Human Cytomegalovirus Immediate-Early mRNA Detection by Nucleic Acid Sequence-Based Amplification as a New Parameter for Preemptive Therapy in Bone Marrow Transplant Recipients

This Article

	Full Text
	Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Reprints and Permissions
	Copyright Information
	Books from ASM Press
	MicrobeWorld

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Gerna, G.
	Articles by Revello, M. G.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Gerna, G.
	Articles by Revello, M. G.

Previous Article | Next Article

Journal of Clinical Microbiology, May 2000, p. 1845-1853, Vol. 38, No. 5
0095-1137/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Human Cytomegalovirus Immediate-Early mRNA Detection by Nucleic Acid Sequence-Based Amplification as a New Parameter for Preemptive Therapy in Bone Marrow Transplant Recipients

Giuseppe Gerna,¹^,^* Fausto Baldanti,¹ Daniele Lilleri,¹ Maurizio Parea,¹ Emilio Alessandrino,² Ambrogio Pagani,³ Franco Locatelli,⁴ Jaap Middeldorp,⁵ and M. Grazia Revello¹

Servizio di Virologia,¹ Divisione di Ematologia,² Servizio di Immunoematologia e Transfusione,³ and Dipartimento di Pediatria,⁴ Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Università di Pavia, 27100 Pavia, Italy, and Organon Teknika B.V., 5280 AB Boxtel, The Netherlands⁵

Received 1 November 1999/Returned for modification 7 January 2000/Accepted 14 February 2000

Human cytomegalovirus (HCMV) infection was monitored retrospectively by qualitative determination of immediate-early (IE)mRNA by nucleic acid sequence-based amplification (NASBA) in aseries of 51 bone marrow transplant (BMT) recipients. The qualitativeresults for IE mRNA obtained by NASBA were compared with thoseobtained by prospective quantitation of HCMV viremia and antigenemiaand retrospective quantitation of DNA in blood (DNAemia) by PCRas well as by qualitative determination of late pp67 mRNA by NASBA.On the whole, of the 39 HCMV-positive patients (all asymptomatic),HCMV was detected in 14 (35.9%) by quantitation of viremia, 15(38.5%) by detection of pp67 mRNA by NASBA, 32 (82.1%) by quantitationof DNAemia, and 33 (84.6%) by quantitation of antigenemia, whileHCMV was detected in 38 (97.4%) patients by detection of IE mRNAby NASBA. In the immunocompetent host, IE mRNA was not detectedby NASBA in 100 blood donors or during reactivated infectionsin 30 breast-feeding mothers. Likewise, NASBA did not detect IEmRNA in 56 solid-organ transplant recipients in the first 21 daysafter transplantation. By using NASBA for detection of IE mRNAas the reference standard for detection of HCMV infection in bloodsamples, the diagnostic sensitivities were 67.7% for quantitationof DNAemia, 59.0% for quantitation of antigenemia, 18.3% for detectionof pp67 mRNA by NASBA, and 16.0% for quantitation of viremia.Specificities and negative and positive predictive values were>90.0, >70.0, and >80.0%, respectively, for all four assays. Themean times to first HCMV detection after bone marrow transplantationwere 37.7 ± 15.4 days for detection of IE mRNA by NASBA, 39.6± 15.6 days for quantitation of antigenemia, 40.9 ± 15.2 daysfor quantitation of DNAemia, and 43.7 ± 16.3 or 43.7 ± 17.5 daysfor quantitation of viremia and detection of pp67 mRNA by NASBA,respectively. On the whole, 31 BMT recipients received preemptivetherapy by using confirmed antigenemia positivity as a cutoff,while 35 patients could have been treated by using NASBA positivityas a cutoff and 31 could have been treated by using quantitationof DNAemia as a cutoff. In single patients, IE mRNA was detectedin every episode of active HCMV infection, mostly preceding andsometimes accompanying antigenemia and DNAemia, whereas pp67 mRNAwas detected only concomitantly with the highest peaks of infection.HCMV IE mRNA detection may represent a useful parameter for initiationof preemptive therapy in BMTrecipients.

^* Corresponding author. Mailing address: Servizio di Virologia, IRCCS Policlinico San Matteo, Via Taramelli 5, 27100 Pavia,Italy. Phone: 39-0382-502644. Fax: 39-0382-502599. E-mail: g.gerna{at}smatteo.pv.it.

Journal of Clinical Microbiology, May 2000, p. 1845-1853, Vol. 38, No. 5
0095-1137/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

This article has been cited by other articles:

Meijer, E., Boland, G. J., Verdonck, L. F. (2003). Prevention of Cytomegalovirus Disease in Recipients of Allogeneic Stem Cell Transplants. Clin. Microbiol. Rev. 16: 647-657 [Abstract] [Full Text]
Baldanti, F., Gerna, G. (2003). Human cytomegalovirus resistance to antiviral drugs: diagnosis, monitoring and clinical impact. J Antimicrob Chemother 52: 324-330 [Abstract] [Full Text]
Gerna, G., Lilleri, D., Baldanti, F., Torsellini, M., Giorgiani, G., Zecca, M., De Stefano, P., Middeldorp, J., Locatelli, F., Revello, M. G. (2003). Human cytomegalovirus immediate-early mRNAemia versus pp65 antigenemia for guiding pre-emptive therapy in children and young adults undergoing hematopoietic stem cell transplantation: a prospective, randomized, open-label trial. Blood 101: 5053-5060 [Abstract] [Full Text]
Revello, M. G., Gerna, G. (2002). Diagnosis and Management of Human Cytomegalovirus Infection in the Mother, Fetus, and Newborn Infant. Clin. Microbiol. Rev. 15: 680-715 [Abstract] [Full Text]
Sanchez, J. L., Storch, G. A. (2002). Multiplex, Quantitative, Real-Time PCR Assay for Cytomegalovirus and Human DNA. J. Clin. Microbiol. 40: 2381-2386 [Abstract] [Full Text]
Solano, C., Munoz, I., Gutierrez, A., Farga, A., Prosper, F., Garcia-Conde, J., Navarro, D., Gimeno, C. (2001). Qualitative Plasma PCR Assay (AMPLICOR CMV Test) versus pp65 Antigenemia Assay for Monitoring Cytomegalovirus Viremia and Guiding Preemptive Ganciclovir Therapy in Allogeneic Stem Cell Transplantation. J. Clin. Microbiol. 39: 3938-3941 [Abstract] [Full Text]
Stevens, S. J. C., Pronk, I., Middeldorp, J. M. (2001). Toward Standardization of Epstein-Barr Virus DNA Load Monitoring: Unfractionated Whole Blood as Preferred Clinical Specimen. J. Clin. Microbiol. 39: 1211-1216 [Abstract] [Full Text]
Greijer, A. E., Verschuuren, E. A. M., Harmsen, M. C., Dekkers, C. A. J., Adriaanse, H. M. A., The, T. H., Middeldorp, J. M. (2001). Direct Quantification of Human Cytomegalovirus Immediate-Early and Late mRNA Levels in Blood of Lung Transplant Recipients by Competitive Nucleic Acid Sequence-Based Amplification. J. Clin. Microbiol. 39: 251-259 [Abstract] [Full Text]
Sullivan, K. M., Dykewicz, C. A., Longworth, D. L., Boeckh, M., Baden, L. R., Rubin, R. H., Sepkowitz, K. A. (2001). Preventing Opportunistic Infections After Hematopoietic Stem Cell Transplantation: The Centers for Disease Control and Prevention, Infectious Diseases Society of America, and American Society for Blood and Marrow Transplantation Practice Guidelines and Beyond. ASH Education Book 2001: 392-421 [Abstract] [Full Text]
Boivin, G., Bélanger, R., Delage, R., Béliveau, C., Demers, C., Goyette, N., Roy, J. (2000). Quantitative Analysis of Cytomegalovirus (CMV) Viremia Using the pp65 Antigenemia Assay and the COBAS AMPLICOR CMV MONITOR PCR Test after Blood and Marrow Allogeneic Transplantation. J. Clin. Microbiol. 38: 4356-4360 [Abstract] [Full Text]
Blok, M. J., Lautenschlager, I., Goossens, V. J., Middeldorp, J. M., Vink, C., Höckerstedt, K., Bruggeman, C. A. (2000). 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. J. Clin. Microbiol. 38: 4485-4491 [Abstract] [Full Text]

Antimicrob. Agents Chemother.	Clin. Microbiol. Rev.

Clin. Vaccine Immunol.	ALL ASM JOURNALS