Use of CMV transcripts for monitoring of CMV infections in transplant recipients

Abstract

The development of the nucleic acid sequence-based amplification (NASBA) technology has allowed qualitative determination of human cytomegalovirus (HCMV) immediate-early (IE) and late (pp67) transcripts for monitoring of HCMV infections in the post transplantation period. pp67-mRNA NASBA was shown to be less sensitive than pp65 antigenemia and leukoDNAemia, yet more sensitive than viremia in (i) detecting HCMV infection in both patients and blood samples and (ii) anticipating diagnosis of HCMV infection in solid organ (heart, lung) transplant recipients (SOTR). Use of pp67-mRNA NASBA, as a parameter for initiation of pre-emptive therapy, could be employed as an alternative to detecting antigenemia or DNAemia in SOTR, whereas in bone marrow transplant recipients (BMTR) its use would be too risky because of the delayed detection of HCMV infection. On the other hand, IE-mRNA NASBA was shown to be largely superior to the other assays both in detecting HCMV infection in patients and blood samples and in anticipating diagnosis of HCMV infection. This appears particularly useful in BMTR, where early initiation of antiviral treatment is mandatory in order to prevent the appearance of HCMV interstitial pneumonia. Pre-emptive therapy in BMTR, however, if based upon IE-mRNA NASBA would imply treatment of a greater number of patients as compared with antigenemia- or DNAemia-guided treatment. The clinical usefulness of this approach should be evaluated in prospective trials in the near future, pp67-mRNA NASBA in SOTR with reactivated HCMV infections and IE-mRNA NASBA in BMTR could represent two new virologic parameters to be used as a cutoff for pre-emptive therapy control of HCMV infections in the post-transplant period. Viral transcripts are more direct markers of viral replication in vivo and their disappearance indicates block of the replication process.