Early diagnosis of human cytomegalovirus disease in transplant recipients by DNA amplification in plasma

Abstract

Human cytomegalovirus (HCMV) infection in transplant recipients is often complicated by invasive visceral disease. The most reliable marker for HCMV disease is viremia, currently defined by detection of the virus in white blood cells. In this study we employed the polymerase chain reaction (PCR) to detect HCMV DNA in the plasma of transplant recipients. The utility of plasma PCR in the early diagnosis of active HCMV infection and disease was determined in 83 bone marrow transplant recipients and 6 kidney transplant recipients. All 46 patients who had a positive leukocyte culture were positive by plasma-PCR. PCR detection preceded culture isolation by a median interval of one week and remained positive for a longer period, with a median lag interval of two weeks in uncomplicated infection. Lack of PCR resolution predicted disease development in 11 patients and culture relapse in three. Of the 11 patients who were culture-negative but positive by plasma-PCR, 8 (73%) subsequently developed HCMV disease; 32 (74%) of 43 leukocyte culture-negative patients remained plasma PCR-negative, regardless of concomitant 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 detection preceded disease development by a median interval of 3 weeks. Plasma PCR is a rapid, specific, and highly sensitive method for the early diagnosis of HCMV disease and should prove useful in guiding prophylactic therapy in transplant recipients.