Neurotoxoplasmosis


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Micrograph of sphere wit red dots.
This Toxoplasma gondii cyst, observed in mouse brain tissue, contains thousands of inactive parasites. (credit: modification of work by USDA)

OpenStax Microbiology

Toxoplasma gondii is an ubiquitous intracellular parasite that can cause neonatal infections. Cats are the definitive host, and humans can become infected after eating infected meat or, more commonly, by ingesting oocysts shed in the feces of cats. T. gondii enters the circulatory system by passing between the endothelial cells of blood vessels. Most cases of toxoplasmosis are asymptomatic. However, in immunocompromised patients, neurotoxoplasmosis caused by T. gondii infections are one of the most common causes of brain abscesses. The organism is able to cross the blood-brain barrier by infecting the endothelial cells of capillaries in the brain. The parasite reproduces within these cells, a step that appears to be necessary for entry to the brain, and then causes the endothelial cell to lyse, releasing the progeny into brain tissues. This mechanism is quite different than the method it uses to enter the bloodstream in the first place.

The brain lesions associated with neurotoxoplasmosis can be detected radiographically using MRI or CAT scans. Diagnosis can be confirmed by direct observation of the organism in CSF. RT-PCR assays can also be used to detect T. gondii through genetic markers.

Treatment of neurotoxoplasmosis caused by T. gondii infections requires six weeks of multi-drug therapy with pyrimethamine, sulfadiazine, and folinic acid. Long-term maintenance doses are often required to prevent recurrence.

Chronic toxoplasmosis and sleepiness in obstructive sleep apnea

Sleepiness is the main clinical expression of obstructive sleep apnea (OSA) syndrome resulting from upper airway collapse. Recent studies have discussed the fact that the presence of T. gondii cysts in the brain and the resulting biochemical and immunological mechanisms could be linked to neurobehavioral disorders. The aim of the present study was to explore the potential impact of chronic toxoplasmosis on sleepiness and on obstructive sleep apnea (OSA) severity in OSA obese patients. https://doi.org/10.1371/journal.pone.0235463

Association between Toxoplasma gondii infection and depression

Toxoplasma gondii (Tgondii) is an obligate intracellular opportunistic parasite that is the causative agent of toxoplasmosis. This parasite accounts for mental disorders; however, the relationship between Tgondii infection and depressive disorder is unclear. Regarding this, the present systematic review and meta-analysis was conducted to investigate the scientific evidence regarding the potential association between major depression disorder (MDD) and Toxoplasma infection.

As the findings of the reviewed articles indicated, toxoplasmosis is not a risk factor for major depression disorder. However, it is necessary to perform further research to clarify the detailed association between Tgondii and dysthymia or mild and moderate depression. Furthermore, it is recommended to better investigate the effect of antibody titers on the relationship between depression and Tgondii infection. https://doi.org/10.1371/journal.pone.0218524

Effects of Latent Toxoplasmosis on Autoimmune Thyroid Diseases in Pregnancy

Toxoplasmosis, one of the most common zoonotic diseases worldwide, can induce various hormonal and behavioural alterations in infected hosts, and its most common form, latent toxoplasmosis, influences the course of pregnancy. Autoimmune thyroid diseases (AITD) belong to the well-defined risk factors for adverse pregnancy outcomes. The aim of this study was to investigate whether there is a link between latent toxoplasmosis and maternal autoimmune thyroid disease in pregnancy.

Latent toxoplasmosis was associated with a mild increase in thyroid hormone production in pregnancy. The observed Toxoplasma-associated changes in the parameters of autoimmune thyroid disease are mild and do not seem to be clinically relevant; however, they could provide new clues to the complex pathogenesis of autoimmune thyroid diseases. https://doi.org/10.1371/journal.pone.0110878

Modeling Toxoplasma gondii infection in human cerebral organoids

Pluripotent stem cell-derived cerebral organoids have the potential to recapitulate the pathophysiology of in vivo human brain tissue, constituting a valuable resource for modeling brain disorders, including infectious diseases. Toxoplasma gondii, an intracellular protozoan parasite, infects most warm-blooded animals, including humans, causing toxoplasmosis. In immunodeficient patients and pregnant women, infection often results in severe central nervous system disease and fetal miscarriage. However, understanding the molecular pathophysiology of the disease has been challenging due to limited in vitro model systems. Here, we developed a new in vitro model system of T. gondii infection using human brain organoids. We observed that tachyzoites can infect human cerebral organoids and are transformed to bradyzoites and replicate in parasitophorous vacuoles to form cysts, indicating that the T. gondii asexual life cycle is efficiently simulated in the brain organoids. Transcriptomic analysis of T. gondii-infected organoids revealed the activation of the type I interferon immune response against infection. In addition, in brain organoids, T. gondii exhibited a changed transcriptome related to protozoan invasion and replication. This study shows cerebral organoids as physiologically relevant in vitro model systems useful for advancing the understanding of T. gondii infections and host interactions. https://pubmed.ncbi.nlm.nih.gov/32820712/

Can Toxoplasma gondii Pave the Road for Dementia?

Dementia is an ominous neurological disease. Scientists proposed a link between its occurrence and the presence of Toxoplasma gondii (T. gondii). The long-term sequels of anti-Toxoplasma premunition, chiefly dominated by TNF-α, on the neurons and their receptors as the insulin-like growth factor-1 receptor (IGF-1R), which is tangled in cognition and synaptic plasticity, are still not clear. IGF-1R mediates its action via IGF-1, and its depletion is incorporated in the pathogenesis of dementia. The activated TNF-α signaling pathway induces NF-κβ that may induce or inhibit neurogenesis. This study speculates the potential impact of anti-Toxoplasma immune response on the expression of IGF-1R in chronic cerebral toxoplasmosis. The distributive pattern of T. gondii cysts was studied in association with TNF-α serum levels, the in situ expression of NF-κβ, and IGF-1R in mice using the low virulent ME-49 T. gondii strain. There was an elevation of the TNF-α serum level ( value ≤ 0.004) and significant upsurge in NF-κβ whereas IGF-1R was of low abundance ( value < 0.05) compared to the controls. TNF-α had a strong positive correlation with the intracerebral expression of NF-κβ ( value ≈ 0.943, value ≈ 0.005) and a strong negative correlation to IGF-1R ( value -0.584 and -0.725 for area% and O.D., respectively). This activated TNF-α/NF-κβ keeps T. gondii under control at the expense of IGF-1R expression, depriving neurons of the effect of IGF-1, the receptor’s ligand. We therefore deduce that T. gondii immunopathological reaction may be a road paver for developing dementia. https://pubmed.ncbi.nlm.nih.gov/32802484/

Cerebral Toxoplasmosis in a Rheumatoid Arthritis Patient on Immunosuppressive Therapy

Cerebral toxoplasmosis is a life-threatening infection most commonly found in immunocompromised hosts such as acquired immunodeficiency syndrome (AIDS) or transplant patients. However, it is not known to affect patients with chronic inflammatory disorders on immunosuppressive therapy. We describe the case of a 70-year-old female with rheumatoid arthritis (RA) on chronic therapy with methotrexate and infliximab, who presented to the hospital after two weeks of right-sided weakness. Imaging revealed bilateral ring-enhancing lesions in the basal ganglia (left greater than right). A diagnosis of cerebral toxoplasmosis was made on brain biopsy. Apart from the immunosuppressive therapy and owning a cat, she had no other risk factors for developing the infection. The patient’s immunosuppressive medications were discontinued, and she was started on high-dose trimethoprim-sulfamethoxazole (TMP-SMX). Upon literature review using PubMed, we found seven other published reports on similar cases of toxoplasmosis in RA patients on immunosuppressive therapy; however, there was a lack of recommendations for diagnosis, treatment, and prophylaxis in this patient population. With the growing use of immunosuppressive therapies in chronic inflammatory disorders, further data is needed regarding the management of toxoplasmosis in these patients. This case report is an investigation of the relationship between immunosuppressive medications in RA patients and cerebral toxoplasmosis and an exploration of the available recommendations for its management. https://pubmed.ncbi.nlm.nih.gov/32670684/

Source:

Parker, N., Schneegurt, M., Thi Tu, A.-H., Forster, B. M., & Lister, P. (n.d.). Microbiology. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/microbiology

https://doi.org/10.1371/journal.pone.0235463

https://doi.org/10.1371/journal.pone.0218524

https://doi.org/10.1371/journal.pone.0110878

https://pubmed.ncbi.nlm.nih.gov/32820712/

https://pubmed.ncbi.nlm.nih.gov/32802484/

https://pubmed.ncbi.nlm.nih.gov/32670684/