Primary Cytomegalovirus Infection in an Outpatient Setting—Laboratory Markers and Clinical Aspects

Abstract.

Background:

Occasionally, primary cytomegalovirus (CMV) infection may give rise to more or less severe clinical illness in immunocompetent adults. We retrospectively analyzed cases of acute CMV infection in medical outpatients.

Patients and Methods:

Over a 6-year period, we identified 22 patients with a febrile illness and hepatitis suffering from primary CMV infection. This was diagnosed on the basis of a strongly positive CMV IgM antibody test result and/or CMV IgG seroconversion. Clinical features as well as relevant laboratory results were analyzed. We also tested available samples for CMV glycoprotein B-specific antibodies and CMV IgG avidity and analyzed results of Epstein-Barr virus (EBV)-specific antibody assays. In addition, current age-specific CMV IgG seroprevalence rates were determined using 9,870 routine patient samples.

Results:

At presentation, all patients complained of malaise and fever higher than 38 °C, and many also complained of cephalgia. Most patients who underwent abdominal ultrasonography had an enlargement of the spleen. Most patients had a relative lymphocytosis but only three had a mild leukocytosis. C-reactive protein was only slightly elevated in 13 patients; all 22 patients had elevated levels of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). Half the patients reported travel to areas outside western Europe, mostly to tropical and subtropical areas, within 3 weeks before onset of illness. Primary CMV infection was confirmed by negative anti-gB antibody test results and the absence of high-avidity CMV antibodies. In contrast, despite past EBV infection demonstrated by positive anti-EBNA-1 results, 15 out of 21 patients tested for EBV markers had positive or nonspecific IgM test results. The overall CMV IgG seroprevalence rate in the routine samples was 64.4%, with marked age-dependent increases.

Conclusion:

CMV is a relevant differential diagnosis in feverish illnesses accompanied by hepatitis in otherwise healthy adults, about 40% of whom are CMV-naïve. Half our patients seem to have acquired their CMV infection abroad, so that a diagnosis of CMV infection needs to be taken into account in travelers, in addition to infectious illnesses more commonly considered in this context, such as dengue or hepatitis A. For diagnosis, both CMV and EBV antibody studies should be performed and the inclusion of assays able to demonstrate past infection is helpful for achieving a definite diagnosis.