Objectives: In the organ donation process, screening for serologic markers for a selection of agents is essential to prevent infection transmission. The screening of donors for specific potential infections can never absolutely exclude the risk of transmission. For reevaluation of serology tests, we analyzed results of tests requested for all brain-dead donors.
Materials and Methods: Our study included all actual brain-dead donors who were seen from January 2017 to February 2018, received ancillary tests, and had final confirmation of brain death at our organ procurement unit.
Results: Most candidates for organ and tissue donation were seronegative for intended agents. We found that 14.4% of the samples were suspicious for infectious and needed further evaluation; 12.2% of donors had positive results corresponding to hepatitis B, and only 1.9% were rejected from donation. Requisiteness to DNA detection for hepatitis B virus infection was mainly related to age over 50 years.
Conclusions: The process of donor screening must systemically assess the donor. At the final stage, essential biomarkers must be investigated. Application of more caution in evaluation of older donors, including more screening tests before transfer to the operating room, remains mandatory.
Key words : Brain death, Deceased donor, Infection, Serology, Transmission
In the organ donation process, screens for serologic markers of a selection of agents is essential to prevent infection transmission.1 However, with consideration of graft shortages, there are risks of eliminating noninfectious seropositive donors, thus increasing mortality of patients on transplant wait lists. However, because there are still possibilities of infectious transmission by seronegative donors, prevention of transmission during transplant must be based on donor screening by exact selection protocols and tests.2
In general, laboratory screening is performed for hepatitis B virus (HBV) and hepatitis C virus (HCV), human immunodeficiency virus (HIV), and syphilis. However, serology for human T-cell lymphotropic virus (HTLV-1/HTLV-2) is not routinely performed and depends on the donor’s origin from high-inci-dence areas. Serology tests for pestiviruses, Cytomegalovirus, herpes simplex viruses 1 and 2, varicella zoster virus, and Epstein-Barr virus are routine, with some vari-ations between organ donation centers.3
Challine and associates4 provided valuable results corresponding to the prevalence of viral biomarkers among a general population and in brain-dead donors. They reported a 16.7% false-positive result in cornea donors and found that the prevalence of viral markers was higher than shown in a French general population.4 In more detail, prevalence rates of hepatitis B surface antigen (HBsAg), HIV antibody, and HCV antibody were 0.68%, 0.16%, and 0.86% in the general population and 1.56%, 1.15%, and 3.54% in brain-dead donors. The exact cause of this difference was not discussed, and more research in this field is necessary.
There are many reports on the possibility of organ transplant from infected donors and transmission of agents from recipients.5-7 Evaluation of donors for uncommon agents or nonendemic ones may be time consuming and expensive. However, obtaining a history of traveling and accurate physical exam-inations of the potential donor could lessen the cost-benefit burden. Today, evaluation of donors by serology tests is a tool for proper organ allocation rather than exclusion of organs. In an effort to reevaluate serology tests, we analyzed the results of tests requested for all brain-dead donors.
Materials and Methods
This study was performed at the Masih Daneshvari Hospital of Shahid Beheshti University of Medical Sciences (Tehran, Iran). From January 2017 to February 2018 after performance of ancillary tests and final confirmation of brain death, all actual donors were included in this study.
To screen donors, documentation of medical history and physical examination were first obtained. Any unusual neurologic presentation should be considered and the exact cause of death must be specified. For those not excluded by drug, social, and physical examinations, blood samples were collected to assess for viral infections. All tests were performed in a referral laboratory center.
For hepatitis B, HBsAg and anti-hepatitis B core antibody (anti-HBc), Vitros assays (Ortho-Clinical Diagnostics, Raritan, NJ, USA) were checked; if seropositive results were shown, polymerase chain reaction was conducted.
For hepatitis C, HCV antibody was detected with the Vitros anti-HCV assay (Ortho-Clinical Diagnostics) and the Access HCV antibody Plus method (Pasteur-Bio-Rad, Veenendaal, The Netherlands). In addition, detection of HIV antigen was with the Vidas HIV p24 II method (bioMerieux Inc., Craponne, France), and its presence was systematically confirmed by neutra-lization. Anti-HTLV-1 antibodies were detected with the Murex HTLV-1 and HTLV-2 enzyme immuno-assay (Abbott Laboratories, Abbott Park, IL, USA).
Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 22, IBM Corporation, Armonk, NY, USA). For quantitative and qualitative variables, t tests or chi-square tests were used, with significance level of P ≤ .05.
Of 263 total cases, it was striking that 85.6% had completely negative results. Serology tests cate-gorized brain-dead donors as completely negative donors (CND) and suspicious donors (SD), with mean age of 32.8 and 43.2 years, respectively (P = .02), although 87.5% were above 50 years old. We found that 62% of CNDs and 66% of SDs were male, with no significant difference in male versus female donors (P = .2).
In CNDs, causes of brain death included trauma (42%), although most were due to cerebrovascular accident (56%; P = .01). Among the SD group, history of recreational drug abuse or drug addiction was shown in 32%, which was different from CNDs with 35% showing such history (P = .2). Most cases needed PCR (mostly because of anti-HBc positivity).
Although 1.9% (n = 5) of cases were excluded by antigen/antibody results, PCR results did not exclude any cases. Table 1 summarizes the prevalence of positive and negative results. Abbreviations of serology tests are presented in Table 2.
Our study demonstrated that most brain-dead candidates for organ and tissue donation were seronegative for viral agents that are considered in Iranian protocols of organ procurement. Only 14.4% of samples were suspicious for infection and needed further evaluation.
Organ transplant may expose recipients to numerous infectious agents, including bacterial, viral, and fungal contaminations, as well as infection by other rare agents such as parasitic and prion, which could be transmitted via organ and tissue allografts.8 However, screening donors by viral biomarkers is a double-edged sword, which can indicate seronegative blood samples but exclude noninfectious seropositive samples.3 Indeed, false-positive results for donor samples9 and HIV trans-mission from a seronegative donor to 7 recipients10 have been reported in the literature.
Organ donation in Iran involves a centralized model: each medical university has its own organ procurement unit (OPU) for all hospitals under its coverage. Any potential brain-dead donor must be referred and transferred to the related OPU. Official brain death confirmation, final organ evaluation, organ allocation, and organ retrieval are all executed in the OPU.11 Apart from the legal dimension, the whole process in the OPU could be seen as an effort to maximize the quantity and quality of trans-plantable organs. According to strict safety regu-lations from the Iran Ministry of Health, all deceased cases transferred to OPUs must pass comprehensive virology tests in a reference laboratory (even if they have negative or nonreactive results in the first hospital laboratory). After known cases of viral infections are excluded, at first visit by the organ donation team, additional evaluations would be performed. These tests include detecting antibody titers for hepatitis B and C (HBsAg, anti-HBs, anti-HBc, anti-HBe, and HCV antibody), other agents (including HIV antibody, cytomegalovirus immuno-globulin G [IgG] antibody, Toxoplasma IgG antibody, Epstein-Barr IgG antibody, HTLV IgG antibody, the venereal disease research laboratory test), and P24 (in high-risk cases). In cases of any suspicious or borderline results, a related PCR must be conducted (usually for anti-HBc-positive cases).
Procured organs from identified donors with positive tests may be utilized for specific recipients on wait lists after informed consent is received, based on the patient’s condition. Hepatitis B virus infection is extremely prevalent worldwide.12 Therefore, a donor’s blood is screened for HBsAg and anti-HBc in most countries and for anti-HBs in some countries.4 Our study showed that 12.2% of donors were suspicious for HBV infectious, which would need more evaluation to confirm active infection. We did not perform anti-HBs tests due to the national Iranian vaccination program; however, HBV DNA was detected in 0.07% of the donors with either seronegative or anti-HBs-positive results.13 In general, donors with HBsAg are excluded from donation, but there have been previous successful renal transplants from HBsAg-positive donors in 6 patients.14
In case of HCV-infected organs, there is contro-versy regarding transplantation, and these organs are commonly used for HCV-infected recipients. Our data showed no HCV infection among the 263 actual brain-dead donors.
Other agents such as Toxoplasma gondii, which is more related to cardiac transplantation, are also considered by both donation and transplant teams. In a retrospective study in Canada, Toxoplasma seroconversion, transmission, and donor-recipient mismatch were evaluated over a period of 14 years. The mismatch condition was in 9.5% between donors and recipients. With respect to annual laboratory cost, the authors concluded that routine screening for Toxoplasma is not necessary, particularly in transplant centers that use routine prophylaxis.15
Regarding the use of organs procured from HIV-positive cases, as shown in a South African study,16 it is important to make strategic decisions to extend the organ donation pool using HIV-positive donors. A nationwide investigation in the United States described an annual average of 494 potential donation from HIV-positive cases as donors.17 In these donors, however, comorbid factors such as coinfection of hepatitis and aging should be considered. In a previous national survey, 71.9% of HIV-positive patients agreed to be organ donors.18 However, 7965 patients were on the organ transplant wait list, while only 366 patients received organ transplants in 2015.18 Obviously, the increased longevity of HIV-positive patients and occurrence of organ failure among them are other motivating factors to accept these organs.
The special situation of organ recipients leaves no room for any risk, and a thorough approach to screen all infections seems reasonable. The PCR is a very expensive test and can easily triple the final bill for OPUs. In our study, we did not discuss costs of laboratory tests.
Because there have been reports of rabies virus transmission through solid-organ transplant,19 it should be noted that screening of donors for potential infections does not absolutely exclude all risks. However, rabies transmission is an uncommon event. Indeed, the process of donor screening must systemically assess the donor with essential biomarkers. However, if infectious transmissions can be registered in a unique database and be made available to all transplanted team, it would be easier to assess an infected organ. In other words, whether to be on a wait list for an SD organ or no organ, which is the best option?
We recommend a revision in the serology test protocol, PCR indications for deceased donors, and the status of the reference laboratory. In addition, more caution should be applied in evaluations of older donors and more screening tests should be conducted before transfer of potential brain-dead donors to the OPU.
Volume : 17
Issue : 1
Pages : 260 - 263
DOI : 10.6002/ect.MESOT2018.P114
From the 1Organ Procurement Unit (OPU), Lung Transplantation Research Center
(LTRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD),
Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran; and the
2Tracheal Diseases Research center (TDRC), National Research Institute of
Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid
Beheshti University of Medical Sciences, Tehran, Iran
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Farahnaz Sadegh Beigee, Organ Procurement Unit (OPU), Lung Transplantation Research Center (LTRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences (SBMU), Darabad, Niavaran, Tehran, Iran 19569-44413
Phone: +98 2127212032
Table 1. Results of Serology Tests for Brain-Dead Donors
Table 2. Abbreviations of Serology Tests