1887

Chapter 100 : Human Cytomegalovirus

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $30.00

Preview this chapter:
Zoom in
Zoomout

Human Cytomegalovirus, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817381/9781555817381.ch100-1.gif /docserver/preview/fulltext/10.1128/9781555817381/9781555817381.ch100-2.gif

Abstract:

Cytomegalovirus (CMV) belongs to a large family of herpesviruses that commonly infect humans of all ages. Although infections with this virus are normally asymptomatic in healthy children and adults, CMV is one of the most notable viral pathogens causing serious diseases in newborns and individuals with compromised immune systems. This chapter emphasizes the fundamental characteristics and clinical importance of CMV and focuses on the laboratory tests that can be used to identify the virus and monitor and predict disease and susceptibility to antiviral therapy and the philosophy behind the interpretation and reporting of test results in various defined patient populations.

Citation: Hodinka R. 2015. Human Cytomegalovirus, p 1718-1737. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch100
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

Fixed hematoxylin and eosin-stained lung tissue from a patient with interstitial pneumonia. Note the numerous giant cells that possess large intranuclear inclusions surrounded by characteristically clear halos (arrows). Less pronounced granular inclusions may also be present in the cytoplasm (inset). (Courtesy of Eduardo Ruchelli.) doi:10.1128/9781555817381.ch100.f1

Citation: Hodinka R. 2015. Human Cytomegalovirus, p 1718-1737. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch100
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

CMV antigen-positive polymorphonuclear leukocytes. Note the nuclear staining when a monoclonal antibody directed against pp65 is used. Magnification, ×100 (A) or ×400 (B). doi:10.1128/9781555817381.ch100.f2

Citation: Hodinka R. 2015. Human Cytomegalovirus, p 1718-1737. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch100
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3
FIGURE 3

CPE produced by a CMV isolate in human skin fibroblasts 10 days postinoculation. Unstained preparation; magnification, ×100. (Courtesy of Sergio Stagno.) doi:10.1128/9781555817381.ch100.f3

Citation: Hodinka R. 2015. Human Cytomegalovirus, p 1718-1737. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch100
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4
FIGURE 4

Demonstration of CMV early antigens in the nuclei (arrows) of infected MRC-5 cells following shell vial culture and IFA staining. (A) Staining of immediate early antigen appears as an even matte yellow to green fluorescence with specks of brighter yellow to green. (B) Viral inclusions (owl’s eyes) may be visible in the nuclei. Magnification, ×400. doi:10.1128/9781555817381.ch100.f4

Citation: Hodinka R. 2015. Human Cytomegalovirus, p 1718-1737. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch100
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555817381.mcm11.ch100
1. Pignatelli S,, Dal Monte P,, Rossini G,, Landini MP. 2004. Genetic polymorphisms among human cytomegalovirus (HCMV) wild-type strains. Rev Med Virol 14:383410.
2. Boeckh M,, Geballe AP. 2011. Cytomegalovirus: pathogen, paradigm, and puzzle. J Clin Invest 121:16731680.
3. Manicklal S,, Emery VC,, Lazzarotto T,, Boppana SB,, Gupta RK. 2013. The “silent” global burden of congenital cytomegalovirus. Clin Microbiol Rev 26:86101.
4. O’Connor S,, Taylor C,, Campbell LA,, Epstein S,, Libby P. 2001. Potential infectious etiologies of atherosclerosis: a multifactorial perspective. Emerg Infect Dis 7:780788.
5. Osawa R,, Singh N. 2009. Cytomegalovirus infection in critically ill patients: a systematic review. Crit Care 13:R68.
6. Rafailidis PI,, Mourtzoukou EG,, Varbobitis IC,, Falagas ME. 2008. Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review. Virol J 5:47.
7. Limaye AP,, Boeckh M. 2010. Cytomegalovirus (CMV) in critically-ill patients: pathogen or bystander? Rev Med Virol 20:372379.
8. Husain S,, Pietrangeli CE,, Zeevi A. 2009. Delayed onset CMV disease in solid organ transplant recipients. Transplant Immunol 21:19.
9. Razonable RR. 2010. Strategies for managing cytomegalovirus in transplant recipients. Expert Opin Pharmacother 11:19831997.
10. Eid AJ,, Razonable RR. 2010. New developments in the management of cytomegalovirus infection after solid organ transplantation. Drugs 70:965981.
11. Dasari V,, Smith C,, Khanna R. 2013. Recent advances in designing an effective vaccine to prevent cytomegalovirus-associated clinical diseases. Expert Rev Vaccines 12:661676.
12. Cortez KJ,, Fischer SH,, Fahle GA,, Calhoun LB,, Childs RW,, Barrett AJ,, Bennett JE. 2003. Clinical trial of quantitative real-time polymerase chain reaction for detection of cytomegalovirus in peripheral blood of allogeneic hematopoietic stem-cell transplant recipients. J Infect Dis 188:967972.
13. Mengelle C,, Sandres-Saune K,, Pasquier C,, Rostaing L,, Mansuy J-M,, Marty M,, Da Silva I,, Attal M,, Massip P,, Izopet J. 2003. Automated extraction and quantitation of human cytomegalovirus DNA in whole blood by real-time PCR assay. J Clin Microbiol 41:38403845.
14. Razonable RR,, Brown RA,, Wilson J,, Groettum C,, Kremers W,, Espy M,, Smith TF,, Paya C. 2002. The clinical use of various blood compartments for cytomegalovirus (CMV) DNA quantitation in transplant recipients with CMV disease. Transplantation 73:968973.
15. Spector SA,, Merrill R,, Wolf D,, Dankner WM. 1992. Detection of human cytomegalovirus in plasma of AIDS patients during acute visceral disease by DNA amplification. J Clin Microbiol 30:23592365.
16. Kraft CS,, Armstrong WS,, Caliendo AM. 2012. Interpreting quantitative cytomegalovirus DNA testing: understanding the laboratory perspective. Clin Infect Dis 54:17931797.
17. Garrigue I,, Boucher S,, Couzi L,, Caumont A,, Dromer C,, Neau-Cransac M,, Tabrizi R,, Schrive M-H,, Fleury H,, Lafon M-E. 2006. Whole blood real-time quantitative PCR for cytomegalovirus infection follow-up in transplant recipients. J Clin Virol 36:7275.
18. Koidl C,, Bozic M,, Marth E,, Kessler HH. 2008. Detection of CMV DNA: is EDTA whole blood superior to EDTA plasma? J Virol Methods 154:210212.
19. Lisboa LF,, Asberg A,, Kumar D,, Pang X,, Hartmann A,, Preiksaitis JK,, Pescovitz MD,, Rollag H,, Jardine AG,, Humar A. 2011. The clinical utility of whole blood versus plasma cytomegalovirus viral load assays for monitoring therapeutic response. Transplantation 91:231236.
20. Sanchez JL,, Storch GA. 2002. Multiplex, quantitative, real-time PCR assay for cytomegalovirus and human DNA. J Clin Microbiol 40:23812386.
21. Landry ML,, Ferguson D,, Cohen S,, Huber K,, Wetherill P. 1995. Effect of delayed specimen processing on cytomegalovirus antigenemia test results. J Clin Microbiol 33:257259.
22. Boeckh M,, Woogerd PM,, Stevens-Ayers T,, Ray CG,, Bowden RA. 1994. Factors influencing detection of quantitative cytomegalovirus antigenemia. J Clin Microbiol 32:832834.
23. Schafer P,, Tenschert W,, Gutensohn K,, Laufs R. 1997. 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 35-741745.
24. Abdul-Ali D,, Kraft CS,, Ingersoll J,, Frempong M,, Caliendo AM. 2011. Cytomegalovirus DNA stability in EDTA anti-coagulated whole blood and plasma samples. J Clin Virol 52:222224.
25. Landini MP,, Lazzarotto T. 1999. Prenatal diagnosis of congenital cytomegalovirus infection: light and shade. HERPES 6:4549.
26. Boppana SB,, Ross SA,, Novak Z,, Shimamura M,, Tolan RWJr,, Palmer AL,, Ahmed A,, Michaels MG,, Sanchez PJ,, Bernstein DI,, Britt WJ,, Fowler KB. 2010. Dried blood spot real-time polymerase chain reaction assays to screen newborns for congenital cytomegalovirus infection. JAMA 14:13751382.
27. Piccirilli G,, Chiereghin A,, Gabrielli L,, Lazzarotto T. 2014. Diagnosis and monitoring of cytomegalovirus infection by the quantification of viral load in dried blood spot samples. Expert Rev Mol Diagn 14:139142.
28. De Vries JJC,, Wessels E,, Korver AMH,, van der Eijk AA,, Rusman LG,, Kroes ACM,, Vossen ACTM. 2012. Rapid genotyping of cytomegalovirus in dried blood spots by multiplex real-time PCR assays targeting the envelope glycoprotein gB and gH genes. J Clin Microbiol 50:232237.
29. Boppana SB,, Ross SA,, Shimarmura M,, Palmer AL,, Ahmed A,, Michaels MG,, Sanchez PJ,, Bernstein DI,, Tolan Jr RW,, Novak Z,, Chowshury N,, Britt WJ,, Fowler KB, for the National Institute on Deafness and Other Communication Disorders CHIMES Study. 2011. Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. N Engl J Med 364:21112118.
30. Landry ML,, Ferguson D. 2000. Reduced ability to culture cytomegalovirus from peripheral blood leukocytes isolated by direct erythrocyte lysis. J Clin Microbiol 38:3906.
31. Adler SP,, Wang JB. 1996. Salivary antibodies to cytomegalovirus (CMV) glycoprotein B accurately predict CMV infections among preschool children. J Clin Microbiol 34:26322634.
32. Manuel O. 2013. Clinical experience with immune monitoring for cytomegalovirus in solid-organ transplant recipients. Curr Infect Dis Rep 15:491496.
33. Egli A,, Humar A,, Kumar D. 2012. State-of-the-art monitoring of cytomegalovirus-specific cell-mediated immunity after organ transplant: a primer for the clinician. Clin Infect Dis 55:16781689.
34. Kotton CN,, Kumar D,, Caliendo AM,, Asberg A,, Chou S,, Danziger-Isakov L,, Humar A, on behalf of The Transplantation Society International CMV Consensus Group. 2013. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation 96:333360.
35. Razonable RR,, Hayden RT. 2013. Clinical utility of viral load in management of cytomegalovirus infection after solid organ transplantation. Clin Microbiol Rev 26:703727.
36. Pillet S,, Roblin X,, Cornillon J,, Mariat C,, Pozzetto B. 2014. Quantification of cytomegalovirus viral load. Expert Rev Anti Infect Ther 12:193210.
37. Gerna G,, Revello MG,, Percivalle E,, Zavattoni M,, Parea M,, Battaglia M. 1990. Quantitation of human cytomegalovirus viremia by using monoclonal antibodies to different viral proteins. J Clin Microbiol 28:26812688.
38. Landry ML,, Ferguson D. 1993. Comparison of quantitative cytomegalovirus antigenemia assay with culture methods and correlation with clinical disease. J Clin Microbiol 31:28512856.
39. Gerna G,, Zipeto D,, Parea M,, Revello MG,, Silini E,, Percivalle E,, Zavattoni M,, Grossi P,, Milanesi G. 1991. Monitoring of human cytomegalovirus infections and ganciclovir treatment in heart transplant recipients by determination of viremia, antigenemia, and DNAemia. J Infect Dis 164:488498.
40. van den Berg AP,, Tegzess AM,, Scholten-Sampson A,, Schirm J,, van der Giessen M,, The TH,, van Son WJ. 1992. Monitoring antigenemia is useful in guiding treatment of severe cytomegalovirus disease after organ transplantation. Transplant Int 5:101107.
41. Baldanti F,, Lilleri D,, Gerna G. 2008. Human cytomegalovirus load measurement and its applications for pre-emptive therapy in patients undergoing hematopoietic stem cell transplantation. Hematol Oncol 26:123130.
42. Tan BH,, Chlebicka NL,, Hong Low JG,, Chong TYR,, Chan KP,, Goh YT. 2008. Use of the cytomegalovirus pp65 antigenemia assay for preemptive therapy in allogeneic hematopoietic stem cell transplantation: a real-world review. Transplant Infect Dis 10:325332.
43. Revello MG,, Percivalle E,, Sarasini A,, Baldanti F,, Furione M,, Gerna G. 1994. Diagnosis of human cytomegalovirus infection of the nervous system by pp65 detection in polymorphonuclear leukocytes of cerebrospinal fluid from AIDS patients. J Infect Dis 170:12751279.
44. Arav-Boger R,, Pass R. 2007. Viral load in congenital cytomegalovirus infection. HERPES 14:1722.
45. Jang EY,, Park SY,, Lee EJ,, Song EH,, Chong YP,, Lee S-O,, Choi S-O,, Woo JH,, Kim YS,, Kim S-H. 2009. Diagnostic performance of the cytomegalovirus (CMV) antigenemia assay in patients with CMV gastrointestinal disease. Clin Infect Dis 48:e121e124.
46. Gerna G,, Zavattoni M,, Baldanti F,, Furione M,, Chezzi L,, Revello MG,, Percivalle E. 1998. Circulating cytomegalic endothelial cells are associated with high human cytomegalovirus (HCMV) load in AIDS patients with late-stage disseminated HCMV disease. J Med Virol 55:6474.
47. Salzberger B,, Myerson D,, Boeckh M. 1997. Circulating cytomegalovirus (CMV)-infected endothelial cells in marrow transplant patients with CMV disease and CMV infection. J Infect Dis 176:778781.
48. Cariani E,, Pollara CP,, Valloncini B,, Perandin F,, Bonfanti C,, Manca N. 2007. Relationship between pp65 antigenemia levels and real-time quantitative DNA PCR for human cytomegalovirus (HCMV) management in immunocompromised patients. BMC Infect Dis 7:138.
49. Gerna G,, Furione M,, Baldanti F,, Sarasini A. 1994. Comparative quantitation of human cytomegalovirus DNA in blood leukocytes and plasma of transplant and AIDS patients. J Clin Microbiol 32:27092717.
50. Mengoli C,, Cusinato R,, Biasolo MA,, Cesaro S,, Parolin C,, Palu G. 2004. Assessment of CMV load in solid organ trnasplant recipients by pp65 antigenemia and real-time quantitative DNA PCR assay: correlation with pp67 RNA detection. J Med Virol 74:7884.
51. Sanghavi SK,, Abu-Elmagd K,, Keightley MC,, St. George K,, Lewandowski K,, Boes SS,, Bullotta A,, Dare R,, Lassak M,, Jusain S,, Kwak EJ,, Paterson DL,, Rinaldo CR. 2008. Relationship of cytomegalovirus load assessed by real-time PCR to pp65 antigenemia in organ transplant recipients. J Clin Virol 42:335342.
52. The TH,, van der Ploeg M,, van den Berg AP,, Vlieger AM,, van der Giessen M,, van Son WJ. 1992. Direct detection of cytomegalovirus in peripheral blood leukocytes—a review of the antigenemia assay and polymerase chain reaction. Transplantation 54:193198.
53. Ho SKN,, Lo C-Y,, Cheng IKP,, Chan T-M. 1998. Rapid cytomegalovirus pp65 antigenemia assay by direct erythrocyte lysis and immunofluorescence staining. J Clin Microbiol 36:638640.
54. Gerna G,, Percivalle E,, Torsellini M,, Revello MG. 1998. Standardization of the human cytomegalovirus antigenemia assay by means of in vitro-generated pp65-positive peripheral blood polymorphonuclear leukocytes. J Clin Microbiol 36:35853589.
55. The TH,, van den Berg AP,, Harmsen MC,, van der Bij W,, van Son WJ. 1995. The cytomegalovirus antigenemia assay: a plea for standardization. Scand J Infect Dis Suppl 99:2529.
56. Verschuuren EA,, Harmsen MC,, Limburg PC,, van der Bij W,, van den Berg AP,, Kas-Deelen AM,, Meedendorp B,, van Son WJ,, The TH. 1999. Toward standardization of the human cytomegalovirus antigenemia assay. Intervirology 42:382389.
57. Landry ML,, D. Ferguson D,, Stevens-Ayers T,, de Jonge MWA,, Boeckh M. 1996. Evaluation of CMV Brite kit for detection of cytomegalovirus pp65 antigenemia in peripheral blood leukocytes by immunofluorescence. J Clin Microbiol 34:13371339.
58. St. George K,, Boyd MJ,, Lipson SM,, Ferguson D,, Cartmell GF,, Falk LH,, Rinaldo CR,, Landry ML. 2000. A multisite trial comparing two cytomegalovirus (CMV) pp65 antigenemia test kits, Biotest CMV Brite and Bartels/Argene CMV antigenemia. J Clin Microbiol 38:14301433.
59. Landry ML,, Ferguson D. 2000. Two-hour cytomegalovirus pp65 antigenemia assay for rapid quantitation of cytomegalovirus in blood samples. J Clin Microbiol 38:427428.
60. Visser CE,, van Zeijl CJ,, de Klerk EP,, Schillizi BM,, Beersma MF,, Kroes AC. 2000. First experiences with an accelerated CMV antigenemia test: CMV Brite Turbo assay. J Clin Virol 17:6568.
61. May G,, Kuhn JE,, Eing BR. 2006. Comparison of two commercially available pp65 antigenemia tests and COBAS Amplicor CMV Monitor for early detection and quantification of episodes of human CMV-viremia in transplant recipients. Intervirology 49:261265.
62. Percivalle E,, Genini E,, Chiesa A,, Gerna G. 2008. Comparison of a new Light Diagnostics and the CMV Brite to an in-house developed human cytomegalovirus antigenemia assay. J Clin Virol 43:1317.
63. Demmler GJ,, Buffone J,, Schimbor CM,, May RA. 1988. Detection of cytomegalovirus in urine from newborns by using polymerase chain reaction DNA amplification. J Infect Dis 158:11771184.
64. Hsia K,, Spector DH,, Lawrie J,, Spector SA. 1989. Enzymatic amplification of human cytomegalovirus sequences by polymerase chain reaction. J Clin Microbiol 27:18021809.
65. Olive DM,, Simsek M,, Al-Mufti S. 1989. Polymerase chain reaction assay for detection of human cytomegalovirus. J Clin Microbiol 27:12381242.
66. Shibata D,, Martin WJ,, Appelman MD,, Causey DM,, Leedom JM,, Arnheim N. 1988. Detection of cytomegalovirus DNA in peripheral blood of patients with human immunodeficiency virus. J Infect Dis 158:11851192.
67. Wolf DG,, Spector SA. 1992. Diagnosis of human cytomegalovirus central nervous system disease in AIDS patients by DNA amplification from cerebrospinal fluid. J Infect Dis 166:14121415.
68. Gerna G,, Zipeto D,, Parea M,, Percivalle E,, Zavattoni M,, Gaballo A,, Milanesi G. 1991. Early virus isolation, early structural antigen detection and DNA amplification by the polymerase chain reaction in polymorphonuclear leukocytes from AIDS patients with human cytomegalovirus viraemia. Mol Cell Probes 5:365374.
69. Theiler RN,, Caliendo AM,, Pargman S,, Raynor BD,, Berga S,, McPheeters M,, Jamieson DJ. 2006. Umbilical cord blood screening for cytomegalovirus DNA by quantitative PCR. J Clin Virol 37:313316.
70. Bitsch A,, Kirchner H,, Dennin R,, Hoyer J,, Fricke L,, Steinhoff J,, Sack K,, Bein G. 1993. Long persistence of CMV DNA in the blood of renal transplant patients after recovery from CMV infection. Transplantation 56:108113.
71. Stanier P,, Taylor DL,, Kitchen AD,, Wales N,, Tryhorn Y,, Tyms AS. 1989. Persistence of cytomegalovirus in mononuclear cells in peripheral blood from blood donors. Br Med J 299:897898.
72. Baldanti F,, Lilleri D,, Gerna G. 2008. Monitoring human cytomegalovirus infection in transplant recipients. J Clin Virol 41:237241.
73. Gerna G,, Lilleri D. 2006. Monitoring transplant patients for human cytomegalovirus: diagnostic update. HERPES 13:411.
74. Gault E,, Michael Y,, Dehee A,, Belabani C,, Nicolas JC,, Garbarg-Chenon A. 2001. Quantitation of human cytomegalovirus DNA by real-time PCR. J Clin Microbiol 39:772775.
75. Gourlain K,, Salmon D,, Gault E,, Leport C,, Katlama C,, Matheron S,, Costagliola D,, Mazeron MC,, Fillet AM, and Predivir Study Group and CMV AC11 Study Group. 2003. Quantitation of cytomegalovirus (CMV) DNA by real-time PCR for occurrence of CMV disease in HIV-infected patients receiving highly active antiretroviral therapy. J Med Virol 69:401407.
76. Griscelli F,, Barrois M,, Chauvin S,, Lastere S,, Bellet D,, Bourhis J-H. 2001. Quantification of human cytomegalovirus DNA in bone marrow transplant recipients by real-time PCR. J Clin Microbiol 39:43624369.
77. Guiver M,, Fox AJ,, Mutton K,, Mogulkoc N,, Egan J. 2001. Evaluation of CMV viral load using TaqMan CMV quantitative PCR and comparison with CMV antigenemia in heart and lung transplant recipients. Transplantation 71:16091615.
78. Leruez-Ville M,, Ouachee M,, Delarue R,, Sauget A-S,, Blanche S,, Buzyn A,, Rouzioux C. 2003. Monitoring cytomegalovirus infection in adult and pediatric bone marrow transplant recipients by a real-time PCR assay performed with blood plasma. J Clin Microbiol 41:20402026.
79. Machida U,, Kami M,, Fukui T,, Kazuyama Y,, Kinoshita M,, Tanaka Y,, Kanda Y,, Ogawa S,, Honda H,, Chiba S,, Mitani K,, Muto Y,, Osumi K,, Kimura S,, Hirai H. 2000. Real-time automated PCR for early diagnosis and monitoring of cytomegalovirus infection after bone marrow transplantation. J Clin Microbiol 38:25362542.
80. Mengelle C,, Pasquier C,, Rostaing L,, Sandres-Saune K,, Puel J,, Berges L,, Righi L,, Bouquies C,, Izopet J. 2003. Quantitation of human cytomegalovirus in recipients of solid organ transplants by real-time quantitative PCR and pp65 antigenemia. J Med Virol 69:225231.
81. Ono Y,, Ito Y,, Kaneko K,, Shibata-Watanabe Y,, Tainaka T,, Sumida W,, Nakamura T,, Kamei H,, Kiuchi T,, Ando H,, Kimura H. 2008. Simultaneous monitoring by real-time polymerase chain reaction of Epstein-Barr virus, human cytomegalovirus, and human herpesvirus-6 in juvenile and adult liver transplant recipients. Transplant Proc 40:35783582.
82. Wada K,, Kubota N,, Ito Y,, Yagasaki H,, Kato K,, Yoshikawa T,, Ono Y,, Ando H,, Fujimoto Y,, Kiuchi T,, Kojima S,, Nishiyama Y,, Kimura H. 2007. Simultaneous quantification of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 DNA in samples from transplant recipients by multiplex real-time PCR assay. J Clin Microbiol 45:14261432.
83. Bestetti A,, Pierotti C,, Terreni M,, Zappa A,, Vago L,, Lazzarin A,, Cinque P. 2001. Comparison of three nucleic acid amplification assays of cerebrospinal fluid for diagnosis of cytomegalovirus encephalitis. J Clin Microbiol 39:11481151.
84. Blank BS,, Meenhorst PL,, Mulder JW,, Weverling GJ,, Putter H,, Pauw W,, van Dijk WC,, Smits P,, Lie-A-Ling S,, Reiss P,, Lange JM. 2000. Value of different assays for detection of human cytomegalovirus (HCMV) in predicting the development of HCMV disease in human immunodeficiency virus-infected patients. J Clin Microbiol 38:563569.
85. Pellegrin I,, Garrigue I,, Ekouevi D,, Couzi L,, Merville P,, Merel P,, Chene G,, Schrive MH,, Trimoulet P,, Lafon ME,, Fleury H. 2000. New molecular assays to predict occurrence of cytomegalovirus disease in renal transplant recipients. J Infect Dis 182:3642.
86. Razonable RR,, Brown RA,, Espy MJ,, Rivero A,, Kremers W,, Wilson J,, Groettum C,, Smith TF,, Paya CV. 2001. Comparative quantitation of cytomegalovirus (CMV) DNA in solid organ transplant recipients with CMV infection by using two high-throughput automated systems. J Clin Microbiol 39:44724476.
87. Tong CY,, Cuevas LE,, Williams H,, Bakran A. 2000. Comparison of two commercial methods for measurement of cytomegalovirus load in blood samples after renal transplantation. J Clin Microbiol 38:12091213.
88. Wattanamano P,, Clayton JL,, Kopicko JJ,, Kissinger P,, Elliot S,, Jarrott C,, Rangan S,, Beilke MA. 2000. Comparison of three assays for cytomegalovirus detection in AIDS patients at risk for retinitis. J Clin Microbiol 38:727732.
89. Drouet E,, Colimon R,, Michelson S,, Fourcade N,, Niveleau A,, Ducerf C,, Boibieux A,, Chevallier M,, Denoyel G. 1995. Monitoring levels of human cytomegalovirus DNA in blood after liver transplantation. J Clin Microbiol 33:389394.
90. Gerdes JC,, Spees EK,, Fitting K,, Hiraki J,, Sheehan M,, Duda D,, Jarvi T,, Roehl C,, Robertson AD. 1993. Prospective study utilizing a quantitative polymerase chain reaction for detection of cytomegalovirus DNA in the blood of renal transplant patients. Transplant Proc 25:14111413.
91. Zipeto D,, Baldanti F,, Zella D,, Furione M,, Cavicchini A,, Milanesi G,, Gerna G. 1993. Quantification of human cytomegalovirus DNA in peripheral blood polymorphonuclear leukocytes of immunocompromised patients by the polymerase chain reaction. J Virol Methods 44:4556.
92. Rasmussen L,, Morris S,, Zipeto D,, Fessel J,, Wolitz R,, Dowling A,, Merigan TC. 1995. Quantitation of human cytomegalovirus DNA from peripheral blood cells of human immunodeficiency virus-infected patients could predict cytomegalovirus retinitis. J Infect Dis 171:177182.
93. Zipeto D,, Morris S,, Hong C,, Dowling A,, Wolitz R,, Merigan TC,, Rasmussen L. 1995. Human cytomegalovirus (CMV) DNA in plasma reflects quantity of CMV DNA present in leukocytes. J Clin Microbiol 33:26072611.
94. Fox JC,, Griffiths PD,, Emery VC. 1992. Quantification of human cytomegalovirus DNA using the polymerase chain reaction. J Gen Virol 73:24052408.
95. Revello MG,, Gerna G. 2002. Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant. Clin Microbiol Rev 15:680715.
96. Shinkai M,, Spector S. 1995. Quantitation of human cytomegalovirus (HCMV) DNA in cerebrospinal fluid by competitive PCR in AIDS patients with different HCMV central nervous system diseases. Scand J Infect Dis 27:559561.
97. Caliendo AM,, Ingersoll J,, Fox-Canale AM,, Pargman S,, Bythwood T,, Hayden MK,, Bremer JW,, Lurain NS. 2007. Evaluation of real-time PCR laboratory-developed tests using analyte specific reagents for cytomegalovirus quantification. J Clin Microbiol 45:17231727.
98. Gimeno C,, Solano C,, Latorre JC,, Hernandez-Boluda JC,, Clari MA,, Remigia MJ,, Furio S,, Calabuig M,, Tormo N,, Navarro D. 2008. Quantification of DNA in plasma by an automated real-time PCR assay (cytomegalovirus PCR kit) for surveillance of active cytomegalovirus infection and guidance of preemptive therapy for allogeneic hematopoietic stem cell transplant recipients. J Clin Microbiol 46:33113318.
99. Clari MA,, Bravo D,, Costa E,, Munoz-Cobo B,, Solano C,, Remigia MJ,, Gimenez E,, BenMarzouk-Hidalgo OJ,, Perez-Romero P,, Navarro D. 2013. Comparison of the new Abbott real time CMV assay and the Abbott CMV PCR kit for the quantitation of plasma cytomegalovirus DNAemia. Diagn Microbiol Infect Dis 75:207209.
100. Schnepf N,, Scieux C,, Resche-Riggon M,, Feghoul L,, Xhaard A,, Gallien S,, Molina JM,, Socie G,, Viglietti D,, Simon F,, Mazeron MC,, Legoff J. 2013. Fully automated quantification of cytomegalovirus (CMV) in whole blood with the new sensitive Abbott real time CMV assay in the era of the CMV international standard. J Clin Microbiol 51:20962102.
101. Gouarin S,, Vabret A,, Scieux C,, Agbalika F,, Cherot J,, Mengelle C,, Deback C,, Petitjean J,, Dina J,, Freymuth F. 2007. Multicentric evaluation of a new commercial cytomegalovirus real-time PCR quantitation assay. J Virol Methods 146:147154.
102. Michelin BDA,, Hadzisejdic I,, Bozic M,, Grahovac M,, Hess M,, Grahovac B,, Marth E,, Kessler HH. 2008. Detection of cytomegalovirus (CMV) DNA in EDTA whole-blood samples: evaluation of the quantitative artus CMV LightCycler PCR kit in conjunction with automated sample preparation. J Clin Microbiol 46:12411245.
103. Abbate I,, Finnstrom N,, Zaniratti S,, Solmone MC,, Selvaggini S,, Bennici E,, Neri S,, Brega C,, Paterno M,, Capobianchi MR. 2008. Evaluation of an automated extraction system in combination with Affigene CMV Trender for CMV DNA quantitative determination: comparison with nested PCR and pp65 antigen test. J Virol Methods 151:6165.
104. Gracia-Ahufinger I,, Tormo N,, Espigado I,, Solano C,, Urbano-Ispizua A,, Clari MA,, de la Cruz-Vicente F,, Navarro D,, Perez-Romero P. 2010. Differences in cytomegalovirus plasma viral loads measured in allogeneic hematipoietic stem cell transplant receipients using two commercial real-time PCR assays. J Clin Virol 48:142146.
105. Binnicker MJ,, Espy ME. 2013. Comparison of six real-time PCR assays for qualitative detection of cytomegalovirus in clinical specimens. J Clin Microbiol 11:37493752.
106. Allice T,, Cerutti F,, Pittaluga F,, Varetto S,, Franchello A,, Salizzoni M,, Ghisetti V. 2008. Evaluation of a novel real-time PCR system for cytomegalovirus DNA quantitation on whole blood and correlation with pp65-antigen test in guiding pre-emptive antiviral treatment. J Virol Methods 148:916.
107. Khare R,, Espy MJ,, Mandrekar JN,, Binnicker MJ. 2014. Comparison of a transplant multiplex viral panel on the ICEPlex System with real-time PCR for the detection of cytomegalovirus, Epstein-Barr virus and BK virus in clinical specimens. J Clin Microbiol 52:17111713.
108. Hanson KE,, Reller LB,, Kurtzberg J,, Horwitz M,, Long G,, Alexander BD. 2007. Comparison of the Digen Hybrid Capture System Cytomegalovirus (CMV) DNA (Version 2.0), Roche CMV UL54 analyte-specific reagent, and QIAGEN RealArt CMV LightCycler PCR reagent tests using AcroMetrix OptiQuant CMV DNA quantification panels and specimens from allogeneic-stem-cell transplant recipients. J Clin Microbiol 45:19721973.
109. Pritt BS,, Germer JJ,, Gomez-Urena E,, Bishop CJ,, Mandrekar JN,, Irish CL,, Yao JDC. 2013. Coversion to the COBAS AmpliPrep/COBAS TaqMan CMV Test for management of CMV disease in transplant recipients. Diagn Microbiol Infect Dis 75:440442.
110. Cardenoso L,, Pinsky BA,, Lautenschlager I,, Aslam S,, Cobb B,, Vilchez RA,, Hirsch HH. 2013. CMV antigenemia and quantitative viral load assessments in hematopoietic stell cell transplant recipients. J Clin Virol 56:108112.
111. Boaretti M,, Sorrentino A,, Zantedeschi C,, Forni A,, Boschiero L,, Fontana R. 2013. Quantification of cytomegalovirus DNA by a fully automated real-time PCR for early diagnosis and monitoring of active viral infection in solid organ transplant recipients. J Clin Virol 56:124128.
112. Kerschner H,, Bauer C,, Schlag P,, Lee S,, Goedel S,, Popow-Kraupp T. 2011. Clinical evaluation of a fully automated CMV PCR assay. J Clin Virol 50:281286.
113. Boivin G,, Belanger R,, Delage R,, Beliveau 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 38:43564360.
114. Caliendo AM,, Schuurman B,, Yen-Lieberman B,, Spector SA,, Andersen J,, Manjiry R,, Crumpacker C,, Lurain NS,, Erice A for the CMV Working Group of the Complications of HIV Disease RAC, AIDS Clinical Trials Group. 2001. Comparison of quantitative and qualitative PCR assays for cytomegalovirus DNA in plasma. J Clin Microbiol 39:13341338.
115. Caliendo AM,, St. George K,, Allega J,, Bullotta AC,, Gilbane L,, Rinaldo CR. 2002. Distinguishing cytomegalovirus (CMV) infection and disease with CMV nucleic acid assays. J Clin Microbiol 40:15811586.
116. Sia IG,, Wilson JA,, Espy MJ,, Paya CV,, Smith TF. 2000. Evaluation of the COBAS AMPLICOR CMV MONITOR Test for detection of viral DNA in specimens taken from patients after liver transplantation. J Clin Microbiol 38:600606.
117. Tang W,, Elmore SH,, Fan H,, Thorne LB,, Gulley ML. 2008. Cytomegalovirus DNA measurement in blood and plasma using Roche LightCycler CMV quantitative reagents. Diagn Mol Pathol 17:166173.
118. Caliendo AM,, Shahbazian MD,, Schaper C,, Ingersoll J,, Abdul-Ali D,, Boonyaratanakornkit J,, Pang X-L,, Fox J,, Preiksaitis J,, Schonbrunner ER. 2009. A commutable cytomegalovirus calibrator is required to improve the agreement of viral load values between laboratories. Clin Chem 55:9.
119. Pang XL,, Fox JD,, Fenton JM,, Miller GG,, Caliendo AM,, Preiksaitis JK for the American Society of Transplantation Infectious Diseases Community of Practice and the Canadian Society of Transplantation. 2009. Interlaboratory comparison of cytomegalovirus viral load assays. Am J Transplant 9:258268.
120. Wolff DJ,, Heaney DL,, Neuwald PD,, Stellrecht KA,, Press RD. 2009. Multi-site PCR-based CMV viral load assessment-assays demonstrate linearity and precision, but lack numeric standardization. J Mol Diagn 11:8792.
121. Hayden RT,, Yan X,, Wick MT,, Rodriguez AB,, Xiong X,, Ginocchio CC,, Mitchell MJ,, Caliendo AM. 2012. Factors contributing to variability of quantitative viral PCR results in proficiency testing samples: a multivariate analysis. J Clin Microbiol 50:337345.
122. Haynes RJ,, Kline MC,, Toman B,, Scott C,, Wallace P,, Butler JM,, Holden MJ. 2013. Standard reference material 2366 for measurement of human cytomegalovirus DNA. J Mol Diagn 15:177185.
123. Hayden RT,, Shahbazian MD,, Valsamakis A,, Boonyaratanakornkit J,, Cook L,, Pang XL,, Preiksaitis JK,, Schonbrunner ER,, Caliendo AM. 2013. Multicenter evaluation of a commercial cytomegalovirus quantitative standard: effects of commutability on interlaboratory concordance. J Clin Microbiol 51:38113817.
124. Hirsch HH,, Lautenschlager I,, Pinsky BA,, Cardenoso L,, Aslam S,, Cobb B,, Vilchez RA,, Valsamakis A. 2013. An international multicenter performance analysis of cytomegalovirus load tests. Clin Infect Dis 56:367373.
125. Razonable RR,, Asberg A,, Rollag H,, Duncan J,, Boisvert D,, Yao JD,, Caliendo AM,, Humar A,, Do TD. 2013. 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 56:15461553.
126. Hayden RT,, Gu Z,, Ingersoll J,, Abdul-Ali D,, Shi L,, Pounds S,, Caliendo AM. 2013. Comparison of droplet digital PCR to real-time PCR for quantitative detection of cytomegalovirus. J Clin Microbiol 51:540546.
127. Paya CV,, Wold AD,, Ilstrup DM,, Smith TF. 1988. Evaluation of number of shell vial cell cultures per clinical specimen for rapid diagnosis of cytomegalovirus infection. J Clin Microbiol 26:198200.
128. Wunderli W,, Kagi MK,, Gruter E,, Auracher JD. 1989. Detection of cytomegalovirus in peripheral leukocytes by different methods. J Clin Microbiol 27:19161917.
129. Patel R,, Klein DW,, Espy MJ,, Harmsen WS,, Ilstrup DM,, Paya CV,, Smith TF. 1995. Optimization of detection of cytomegalovirus viremia in transplantation recipients by shell vial assay. J Clin Microbiol 33:29842986.
130. Hodinka RL,. 2010. Serological tests in clinical virology, p 133150. In Jerome KR (ed.), Lennette’s Laboratory Diagnosis of Viral Infections, 4th ed. Informa Healthcare USA, Inc., New York, NY.
131. Novak Z,, Ross SA,, Patro RK,, Pati SK,, Reddy MK,, Purser M,, Britt WJ,, Boppana SB. 2009. Enzyme-linked immunosorbent assay method for detection of cytomegalovirus strain-specific antibody responses. Clin Vaccine Immunol 16:288290.
132. Landini MP,, Lazzarotto T,, Maine GT,, Ripalti A,, Flanders R. 1995. Recombinant mono- and polyantigens to detect cytomegalovirus-specific immunoglobulin M in human sera by enzyme immunoassay. J Clin Microbiol 33:25352542.
133. Vornhagen R,, Plachter B,, Hinderer W,, The TH,, van Zanten J,, Matter L,, Schmidt CA,, Sonneborn H-H,, Jahn G. 1994. Early serodiagnosis of acute human cytomegalovirus infection by enzyme-linked immunosorbent assay using recombinant antigens. J Clin Microbiol 32:981986.
134. Grangeot-Keros L,, Mayaux MJ,, Lebon P,, Freymuth F,, Eugene G,, Stricker R,, Dussaix E. 1997. Value of cytomegalovirus (CMV) IgG avidity index for the diagnosis of primary CMV infection in pregnant women. J Infect Dis 175:944946.
135. Lazzarotto T,, Spezzacatena P,, Pradelli P,, Abate DA,, Varani S,, Landini MP. 1997. Avidity of immunoglobulin G directed against human cytomegalovirus during primary and secondary infections in immunocompetent and immunocompromised subjects. Clin Diagn Lab Immunol 4:469473.
136. Lazzarotto T,, Varani S,, Spezzacatena P,, Pradelli P,, Potena L,, Lombardi A,, Ghisetti V,, Gabrielli L,, Abate DA,, Magelli C,, Landini MP. 1998. Delayed acquisition of high-avidity anti-cytomegalovirus antibody is correlated with prolonged antigenemia in solid organ transplant recipients. J Infect Dis 178:11451149.
137. Curdt I,, Praast G,, Sickinger E,, Schultess J,, Herold I,, Braun HB,, Bernhardt S,, Maine GT,, Smith DD,, Hsu S,, Christ HM,, Pucci D,, Hausmann M,, Herzogenrath J. 2009. Development of fully automated determination of marker specific immunoglobulin G (IgG) avidity based on the avidity competition assay format: application for Abbott Architect CMV and Toxo IgG avidity assays. J Clin Microbiol 47:603613.
138. Prince HE,, Leber AL. 2002. Validation of an in-house assay for cytomegalovirus immunoglobulin G (CMV IgG) avidity and relationship of avidity to CMV IgM levels. Clin Diagn Lab Immunol 9:824827.
139. Abate D,, Saldan A,, Mengoli C,, Fiscon M,, Silvestre C,, Fallico L,, Peracchi M,, Furian L,, Cusinato R,, Bonfante L,, Rossi B,, Marchini F,, Sgarabotto D,, Rigotti P,, Palu G. 2013. Comparison of cytomegalovirus (CMV) enzyme-linked immunosorbent spot and CMV quantiferon gamma interferon-releasing assays in assessing risk of CMV infection in kidney transplant recipients. J Clin Microbiol 51:25012507.
140. Lurain NS,, Chou S. 2010. Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev 23:689712.
141. Hakki M,, Chou S. 2011. The biology of cytomegalovirus drug resistance. Curr Opin Infect Dis 24:605611.
142. Le Page AK,, Jager MM,, Iwasenko JM,, Scott GM,, Alain S,, Rawlinson WD. 2013. Clinical aspects of cytomegalovirus antiviral resistance in solid organ transplant recipients. Clin Infect Dis 56:10181029.
143. Arens MQ,, Swierkosz EM,. 2011. Susceptibility test methods: viruses, p 17291743. In Versalovic J,, Carroll KC,, Funke G,, Jorgensen JH,, Landry ML,, Warnock DW (ed), Manual of Clinical Microbiology, 10th ed. ASM Press, Washington, DC.
144. Baldanti F,, Sarasini A,, Silini E,, Barbi M,, Lazzarin A,, Biron KK,, Gerna G. 1995. Four dually resistant human cytomegalovirus strains from AIDS patients: single mutations in UL97 and UL54 open reading frames are responsible for ganciclovir- and foscarnet-specific resistance, respectively. Scand J Infect Dis Suppl 99:103104.
145. Chou S,, Guentzel S,, Michels KR,, Miner RC,, Drew WL. 1995. Frequency of UL97 phosphotransferase mutations related to ganciclovir resistance in clinical cytomegalovirus isolates. J Infect Dis 172:239242.
146. Smith IL,, Cherrington JM,, Jiles RE,, Fuller MD,, Freeman WR,, Spector SA. 1997. High-level resistance of cytomegalovirus to ganciclovir is associated with alterations in both the UL97 and DNA polymerase genes. J Infect Dis 176:6977.
147. Daikoku T,, Saito K,, Aihara T,, Ikeda M,, Takahashi Y,, Hosoi H,, Nishida T,, Takemoto M,, Shiraki K. 2103. Rapid detection of human cytomegalovirus UL97 and UL54 mutations for antiviral resistance in clinical specimens. Microbiol Immunol 57:396399.
148. Hall Sedlak R,, Castor J,, Butler-Wu SM,, Chan E,, Cook L,, Limaye AP,, Jerome KR. 2013. Rapid detection of human cytomegalovirus UL97 and UL54 mutations directly from patient samples. J Clin Microbiol 51:23542359.
149. Sahoo MK,, Lefterova MI,, Yamamoto F,, Waggoner JJ,, Chou S,, Holmes SP,, Anderson MW,, Pinsky BA. 2013. Detection of cytomegalovirus drug resistance mutations by next-generation sequencing. J Clin Microbiol 11:37003710.
150. de Vries JJC,, van der Eijk AA,, Wolthers KC,, Rusman LG,, Pas SD,, Molenkamp R,, Claas EC,, Kroes ACM,, Vossen ACTM. 2012. Real-time PCR versus viral culture on urine as a gold standard in the diagnosis of congenital cytomegalovirus infection. J Clin Virol 53:167170.
151. Lazzarotto T,, Guerra B,, Lanari M,, Gabrielli L,, Landini MP. 2008. New advances in the diagnosis of congenital cytomegalovirus infection. J Clin Virol 41:192197.
152. Boppana SB,, Fowler KB,, Pass RF,, Rivera LB,, Bradford RD,, Lakeman FD,, Britt WJ. 2005. Congenital cytomegalovirus infection: association between virus burden in infancy and hearing loss. J Pediatr 146:817823.
153. Bradford RD,, Cloud G,, Lakeman FD,, Boppana S,, Kimberlin DW,, Jacobs R,, Demmler G,, Sanchez P,, Britt W,, Soong S-J,, Whitley RJ, the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. 2005. Detection of cytomegalovirus (CMV) DNA by polymerase chain reaction is associated with hearing loss in newborns with symptomatic congenital CMV infection involving the central nervous system. J Infect Dis 191:227233.
154. Goegebuer T,, Van Meensel B,, Beuselinck K,, Cossey V,, Van Ranst M,, Hanssens M,, Lagrou K. 2009. Clinical predictive value of real-time PCR quantification of human cytomegalovirus DNA in amniotic fluid samples. J Clin Microbiol 47:660665.

Tables

Generic image for table
TABLE 1

Available commercial CMV antigenemia assays

Citation: Hodinka R. 2015. Human Cytomegalovirus, p 1718-1737. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch100
Generic image for table
TABLE 2

Selected commercial molecular assays available for qualitative and quantitative detection of CMV

Citation: Hodinka R. 2015. Human Cytomegalovirus, p 1718-1737. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch100
Generic image for table
TABLE 3

Immunoassay systems for CMV IgG and IgM antibody detection

Citation: Hodinka R. 2015. Human Cytomegalovirus, p 1718-1737. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch100

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error