Transplantation microbiology: an evolving pillar of transplant care.

Among major advances in solid organ transplantation isthe development of a rational basis for the prevention,diagnosis and management of viral infections (i.e. cy-tomegalovirus (CMV) (1). These strategies are the resultof the availability and deployment of effective antimicrobialagents coupled with quantitative molecular and antigen-based microbiologic assays for these pathogens. Nucleicacid-based tests (NAT) have been developed for manypathogens, including Epstein Barr virus (EBV) and BK poly-omavirus, and are available commercially, at public healthlaboratories, and as ‘home brew’ diagnostic tools. Theseassays have become the basis of ‘pre-emptive’ antiviraltherapies which use sensitive, quantitative assays to de-tect presymptomatic infections as a basis for the initiationof antimicrobial therapy. Quantitative molecular assays areroutinely used to monitor responses to antiviral therapiesfor e.g. CMV, BK and EBV-associated processes. The pres-ence of viral infections is also often used as an indirectindicator of excessive immunosuppression.Transplant infectious disease physicians have long sus-pected that quantitative CMV and EBV assay results couldnot be compared between laboratories using different sub-strates (e.g. whole blood vs. serum), assay platforms ormolecular primers. The degree to which these data variedhas now been documented in a pair of important studiespublished in this issue by Preiksaitis et al. and Pang et al.(2,3). These studies are fairly unique in that they includedlaboratories from Canada and the United States and weresponsored by professional societies (the American Societyof Transplantation and the Canadian Society of Transplan-tation), indicating the importance of NAT testing to the cur-rent clinical practice of organ transplantation. The studiesindicate that ‘only 47.0% of all results fell within accept-able standards of variation’ for EBV viral load detection and‘only 57.6% of results fell within acceptable standards’ forCMV viral load detection (2,3). Variability in commercial as-says was lower than that for laboratory-developed assays.The greatest variation was in the sensitivity or lower limitsof detection for each assay (i.e. the ability to detect earlyviral infection), which must be sufﬁcient to allow ‘early’detection and treatment of infection while avoiding falsepositive tests or the detection of clinically irrelevant levelsof infection.The development of internationally accepted referencestandards would be a major step in standardization of as-says now used routinely in clinical care. Such standardscould be used in the development of internal controls forclinical assays, the production of proﬁciency panels for lab-oratory quality assessment and as a basis (‘gold standard’)for the development of new diagnostic technologies. Theavailability of laboratory proﬁciency testing also implies thedevelopment of performance standards to assure techni-cal competence and consistency within clinical laborato-ries. Thus, standards for checking, recording and reportingof assay results would limit the risk of miscommunica-tion between clinical laboratories and clinical centers—aﬂaw recently associated with at least one cluster of donor-derived infections due to HIV (4). Until such standardizationis achieved, viral infections in individual patients must bemonitored using a single, quantitative assay from a singleclinical laboratory.These data raise a series of challenges for the trans-plant community and opportunities for commercial de-velopment of diagnostic assays. Recent clusters of or-gan donor-derived infections, including HIV, hepatitis Cvirus and lymphocytic choriomeningitis virus (LCMV), havedemonstratedtheneedforimprovedandexpandedtestingof organ donors (5). Improved microbiological screening oforgan donors will depend on the development of a con-sensus regarding a ‘list’ of pathogens to assay and regard-ing the optimal assay characteristics for each pathogen. Inparticular, studies must be conducted of organ donors todetermine the level of sensitivity for each assay that willprotect recipients while minimizing the exclusion of use-able organs and tissues by false positive microbiologic as-says. Such assays could be multiplexed (multiple simul-taneous) NAT tests or based in other detection technolo-gies. They must be rapid, easily performed, cost-effectiveandstandardized.Suchmicrobiologicalassaypanelswouldlargely supplant the ‘high risk donor’ exclusion criteriabased in social and epidemiological characteristics and