Cytomegalovirus (CMV) infection typically occurs early in childhood and is relatively asymptomatic. In immunocompromised persons, such as transplant patients or those with human immunodeficiency virus infection, reactivation of CMV infection can cause severe complications, as can vertical transmission to a fetus when the mother acquires primary CMV infection during pregnancy. When Wreghitt and associates encountered relatively symptomatic CMV infections in older persons who had acquired the infection from their grandchildren (dubbed “the feverish granny syndrome”), it piqued their interest in the diagnosis of primary CMV infection in immunocompetent persons beyond childhood.

General practitioners in the Cambridge and Chelsford communities in England referred previously healthy patients seen in the office with symptoms suggestive of CMV infection, such as fever, malaise, hepatitis, lymphadenopathy, sore throat, and sweats. The investigators also screened hospitalized patients in their area for these symptoms. The diagnosis of primary CMV infection was established by finding increased IgM antibodies for CMV, with no increased titers for CMV IgG antibodies.

Of the 7,630 patients screened, documented CMV infection was present in 124 patients (1.6 percent). The age range of infected patients was 16 to 86 years, with equal numbers of males and females infected. The most common finding was elevated liver enzyme levels (mean alanine transaminase level of 121 U per L), while the most frequently encountered symptoms were malaise, fever and sweats, respiratory symptoms, myalgias, lymphadenopathy, and jaundice (see accompanying table).

IgM antibodies for CMV persisted for four to six months after the onset of symptoms, and IgG antibodies appeared within two to three weeks of infection. Fifteen patients (12 percent) had a relapsing course, marked by initial improvement that was followed by recurrent symptoms. The total duration of illness in relapsing patients ranged from one to 32 weeks. Follow-up questionnaires sent to the referring physicians for established CMV infection cases revealed no prior use of immunosuppressive medications (other than steroid use in four patients) and no subsequently diagnosed malignancies. Four patients were pregnant at the time of primary CMV infection, resulting in one infant who was delivered with intrauterine growth retardation and severe hearing impairment.

The authors conclude that primary CMV infection accounts for about 2 percent of adults with febrile illnesses, a number significant enough to warrant referral for testing by a medical examiner. The most common clinical factor that distinguished primary CMV infection among these febrile patients was elevated liver enzyme levels.