CYTOMEGALO VIRUS DISEASE
CMV differs from HSV and VZV by not causing skin disease, but CMV is similar in its ability to establish latent infection. CMV produces visceral disease, including a mononucleosis syndrome in otherwise healthy individuals. Its major contribution to human misery is a high rate of congenital infection (1% of all infants; 40,000 in the United States per year), most of whom are asymptomatic; however, some 20% may have neurologic impairment. CMV is also an important cause of morbidity and mortality in immunocompromised patients with either primary or reactivation disease.
CMV is ubiquitous, and in developed countries approximately 50% of adults have devel-oped antibody. Age-specific prevalence rates show that approximately 10 to 15% of children are infected by CMV during the first 5 years of life, after which the rate of new infections levels off. The rate subsequently increases by 1 to 2% per year during adulthood, probably through close personal contact, including sexual, with a virus-excreting person. CMV has been isolated from saliva, cervical secretions, semen, urine, and white blood cells for months to years following infection. Excretion of CMV is especially prolonged after con-genital and perinatal infections, with 35% of infected infants excreting virus for as long as 5 years after birth. Transmission of infection in day-care centers has been shown to occur from asymptomatic excreters to other children and, in turn, to seronegative parents. By age 18 months, up to 80% of infants in a day-care center are infected and actively excreting virus in saliva and urine. Seroconversion rates in seronegative parents who have children at-tending day-care centers are approximately 20% per year. This increases to approximately 30% if the child is shedding virus and up to 40% if the child is also under 18 months of age. In contrast to day-care centers, there is no substantial evidence of spread of CMV infection to health care workers in the hospital.
Latent infection, which occurs in leukocytes and their precursors, accounts for transfu-sion transmission, but this route is relatively infrequent; only 1 to 2% of blood units are be-lieved to be infectious. Organ donation may also transmit latent virus, which causes pri-mary infection in CMV-seronegative recipients and reinfection in seropositive patients.
As previously mentioned, CMV infects epithelial cells and leukocytes and produces char-acteristic inclusions in the former. In vitro, CMV DNA can be demonstrated in monocytes showing no cytopathology, indicating a restricted growth potential in these cells. It is con-jectured that these are the cells of latency for CMV.
CMV can cause disease by a variety of different mechanisms, including direct tissue damage and immunologic damage. While direct infection and damage of mucosal epithe-lial cells in the lung is a potential mechanism for pneumonia, animal models have sug-gested that immunologic destruction of the lung by the host immune response to CMV in-fection may be the major mechanism of viral disease in this tissue. This hypothesis is supported by the observation that the degree of viral infection in lung tissue cannot ac-count for the severity of CMV pneumonia; likewise, the disease does not respond well to antiviral therapy. While cytolytic T-lymphocyte activity may contribute to lung pathology, cytokines released by these cells have also been implicated.
Both humoral and cellular immune responses are important in CMV infections. In immuno-competent persons, clinical disease, if it occurs at all, results from primary infection, and re-activation with viral excretion in cervical excretions or semen is invariably subclinical. In immunocompromised patients, both primary infection and reactivation are much more likely to be symptomatic. Furthermore, CMV infection of monocytes results in dysfunction of these phagocytes in immunocompromised patients, which may increase predisposition to fungal and bacterial superinfection. When latently infected monocytes are in contact with activated T lymphocytes, the former are activated to differentiate into macrophages that pro-duce infectious virus. These monocyte–T cell interactions may occur following transfusion or transplantation and may explain not only transmission of CMV but also activation of latent virus in the allograft recipient. Vascular endothelial cells may be other sites of CMV latency.
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