Jianchun Xiao1, Fiona Bhondoekhan2, Eric C Seaberg2, Otto Yang3, Valentina Stosor4, Joseph B Margolick5, Robert H Yolken1, Raphael P Viscidi6. 1. Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. 2. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. 3. Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. 4. Division of Infectious Diseases and Organ Transplantation, Department of Medicine and Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 5. Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. 6. Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
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.
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.
Authors: Y Suzuki; S Y Wong; F C Grumet; J Fessel; J G Montoya; A R Zolopa; A Portmore; F Schumacher-Perdreau; M Schrappe; S Köppen; B Ruf; B W Brown; J S Remington Journal: J Infect Dis Date: 1996-01 Impact factor: 5.226
Authors: Jianchun Xiao; Stephen L Buka; Tyrone D Cannon; Yasuhiro Suzuki; Raphael P Viscidi; E Fuller Torrey; Robert H Yolken Journal: Microbes Infect Date: 2009-07-26 Impact factor: 2.700
Authors: Jianchun Xiao; Ye Li; Emese Prandovszky; Geetha Kannan; Raphael P Viscidi; Mikhail V Pletnikov; Robert H Yolken Journal: PLoS Negl Trop Dis Date: 2016-04-28