Human CMV and the other human herpesviruses share certain common features. All human herpesviruses contain large DNA genomes, and CMV has the largest with a DNA molecular weight of 150 million. In addition, they all feature a nucleic acid core, a nucleocapsid, and an envelope glycoprotein derived primarily from the cell membrane when mature virions bud from within one cell to another. This cell membrane makes the virus very susceptible to inactivation by common disinfectants.

A transient viremia is produced by a primary infection with CMV. For immunocompetent individuals, primary CMV infections are usually always asymptomatic, although CMV occasionally causes an infectious mononucleosis syndrome in adults often consisting of fatigue and low-grade fever. For immunocompromised patients, particularly those immunosuppressed because of the acquired immunodeficiency syndrome (AIDS) or stem cell transplantation, CMV infections may cause severe disease in almost any organ system. CMV replicates in all tissues and organs, and when cell-mediated immunity is deficient, reactivation of latent CMV infections is common. The severity and location of tissue inflammation associated with CMV depend on the degree of immunosuppression. Among transplant recipients of solid organs, those who are seronegative before transplantation and acquire CMV via a donor organ or infected blood have the most severe CMV disease after transplantation. This disease is often associated with fever, neutropenia, and accelerated organ rejection.

CMV infections are best diagnosed by recovery of the virus from infected tissues or organs. In tissues with high titers of virus, histopathologic examination may reveal the presence of CMV inclusion cells. In immunocompromised patients, viremia is very common. In immunocompetent individuals, viremia occurs only transiently during a primary infection. The virus eludes antibody neutralization within tissues when it buds from cell to cell, thus causing, in most cases, a focal infection. Viral excretion in saliva or urine of the original infecting strain may resume at any time; therefore, CMV apparently becomes latent. Such latency is most frequently noted in individuals with severely impaired cellular immunity; in these individuals, a secondary viremia may disseminate the virus to all organs and tissues. Not only can a latent infection recur, but reinfection with a second strain of CMV may occur in both immunocompetent and immunocompromised individuals. To date, no studies have revealed the precise frequency of reinfection among immune (seropositive) individuals (1,2, 3, 4, 5 and 6).

Because CMV is ubiquitous in the human population, nearly all individuals eventually become infected. The percentage of seropositive individuals in central Virginia increases with age approximately 1% or 2% per year, and a mean of about 50% of the population possesses antibodies to the virus (7). Nearly 100% of these individuals are seropositive by age 70. Around the world, the mean seropositivity rate for particular populations varies with location, the frequency of breast feeding, and socioeconomic status; regardless of location, however, nearly all individuals eventually become seropositive (8, 9, 10, 11, 12 and 13).

One can also examine the prevalence of CMV infection within a particular population by determining the frequency of viral excretion. The rate of excretion for any age group depends on many factors, including geographic location, and is extremely variable. The congenital infection rate worldwide, however, is remarkably constant; in any population, between 0.5% and 2% of newborns will be excreting CMV (14,15, 16, 17 and 18).

For the most part, CMV produces no disease when acquired postnatally. Adults occasionally develop an infectious mononucleosis syndrome. Viremia will persist for a few days or weeks following a primary infection. CMV DNA in the blood detected by polymerase chain reaction and prolonged viral excretion in saliva and urine may persist for weeks or months. After infection, young children excrete CMV in saliva and urine for a period of 12 to 40 months, significantly longer than adults do (1). Immunoglobulin G antibodies to CMV appear 2 to 3 weeks following a primary infection and persist for life in both children and adults.

When, where, and how is CMV transmitted? In up to 2% of all pregnancies, transplacental transmission will occur. In the majority of cases of transmission, the mother is seropositive prior to becoming pregnant, and the infants become congenitally infected in utero following a recurrence of the mother’s infection. Although primary maternal infection during pregnancy is responsible for only a small percentage of the total number of congenitally infected newborns, it is responsible for the majority of the symptomatic infections and severe handicaps caused by congenital infection (14,15, 16, 17 and 18). Perinatal transmission rather than transplacental transmission accounts for the majority of CMV infections acquired by infants. Breast milk is the most common form of transmission of CMV from seropositive mothers and accounts for up to 50% of transmitted infections; 10% to 20% transmit the infection via cervical and vaginal secretions (19). Also, CMV can be acquired postnatally from other children, as in a day care setting; intrafamilial transmission is frequent following a primary infection in a single family member, with a rate of transmission of about 50% (20).

CMV is frequently excreted in semen and cervical secretions. In addition, CMV infections are more prevalent among those who have multiple sex partners. However, the frequency of sexual transmission of CMV is problematic, because the virus can be transmitted orally or by close and frequent contact.

There is clear evidence of how slowly CMV is transmitted, even under optimal circumstances, which has been documented in studies of CMV transmission among children in day care. Children initially shed CMV at a concentration of about 104 plaque-forming units per milliliter of urine following a primary infection; this titer declines slowly thereafter (21). Those under 2 years of age shed CMV for between 6 and 40 months, with a mean of about 2 years (1).

Our group monitored three day care centers in Richmond for 3 years (1). At the three centers, 14%, 27%, and 45% of the children became infected, with the majority becoming infected in the second year of life. The most significant data indicate that even at the center with the highest rate of infection, on average only one child per month acquired a primary CMV infection. Therefore, even under ideal transmission conditions of close, intimate daily contact (i.e., children playing daily together in the same room), the virus is transmitted slowly.

The period for CMV transmission from infected children to their mothers or caregivers is also very slow and depends on the age of an infected child (22). We observed that among the seronegative mothers of infected children, 16 (57%) of 28 mothers with infected children 20 months of age or younger acquired CMV from their children, while only 3 (14%) of 22 mothers with infected children over 20 months of age acquired the infection (p < .007). In the group of mothers with infected children <20 months of age, the average interval between identification of the child’s infection and transmission to the mother was 8 months (SD = ±6 months).

Caregivers can also be infected with CMV through transmission from children (23, 24 and 25). We studied 614 caregivers in Richmond, and the rate of CMV infections among caregivers was independently associated with the age and race of the caregiver and the ages of children for whom they cared. The highest rate of CMV infections occurred in women caring for children younger than 2 years independently of age and race (23,24). For the caregivers in our study, the annual seroconversion rate was 11% for a group of 202 initially seronegative women, compared with a 2% rate for hospital employees during the same period.