Latent toxoplasmosis is associated with neurocognitive impairment in young adults with and without chronic HIV infection

Highlights

• We found a significant main effect for Toxoplasmosis and HIV on cognitive performance

• In HIV-infected participants lower T. gondii IgG levels were associated with worse cognitive performance

• Latent toxoplasmosis was not associated with behavioral changes and risk-taking behaviors in study participants

• In HIV-infected patients, latent toxoplasmosis is a risk factor for neurocognitive impairment

Abstract

We evaluated the impact of latent toxoplasmosis (LT) on neurocognitive (NC) and neurobehavioural functioning in young adults with and without chronic HIV infection, using a standardised NC test battery, self-reported Beck Depression Inventory, Frontal System Behavior Scale, MINI-International Neuropsychiatric Interview and risk-assessment battery.

194 young adults (median age 24 years, 48.2% males) with chronic HIV infection (HIV +) since childhood and 51 HIV seronegative (HIV −) participants were included. HIV + individuals had good current immunological status (median CD4: 479 cells/μl) despite a low CD4 nadir (median: 93 cells/μl). LT (positive anti-Toxoplasma IgG antibodies) was present in one third of participants. The impairment rates in the HIV − with and without Toxo were not significantly different (p = 0.17). However, we observed an increasing trend (p < 0.001) in impairment rates with HIV and LT status: HIV −/LT − (6.1%); HIV −/LT + (22%), HIV +/LT − (31%), HIV +/LT + (49%). In a multivariable analysis using the entire study group there were main effects on cognition for HIV and also for LT. Within the HIV + group LT was associated with worse performance globally (p = 0.006), in memory (p = 0.009), speed of information processing (p = 0.01), verbal (p = 0.02) and learning (p = 0.02) domains. LT was not associated with depressive symptoms, frontal systems dysfunction or risk behaviors in any of the groups. HIV participants with lower Toxoplasma antibody concentration had worse NC performance, with higher GDS values (p = 0.03) and worse learning (p = 0.002), memory (p = 0.006), speed of information processing (p = 0.01) T scores.

Latent Toxoplasmosis may contribute to NC impairment in young adults, including those with and without chronic HIV infection.

Introduction

Latent Toxoplasma gondii (LT) infection had long been assumed to be asymptomatic, but increased evidence links its presence to increased risk for psychiatric conditions such as schizophrenia (Nimgaonkar & Yolken, 2012), bipolar disorder (Dickerson et al., 2014) and suicidal behavior (Okusaga and Postolache, 2012, Zhang et al., 2012). The presence of Toxoplasma gondii antibodies has also been associated with neurodegenerative syndromes such as Parkinson's Disease (Miman et al., 2010).

Several studies reported the association between Toxoplasma gondii seropositivity and poor cognitive scores, especially in certain groups of people with low-income (Pearce et al., 2014) and low education (Gale et al., 2014a). Worse performance on cognitive tests associated with Toxoplasma gondii was reported for reaction time, concentration (Havlicek et al., 2001), learning and memory (Gajewski et al., 2014). Moreover, latent toxoplasmosis was associated with impulsive behaviours such as higher risk for work- and traffic- accidents (Alvarado-Esquivel et al., 2012, Flegr, 2013, Yereli et al., 2006).

Toxoplasma gondii tachyzoites are capable of invading microglia, astrocytes, and neurons (Koshy & Cabral, 2014); the parasite thereafter forms cysts within these cells (Luder et al., 1999, Carruthers and Suzuki, 2007). Parasite strains can differ greatly in their aggressiveness during infection and in their propensity to form cysts for long-term survival (Song et al., 2013). Significant production of dopamine by Toxoplasma gondii induces increased production of tachyzoites and destruction of cyst walls (Strobl et al., 2012) and may be responsible for behavioural changes (Prandovszky et al., 2011). Higher anti-Toxoplasma antibody levels have correlated with more severe psychiatric symptoms (Hinze-Selch et al., 2010, Hinze-Selch et al., 2007), although the relationship between antibody levels and cognition is not always clear (Havlicek et al., 2001).

Almost half of the HIV-infected population has neurocognitive (NC) impairment, typically mild to moderate in severity (Heaton et al., 2010, Chan and Brew, 2014). While conditions like ageing, drug abuse and chronic hepatitis C can contribute to NC impairment in HIV-infected patients (Schuster & Gonzalez, 2012), the influence of LT has received only limited attention (Bharti et al., 2012).

We aimed to evaluate the contribution of latent infection with Toxoplasma gondii on NC performance and neuropsychiatric conditions (depression and suicidal risk, conditions associated with frontal-subcortical circuitry damage and risk taking behaviors) in a group of young adults with and without chronic HIV infection since childhood.