Limitations of available tests for diagnosis of infectious mononucleosis

Among 500 students seen at a university health service for illnesses resembling infectious mononucleosis (IM), the diagnosis of IM was established in 124 (25%) on the basis of the initial presence or subsequent emergence of the spectrum of Epstein-Barr virus (EBV) antibodies characteristic of a primary EBV infection. Of these 124 patients, 113 had an EBV-specific antibody pattern in the initial serum indicative of current primary infection; however, 11 (9%) had no detectable immunoglobulin G antibodies to EBV-specific antigens in their first serum. The sensitivity of this panel of EBV antibody assays was 91% and the specificity was 100%. Initial sera had detectable heterophil antibodies for 107 (86%) of the 124 students with IM and for 2 with other illnesses. Among our patients, the Monospot (Ortho Diagnostics Inc.) test had a sensitivity of 86% and a specificity of 99%. Reliance on hematological criteria (lymphocyte count greater than or equal to 50% and atypical lymphocyte count greater than or equal to 10%) gave a sensitivity of only 39%, but a specificity of 99%. Students with IM who showed a delayed emergence of the spectrum of EBV-specific antibodies characteristic of an acute infection were compared with control patients who had such antibodies at the time of their initial visit to the health service. They were found to have a briefer duration of illness (P greater than 0.05), lower leukocyte (P less than 0.005), lymphocyte (P less than 0.005), and atypical lymphocyte (P less than 0.05) counts, and a less frequent occurrence of heterophil antibodies (P less than 0.05).