key: cord-0883847-9n6gc2b3 authors: Fischer, S. A.; Avery, R. K. title: Screening of Donor and Recipient Prior to Solid Organ Transplantation date: 2009-12-16 journal: Am J Transplant DOI: 10.1111/j.1600-6143.2009.02888.x sha: 5508719afd0e1691a5acfe016f06a28d6abfd77c doc_id: 883847 cord_uid: 9n6gc2b3 nan Pretransplant screening of potential organ donors and recipients is essential to the success of solid organ transplantation (1) (2) (3) (4) . The goals of pretransplant infectious disease screening are: (1) to identify conditions which may disqualify either donor or recipient, (2) to identify and treat active infection pretransplant, (3) to define the risk of infection and determine strategies for preventing and mitigating posttransplant infection and (4) to implement preventative interventions, such as updating of vaccination status. Although there is general agreement on the major infections for which screening is performed, there is some variation between centers in the types of screening used and actions taken as a result. In the course of pretransplant evaluation, recipients should be evaluated for infection risk by obtaining a thorough infection and travel history, as well as history of animal and environmental exposures. The pretransplant period is an ideal time for detailed counseling of the recipient and his/her family about safe food handling and the risk of infection associated with pets, travel, and hobbies such as gardening and woodworking. Infection prevention approaches including hand hygiene, prophylactic antimicrobials, postexposure prophylaxis, and updating of immunizations should be addressed as well. A variety of pathogens may be transmitted by transplantation (5) (Table 1) . Guidelines for pretransplant screening have been the subject of several publications including a consensus conference of the Immunocompromised Host Society (ICHS) (6, 7) , the American Society for Transplantation (AST) Clinical Practice Guidelines on the evaluation of renal transplant candidates (8) , and the ASTP Clinical Practice Guidelines on the evaluation of living renal transplant donors (9) . Recommendations regarding hepatitis status of the donor have been summarized in the March 2001 Crystal City Meeting (10) and in a review by Chung, Feng and Delmonico (11) . In addition, the Centers for Disease Control and Prevention (CDC), the Infectious Diseases Society of America (IDSA) and the American Society for Blood and Marrow Transplantation (ASBMT) have published guidelines in 2000 for prevention of infection in hematopoietic stem cell transplant recipients (12) , and the CDC has published guidelines for the prevention of HIV transmission through transplantation (13) . While traditional screening strategies are very effective in most cases, they are not a guarantee against donor-derived infections. There have been a number of high-profile donorderived transmission incidents over the last several years, including rabies (14) , lymphocytic choriomeningitis virus (15) , West Nile virus (WNV, 16) , HIV (17) (18) (19) and hepatitis C (HCV) (18) (19) (20) , which have renewed discussion of the issues surrounding donor screening. The recently formed United Network for Organ Sharing (UNOS) Donor Transmission Advisory Group (DTAG), the Transplantation Transmission Sentinel Network of the CDC (21) and other new initiatives have been formed to address donor-transmitted infection and current screening practices (21) (22) (23) . After a discussion of the differences in screening between living and deceased donors, this review will summarize current opinion on screening for bacterial, mycobacterial, fungal, parasitic and viral infections in the donor and recipient ( Table 2 ). More detailed discussions of these infections, posttransplant monitoring, prophylaxis, and treatment are found in other sections of these guidelines. Because issues concerning the viral serologies of donor and recipient are intertwined, these will be discussed together. Given the limited pool of donors, it has become necessary to consider marginal candidates, including those with infection at the time of donation, higher-risk serologic profiles, or a social history indicating potential exposures to bloodborne pathogens such as HIV or HCV. The nature of any potential donor infection, the severity of end-stage organ disease in the recipient, and the likelihood of another organ offer for the patient on the transplant waiting list are important considerations when determining the acceptability of the potentially infected donor. Fischer et al. (30) . Lung transplantation deserves special attention (31) . Donor bacterial colonization is common, as the lungs are in contact with the external environment, and the mouth and upper airways are a site for colonization with multiple organisms. Donor bronchoscopy with cultures performed at the time of evaluation and/or procurement allows for the administration of antibiotics directed at these colonizing organisms, and can prevent invasive infection in the recipient (III) (31) . Allograft contamination may occur during procurement or processing (32) . Rubin recommends treatment of the recipient if organisms are isolated in perfusates or organ transplant medium, citing the risk of mycotic aneurysm formation (28) , although culture contamination must be considered as well (33) Active systemic fungal infection in the donor is a contraindication to transplantation. The endemic mycoses in particular may be present in dormant form. Transmission of histoplasmosis by transplantation has been described (39) , but most cases appear to be the result of reactivation of past infection in the recipient. In many individuals from the Midwestern United States, calcified pulmonary, hilar and splenic granulomata on X-ray may be the visible residua of old Histoplasma infection, but such radiographic signs have not traditionally been considered a contraindication to donation (III). Transmission of coccidioidomycosis by lung transplantation has been reported in the Southwestern United States (40) , although reactivation of coccidioidomycosis in the recipient appears to be far more common (41) . As yet, uniform recommendations for donor screening for endemic mycoses have not emerged. Toxoplasmosis is a major concern particularly in heart transplantation, where the Toxoplasma-seronegative recipient of a Toxoplasma-seropositive heart is at highest risk for developing active toxoplasmosis posttransplant (42) . Toxoplasmosis has also rarely been transmitted to liver and kidney recipients (43) . Donor seropositivity is not a contraindication to heart donation but allows for appropriate prophylaxis to be administered to the recipient; routine trimethoprim-sulfamethoxazole prophylaxis against Pneumocystis jiroveci is effective in preventing toxoplasmosis and may negate the need for serologic testing in areas of low prevalence (44) . Screening of donors for Toxoplasma is not routinely performed for noncardiac donors but may be part of the screening panel at some centers. States. Further discussion of these issues is found in the Parasitology section of these Guidelines. The following sections will discuss both donor and recipient screening for viral infections as the serologic status of both donor and recipient is often crucial in determining the risk of infection ( Table 3) . Each of the viruses mentioned here are discussed in more detail in other sections of these Guidelines. transplantation, and although HCV recurrence is common posttransplant, patient and liver graft survival are not significantly worse than with other pretransplant diagnoses. HCV seropositive renal transplant candidates are at higher risk for liver disease and sepsis after transplant than are their HCV seronegative counterparts, but compared with no transplantation as the alternative, the balance of benefit often falls on the side of transplantation in most cases (61) . The role of pretransplant viral load reduction is under study. Strategies for management of HCV in the recipient are discussed in detail in a later section. In the future, rapid molecular testing will likely be increasingly performed in the time frame needed for donor evaluation. (62) . When compared with remaining on the waiting list, there was a survival advantage to receiving a kidney from an HCV+ donor (63) . Thus, survival with a kidney from an HCV+ donor, while less than that seen in the setting of an HCV negative donor, appears to be associated with better survival than remaining on dialysis (64 (66) . However, one series identified an excess of rapidly progressive cholestatic hepatitis and an increased mortality overall for HCV-recipients of HCV+ donor hearts on mycophenolate-based immunosuppression (67) . Whether specific immunosuppressive regimens are preferred in such situations requires further study. In any event, whenever an HCV seropositive donor is utilized, stringent informed consent is advisable. As recent transmission events have proven, HCV can be transmitted to multiple organ and tissue transplant recipients from a seronegative donor (19, 20) . (19) . (68) . The complex issues involved are more fully discussed in the HIV section of these Guidelines. (70) (71) (72) . (74, 75) . (76, 77 There is also concern that false positive NAAT may result in loss of noninfected organs and net loss of life particularly for liver and heart candidates on the waiting list (78) . In some regions of Canada, prospective donors are tested for WNV NAAT. Lymphocytic choriomeningitis virus (LCMV), a rodentassociated arenavirus, has been reported in several clusters of donor-derived transmission to multiple organ recipients, most of whom had fatal infection (15, 79) . In one cluster, the outbreak originated from a new pet hamster in the donor's home (15) . Strikingly, however, the donor's LCMV serology was negative, raising questions as to what kind of screening measures could have detected and prevented this transmission (15) . The CDC has issued interim guidelines for minimizing risk of LCMV related to pet rodents (80) . and now a comprehensive reporting system introduced by the CDC (21, 22) . A recent report of donor-derived transmission of a new related arenavirus to multiple recipients has also highlighted the use of new molecular technologies for identification of unknown pathogens (81) . Rabies is another potentially fatal donor-derived infection (14, 82) . Recipients of transplants from a donor who died of cerebral hemorrhage acquired a rapidly progressive neurologic illness which was found to be rabies; retrospectively, the donor was found to have had a recent bat bite (14, 82 (35) . Recently, the availability of the IGRA has generated interest (36) , particularly with regards to patients who received Bacillus Calmette-Guerin (BCG) vaccination as the IGRA assay has the potential to distinguish PPD positivity related to BCG from that related to LTBI (87) . 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