Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Approach to the diagnosis of cytomegalovirus infection

Angela M Caliendo, MD, PhD
Section Editor
Martin S Hirsch, MD
Deputy Editor
Sheila Bond, MD


Cytomegalovirus (CMV) is a common infection, and, although serious disease is rare in immunocompetent individuals, CMV is a major pathogen for immunocompromised patients, including solid organ transplant recipients, hematopoietic cell transplant recipients, HIV-infected patients, and patients treated with immunomodulating drugs.

The range of clinical disease due to CMV in immunocompromised patients is broad and includes febrile syndromes, hepatitis, pneumonitis, retinitis, encephalitis, esophagitis, and colitis. Since the signs and symptoms of CMV disease often overlap with other infectious processes and rejection, the diagnosis is made by integrating the clinical history, clinical presentation, and laboratory data. Because CMV produces lifelong latent infection, distinguishing active disease from latent infection and asymptomatic reactivation presents an additional diagnostic challenge.

The diagnosis and monitoring of CMV infection and tissue invasive disease will be discussed here, with an emphasis on the role of diagnostic tests and their strengths and limitations. An overview of the diagnostic tests for CMV is presented separately. The manifestations of CMV in immunocompetent and immunocompromised patients are also discussed elsewhere. (See "Overview of diagnostic tests for cytomegalovirus infection" and "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults" and "Clinical manifestations, diagnosis, and treatment of cytomegalovirus infection in lung transplant recipients" and "Clinical manifestations, diagnosis, and management of cytomegalovirus disease in kidney transplant recipients" and "Pathogenesis, clinical manifestations, and diagnosis of AIDS-related cytomegalovirus retinitis" and "AIDS-related cytomegalovirus gastrointestinal disease" and "Cytomegalovirus infection as a cause of pulmonary disease in HIV-infected patients" and "AIDS-related cytomegalovirus neurologic disease" and "Acquired cytomegalovirus infection in children" and "Cytomegalovirus infection in pregnancy" and "Congenital cytomegalovirus infection: Clinical features and diagnosis" and "Congenital cytomegalovirus infection: Management and outcome".)


Cytomegalovirus (CMV) infection and disease are not synonymous terms; not all patients with infection develop overt clinical disease.

CMV infection refers to virus isolation or detection of viral proteins (antigens) or nucleic acid in any body fluid or tissue specimen regardless of symptoms or signs [1,2].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Dec 07, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Razonable RR, Humar A, AST Infectious Diseases Community of Practice. Cytomegalovirus in solid organ transplantation. Am J Transplant 2013; 13 Suppl 4:93.
  2. Ljungman P, Boeckh M, Hirsch HH, et al. Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials. Clin Infect Dis 2017; 64:87.
  3. Razonable RR, Hayden RT. Clinical utility of viral load in management of cytomegalovirus infection after solid organ transplantation. Clin Microbiol Rev 2013; 26:703.
  4. Kotton CN, Kumar D, Caliendo AM, et al. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation 2013; 96:333.
  5. Eguchi H, Horita N, Ushio R, et al. Diagnostic test accuracy of antigenaemia assay for PCR-proven cytomegalovirus infection-systematic review and meta-analysis. Clin Microbiol Infect 2017; 23:907.
  6. Cope AV, Sabin C, Burroughs A, et al. Interrelationships among quantity of human cytomegalovirus (HCMV) DNA in blood, donor-recipient serostatus, and administration of methylprednisolone as risk factors for HCMV disease following liver transplantation. J Infect Dis 1997; 176:1484.
  7. Ferreira-Gonzalez A, Fisher RA, Weymouth LA, et al. Clinical utility of a quantitative polymerase chain reaction for diagnosis of cytomegalovirus disease in solid organ transplant patients. Transplantation 1999; 68:991.
  8. Roberts TC, Brennan DC, Buller RS, et al. Quantitative polymerase chain reaction to predict occurrence of symptomatic cytomegalovirus infection and assess response to ganciclovir therapy in renal transplant recipients. J Infect Dis 1998; 178:626.
  9. Weinberg A, Hodges TN, Li S, et al. Comparison of PCR, antigenemia assay, and rapid blood culture for detection and prevention of cytomegalovirus disease after lung transplantation. J Clin Microbiol 2000; 38:768.
  10. Hassan-Walker AF, Kidd IM, Sabin C, et al. Quantity of human cytomegalovirus (CMV) DNAemia as a risk factor for CMV disease in renal allograft recipients: relationship with donor/recipient CMV serostatus, receipt of augmented methylprednisolone and antithymocyte globulin (ATG). J Med Virol 1999; 58:182.
  11. Kraft CS, Armstrong WS, Caliendo AM. Interpreting quantitative cytomegalovirus DNA testing: understanding the laboratory perspective. Clin Infect Dis 2012; 54:1793.
  12. Caliendo AM. The long road toward standardization of viral load testing for cytomegalovirus. Clin Infect Dis 2013; 56:374.
  13. Preiksaitis JK, Hayden RT, Tong Y, et al. Are We There Yet? Impact of the First International Standard for Cytomegalovirus DNA on the Harmonization of Results Reported on Plasma Samples. Clin Infect Dis 2016; 63:583.
  14. Aitken C, Barrett-Muir W, Millar C, et al. Use of molecular assays in diagnosis and monitoring of cytomegalovirus disease following renal transplantation. J Clin Microbiol 1999; 37:2804.
  15. Humar A, Gregson D, Caliendo AM, et al. Clinical utility of quantitative cytomegalovirus viral load determination for predicting cytomegalovirus disease in liver transplant recipients. Transplantation 1999; 68:1305.
  16. Sia IG, Wilson JA, Espy MJ, et al. Evaluation of the COBAS AMPLICOR CMV MONITOR test for detection of viral DNA in specimens taken from patients after liver transplantation. J Clin Microbiol 2000; 38:600.
  17. Sia IG, Wilson JA, Groettum CM, et al. Cytomegalovirus (CMV) DNA load predicts relapsing CMV infection after solid organ transplantation. J Infect Dis 2000; 181:717.
  18. Martín-Gandul C, Pérez-Romero P, Sánchez M, et al. Determination, validation and standardization of a CMV DNA cut-off value in plasma for preemptive treatment of CMV infection in solid organ transplant recipients at lower risk for CMV infection. J Clin Virol 2013; 56:13.
  19. Emery VC, Sabin CA, Cope AV, et al. Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation. Lancet 2000; 355:2032.
  20. Chemaly RF, Yen-Lieberman B, Castilla EA, et al. Correlation between viral loads of cytomegalovirus in blood and bronchoalveolar lavage specimens from lung transplant recipients determined by histology and immunohistochemistry. J Clin Microbiol 2004; 42:2168.
  21. Westall GP, Michaelides A, Williams TJ, et al. Human cytomegalovirus load in plasma and bronchoalveolar lavage fluid: a longitudinal study of lung transplant recipients. J Infect Dis 2004; 190:1076.
  22. Riise GC, Andersson R, Bergström T, et al. Quantification of cytomegalovirus DNA in BAL fluid: a longitudinal study in lung transplant recipients. Chest 2000; 118:1653.
  23. Wallace JM, Hannah J. Cytomegalovirus pneumonitis in patients with AIDS. Findings in an autopsy series. Chest 1987; 92:198.
  24. Uberti-Foppa C, Lillo F, Terreni MR, et al. Cytomegalovirus pneumonia in AIDS patients: value of cytomegalovirus culture from BAL fluid and correlation with lung disease. Chest 1998; 113:919.
  25. Millar AB, Patou G, Miller RF, et al. Cytomegalovirus in the lungs of patients with AIDS. Respiratory pathogen or passenger? Am Rev Respir Dis 1990; 141:1474.
  26. Miles PR, Baughman RP, Linnemann CC Jr. Cytomegalovirus in the bronchoalveolar lavage fluid of patients with AIDS. Chest 1990; 97:1072.
  27. Mann M, Shelhamer JH, Masur H, et al. Lack of clinical utility of bronchoalveolar lavage cultures for cytomegalovirus in HIV infection. Am J Respir Crit Care Med 1997; 155:1723.
  28. Durand CM, Marr KA, Arnold CA, et al. Detection of cytomegalovirus DNA in plasma as an adjunct diagnostic for gastrointestinal tract disease in kidney and liver transplant recipients. Clin Infect Dis 2013; 57:1550.
  29. Revello MG, Percivalle E, Sarasini A, et al. Diagnosis of human cytomegalovirus infection of the nervous system by pp65 detection in polymorphonuclear leukocytes of cerebrospinal fluid from AIDS patients. J Infect Dis 1994; 170:1275.
  30. Arribas JR, Clifford DB, Fichtenbaum CJ, et al. Level of cytomegalovirus (CMV) DNA in cerebrospinal fluid of subjects with AIDS and CMV infection of the central nervous system. J Infect Dis 1995; 172:527.
  31. Flood J, Drew WL, Miner R, et al. Diagnosis of cytomegalovirus (CMV) polyradiculopathy and documentation of in vivo anti-CMV activity in cerebrospinal fluid by using branched DNA signal amplification and antigen assays. J Infect Dis 1997; 176:348.
  32. Lisboa LF, Asberg A, Kumar D, et al. The clinical utility of whole blood versus plasma cytomegalovirus viral load assays for monitoring therapeutic response. Transplantation 2011; 91:231.
  33. Caliendo AM, St George K, Allega J, et al. Distinguishing cytomegalovirus (CMV) infection and disease with CMV nucleic acid assays. J Clin Microbiol 2002; 40:1581.
  34. Caliendo AM, St George K, Kao SY, et al. Comparison of quantitative cytomegalovirus (CMV) PCR in plasma and CMV antigenemia assay: clinical utility of the prototype AMPLICOR CMV MONITOR test in transplant recipients. J Clin Microbiol 2000; 38:2122.
  35. Razonable RR, Åsberg A, Rollag H, et al. Virologic suppression measured by a cytomegalovirus (CMV) DNA test calibrated to the World Health Organization international standard is predictive of CMV disease resolution in transplant recipients. Clin Infect Dis 2013; 56:1546.
  36. Humar A, Kumar D, Boivin G, Caliendo AM. Cytomegalovirus (CMV) virus load kinetics to predict recurrent disease in solid-organ transplant patients with CMV disease. J Infect Dis 2002; 186:829.
  37. Lurain NS, Chou S. Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev 2010; 23:689.
  38. Le Page AK, Jager MM, Iwasenko JM, et al. Clinical aspects of cytomegalovirus antiviral resistance in solid organ transplant recipients. Clin Infect Dis 2013; 56:1018.
  39. Gilbert C, Boivin G. Human cytomegalovirus resistance to antiviral drugs. Antimicrob Agents Chemother 2005; 49:873.
  40. Razonable RR, Limaye RR. Cytomegalovirus infection after solid organ transplantation. In: Transplant Infections, 3rd ed, Bowden RA, Ljungman P, Snydman DR (Eds), Lippincott Williams and Wilkins, Philadelphia 2010. p.328.
  41. Boivin G, Goyette N, Gilbert C, Covington E. Analysis of cytomegalovirus DNA polymerase (UL54) mutations in solid organ transplant patients receiving valganciclovir or ganciclovir prophylaxis. J Med Virol 2005; 77:425.
  42. Chou S, Marousek GI, Van Wechel LC, et al. Growth and drug resistance phenotypes resulting from cytomegalovirus DNA polymerase region III mutations observed in clinical specimens. Antimicrob Agents Chemother 2007; 51:4160.
  43. Smith IL, Cherrington JM, Jiles RE, et al. High-level resistance of cytomegalovirus to ganciclovir is associated with alterations in both the UL97 and DNA polymerase genes. J Infect Dis 1997; 176:69.
  44. Hakki M, Chou S. The biology of cytomegalovirus drug resistance. Curr Opin Infect Dis 2011; 24:605.
  45. Revello MG, Zavattoni M, Sarasini A, et al. Human cytomegalovirus in blood of immunocompetent persons during primary infection: prognostic implications for pregnancy. J Infect Dis 1998; 177:1170.
  46. Navalpotro D, Gimeno C, Navarro D. PCR detection of viral DNA in serum as an ancillary analysis for the diagnosis of acute mononucleosis-like syndrome due to human cytomegalovirus (HCMV) in immunocompetent patients. J Clin Virol 2006; 35:193.
  47. Limaye AP, Boeckh M. CMV in critically ill patients: pathogen or bystander? Rev Med Virol 2010; 20:372.
  48. Limaye AP, Kirby KA, Rubenfeld GD, et al. Cytomegalovirus reactivation in critically ill immunocompetent patients. JAMA 2008; 300:413.
  49. Heininger A, Haeberle H, Fischer I, et al. Cytomegalovirus reactivation and associated outcome of critically ill patients with severe sepsis. Crit Care 2011; 15:R77.
  50. De Vlieger G, Meersseman W, Lagrou K, et al. Cytomegalovirus serostatus and outcome in nonimmunocompromised critically ill patients. Crit Care Med 2012; 40:36.