EARLY DIAGNOSIS OF HUMAN CYTOMEGALOVIRUS DISEASE IN TRANSPLANT RECIPIENTS BY DNA AMPLIFICATION IN PLASMA

Human cytomegalovirus (HCMV) infection in transplant recipients is oft en complicated by invasive visceral disease. The most reliable marker for HCMV disease is viremia, currently defined by detection of the vir us in white blood cells. In this study we employed the polymerase chai n reaction (PCR) to detect HCMV DNA in the plasma of transplant recipi ents. The utility of plasma PCR in the early diagnosis of active HCMV infection and disease was determined in 83 bone marrow transplant reci pients and 6 kidney transplant recipients. All 46 patients who had a p ositive leukocyte culture were positive by plasma-PCR. PCR detection p receded culture isolation by a median interval of one week and remaine d positive for a longer period, with a median lag interval of two week s in uncomplicated infection. Lack of PCR resolution predicted disease development in 11 patients and culture relapse in three. Of the 11 pa tients who were culture-negative but positive by plasma-PCR, 8 (73%) s ubsequently developed HCMV disease; 32 (74%) of 43 leukocyte culture-n egative patients remained plasma PCR-negative, regardless of concomita nt viral shedding in 11. In bone marrow transplant recipients, plasma PCR was associated with a positive predictive value of 60% for disease development and with a negative predictive value of 97%. PCR detectio n preceded disease development by a median interval of 3 weeks. Plasma PCR is a rapid, specific, and highly sensitive method for the early d iagnosis of HCMV disease and should prove useful in guiding prophylact ic therapy in transplant recipients.