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For further information, see CMDT Part 32-01: Human Herpesviruses

Key Features

Essentials of Diagnosis

  • Mononucleosis-like syndrome

  • Frequent pathogen seen in populations with compromised cellular immunity, such as transplant populations

  • Diverse clinical syndromes in HIV-infected individuals (retinitis, esophagitis, pneumonia, encephalitis)

  • Most important infectious cause of congenital abnormalities

General Considerations

  • There are three recognizable clinical syndromes

    • Perinatal disease and CMV inclusion disease

    • Disease in immunocompetent persons

    • Disease in immunocompromised persons

Transmission and perinatal disease

  • Occurs through sexual contact, breastfeeding, blood products, or transplantation

  • May also be transmitted person to person (eg, day care centers) or be transmitted as a congenital infection

  • Much higher transmission from mothers with primary disease than from those with reactivation (40% vs 0.2–1.8%)

Disease in immunocompetent persons

  • Acute infection is most common cause of mononucleosis-like syndrome with negative heterophile antibodies

  • May be involved in the malignant manifestations of glioblastoma multiforme

  • Has been associated with

    • Inflammatory bowel disease

    • Atherosclerosis

    • Cognitive decline

    • Breast cancer

Disease in immunocompromised persons

  • Usually disseminated, leading to varying clinical manifestations

  • Solid organ and bone marrow transplantation patients are at highest risk for disease

    • From CMV reactivation for 1 year after allograft transplantation (but especially during the first 100 days post-transplantation)

    • When graft-versus-host disease is present

    • When the donor is CMV seropositive and the recipient is seronegative

  • Depending on the serostatus of the donor and recipient, disease may present as primary infection or reactivation

  • The risk of CMV disease is proportionate to the degree of immunosuppression and manifestations may differ by the cause

    • CMV may contribute to transplanted organ dysfunction, which often mimics organ rejection

    • CMV retinitis may develop after solid organ or bone marrow transplantation

    • CMV disease in people living with HIV (retinitis, serious gastrointestinal disease)

      • Occurs most prominently when the CD4 cell count is < 50 cells/mcL

      • Can be a marker for increased mortality

  • Serious gastrointestinal CMV disease occurs after

    • Organ transplantation

    • Cancer chemotherapy

    • Corticosteroid therapy

  • CMV pneumonitis in hematologic malignancies (eg, lymphoma) is increasingly reported

  • Neurologic CMV in patients with advanced AIDS is usually associated with disseminated CMV infection


  • Congenital infection

    • In the United States, an estimated 0.5–0.7% of infants (approximately 20,000–30,000 annually) are born with congenital CMV infection

    • The prevalence is even higher in low- and middle-income countries

  • Seroprevalence: 60–80% in adults of Western developed countries but higher in developing countries

Clinical Findings

Symptoms and Signs

Perinatal disease and CMV inclusion disease

  • Characterized by hepatitis, thrombocytopenia, microcephaly, periventricular CNS calcifications, cognitive impairment, and motor disability

  • Hearing loss develops in > 50% of infants who are symptomatic at birth, making CMV a leading cause of pediatric hearing loss

  • Most ...

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