Clinical utility of CMV early and late transcript detection with NASBA in bronchoalveolar lavages.
BACKGROUND
Cytomegalovirus (CMV) infection can cause severe disease in immunocompromised individuals, with CMV pneumonia, most commonly seen in lung or bone marrow transplant recipients, carrying a particularly high fatality rate. Early and accurate diagnosis of CMV pneumonia is therefore critical.


OBJECTIVE
Current diagnostic tests for CMV pneumonia in bronchoalveolar lavage (BAL) specimens are either insensitive or poor prognostic indicators of disease. We therefore examined nucleic acid sequence-based amplification (NASBA) assays for CMV transcripts in BAL for the prediction of CMV pneumonia and associated diseases.


METHODS
A total of 220 BAL specimens from lung transplant recipients and other patients with suspected viral pneumonia were studied. Ninety-nine samples had previously tested positive for CMV by shell vial (SV) culture, while the other 121 had tested negative. All specimens were assayed for CMV pp67 and immediate early (IE) transcripts by NASBA. Results were correlated with evidence of concurrent or subsequent CMV pneumonia, rejection, and infection with other microbes.


RESULTS
From a total of 220 BAL specimens, 27 tested positive for pp67 mRNA, 25 tested positive for IE mRNA, and 17 tested positive for both. Only 10 specimens tested positive for CMV by either or both NASBA assays while testing negative by SV assay. However, 74 specimens were SV positive but negative in both NASBA assays. Detection of CMV by any of the three methods was associated with an increased prevalence of pneumonia (i.e., pulmonary interstitial inflammation with radiographic or clinical evidence of lung injury), but not with pulmonary CMV pathology. Detection of CMV by SV was associated with moderate to severe graft rejection. There was no evidence of increased bacterial or fungal pulmonary infections associated with a positive CMV result by any of the three assays.


CONCLUSIONS
Detection of either CMV pp67 or IE mRNA transcripts by NASBA in BAL specimens can occasionally identify CMV infections that are negative by conventional shell vial culture, but does not have sufficient sensitivity or positive predictive value to be employed routinely for pre emptive management of pulmonary CMV disease in transplant recipients.
Keightley
Maria Cristina
MC
Clinical Virology Laboratory, University of Pittsburgh Medical Center, A-912, Presbyterian, 200 Lothrop St., Pittsburgh, PA 15213, United States.
Rinaldo
Charles
C
Bullotta
Arlene
A
Dauber
James
J
St George
Kirsten
K
D018893:Bronchoalveolar Lavage; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000175:diagnosis* / Q000821:virology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D014764:Viral Proteins / Q000235:genetics
D012333:RNA, Messenger; D014764:Viral Proteins