Cytomegalovirus

Clinical Background

Cytomegalovirus (CMV), generally asymptomatic in immunocompetent children and adults, is a potentially significant disease in immunocompromised hosts, neonates and pregnant females.

Epidemiology

Incidence - a large segment of the adult U.S. population has previously been infected with CMV
Transmission
- Transplacental
- Blood transfusion
- Organ transplantation
- Infectious droplet (normal childhood route)

Organism

Largest member of the Herpes virus family
Ability to remain latent (feature of all Herpes viruses)
Large nuclear inclusions produced in tissues by CMV are the hallmark of the disease

Clinical Presentation

Infection in utero or at birth
- CMV infection may result in congenital abnormalities, including hepatosplenomegaly, deafness and mental retardation

CMV Diseases and Related Syndromes
CMV disease	Principal syndrome	Risk factors
AIDS	Retinitis GI disease CNS disease	<100 CD 4+ cells per mL CMV+
Fetus	Cytomegalic inclusion disease	Primary early maternal infection
Organ transplant	Pneumonia GI disease Disseminated disease	Seropositive donor Intensive immunosuppression
Bone marrow transplant	Pneumonia GI disease Disseminated disease	Older age Seropositive donor Graft vs. host disease
(Adapted with permission from Hirsch, et al., 2005, 1049)

Associated illnesses - hepatitis, pneumonia or a mononucleosis-like illness with little or no exudative pharyngitis or adenopathy (heterophile antibody negative mononucleosis)

Treatment

CMV syndromes are often treatable
CMV prophylaxis is useful in high-risk patients

Prevention

Blood transfusions
- Seronegative individuals transfused with blood from seropositive donors have a high risk of developing CMV infection
- Serologic testing for CMV is important in screening blood for transfusion to neonates or to immunocompromised patients
Patients with altered cellular immunity (e.g., AIDS, recipients of organ transplants or cancer patients in active treatment)
- Serologic testing is important for screening organ donors
- CMV infection is frequent and severe in transplant recipients
- IgG titers may not be reliable as a means to detect reactivation of latent virus
  - Most AIDS patients are seropositive for CMV before HIV infection is diagnosed

See Also

Adenovirus

Cryoglobulinemia - Cryoglobulin

Epstein-Barr Virus - EBV

Neuropathic Disease

Respiratory Syncytial Virus - RSV

Varicella-Zoster Virus - VZV

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Cytomegalovirus Rapid Culture

ARUP #: 0065004

Methodology: Cell Culture/Immunofluorescence

Use:

Diagnose CMV infection

Gold standard test for tissue

Limitations:

Follow-up:

Test name: Cytomegalovirus by PCR

ARUP #: 0060040

Methodology: Polymerase Chain Reaction

Use:

Rapid test for diagnosing CMV in immunocompromised patients or solid organ donors (not tissue donors)

Limitations:

Follow-up:

Test name: Cytomegalovirus DNA Quantitation by PCR

ARUP #: 0056052

Methodology: Polymerase Chain Reaction

Use:

Diagnose CMV infection

Monitor disease state in organ transplant and HIV patients

Limitations:

Follow-up:

May be useful for monitoring response to therapy

Test name: Cytomegalovirus by PCR, Whole Blood or Bone Marrow

ARUP #: 0060031

Methodology: Polymerase Chain Reaction

Use:

Diagnose CMV infection

Limitations:

Follow-up:

Test name: Cytomegalovirus Antibodies, IgG & IgM

ARUP #: 0050622

Methodology: Refer to individual components.

Use:

Screen pregnant women and infants possibly infected with CMV

Infants may test positive during first 6 months due to maternal antibodies

Discriminate between current (IgM) and prior infections (IgG)

Limitations:

Not recommended for immunocompromised patients. A rise in CMV antibody level may occur in patients with measles, varicella-zoster or herpes simplex virus due to antigenic cross-reactivity within the herpes virus family

Follow-up:

Test name: Cytomegalovirus Antibodies (Total)

ARUP #: 0050166

Methodology: Solid Phase Agglutination

Use:

Screen solid organ donors; not appropriate for tissues such as corneal

Limitations:

A rise in CMV antibody level may occur in patients with measles, varicella-zoster or herpes simplex virus due to antigenic cross-reactivity within the herpes virus family

Follow-up:

Test name: Immunohistochemistry Stain Offering

ARUP #: arup005

Methodology: Immunohistochemistry

Use:

For fixed tissue samples, consultative services as well as immunohistochemical staining for the presence of CMV are available

Additional Tests Available

Test name: Cytomegalovirus Antibody, IgM

ARUP #: 0050553

Methodology: Enzyme-Linked Immunosorbent Assay

Comments:

Test name: Cytomegalovirus Antibody, IgG

ARUP #: 0050165

Methodology: Chemiluminescent Immunoassay

Comments:

Test name: Viral Culture & Cytomegalovirus Rapid Culture

ARUP #: 0065034

Methodology: Cell Culture/Immunofluorescence

Comments:

Test name: TORCH Antibodies, IgG

ARUP #: 0050772

Methodology: Chemiluminescent Immunoassay

Comments:

Test name: TORCH Antibodies, IgM

ARUP #: 0050665

Methodology: Refer to individual components

Comments:

Additional Information

If antibody test results are equivocal, consider retesting in 10-14 days.

References

Guidelines

Preiksaitis JK, Brennan DC, Fishman J, Allen U. Canadian society of transplantation consensus workshop on cytomegalovirus management in solid organ transplantation final report. Am J Transplant. 2005;5(2):218-227.

Recommended immunization schedules for children and adolescents: United States, 2007. American Academy of Family Physicians - Medical Specialty Society American Academy of Pediatrics - Medical Specialty Society Centers for Disease Control and Prevention - Federal Government Agency [U.S.]. 2004 Apr 30 (revised 2007 Jan). 4 pages. NGC:005439

Steininger C, Puchhammer-Stockl E, Popow-Kraupp T. Cytomegalovirus disease in the era of highly active antiretroviral therapy (HAART). J Clin Virol. 2006;37(1):1-9.

Whitley RJ, Jacobson MA, Friedberg DN, Holland GN, Jabs DA, Dieterich DT, Hardy WD, Polis MA, Deutsch TA, Feinberg J, Spector SA, Walmsley S, Drew WL, Powderly WG, Griffiths PD, Benson CA, Kessler HA. Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA. Arch Intern Med. 1998;158(9):957-969.

Cited References

Hirsch MS et al. Cytomegalovirus and Human Herpesvirus Types 6, 7, and 8. In Kasper D et al. eds. Harrison's Principles of Internal Medicine, 16th ed. New York: McGraw-Hill, 2005. pp. 1049-1053.

General References

Burny W, Liesnard C, Donner C, Marchant A. Epidemiology, pathogenesis and prevention of congenital cytomegalovirus infection. Expert Rev Anti Infect Ther. 2004;2(6):881-894.

Gandhi MK, Khanna R. Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments. Lancet Infect Dis. 2004;4(12):725-738.

Griffiths PD, Walter S. Cytomegalovirus. Curr Opin Infect Dis. 2005;18(3):241-245.

Mace M, Sissoeff L, Rudent A, Grangeot-Keros L. A serological testing algorithm for the diagnosis of primary CMV infection in pregnant women. Prenat Diagn. 2004;24(11):861-863.

Ross SA, Boppana SB. Congenital cytomegalovirus infection: outcome and diagnosis. Semin Pediatr Infect Dis. 2005;16(1):44-49.

Rowshani AT, Bemelman FJ, van Leeuwen EM, van Lier RA, ten Berge I. Clinical and immunologic aspects of cytomegalovirus infection in solid organ transplant recipients. Transplantation. 2005;79(4):381-386.

Cytomegalovirus. Am J Transplant. 2004;4 Suppl 10:51-58.

References from the ARUP Institute for Clinical and Experimental Pathology Research®

Owen WE, Martins TB, Litwin CM, Roberts WL. Performance characteristics of six IMMULITE 2000 TORCH assays. Am J Clin Pathol. 2006;126(6):900-905.

Medical Reviewers

Hillyard, David R., M.D. Medical Director, Molecular Infectious Diseases at ARUP Laboratories; Associate Professor, Pathology, University of Utah

Litwin, Christine, M.D. Medical Director, Immunology at ARUP Laboratories; Professor, Clinical Pathology, University of Utah

Petti, Cathy A., M.D. Medical Director, Infectious Diseases at ARUP Laboratories; Assistant Professor, Pathology and Medicine, University of Utah

Roberts, William L. , M.D., Ph.D. Medical Director, Automated Core Laboratory at ARUP Laboratories; Professor, Pathology, University of Utah

Comprehensive Review: November 2007
Last Update: September 2007