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Toxoplasma gondii & Human Phenotype

Compendium of Known Effects and Ongoing Research

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Latent toxoplasma infection in real-world schizophrenia: Results from the national FACE-SZ cohort

February 12, 2018
Fond,G., Boyer, L. ,Schurhoff, F. ., Berna,F. , Godin, O., Bulzacka, E., Andrianarisoa, M. Brunel, ,L. ,Aouizerate, B. , Capdevielle, D.,Chereau, I. , Coulon, N., D'Amato, T. , Dubertret,C. , Dubreucq, J.,Faget, C.,. Lancon, Leignier,S., Mallet,J., Misdrahi, D., Passerieux, C., Rey,R., Schandrin,A., Urbach,M., Vidailhet,P., Llorca, P. M., Leboyer, M., Grp,F.S.
Schizophrenia Research 2018; 201: 373-380
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Objective: Latent Toxoplasma infection has been associated with widespread brain immune activation, increased blood brain barrier permeability, neural disruption, increased dopamine release in dopaminergic neurons, with NMDA activation and with schizophrenia (SZ) onset risk. Toxoplasma has been suggested to be a source of chronic low-grade inflammation and this inflammation has been associated with cognitive impairment in SZ. The objective of the present study were (i) to determine if latent Toxoplasma infection was associated with specific clinical features in stabilized SZ subjects, with cognitive impairment and with increased low-grade peripheral inflammation and (ii) to determine if Treatments with Anti-Toxoplasmic Activity (TATA) were associated with improved outcomes in subjects with latent Toxoplasma infection. Methods: A comprehensive 2 daylong clinical and neuropsychological battery was administered in 250 SZ subjects included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort. Solid phase-enzyme microplate immunoassay methods were used to measure IgG class of antibodies to T. gondii in blood sample. Latent Toxoplasma infection was defined by T. gondii IgG ratio >= 0.8, equivalent to >= 10 international units. Chronic peripheral inflammation was defined by highly sensitive Creactive protein blood level >= 3 mg/L. Results: Latent Toxoplasma infection has been found in 184 (73.6%) of this national multicentric sample. In the multivariate analyses, latent Toxoplasma infection has been significantly associated with higher PANSS negative (aOR = 1.1 [1.1-1.1], p = 0.04) and excitement subscores (aOR = 1.3 [1.1-1.6], p = 0.01), with two specific symptoms (i.e., reference delusion (aOR = 3.6 [1.2-10.6] p = 0.01) and alogia (aOR = 16.7 [2.0-134.7], p = 0.008)) and with chronic low-grade peripheral inflammation (27.2% vs. 7.6%, aOR = 3.8 [1.4-10.3], p = 0.004). Extrapyramidal symptoms remained significantly associated with latent Toxoplasma infection. On the opposite, no significant association of latent Toxoplasma infection with age, gender, age at SZ onset, suicide behavior or cognitive deficits has been found in these models (all p > 0.05). TATA were associated with lower depressive symptoms (aOR = 0.8[0.7-0.9], p = 0.01), and with lower rates of chronic peripheral inflammation (20.9% vs. 48.6%, aOR = 3.5 [1.5-7.9], p = 0.003) but not with higher cognitive scores (p > 0.05). Conclusion: The present findings suggest that Toxoplasma is almost 3 times more frequent in SZ population compared to general population in France. The potential cerebral underpinnings of the association of latent Toxoplasma infection and the above-mentioned outcomes have been discussed. Future studies should confirm that TATA may be effective to reduce Toxoplasma-associated depressive symptoms and low-grade peripheral inflammation.

Tagged: activation, delusions, disorders, gondii infection, inflammation, markers, premorbid intelligence levels, psychosis, reliability, Schizophrenia, suicide attempts, symptoms, Toxoplasma gondii, treatment, validity

Mental health

Toxoplasma gondii and schizophrenia: a review of published RCTs

October 2, 2017 14 Comments
Chorlton, S.D.
Parasitology Research 2017; 116: 1793-1799
Click for abstract
Over the last 60 years, accumulating evidence has suggested that acute, chronic, and maternal Toxoplasma gondii infections predispose to schizophrenia. More recent evidence suggests that chronically infected patients with schizophrenia present with more severe disease. After acute infection, parasites form walled cysts in the brain, leading to lifelong chronic infection and drug resistance to commonly used antiparasitics. Chronic infection is the most studied and closely linked with development and severity of schizophrenia. There are currently four published randomized controlled trials evaluating antiparasitic drugs, specifically azithromycin, trimethoprim, artemisinin, and artemether, in patients with schizophrenia. No trials have demonstrated a change in psychopathology with adjunctive treatment. Published trials have either selected drugs without evidence against chronic infection or used them at doses too low to reduce brain cyst burden. Furthermore, trials have failed to achieve sufficient power or account for confounders such as previous antipsychotic treatment, sex, age, or rhesus status on antiparasitic effect. There are currently no ongoing trials of anti-Toxoplasma therapy in schizophrenia despite ample evidence to justify further testing.

Tagged: antibodies, artemisinin, azithromycin, bipolar disorder, chronic, efficacy, infection, metaanalysis, mice, minocycline, Schizophrenia, Toxoplasma, treatment, trimethoprim

Mental health

Cerebral toxoplasmosis in a diffuse large B cell lymphoma patient

May 24, 2016
Savsek, L., Opaskar, T.R.
Radiology and Onkology 2016; 50: 87-93
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Background. Toxoplasmosis is an opportunistic protozoal infection that has, until now, probably been an underestimated cause of encephalitis in patients with hematological malignancies, independent of stem cell or bone marrow transplant. T and B cell depleting regimens are probably an important risk factor for reactivation of a latent toxoplasma infection in these patients. Case report. We describe a 62-year-old HIV-negative right-handed Caucasian female with systemic diffuse large B cell lymphoma who presented with sudden onset of high fever, headache, altered mental status, ataxia and findings of pancytopenia, a few days after receiving her final, 8th cycle of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisolone (R-CHOP) chemotherapy regimen. A progression of lymphoma to the central nervous system was suspected. MRI of the head revealed multiple on T2 and fluid attenuated inversion recovery (FLAIR) hyperintense parenchymal lesions with mild surrounding edema, located in both cerebral and cerebellar hemispheres that demonstrated moderate gadolinium enhancement. The polymerase chain reaction on cerebrospinal fluid (CSF PCR) was positive for Toxoplasma gondii. The patient was diagnosed with toxoplasmic encephalitis and successfully treated with sulfadiazine, pyrimethamine and folic acid. Due to the need for maintenance therapy with rituximab for lymphoma remission, the patient now continues with secondary prophylaxis of toxoplasmosis. Conclusions. With this case report, we wish to emphasize the need to consider cerebral toxoplasmosis in patients with hematological malignancies on immunosuppressive therapy when presenting with new neurologic deficits. In such patients, there are numerous differential diagnoses for cerebral toxoplasmosis, and the CNS lymphoma is the most difficult among all to distinguish it from. If left untreated, cerebral toxoplasmosis has a high mortality rate; therefore early recognition and treatment are of essential importance.

Tagged: aids patients, b-cell, bone-marrow-transplantation, central-nervous-system, cerebral, diseases, encephalitis, hiv, hosts, immunocompromised, infections, lymphoma, magnetic resonance imaging, prevention, rituximab, strategies, toxoplasmosis, treatment

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Recent articles

  • Mortality Patterns of Toxoplasmosis and Its Comorbidities in Tanzania: A 10-Year Retrospective Hospital-Based Survey February 6, 2020
  • The role of latent toxoplasmosis in the aetiopathogenesis of schizophrenia–the risk factor or an indication of a contact with cat? February 6, 2020
  • The Association between Toxoplasma gondii Infection and Risk of Parkinson’s Disease: A Systematic Review and Meta-Analysis February 6, 2020

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