mechanisms
Seroprevalence and serointensity of latent Toxoplasma gondii in a sample of elderly adults with and without Alzheimer disease
Perry, C. E., Gale, S. D., Erickson, L., Wilson, E., Nielsen, B., Kauwe, J., Hedges, D. W.
Alzheimer Disease and Associated Disorders 2016; 30: 123-126
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Introduction: Latent infection with Toxoplasma gondii has been associated with behavioral and cognitive changes in animal models and in humans. Early findings have suggested an association between latent toxoplasmosis and Alzheimer disease (AD). On the basis of these factors, we sought to determine whether there is an association between latent toxoplasmosis and AD using a large, well-characterized sample of subjects with AD and age-matched and sex-matched controls without dementia.
Methods: Using ELISA, we determined anti-T. gondii IgG antibody titers in 114 control subjects and in 105 subjects diagnosed with AD through an Alzheimer's Disease Research Center.
Results: There were no group differences between groups in age, ethnicity, or sex. Education and socioeconomic status was slightly higher in the control group. Neither the prevalence of anti-T. gondii IgG antibodies (33% in the nondemented control group compared with 41% in the AD group, P= 0.25) nor log-transformed antibody concentration (106.6 IU/mL in the control group compared with 140.9 IU/mL in the AD group, P= 0.85) differed between the control and AD groups.
Discussion: In this sample, we found neither a higher prevalence of latent toxoplasmosis in the AD group compared with the control group nor differences in serum anti-T. gondii IgG titers between groups.
Neurobiological studies on the relationship between toxoplasmosis and neuropsychiatric diseases
Fabiani, S., Pinto, B., Bonuccelli, U., Bruschi, F.
Journal of the Neurological Sciences 2015; 35:3-8
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Toxoplasma gondii is a widespread protozoan parasite infecting approximately one third of the world population. After proliferation of tachyzoites during the acute stage, the parasite forms tissue cysts in various anatomical sites including the Central Nervous tissue, and establishes a chronic infection. Clinical spectrum normally ranges from a completely asymptomatic infection to severe multi-organ involvement. Many studies have suggested T. gondii infection as a risk factor for the development of some neuropsychiatric disorders, particularly schizophrenia. During the last years, a potential link with other neurobiological diseases such as Parkinson disease and Alzheimer disease has also been suggested. This review will focus on neurobiological and epidemiological data relating infection with T. gondii to neuropsychiatric diseases. (C) 2015 Elsevier B.V. All rights reserved.
Toxoplasma gondii infection and self-directed violence in mothers
Pedersen, M. G., Mortensen, P. B., Norgaard-Pedersen, B., Postolache, T. T.
Archives of General Psychiatry 2012; 69: 1123-1130
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Context: Two studies based on clinical samples have found an association between Toxoplasma gondii infection and history of suicide attempt. To our knowledge, these findings have never been replicated in a prospective cohort study.
Objective: To examine whether T gondii-infected mothers have an increased risk of self-directed violence, violent suicide attempts, and suicide and whether the risk depends on the level of T gondii IgG antibodies.
Design: Register-based prospective cohort study. Women were followed up from the date of delivery, 1992 to 1995 until 2006.
Setting: Denmark.
Participants: A cohort of 45 788 women born in Denmark whose level of Toxoplasma-specific IgG antibodies was measured in connection with child birth between 1992 and 1995.
Main Outcome Measures: Incidence rates of self-directed violence, violent suicide attempts, and suicide in relation to T gondii seropositivity and serointensity.
Results: T gondii-infected mothers had a relative risk of self-directed violence of 1.53 (95% CI, 1.27-1.85) compared with noninfected mothers, and the risk seemed to increase with increasing IgG antibody level. For violent suicide attempts, the relative risk was 1.81 (95% CI, 1.13-2.84) and for suicide, 2.05 (95% CI, 0.78-5.20). A similar association was found for repetition of self-directed violence, with a relative risk of 1.54 (95% CI, 0.98-2.39).
Conclusion: Women with a T gondii infection have an increased risk of self-directed violence. Arch Gen Psychiatry. 2012;69(11):1123-1130. Published online July 2, 2012. doi:10.1001/archgenpsychiatry.2012.668
Autism spectrum disorders may be due to cerebral toxoplasmosis associated with chronic neuroinflammation causing persistent hypercytokinemia that resulted in an increased lipid peroxidation, oxidative stress, and depressed metabolism of endogenous and exogenous substances
Prandota J.
Research in Autism Spectrum Disorders 2010; 4: 119-155
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Worldwide, approximately 2 billion people are chronically infected with Toxoplasma gondii with largely yet unknown consequences. Patients with autism spectrum disorders (ASD) similarly as mice with chronic toxoplasmosis have persistent neuroinflammation, hypercytokinemia with hypermetabolism associated with enhanced lipid peroxidation, and extreme changes in the weight resulting in obesity or wasting. Data presented in this review suggest that environmental triggering factors such as pregnancy, viral/bacterial infections, vaccinations, medications, and other substances caused reactivation of latent cerebral toxoplasmosis because of changes in intensity of latent central nervous system T. gondii infection/inflammation and finally resulted in development of ASD. Examples of such environmental factors together with their respective biomarker abnormalities are: pregnancy (increased NO, IL-1 beta, TNF-alpha, IL-6, IL-10, prolactin: decreased IFN-gamma, IL-12), neuroborreliosis (increased IL-1 beta, sIL-1R2, TNF-alpha, IFN-gamma, IL-6, IL-10, IL-12, IL-18, transforming growth factor-beta 1 (TGF-beta 1)), vital infections (increased IL-1 beta, IL-6, IL-8, TNF-alpha, IFN-gamma/alpha/beta,TGF-beta 1), thimerosal (increased IL-5, IL-13; decreased IFN-gamma,TNF-alpha,IL-6, IL-12p70, NOS), and valproic acid (increased NO, reactive oxygen species; decreased TNF-alpha, IL-6, IFN-gamma). The imbalances in pro- and antiinflammatory processes could markedly hinder [lost defense mechanisms important for immune control of the parasite, such as the production of NO, cytokines, and reactive oxygen/nitrogen species, tryptophan degradation by indoleamine 2,3-dioxygenase and/or tryptophan 2,3-dioxygenase, limitation of the availability of intracellular iron to T gondii, and the mechanisms mediated by an IFN-gamma responsive gene family. These fluctuations could result in a recurrent profuse multiplication of T. gondii in the brain associated with persistent neuroinflammation, chronic overproduction of pro- and antiinflammatory cytokines, and NO causing increased oxidative stress, and significantly depressed activity of several enzymes including cytochrome P450 monooxygenase family responsible for metabolism of physiological substrates and xenobiotics, such as steroids, fatty acids, prostaglandins, drugs, pollutants, and carcinogens, finally leading to development of ASD. This reasoning may be supported by such abnormal metabolic events as: (1) patients with ASD have significantly decreased melatonin levels caused by marked deficit in acetylserotonin methyltransferase activity, possibly resulting from maternal and/or fetal/postnatal overproduction of NO, characteristic for this clinical entity; (2) thimerosal inhibited both insulin-like growth factor-1- and dopamine-stimulated methylation reactions, and depressed methionine synthase activity, the metabolic events important for promoting normal neurodevelopment; (3) valproic acid, a strong histone deacetylase inhibitor, have potent anti-T. gondii activity. Thus, patients with ASD should be tested for T. gondii infection. (C) 2009 Elsevier Ltd. All rights reserved
Anti-Toxoplasma gondii antibodies in patients with chronic heart failure
Yazar, S., Gur, M., Ozdogru, I., Yaman, O., Oguzhan, A., Sahin, I.
Journal of Medical Microbiology 2006; 55: 89-92
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Chronic heart failure (CHF) involves interactions between the cardiovascular, neuroendocrine and immune systems. This study investigated the seropositivity rate for anti-Toxoplasma IgG and IgM antibodies by ELISA in patients with CHF. Ninety-seven patients with CHF and 50 healthy volunteers were selected for this investigation. The seropositivity rate for anti-Toxoplasma IgG antibodies among CHF patients (68%) was significantly higher than in healthy volunteers (36%). Thus, parasitological screening of this group of patients should be periodically performed to prevent the possible dissemination of toxoplasmosis.