Toxoplasma gondii infection is associated with changes in chronic outcomes in traumatic brain injury

Traumatic brain injury (TBI) can lead to lasting neurological and emotional effects. Latent Toxoplasma gondii (T. gondii) infection, prevalent worldwide, may exacerbate these outcomes by altering immune and neurochemical pathways. This cross-sectional observational study investigated whether chronic T. gondii infection is associated with structural brain differences and long-term outcomes in survivors of moderate-to-severe TBI ≥ 10 years post-injury. 89 TBI survivors (≥10 years post-injury) were recruited from a tertiary-centre database; 35 (39%) tested positive for latent T. gondii via plasma IgG. Thirty-two age- and sex-matched controls without TBI were included (25% T. gondii-seropositive). Nonparametric regression analyses adjusted for age, sex, and intracranial volume, with false discovery rate corrections applied. Primary outcomes were MRI-based measures of white matter microstructure, cortical thickness, and subcortical volumes. Secondary outcomes included neuropsychological assessments of anxiety, depression, cognition, and TBI blood biomarkers. Within the TBI group, T. gondii-positive individuals had reduced fibre density and increased diffusivity in the posterior corpus callosum, increased cortical thickness (insula, cuneus), and reduced brainstem volume. They also reported higher anxiety and mediation analysis showed brainstem volume partially mediated the link between infection and anxiety. Within controls, T. gondii infection was not significantly associated with anxiety, cognition, white matter microstructure, or blood biomarkers. However, controls with T. gondii infection did have increased cortical thickness in the left inferior temporal gyrus and reduced volume in the left caudate compared to their uninfected counterparts. Taken together, latent T. gondii infection may alter brain structure and exacerbate anxiety in chronic TBI. These findings support considering infection status in TBI prognostics and call for further research into its mechanistic and clinical implications.