Latent toxoplasmosis is associated with neurocognitive impairment in young adults with and without chronic HIV infection
Graphical abstract
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.
Section snippets
Study participants
We included in the current study all 194 HIV + and 51 HIV −, age-matched participants recruited until 1-Oct-2014 in a cross-sectional study of the long-term effects of chronic HIV infection on the developing brain. The HIV + participants had previously documented HIV infection, epidemiological data supporting parenteral non-IDU route of HIV transmission during the Romanian HIV Paediatric epidemic. Inclusion criteria were: at least 8 years of education, no NC impairment unrelated to HIV or
HIV + and HIV − group characteristics
Demographic and disease characteristics are summarized in Table 1. HIV + and HIV − participants did not differ in age, gender, or body mass index (BMI). Three participants had chronic hepatitis C infection; none had current or past Toxoplasma encephalitis.
The prevalence of positive Toxoplasma IgG antibodies was 35.3% in the HIV − group and 32.4% in the HIV + group. None of the participants had IgM antibodies.
Overall, NCI was more common among HIV + subjects, compared to HIV − participants (36.5% vs.
Discussion
In this analysis of nearly 250 HIV + and HIV − adults, we found latent Toxoplasmosis was associated with worse overall cognitive performance. While HIV + participants as a group performed more poorly than the HIV- participants, the presence of anti-Toxoplasma IgG antibodies was also associated with a significantly higher rate of overall impairment in HIV + individuals, supporting the hypothesis that latent Toxoplasma infection contributes to the brain injury that can occur in adults with chronic
Funding
This work was supported by 1R01MH094159 and P30 MH62512 from National Institute of Mental Health.
Authors declaration
I, Luminita Ene certify herby that this manuscript contains original work and that it has not been published or submitted for publication elsewhere.
Acknowledgements
We also want to thank to all the participants in the study, Mr. Terence Hendrix from the HIV Neurobehavioural Research Center, Drs., Roxana Radoi, Ruxandra Burlacu, Simona Tetradov and Psych. Anca Luca, Psych Adina Bulacu-Talnariu, Psych. Adrian Luca for neurocognitive and neuropsychological testing.
This work was presented in part at the 13th International Symposium on NeuroVirology, June 2-6, 2015 San Diego, California, USA, abstract P40.
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