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Toxoplasma gondii & Human Phenotype

Compendium of Known Effects and Ongoing Research

cerebral

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

Mental healthPhysical health

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

October 19, 2010
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

Tagged: abnormalities, abnormality, acid, acids, aktivity, autism, autistic spectrum disorders, availability, beta, biomarker, brain, cell-mediated-immunity, central-nervous-system, cerebral, Cerebral toxoplasmosis, change, changes, chronic, chronic neuroinflammation, chronic toxoplasmosis, clinical, congenital cytomegalovirus-infection, consequence, consequences, control, could, cytochrome, cytochrome p450, cytokine, cytokines, data, defense, defense-mechanisms, deficit, degradation, depressed enzyme activities, development, disorder, disorders, drug, drugs, environmental, environmental factors, enzyme, enzymes, event, events, example, families, family, fluctuation, fluctuations, gene, gene families, gene family, gondii, gondii infection, growth, growth-factor-beta, hepatic drug-metabolism, herpes-simplex-virus, histone, histone deacetylase, hypercytokinemia, hypermetabolic state, il-1, il-10, il-12, il-13, il-6, immune, immune irregularities, important, infection, infections, inhibitor, insulin-like, intensity, interferon-inducing agents, intracellular, iron, latent, level, limitation, lipid, lipid-peroxidation, maternal, mechanism, mechanisms, medication, melatonin, metabolism, methionine, methylation, methyltransferase, methyltransferase aktivity, mice, multiplication, nervous, nervous system, neurodevelopment, nf-kappa-b, nitric oxide, nitric-oxide synthase, obesity, or, overproduction, oxidative stress, oxygen, p-450-dependent monooxygenase systems, Parasite, patient, patients, people, persistent, pregnancies, pregnancy, proces, prolactin, prostaglandins, reaction, reactivation, review, species, spectrum, spectrum disorders, spektra, steroids, stress, substrate, systém, t, tgf-beta, tnf-alpha, Toxoplasma, Toxoplasma gondii, toxoplasmosis, tryptophan, tumor-necrosis-factor, vaccination, vital, weight, xenobiotics

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