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  • Updated 12.09.2019
  • Released 01.03.1994
  • Expires For CME 12.09.2022

Acquired human cytomegalovirus

Introduction

Overview

Human cytomegalovirus (HCMV), also known as human herpesvirus 5, is a common pathogen that infects a majority of the adult population. After acute infection, the virus remains in a latent state but can reactivate to generate viremia or viruria, typically in the setting of immune system dysfunction. Human cytomegalovirus infection in immunocompetent hosts is often asymptomatic or self-limited whereas immunocompromised individuals can experience a more severe, life-threatening clinical course. Human cytomegalovirus infection can have a variety of clinical neurologic presentations including retinitis, encephalitis, or radiculitis, and has also been implicated in cancer and vascular disease in immunocompetent individuals. Diagnosis is made through serological testing and molecular assays among individuals with a compatible clinical presentation, and current treatments are typically effective at controlling clinical symptoms.

Key points

• Cytomegalovirus infection is a public health concern due to its widespread prevalence and the increasing number of immunosuppressed individuals, including those with HIV/AIDS and transplant recipients.

• Acute human cytomegalovirus infection is followed by a period of latency during which the virus lays dormant, commonly in cells of myeloid lineage. The mechanism of reactivation is still unclear but more commonly occurs in the setting of immunodeficiency, particularly of cell-mediated immunity. The role of human cytomegalovirus in oncomodulation, immunosenescence, and vascular damage is being actively studied.

• Initial human cytomegalovirus infection in immunocompetent hosts may be asymptomatic or present as mononucleosis. In more severe cases, acute infection can be associated with pancytopenia, encephalitis, radiculitis, retinitis, colitis, or pneumonitis. Acquired human cytomegalovirus infection should be suspected in immunocompromised individuals with acute illness.

• Diagnosis of human cytomegalovirus infection can be established by detection of viral DNA in blood or other tissue fluids, by demonstration of a 4-fold increase in antibody titers (IgG) in serum, or by antigen quantification in blood or other tissue fluids. CSF should be assayed for viral DNA if nervous system involvement is suspected.

• Treatment of human cytomegalovirus infection depends on the patient profile. Four established and widely-used antiviral agents are ganciclovir, valganciclovir, cidofovir, and foscarnet. Letermovir has been FDA approved as the first drug for human cytomegalovirus prophilaxis in transplant patients. Infections due to antiviral drug-resistant human cytomegalovirus strains are an emerging problem, leading to investigation into new antiviral agents and virus-specific immune therapies.

Historical note and terminology

Large inclusion-bearing cells were first described in the early 20th century in tissue samples of stillborn infants. Characterized by eccentrically placed nuclei and a “central nuclear body,” these cells were thought to represent a protozoan or syphilitic infection. Later, these inclusion-bearing cells were found in the salivary glands of patients with lethal congenital infections, characterized by hepatosplenomegaly and intracerebral calcifications. Wyatt and colleagues suggested the name “cytomegalic inclusion disease” in 1950 (46). The virus was later isolated by Margaret Smith, WP Rowe, and Thomas Weller, who then named it “cytomegalovirus” based on its distinctive histopathology.

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