Cytomegalovirus (CMV) infection

Infection with CMV is found world-wide and has its most profound effects as an opportunistic infection in the immunocompromised, particularly in recipients of bone-marrow and solid organ transplants and in patients with AIDS. Over 50% of the adult population have serological evidence of latent infection with the virus, although infection is generally symptomless. As with all herpesviruses, the virus persists for life, usually as a latent infection in which the naked DNA is situated extrachromosomally in the nuclei of the cells in the endothelium of the arterial wall and in T lymphocytes.

Clinical features

In healthy adults CMV infection is usually asymptomatic but may cause an illness similar to infectious mononucleosis, with fever, occasionally lymphocytosis with atypical lymphocytes, and hepatitis with or without jaundice. The Paul-Bunnell test for heterophile antibody is negative. Infection may be spread by kissing, sexual intercourse or blood transfusion, and transplacentally to the fetus. Disseminated fatal infection with widespread visceral involvement occurs in the immunocompromised and may cause encephalitis, retinitis, pneumonitis and diffuse involvement of the gastrointestinal tract.

Intrauterine infection usually occurs in primary infection acquired during pregnancy and may have serious consequences in the fetus; CNS involvement may cause microcephaly and motor disorders. Jaundice and hepatosplenomegaly are common, and thrombocytopenia and haemolytic anaemia also occur. Evidence of CNS involvement may be provided by demonstration of periventricular calcification on X-ray.

Diagnosis

Serological tests can identify latent (IgG) or primary (IgM) infection. The virus can also be identified in tissues by the presence of characteristic intranuclear 'owl's eye' inclusions on histological staining and by direct immunofluorescence. Culture in human embryo fibroblasts is usually slow but diagnosis can be accelerated by immunofluorescent detection of antigen in the cultures. The polymerase chain reaction, which can be quantitative, provides a sensitive way of detecting CMV in blood and other body fluids.

Treatment

In the immunocompetent, infection is usually self-limiting and no specific treatment is required. In the immunosuppressed, ganciclovir (5 mg/kg daily for 14-21 days) reduces retinitis and gastrointestinal damage and can eliminate CMV from blood, urine and respiratory secretions. It is less effective against pneumonitis. In patients who are continually immunocompromised, particularly those with AIDS, maintenance therapy may be necessary. Drug resistance has been reported in AIDS patients and transplant recipients. Bone marrow toxicity is common. No antiviral drugs are currently available for routine treatment of CMV in neonates and the toxicity of ganciclovir prohibits its use in most cases. Two other drugs, foscarnet and cidofovir, are available for the treatment of CMV infection but both are nephrotoxic and their use should be restricted to those with severe disease.