Serological Responses to Toxoplasma gondii and Matrix Antigen 1 Predict the Risk of Subsequent Toxoplasmic Encephalitis in People Living With Human Immunodeficiency Virus (HIV)

Abstract

Background: Clinically useful predictors for fatal toxoplasmosis are lacking. We investigated the value of serological assays for antibodies to whole Toxoplasma antigens and to peptide antigens of the Toxoplasma cyst matrix antigen 1 (MAG1), for predicting incident toxoplasmic encephalitis (TE) in people living with human immunodeficiency virus (HIV; PLWH).

Methods: We performed a nested case control study, conducted within the Multicenter AIDS Cohort Study (MACS), using serum samples obtained 2 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 enzyme-linked immunosorbent assay (ELISA).

Results: Two years prior to clinical diagnosis, 68% of TE cases were MAG1_4.2 seropositive compared with 16% of controls (odds ratio [OR] 25.0, 95% confidence interval [CI] 3.14-199.18). Corresponding results for MAG1_5.2 seropositivity were 36% and 14% (OR 3.6, 95% CI .95-13.42). Higher levels of antibody to MAG1_4.2 (OR 18.5 per doubling of the optical density [OD] value, 95% CI 1.41-242) and to 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: Antibodies to MAG1 showed predictive value on the occurrence of TE in PLWH, and the predictive performance was further improved by adding the levels of Toxoplasma antibody. These measures could be clinically useful for predicting subsequent diseases in multiple at-risk populations.

Keywords: Toxoplasma gondii; HIV; matrix antigen 1; predict; serological responses; toxoplasmic encephalitis.

Figure 1.

Flowchart to show case and control identification. Abbreviations: HIV, human immunodeficiency virus; TE, toxoplasmic encephalitis.

Figure 2.

Distribution of antibodies to MAG1_4.2 (A), MAG1_5.2 (B), and Toxoplasma (C) by cases and controls 2 years before the diagnosis of toxoplasmic encephalitis. The length of the box corresponds to the interquartile range with the upper boundary of the box representing the 75th percentile and the lower boundary the 25th percentile. The horizontal line in the box represents the median value. The whiskers represent the minimum and maximum. The scatter plot shows individual values. Log₂-transformed values for MAG1 data were used. Abbreviations: MAG1, matrix antigen 1.