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Cytomegalovirus (CMV) Infection

(Cytomegalic Inclusion Disease)

by Kenneth M. Kaye, MD

Cytomegalovirus (CMV) can cause infections that have a wide range of severity. A syndrome that is similar to infectious mononucleosis but lacks severe pharyngitis is common. Severe focal disease, including retinitis, can develop in HIV-infected patients and, rarely, 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 had CMV infection. Lower socioeconomic groups tend to have a higher prevalence.

Congenital infection (see Congenital and Perinatal Cytomegalovirus Infection (CMV)) may be asymptomatic or may cause abortion, stillbirth, or postnatal death. Complications include extensive hepatic or CNS damage.

Acquired infections are often asymptomatic. An acute febrile illness, termed CMV mononucleosis, may cause chemical hepatitis with elevated aminotransferases, and atypical lymphocytosis similar to infectious (Epstein-Barr virus [EBV]) mononucleosis.

Postperfusion/posttransfusion syndrome can develop 2 to 4 wk after transfusion with blood products containing CMV. It causes fever lasting 2 to 3 wk 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, GI 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 GI bleeding) or of the esophagus (with odynophagia) may occur.

Diagnosis

  • Usually clinical evaluation

  • Detection of CMV antigen or DNA

  • Urine culture in infants

  • Often biopsy in immunocompromised patients

CMV infection is suspected in healthy people with mononucleosis-like syndromes; immunocompromised patients with GI, CNS, or retinal symptoms; and neonates with systemic disease.

CMV mononucleosis can sometimes be differentiated from infectious (EBV) mononucleosis by the absence of pharyngitis, a negative heterophil antibody test, and 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.

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 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 elevated or rising CMV titers are often highly suggestive of invasive disease. Diagnosis in infants can be made by urine culture.

Treatment

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

CMV retinitis (see Cytomegalovirus), 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.

Retinitis

Most patients receive induction therapy with either ganciclovir 5 mg/kg IV bid for 2 to 3 wk or valganciclovir 900 mg po bid for 21 days. If induction fails more than once, another drug should be used. After induction, patients receive maintenance or suppressive therapy with valganciclovir 900 mg po once/day to delay progression. Maintenance therapy with ganciclovir 5 mg/kg IV once/day can also be used to prevent recurrence. Alternatively, foscarnet can be given with or without ganciclovir. Foscarnet 60 mg/kg IV q 8 h for 2 to 3 wk is used for induction, followed by 90 to 120 mg/kg IV once/day for maintenance therapy. 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 consists of 5 mg/kg IV once/wk (induction) for 2 wk, followed by a similar dose every other week for maintenance. Efficacy is similar to ganciclovir or foscarnet. Significant adverse effects, including renal failure, limit its use. Cidofovir may cause iritis or ocular hypotony. 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.

Even patients receiving ocular injections need systemic therapy to prevent CMV in the contralateral eye and extraocular tissues. Ultimately, improvement of CD4+ count to > 100 cells/μL with systemic retroviral therapy should prevent the need for ocular implants and chemoprophylaxis.

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 had CMV infection.

  • Healthy children and adults usually have mild, nonspecific symptoms or sometimes a mononucleosis-like syndrome.

  • 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, GI 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.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • CYTOVENE
  • VISTIDE
  • VALCYTE
  • FOSCAVIR
  • No US brand name

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