- Microbiology
- Epidemiology
- Pathogenesis
- Clinical Manifestations
- Congenital CMV Infection
- Perinatal CMV Infection
- CMV Mononucleosis
- CMV Infection in Immunocompromised Pts
- Diagnosis
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.
CMV disease is found worldwide. In many regions, nearly all adults are seropositive, as are ∼50% of adults in the United States and Canada. 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).
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.
The most common presentation is CMV mononucleosis in immunocompetent pts, but disease can be more severe in immunocompromised pts (including newborns).
Of infants born to mothers with primary CMV infections during pregnancy, 5-20% will develop clinical manifestations, with a mortality rate of ∼5%.
- 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.
- Infants with severe disease have ongoing intellectual and/or hearing difficulties.
- Of asymptomatically infected infants, 5-25% develop significant psychomotor, hearing, ocular, or dental abnormalities over the next several years.
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 disease can occur.
Signs and 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 Immunocompromised Pts 
CMV is the most common viral pathogen complicating organ transplantation, with the greatest risk of infection 1-4 months after transplantation. HIV-infected pts with CD4+ T cell counts of <50-100/µL also are at risk for severe CMV disease.
- Primary CMV infection (including reinfection with a new, donor-derived strain) is more likely than reactivation to cause severe disease with high viral loads.
- Reactivation infection is common but less important clinically.
- The transplanted organ is at particular risk; e.g., CMV pneumonitis tends to follow lung transplantation.
- The risk of severe disease is reduced by antiviral prophylaxis or preemptive therapy.
- Pts present initially with prolonged fever, malaise, anorexia, fatigue, night sweats, and arthralgias or myalgias but can ultimately have multiorgan involvement.
- Respiratory involvement is evidenced by tachypnea, hypoxia, unproductive cough, and chest radiographs demonstrating bilateral interstitial or reticulonodular infiltrates.
- GI involvement often includes hepatitis and ulcer formation. Colitis is the most common manifestation in organ transplant recipients.
- CMV encephalitis, particularly in HIV-infected pts, can occur as either progressive dementia or ventriculoencephalitis characterized by cranial nerve deficits, disorientation, and lethargy.
- CMV retinitis is an important cause of blindness in pts with advanced AIDS.
Diagnosis requires isolation of CMV or detection of its antigens or DNA in appropriate clinical specimens in conjunction with a compatible clinical syndrome. Immunofluorescence assays for CMV antigens (pp65), PCR, viral culture, and serology are all useful means of detection.
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Cytomegalovirus Infections
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