Jianchun Xiao (Baltimore, MD / US), Fiona Bhondoekhan (Baltimore, MD / US), Eric Seaberg (Baltimore, MD / US), Otto Yang (Los Angeles, CA / US), Valentina Stosor (Chicago, IL / US), Joseph Margolick (Baltimore, MD / US), Robert Yolken (Baltimore, MD / US), Raphael Viscidi (Baltimore, MD / US)
Background: There is a lack of clinically useful predictors for fatal toxoplasmosis. We investigated the value of serological assays for antibodies to whole Toxoplasma antigens and to peptide antigens of the Toxoplasma cyst protein MAG1 for predicting incident toxoplasmic encephalitis (TE) in people living with HIV (PLWH).
Methods: We performed a nested case-control study, conducted within the Multicenter AIDS Cohort Study (MACS), using serum samples obtained two years prior to diagnosis of TE from 28 cases and 37 HIV disease-matched Toxoplasma seropositive controls at matched time points. Sera were tested for Toxoplasma antibodies using a commercial assay and for antibodies to MAG1_4.2 and MAG1_5.2 peptides in ELISA.
Results: Two years before clinical diagnosis, 68% of TE cases were MAG1_4.2 seropositive, as compared to 16% of controls (OR 25.0, 95% CI 3.14-199.18). The results for MAG1_5.2 seropositivity were 36% and 14% (OR 3.6, 95% CI 0.95-13.42). Higher levels of antibody to MAG1_4.2 (OR 18.5 per doubling of the OD value, 95% CI 1.41-242) and Toxoplasma (OR 2.91 for each OD unit increase, 95% CI 1.48-5.72) were also associated with the risk of TE. When seropositivity was defined as the presence of MAG1 antibody or relatively high levels of Toxoplasma antibody, the sensitivity was 89%, and specificity was 68% for subsequent TE.
Conclusions: The presence of antibodies to MAG1 in PLWH can predict the occurrence of TE. The predictive performance of these antibodies is further improved by adding the levels of Toxoplasma antibodies. These measures could be clinically helpful in predicting subsequent diseases in multiple at-risk populations.