Toxoplasma gondii infection link with neuro-cognitive impairment

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Toxoplasma gondii infection was associated with neuro-cognitive impairment among patients with HIV, Healio reports according to a University of California study. The association was particularly strong in those with higher CD-4 counts, the researchers reported.

“(HIV)-associated neuro-cognitive disorder (HAND) is a well-recognized complication of HIV-1 infection that can impede employment, activities of daily living and ultimately survival. … Recent evidence from animal and human studies suggests that (latent Toxoplasma infection) can result in behavioural changes, including increased impulsivity, aggression and suicide attempts; difficulties with learning in mice; and with memory, reaction time and higher risk of traffic accidents in humans,” Dr Ajay R Bharti, of the department of medicine at the University of California – San Diego, and colleagues wrote.

Researchers performed neuro-cognitive assessments on 263 patients with HIV and tested them for latent Toxoplasma infection – 70% were receiving ART, most participants were white (59%) and 90% were men. Mean age was 42 years, and mean duration of education was 12.6 years. Median CD-4 count was 387 cells/µL (interquartile range, 231-582 cells/µL).

Thirty (11.4%) participants had latent Toxoplasma infection, Bharti and colleagues reported, with no differences in race or ethnicity associated with infection (P > .8).

Undetectable levels of HIV RNA were present in fewer than half of patients in the study. However, the percentage of participants with detectable HIV-RNA was higher among those with Toxoplasma than those without the infection (57% vs 44%; P = .18).

Bharti and colleagues reported that 57% of patients with Toxoplasma infection had neuro-cognitive impairment, compared with 34% of uninfected patients, indicating a significant association between the infection and neuro-cognitive impairment (OR = 1.67; 95% CI, 1.17-2.4). The probability of neuro-cognitive impairment increased alongside rising CD-4 counts in Toxoplasma-infected patients (P = .001), and had an inverse relationship to CD-4 counts in uninfected patients (P = .021).

“Longitudinal studies of patients before and after ART initiation could test our hypothesis that immune reconstitution plays a role in the pathogenesis of cognitive impairment in patients with (latent Toxoplasma infection). Intervention trials with existing or investigational drugs active against Toxoplasma cysts would further strengthen our findings and could lead to new treatments for HAND in people living with (latent Toxoplasma infection),” Bharti and colleagues wrote.

Abstract
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.

Authors
Ajay R Bharti, Allen McCutchan, Reena Deutsch, Davey M Smith, Ronald J Ellis, Mariana Cherner, Steven P Woods, Robert K Heaton, Igor Grant, Scott L Letendre

Healio report
Clinical Infectious Diseases abstract


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