Cytomegalovirus

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Chapter 247 Cytomegalovirus

Human cytomegalovirus (CMV) is widely distributed. Most CMV infections are inapparent, but the virus can cause a variety of clinical illnesses that range in severity from mild to fatal. CMV is the most common cause of congenital infection, which occasionally causes the syndrome of cytomegalic inclusion disease (hepatosplenomegaly, jaundice, petechia, purpura, and microcephaly) in neonates. In immunocompetent adults, CMV infection is occasionally characterized by a mononucleosis-like syndrome. In immunosuppressed persons, including transplant recipients and patients with AIDS, CMV pneumonitis, retinitis, and gastrointestinal disease are common and can be fatal.

Primary infection occurs in a seronegative, susceptible host. Recurrent infection represents reactivation of latent infection or reinfection of a seropositive immune host. Disease may result from primary or recurrent CMV infection, but the former is more commonly associated with severe disease.

Epidemiology

Seroepidemiologic surveys demonstrate CMV infection in every population examined worldwide. The prevalence of infection increases with age and is higher in developing countries and among lower socioeconomic strata of the more developed nations.

Transmission sources of CMV include saliva, breast milk, cervical and vaginal secretions, urine, semen, tears, blood products, and organ allographs. The spread of CMV requires very close or intimate contact because it is very labile. Transmission occurs by direct person-to-person contact, but indirect transmission is possible via contaminated fomites.

The incidence of congenital CMV infection ranges from 0.2% to 2.2% (average 1%) of all live births, with the higher rates among populations with a lower economic standard of living. The risk for fetal infection is greatest with maternal primary CMV infection (30%) and much less likely with recurrent infection (<1%). In the USA, 1-4% of pregnant women acquire primary CMV infection, and as many as 8,000 newborns have neurodevelopmental sequelae associated with congenital CMV infection.

Perinatal transmission is common, accounting for an incidence of 10-60% through the 1st 6 mo of life. The most important perinatal sources of virus are genital tract secretions at delivery and breast milk. Among CMV-seropositive mothers, virus is detectable in breast milk in 96%, with postnatal transmission occurring in approximately 38% of infants, resulting in symptomatic infection in nearly half of very low birthweight infants. Infected infants may excrete virus for years in saliva and urine.

After the 1st year of life, the prevalence of infection depends on group activities, with child-care centers contributing to rapid spread of CMV among children. Infection rates of 50-80% during childhood are common. For children who are not exposed to other toddlers, the rate of infection increases very slowly throughout the 1st decade of life. A 2nd peak occurs in adolescence as a result of sexual transmission. Seronegative child-care workers and parents of young children shedding CMV have a 10-20% annual risk of acquiring CMV, in contrast to the risk of 1-3% per year for the general population.

Hospital workers are not at increased risk for acquiring CMV infection from patients. With the implementation of universal precautions, the risk of nosocomial transmission of CMV to health care workers is expected to be lower than the risk of acquiring the infection in the community.

CMV infection may be transmitted in transplanted organs (kidney, heart, bone marrow). Following transplantation, many patients excrete CMV as a result of infection acquired from the donor organ or from reactivation of latent infection caused by immunosuppression. Seronegative transplant recipients of organs from seropositive donors are at greatest risk for severe disease.

Nosocomial infection is a hazard of transfusion of blood and blood products. In a population with a 50% prevalence of CMV infection, the risk has been estimated at 2.7% per unit of whole blood. Leukocyte transfusions pose a much greater risk. Infection is usually asymptomatic, but even in well children and adults there is a risk for disease if the recipient is seronegative and receives multiple units. Immunocompromised patients and seronegative premature infants have a much higher (10-30%) risk for disease.