onset – Toxoplasma gondii & Human Phenotype

Toxoplasma gondii as a possible causative pathogen of type-1 diabetes mellitus: Evidence from case-control and experimental studies

September 3, 2018
Beshay, E. V. N., El-Refai, S. A., Helwa, M. A., Atia, A. F., Dawoud, M. M.
Experimental Parasitology 2018; 188: 93-101

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Toxoplasma gondii is the causative parasite of an important worldwide disease. This obligate intracellular parasite can infect and replicate inside any nucleated cells including those of pancreas. Insulin is a hormone secreted by the pancreas and is responsible for controlling blood glucose concentration. Deficiency of insulin production accounts for the occurrence of type-1 diabetes mellitus (T1D). Thus, theoretically, toxoplasmosis could play a possible role in the development of T1D. However, the studies on this theory are still insufficient; therefore, this work was designed. Interestingly, in the case-control study, seropositivity of anti-Toxoplasma IgG was significantly higher among T1D (86.37%) in comparison with T2D (66.67%) and the control group (60%). Moreover, the odd ratio of chronic toxoplasmosis was 4.2 folds higher among T1D patients than among controls. The experimental study included acute and chronic Me49 T gondii infected mice groups in addition to a control group. Pathological examination revealed the presence of T gondii zoites adjacent to the islets of Langerhans and in pancreatic parenchyma of acutely infected mice. With chronic infection, there was a significant reduction of islets number and sizes in association with grade-1 insulitis. Additionally, the immunohistochemical study showed significant infiltration of the islets of chronically infected mice by CD8(+) and CD45(+) immune cells. In contrary to the control group, the islets of the chronic group showed significantly higher expression of the apoptotic marker caspase-3 and a significantly lower expression of the proliferation marker Ki69. Finally, a significant reduction of insulin expression in the islets of chronic infection group was detected in association with a significant increase in serum glucose concentrations; however, the establishment of diabetes did not occur throughout this work. Thus, this study presents an evidence for the probable role of chronic toxoplasmosis in the development of T1D which should be considered in further studies

Toxoplasma gondii exposure and Parkinson’s disease: a case-control study

October 3, 2017
Alvarado-Esquivel, C., Mendez-Hernandez, E. M., Salas-Pacheco, J. M., Ruano-Calderon, L. A., Hernandez-Tinoco, J., Arias-Carrion, O., Sanchez-Anguiano, L. F., Castellanos-Juarez, F. X., Sandoval-Carrillo, A. A., Liesenfeld, O., Ramos-Nevarez, A.
Bmj Open 2017; 7

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Objectives: To determine the association between Toxoplasma gondii infection and Parkinson's disease and to investigate whether T. gondii seropositivity is associated with the general characteristics of patients with Parkinson's disease. Design: Case-control study. Setting: Cases and controls were enrolled in Durango City, Mexico. Participants: 65 patients with Parkinson's disease and 195 age-and gender-matched control subjects without Parkinson's disease. Primary and secondary outcome measures: Serum samples of participants were analysed for anti-T. gondii IgG and IgM antibodies by commercially available enzyme-linked immunoassays. Prevalence of T. gondii DNA was determined in seropositive subjects using PCR. The association between clinical data and infection was examined by bivariate analysis. Results: Anti-T. gondii IgG antibodies were found in 6/65 cases (9.2%) and in 21/195 controls (10.8%) (OR 0.84; 95% CI 0.32 to 2.18; p=0.81). The frequency of high (>150 IU/mL) antibody levels was similar among cases and controls (p=0.34). None of the anti-T. gondii IgG positive cases and four of the anti-T. gondii IgG positive controls had anti-T. gondii IgM antibodies (p=0.54). The prevalence of T. gondii DNA was comparable in seropositive cases and controls (16.7% and 25%, respectively; p=1.0). Seroprevalence of T. gondii infection was associated with a young age onset of disease (p=0.03), high Unified Parkinson Disease Rating Scale scores (p=0.04) and depression (p=0.02). Seropositivity to T. gondii infection was lower in patients treated with pramipexole than in patients without this treatment (p=0.01). However, none of the associations remained significant after Bonferroni correction. Conclusions: The results do not support an association between T. gondii infection and Parkinson's disease. However, T. gondii infection might have an influence on certain symptoms of Parkinson's disease. Further research to elucidate the role of T. gondii exposure on Parkinson's disease is warranted.

Treatment with anti-toxoplasmic activity (TATA) for Toxoplasma positive patients with bipolar disorders or schizophrenia: A cross-sectional study

October 9, 2015
Fond, G., Boyer, L., Gaman, A., Laouamri, H., Attiba, D., Richard, J. R., Delavest, M., Houenou, J., Le Corvoisier, P., Charron, D., Krishnamoorthy, R., Oliveira, J., Tamouza, R., Yolken, R., Dickerson, F., Leboyer, M., Hamdani, N.
Journal of Psychiatric Research 2015; 63: 58-64.

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Objective: The association between Toxoplasma gondii seropositivity and respectively Bipolar Disorder (BD) and Schizophrenia/Schizoaffective disorder (SZ) is one of the most studied link between one pathogen and psychiatric disorders. The aim of the present study was thus to retrospectively determine if the administration of an antipsychotic and/or a mood stabilizer having known in vitro Anti-Toxoplasmic Activity (TATA+) was associated with a better clinical outcome in a population of 152 BD or 114 SZ patients and seropositive for T gondii infection compared to patients receiving a treatment without anti-toxoplasmic activity (TATA-). Methods: This multicenter study was conducted in an academic public hospital during a 3-years period between 2009 and 2011. All consecutive inpatients and outpatients with SZ or BD diagnosis with a stable treatment for more than 4 weeks were recruited. socio-demographic and clinical characteristics measured with validated scales as well as a serological status for toxoplasmic infection were included. Treatments were classified according to their in vitro antitoxoplasmic activity. A multivariate model was used to determine the clinical characteristics that were significantly different between patients receiving a treatment with no antitoxoplasmic activity compared to others. Results: BD patients with positive serum antibodies against T gondii presented more lifetime depressive episodes (p = 0.048) after adjustment forage, sex and sociodemographic characteristics when treated by drug having no anti-toxo activity, compared to patients having received drugs with anti-toxo activity. A significant difference was not found in BD toxonegative patients and in SZ toxopositive or toxonegative patients. Conclusions: It seems to be of importance to consider prescribing a drug with a clear anti-toxoplasmic activity (TATA+) for BD patients seropositive to T. gondii, in particular valproate that was found as the mood stabilizer with the highest antitoxoplasmic activity. Prospective randomized controlled trials are warranted to confirm this preliminary data.

Does Toxoplasma gondii play a role in obsessive-compulsive disorder?

October 11, 2012
Taboas W, McKay D, Taylor S.
Psychiatry Research 2012; 198: 176-177