Estimations of the number people with mental diseases associated with toxoplasmosis and identification of risk factors by continent

Exposure to infectious agents like herpesvirus, influenza, and Toxoplasma gondii has been identified as risk factors for psychiatric diseases (Barichello et al., 2016). In particular, Toxoplasma gondii, a neurotropic parasite, is associated with many important mental diseases such as schizophrenia (Sutterland et al., 2013), bipolar disorder (de Barros et al., 2017), obsessive compulsive disorder (Nayeri Chegeni et al., 2019a) and suicidal behavior (Sutterland et al., 2019). Solid evidence has emerged through clinical (Fond et al., 2018), serological (Torrey et al., 2007), pharmacological (Fond et al., 2015), pathological (Hayes et al., 2014), genomic (Wang et al., 2019) and experimental studies (Elsheikha et al., 2016) that toxoplasmosis increases risks for schizophrenia (Sutterland et al., 2013), bipolar disorder (Sutterland et al., 2013), suicidal behavior (Sutterland et al., 2019) and obsessive-compulsive disorder (Nayeri Chegeni et al., 2019a), but not major depression (Nayeri Chegeni et al., 2019c), or Alzheimer disease (Nayeri Chegeni et al., 2019b) or Parkinson disease (Bayani et al., 2019; Zhou et al., 2019).

The association of toxoplasmosis with certain mental disorders can be explained by the location of parasite on specific anatomical regions of the brain as shown by the mouse model (Berenreiterová et al., 2011) and pathological descriptions on the human brain (McConkey et al., 2013; Strittmatter et al., 1992). Results are supported by changes observed on the neurotransmitter dopamine distribution (Hsu et al., 2014; Skallova et al., 2006) and in the brain architecture (Horacek et al., 2012). Focalized neuroimmune response during Toxoplasma infection can be the key component at the basis of the effect on the brain (Frickel and Hunter, 2021). Experimental studies on rodents demonstrated the preference of T. gondii for glia and neurons cells within the brain, and preferential localization in amygdala and cortex prefrontal regions that have important impact upon behavioral and emotional decisions (Berenreiterová et al., 2011). Toxoplasma infection remains in latent stage in the form of tissue cysts containing bradyzoites that replicate slowly but which have sporadic bursts of proliferation (Frickel and Hunter, 2021). Studies have suggested that neuroinflammation derived from these episodes might be responsible for behavioral changes, with cyst burden as the major driver of inflammatory response in the brain (Xiao, 2020).

Estimations of the public health impact caused by Toxoplasma infection have been made for encephalitis in HIV patients (Wang et al., 2017b) and for congenital toxoplasmosis (Torgerson and Mastroiacovo, 2013) but not for psychiatric disorders, therefore urgent calls were made for assessment of the impact that toxoplasmosis can have associated to mental diseases (Kirby, 2012; The Lancet Infectious Diseases, 2012). Previous work estimated the attributable fraction for some mental diseases (Milne et al., 2020; Smith, 2014) but a complete estimation of the global burden has not been made, this can be explained -in part- by the lack of prevalence data for some regions in the world.

This study first updated the information from meta-analysis to obtain the attributable fraction according to this information and then estimate the number of people with mental disease associated with toxoplasmosis. Then, by using a Bayesian prevalence prediction model that incorporated recent knowledge about risk factors for the general population, prevalence was obtained for countries with lack of information and the risk factors linked to toxoplasmosis associated with mental diseases by continent were identified.

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