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Journal of Clinical Microbiology, June 2007, p. 1804-1810, Vol. 45, No. 6
0095-1137/07/$08.00+0     doi:10.1128/JCM.01362-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Frequent Occult Infection with Cytomegalovirus in Cardiac Transplant Recipients despite Antiviral Prophylaxis

Luciano Potena,^1, Cecile T. J. Holweg,¹ Marcy L. Vana,² Leena Bashyam,² Jaya Rajamani,² A. Louise McCormick,^2,3 John P. Cooke,¹ Hannah A. Valantine,¹ and Edward S. Mocarski^2,3*

Departments of Medicine,¹ Microbiology & Immunology, Stanford University School of Medicine, Stanford, California,² Department of Microbiology & Immunology, Emory University School of Medicine, Atlanta, Georgia³

Received 3 July 2006/ Returned for modification 28 August 2006/ Accepted 27 March 2007

Despite antiviral prophylaxis, a high percentage (over 90%) of heart transplant patients experience active cytomegalovirus (CMV) infection, diagnosed by detection of viral DNA in peripheral blood polymorphonuclear leukocytes within the first few months posttransplantation. Viral DNA was detected in mononuclear cells prior to detection in granulocytes from CMV-seropositive recipients (R⁺) receiving a heart from a CMV-seropositive donor (D⁺). Based on assessment of systemic infection in leukocyte populations, both R⁺ subgroups (R⁺/D^– and R⁺/D⁺) experienced a greater infection burden than the R^–/D⁺ subgroup, which was aggressively treated because of a higher risk of acute CMV disease. Despite widespread systemic infection in all at-risk patient subgroups, CMV DNA was rarely (<3% of patients) detected in transplanted heart biopsy specimens. The R⁺ patients more frequently exceeded the 75th percentile of the CMV DNA copy number distribution in leukocytes (110 copies/10⁵ polymorphonuclear leukocytes) than the R^–/D⁺ subgroup. Therefore, active systemic CMV infection involving leukocytes is common in heart transplant recipients receiving prophylaxis to reduce acute disease. Infection of the transplanted organ is rare, suggesting that chronic vascular disease attributed to CMV may be driven by the consequences of systemic infection.

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* Corresponding author. Mailing address: Department of Microbiology & Immunology, Emory University School of Medicine, Room 429, 1462 Clifton Rd. NE, Atlanta, GA 30322. Phone: (404) 727-9442. Fax: (404) 736-0194. E-mail: mocarski{at}emory.edu

Published ahead of print on 4 April 2007.

Present address: Institute of Cardiology, University of Bologna, via Massarenti, 9, 40138 Bologna, Italy.

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Journal of Clinical Microbiology, June 2007, p. 1804-1810, Vol. 45, No. 6
0095-1137/07/$08.00+0     doi:10.1128/JCM.01362-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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