Cytomegalovirus (CMV) Infection

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

Demographics

• 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 ...