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INTRODUCTION

CYTOMEGALOVIRUS (CMV)

Microbiology

CMV is a herpesvirus, has double-stranded DNA, and renders infected cells 2–4 times the size of surrounding cells. These cytomegalic cells contain an eccentrically placed intranuclear inclusion surrounded by a clear halo, with an "owl's-eye" appearance.

Epidemiology

CMV disease is found worldwide. Perinatal and early childhood infections are common; ∼1% of U.S. newborns are infected.

  • The virus can be spread in breast milk, saliva, feces, and urine.

  • Transmission requires repeated or prolonged contact as opposed to casual contact. Sexual transmission is common among adolescents and adults, and CMV has been identified in semen and cervical secretions.

  • Latent CMV infection persists throughout life unless reactivation is triggered by depressed cell-mediated immunity (e.g., in transplant recipients or HIV-infected pts).

Pathogenesis

Primary CMV infection is associated with a vigorous T lymphocyte response; activated CD8+ T cells predominate among atypical lymphocytes.

  • Latent infection occurs in multiple cell types and various organs. Chronic antigen stimulation in the presence of immunosuppression (e.g., in the transplantation setting) and certain immunosuppressive agents (e.g., antithymocyte globulin) promote CMV reactivation.

  • CMV disease increases the risk of infection with opportunistic pathogens by depressing T lymphocyte responsiveness.

Clinical Manifestations

The most common presentation is CMV mononucleosis in immunocompetent pts, but disease can be more severe in immunocompromised pts (including newborns).

Congenital CMV Infection

Cytomegalic inclusion disease occurs in ∼5% of infected fetuses in the setting of primary maternal CMV infection in pregnancy.

  • Petechiae, hepatosplenomegaly, and jaundice are present in 60–80% of cases; microcephaly with or without cerebral calcifications, intrauterine growth retardation, prematurity, and chorioretinitis are less common.

  • Laboratory findings include elevated values in LFTs, thrombocytopenia, conjugated hyperbilirubinemia, hemolysis, and increased CSF protein levels.

  • The mortality rate is 20–30% among infants with severe disease; survivors have intellectual or hearing difficulties.

Perinatal CMV Infection

Perinatal infection with CMV is acquired by breast-feeding or contact with infected maternal secretions (e.g., in the birth canal). Although most pts are asymptomatic, disease similar to—but less severe than—congenital CMV can occur.

CMV Mononucleosis

Symptoms last 2–6 weeks and include high fevers, profound fatigue and malaise, myalgias, headache, and splenomegaly; in contrast to EBV infection, exudative pharyngitis and cervical lymphadenopathy are rare in CMV infection.

  • Laboratory findings include relative lymphocytosis with >10% atypical lymphocytes, transaminitis, and immunologic abnormalities (e.g., the presence of cryoglobulins, rheumatoid factor, or cold agglutinins).

  • The incubation period ranges from 20 to 60 days.

  • Recovery is generally complete, but postviral asthenia can persist for months.

CMV Infection in the Immunocompromised Host

CMV is the most common and important viral pathogen complicating organ transplantation, with the greatest ...

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