A Prospective Evaluation of Heterophile and Epstein-Barr Virus-Specific IgM Antibody Tests in Clinical and Subclinical Infectious Mononucleosis: Specificity and Sensitivity of the Tests and Persistence of Antibody

Abstract

Three heterophile antibody tests and a test specific for IgM antibody to Epstein-Barr virus were evaluated during prospective studies of infectious mononucleosis. Specificity was judged by the frequency of false-positive results in sera of known qualities taken before illness; except for two patients bled during early, unrecognized illnes,, titers of greater than or equal to 1:40 were detected in 12% by the absorbed sheep red cell test, in 6.7% by the absorbed horse red cell test, and in none by the beef cell hemolysin test. None had IgM antibody specific for Epstein-Barr virus in sera obtained before illness. In addition, no rises in titer of heterophile antibody were detected by the horse cell test in 38 patients with proved rubella and/or influenza infection. In terms of sensitivity (indicated by the percentage of cases with diagnostic titers during infectious mononucleosis), 97% were positive by the Epstein-Barr virus IgM test, 96% by the horse cell agglutination test, 85% by the beef hemolysin test, and 81% by the sheep cell agglutination test. Persistence of antibody was judged by serial bleedings up to three years after illness; titers of heterophile antibody by the sheep agglutination and beef hemolysin tests as well as titers of IgM antibody to Epstein-Barr virus returned to normal in two to three months, whereas the horse cell heterophile test remained positive for a year or more in 75%. Inapparent and mild infections with Epstein-Barr virus resulted in the production of horse cell heterophile antibody in 48.4% of 122 subjects.

Serological diagnosis of infectious mononucleosis using three anti-Epstein-Barr virus recombinant ELISAs

“…However, when the antibody response to individual viral polypeptides was determined by immunoblot, IgG and IgM reactivity to the EA polypeptides ~138 and ~45-52 was detectable in the first serum samples of all acutely infected IM patients (Middeldorp and Herbrink, 1988). Recently, Gorgievski-Hrisoho et al (1990) tested several recombinant EBV antigens, selected by Wolf et al (1985) and Motz et al (1986), with respect to reactivity among well-defined IM sera. It was shown, that particularly the EA proteins ~138 and p54 were excellently recognized by sera from patients with acute IM.…”

“…Testing for heterophile antibodies is still widespread in routine diagnosis. However, despite the relatively high degree of specificity of the Paul-Bunnell agglutinins for the early stage of IM the test fails in some cases particularly with young children (Evans et al, 1975, Schmitz et al, 1972. Therefore, serodiagnosis of IM by measuring the specific antibody response is clearly to be preferred.…”

“…Several putative test-antigens have been evaluated extensively recently. (Hinderer et al, 1988, Gorgievski-Hrisoho et al, 1990. Three were used to develop a new generation of EBV-ELISA ('Biotest Anti-EBV recombinant') for detecting IgG and IgM antibodies to EA (~138 and ~54) and IgG antibodies to EBNA (~72).…”

Limitations of available tests for diagnosis of infectious mononucleosis

“…Reliance on the presence of HA and the hematological findings is the general practice for college students (4,12,14). Studies of patients with IM have shown that the majority have a positive test for HA and an absolute lymphocytosis, with 10% or more atypical cells (1,4,13,15,17,18,20).…”

“…Studies of patients with IM have shown that the majority have a positive test for HA and an absolute lymphocytosis, with 10% or more atypical cells (1,4,13,15,17,18,20). Evans and colleagues (4) found …”