What is cytomegalovirus (CMV)?

Causes and Symptoms

Cytomegalovirus (CMV) is a member of the herpesvirus group that includes such viruses as the Epstein-Barr virus, which causes infectious mononucleosis, and the varicella-zoster virus, which causes chickenpox. CMV is a ubiquitous virus that is transmitted in a number of different ways. A newly infected woman may transmit the virus across the placenta to her unborn child. Infection may also occur in the birth canal or via mother’s milk. Young children commonly transmit CMV by means of saliva. Sexual transmission is common in adults. Blood transfusions and organ transplants may also transmit cytomegalovirus to recipients. As many as 80 percent of adults worldwide have antibodies indicating exposure to cytomegalovirus.

Congenital cytomegaloviral infection is universally common and especially prevalent in developing nations. According to the Centers for Disease Control and Prevention, about 0.7 percent of children are born infected. Most congenitally infected infants exhibit no symptoms. Normal development may follow, but some infants experience problems such as hearing loss, visual impairment, and developmental disabilities. Approximately 10 to 20 percent exhibit clinically obvious evidence of cytomegalic inclusion disease: hepatosplenomegaly, jaundice, microcephaly, deafness, seizures, cerebral palsy, and blood disorders such as thrombocytopenia (a decrease in platelets) and hemolytic anemia (in which red blood cells are destroyed). Giant
cells having nuclei containing large inclusions are found in affected organs. Cytomegalovirus is a leading cause of developmental disabilities and has also been linked to microcephaly.

In immunocompetent adults and older children, cytomegalovirus can cause heterophil-negative mononucleosis, an infectious mononucleosis in which no heterophil antibodies are formed. Such antibodies are found in infectious mononucleosis caused by the Epstein-Barr virus. Heterophil-negative mononucleosis is characterized by fever, hepatitis, lethargy, and abnormal lymphocytes in blood.

Severe systemic cytomegalovirus infections are frequently seen in the immunocompromised. Transplant patients are intentionally immunosuppressed to reduce the likelihood of graft rejection, making them vulnerable to infection by cytomegalovirus either by reactivation or by acquisition of the virus from the donor organ. Resulting systemic infections are manifested in diseases such as pneumonia, hepatitis, and retinitis. In addition to these CMV diseases, Acquired immunodeficiency syndrome (AIDS)
patients may experience infections of the central nervous system and gastrointestinal tract. Their blood cells may also be affected, resulting in disorders such as thrombocytopenia. AIDS patients frequently have intestinal CMV infections leading to chronic diarrhea. Cytomegalovirus retinitis in AIDS patients is particularly serious and may lead to retinal detachment and blindness. This is the most common sight-damaging opportunistic eye infection found in AIDS patients.

Treatment and Therapy

Ganciclovir, valganciclovir, foscarnet, and cidofovir are all antiviral agents that have been found useful in treating CMV infections in immunocompromised patients. Toxic properties, however, can limit their long-term administration. Ganciclovir exhibits hematopoietic toxicity; that is, it has an adverse affect on blood cells that may result in neutropenia, a decrease in the number of neutrophils in the blood. Foscarnet has more side effects than ganciclovir. It is a nephrotoxic substance, which means that it may damage the kidneys and thus cannot be used in patients with renal failure.

Valganciclovir, the oral form of ganciclovir, has been used effectively to prevent CMV infection in transplant recipients. It is administered to CMV-seronegative transplant patients receiving organs from CMV-seropositive donors as well as in CMV-seropositive recipients who will be undergoing immunosuppression to prevent rejection of transplanted organs. Another material employed as a prophylaxis for bone marrow and renal transplant recipients is intravenous cytomegalovirus immune globulin.

Therapy for CMV retinitis involves intravenous treatment with either ganciclovir, foscarnet, or cidofovir plus oral probenecid or oral valganciclovir. Alternatively, an intraocular ganciclovir implant may be used along with one of the systemic treatments mentioned above. Therapy of retinitis as well as other types of CMV infection in AIDS patients should be accompanied by highly effective antiretroviral therapy (HAART) to treat the human immunodeficiency virus and improve the immune function in the the patient. Successful HAART may allow the CMV antiviral therapy to be discontinued, but the patient must be carefully monitored for relapse of the CMV infection.

Retinal detachment is another complication arising from cytomegalovirus retinitis. It may occur even in those undergoing successful antiviral treatment. Surgical intervention is required to restore functional vision in these cases.

Perspective and Prospects

The term cytomegalia was first used in 1921 to describe the condition of an infant with intranuclear inclusions in the lungs, kidney, and liver. This condition in an adult was first attributed to a virus of the herpes group in 1925. Twenty-five cases of apparent cytomegalic inclusion disease had been described by 1932. Cytomegalovirus was pursued and isolated in the mid-1950s by researcher Margaret Smith. Around the same time, independently and serendipitously, groups in Boston, Massachusetts, and Bethesda, Maryland, also isolated the virus.

Development of new antiviral drugs and measures to reduce the immunocompromised state should continue to progress and improve the outcomes for patients infected with CMV.

Bibliography

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A.D.A.M. Medical Encyclopedia. "Cytomegalovirus Retinitis." MedlinePlus, December 6, 2011.

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National Center for Immunization and Respiratory Diseases, Division of Viral Diseases. "Cytomegalovirus (CMV) and Congenital CMV Infection." Centers for Disease Control and Prevention, December 6, 2010.

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