Predictive value of quantitative PCR-based viral burden analysis for eighthuman herpesviruses in pediatric solid organ transplant patients

Human herpesviruses can cause significant morbidity and mortality in pediat ric solid organ transplant recipients. It was hypothesized that viral burde n quantification by polymerase chain reaction using an internal calibration standard could aid in distinguishing between viral disease and latency. He re we report the results of a 2-year prospective study of 27 pediatric soli d organ (liver, kidney, or heart) transplant recipients in which multiple s amples were analyzed for levels of all eight human herpesviruses by interna l calibration standard-polymerase chain reaction. Herpes simplex viruses 1 and 2, varicella-zoster virus, and Kaposi's sarcoma-associated herpesvirus were not detected in anp of these samples. Human herpesvirus types 6 and 7 were detected in half of the patients, but were present at low levels, simi lar to those found in reference populations. Epstein-Barr virus (EBV) and c ytomegalovirus (CMV) were detected in 89% and 56% of the patients, respecti vely. Viral burden analysis suggested distinct patient populations for CMV, with a natural cutoff of 10,000 viral targets/ml blood strongly associated with disease. In some cases, a dramatic increase in CMV levels preceded cl inical evidence of disease by several weeks, EBV viral burden was relativel y high in the only patient presenting with an EBV syndrome. However, two ot her patients without evidence of EBV disease had single samples with high E BV burden. Rapid reduction in both EBV and CMV burden occurred with antivir al treatment. These data suggest that viral burden analysis sis using inter nal calibration standard-polymerase chain reaction for CMV, and possibily o ther herpesviruses, is an effective method for monitoring pediatric transpl ant patients for significant herpesvirus infection and response to therapy.