Cytomegalovirus (CMV) Infection

(Cytomegalic Inclusion Disease)

ByKenneth M. Kaye, MD, Harvard Medical School
Reviewed/Revised Dec 2023
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(See also Overview of Herpesvirus Infections and Congenital and Perinatal Cytomegalovirus Infection.)

CMV (human herpesvirus type 5) is transmitted through blood, body fluids, or transplanted organs. Infection may be acquired transplacentally or during birth.

Prevalence increases with age; 50 to 90% of adults have CMV infection (resulting in lifelong latent infection) (1). Lower socioeconomic groups tend to have a higher prevalence.

Congenital CMV infection may be asymptomatic or may cause abortion, stillbirth, or postnatal death. Complications include extensive hepatic and central nervous system (CNS) damage.

Acquired infections are often asymptomatic.

An acute febrile illness, termed CMV mononucleosis, may cause hepatitis with elevated aminotransferases (usually subclinical without jaundice), and atypical lymphocytosis similar to infectious mononucleosis due to Epstein-Barr virus (EBV).

Postperfusion/posttransfusion syndrome can develop 2 to 4 weeks after transfusion with blood products containing CMV. It causes fever lasting 2 to 3 weeks and the same manifestations as CMV mononucleosis.

In patients who are immunocompromised, CMV is a major cause of morbidity and mortality. Disease often results from reactivation of latent virus. The lungs, gastrointestinal tract, or CNS may be involved. In the terminal phase of AIDS, CMV infection causes retinitis about 30% of patients and causes funduscopically visible retinal abnormalities (2). Ulcerative disease of the colon (with abdominal pain and gastrointestinal bleeding) or of the esophagus (with odynophagia) may occur.

General references

  1. 1. Staras SA, Dollard SC, Radford KW, et al: Seroprevalence of cytomegalovirus infection in the United States, 1988-1994. Clin Infect Dis 43(9):1143-1151, 2006. doi:10.1086/508173

  2. 2. Sugar EA, Jabs DA, Ahuja A, et al: Incidence of cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Am J Ophthalmol 153(6):1016-24.e5, 2012. doi:10.1016/j.ajo.2011.11.014

Diagnosis of Cytomegalovirus

  • Detection of CMV antigen or DNA

  • Urine culture in infants

  • Biopsy of tissue that may be infected in patients who are immunocompromised

  • Serologic testing

CMV infection is suspected in

  • Healthy people with mononucleosis-like syndromes

  • Patients who are immunocompromised and have gastrointestinal, lung, CNS, or retinal symptoms

  • Neonates with systemic disease

CMV mononucleosis can be differentiated from infectious (EBV) mononucleosis by the usual lack of pharyngitis, a negative heterophile antibody test, and positive CMV serologic testing. CMV infection affecting the liver can be differentiated from other viral hepatitis infections by hepatitis serologic testing. Laboratory confirmation of primary CMV infection is necessary only to differentiate it from other, particularly treatable, conditions or serious disease, such as primary HIV.

Seroconversion can be demonstrated by development of CMV antibodies and indicates new CMV infection. However, CMV disease can also result from reactivation of latent disease in immunocompromised hosts. Reactivation of CMV can result in virus in the urine, other body fluids, or tissues, but the presence of CMV in body fluids and tissues does not always indicate disease and may merely represent viral shedding. Therefore, biopsy showing CMV-induced abnormalities in infected tissue is often necessary to demonstrate invasive disease. Quantitative detection of CMV antigen or DNA in the peripheral blood can also be very helpful because an elevated or rising CMV viral load is often highly suggestive of invasive disease. Such CMV detection can be particularly helpful in patients who are severely immunocompromised with compatible clinical syndromes in whom biopsy may not be feasible.

Diagnosis of CMV infection in infants can be made by urine culture.

Treatment of Cytomegalovirus

CMV retinitis, which occurs mostly in AIDS patients, is treated with systemic antivirals.

Anti-CMV medications are used to treat severe disease other than retinitis but are less consistently effective than in retinitis.

CMV retinitis

Medications used to treat CMV retinitis in induction and maintenance regimens include

Most patients receive induction therapy

Maintenance (suppressive) therapy

With any of the maintenance regimens, clinicians can consider stopping maintenance therapy after 3 months of CMV therapy in HIV-infected patients who are taking antiretroviral therapy (ART) and have had a CD4 count of ≥ 100 cells/mL for 3 months.

Intravitreal antiviral therapy should be used in combination with systemic therapy for patients with CMV retinitis that immediately threatens sight (ie, disease involving or close to the optic nerve or macula). Even patients receiving ocular injections need systemic therapy to prevent CMV in the contralateral eye and extraocular tissues.

Prevention of Cytomegalovirus

Key Points

  • Fifty to 90% of adults have latent CMV infection.

  • Healthy children and adults can have mild, nonspecific symptoms or sometimes a mononucleosis-like syndrome when first infected with CMV.

  • Congenital infection may cause stillbirth or severe, sometimes fatal postnatal complications including extensive hepatic or CNS damage.

  • Patients who are severely immunocompromised may have severe disease involving the retina, lungs, gastrointestinal tract, or CNS.

  • Antivirals may help treat retinitis but are less effective when other organs are affected.

  • Transplant patients at risk of CMV infection require prophylactic antivirals or close monitoring for early indications of infection.

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