Distinguishing cytomegalovirus (CMV) infection and disease with CMV nucleic acid assays

Abstract

Human cytomegalovirus (CMV) continues to be a significant cause of morbidity and mortality among transplant recipients. Molecular assays have been developed for the detection and quantification of CMV nucleic acid. In evaluating the clinical utility of these assays, correlations with clinical outcome are essential. The Amplicor CMV Monitor and NucliSens CMV pp67 tests were compared to the CMV antigenemia assay for 45 transplant recipients and 1 patient with Wegener's granulomatosis. Twenty-three patients remained antigenemia negative throughout the monitoring period, none of whom developed CMV disease. In this patient group, both the Amplicor and NucliSens assays showed very high specificity; only 1 of the 324 specimens assayed by NucliSens and none of the 303 specimens assayed by Amplicor were positive. Twenty-three patients were antigenemia positive during the monitoring period, 12 of whom developed 13 episodes of symptomatic CMV disease. In this patient group, the NucliSens assay was positive at or before the development of symptoms in 12 of the 13 episodes of CMV disease. All eight patients with symptomatic CMV disease who were tested by the Amplicor assay were positive at or before the development of disease. For the 11 asymptomatic patients, the NucliSens assay was positive less frequently than the antigenemia or Amplicor assays. The NucliSens assay was more likely to be positive at higher antigenemia or viral load levels. Both the NucliSens and Amplicor assays appear to have clinical utility in monitoring patients for CMV disease.

FIG. 1.

Comparison of CMV pp65 antigenemia, quantitative PCR, and NASBA mRNA results for four of the patients with active CMV disease. (a) Thirty-eight-year-old male lung transplant patient, D+R−; (b) 64-year-old male renal transplant patient, D+R−; (c) 33-year-old Caucasian male renal and bone marrow transplant patient, D−R+; (d) 25-year-old Caucasian male renal transplant patient, D+R−. ↓, an episode of symptomatic CMV disease; ▵, NASBA negative; ▴, NASBA positive; ▪, acyclovir; ░⃞, intravenous ganciclovir; ▨, oral ganciclovir; ▩, foscarnet; ▧, cytogram. D, donor; R, recipient.

FIG. 2.

Comparison of CMV pp65 antigenemia, quantitative PCR, and NASBA mRNA results for five of the patients with asymptomatic CMV infection. (a) Twenty-one-year-old male bone marrow transplant patient, D?R+; (b) 54-year-old female lung transplant patient, D+R−; (c) 65-year-old Caucasian male kidney transplant patient, D+R−; (d) 25-year-old male heart transplant patient, D?R−; (e) 39-year-old black female liver transplant patient (two times), D−R+. ↓, an episode of symptomatic CMV disease; ▵, NASBA negative; ▴, NASBA positive; ▪, acyclovir; ░⃞, intravenous ganciclovir; ▨, oral ganciclovir; ▩, foscarnet; ▧, cytogram. D, donor; R, recipient.

FIG. 2.

Comparison of CMV pp65 antigenemia, quantitative PCR, and NASBA mRNA results for five of the patients with asymptomatic CMV infection. (a) Twenty-one-year-old male bone marrow transplant patient, D?R+; (b) 54-year-old female lung transplant patient, D+R−; (c) 65-year-old Caucasian male kidney transplant patient, D+R−; (d) 25-year-old male heart transplant patient, D?R−; (e) 39-year-old black female liver transplant patient (two times), D−R+. ↓, an episode of symptomatic CMV disease; ▵, NASBA negative; ▴, NASBA positive; ▪, acyclovir; ░⃞, intravenous ganciclovir; ▨, oral ganciclovir; ▩, foscarnet; ▧, cytogram. D, donor; R, recipient.

FIG. 3.

Comparison of antigenemia and Amplicor assays. All time points at which both assays were positive are included in the graph, regardless of whether the patient was receiving therapy. Time points were included from both symptomatic and asymptomatic patients.