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Chapter 4 : Cytomegalovirus

Authors: M. Veronica Dioverti1, Raymund R. Razonable2
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Affiliations: 1: Division of Infectious Diseases, Department of Medicine; 2: Division of Infectious Diseases, Department of Medicine; 3: The William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic College of Medicine, Rochester, MN 55905
Content Type: Monograph
Publication Year: 2016

Category: Clinical Microbiology

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Cytomegalovirus, Page 1 of 2

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Abstract:

Cytomegalovirus (CMV), the fifth member of the human herpesvirus family, is one of the largest viruses known to cause clinical disease. It is a double-stranded DNA virus that belongs to the beta-herpesvirus subfamily, along with human herpesviruses 6A, 6B, and 7. CMV was first associated with an infectious mononucleosis-like illness in healthy individuals in 1965 ( ). Currently, it is known to cause a wide range of clinical syndromes, from asymptomatic infection in healthy hosts, to severe and even fatal disease in immunocompromised individuals, such as transplant recipients.

Citation: Dioverti M, Razonable R. 2016. Cytomegalovirus, p 97-125. In Hayden R, Wolk D, Carroll K, Tang Y (ed),

Diagnostic Microbiology of the Immunocompromised Host, Second Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.DMIH2-0022-2015
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Cytomegalovirus
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Citation: Dioverti M, Razonable R. 2016. Cytomegalovirus, p 97-125. In Hayden R, Wolk D, Carroll K, Tang Y (ed),

Diagnostic Microbiology of the Immunocompromised Host, Second Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.DMIH2-0022-2015
/content/10.1128/9781555819040.chap4.fig4-1
Figure 1

Cytomegalovirus-induced cytopathic effects. Unstained preparation; 100X magnification.

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Figure 1

Cytomegalovirus-induced cytopathic effects. Unstained preparation; 100X magnification.

Citation: Dioverti M, Razonable R. 2016. Cytomegalovirus, p 97-125. In Hayden R, Wolk D, Carroll K, Tang Y (ed),

Diagnostic Microbiology of the Immunocompromised Host, Second Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.DMIH2-0022-2015
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Figure 2

Detection of CMV antigens in the nucleic acid of infected MCR-5 cells. Following shell-vial culture, cells are stained with fluorescently-labeled antibodies which detect CMV immediate early antigen. Magnification 200X.

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Image of Figure 2
Figure 2

Detection of CMV antigens in the nucleic acid of infected MCR-5 cells. Following shell-vial culture, cells are stained with fluorescently-labeled antibodies which detect CMV immediate early antigen. Magnification 200X.

Citation: Dioverti M, Razonable R. 2016. Cytomegalovirus, p 97-125. In Hayden R, Wolk D, Carroll K, Tang Y (ed),

Diagnostic Microbiology of the Immunocompromised Host, Second Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.DMIH2-0022-2015
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Figure 3

This biopsy specimen from a patient with cytomegalovirus colitis shows a classic “owl-eye” intranuclear inclusion (arrow) and intracytoplasmic inclusions. The dense intranuclear inclusion with surrounding halo is formed when the mass of viral particles shrinks away from the nuclear membrane during fixation. While herpes simplex virus intranuclear inclusions can have a similar appearance, CMV is the only member of the herpesviridae family that contains both intranuclear and intracytoplasmic inclusions. Hematoxylin and eosin stain, 1000x oil immersion.

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Image of Figure 3
Figure 3

This biopsy specimen from a patient with cytomegalovirus colitis shows a classic “owl-eye” intranuclear inclusion (arrow) and intracytoplasmic inclusions. The dense intranuclear inclusion with surrounding halo is formed when the mass of viral particles shrinks away from the nuclear membrane during fixation. While herpes simplex virus intranuclear inclusions can have a similar appearance, CMV is the only member of the herpesviridae family that contains both intranuclear and intracytoplasmic inclusions. Hematoxylin and eosin stain, 1000x oil immersion.

Citation: Dioverti M, Razonable R. 2016. Cytomegalovirus, p 97-125. In Hayden R, Wolk D, Carroll K, Tang Y (ed),

Diagnostic Microbiology of the Immunocompromised Host, Second Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.DMIH2-0022-2015
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Figure 4

Immunoperoxidase staining of CMV antigens in a biopsy from a patient with CMV colitis. Viral inclusions stain brown (blue counterstain, 1000x oil immersion).

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Image of Figure 4
Figure 4

Immunoperoxidase staining of CMV antigens in a biopsy from a patient with CMV colitis. Viral inclusions stain brown (blue counterstain, 1000x oil immersion).

Citation: Dioverti M, Razonable R. 2016. Cytomegalovirus, p 97-125. In Hayden R, Wolk D, Carroll K, Tang Y (ed),

Diagnostic Microbiology of the Immunocompromised Host, Second Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.DMIH2-0022-2015
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Figure 5

Diagnostic algorithm for transplant recipients and their donors with the use of CMV serology.

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Figure 5

Diagnostic algorithm for transplant recipients and their donors with the use of CMV serology.

Citation: Dioverti M, Razonable R. 2016. Cytomegalovirus, p 97-125. In Hayden R, Wolk D, Carroll K, Tang Y (ed),

Diagnostic Microbiology of the Immunocompromised Host, Second Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.DMIH2-0022-2015
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Figure 6

An illustrative algorithm utilizing various diagnostic assays in a transplant recipient prior to transplantation and during the period following transplantation.

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Image of Figure 6
Figure 6

An illustrative algorithm utilizing various diagnostic assays in a transplant recipient prior to transplantation and during the period following transplantation.

Citation: Dioverti M, Razonable R. 2016. Cytomegalovirus, p 97-125. In Hayden R, Wolk D, Carroll K, Tang Y (ed),

Diagnostic Microbiology of the Immunocompromised Host, Second Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.DMIH2-0022-2015
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Figure 7

Algorithm for the diagnosis of CMV disease in an immunocompromised patient.

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Image of Figure 7
Figure 7

Algorithm for the diagnosis of CMV disease in an immunocompromised patient.

Citation: Dioverti M, Razonable R. 2016. Cytomegalovirus, p 97-125. In Hayden R, Wolk D, Carroll K, Tang Y (ed),

Diagnostic Microbiology of the Immunocompromised Host, Second Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.DMIH2-0022-2015
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References

/content/book/10.1128/9781555819040.chap4
1. Klemola E,, Kääriäinen L . 1965. Cytomegalovirus as a possible cause of a disease resembling infectious mononucleosis. Br Med J 2 : 1099– 1102.[CrossRef]
2. Razonable RR,, Paya CV,, Smith TF . 2002. Role of the laboratory in diagnosis and management of cytomegalovirus infection in hematopoietic stem cell and solid-organ transplant recipients. J Clin Microbiol 40 : 746– 752.[CrossRef]
3. Bate SL,, Dollard SC,, Cannon MJ . 2010. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988–2004. Clin Infect Dis 50 : 1439– 1447.[CrossRef]
4. Lanzieri TM,, Kruszon-Moran D,, Amin MM,, Bialek SR,, Cannon MJ,, Carroll MD,, Dollard SC . 2015. Seroprevalence of cytomegalovirus among children 1 to 5 years of age in the United States from the National Health and Nutrition Examination Survey of 2011 to 2012. Clin Vaccine Immunol 22 : 245– 247.[CrossRef]
5. Stowell JD,, Forlin-Passoni D,, Din E,, Radford K,, Brown D,, White A,, Bate SL,, Dollard SC,, Bialek SR,, Cannon MJ,, Schmid DS . 2012. Cytomegalovirus survival on common environmental surfaces: opportunities for viral transmission. J Infect Dis 205 : 211– 214.[CrossRef]
6. Ho M,, Suwansirikul S,, Dowling JN,, Youngblood LA,, Armstrong JA . 1975. The transplanted kidney as a source of cytomegalovirus infection. N Engl J Med 293 : 1109– 1112.[CrossRef]
7. Ljungman P,, Hakki M,, Boeckh M . 2011. Cytomegalovirus in hematopoietic stem cell transplant recipients. Hematol Oncol Clin North Am 25 : 151– 169.[CrossRef]
8. Razonable RR,, Hayden RT . 2013. Clinical utility of viral load in management of cytomegalovirus infection after solid organ transplantation. Clin Microbiol Rev 26 : 703– 727.[CrossRef]
9. Kekre N,, Tokessy M,, Mallick R,, McDiarmid S,, Huebsch L,, Bredeson C,, Allan D,, Tay J,, Tinmouth A,, Sheppard D . 2013. Is cytomegalovirus testing of blood products still needed for hematopoietic stem cell transplant recipients in the era of universal leukoreduction? Biol Blood Marrow Transplant 19 : 1719– 1724.[CrossRef]
10. Bowden RA,, Sayers M,, Flournoy N,, Newton B,, Banaji M,, Thomas ED,, Meyers JD . 1986. Cytomegalovirus immune globulin and seronegative blood products to prevent primary cytomegalovirus infection after marrow transplantation. N Engl J Med 314 : 1006– 1010.[CrossRef]
11. Escobar MR,, Allison MJ,, Dalton HP . 1970. Etiology and laboratory diagnosis of infectious mononucleosis: II. Cytomegalovirus (CMV) mononucleosis. Va Med Mon (1918) 97 : 191– 192.
12. Plachter B,, Sinzger C,, Jahn G . 1996. Cell types involved in replication and distribution of human cytomegalovirus. Adv Virus Res 46 : 195– 261.[CrossRef]
13. Vauloup-Fellous C,, Berth M,, Heskia F,, Dugua JM,, Grangeot-Keros L . 2013. Re-evaluation of the VIDAS((R)) cytomegalovirus (CMV) IgG avidity assay: determination of new cut-off values based on the study of kinetics of CMV-IgG maturation. J Clin Virol 56 : 118– 123.[CrossRef]
14. Paya CV,, Razonable RR, . 2003. Cytomegalovirus infection after solid organ transplantation, p 298– 325. In Bowden R,, Ljungman P,, Paya C (ed), Transplant Infections, 2 nd ed, vol 1. Lippincott Williams and Wilkins, Philadelphia, PA.
15. Dunn HS,, Haney DJ,, Ghanekar SA,, Stepick-Biek P,, Lewis DB,, Maecker HT . 2002. Dynamics of CD4 and CD8 T cell responses to cytomegalovirus in healthy human donors. J Infect Dis 186 : 15– 22.[CrossRef]
16. Eid AJ,, Brown RA,, Arthurs SK,, Lahr BD,, Eckel-Passow JE,, Larson RS,, Razonable RR . 2010. A prospective longitudinal analysis of cytomegalovirus (CMV)-specific CD4+ and CD8+ T cells in kidney allograft recipients at risk of CMV infection. Transpl Int 23 : 506– 513.[CrossRef]
17. Watkins RR,, Lemonovich TL,, Razonable RR . 2012. Immune response to CMV in solid organ transplant recipients: current concepts and future directions. Expert Rev Clin Immunol 8 : 383– 393.[CrossRef]
18. Gallant JE,, Moore RD,, Richman DD,, Keruly J,, Chaisson RE . 1992. Incidence and natural history of cytomegalovirus disease in patients with advanced human immunodeficiency virus disease treated with zidovudine. The Zidovudine Epidemiology Study Group. J Infect Dis 166 : 1223– 1227.[CrossRef]
19. Rahhal FM . 1999. Treatment advances for CMV retinitis. AIDS Read 9 : 28, 31–34.
20. Evans TG,, Bonnez W,, Soucier HR,, Fitzgerald T,, Gibbons DC,, Reichman RC . 1998. Highly active antiretroviral therapy results in a decrease in CD8+ T cell activation and preferential reconstitution of the peripheral CD4+ T cell population with memory rather than naive cells. Antiviral Res 39 : 163– 173.[CrossRef]
21. Verbraak FD,, Boom R,, Wertheim-van Dillen PM,, van den Horn GJ,, Kijlstra A,, de Smet MD . 1999. Influence of highly active antiretroviral therapy on the development of CMV disease in HIV positive patients at high risk for CMV disease. Br J Ophthalmol 83 : 1186– 1189.[CrossRef]
22. Ford N,, Shubber Z,, Saranchuk P,, Pathai S,, Durier N,, O’Brien DP,, Mills EJ,, Pascual F,, Hoen E,, Holland GN,, Heiden D . 2013. Burden of HIV-related cytomegalovirus retinitis in resource-limited settings: a systematic review. Clin Infect Dis 57 : 1351– 1361.[CrossRef]
23. Razonable RR,, Humar A ; AST Infectious Diseases Community of Practice . 2013. Cytomegalovirus in solid organ transplantation. Am J Transplant 13( Suppl 4) : 93– 106.[CrossRef]
24. Emery VC,, Hassan-Walker AF,, Burroughs AK,, Griffiths PD . 2002. Human cytomegalovirus (HCMV) replication dynamics in HCMV-naive and -experienced immunocompromised hosts. J Infect Dis 185 : 1723– 1728.[CrossRef]
25. Krogsgaard K,, Boesgaard S,, Aldershvile J,, Arendrup H,, Mortensen SA,, Petterson G . 1994. Cytomegalovirus infection rate among heart transplant patients in relation to anti-thymocyte immunoglobulin induction therapy. Copenhagen Heart Transplant Group. Scand J Infect Dis 26 : 239– 247.[CrossRef]
26. Beam E,, Razonable RR . 2012. Cytomegalovirus in solid organ transplantation: epidemiology, prevention, and treatment. Curr Infect Dis Rep 14 : 633– 641.[CrossRef]
27. Razonable R . 2010. Direct and indirect effects of cytomegalovirus: can we prevent them? Enferm Infecc Microbiol Clin 28 : 1– 5.[CrossRef]
28. George B,, Pati N,, Gilroy N,, Ratnamohan M,, Huang G,, Kerridge I,, Hertzberg M,, Gottlieb D,, Bradstock K . 2010. Pre-transplant cytomegalovirus (CMV) serostatus remains the most important determinant of CMV reactivation after allogeneic hematopoietic stem cell transplantation in the era of surveillance and preemptive therapy. Transpl Infect Dis 12 : 322– 329.[CrossRef]
29. Travi G,, Pergam SA . 2013. Cytomegalovirus pneumonia in hematopoietic stem cell recipients. J Intensive Care Med 29 : 200– 212.[CrossRef]
30. Gooley TA,, Chien JW,, Pergam SA,, Hingorani S,, Sorror ML,, Boeckh M,, Martin PJ,, Sandmaier BM,, Marr KA,, Appelbaum FR,, Storb R,, McDonald GB . 2010. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med 363 : 2091– 2101.[CrossRef]
31. Green ML,, Leisenring W,, Stachel D,, Pergam SA,, Sandmaier BM,, Wald A,, Corey L,, Boeckh M . 2012. Efficacy of a viral load-based, risk-adapted, preemptive treatment strategy for prevention of cytomegalovirus disease after hematopoietic cell transplantation. Biol Blood Marrow Transplant 18 : 1687– 1699.[CrossRef]
32. Nichols WG,, Corey L,, Gooley T,, Davis C,, Boeckh M . 2002. High risk of death due to bacterial and fungal infection among cytomegalovirus (CMV)-seronegative recipients of stem cell transplants from seropositive donors: evidence for indirect effects of primary CMV infection. J Infect Dis 185 : 273– 282.[CrossRef]
33. Hebart H,, Jahn G,, Sinzger C,, Kanz L,, Einsele H . 2000. CMV infection in bone marrow and solid organ transplant patients in the era of antiviral prophylaxis. Herpes 7 : 13– 17.
34. Boeckh M,, Nichols WG . 2004. The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy. Blood 103 : 2003– 2008.[CrossRef]
35. Stagno S,, Pass RF,, Cloud G,, Britt WJ,, Henderson RE,, Walton PD,, Veren DA,, Page F,, Alford CA . 1986. Primary cytomegalovirus infection in pregnancy. Incidence, transmission to fetus, and clinical outcome. JAMA 256 : 1904– 1908.[CrossRef]
36. Boppana SB,, Rivera LB,, Fowler KB,, Mach M,, Britt WJ . 2001. Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity. N Engl J Med 344 : 1366– 1371.[CrossRef]
37. Boppana SB,, Ross SA,, Fowler KB . 2013. Congenital cytomegalovirus infection: clinical outcome. Clin Infect Dis 57( Suppl 4) : S178– S181.[CrossRef]
38. Ross SA,, Novak Z,, Pati S,, Boppana SB . 2011. Overview of the diagnosis of cytomegalovirus infection. Infect Disord Drug Targets 11 : 466– 474.[CrossRef]
39. Faderl S,, Thomas DA,, O’Brien S,, Garcia-Manero G,, Kantarjian HM,, Giles FJ,, Koller C,, Ferrajoli A,, Verstovsek S,, Pro B,, Andreeff M,, Beran M,, Cortes J,, Wierda W,, Tran N,, Keating MJ . 2003. Experience with alemtuzumab plus rituximab in patients with relapsed and refractory lymphoid malignancies. Blood 101 : 3413– 3415.[CrossRef]
40. Garrido E,, Carrera E,, Manzano R,, Lopez-Sanroman A . 2013. Clinical significance of cytomegalovirus infection in patients with inflammatory bowel disease. World J Gastroenterol 19 : 17– 25.[CrossRef]
41. Kim JJ,, Simpson N,, Klipfel N,, Debose R,, Barr N,, Laine L . 2010. Cytomegalovirus infection in patients with active inflammatory bowel disease. Dig Dis Sci 55 : 1059– 1065.[CrossRef]
42. Maher MM,, Nassar MI . 2009. Acute cytomegalovirus infection is a risk factor in refractory and complicated inflammatory bowel disease. Dig Dis Sci 54 : 2456– 2462.[CrossRef]
43. Asberg A,, Humar A,, Rollag H,, Jardine AG,, Mouas H,, Pescovitz MD,, Sgarabotto D,, Tuncer M,, Noronha IL,, Hartmann A ; VICTOR Study Group . 2007. Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 7 : 2106– 2113.[CrossRef]
44. 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 : 1546– 1553.[CrossRef]
45. Sia IG,, Wilson JA,, Groettum CM,, Espy MJ,, Smith TF,, Paya CV . 2000. Cytomegalovirus (CMV) DNA load predicts relapsing CMV infection after solid organ transplantation. J Infect Dis 181 : 717– 720.[CrossRef]
46. Razonable RR,, Paya CV . 2004. Valganciclovir for the prevention and treatment of cytomegalovirus disease in immunocompromised hosts. Expert Rev Anti Infect Ther 2 : 27– 41.[CrossRef]
47. Painter W,, Robertson A,, Trost LC,, Godkin S,, Lampert B,, Painter G . 2012. First pharmacokinetic and safety study in humans of the novel lipid antiviral conjugate CMX001, a broad-spectrum oral drug active against double-stranded DNA viruses. Antimicrob Agents Chemother 56 : 2726– 2734.[CrossRef]
48. Marty FM,, Winston DJ,, Rowley SD,, Vance E,, Papanicolaou GA,, Mullane KM,, Brundage TM,, Robertson AT,, Godkin S,, Momméja-Marin H,, Boeckh M ; CMX001-201 Clinical Study Group . 2013. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med 369 : 1227– 1236.[CrossRef]
49. Stoelben S,, Arns W,, Renders L,, Hummel J,, Muhlfeld A,, Stangl M,, Fischereder M,, Gwinner W,, Suwelack B,, Witzke O,, Dürr M,, Beelen DW,, Michel D,, Lischka P,, Zimmermann H,, Rübsamen-Schaeff H,, Budde K . 2014. Preemptive treatment of cytomegalovirus infection in kidney transplant recipients with letermovir: results of a phase 2a study. Transpl Int 27 : 77– 86.[CrossRef]
50. Winston DJ,, Saliba F,, Blumberg E,, Abouljoud M,, Garcia-Diaz JB,, Goss JA,, Clough L,, Avery R,, Limaye AP,, Ericzon BG,, Navasa M,, Troisi RI,, Chen H,, Villano SA,, Uknis ME ; 1263-301 Clinical Study Group . 2012. Efficacy and safety of maribavir dosed at 100 mg orally twice daily for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, double-blind, multicenter controlled trial. Am J Transplant 12 : 3021– 3030.[CrossRef]
51. Gleaves CA,, Smith TF,, Shuster EA,, Pearson GR . 1985. Comparison of standard tube and shell vial cell culture techniques for the detection of cytomegalovirus in clinical specimens. J Clin Microbiol 21 : 217– 221.
52. Paya CV,, Smith TF,, Ludwig J,, Hermans PE . 1989. Rapid shell vial culture and tissue histology compared with serology for the rapid diagnosis of cytomegalovirus infection in liver transplantation. Mayo Clin Proc 64 : 670– 675.[CrossRef]
53. Shuster EA,, Beneke JS,, Tegtmeier GE,, Pearson GR,, Gleaves CA,, Wold AD,, Smith TF . 1985. Monoclonal antibody for rapid laboratory detection of cytomegalovirus infections: characterization and diagnostic application. Mayo Clin Proc 60 : 577– 585.[CrossRef]
54. Paya CV,, Holley KE,, Wiesner RH,, Balasubramaniam K,, Smith TF,, Espy MJ,, Ludwig J,, Batts KP,, Hermans PE,, Krom RA . 1990. Early diagnosis of cytomegalovirus hepatitis in liver transplant recipients: role of immunostaining, DNA hybridization and culture of hepatic tissue. Hepatology 12 : 119– 126.[CrossRef]
55. Denijn M,, Schuurman HJ,, Jacobse KC,, De Weger RA . 1992. In situ hybridization: a valuable tool in diagnostic pathology. APMIS 100 : 669– 681.[CrossRef]
56. McClintock JT,, Thaker SR,, Mosher M,, Jones D,, Forman M,, Charache P,, Wright K,, Keiser J,, Taub FE . 1989. Comparison of in situ hybridization and monoclonal antibodies for early detection of cytomegalovirus in cell culture. J Clin Microbiol 27 : 1554– 1559.
57. Delforge ML,, Desomberg L,, Montesinos I . 2015. Evaluation of the new LIAISON CMV IgG, IgM and IgG Avidity II assays. J Clin Virol 72 : 42– 45.[CrossRef]
58. 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 : 469– 473.
59. Crough T,, Khanna R . 2009. Immunobiology of human cytomegalovirus: from bench to bedside. Clin Microbiol Rev 22 : 76– 98.[CrossRef]
60. Abate D,, Saldan A,, Fiscon M,, Cofano S,, Paciolla A,, Furian L,, Ekser B,, Biasolo MA,, Cusinato R,, Mengoli C,, Bonfante L,, Rossi B,, Rigotti P,, Sgarabotto D,, Barzon L,, Palù G . 2010. Evaluation of cytomegalovirus (CMV)-specific T cell immune reconstitution revealed that baseline antiviral immunity, prophylaxis, or preemptive therapy but not antithymocyte globulin treatment contribute to CMV-specific T cell reconstitution in kidney transplant recipients. J Infect Dis 202 : 585– 594.[CrossRef]
61. Kumar D,, Chernenko S,, Moussa G,, Cobos I,, Manuel O,, Preiksaitis J,, Venkataraman S,, Humar A . 2009. Cell-mediated immunity to predict cytomegalovirus disease in high-risk solid organ transplant recipients. Am J Transplant 9 : 1214– 1222.[CrossRef]
62. Lisboa LF,, Kumar D,, Wilson LE,, Humar A . 2012. Clinical utility of cytomegalovirus cell-mediated immunity in transplant recipients with cytomegalovirus viremia. Transplantation 93 : 195– 200.[CrossRef]
63. Manuel O,, Husain S,, Kumar D,, Zayas C,, Mawhorter S,, Levi ME,, Kalpoe J,, Lisboa L,, Ely L,, Kaul DR,, Schwartz BS,, Morris MI,, Ison MG,, Yen-Lieberman B,, Sebastian A,, Assi M,, Humar A . 2013. Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study. Nephrol Dial Transplant 56 : 817– 824.[CrossRef]
64. Cantisán S,, Lara R,, Montejo M,, Redel J,, Rodríguez-Benot A,, Gutiérrez-Aroca J,, González-Padilla M,, Bueno L,, Rivero A,, Solana R,, Torre-Cisneros J . 2013. Pretransplant interferon-γ secretion by CMV-specific CD8+ T cells informs the risk of CMV replication after transplantation. Am J Transplant 13 : 738– 745.[CrossRef]
65. Tey SK,, Kennedy GA,, Cromer D,, Davenport MP,, Walker S,, Jones LI,, Crough T,, Durrant ST,, Morton JA,, Butler JP,, Misra AK,, Hill GR,, Khanna R . 2013. Clinical assessment of anti-viral CD8+ T cell immune monitoring using QuantiFERON-CMV(R) assay to identify high risk allogeneic hematopoietic stem cell transplant patients with CMV infection complications. PLoS One 8 : e74744. doi:10.1371/journal.pone.0074744 [CrossRef]
66. 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 : 1430– 1433.
67. Lautenschlager I,, Halme L,, Höckerstedt K,, Krogerus L,, Taskinen E . 2006. Cytomegalovirus infection of the liver transplant: virological, histological, immunological, and clinical observations. Transpl Infect Dis 8 : 21– 30.[CrossRef]
68. St George K,, Rinaldo CR Jr . 1999. Comparison of cytomegalovirus antigenemia and culture assays in patients on and off antiviral therapy. J Med Virol 59 : 91– 97.[CrossRef]
69. Wolf DG,, Spector SA . 1993. Early diagnosis of human cytomegalovirus disease in transplant recipients by DNA amplification in plasma. Transplantation 56 : 330– 334.[CrossRef]
70. Garrigue I,, Doussau A,, Asselineau J,, Bricout H,, Couzi L,, Rio C,, Merville P,, Fleury H,, Lafon ME,, Thiébaut R . 2008. Prediction of cytomegalovirus (CMV) plasma load from evaluation of CMV whole-blood load in samples from renal transplant recipients. J Clin Microbiol 46 : 493– 498.[CrossRef]
71. Allice T,, Enrietto M,, Pittaluga F,, Varetto S,, Franchello A,, Marchiaro G,, Ghisetti V . 2006. Quantitation of cytomegalovirus DNA by real-time polymerase chain reaction in peripheral blood specimens of patients with solid organ transplants: comparison with end-point PCR and pp65 antigen test. J Med Virol 78 : 915– 922.[CrossRef]
72. Larsson S,, Söderberg-Naucler C,, Wang FZ,, Moller E . 1998. Cytomegalovirus DNA can be detected in peripheral blood mononuclear cells from all seropositive and most seronegative healthy blood donors over time. Transfusion 38 : 271– 278.[CrossRef]
73. Hebart H,, Lengerke C,, Ljungman P,, Paya CV,, Klingebiel T,, Loeffler J,, Pfaffenrath S,, Lewensohn-Fuchs I,, Barkholt L,, Tomiuk J,, Meisner C,, Lunenberg J,, Top B,, Razonable RR,, Patel R,, Litzow MR,, Jahn G,, Einsele H . 2011. Prospective comparison of PCR-based vs late mRNA-based preemptive antiviral therapy for HCMV infection in patients after allo-SCT. Bone Marrow Transplant 46 : 408– 415.[CrossRef]
74. Schäfer 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 : 741– 744.
75. 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 : 222– 224.[CrossRef]
76. Hayden RT,, Yan X,, Wick MT,, Rodriguez AB,, Xiong X,, Ginocchio CC,, Mitchell MJ,, Caliendo AM ; College of American Pathologists Microbiology Resource Committee . 2012. Factors contributing to variability of quantitative viral PCR results in proficiency testing samples: a multivariate analysis. J Clin Microbiol 50 : 337– 345.[CrossRef]
77. Gerna G,, Baldanti F,, Lilleri D,, Parea M,, Torsellini M,, Castiglioni B,, Vitulo P,, Pellegrini C,, Viganò M,, Grossi P,, Revello MG . 2003. Human cytomegalovirus pp67 mRNAemia versus pp65 antigenemia for guiding preemptive therapy in heart and lung transplant recipients: a prospective, randomized, controlled, open-label trial. Transplantation 75 : 1012– 1019.[CrossRef]
78. Revello MG,, Lilleri D,, Zavattoni M,, Stronati M,, Bollani L,, Middeldorp JM,, Gerna G . 2001. Human cytomegalovirus immediate-early messenger RNA in blood of pregnant women with primary infection and of congenitally infected newborns. J Infect Dis 184 : 1078– 1081.[CrossRef]
79. Gerna G,, Baldanti F,, Lilleri D,, Parea M,, Alessandrino E,, Pagani A,, Locatelli F,, Middeldorp J,, Revello MG . 2000. Human cytomegalovirus immediate-early mRNA detection by nucleic acid sequence-based amplification as a new parameter for preemptive therapy in bone marrow transplant recipients. J Clin Microbiol 38 : 1845– 1853.
80. Randhawa PS,, Manez R,, Frye B,, Ehrlich GD . 1994. Circulating immediate-early mRNA in patients with cytomegalovirus infections after solid organ transplantation. J Infect Dis 170 : 1264– 1267.[CrossRef]
81. Gozlan J,, Salord JM,, Chouaïd C,, Duvivier C,, Picard O,, Meyohas MC,, Petit JC . 1993. Human cytomegalovirus (HCMV) late-mRNA detection in peripheral blood of AIDS patients: diagnostic value for HCMV disease compared with those of viral culture and HCMV DNA detection. J Clin Microbiol 31 : 1943– 1945.
82. Paya CV,, Wilson JA,, Espy MJ,, Sia IG,, DeBernardi MJ,, Smith TF,, Patel R,, Jenkins G,, Harmsen WS,, Vanness DJ,, Wiesner RH . 2002. Preemptive use of oral ganciclovir to prevent cytomegalovirus infection in liver transplant patients: a randomized, placebo-controlled trial. J Infect Dis 185 : 854– 860.[CrossRef]
83. Meyer-Koenig U,, Weidmann M,, Kirste G,, Hufert FT . 2004. Cytomegalovirus infection in organ-transplant recipients: diagnostic value of pp65 antigen test, qualitative polymerase chain reaction (PCR) and quantitative Taqman PCR. Transplantation 77 : 1692– 1698.[CrossRef]
84. Hirsch HH,, Lautenschlager I,, Pinsky BA,, Cardeñoso L,, Aslam S,, Cobb B,, Vilchez RA,, Valsamakis A . 2013. An international multicenter performance analysis of cytomegalovirus load tests. Clin Infect Dis 56 : 367– 373.[CrossRef]
85. Emery VC,, Cope AV,, Bowen EF,, Gor D,, Griffiths PD . 1999. The dynamics of human cytomegalovirus replication in vivo . J Exp Med 190 : 177– 182.[CrossRef]
86. Emery VC,, Sabin CA,, Cope AV,, Gor D,, Hassan-Walker AF,, Griffiths PD . 2000. Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation. Lancet 355 : 2032– 2036.[CrossRef]
87. Humar A,, Kumar D,, Boivin G,, Caliendo AM . 2002. Cytomegalovirus (CMV) virus load kinetics to predict recurrent disease in solid-organ transplant patients with CMV disease. J Infect Dis 186 : 829– 833.[CrossRef]
88. 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 : 4472– 4476.[CrossRef]
89. Razonable RR,, Brown RA,, Wilson J,, Groettum C,, Kremers W,, Espy M,, Smith TF,, Paya CV . 2002. The clinical use of various blood compartments for cytomegalovirus (CMV) DNA quantitation in transplant recipients with CMV disease. Transplantation 73 : 968– 973.[CrossRef]
90. Razonable RR,, van Cruijsen H,, Brown RA,, Wilson JA,, Harmsen WS,, Wiesner RH,, Smith TF,, Paya CV . 2003. Dynamics of cytomegalovirus replication during preemptive therapy with oral ganciclovir. J Infect Dis 187 : 1801– 1808.[CrossRef]
91. 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 : 2709– 2717.
92. Garrigue I,, Boucher S,, Couzi L,, Caumont A,, Dromer C,, Neau-Cransac M,, Tabrizi R,, Schrive MH,, Fleury H,, Lafon ME . 2006. Whole blood real-time quantitative PCR for cytomegalovirus infection follow-up in transplant recipients. J Clin Virol 36 : 72– 75.[CrossRef]
93. 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 : 231– 236.[CrossRef]
94. Saltzman RL,, Quirk MR,, Jordan MC . 1992. High levels of circulating cytomegalovirus DNA reflect visceral organ disease in viremic immunosuppressed patients other than marrow recipients. J Clin Invest 90 : 1832– 1838.[CrossRef]
95. Cunningham R,, Harris A,, Frankton A,, Irving W . 1995. Detection of cytomegalovirus using PCR in serum from renal transplant recipients. J Clin Pathol 48 : 575– 577.[CrossRef]
96. Eckart P,, Brouard J,, Vabret A,, Freymuth F,, Guillot M,, Ryckelynck JP,, Hurault de Ligny B . 1997. Detection of human cytomegalovirus in renal transplantation: comparison of four diagnostic methods: DNA in sera by polymerase chain reaction (PCR), DNA in leukocyte by PCR, pp65 leukocytic antigenemia, and viremia. Transplant Proc 29 : 2387– 2389.[CrossRef]
97. Evans PC,, Soin A,, Wreghitt TG,, Alexander GJ . 1998. Qualitative and semiquantitative polymerase chain reaction testing for cytomegalovirus DNA in serum allows prediction of CMV related disease in liver transplant recipients. J Clin Pathol 51 : 914– 921.[CrossRef]
98. Boeckh M,, Huang M,, Ferrenberg J,, Stevens-Ayers T,, Stensland L,, Nichols WG,, Corey L . 2004. Optimization of quantitative detection of cytomegalovirus DNA in plasma by real-time PCR. J Clin Microbiol 42 : 1142– 1148.[CrossRef]
99. Preiser W,, Rabenau HF,, Vogel JU,, Brixner V,, Doerr HW . 2002. Performance characteristics of an automated PCR assay for the quantification of cytomegalovirus DNA in plasma. J Virol Methods 101 : 149– 157.[CrossRef]
100. 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 : 1275– 1279.[CrossRef]
101. Shinkai M,, Spector SA . 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 : 559– 561.[CrossRef]
102. Arribas JR,, Clifford DB,, Fichtenbaum CJ,, Commins DL,, Powderly WG,, Storch GA . 1995. Level of cytomegalovirus (CMV) DNA in cerebrospinal fluid of subjects with AIDS and CMV infection of the central nervous system. J Infect Dis 172 : 527– 531.[CrossRef]
103. Eid AJ,, Bakri SJ,, Kijpittayarit S,, Razonable RR . 2008. Clinical features and outcomes of cytomegalovirus retinitis after transplantation. Transpl Infect Dis 10 : 13– 18.[CrossRef]
104. Harper TW,, Miller D,, Schiffman JC,, Davis JL . 2009. Polymerase chain reaction analysis of aqueous and vitreous specimens in the diagnosis of posterior segment infectious uveitis. Am J Ophthalmol 147 : 140– 147. e142.[CrossRef]
105. Kerschner H,, Jaksch P,, Karigl G,, Popow-Kraupp T,, Klepetko W,, Puchhammer-Stöckl E . 2009. Cytomegalovirus DNA load patterns developing after lung transplantation are significantly correlated with long-term patient survival. Transplantation 87 : 1720– 1726.[CrossRef]
106. Chemaly RF,, Yen-Lieberman B,, Castilla EA,, Reilly A,, Arrigain S,, Farver C,, Avery RK,, Gordon SM,, Procop GW . 2004. Correlation between viral loads of cytomegalovirus in blood and bronchoalveolar lavage specimens from lung transplant recipients determined by histology and immunohistochemistry. J Clin Microbiol 42 : 2168– 2172.[CrossRef]
107. Chemaly RF,, Yen-Lieberman B,, Chapman J,, Reilly A,, Bekele BN,, Gordon SM,, Procop GW,, Shrestha N,, Isada CM,, Decamp M,, Avery RK . 2005. Clinical utility of cytomegalovirus viral load in bronchoalveolar lavage in lung transplant recipients. Am J Transplant 5 : 544– 548.[CrossRef]
108. Kotsimbos AT,, Sinickas V,, Glare EM,, Esmore DS,, Snell GI,, Walters EH,, Williams TJ . 1997. Quantitative detection of human cytomegalovirus DNA in lung transplant recipients. Am J Respir Crit Care Med 156 : 1241– 1246.[CrossRef]
109. Stéphan F,, Fajac A,, Grenet D,, Honderlick P,, Ricci S,, Frachon I,, Friard S,, Caubarrere I,, Bernaudin JF,, Stern M . 1997. Predictive value of cytomegalovirus DNA detection by polymerase chain reaction in blood and bronchoalveolar lavage in lung transplant patients. Transplantation 63 : 1430– 1435.[CrossRef]
110. Kerschner H,, Jaksch P,, Zweytick B,, Puchhammer-Stöckl E . 2010. Detection of human cytomegalovirus in bronchoalveolar lavage fluid of lung transplant recipients reflects local virus replication and not contamination from the throat. J Clin Microbiol 48 : 4273– 4274.[CrossRef]
111. Costa C,, Delsedime L,, Solidoro P,, Curtoni A,, Bergallo M,, Libertucci D,, Baldi S,, Rinaldi M,, Cavallo R . 2010. Herpesviruses detection by quantitative real-time polymerase chain reaction in bronchoalveolar lavage and transbronchial biopsy in lung transplant: viral infections and histopathological correlation. Transplant Proc 42 : 1270– 1274.[CrossRef]
112. Evans PC,, Gray J,, Wreghitt TG,, Alexander GJ . 1998. Optimisation of the polymerase chain reaction and dot-blot hybridisation for detecting cytomegalovirus DNA in urine: comparison with detection of early antigen fluorescent foci and culture. J Virol Methods 73 : 41– 52.[CrossRef]
113. Cope AV,, Sweny P,, Sabin C,, Rees L,, Griffiths PD,, Emery VC . 1997. Quantity of cytomegalovirus viruria is a major risk factor for cytomegalovirus disease after renal transplantation. J Med Virol 52 : 200– 205.[CrossRef]
114. Sia IG,, Patel R . 2000. New strategies for prevention and therapy of cytomegalovirus infection and disease in solid-organ transplant recipients. Clin Microbiol Rev 13 : 83– 121.[CrossRef]
115. Yerly S,, Perrin L,, Van Delden C,, Schaffer S,, Thamm S,, Wunderli W,, Kaiser L . 2007. Cytomegalovirus quantification in plasma by an automated real-time PCR assay. J Clin Virol 38 : 298– 303.[CrossRef]
116. 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 : 147– 154.[CrossRef]
117. Piiparinen H,, Höckerstedt K,, Grönhagen-Riska C,, Lautenschlager I . 2004. Comparison of two quantitative CMV PCR tests, Cobas Amplicor CMV Monitor and TaqMan assay, and pp65-antigenemia assay in the determination of viral loads from peripheral blood of organ transplant patients. J Clin Virol 30 : 258– 266.[CrossRef]
118. Pang XL,, Chui L,, Fenton J,, LeBlanc B,, Preiksaitis JK . 2003. Comparison of LightCycler-based PCR, COBAS amplicor CMV monitor, and pp65 antigenemia assays for quantitative measurement of cytomegalovirus viral load in peripheral blood specimens from patients after solid organ transplantation. J Clin Microbiol 41 : 3167– 3174.[CrossRef]
119. Pang XL,, Fox JD,, Fenton JM,, Miller GG,, Caliendo AM,, Preiksaitis JK ; Canadian Society of Transplantation . 2009. Interlaboratory comparison of cytomegalovirus viral load assays. Am J Transplant 9 : 258– 268.[CrossRef]
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: a report of the association for molecular pathology. J Mol Diagn 11 : 87– 92.[CrossRef]
121. Fryer JF,, Heath AB,, Anderson R,, Minor PD ; Collaborative Study Group . 2010. Collaborative study to evaluate the proposed 1st WHO international standard for human cytomegalovirus for nucleic acid amplification-based assays. WHO/BS/10.2138. http://www.who.int/iris/handle/10665/70521
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 : 177– 185.[CrossRef]
123. Hayden RT,, Preiksaitis J,, Tong Y,, Pang X,, Sun Y,, Tang L,, Cook L,, Pounds S,, Fryer J,, Caliendo AM . 2015. Commutability of the First World Health Organization International Standard for Human Cytomegalovirus. J Clin Microbiol 53 : 3325– 3333.[CrossRef]
124. Furione M,, Rognoni V,, Cabano E,, Baldanti F . 2012. Kinetics of human cytomegalovirus (HCMV) DNAemia in transplanted patients expressed in international units as determined with the Abbott RealTime CMV assay and an in-house assay. J Clin Virol 55 : 317– 322.[CrossRef]
125. Jabs DA,, Martin BK,, Forman MS,, Hubbard L,, Dunn JP,, Kempen JH,, Davis JL,, Weinberg DV ; Cytomegalovirus Retinitis and Viral Resistance Study Group . 2003. Cytomegalovirus resistance to ganciclovir and clinical outcomes of patients with cytomegalovirus retinitis. Am J Ophthalmol 135 : 26– 34.[CrossRef]
126. Eckle T,, Jahn G,, Hamprecht K . 2004. The influence of mixed HCMV UL97 wildtype and mutant strains on ganciclovir susceptibility in a cell associated plaque reduction assay. J Clin Virol 30 : 50– 56.[CrossRef]
127. Lurain NS,, Weinberg A,, Crumpacker CS,, Chou S ; Adult AIDS Clinical Trials Group-CMV Laboratories . 2001. Sequencing of cytomegalovirus UL97 gene for genotypic antiviral resistance testing. Antimicrob Agents Chemother 45 : 2775– 2780.[CrossRef]
128. Erice A,, Gil-Roda C,, Pérez JL,, Balfour HH Jr,, Sannerud KJ,, Hanson MN,, Boivin G,, Chou S . 1997. Antiviral susceptibilities and analysis of UL97 and DNA polymerase sequences of clinical cytomegalovirus isolates from immunocompromised patients. J Infect Dis 175 : 1087– 1092.[CrossRef]
129. Boivin G,, Chou S,, Quirk MR,, Erice A,, Jordan MC . 1996. Detection of ganciclovir resistance mutations quantitation of cytomegalovirus (CMV) DNA in leukocytes of patients with fatal disseminated CMV disease. J Infect Dis 173 : 523– 528.[CrossRef]
130. Kasprzak A,, Zabel M,, Wysocki J,, Biczysko W,, Surdyk-Zasada J,, Olejnik A,, Gorczyński J,, Jurczyszyn D . 2000. Detection of DNA, mRNA and early antigen of the human cytomegalovirus using the immunomax technique in autopsy material of children with intrauterine infection. Virchows Arch 437 : 482– 490.[CrossRef]
131. Wood NB,, Sheikholeslami M,, Pool M,, Coon JS . 1994. PCR production of a digoxigenin-labeled probe for the detection of human cytomegalovirus in tissue sections. Diagn Mol Pathol 3 : 200– 208.[CrossRef]
132. Mills AM,, Guo FP,, Copland AP,, Pai RK,, Pinsky BA . 2013. A comparison of CMV detection in gastrointestinal mucosal biopsies using immunohistochemistry and PCR performed on formalin-fixed, paraffin-embedded tissue. Am J Surg Pathol 37 : 995– 1000.[CrossRef]
133. Humar A,, Mazzulli T,, Moussa G,, Razonable RR,, Paya CV,, Pescovitz MD,, Covington E,, Alecock E ; Valganciclovir Solid Organ Transplant Study Group . 2005. Clinical utility of cytomegalovirus (CMV) serology testing in high-risk CMV D+/R- transplant recipients. Am J Transplant 5 : 1065– 1070.[CrossRef]
134. Bradford RD,, Cloud G,, Lakeman AD,, Boppana S,, Kimberlin DW,, Jacobs R,, Demmler G,, Sanchez P,, Britt W,, Soong SJ,, Whitley RJ ; 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 : 227– 233.[CrossRef]
135. Hebart H,, Rudolph T,, Loeffler J,, Middeldorp J,, Ljubicic T,, Jahn G,, Einsele H . 2002. Evaluation of the NucliSens CMV pp67 assay for detection and monitoring of human cytomegalovirus infection after allogeneic stem cell transplantation. Bone Marrow Transplant 30 : 181– 187.[CrossRef]
136. Loginov R,, Höckerstedt K,, Lautenschlager I . 2003. Detection of CMV-DNA in peripheral blood leukocytes of liver transplant patients after ganciclovir treatment. Arch Virol 148 : 1269– 1274.
137. Mengoli C,, Cusinato R,, Biasolo MA,, Cesaro S,, Parolin C,, Palù G . 2004. Assessment of CMV load in solid organ transplant recipients by pp65 antigenemia and real-time quantitative DNA PCR assay: correlation with pp67 RNA detection. J Med Virol 74 : 78– 84.[CrossRef]
138. Feinberg J . 1996. The status of CMV viral load testing. AIDS Clin Care 8 : 81.
139. Boivin G . 2004. Diagnosis of herpesvirus infections of the central nervous system. Herpes 11( Suppl 2) : 48A– 56A.
140. Griffiths P . 2004. Cytomegalovirus infection of the central nervous system. Herpes 11( Suppl 2) : 95A– 104A.
141. Barbi M,, Binda S,, Caroppo S . 2006. Diagnosis of congenital CMV infection via dried blood spots. Rev Med Virol 16 : 385– 392.[CrossRef]
142. Barbi M,, Binda S,, Primache V,, Caroppo S,, Didò P,, Guidotti P,, Corbetta C,, Melotti D . 2000. Cytomegalovirus DNA detection in Guthrie cards: a powerful tool for diagnosing congenital infection. J Clin Virol 17 : 159– 165.[CrossRef]
143. Humar A,, Gregson D,, Caliendo AM,, McGeer A,, Malkan G,, Krajden M,, Corey P,, Greig P,, Walmsley S,, Levy G,, Mazzulli T . 1999. Clinical utility of quantitative cytomegalovirus viral load determination for predicting cytomegalovirus disease in liver transplant recipients. Transplantation 68 : 1305– 1311.[CrossRef]
144. Razonable RR,, Emery VC ; 11th Annual Meeting of the IHMF (International Herpes Management Forum) . 2004. Management of CMV infection and disease in transplant patients. 27–29 February 2004. Herpes 11 : 77– 86.
145. Yamamoto N,, Wakabayashi T,, Murakami K,, Hommura S . 2003. Detection of CMV DNA in the aqueous humor of AIDS patients with CMV retinitis by AMPLICOR CMV test. Ophthalmologica 217 : 45– 48.[CrossRef]
146. Jabs DA,, Martin BK,, Forman MS,, Ricks MO ; Cytomegalovirus Retinitis and Viral Resistance Research Group . 2005. Cytomegalovirus (CMV) blood DNA load, CMV retinitis progression, and occurrence of resistant CMV in patients with CMV retinitis. J Infect Dis 192 : 640– 649.[CrossRef]
147. Erice A,, Tierney C,, Hirsch M,, Caliendo AM,, Weinberg A,, Kendall MA,, Polsky B ; AIDS Clinical Trials Group Protocol 360 Study Team . 2003. Cytomegalovirus (CMV) and human immunodeficiency virus (HIV) burden, CMV end-organ disease, and survival in subjects with advanced HIV infection (AIDS Clinical Trials Group Protocol 360). Clin Infect Dis 37 : 567– 578.[CrossRef]
148. Wohl DA,, Kendall MA,, Andersen J,, Crumpacker C,, Spector SA,, Feinberg J,, Alston-Smith B,, Owens S,, Chafey S,, Marco M,, Maxwell S,, Lurain N,, Jabs D,, Benson C,, Keiser P,, Jacobson MA ; A5030 Study Team . 2009. Low rate of CMV end-organ disease in HIV-infected patients despite low CD4+ cell counts and CMV viremia: results of ACTG protocol A5030. HIV Clin Trials 10 : 143– 152.[CrossRef]
149. Mizushima D,, Nishijima T,, Gatanaga H,, Tsukada K,, Teruya K,, Kikuchi Y,, Oka S . 2013. Preemptive therapy prevents cytomegalovirus end-organ disease in treatment-naïve patients with advanced HIV-1 infection in the HAART era. PLoS One 8 : e65348. doi:10.1371/journal.pone.0065348
150. Patil AJ,, Sharma A,, Kenney MC,, Kuppermann BD . 2010. Valganciclovir in the treatment of cytomegalovirus retinitis in HIV-infected patients. Clin Ophthalmol 4 : 111– 119.
151. Drago L,, Lombardi A,, De Vecchi E,, Giuliani G,, Bartolone R,, Gismondo MR . 2004. Comparison of nested PCR and real time PCR of Herpesvirus infections of central nervous system in HIV patients. BMC Infect Dis 4 : 55. [CrossRef]
152. Cheung TW,, Teich SA . 1999. Cytomegalovirus infection in patients with HIV infection. Mt Sinai J Med 66 : 113– 124.
153. Emery V,, Zuckerman M,, Jackson G,, Aitken C,, Osman H,, Pagliuca A,, Potter M,, Peggs K,, Clark A ; British Committee for Standards in Haematology; British Society of Blood and Marrow Transplantation; UK Virology Network . 2013. Management of cytomegalovirus infection in haemopoietic stem cell transplantation. Br J Haematol 162 : 25– 39.[CrossRef]
154. Ariza-Heredia EJ,, Nesher L,, Chemaly RF . 2014. Cytomegalovirus diseases after hematopoietic stem cell transplantation: a mini-review. Cancer Lett 342 : 1– 8.[CrossRef]
155. Kakugawa Y,, Kami M,, Kozu T,, Kobayashi N,, Shoda H,, Matsuda T,, Saito Y,, Oda I,, Gotoda T,, Mori S,, Tanosaki R,, Murashige N,, Hamaki T,, Mineishi S,, Takaue Y,, Shimoda T,, Saito D . 2006. Endoscopic evaluation for cytomegalovirus enterocolitis after allogeneic haematopoietic stem cell transplantation. Gut 55 : 895– 896.[CrossRef]
156. Mori T,, Mori S,, Kanda Y,, Yakushiji K,, Mineishi S,, Takaue Y,, Gondo H,, Harada M,, Sakamaki H,, Yajima T,, Iwao Y,, Hibi T,, Okamoto S . 2004. Clinical significance of cytomegalovirus (CMV) antigenemia in the prediction and diagnosis of CMV gastrointestinal disease after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 33 : 431– 434.[CrossRef]
157. Reddy SM,, Winston DJ,, Territo MC,, Schiller GJ . 2010. CMV central nervous system disease in stem-cell transplant recipients: an increasing complication of drug-resistant CMV infection and protracted immunodeficiency. Bone Marrow Transplant 45 : 979– 984.[CrossRef]
158. Wu M,, Huang F,, Jiang X,, Fan Z,, Zhou H,, Liu C,, Jiang Q,, Zhang Y,, Zhao K,, Xuan L,, Zhai X,, Zhang F,, Yin C,, Sun J,, Feng R,, Liu Q . 2013. Herpesvirus-associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation. PLoS One 8 : e77805. doi:10.1371/journal.pone.0077805 [CrossRef]
159. Boeckh M,, Ljungman P . 2009. How we treat cytomegalovirus in hematopoietic cell transplant recipients. Blood 113 : 5711– 5719.[CrossRef]
160. Gimeno C,, Solano C,, Latorre JC,, Hernández-Boluda JC,, Clari MA,, Remigia MJ,, Furió 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 : 3311– 3318.[CrossRef]
161. Halfon P,, Berger P,, Khiri H,, Martineau A,, Pénaranda G,, Merlin M,, Faucher C . 2011. Algorithm based on CMV kinetics DNA viral load for preemptive therapy initiation after hematopoietic cell transplantation. J Med Virol 83 : 490– 495.[CrossRef]
162. Li H,, Dummer JS,, Estes WR,, Meng S,, Wright PF,, Tang YW . 2003. Measurement of human cytomegalovirus loads by quantitative real-time PCR for monitoring clinical intervention in transplant recipients. J Clin Microbiol 41 : 187– 191.[CrossRef]
163. Einsele H,, Hebart H,, Kauffmann-Schneider C,, Sinzger C,, Jahn G,, Bader P,, Klingebiel T,, Dietz K,, Löffler J,, Bokemeyer C,, Müller CA,, Kanz L . 2000. Risk factors for treatment failures in patients receiving PCR-based preemptive therapy for CMV infection. Bone Marrow Transplant 25 : 757– 763.[CrossRef]
164. Kotton CN,, Kumar D,, Caliendo AM,, Asberg A,, Chou S,, Danziger-Isakov L,, Humar A ; Transplantation Society International CMV Consensus Group . 2013. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation 96 : 333– 360.[CrossRef]
165. Eid AJ,, Arthurs SK,, Deziel PJ,, Wilhelm MP,, Razonable RR . 2010. Clinical predictors of relapse after treatment of primary gastrointestinal cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 10 : 157– 161.[CrossRef]
166. Schlischewsky E,, Fuehner T,, Warnecke G,, Welte T,, Haverich A,, Ganzenmueller T,, Heim A,, Gottlieb J . 2013. Clinical significance of quantitative cytomegalovirus detection in bronchoalveolar lavage fluid in lung transplant recipients. Transpl Infect Dis 15 : 60– 69.[CrossRef]
167. Baroco AL,, Oldfield EC . 2008. Gastrointestinal cytomegalovirus disease in the immunocompromised patient. Curr Gastroenterol Rep 10 : 409– 416.[CrossRef]
168. Paya C,, Humar A,, Dominguez E,, Washburn K,, Blumberg E,, Alexander B,, Freeman R,, Heaton N,, Pescovitz MD ; Valganciclovir Solid Organ Transplant Study Group . 2004. Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 4 : 611– 620.[CrossRef]
169. Lisboa LF,, Preiksaitis JK,, Humar A,, Kumar D . 2011. Clinical utility of molecular surveillance for cytomegalovirus after antiviral prophylaxis in high-risk solid organ transplant recipients. Transplantation 92 : 1063– 1068.[CrossRef]
170. Lazzarotto T,, Gabrielli L,, Lanari M,, Guerra B,, Bellucci T,, Sassi M,, Landini MP . 2004. Congenital cytomegalovirus infection: recent advances in the diagnosis of maternal infection. Hum Immunol 65 : 410– 415.[CrossRef]
171. Lazzarotto T,, Varani S,, Spezzacatena P,, Gabrielli L,, Pradelli P,, Guerra B,, Landini MP . 2000. Maternal IgG avidity and IgM detected by blot as diagnostic tools to identify pregnant women at risk of transmitting cytomegalovirus. Viral Immunol 13 : 137– 141.[CrossRef]
172. Lazzarotto T,, Varani S,, Guerra B,, Nicolosi A,, Lanari M,, Landini MP . 2000. Prenatal indicators of congenital cytomegalovirus infection. J Pediatr 137 : 90– 95.[CrossRef]
173. Revello MG,, Furione M,, Zavattoni M,, Tassis B,, Nicolini U,, Fabbri E,, Gerna G . 2008. Human cytomegalovirus (HCMV) DNAemia in the mother at amniocentesis as a risk factor for iatrogenic HCMV infection of the fetus. J Infect Dis 197 : 593– 596.[CrossRef]
174. Enders G,, Bäder U,, Lindemann L,, Schalasta G,, Daiminger A . 2001. Prenatal diagnosis of congenital cytomegalovirus infection in 189 pregnancies with known outcome. Prenat Diagn 21 : 362– 377.[CrossRef]
175. Demmler GJ,, Buffone GJ,, Schimbor CM,, May RA . 1988. Detection of cytomegalovirus in urine from newborns by using polymerase chain reaction DNA amplification. J Infect Dis 158 : 1177– 1184.[CrossRef]
176. Warren WP,, Balcarek K,, Smith R,, Pass RF . 1992. Comparison of rapid methods of detection of cytomegalovirus in saliva with virus isolation in tissue culture. J Clin Microbiol 30 : 786– 789.
177. Nelson CT,, Istas AS,, Wilkerson MK,, Demmler GJ . 1995. PCR detection of cytomegalovirus DNA in serum as a diagnostic test for congenital cytomegalovirus infection. J Clin Microbiol 33 : 3317– 3318.
178. Boppana SB,, Ross SA,, Shimamura M,, Palmer AL,, Ahmed A,, Michaels MG,, Sánchez PJ,, Bernstein DI,, Tolan RW Jr,, Novak Z,, Chowdhury N,, Britt WJ,, Fowler KB ; 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 : 2111– 2118.[CrossRef]
179. Boppana SB,, Ross SA,, Novak Z,, Shimamura M,, Tolan RW Jr,, Palmer AL,, Ahmed A,, Michaels MG,, Sánchez PJ,, Bernstein DI,, Britt WJ,, Fowler KB ; National Institute on Deafness and Other Communication Disorders CMV and Hearing Multicenter Screening (CHIMES) Study . 2010. Dried blood spot real-time polymerase chain reaction assays to screen newborns for congenital cytomegalovirus infection. JAMA 303 : 1375– 1382.[CrossRef]
180. Swanson EC,, Schleiss MR . 2013. Congenital cytomegalovirus infection: new prospects for prevention and therapy. Pediatr Clin North Am 60 : 335– 349.[CrossRef]
181. Boivin G,, Goyette N,, Gilbert C,, Roberts N,, Macey K,, Paya C,, Pescovitz MD,, Humar A,, Dominguez E,, Washburn K,, Blumberg E,, Alexander B,, Freeman R,, Heaton N,, Covington E . 2004. Absence of cytomegalovirus-resistance mutations after valganciclovir prophylaxis, in a prospective multicenter study of solid-organ transplant recipients. J Infect Dis 189 : 1615– 1618.[CrossRef]
182. Myhre HA,, Haug Dorenberg D,, Kristiansen KI,, Rollag H,, Leivestad T,, Asberg A,, Hartmann A . 2011. Incidence and outcomes of ganciclovir-resistant cytomegalovirus infections in 1244 kidney transplant recipients. Transplantation 92 : 217– 223.[CrossRef]
183. Razonable RR,, Paya CV . 2003. Herpesvirus infections in transplant recipients: current challenges in the clinical management of cytomegalovirus and Epstein-Barr virus infections. Herpes 10 : 60– 65.
184. Hu H,, Jabs DA,, Forman MS,, Martin BK,, Dunn JP,, Weinberg DV,, Davis JL ; Cytomegalovirus Retinitis and Viral Resistance Study Group . 2002. Comparison of cytomegalovirus (CMV) UL97 gene sequences in the blood and vitreous of patients with acquired immunodeficiency syndrome and CMV retinitis. J Infect Dis 185 : 861– 867.[CrossRef]
185. Lurain NS,, Chou S . 2010. Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev 23 : 689– 712.[CrossRef]
186. Gracia-Ahufinger I,, Gutiérrez-Aroca J,, Cordero E,, Vidal E,, Cantisán S,, del Castillo D,, Martín-Gandul C,, Rivero A,, Torre-Cisneros J . 2013. Use of high-dose ganciclovir for the treatment of cytomegalovirus replication in solid organ transplant patients with ganciclovir resistance-inducing mutations. Transplantation 95 : 1015– 1020.[CrossRef]