Overview of diagnostic tests for cytomegalovirus infection
- Angela M Caliendo, MD, PhD
Angela M Caliendo, MD, PhD
- Executive Vice Chair of Medicine
- Brown University
Cytomegalovirus (CMV) generally produces an asymptomatic or minimally symptomatic acute illness in immunocompetent patients. In immunocompromised hosts, however, CMV infection can result in a broad array of clinical presentations, including a nonspecific syndrome (which may include fever, malaise, weakness, myalgias, arthralgias, leukopenia, and/or thrombocytopenia in the setting of viremia) or end-organ disease such as retinitis, pneumonitis, encephalitis, hepatitis, or gastrointestinal tract ulceration. These manifestations are associated with significant morbidity and mortality.
An overview of the diagnostic tests for the diagnosis of CMV infections will be presented here. The approach to the diagnosis of CMV is discussed separately. The manifestations of CMV in immunocompetent and immunocompromised patients are also presented elsewhere. (See "Approach to the diagnosis of cytomegalovirus infection" and "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults" and "Cytomegalovirus infection in pregnancy" and "Acquired cytomegalovirus infection in children", section on 'Laboratory diagnosis' and "Pathogenesis, clinical manifestations, and diagnosis of AIDS-related cytomegalovirus retinitis", section on 'Diagnosis' and "Cytomegalovirus infection as a cause of pulmonary disease in HIV-infected patients" and "AIDS-related cytomegalovirus gastrointestinal disease" 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".)
The clinical features, diagnosis, and management of congenital CMV infection are also presented separately. (See "Congenital cytomegalovirus infection: Clinical features and diagnosis" and "Congenital cytomegalovirus infection: Management and outcome".)
The testing methods described in this topic have advantages and disadvantages and must be interpreted in the context of the clinical presentation and other diagnostic assessments. Molecular amplification methods are now the standard of care for diagnosing cytomegalovirus (CMV) infection; in the past, serologic testing and viral cultures from multiple sites were the cornerstones of diagnosis.
Appropriate diagnostic tests are essential for the management of CMV infection and disease in immunocompromised patients. Several diagnostic modalities are available, including serology, qualitative and quantitative polymerase chain reaction, pp65 antigenemia, culture, and histopathology (table 1). The techniques for detecting CMV (quantitative polymerase chain reaction and CMV pp65 antigenemia) have improved considerably.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:
- Hodinka R. Human Cytomegalovirus. In: Manual of Clinical Microbiology, 10th ed, Versalovic J, Carroll K, Funke G, et al (Eds), ASM Press, 2011. p.1558.
- Chou S. Newer methods for diagnosis of cytomegalovirus infection. Rev Infect Dis 1990; 12 Suppl 7:S727.
- Razonable RR, Hayden RT. Clinical utility of viral load in management of cytomegalovirus infection after solid organ transplantation. Clin Microbiol Rev 2013; 26:703.
- Roche Molecular Diagnostics. COBAS AmpliPrep/COBAS TaqMan CMV test. http://molecular.roche.com/assays/Pages/COBASAmpliPrepCOBASTaqManCMVTest.aspx (Accessed on July 10, 2012).
- US Food and Drug Administration News Release http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm310691.htm (Accessed on July 09, 2012).
- US Food and Drug Administration. artus CMV RGQ MDx Kit - P130027. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm403315.htm (Accessed on March 23, 2015).
- Kraft CS, Armstrong WS, Caliendo AM. Interpreting quantitative cytomegalovirus DNA testing: understanding the laboratory perspective. Clin Infect Dis 2012; 54:1793.
- Caliendo AM. The long road toward standardization of viral load testing for cytomegalovirus. Clin Infect Dis 2013; 56:374.
- 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.
- Hayden RT, Gu Z, Sam SS, et al. Comparative Performance of Reagents and Platforms for Quantitation of Cytomegalovirus DNA by Digital PCR. J Clin Microbiol 2016; 54:2602.
- Hirsch HH, Lautenschlager I, Pinsky BA, et al. An international multicenter performance analysis of cytomegalovirus load tests. Clin Infect Dis 2013; 56:367.
- Pang XL, Fox JD, Fenton JM, et al. Interlaboratory comparison of cytomegalovirus viral load assays. Am J Transplant 2009; 9:258.
- 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.
- Razonable RR, Brown RA, Wilson J, et al. The clinical use of various blood compartments for cytomegalovirus (CMV) DNA quantitation in transplant recipients with CMV disease. Transplantation 2002; 73:968.
- 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.
- Yen-Lieberman B, Starkey C, Kohn D. The effect of storage conditions on the stability of CMV DNA in whole blood and plasma specimens. Abstract C-143, American Society of Microbiology 101st Meeting. Orlando, FL 2001.
- Schäfer P, Tenschert W, Gutensohn K, Laufs R. Minimal effect of delayed sample processing on results of quantitative PCR for cytomegalovirus DNA in leukocytes compared to results of an antigenemia assay. J Clin Microbiol 1997; 35:741.
- Abdul-Ali D, Kraft CS, Ingersoll J, et al. Cytomegalovirus DNA stability in EDTA anti-coagulated whole blood and plasma samples. J Clin Virol 2011; 52:222.
- Bek B, Boeckh M, Lepenies J, et al. High-level sensitivity of quantitative pp65 cytomegalovirus (CMV) antigenemia assay for diagnosis of CMV disease in AIDS patients and follow-up. J Clin Microbiol 1996; 34:457.
- van den Berg AP, Klompmaker IJ, Haagsma EB, et al. Antigenemia in the diagnosis and monitoring of active cytomegalovirus infection after liver transplantation. J Infect Dis 1991; 164:265.
- van den Berg AP, van der Bij W, van Son WJ, et al. Cytomegalovirus antigenemia as a useful marker of symptomatic cytomegalovirus infection after renal transplantation--a report of 130 consecutive patients. Transplantation 1989; 48:991.
- van der Bij W, Schirm J, Torensma R, et al. Comparison between viremia and antigenemia for detection of cytomegalovirus in blood. J Clin Microbiol 1988; 26:2531.
- Rayes N, Seehofer D, Lullius SG, et al. Monitoring of human cytomegalovirus, HHV-6 and HHV-7 infection in kidney transplant recipients by molecular methods to predict HCMV disease after transplantation: a prospective study. Ann Transplant 2005; 10:23.
- Schröeder R, Michelon T, Fagundes I, et al. Antigenemia for cytomegalovirus in renal transplantation: choosing a cutoff for the diagnosis criteria in cytomegalovirus disease. Transplant Proc 2005; 37:2781.
- 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.
- Wreghitt TG, Teare EL, Sule O, et al. Cytomegalovirus infection in immunocompetent patients. Clin Infect Dis 2003; 37:1603.
- Razonable RR, Paya CV, Smith TF. Role of the laboratory in diagnosis and management of cytomegalovirus infection in hematopoietic stem cell and solid-organ transplant recipients. J Clin Microbiol 2002; 40:746.
- Klemola E, von Essen R, Wager O, et al. Cytomegalovirus mononucleosis in previously healthy individuals. Five new cases and follow-up of 13 previously published cases. Ann Intern Med 1969; 71:11.
- Lurain NS, Chou S. Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev 2010; 23:689.
- Recent or acute infection
- Past infection
- Risk of acquisition
- MOLECULAR ASSAYS (PCR)
- International standard
- Comparisons of tests
- - Whole blood versus plasma
- CMV ANTIGENEMIA ASSAYS
- Conventional culture
- Shell vial culture
- RESISTANCE TESTING
- SOCIETY GUIDELINE LINKS