed by the first report. Many national and international regulatory authorities have designed vigilance and safety programs to improve the safety of MPHO, knowing that the benefit risk equation in life saving organ and cell transplantation is complex. It might make sense to ban people from donating blood with even the smallest risk of transmitting new variant Creutzfeld Jacob Disease (nvCJD) using a screening questionnaire but applying that protocol to organ transplantation would have stopped all programs in the United Kingdom, and for example, reduced Australian donation programs by >20%, leading to many more deaths from missed transplantation opportunities than could ever be saved from avoiding nvCJD. These national “competent authority” programs have been created to collect, analyze, and report the data on such adverse events7,8 and they now provide those data to the Notify Library to ensure that we all learn from each other.
There is indeed a better answer to resolving medical suitability risks, available today thanks to the efforts of the CNT and Project Notify Team. The Notify Library is there for you to use.
1. Ho M, Suwansirikul S, Dowling JN, et al. The transplanted kidney as a source of cytomegalovirus infection. N Engl J Med. 1975;293:1109–1112.
3. Palacios G, Druce J, Du L, et al. A new arenavirus in a cluster of fatal transplant-associated diseases. N Engl J Med. 2008;358:991–998.
4. World Health Organization. WHO guiding principles on human cell, tissue and organ transplantation. Transplantation. 2010;90:229–233.
5. World Health Organisation Global Observatory on Donation and Transplantation. Available at http://www.transplant-observatory.org/
. Accessed November 24, 2020.
6. Petrisli E, Carella C, Navarro A, et al. Vigilance for medical products of human origin – progress on the Notify Library’s global effort to share information and learning. Transplantation. 2021;1921–1929
7. The Notify Library. Available at https://www.notifylibrary.org
/. Accessed November 24, 2020.
8. Green M, Covington S, Taranto S, et al. Donor-derived transmission events in 2013: a report of the Organ Procurement Transplant Network Ad Hoc Disease Transmission Advisory Committee. Transplantation. 2015;99:282–287.
9. SOHO V&S Guidance for Competent Authorities. Communication and investigation of serious adverse events and reactions associated with human tissues and cells
. Available at http://www.notifylibrary.org/sites/default/files/SOHO%20V%26S%20Communication%20and%20Investigation%20Guidance
. Accessed November 24, 2020.