Infection with cytomegalovirus (CMV), a herpes virus, is common in the general population, with multiple mechanisms for transmission, often during childhood and adolescence. CMV is associated with pregnancy and can be a congenital disease. CMV is also associated with immunocompromised states and may be life-threatening.

CMV

Heterophil-negative mononucleosis

Cytomegalic inclusion disease virus

• Seroprevalence is widespread: 60% to 90% antibody positivity in adults.
• Increased infection develops perinatally, in day care exposure, and then during reproductive age, related to sexual activity.

• Blood transfusions
• Sexually transmitted diseases (STDs) via uterus, cervix, and semen
• Perinatally via breast milk
• Transplant of organs-bone marrow, kidneys, liver, heart, or lung
• Saliva

• Human herpesvirus (HHV)-5
• CMV infection can remain latent and reactivate with immunosuppression

Congenital:

• Acute viral, bacterial, parasitic infections including other congenitally transmitted agents (toxoplasmosis, rubella, syphilis, pertussis, croup, bronchitis)

Acquired:

• EBV mononucleosis
• Viral hepatitis-A, B, C
• Cryptosporidiosis
• Toxoplasmosis
• Mycobacterium avium infections
• Human herpesvirus 6
• Acute HIV infection

• Laboratory confirmation combined with clinical findings often with leukopenia, thrombocytopenia, lymphocytosis. Diagnostic modalities include serologic assays, PCR, detection of CMV PP25 antigen in leukocytes, isolation of virus from body fluids and urine, and cytopathic demonstration of “owl eye” intracellular inclusions
• Serology:
  1. Detection of CMV-IgM antibodies suggests recent infection. CMV-IgG antibodies usually appear 2 to 3 wk after infection.
  2. Molecular assays (polymerase chain reaction [PCR] viral loads): On plasma.
  3. CMV antigenemia assays: Detects antibodies to the pp65 protein of the virus in peripheral blood leukocytes. These tests and the PCR tests are used in immunocompromised, AIDS, and transplant patients.
• Cultures: Using human fibroblast cultures of blood, cerebrospinal fluid, urine, bronchoalveolar lavage, and biopsy specimens but can take 1 to 6 wk
• Funduscopic-necrotic patches with white granular component of retina
• Biopsy-“owl eye” inclusion bodies on tissue sample
• HIV

• Chest x-ray examination-if pneumonitis suspected, consider bronchoscopy
• Endoscopy-if GI involvement
• Computed tomography scan/MRI-if CNS involvement

• Strict handwashing and standard precautions limit CMV transmission in health care facilities.
• Antiretroviral therapy (ART) in patients with CD4 count <50/mm³ for the goal of CD4 >100/mm³ for a 3- to 6-mo period.

Antiviral therapy with intravenous ganciclovir or oral valganciclovir is appropriate in immunocompromised patients. It can also be used in immunocompetent patients with severe disease.

For compromised hosts with CMV retinitis or pneumonitis:

• Ganciclovir 5 mg/kg q12h intravenous (IV) × 14 to 21 days, then valganciclovir: 900 mg PO q24h or alternative regimen
• Ganciclovir intraocular implant plus valganciclovir 900 mg PO q24h or alternative regimen
• Foscarnet 90 mg/kg q12h × 14 to 21 days, then 90 mg to 120 mg/kg IV q24h or alternative regimen
• Cidofovir 5 mg/kg IV q day × 14 days, then 5 mg/kg IV q2wk
• Fomivirsen-salvage therapy for CMV retinitis 300 μg injected into vitreous
• Letermovir, in IV and oral form, is approved for prevention of CMV infection and disease in recipients of an allogenic stem cell transplant

• CMV infection in patients who are immunocompromised (especially those with AIDS, bone marrow and solid organ transplant recipients, and disorders of cell-mediated immune function) will need expert, long-term follow-up by an infectious disease specialist or immunologist familiar with the care of such patients.
• CMV mononucleosis, hepatitis, pharyngitis, etc. in immunologically normal hosts are usually self-limiting infections requiring no special follow-up plans.

• To an ophthalmologist if CMV retinitis is present
• To an infectious disease specialist or AIDS specialist for patients who are HIV-positive with CMV disease
• To a cellular immunologist or transplant specialist in the case of CMV infection in a transplant recipient
• To a pediatric infectious disease specialist for congenital CMV infection