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.

Prevalence of human cytomegalovirus co-infection in patients with chronic viral hepatitis B and C: A comparison of clinical and histological aspects

“…[37][38][39][40][41][42][43][44] The quantitative PCR method has the advantage that it can provide an estimate of the number of HCMV genomes (viral load) present in clinical samples, which would be of additional use in prospectively identifying persons at highest risk for developing HCMV disease. 15 In this study, determination of HCMV viral load was performed for the first time from liver tissue by qPCR in a group of patients at high risk for HCMV infection.…”

Diagnosing norovirus-associated infectious intestinal disease using viral load

“…However, if the relationship between the occurrence of disease and viral load is consistent, regardless of whether high viral loads are a cause or a consequence of disease, viral load will be a good marker of norovirus-associated IID and the approach developed here is valid. Viral load is routinely used to predict outcome and guide clinical management for a number of viruses that cause chronic infections, such as Epstein-Barr virus [37] and cytomegalovirus [38] in transplant patients, HIV [39], hepatitis C [40] and HTLV [41]. However this is the first time, to our knowledge, that viral load has been used as a tool for diagnosing enteric viruses as the cause of acute IID.…”

Cytomegalovirus infection and ganciclovir resistance caused by UL97 mutations in pediatric transplant recipients

“…The change in viral load after treatment has been reported to be a useful predictor for the development and/or relapse of CMV disease . The pediatric patients in our study with high viral loads were likely to have poor host immune responses after transplantation because of age and immunosuppression, and received extended antiviral therapy.…”