title: Quantitation of cytomegalovirus DNA by the polymerase chain reaction as a predictor of disease in solid organ transplantation.
abstract: Cytomegalovirus (CMV) infection is an important cause of morbidity in solid organ recipients. Early markers to identify the progress of the infection and patients at high risk are required in order to apply a strategy of pre-emptive therapy. The efficacy of pre-emptive therapy relies on accurate laboratory tests to monitor CMV infection. The evaluation of CMV DNA kinetics by the polymerase chain reaction (PCR) is widely used for the management of CMV infection but markers predicting the progression of the infection and standardization of the technique are essential for the clinical interpretation of PCR results. A commercially available PCR system, the COBAS AMPLICOR Monitor (Roche Diagnostics, Brachburg, NJ), was used for the quantitation of CMV DNA in weekly blood samples (n = 504) from 47 solid organ recipients in the first 6 months after transplantation. PCR results were evaluated according to the development of clinical disease in order to find a DNA threshold and time points predicting the progression of CMV infection. Week 4 from transplantation was the earliest time point to note a significant difference between those patients who eventually developed CMV disease (n = 30) and those who remained asymptomatically infected (n = 17). At week 4, viral loads were significantly higher in patients who developed CMV disease than in asymptomatic infections (median value: 4 log(10)/10(6) leukocytes vs. 2.8, P < 0.0001). At week 4, a DNA level >/=4 log(10)/10(6) leukocytes was associated with a 45.37 odds ratio for CMV disease. Any increase >/=1 log from the first DNA detection to week 4 correlated with the clinical progression of CMV infection (odds ratio 1.74). In those patients who were treated with anti-CMV therapy, a >97% reduction of the baseline viral load was associated with a complete therapeutic success. In conclusion, CMV infection is a highly dynamic process and the quantitation of CMV DNA by PCR is a powerful marker to control successfully the infection, but a strict follow-up of the recipient and standardized PCR tests are mandatory for the best management of the infection.
authors.affiliation: Microbiology Laboratory, Molinette Hospital, Turin, Italy. vghisetti@molinette.piemonte.it
authors.forename: Valeria
authors.initials: V
authors.lastname: Ghisetti
authors.forename: Anna
authors.initials: A
authors.lastname: Barbui
authors.forename: Alessandro
authors.initials: A
authors.lastname: Franchello
authors.forename: Silvia
authors.initials: S
authors.lastname: Varetto
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Pittaluga
authors.forename: Marco
authors.initials: M
authors.lastname: Bobbio
authors.forename: Mauro
authors.initials: M
authors.lastname: Salizzoni
authors.forename: Giovanna
authors.initials: G
authors.lastname: Marchiaro
mesh_terms: D002353:Carrier State / Q000821:virology; D003587:Cytomegalovirus / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000821:virology*; D004279:DNA, Viral / Q000097:blood*; D016027:Heart Transplantation; D006801:Humans; D007165:Immunosuppression Therapy; D007700:Kinetics; D016031:Liver Transplantation; D016377:Organ Transplantation; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011933:Reagent Kits, Diagnostic; D012680:Sensitivity and Specificity; D019562:Viral Load; D014766:Viremia
chemical_list: D004279:DNA, Viral; D011933:Reagent Kits, Diagnostic