Toxoplasmosis and Neuropsychological Effects

Toxoplasma gondii is an intracellular protozoan parasite. Approximately 30% of the global population is infected by T. gondii. In chronically infected individuals, the parasite resides in tissue cysts, especially in the brain. There is a growing interest in the role of parasitologic agents in the causation of neuropsychological disorders. In this review, we have explained the interactions between Toxoplasma and its host, mechanisms, and consequences on neural and psychological diseases.

Cerebrospinal fluid kynurenine and kynurenic acid concentrations are associated with coma duration and long-term neurocognitive impairment in Ugandan children with cerebral malaria.

BACKGROUND: One-fourth of children with cerebral malaria (CM) retain cognitive sequelae up to 2 years after acute disease. The kynurenine pathway of the brain, forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid (KYNA), has been implicated in long-term cognitive dysfunction in other CNS infections. In the present study, the association between the kynurenine pathway and neurologic/cognitive complications in children with CM was investigated. METHODS: Cerebrospinal fluid (CSF) concentrations of KYNA and its precursor kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala, Uganda, between 2008 and 2013 were assessed. CSF kynurenine and KYNA were compared to CSF cytokine levels, acute and long-term neurologic complications, and long-term cognitive impairments. CSF kynurenine and KYNA from eight Swedish children without neurological or infectious disease admitted to Astrid Lindgren's Children's Hospital were quantified and used for comparison. RESULTS: Children with CM had significantly higher CSF concentration of kynurenine and KYNA than Swedish children (P < 0.0001 for both), and CSF kynurenine and KYNA were positively correlated. In children with CM, CSF kynurenine and KYNA concentrations were associated with coma duration in children of all ages (P = 0.003 and 0.04, respectively), and CSF kynurenine concentrations were associated with worse overall cognition (P = 0.056) and attention (P = 0.003) at 12-month follow-up in children ≥5 years old. CONCLUSIONS: CSF KYNA and kynurenine are elevated in children with CM, indicating an inhibition of glutamatergic and cholinergic signaling. This inhibition may lead acutely to prolonged coma and long-term to impairment of attention and cognition.

Elevated cerebrospinal fluid tumour necrosis factor is associated with acute and long-term neurocognitive impairment in cerebral malaria.

Systemic tumour necrosis factor-α (TNF-α) may contribute to the pathogenesis of cerebral malaria (CM) by promoting endothelial activation and parasite sequestration. However, less is known about the role of central nervous system (CNS) TNF-α in CM. We assessed plasma (n=249) and cerebrospinal fluid (CSF) (n=167) TNF-α levels in Ugandan children with CM, plasma TNF-α in Ugandan community control children (n=198) and CSF TNF-α in North American control children who had recovered from leukaemia (n=13). Plasma and CSF TNF-α were measured by magnetic bead assay. We compared plasma and CSF TNF-α levels in children with CM to mortality, acute and chronic neurologic deficits and long-term neurocognitive impairment. Plasma and CSF TNF-α levels were higher in CM than control children (P<.0001 for both). CSF TNF-α levels were higher in children who had neurologic deficits at discharge or 6-month follow-up (P≤.05 for both). Elevated CSF but not plasma TNF-α was associated with longer coma duration (Spearman's rho .18, P=.02) and deficits in overall cognition in children 5 years and older (ß coefficient -.74, 95% CI -1.35 to -0.13, P=.02). The study findings suggest that CNS TNF-α may be involved in the development of acute and chronic neurologic and cognitive sequelae in children with CM.

Latent Toxoplasma Infection and Higher Toxoplasma gondii Immunoglobulin G Levels Are Associated With Worse Neurocognitive Functioning in HIV-Infected Adults.

BACKGROUND: Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist despite suppressive antiretroviral therapy (ART). Because latent Toxoplasma infection (LTI) may adversely impact brain function, we investigated its impact on neurocognitive impairment (NCI) in people living with HIV disease. METHODS: Two hundred sixty-three HIV-infected adults underwent comprehensive neurocognitive assessments and had anti-Toxoplasma gondii immunoglobulin G (anti-Toxo IgG) measured by qualitative and quantitative enzyme-linked immunosorbent assays. RESULTS: Participants were mostly middle-aged white men who were taking ART (70%). LTI was detected in 30 (11.4%) participants and was associated with a significantly greater prevalence of global NCI (LTI positive [LTI+] = 57% and LTI negative [LTI-] = 34%) (odds ratio, 1.67; 95% confidence interval, 1.17-2.40; P = .017). Deficits were more prevalent in the LTI+ vs the LTI- group in 6 of 7 cognitive domains with statistical significance reached for delayed recall (P < .01). The probability of NCI increased with higher CD4+ T-cell counts among LTI+ individuals but with lower CD4+ T-cell counts in LTI- persons. A strong correlation (r = .93) between anti-Toxo IgG levels and global deficit score was found in a subgroup of 9 patients. Biomarkers indicative of central nervous system inflammation did not differ between LTI+ and LTI- participants. CONCLUSIONS: In this cross-sectional analysis, LTI was associated with NCI, especially in those with higher CD4+ T-cell counts. Longitudinal studies to investigate the role of neuroinflammation and neuronal injury in LTI patients with NCI and trials of anti-Toxoplasma therapy should be pursued.

A case of vivax malaria presenting with psychosis.

The first case of psychosis due to Plasmodium vivax malaria, imported from India is reported. A 44-year-old Trinidadian male presented with fever, and psychotic episodes in association with vivax malaria. The symptoms of both malaria and psychosis were resolved following the standard chloroquine-primaquine therapy.