Validation of clinical application of cytomegalovirus plasma DNA load measurement and definition of treatment criteria by analysis of correlation to antigen detection.
Successful preemptive cytomegalovirus (CMV) therapy in transplant patients depends on the availability of sensitive, specific, and timely diagnostic tests for CMV infections. The pp65 antigenemia assay has been used for this purpose with considerable success. Quantification of CMV DNA is currently regarded to be an alternative diagnostic approach. The precise relationship between these two methods has still to be defined, but is essential to compare diagnostic results. This study compared the results of both assays with a large series of transplant recipients in different categories. An internally controlled quantitative real-time CMV DNA PCR was used to test 409 plasma samples from solid organ transplant (SOT) and stem cell transplant (SCT) patients. Levels of CMV DNA in plasma correlated well with classified outcomes of the pp65 antigenemia test. Despite this correlation, the quantitative CMV PCR values in a class of antigen test results were within a wide range, and the definition of an optimal cutoff value for initiating treatment required further analysis by a receiver-operating characteristic curve analysis. This is essential for reactivating infections in particular. For the SCT patients the optimal cutoff value of CMV DNA load defining relevant viral reactivation (in this assay, 10,000 copies/ml) was slightly higher than that for the SOT patients (6,300 copies/ml). Based on a comparison with the established pp65 antigenemia assay, quantification of CMV DNA in plasma appeared to be capable of guiding the clinical management of transplant recipients. This approach may have important advantages, which include a superior reproducibility and sensitivity, allowing the inclusion of kinetic criteria in clinical guidelines.
Kalpoe
Jayant S
JS
Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands. J.S.Kalpoe@lumc.nl
Kroes
Aloys C M
AC
de Jong
Menno D
MD
Schinkel
Janke
J
de Brouwer
Caroline S
CS
Beersma
Matthias F C
MF
Claas
Eric C J
EC
D000942:Antigens, Bacterial / Q000097:blood; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000517:prevention & control* / Q000821:virology; D004279:DNA, Viral / Q000097:blood*; D006801:Humans; D016377:Organ Transplantation / Q000009:adverse effects*; D010750:Phosphoproteins / Q000097:blood; D016133:Polymerase Chain Reaction / Q000379:methods*; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D019562:Viral Load / Q000592:standards*; D014763:Viral Matrix Proteins / Q000097:blood
D000942:Antigens, Bacterial; D004279:DNA, Viral; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa