Infections and Organ Transplantation

SECTION 1: ORGAN, TISSUE, AND CELL VIGILANCE IN ITALY Alessandro Nanni Costa, and Deirdre Fehily As the regulation of organ, tissue, and cell donation and transplantation has developed in the European Union, the Italian Transplant Network, coordinated by National Transplant Centre (CNT), has led the implementation of the legislative requirements in Italy, focusing efforts on ensuring safety from the moment of donor identification to the clinical follow-up of recipients. The European legal framework covers substances of human origin and comprises a series of Directives, the most recent of which defines the requirements for organ donation and transplantation (Figure 1).FIGURE 1: The development of EU Regulation of substances of human origin.Vigilance is a fundamental element identified in all of these Directives, with a requirement for the notification of serious adverse events (SAEs) and reactions (SARs). Safety and Risk in Organ Transplantation All types of transplantation imply inherent risks that must be minimized through the application of stringent safety procedures. In the case of organ transplantation particularly, the associated risks must be weighed against the benefits of receiving a transplant in the context of organ shortage. Italian transplantation guidelines identify five levels of risk: Unacceptable risk An increased but acceptable risk Calculated risk Non-assessable risk or potentially high risk for infectious disease transmission Standard risk An example of risk level 4 would be a case where during 2 weeks before donation, the donor had participated in high-risk behavior for infectious disease transmission (e.g., prostitution or drug injection), the possible positivity for which might not be detected even through the most sensitive techniques of molecular biology are applied. Only those potential recipients who signed a specific consent form when they were entered on the waiting list can receive organs categorized with this risk level. Although the Italian guidelines are now well established, each case is different and individual decisions are frequently required to ensure that valuable organs are not lost and recipients are not exposed to unjustifiable risk. This process is supported by a system of “Second Opinion” for evaluation of risk. A 24 hr a day, 7 days a week support is provided by a team of specialists in infectious disease, pathology, legal medicine, intensive therapy and immunological disease. Two National Coordinators are available for a second opinion on organ suitability and therapeutic suggestions for donors or recipients. In the case of donor malignancies, considerable improvements have been achieved in detection before transplantation (Figure 2). All the centers transplanting organs from infected or neoplastic donors are asked to supply regular follow-up data to the National Centre for Transplantation, so that the implications of transplanting organs with elevated risk are closely monitored.FIGURE 2: Timing of neoplasia identification.Table 1 shows the donations classified as involving “Calculated Risk” and demonstrates the value, in terms of effective transplants, of applying this approach to donor selection.TABLE 1: Transplants with calculated risk 2003–2010Risk reduction and management requires continual reevaluation of changing and emerging risk. In Italy, the arrival of West Nile Virus required additional monitoring and the application of safety measures to reduce any risk of transmission by transplantation (1). Retrospective screening of organ donors in 2009 provided valuable information regarding the spread of West Nile Virus (2). Vigilance However, despite the application of safety guidelines and the establishment of advisory networks, mistakes can happen and unexpected transmissions occur. The most important serious adverse reaction (SAR) in the field of organ transplantation in Italy in recent years was the transmission of HIV to three organ recipients after a transcription error in a testing laboratory (3). The incident resulted in a thorough review of the safety system, the establishment of a National Safety Audit Commission and a survey and audit program of testing laboratories. When tragic incidents of this type occur, it is essential that the outcomes and lessons learned be effectively communicated to all those involved in the network, so that appropriate measures can be taken to prevent recurrence. Since February 2007, CNT has been collecting information regarding all SARs and SAEs occurring nationally within the transplant network, applying the definitions used in the European Directives (“serious adverse event” means any untoward occurrence associated with the procurement, testing, processing, storage, and distribution of tissues and cells that might lead to the transmission of a communicable disease, to death or life-threatening, disabling, or incapacitating conditions for patients or which might result in, or prolong, hospitalization or morbidity. “Serious adverse reaction” means an unintended response, including a communicable disease, in the donor or in the recipient associated with the procurement or human application of tissues and cells that is fatal, life-threatening, disabling, incapacitating or which results in, or prolongs, hospitalization or morbidity). A national reporting form was adopted in May 2010, which is submitted together with a detailed report for each notification. Adverse events, where no patient has been harmed but an incident has occurred which implied or still implies risk, are considered important within the Italian system where they allow the sharing of information for the prevention of harm. Reports indicate that serious adverse reactions or events (SARE) occur at all stages of the process from donation to transplantation (Figure 3).FIGURE 3: Reports of Serious Adverse Events and Reactions in the field of Transplantation in Italy.European Union funded projects, particularly EUSTITE (European Union Standards and for the of and (European for the of Organ have developed important of and evaluation to support have been in the Italian system where they support the process of of and the of any or The of is by the of a for the of adverse events and reactions on a to the Italian Transplant The Italian demonstrates that the and of outcomes in transplantation are essential for ensuring and an level of risk for donors and recipients. Nanni taken to reduce the risk of West Nile transmission by transplantation in on of the Italian Transplant Retrospective screening of organ donors in Italy, of West Nile Nanni organs used for transplant in Italy to human SECTION 2: VIGILANCE AND and malignancies, have been a of in the events has required an involving transplant organ procurement and the Organ and Transplantation from review of potential transmission events has the for of involved in disease The for in the was developed in with the of specific and the National Organ Transplant of which the and Organ system and requires to prevent the procurement and transplant of organs from donors infected with HIV (1). In the of and the the to to prevent the of organs from donors infected with as in (2). to guidelines for testing organ donors and transplant recipients for the specific of infectious and that organs from with HIV not be used (3). 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West Nile Virus transmission organ transplantation and SECTION 3: AND This a review of lessons learned from recent transmissions through organ including HIV transmission from and results of a the of testing for organ donor identification of in organ the for data to risk to the of The of and Safety and within for and and with in the and of and transplantation the of a system for organ disease transmission in the for adverse events, including disease on to data to in patient Since HIV was to be through organ transplantation in the a of (e.g., West Nile (e.g., (e.g., and (e.g., have been in the transmission of a was in each from a donor with of disease transmission from donors with in with is that are for HIV and are of for donor In 2007, in an in which HIV and were from a donor to organ transplant recipients This had been before and resulted in the death of with the patients The who was on evaluation to be at elevated risk for HIV was with as is by and for of HIV and but was to be with HIV and as by on at the of organ donor screening with HIV and would have this tragic and be In HIV was to a recipient from a donor the recipient developed an and was to have the donor was with and an was the donor was to be at high risk to behavior who have with and HIV days before organ was was in the donor days before transplant and in the recipient days with donor and recipient As of this now for donor screening no 7 days before organ donor and recipient consent is taken by the transplant must be adopted by the to and can result in a and at the of this is no national for screening of A survey has that recipients who receive organs from high-risk donors are for HIV to of despite to so in the the of and recipient testing, it is that have been HIV transplant transmissions as is on a of a as or to is to from these events, and this is it is to on adverse events and process incidents in organ in the and In the of must be used to the risk of transmission screening and the potential of additional Although is for screening donors for infectious is no for of in donor In a recent the of not for and in donor with of the potential organ donor to the risk of HIV and transmission and the additional reduction of risk by the of The was by in potential organ from donor and to risk. was and for and risk, when was to risk for HIV was from 1 in to 1 in for risk, and from 1 in to 1 in for high risk. was and for and risk, when was to risk was from 1 in to 1 in for risk and from 1 in to 1 in for high risk. these is infected donor that is and to three donors of which are When the risk of HIV and of tissue, and organ it is that high-risk organ donors are to HIV and to In these results that screening screening reduce the of HIV and potential organ donors and patient organ and recipient The transplant on the of in organ donor screening is A report by and of the not to for and as the of for the screening of potential organ donors increased risk the report that be considered to reduce the risk of transmission and potentially organ with the for Although are and not be in this were on of of and of years for all when was used for all However, were a of in this it is that are 1 in on testing laboratory and data be so that it can be was not calculated for of in high-risk even it was so it is the was for of screening was that is to a different of opinion on the of on the of high-risk and that the are HIV risks and not risk for as and have led to efforts to the The on transmission prevention of and and an process to support the The process was developed in five with from the by transplant The is by that developed by the and The was developed from a review of the is no to opinion was or the and was as a The is in and be for after which it be and as In donors at high risk can be identified and the risk to the possible for recipients. 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