To determine the proportion of patients with evidence of an acute infection due to Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), Toxoplasma, or human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag, and to develop a cost-effective testing algorithm for managing such heterophile-negative patients.
We conducted a prospective investigation of 70 selected outpatients who tested negative for heterophile antibody in association with an absolute lymphocytosis or instrument-generated atypical lymphocyte flag. The control population consisted of 50 patients who were heterophile negative and had a normal absolute lymphocyte count and no instrument-generated atypical lymphocyte flag.
A large outpatient laboratory system.
Viral serology for HHV-6 was performed by immunofluorescence, and all other serologies were performed by enzyme-linked immunoassay. All testing was for immunoglobulin (Ig) M antibodies, except in the case of HIV.
The proportion of study patients positive for EBV was 40% (28/70); for CMV, 39% (27/70); for HHV-6, 25% (16/65); for Toxoplasma, 3% (2/70); and for HIV, 0% (0/70). All 50 control patients were negative for EBV IgM antibodies. When patients with more than 1 positive viral test were excluded from analysis, positivity was 20% (9/45) for EBV, 22% (10/45) for CMV, 9% (4/45) for HHV-6, and 2% (1/45) for Toxoplasma. Utilizing hypothesis-generating logistic regression models, Downey type II atypical lymphocytes were significantly associated with EBV positivity (P =.006), while Downey type III lymphocytes were significantly associated with HHV-6 positivity (P =.016), and there was a trend for the association of Downey type I lymphocytes with CMV positivity (P =.097).
A positive viral serology was identified in 70% of study patients. Multiple positive serologies complicate establishing a definitive diagnosis. Potential cost savings may be associated with the use of an appropriate testing algorithm.