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Cytomegalovirus (CMV) Infection

(Cytomegalic Inclusion Disease)

By

Kenneth M. Kaye

, MD, Brigham and Women’s Hospital, Harvard Medical School

Last full review/revision Oct 2019| Content last modified Oct 2019
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Cytomegalovirus (CMV, human herpesvirus type 5) can cause infections that have a wide range of severity. A syndrome of infectious mononucleosis that lacks severe pharyngitis is common. Severe focal disease, including retinitis, can develop in HIV-infected patients and in organ transplant recipients and other immunocompromised patients. Severe systemic disease can develop in neonates and immunocompromised patients. Laboratory diagnosis, helpful for severe disease, may involve culture, serologic testing, biopsy, or antigen or nucleic acid detection. Ganciclovir and other antiviral drugs are used to treat severe disease, particularly retinitis.

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; 60 to 90% of adults have CMV infection (resulting in lifelong latent infection). 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 immunocompromised patients, 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 in up to 40% of patients and causes funduscopically visible retinal abnormalities. Ulcerative disease of the colon (with abdominal pain and gastrointestinal bleeding) or of the esophagus (with odynophagia) may occur.

Diagnosis

  • Detection of CMV antigen or DNA

  • Urine culture in infants

  • Often biopsy in immunocompromised patients

  • Serologic testing

CMV infection is suspected in

  • Healthy people with mononucleosis-like syndromes

  • Immunocompromised patients with gastrointestinal, 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 through CMV serologic testing. CMV infection can be differentiated from viral hepatitis 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, much CMV disease results from reactivation of latent disease in the immunocompromised host. 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 shedding. Therefore, biopsy showing CMV-induced abnormalities 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.

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

Treatment

  • For serious disease, antivirals (eg, ganciclovir, valganciclovir, foscarnet, cidofovir)

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

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

CMV retinitis

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

  • Ganciclovir or valganciclovir

  • Foscarnet, with or without ganciclovir

  • Cidofovir

Most patients receive induction therapy with one of the following:

  • Ganciclovir 5 mg/kg IV every 12 hours for 2 to 3 weeks

  • Valganciclovir 900 mg orally every 12 hours for 21 days

If induction fails more than once, another drug should be used.

Maintenance (suppressive) therapy with one of the following is given after induction:

  • Ganciclovir 5 mg/kg IV once a day

  • Valganciclovir 900 mg po once a day

Alternatively, foscarnet can be given with or without ganciclovir. Dosage is

  • Induction: Foscarnet 60 mg/kg IV every 8 hours for 2 to 3 weeks

  • Maintenance: Foscarnet 90 to 120 mg/kg IV once a day

Adverse effects of IV foscarnet are significant and include nephrotoxicity, symptomatic hypocalcemia, hypomagnesemia, hyperphosphatemia, hypokalemia, and CNS effects. Combination therapy with ganciclovir and foscarnet increases efficacy as well as adverse effects.

Cidofovir therapy is another alternative; it consists of

  • Induction: Cidofovir 5 mg/kg IV once a week for 2 weeks

  • Maintenance: Cidofovir 5 mg/kg IV once every other week

Efficacy of cidofovir is similar to that of ganciclovir or foscarnet. Significant adverse effects, including renal failure, limit its use. Cidofovir may cause iritis or ocular hypotony (intraocular pressure ≤ 5 mm Hg). The potential for nephrotoxicity can be reduced by giving probenecid and prehydration with each dose. However, the adverse effects of probenecid, including rash, headache, and fever, may be significant enough to prevent its use.

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/mcL 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

Prophylaxis or preemptive treatment (actively monitoring patients by viral load and giving antiviral drugs to those with evidence of infection) is effective for preventing CMV disease in solid organ or hematopoietic cell transplant recipients infected with CMV and at risk of CMV disease. Drugs used include ganciclovir, valganciclovir, and foscarnet.

Key Points

  • Sixty 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.

  • Severely immunocompromised patients may have severe disease involving the retina, lungs, gastrointestinal tract, or CNS.

  • Antiviral drugs 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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NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version
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