title: Diagnostic implications of human cytomegalovirus immediate early-1 and pp67 mRNA detection in whole-blood samples from liver transplant patients using nucleic acid sequence-based amplification.
abstract: Nucleic acid sequence-based amplification (NASBA) was used for detection of the human cytomegalovirus (CMV) immediate early-1 (IE) and the late pp67 mRNA in 353 blood samples collected from 34 liver transplant patients. The diagnostic value of these assays was compared to that of the pp65 antigenemia assay. Overall, 95 and 42% of the antigenemia-positive samples were IE NASBA and pp67 NASBA positive, respectively. Although the results from pp67 NASBA and the antigenemia assay appeared to correspond poorly, a clear correlation was seen between pp67 NASBA-negative results and low numbers of pp65 antigen-positive cells. Twenty patients (59%) were treated with ganciclovir after the diagnosis of symptomatic CMV infection. Before initiation of the antiviral therapy, the antigenemia assay detected the onset of symptomatic infection in all patients, whereas 95 and 60% of these patients were IE NASBA and pp67 NASBA positive, respectively. Although the sensitivity of IE NASBA was very high, the positive predictive value (PPV) of this assay for the onset of a symptomatic infection was only 63%. The PPV of the antigenemia assay as well as pp67 NASBA was considerably higher (80 and 86%, respectively). Thus, the detection of IE mRNA using NASBA appears to be particularly useful as a marker for early initiation of antiviral therapy in patients at high risk for the development of a symptomatic infection. Also, IE NASBA was found to be more sensitive than the antigenemia assay for monitoring CMV infection during antiviral therapy. On the contrary, pp67 NASBA did not appear to have additional diagnostic value compared to the antigenemia assay.
authors: Department of Medical Microbiology, University Hospital Maastricht, 6202 AZ Maastricht, The Netherlands. mbl@lmib.azm.nl
authors: M J
authors: MJ
authors: Blok
authors: I
authors: I
authors: Lautenschlager
authors: V J
authors: VJ
authors: Goossens
authors: J M
authors: JM
authors: Middeldorp
authors: C
authors: C
authors: Vink
authors: K
authors: K
authors: Höckerstedt
authors: C A
authors: CA
authors: Bruggeman
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000235:genetics*; D003587:Cytomegalovirus / Q000187:drug effects / Q000302:isolation & purification*; D015774:Ganciclovir / Q000494:pharmacology; D005784:Gene Amplification; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D016031:Liver Transplantation / Q000009:adverse effects*; D010750:Phosphoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D014764:Viral Proteins / Q000235:genetics*; D014766:Viremia / Q000821:virology*
chemical_list: D000956:Antigens, Viral; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D014764:Viral Proteins; C044582:immediate-early proteins, cytomegalovirus; D015774:Ganciclovir