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The parasite Toxoplasma gondii persists in its hosts by converting from replicating tachyzoites to latent bradyzoites housed in tissue cysts. The molecular mechanisms that mediate T. gondii differentiation remain poorly understood. Through a mutagenesis screen, we identified translation initiation factor eIF1.2 as a critical factor for T. gondii differentiation. A F97L mutation in eIF1.2 or the genetic ablation of eIF1.2 (∆eif1.2) markedly impeded bradyzoite cyst formation in vitro and in vivo. We demonstrated, at single-molecule level, that the eIF1.2 F97L mutation impacts the scanning process of the ribosome preinitiation complex on a model mRNA. RNA sequencing and ribosome profiling experiments unveiled that ∆eif1.2 parasites are defective in upregulating bradyzoite induction factors BFD1 and BFD2 during stress-induced differentiation. Forced expression of BFD1 or BFD2 significantly restored differentiation in ∆eif1.2 parasites. Together, our findings suggest that eIF1.2 functions by regulating the translation of key differentiation factors necessary to establish chronic toxoplasmosis.

UNLABELLED: In an effort to identify novel compounds with potent inhibition against Toxoplasma gondii, a phenotypic screen was performed utilizing a library of 683 pure compounds derived primarily from terrestrial and marine fungi. An initial screen with a fixed concentration of 5 µM yielded 91 hits with inhibition comparable to an equal concentration of artemisinin. These compounds were then triaged based on known biological and chemical concerns and liabilities. From these, 49 prioritized compounds were tested in a dose response format with T. gondii and human foreskin fibroblasts (HFFs) for cytotoxicity. Ten compounds were identified with an IC50 less than 150 nM and a selectivity index (SI) greater than 100. An additional eight compounds demonstrated submicromolar IC50 and SI values equal to or greater than 35. While the majority of these scaffolds have been previously implicated against apicomplexan parasites, their activities in T. gondii were largely unknown. Herein, we report the T. gondii activity of these compounds with chemotypes including xanthoquinodins, peptaibols, heptelidic acid analogs, and fumagillin analogs, with multiple compounds demonstrating exceptional potency in T. gondii and limited toxicity to HFFs at the highest concentrations tested. IMPORTANCE: Current therapeutics for treating toxoplasmosis remain insufficient, demonstrating high cytotoxicity, poor bioavailability, limited efficacy, and drug resistance. Additional research is needed to develop novel compounds with high efficacy and low cytotoxicity. The success of artemisinin and other natural products in treating malaria highlights the potential of natural products as anti-protozoan therapeutics. However, the exploration of natural products in T. gondii drug discovery has been less comprehensive, leaving untapped potential. By leveraging the resources available for the malaria drug discovery campaign, we conducted a phenotypic screen utilizing a set of natural products previously screened against Plasmodium falciparum. Our study revealed 18 compounds with high potency and low cytotoxicity in T. gondii, including four novel scaffolds with no previously reported activity in T. gondii. These new scaffolds may serve as starting points for the development of toxoplasmosis therapeutics but could also serve as tool compounds for target identification studies using chemogenomic approach.

Auranofin, an FDA-approved drug for rheumatoid arthritis, has emerged as a promising antiparasitic medication in recent years. The gold(I) ion in auranofin is postulated to be responsible for its antiparasitic activity. Notably, aurothiomalate and aurothioglucose also contain gold(I), and, like auranofin, they were previously used to treat rheumatoid arthritis. Whether they have antiparasitic activity remains to be elucidated. Herein, we demonstrated that auranofin and similar derivatives, but not aurothiomalate and aurothioglucose, inhibited the growth of Toxoplasma gondii in vitro. We found that auranofin affected the T. gondii biological cycle (lytic cycle) by inhibiting T. gondiis invasion and triggering its egress from the host cell. However, auranofin could not prevent parasite replication once T. gondii resided within the host. Auranofin treatment induced apoptosis in T. gondii parasites, as demonstrated by its reduced size and elevated phosphatidylserine externalization (PS). Notably, the gold from auranofin enters the cytoplasm of T. gondii, as demonstrated by scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDS) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).IMPORTANCEToxoplasmosis, caused by Toxoplasma gondii, is a devastating disease affecting the brain and the eyes, frequently affecting immunocompromised individuals. Approximately 60 million people in the United States are already infected with T. gondii, representing a population at-risk of developing toxoplasmosis. Recent advances in treating cancer, autoimmune diseases, and organ transplants have contributed to this at-risk populations exponential growth. Paradoxically, treatments for toxoplasmosis have remained the same for more than 60 years, relying on medications well-known for their bone marrow toxicity and allergic reactions. Discovering new therapies is a priority, and repurposing FDA-approved drugs is an alternative approach to speed up drug discovery. Herein, we report the effect of auranofin, an FDA-approved drug, on the biological cycle of T. gondii and how both the phosphine ligand and the gold molecule determine the anti-parasitic activity of auranofin and other gold compounds. Our studies would contribute to the pipeline of candidate anti-T. gondii agents.

There is a need to reconsider the acceptance of organs from donors considered suboptimal, in the absence of data. Toxoplasma antibody-positive donors (TPD) constitute one such group. The objective of our study was to compare graft survival in deceased donor renal transplant (Tx) recipients, stratified by Toxoplasma IgG status, using the Organ Procurement and Transplantation Network (OPTN) database. A log-linear event history regression model for graft failure categorized by Toxoplasma IgG status, adjusting for confounders was applied to first kidney-only Tx recipients from 2018 to 2022. Of the 51,422 Tx, 4,317 (8.4%) were from TPD. Acute rejection and graft failure (5% each) were similar between groups. Crude graft failure was 7.3 failures per 100 person-years for TPD recipients compared to 6.5 failures per 100 person-years for the Toxoplasma-negative group (p 0.008). The crude failure rate ratio was 1.14 with an adjusted hazard rate ratio of 1.04 (95% CI: 0.94, 1.15, p 0.39). In renal Tx recipients, TPD graft recipients have comparable survival to Tx from Toxoplasma-negative recipients. While caution and close monitoring of recipients post-Tx for surveillance of disseminated toxoplasmosis are still warranted, our study suggests that patients can be successfully managed using TPD organs.

BackgroundInfection with the protozoan parasite Toxoplasma gondii leads to the formation of lifelong cysts in neurons that can have devastating consequences in the immunocompromised. In the immunocompetent individual, anti-parasitic effector mechanisms and a balanced immune response characterized by pro- and anti-inflammatory cytokine production establishes an asymptomatic infection that rarely leads to neurological symptoms. Several mechanisms are known to play a role in this successful immune response in the brain including T cell production of IFNγ and IL-10 and the involvement of CNS resident cells. This limitation of clinical neuropathology during chronic infection suggests a balance between immune response and neuroprotective mechanisms that collectively prevent clinical manifestations of disease. However, how these two vital mechanisms of protection interact during chronic Toxoplasma infection remains poorly understood.Main textThis study demonstrates a previously undescribed connection between innate neutrophils found chronically in the brain, termed "chronic brain neutrophils" (CBNeuts), and neuroprotective mechanisms during Toxoplasma infection. Lack of CBNeuts during chronic infection, accomplished via systemic neutrophil depletion, led to enhanced infection and deleterious effects on neuronal regeneration and repair mechanisms in the brain. Phenotypic and transcriptomic analysis of CBNeuts identified them as distinct from peripheral neutrophils and revealed two main subsets of CBNeuts that display heterogeneity towards both classical effector and neuroprotective functions in an age-dependent manner. Further phenotypic profiling defined expression of the neuroprotective molecules NRG-1 andErbB4 by these cells, and the importance of this signaling pathway during chronic infection was demonstrated via NRG-1 treatment studies.ConclusionsIn conclusion, this work identifies CBNeuts as a heterogenous population geared towards both classical immune responses and neuroprotection during chronic Toxoplasma infection and provides the foundation for future mechanistic studies of these cells.

Toxoplasmosis is a globally significant disease that poses a severe threat to immunocompromised individuals, especially in Brazil, where a high prevalence of virulent and atypical strains of Toxoplasma gondii is observed. In 1998, the EGS strain, exhibiting a unique infection phenotype, was isolated in Brazil, adding to the complexity of strain diversity. The P2X7 receptor is critical in inflammation and controlling intracellular microorganisms such as T. gondii. However, its genetic variability can result in receptor dysfunction, potentially worsening susceptibility. This study investigates the role of the P2X7 receptor during acute infection induced by the EGS atypical strain, offering insight into the mechanisms of T. gondii infection in this context. We infected the female C57BL/6 (WT) or P2X7 knockout (P2X7−/−) by gavage. The EGS infection causes intestinal inflammation. The P2X7−/− mice presented higher parasite load in the intestine, spleen, and liver. The absence of the P2X7 receptor disrupts inflammatory cell balance by reducing NLRP3, IL-1β, and Foxp3 expression while increasing IFN-γ expression and production in the intestine. In the liver, P2X7-/- animals demonstrate diminished inflammatory infiltrate within the portal and lobular regions concurrent with an enlargement of the spleen. In conclusion, the infection of mice with the EGS strain elicited immune alterations, leading to acute inflammation and cytokine dysregulation, while the P2X7 receptor conferred protection against parasitic proliferation across multiple organs. [ABSTRACT FROM AUTHOR]

Background: Toxoplasma gondii is an intracellular opportunistic pathogenic protozoan that poses serious threats, particularly in immunocompromised individuals. In the absence of a robust prophylactic measure, the mitigation and management of toxoplasmosis present formidable challenges to public health. We recently found that GRA72 plays an important role in parasitophorous vacuole (PV) morphology, growth and virulence of T. gondii. However, whether gra72-deficient strain can be used as a vaccine remains unknown. Methods: We first examined the attenuated virulence of gra72 gene knockout strain (PruΔgra72) and the parasite load in organs of the infected mice. Subsequently, we evaluated the immune-protective effects of the PruΔgra72 vaccination against challenge with various types of T. gondii tachyzoites and Pru cysts. Furthermore, levels of antibodies and cytokines induced by PruΔgra72 vaccination were examined. Statistical analysis was conducted by Student's t-test or Mantel-Cox log-rank test based on data obtained from three independent experiments with GraphPad Prism 8.0. Results: We found that PruΔgra72 strain exhibited a significantly attenuated virulence even at the highest dose of 5 × 107 tachyzoites in Kunming mice model. The significant decrease of brain cyst burden and parasite load in the organs of the PruΔgra72-infected mice suggested its potentiality as a live-attenuated vaccine. Hence, we explored the protective immunity of PruΔgra72 vaccination against toxoplasmosis. Results showed that vaccination with 5 × 106 PruΔgra72 tachyzoites triggered a strong and sustained Th1-biased immune response, marked by significantly increased levels of anti-T. gondii IgG antibodies, and significantly higher levels of Th1 type cytokines (IL-2, IL-12 and IFN-γ) compared to that of Th2 type (IL-4 and IL-10). Vaccination with 5 × 106 PruΔgra72 tachyzoites in mice conferred long-term protection against T. gondii infection by less virulent tachyzoites (ToxoDB#9 PYS and Pru strains) and Pru cysts, provided partial protection against acute infection by high virulent Type I RH tachyzoites and significantly decreased brain cyst burden of chronically infected mice. Conclusions: The avirulent PruΔgra72 induced strong protective immunity against acute and chronic T. gondii infection and is a promising candidate for developing a safe and effective live-attenuated vaccine against T. gondii infection. [ABSTRACT FROM AUTHOR]

Background: Toxoplasmosis, caused by Toxoplasma gondii , poses serious health issues for humans and animals. Individuals with impaired immune systems are more susceptible to severe toxoplasmosis. Pregnant women infected by T. gondii can face the possibility of birth defects and miscarriages. While pyrimethamine and sulfadiazine are commonly used drugs in clinical practice, concerns over their side effects and resistance are on the rise. A spider peptide XYP1 isolated from Lycosa coelestis had potent anti-T. gondii effects, but it had a high synthesis cost and strong cytotoxicity. Methods: This study intended to modify XYP1 for producing derived peptides via amino acid truncation and substitution. The anti-T. gondii effect was evaluated by trypan blue staining assay and killing experiment of RH strain tachyzoites. The CCK8 and hemolysis assays were used to compare their safeties. The morphological changes of T. gondii were observed by scanning electron microscope and transmission electron microscope. In addition, the mechanism of XYP1 against T. gondii through RNA-sequencing was further explored. Results: In vivo and in vitro experiments revealed that XYP1-18 and XYP1-18-1 had excellent anti-T. gondii activity with lower cytotoxicity and hemolysis activity than XYP1. XYP1, XYP1-18, and XYP1-18-1 were able to disrupt the surface membrane integrity of T. gondii tachyzoites, forming pores and causing the disruption of organelles. Furthermore, RNA-sequencing analysis indicated that XYP1 could stimulate the host immune response to effectively eliminate T. gondii and lessen the host's inflammatory reaction. Conclusions: XYP1-18 had lower cytotoxicity and hemolysis activity than XYP1, as well as significantly extending the survival time of the mice. XYP1 played a role in host inflammation and immune responses, revealing its potential mechanism. Our research provided valuable insights into the development and application of peptide-based drugs, offering novel strategies and directions for treating toxoplasmosis. [ABSTRACT FROM AUTHOR]

It has recently come to light that toxoplasmosis may be linked to a number of neurological and developmental conditions, including autism, and the current study aimed to screen for anti-Toxoplasma antibodies in children with autism and metabolic changes that may be related to toxoplasmosis. The study was conducted from November 2023 to February 2024 in Baghdad, Iraq. A total of 88 children between the ages of 2-11 years participated in this study. A psychopathologist diagnosed 44 of them with autism, while the remaining 44 were regarded as the control group because they did not exhibit any autistic symptoms. Each child had serum samples drawn and analysed for the following: lipid profile, anthropometric measurements, anti-Toxoplasma antibodies, adiponectin, leptin, chemerine, and Adipocyte Fatty Acid-Binding Protein (AFABP). Metabolic syndrome was assessed in each participant. Of the patients with autism, 31.82% showed anti-Toxoplasma antibodies compared to only 11.36% in the control group. A significant correlation (p<0.01) was found between the seropositivity rates of T. gondii and autism. Four subgroups were established based on previous findings: Autism-Toxoplasma-positive, Autism-Toxoplasma-negative, control-Toxoplasma-positive, and control-Toxoplasma-negative. There was no statistically significant difference in body mass index (BMI) between the control group and the autistic patients, whereas the control group with Toxoplasma +ve had the highest BMI value when compared to the other groups. Cholesterol levels were significantly lower than the control, while no significant differences were observed in cholesterol levels among the four subgroups. No significant differences were observed in HDL levels among the four subgroups. The results also revealed that leptin was the only adipokine that was significantly increased in patients with autism. In contrast, adiponectine, chemerine, and AFABP levels did not significantly vary among the subgroups. Finally, metabolic syndrome was significantly associated with autism (P < 0.05). [ABSTRACT FROM AUTHOR]

Toxoplasmosis is a common cosmopolitan parasitic zoonosis caused by Toxoplasma gondii. Most often asymptomatic, toxoplasmosis can be serious for the foetus if it occurs during pregnancy. The objective of this study was to estimate the seroprevalence of toxoplasmosis among female students to contribute to the knowledge of the epidemiology of this disease. We conducted a cross-sectional study on female medical students in Bouake. The students were included after obtaining informed consent and were interviewed about their socio-demographic characteristics, gynaeco-obstetric history, factors favouring toxoplasmosis, and blood samples were collected. The samples were analysed by ELISA at the Bouake University Hospital laboratory. The collected data were entered and analysed using Word, Excel 2013, and Epi Info 7. The 168 female students included had an average age of 24 years, were married (6%), had a history of pregnancy (23.8%), were nulliparous (91.7%), had a cat (39.3%), and ate undercooked meat (72%). An overall seroprevalence of 67.9% was observed, of which 66.7% was IgG and 3.6% IgM. There was a statistically significant relationship between anti-toxoplasma seropositivity, age and the presence of a cat in the family. The overall seroprevalence of toxoplasmosis among female students at the Bouake Medical Sciences training and research unit was high. Therefore, students whose serology was negative should be made aware of the need to have a check-up in the event of pregnancy, so that appropriate measures can be taken as soon as possible. [ABSTRACT FROM AUTHOR]

Simple Summary: Toxoplasma gondii is a zoonotic pathogenic apicomplexan parasite that infects approximately one third of the global population. In immunosuppressed individuals, the infection may be fatal. Current anti-toxoplasmosis drugs have low efficacy and cause side effects, and no vaccine is available to prevent human toxoplasmosis. To search for potential virulence genes of T. gondii with a view to serving as new drug or vaccine targets for toxoplasmosis, we selected 11 genes of interest (GOIs), which were tentative microneme proteins (MICs) with unknown functions, and applied the CRISPR-Cas9 system to construct 11 epitope tagging strains and gene knockout strains to explore their intracellular localization and biological functions. The results showed that nine tentative MICs were localized or partially localized in the microneme, one GOI was localized in endoplasmic reticulum, and another GOI was localized in the dense granule. Deletion of the 11 genes showed no significant effect on the in vitro growth and virulence of the tachyzoites of T. gondii type I RH strain. This study investigated the role of the 11 tentative mics in T. gondii tachyzoites, which expanded the knowledge of the functionally unknown genes of T. gondii. In the future, roles of these genes in other life stages and other genotypes of T. gondii will be explored. Toxoplasma gondii, a pathogenic apicomplexan parasite, infects approximately one third of the world's population and poses a serious threat to global public health. Microneme proteins (MICs) secreted by the microneme, an apical secretory organelle of T. gondii, play important roles in the invasion, motility, and intracellular survival of T. gondii. In this study, we selected 11 genes of interest (GOIs) of T. gondii, tentative MICs predicted to be localized in micronemes, and we used the CRISPR-Cas9 system to construct epitope tagging strains and gene knockout strains to explore the localization and function of these 11 tentative MICs. Immunofluorescence assay showed that nine tentative MICs (TGME49_243930, TGME49_200270, TGME49_273320, TGME49_287040, TGME49_261710, TGME49_205680, TGME49_304490, TGME49_245485, and TGME49_224620) were localized or partially localized in the microneme, consistent with the prediction. However, TGME49_272380 and TGME49_243790 showed different localizations from the prediction, being localized in the endoplasmic reticulum and the dense granule, respectively. Further functional characterization of the 11 RHΔGOI strains revealed that deletion of these 11 GOIs had no significant effect on plaque formation, intracellular replication, egress, invasion ability, and virulence of T. gondii. Although these 11 GOIs are not essential genes for the growth and virulence of tachyzoites of type I RH strain, they may have potential roles in other developmental stages or other genotypes of T. gondii. Thus, further research should be performed to explore the possible role of the nine mics and the other two GOIs in other life cycle stages and other genotypes of T. gondii. [ABSTRACT FROM AUTHOR]

This work analyzed exhaustion markers in CD8+ T-cell subpopulations in 21 samples of peripheral blood mononuclear cells (PBMCs) from individuals with ocular toxoplasmosis (n = 9), chronic asymptomatic toxoplasmosis (n = 7), and non-infected people (n = 5) by using RT-qPCR and flow cytometry techniques. The study found that gene expression of PD-1 and CD244, but not LAG-3, was higher in individuals with ocular toxoplasmosis versus individuals with asymptomatic infection or uninfected. Expression of PD1 in CD8+ central memory (CM) cells was higher in nine individuals with toxoplasmosis versus five uninfected individuals (p =.003). After ex vivo stimulation, an inverse correlation was found between the exhaustion markers and quantitative clinical characteristics (lesion size, recurrence index, and number of lesions). A total exhaustion phenotype was found in 55.5% (5/9) of individuals with ocular toxoplasmosis. Our results suggest that the CD8+ exhaustion phenotype is involved in the pathogenesis of ocular toxoplasmosis. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral toxoplasmosis is a severe symptom of Toxoplasma gondii (T. gondii) infection that often affects individuals with Human Immunodeficiency Virus (HIV) infection and can be fatal. T. gondii exhibits diverse strains with varied virulence, such as cerebral toxoplasmosis, which is connected with a specific strain. Molecular methods were used to investigate the genotype of the parasite. Some researchers have used genetic markers, such as the dense granule proteins GRA6 and GRA7, in order to identify T. gondii genotype. This study aimed to evaluate the applicability of GRA6 and GRA7 as genetic markers for determining T. gondii strain from cerebrospinal fluid of AIDS patients with toxoplasmic encephalitis. Method: 160 serum and cerebrospinal fluid (CSF) samples were collected from 2013 to 2022. The serum samples were initially tested using ELISA anti Toxoplasma IgG, and the CSF was subsequently PCR of 5'SAG2 gene for those positive IgG. A total of 69 CSF successfully positive on PCR of 5'SAG2 were included for analysis of GRA6 and GRA7 by performing PCR, sequencing and phylogenetic analysis for determination of T. gondii type. Result: The findings of this study indicate that the use of GRA7 is better than GRA6 when using direct clinical samples. Out of the 69 samples analyzed, total of 36 samples (52.17%) were positive for GRA7. The cases can be classified as type I: 86,1% (31/36), type III: 2,7% (1/36) and atypical: 11,1% (4/36). Conclusion: Comparison results between GRA6 and GRA7 for genotype determination shows good results on GRA7. GRA7 can be used as a genetic marker to find out the genotype of T. gondii in direct clinical samples where GRA6 cannot be used. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii (T. gondii)‐associated polymorphic effector proteins are crucial in parasite development and regulating host anti‐T. gondii immune responses. However, the mechanism remains obscure. Here, it is shown that Toxoplasma effector dense granules 4 (GRA4) restricts host IFN‐I activation. Infection with Δgra4 mutant T. gondii strain induces stronger IFN‐I responses and poses a severe threat to host health. Mechanistically, GRA4 binds to phosphorylated TBK1 to promote TRIM27‐catalyzed K48‐ubiquitination at Lys251/Lys372 residues, which enhances its recognition by autophagy receptor p62, ultimately leading to TBK1 autophagic degradation. Furthermore, an avirulent Δgra4 strain (ME49Δompdc/gra4) is constructed for tumor immunotherapy due to its ability to enhance IFN‐I production. Earlier vaccination with ME49Δompdc/gra4 confers complete host resistance to the tumor compared with the classical ME49Δompdc treatment. Notably, ME49Δompdc/gra4 vaccination induces a specific CD64+MAR‐1+CD11b+ dendritic cell subset, thereby enhancing T cell anti‐tumor responses. Overall, these findings identify the negative role of T. gondii GRA4 in modulating host IFN‐I signaling and suggest that GRA4 can be a potential target for the development of T. gondii vaccines and tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Alongside affective episodes, cognitive dysfunction is a core symptom of bipolar disorder. The intracellular parasite T. gondii has been positively associated with both, the diagnosis of bipolar disorder and poorer cognitive performance, across diagnostic boundaries. This study aims to investigate the association between T. gondii seropositivity, serointensity, and cognitive function in an euthymic sample of bipolar disorder. Methods: A total of 76 participants with bipolar disorder in remission were tested for T. gondii-specific IgG and IgM antibodies and for cognitive performance using neuropsychological test battery. Cognitive parameters were categorized into three cognitive domains (attention and processing speed, verbal memory, and executive function). Statistical analysis of associations between continuous indicators of cognitive function as dependent variables in relationship to T. gondii, included multivariate analyses of co-variance for seropositivity, and partial correlations with IgG serointensity in IgG seropositives. All analyses were controlled for age and premorbid IQ. Results: In seropositives (n = 27), verbal memory showed significant inverse partial correlations with IgG antibody levels (short delay free recall (r=–0.539, p = 0.005), long delay free recall (r=–0.423, p = 0.035), and immediate recall sum trial 1–5 (r=–0.399, p = 0.048)). Cognitive function did not differ between IgG seropositive and seronegative individuals in any of the cognitive domains (F (3,70) = 0.327, p = 0.806, n = 76). IgM positives (n = 7) were too few to be analyzed. Conclusions: This investigation is the first to show an association between T. gondii IgG serointensity and memory function in a well-diagnosed bipolar disorder sample. It adds to the existing literature on associations between latent T. gondii infection and cognition in bipolar disorder, while further research is needed to confirm and expand our findings, eliminate potential sources of bias, and establish cause-effect relationships. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion While a penicillin allergy label has been linked to various negative clinical outcomes, limited studies have specifically characterized the implication of sulfonamide allergy labels (SAL) on clinical outcomes. We examined the impact of SAL on clinical outcomes of solid organ transplant recipients.In this retrospective matched cohort study, we utilized the TriNetX US collaborative Network, a multicenter de‐identified US database, and identified solid organ transplant recipients with and without SAL. The 1‐year probability of developing Pneumocystis jirovecii pneumonia (PJP), toxoplasmosis, and nocardiosis was estimated and contrasted between the two study groups. The hazard ratio (HR) and the 95% confidence interval (CI) quantified the strength and direction of the association between SAL and these outcomes.When comparing 1571 solid organ transplant recipients with SAL to an equal number of matched controls, patients with SAL had a higher probability of developing nocardiosis (HR 3.85; 95% CI, 1.44–10.30; p = .004; corrected p = .04), and toxoplasmosis (HR, 1.87; 95% CI, 1.10–3.17; p = .019; corrected p = .19), but no difference in the risk of developing PJP (HR, 1.64; 95% CI, 0.68–3.95; p = .27). There was no mortality difference (HR, 1.31; 95% CI, 0.99–1.75; p = .061; corrected p = .6). SAL influenced antibiotic prescription with overutilization of dapsone, atovaquone, and pentamidine and underutilization of trimethoprim and sulfamethoxazole.SAL is associated with an increased risk of opportunistic infections following solid organ transplantation. Measures to evaluate and de‐label sulfonamide allergy prior to transplantation or desensitizing shortly after transplantation are advisable. [ABSTRACT FROM AUTHOR]

Background & Objective: Toxoplasmosis is a globally prevalent opportunistic zoonotic infection. Rheumatoid arthritis (RA) is an autoimmune disease which is manifested as joint inflammation, pain, stiffness, and swelling. The patients may contract toxoplasmosis, especially when receiving antirheumatic immunosuppressive therapy. However conflicting results have been reported on toxoplasmosis in RA patients. We aimed to evaluate Toxoplasma gondii positivity and associated risk factors in patients with RA in Duhok province, Iraq, and to assess the role of antirheumatic therapy in toxoplasmosis and the possibility of its reactivation. Methodology: This case-control study was carried out in Duhok, Kurdistan Region, Iraq, from February 2022 to June 2023. A total of 88 RA patients, with and without concurrent antirheumatic therapy, were recruited. The diagnosis of RA was according to the 2010 American College of Rheumatology/European League. RA-patients were categorized into three groups: Group 1 - no-therapy (n = 14); Group 2 - conventional therapy (n = 49) and Group 3 - biologics in combination with conventional medications (n = 25). Healthy subjects (n = 61) were also selected as controls. Plasma samples obtained from the participants were screened for T. gondii infection using Human anti-Toxoplasma gondii antibody IgG. IgG positive samples were tested utilizing human anti-Toxoplasma gondii antibody IgM ELISA Kit and the avidity T. gondii IgG ELISA kit was used to determine the state of infection. Results: Of the 88 RA patients, with or without antirheumatic therapy, 76 (86.36%) were females and 12 (13.64%) were males. Patients on therapy (n = 74) received several conventional antirheumatic drugs of which methotrexate was the most frequently used one (86.36%). Among biological therapies, etanercept, a TNF-alpha inhibitor, was mostly used (13.51%). The toxoplasmosis was significantly less in the older age group (> 50 y) compared to individuals under 30 y. Gender had no significant effect. Toxoplasma IgG positivity was found to be significantly higher in the three groups of RA patients in comparison with healthy controls. Further assessment of anti-Toxoplasma IgM positivity and Toxoplasma IgG avidity results to identify the state of T. gondii infection in anti-Toxoplasma IgG positive subjects revealed that the frequency of reactivation of toxoplasmosis in RA patient groups was not significantly different from that of the control counterparts. Conclusion: The study showed higher seroprevalence of anti-Toxoplasma antibodies in patients with RA irrespective of therapy; therefore, we could consider toxoplasmosis interaction with RA in the pathogenesis of both diseases. This seroprevalence was higher in younger age groups, but with no significant role of gender, duration of disease, duration of therapy and its type. No significant difference was noted in rates of reactivation of latent T. gondii infection among RA patients and healthy controls. [ABSTRACT FROM AUTHOR]

Background: Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii and is responsible for gestational and congenital infections worldwide. The current standard therapy is based on the administration of Spiramycin to prevent trans‐placental transmission. Other therapies are being studied to reduce the rates of foetal transmission and symptomatic congenital infection. Objectives: We report our long‐standing experience in maternal toxoplasmosis infection treatment using a combination of Spiramycin–Cotrimoxazole, assessing its effectiveness in preventing vertical transmission compared to the expected incidence of congenital infection. Methods: We retrospectively collected cases of pregnant women referred to our centre for suspected toxoplasmosis infection according to Lebech criteria, treated with Spiramycin–Cotrimoxazole. Results: Of 1364 women referred to our centre, postnatal follow‐up of primary toxoplasmosis was available in 562 cases (73.9%). The overall vertical transmission rate was 3.4% in women treated immediately with Spiramycin–Cotrimoxazole after the diagnosis of infection. In comparison, it was 7.7% in women undergoing the same therapy but late or with poor compliance. The foetal transmission rate was 71.4% in untreated cases. All the infected newborns of mother treated adequately with Spiramycin–Cotrimoxazole were asymptomatic afterbirth, while 6/21 infected infants of the inadequate Spiramycin–Cotrimoxazole therapy group had postnatal sequelae (28.5%). The incidence of transmission after appropriate Spiramycin–Cotrimoxazole therapy was significantly lower than the expected rate reported in literature. Conclusions: A combination of Spiramycin and Cotrimoxazole is safe and effective in preventing foetal congenital toxoplasmosis and reducing sequelae in case of in‐utero infection. The timing and adherence to the therapy are crucial to lowering the risk of congenital infection and neonatal morbidity. [ABSTRACT FROM AUTHOR]

This study investigates the efficacy of nebivolol (NBV) in experimental models of toxoplasmosis, focusing on parasite burden reduction and neuronal protection. In the acute model of experimental toxoplasmosis, Swiss mice infected with RH strain tachyzoites received oral NBV chlorhydrate doses of 2 mg/kg/day and 4 mg/kg/day for 8 days. Treatment with NBV significantly reduced parasite burden compared to vehicle and standard drug (PYR) groups. In the chronic model of experimental toxoplasmosis, C57/BL6 mice infected with the ME49 strain received NBV chlorhydrate 41 days post-infection and were evaluated after 10 days of treatment. NBV chlorhydrate effectively reduced cyst number and area, as well as bradyzoite burden compared to controls. Histological analysis demonstrated that NBV chlorhydrate preserved neuronal count, with the 4 mg/kg/day dose yielding counts similar to non-infected mice. Statistical analysis confirmed significant differences compared to control groups. Furthermore, immunohistochemical analysis revealed a significant reduction in iNOS labeling in the brains of mice treated with NBV chlorhydrate, indicating a decrease in nitric oxide production compared to control groups. These findings suggest NBV’s potential as a promising candidate for toxoplasmosis treatment, highlighting its ability to reduce parasite burden and protect neuronal integrity. Further research is warranted to elucidate NBV’s mechanisms of action and its clinical application in managing toxoplasmosis. [ABSTRACT FROM AUTHOR]

Purpose: To describe the epidemiology, clinical features, and classification of uveitis in a large cohort of Colombian patients. Methods: Data were collected from seven ophthalmological referral centers in the four main cities in Colombia. The study included patients with a confirmed diagnosis of uveitis from January 2010 to December 2022. Information on demographics, ophthalmic examination findings, uveitis classification, and etiology was recorded. Results: The study reviewed 3,404 clinical records of patients with uveitis. The mean age at diagnosis was 41.1 (SD 19.0) years, and 54.2% of the patients were female. Overall, 1,341(39.4%) were infectious, 626 (18.4%) non-infectious, and four masquerade syndromes (0.1%). The most common types of uveitis were unilateral (66.7%), acute (48.3%), and non-granulomatous (83%). Anterior uveitis was the most common anatomical localization (49.5%), followed by posterior uveitis (22.9%), panuveitis (22.3%), and intermediate uveitis (5.2%). A diagnosis was established in 3,252 (95.5%) cases; idiopathic was the most common cause (27.7%), followed by toxoplasmosis (25.3%) and virus-associated uveitis (6.4%). The age group between 30 and 50 exhibited the highest frequency of uveitis. Conclusion: This multicenter study comprehensively describes uveitis characteristics in Colombian patients, providing valuable insights into its demographic and clinical features. The study findings emphasize the need to continue updating the changing patterns of uveitis to improve diagnosis and treatment strategies for diseases associated with intraocular inflammation. [ABSTRACT FROM AUTHOR]

Parasitic diseases have a significant impact on human and animal health, representing a major hazard to the public and causing economic and health damage worldwide. Extracellular vesicles (EVs) have long been recognized as diagnostic and therapeutic tools but are now also known to be implicated in the natural history of parasitic diseases and host immune response modulation. Studies have shown that EVs play a role in parasitic disease development by interacting with parasites and communicating with other types of cells. This review highlights the most recent research on EVs and their role in several aspects of parasite‐host interactions in five key parasitic diseases: Chagas disease, malaria, toxoplasmosis, leishmaniasis and helminthiases. We also discuss the potential use of EVs as diagnostic tools or treatment options for these infectious diseases. [ABSTRACT FROM AUTHOR]

The present study aimed to estimate the global prevalence of ocular toxoplasmosis in the general population and patients with uveitis. Four electronic databases were searched and 130 studies for evaluating the prevalence of OT among the general population and uveitis patients were included. The pooled prevalence of OT among the general population was estimated at 2% (95% CI, 2–3%; 762/486 051). The highest prevalence rate was observed in America 6% (95% CI, 1–11%). In uveitis patients, a prevalence rate of 9% (95% CI, 8–10%; 5668/88 006) was reported. The countries with a lower middle income had higher prevalence rates. The prevalence of OT in posterior uveitis 33% (95%CI, 24–42%) was substantially higher than in panuveitis 7% (95% CI, 5–8%). Our results provide a new perspective on the prevalence of OT. Knowledge of international and regional patterns of disease is essential for the establishment of precise diagnostic protocols and control programs. [ABSTRACT FROM AUTHOR]

To evaluate the association between ocular trauma and activation of ocular toxoplasmosis. Retrospective review of 686 patients with ocular toxoplasmosis and its association with trauma to the eye or the head within 1 week of activation. Ten patients with a history of trauma and activation of ocular toxoplasmosis were detected (10/686; 1.45%). Nine patients showed a primary focus of retinitis without a previous scar and one patient had a recurrent form of ocular toxoplasmosis. From these 10 patients, Toxoplasma IgG was positive in eight of them. The median age of the patients was 35.8 years-old (range 17 to 65). These cases suggest that trauma can be associated with activation of retinal bradyzoite cysts in ocular toxoplasmosis. [ABSTRACT FROM AUTHOR]

We describe the association between active ocular toxoplasmosis and Multiple Evanescent White Dot Syndrome (MEWDS). Retrospective observational case report of a patient who presented with concomitant ocular toxoplasmosis and MEWDS (Erasmus University Hospital, Brussels, Belgium). Clinical record and multimodal imaging including fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral domain optical coherence tomography (SD-OCT) were analyzed. Multimodal imaging of a 25-year-old-woman that presented with concomitant active ocular toxoplasmosis and MEWDS is described. Both clinical entities regressed completely after 8 weeks under steroidal anti-inflammatory drugs and antibiotics. Active ocular toxoplasmosis can be associated with simultaneous multiple evanescent white dot syndrome. Further reports are needed to precise and characterize this clinical relationship and its management. Abbreviations: MEWDS: Multiple Evanescent White Dot Syndrome; Fundus Autofluorescence FAF; BCVA: Best-corrected Visual Acuity; FA: Fluorescein Angiography; ICGA: Indocyanine Green Angiography; SD-OCT: Spectral Domain Optical Coherence Tomography; IR: Infrared. [ABSTRACT FROM AUTHOR]

Background: Demographic characteristics apparently play a critical role in the incidence and prevalence of uveitis in different societies. Numerous studies have investigated the demographic-epidemiological factors and clinical patterns of uveitis in Iran; however, no study has been conducted in the west of the country yet. Objectives: To assessed epidemiologic pattern of uveitis in patients residing in the west of Iran. Methods: This study investigated 358 files of uveitis patients referring to the specialized retina-uveitis clinics in a referral hospital in the west of Iran from March 2016 to September 2022. The demographic characteristics, clinical patterns, and complications of uveitis were evaluated in this study. Results: The uveitis patients' mean age (± SD) at the diagnosis time was 48.14 (± 11.91) years (18 - 72 years), the patients with anterior uveitis had the lowest mean age (45.47 ± 11.54 years), and the patients with panuveitis had the highest mean age (52.90 ± 10.14 years) at the diagnosis time. The prevalence of the disease was equal in both genders; however, posterior uveitis and panuveitis significantly involved males more than females (P < 0.01 and 0.01 respectively). The most common anatomical pattern of involvement belonged to anterior uveitis (34%), followed by panuveitis (23.4%), posterior uveitis (22.9%), and intermediate uveitis (19.5%). The prevalent etiology in anterior, intermediate, and panuveitis were idiopathic and Toxoplasma chorioretinitis was the most common causes in posterior uveitis (34.14%). Moreover, acute clinical course and nongranulomatous pathology were also more prevalent. The most common complications of the disease were cataracts and cystoid macular edema (CME). Also, patients with panuveitis followed by posterior uveitis had the worse visual prognosis. Conclusions: The predominant pattern of involvement in patients referring to the referral center in the west of Iran was in the form of anterior uveitis, acute in terms of clinical course, and non-granulomatous in terms of pathology. This clinical view for evaluation in a referral center differs from the pattern expected to be observed in the general population and even in general ophthalmology centers. [ABSTRACT FROM AUTHOR]

The present in vitro and in vivo study aimed to fabricate and characterize linalool‐zinc oxide nanoparticles (Lin‐ZNP) and evaluate their effectiveness against Toxoplasma gondii infection in terms of inflammation, oxidative stress, and pathogenicity. Lin‐ZNP was synthesized using an ethanolic solution of polyvinyl alcohol. The anti‐Toxoplasma and cytotoxicity activities of Lin‐ZNP were investigated, along with its effects on nitric oxide (NO) production, caspase‐3 activity, and pro‐inflammatory genes. After treating T. gondii‐infected mice with Lin‐ZNP for 14 days, the number and size of tissue cysts, antioxidant potential, pro‐inflammatory cytokines, and T. gondii pathogenicity‐related genes were evaluated by real‐time polymerase chain reaction and Western blot analysis. The Lin‐ZNP composite showed a reduced tendency with an average size of 105 nm. Lin‐ZNP significantly reduced the viability of tachyzoites. The obtained selectivity index higher than 10, indicating high specificity for parasites with low cytotoxicity to normal cells. The Lin‐ZNP significantly (p < 0.05) increased the production of NO, caspase‐3 activity, and the expression levels of pro‐inflammatory genes. Lin‐ZNP significantly (p < 0.001) decreased the size and number of tissue cysts and caused a significant reduction in the level of malondialdehyde and a considerable increase (p < 0.001) in antioxidant enzymes and their expression genes. Lin‐ZNP significantly downregulated both mRNA and protein expression of the inflammation‐related markers associated with the TLRs/NF‐κB pathway. The expression levels of the T. gondii pathogenicity‐related genes were significantly downregulated (p < 0.05). The recent survey indicated that Lin‐ZNP manages T. gondii infection by its antioxidant activity and inhibiting the TLRs/NF‐κB pathway without toxicity in mice. [ABSTRACT FROM AUTHOR]

Simple Summary: Toxoplasmosis is a disease caused by the parasite Toxoplasma gondii, which can infect humans and animals, including dogs. Dogs become infected by accidentally ingesting the parasite's oocysts from the environment and eating infected rodents or other small animals. Following infection, dogs develop antibodies against T. gondii. The current study investigated the percentage of dogs living in Greece that have antibodies against the parasite as an indirect way to assess the level of environmental contamination with T. gondii oocysts. Blood samples were collected from 1282 dogs living in both urban and rural regions of Greece, including Attica and Thessaloniki. Overall, 47.6% of the dogs had antibodies against the parasite, indicating they had been exposed to T. gondii. Seropositive dogs were more commonly found in rural areas (53.8%) than in urban areas (43.9%) (p < 0.001). The findings of this study suggest that T. gondii infection is widespread in dogs across Greece, especially in rural regions, and the parasite is highly present in the environment, posing a potential risk for human exposure in these areas. Control measures are necessary to prevent dogs from being infected and to reduce this risk for dog owners. Dog owners should also follow basic hygiene practices, like washing their hands after petting their dogs, to protect themselves. Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is a zoonotic disease that affects various animal species, including dogs, that can serve as sentinels for indirectly estimating the environmental contamination. The current study aimed to determine the seroprevalence of T. gondii IgG and IgM antibodies in dogs across different regions of Greece and assess their living area as a potential risk factor. In total, 1282 blood samples were collected from dogs in urban and rural areas of Greece, including Attica and Thessaloniki. Serum samples were tested for T. gondii-specific IgG and IgM antibodies using an indirect immunofluorescent antibody test. A chi-square test was performed to assess the association between seropositivity for T. gondii and geographical location (urban/rural). The overall T. gondii seroprevalence was 47.6%, while the seroprevalence of IgG and IgM antibodies was 34.3% and 22.2%, respectively. Dogs from rural areas exhibited a significantly higher seroprevalence (53.8%) than those from urban areas (43.9%) (p < 0.001), with the estimated odds ratio being equal to 1.49 (95% CI, 1.18 to 1.65) and the relative risk increased by 22.4%. Dogs in Greece are highly exposed to T. gondii, particularly in rural areas. Measures to prevent canine infections are necessary, and basic hygiene practices, such as hand washing after petting dogs, are required to reduce human infection risk and safeguard public health. [ABSTRACT FROM AUTHOR]

Ocular toxoplasmosis is the most prevalent clinical manifestation of T. gondii infection, which causes irreversible retinal damage. Different experimental models have been developed to study this pathology. In the present study, a new, ex vivo model is proposed to contribute to the elucidation of disease mechanisms and to possible therapeutic solutions. Ex-vivo retinal explants, prepared from mouse retinas following established protocols, were incubated with T. gondii tachyzoites maintained in Vero cells. At different times, starting at 12 h up to 10 days of incubation, the explants were analyzed with immunofluorescence and Western blot to investigate their responses to parasite infection. T. gondii invasion of the retinal thickness was evident after 3 days in culture, where parasites could be detected around retinal cell nuclei. This was paralleled by putative cyst formation and microglial activation. At the same time, an evident increase in inflammatory and oxidative stress markers was detected in infected explants compared to controls. Cell death also appeared to occur in retinal explants after 3 days of T. gondii infection, and it was characterized by increased necroptotic but not apoptotic markers. The proposed model recapitulates the main characteristics of T. gondii retinal infection within 3 days of incubation and, therefore, allows for studying the very early events of the process. In addition, it requires only a limited number of animals and offers easy manipulation and accessibility for setting up different experimental conditions and assessing the effects of putative drugs for therapy. [ABSTRACT FROM AUTHOR]

Toxoplasmosis represents a significant public health and veterinary concern due to its widespread distribution, zoonotic transmission, and potential for severe health impacts in susceptible individuals and animal populations. The ability to design and produce recombinant proteins with precise antigenic properties is fundamental, as they serve as tools for accurate disease detection and effective immunization strategies, contributing to improved healthcare outcomes and disease control. Most commonly, a prokaryotic expression system is employed for the production of both single antigens and multi-epitope chimeric proteins; however, the cloning strategies, bacterial strain, vector, and expression conditions vary. Moreover, literature reports show the use of alternative microbial systems such as yeast or Leishmania tarentolae. This review provides an overview of the methods and strategies employed for the production of recombinant Toxoplasma gondii antigenic proteins for the serological detection of T. gondii infection and vaccine development. [ABSTRACT FROM AUTHOR]

Toxoplasmosis, caused by the protozoan parasite Toxoplasma gondii (T. gondii), presents a significant global health concern, particularly for immunocompromised individuals and congenitally infected newborns. Despite its widespread prevalence, there are limited data on T. gondii seroprevalence and ocular toxoplasmosis in Romania. This review aims to summarize the research accomplished on the prevalence and epidemiology of human ocular toxoplasmosis in Romania. Ocular toxoplasmosis, a leading cause of infectious posterior uveitis worldwide, involves complex interactions between host immune responses and parasite factors. Clinically, it presents as focal necrotizing retinitis, characterized by active focal retinal lesions with adjacent chorioretinal scarring, often accompanied by vitreous inflammation and anterior chamber reactions. Diagnosis relies on clinical examination supported by fundus photography, optical coherence tomography (OCT), and serological assays. The authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards, conducting a literature review on PubMed, Google Scholar, and Scopus. Our focus was on ocular toxoplasmosis in Romania, and we used keywords and specific MeSH terms. Finally, 17 articles met all the criteria, as summarized in the PRISMA diagram. This study underscores the need for improved diagnostic methods, increased research efforts, and comprehensive public health education to mitigate the burden of toxoplasmosis and ocular toxoplasmosis in Romania. [ABSTRACT FROM AUTHOR]

Gliding motilityproceeds with little changes in cell shape and often results from actively driven surface flows of adhesins binding to the extracellular environment. It allows for fast movement over surfaces or through tissue, especially for the eukaryotic parasites from the phylum apicomplexa, which includes the causative agents of the widespread diseases malaria and toxoplasmosis. We have developed a fully three-dimensional active particle theory which connects the self-organized, actively driven surface flow over a fixed cell shape to the resulting global motility patterns. Our analytical solutions and numerical simulations show that straight motion without rotation is unstable for simple shapes and that straight cell shapes tend to lead to pure rotations. This suggests that the curved shapes of Plasmodium sporozoites and Toxoplasma tachyzoites are evolutionary adaptations to avoid rotations without translation. Gliding motility is also used by certain myxo- or flavobacteria, which predominantly move on flat external surfaces and with higher control of cell surface flow through internal tracks. We extend our theory for these cases. We again find a competition between rotation and translation and predict the effect of internal track geometry on overall forward speed. While specific mechanisms might vary across species, in general, our geometrical theory predicts and explains the rotational, circular, and helical trajectories which are commonly observed for microgliders. Our theory could also be used to design synthetic microgliders. [ABSTRACT FROM AUTHOR]

Introduction: Occupation plays an important role in the spread of infectious diseases in humans. Toxoplasmosis and hydatidosis are world-wide diseases with different routes of transmission. This study aimed to investigate the prevalence of toxoplasmosis and hydatidosis and risk factors associated with these diseases among the butchers of Tabriz City, the northwest of Iran. Methods: In this case-control study conducted in Tabriz city in 2023, 250 serum samples were collected from butchers (n = 125) and outpatients referred to Imam Reza Hospital (n = 125) and. The ELISA test was used to identify IgG and IgM antibodies against toxoplasmosis and IgG antibodies against hydatidosis. The results were analyzed by statistics tests using SPSS v. 16 software. Risk factors' association was tested using Chi square or logistic regression analysis. Results: The results indicated that 66/125 (52.8%) cases and 40/125 controls (32%) were positive for toxoplasmosis IgG antibody. Also, 5/125 (4%) and 1/125 (0.8%) were positive for toxoplasmosis IgM antibody in the case and control groups, respectively. In addition, 10/125 people (8%) were positive for anti-hydatidosis IgG antibody in the case group, while no positive cases were found in the control group. The main risk factors for toxoplasmosis were age (OR: 1.014), education level (OR: 0.638), and work experience(OR: 1.695), these factors for hydatidosis included age and education level (OR: 1.765 and 0.271) respectivily. Conclusions: Our results suggest the high prevalence of toxoplasmosis and in butchers of Tabriz, which required special attention and basic measures. Moreover, the prevalence of hydatidosis IgG antibodies also requires more attention to be focused on breaking the transmission and reducing the infection. [ABSTRACT FROM AUTHOR]

This study aims to investigate the relationship between toxoplasmosis and this pathway, which may be effective in the formation of epilepsy by acting through the HMGB1/RAGE/TLR4/NF‐κB signalling pathway in patients with idiopathic epilepsy. In the study, four different experimental groups were formed by selecting Toxoplasma gondii IgG positive and negative patients with idiopathic epilepsy and healthy controls. Experimental groups were as follows: Group 1: Epilepsy+/Toxo− (E+, T−) (n = 10), Group 2: Epilepsy−/Toxo− (E−, T−) (n = 10), Group 3: Epilepsy−/Toxo+ (E−, T+) (n = 10), Group 4: Epilepsy+/Toxo+ (E+, T+) (n = 10). HMGB1, RAGE, TLR4, TLR1, TLR2, TLR3, IRAK1, IRAK2, IKBKB, IKBKG, BCL3, IL1β, IL10, 1 L8 and TNFα mRNA expression levels in the HMGB/RAGE/TLR4/NF‐κB signalling pathway were determined by quantitative simultaneous PCR (qRT‐PCR) after collecting blood samples from all patients in the groups. Statistical analysis was performed by one‐way ANOVA followed by LSD post‐hoc tests, and p < 0.05 was considered to denote statistical significance. The gene expression levels of HMGB1, TLR4, IL10, IL1B, IL8, and TLR2 were significantly higher in the G1 group than in the other groups (p < 0.05). In the G3 group, RAGE and BCL3 gene expression levels were significantly higher than in the other groups (p < 0.05). In the G4 group, however, IRAK2, IKBKB, and IKBKG gene expression levels were significantly higher than in the other groups (p < 0.05). HMGB1, TLR4, IRAK2, IKBKB, IL10, IL1B, IL1B, and IL8 in this signalling pathway are highly expressed in epilepsy patients in G1 and seizures occur with the stimulation of excitatory mechanisms by acting through this pathway. The signalling pathway in epilepsy may be activated by HMGB1, TLR4, and TLR2, which are considered to increase the level of proinflammatory cytokines. In T. gondii, this pathway is activated by RAGE and BCL3. [ABSTRACT FROM AUTHOR]

Background: Rapid and accurate diagnosis of toxoplasmosis is critical, particularly for immunocompromised patients. Several molecular methods could have value for toxoplasmosis diagnosis, but often require sophisticated and expensive equipment, and as such are impractical for use in resource-limited countries. Our study aimed to develop a new rapid diagnostic test for toxoplasmosis that can be used in developed countries as well as low- or middle-income countries. Methods: Common primers for conventional loop-mediated isothermal amplification (LAMP) and the new LAMP DNA chromatography method were designed based on a 529-bp repeat present in Toxoplasma gondii genomic DNA. A total of 91 clinical samples from 44 patients suspected of having toxoplasmosis who were treated at several hospitals across Japan were tested using the new LAMP DNA chromatography method, conventional LAMP, and nested PCR and the sensitivity and specificity of the methods was compared. Results: The LAMP DNA chromatography method showed better sensitivity and specificity (68.2% and 100%, respectively) compared with the nested PCR (45.4% and 100%, respectively) and conventional LAMP (63.6% and 100%, respectively) methods for diagnosis of toxoplasmosis in immunocompromised patients. LAMP DNA chromatography also has better sensitivity and specificity (75% and 100%, respectively) than nested PCR (50.0% and 93.5%, respectively) and conventional LAMP (62.5% and 100%, respectively) to diagnose toxoplasma encephalitis using CSF samples. Conclusion: We developed a LAMP DNA chromatography method to detect T. gondii DNA in clinical samples. This method also successfully detected T. gondii DNA in CSF from patients with toxoplasma encephalitis. This newly developed method can be a valuable rapid diagnostic test for toxoplasmosis in a range of settings, including resource-limited areas like those in low- or middle-income countries. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionTo demonstrate that the presence of active retinochoroiditis in eyes with previous hyperpigmented old retinochoroidal lesions is not exclusive of ocular toxoplasmosis.A case series was constructed by reviewing medical records.Four Brazilian patients presenting active posterior uveitis in eyes with previous hyperpigmented old retinochoroidal lesions were identified. Ocular toxoplasmosis was ruled out in all cases. One case had viral etiology confirmed through vitreous PCR (HSV-2 was positive), and the other 3 cases had a presumed diagnosis of herpetic posterior uveitis.Focus active retinitis adjacent to an old cicatricial lesion should not be considered pathognomonic of toxoplasmosis and viral etiology must be considered. [ABSTRACT FROM AUTHOR]

Background: Toxoplasma gondii is one of the most common parasites worldwide. It is of great importance to identify new potential drugs that are effective and less harmful in pregnant women and newborns. We investigated nanoemulsion miltefosine (NEM) in treating experimental acute and chronic toxoplasmosis. Methods: A combination of triacetin, Tween 80, and ethanol (1:2) was used for the development of NEM formulations. The size of NEM was calculated to be 17.463 nm by DLS and TEM. To investigate the performance of miltefosine (MLF), NEM, sulfadiazine (SDZ), and pyrimethamine (PYR) (positive control) in vivo, acute toxoplasmosis was induced in mice by an intraperitoneal injection of RH strain tachyzoites. After five days, the mice were examined for the number and condition of tachyzoites and histopathological changes in the liver and spleen. Chronic toxoplasmosis was investigated in rats and the number and size of brain cysts along with histopathological changes were assessed in different groups. Results: The results of the in vivo assessment of drugs in acute toxoplasmosis showed the following order regarding a decrease in the number of tachyzoites and an increase in survival rate: SDZ&PYR > NEM > MLF. The effects of drugs on chronic toxoplasmosis showed a significant effect of NEM (50%) on reducing the number of cysts compared to SDZ&PYR (10%) and MLF (12%) and reducing the size of NEM brain cysts (21%) compared to SDZ&PYR (5 %) and MLF (8%). Conclusion: Increasing the penetration of NEM through the blood-brain barrier (BBB) and subsequently reducing the number and size of T. gondii tissue cysts is a promising new drug in treating chronic toxoplasmosis. [ABSTRACT FROM AUTHOR]

Background: Chronic toxoplasmosis has been strongly implicated in the development of psychosis and schizophrenia. Additionally, the understanding of schizophrenia has been significantly reshaped by insights into N-methyl-D-aspartate receptor (NMDAR) hypofunction. Aim: This study aimed to compare the behavioral, antioxidant, and NMDAR changes in mice subjected to Toxoplasma gondii infection and those treated with ketamine to induce schizophrenia-like symptoms. Methods: Sixty male BALB/c mice were divided into six groups: toxoplasmosis (TOXO) (infected), ketamineinduced schizophrenia (KET), TOXO+KET, TOXO+sulfadiazine-trimethoprim treatment (SDT), TOXO+KET+SDT, and control (CON) (uninfected). After 10 weeks post-infection, behavioral tests were conducted, brain antioxidant status and lipid peroxidation were analyzed, and NMDA-NR1/NR2A expressions were assessed. TOXO and KET induced distinct behaviors: hyperlocomotion, anxiety, and memory impairment. Results: Antioxidant enzyme levels decreased, and lipid peroxidation increased in TOXO and schizophrenic mice brains. NMDAR downregulation, especially NR-1 and NR2A, was evident due to T. gondii and ketamine. Sulfadiazinetrimethoprim ameliorated NMDAR downregulation, but not all of the behavioral alterations. Conclusion: Further studies are needed to elucidate specific NMDAR subunit roles in toxoplasmosis-induced pathophysiology, offering potential therapeutic insights. This investigation highlights the intricate relationship between chronic toxoplasmosis, NMDAR dysfunction, and schizophrenia-like behaviors. Insights gained could pave the way for innovative interventions targeting both cognitive and neurological impairments associated with these conditions. [ABSTRACT FROM AUTHOR]

Background and Aim: Toxoplasmosis is caused by the parasite Toxoplasma gondii. Cats are the only known hosts that excrete resistant oocysts. Wild rats serve as crucial reservoirs and intermediate hosts for T. gondii S survival and dissemination. Consuming soil and water containing oocysts can lead to illness. This study aimed to estimate the prevalence of toxoplasmosis in wild rats through molecular detection as an indicator of environmental contamination in Surabaya. Materials and Methods: One hundred rats were collected from the three areas (housing, dense settlements, and traditional markets) and distributed into the five zones: West, East, Central, North, and South of Surabaya. Brain tissue samples were extracted using a Geneaid™ (New Taipei City, Taiwan) DNA isolation kit and analyzed through the loop-mediated isothermal amplification (LAMP) method. Results: The study analyzed brain tissue from 100 wild rats, consisting of 77 Rattus tanezumi and 33 Rattus norvegicus, displaying 30% LAMP positivity. The study revealed that 30% (30/100) of wild rats tested were infected with T. gondii. The molecular prevalence rate in male rats was 32.35% (22/68), compared to females with 25% (8/32). 41.9% of the housing population, 33.3% of traditional markets, and 22.6% of dense settlements had the highest molecular prevalence. The high positive molecular rate at the trapping site can be attributed to cats and dense populations. Conclusion: Thirty percentage wild rats were tested positive for toxoplasmosis in Surabaya, East Java, Indonesia using LAMP method. Implementing strict control and monitoring is crucial in preventing the transmission of diseases from wild rats to humans. It is necessary to carry out further research related to genetic analysis of T. gondii to determine the type of T. gondii that infects animals and humans in Surabaya through bioassay and molecular test. [ABSTRACT FROM AUTHOR]

Introduction: Toxoplasma gondii can cause symptomatic toxoplasmosis in immunodeficient hosts, including in people living with human immunodeficiency virus (PLWH), mainly because of the reactivation of latent infection. We assessed the prevalence of toxoplasmosis and its associated risk factors in PLWH in the Asia-Pacific region using data from the TREAT Asia Human Immunodeficiency Virus (HIV) Observational Database (TAHOD) of the International Epidemiology Databases to Evaluate AIDS (IeDEA) Asia-Pacific. Methods: This study included both retrospective and prospective cases of toxoplasmosis reported between 1997 and 2020. A matched case-control method was employed, where PLWH diagnosed with toxoplasmosis (cases) were each matched to two PLWH without a toxoplasmosis diagnosis (controls) from the same site. Sites without toxoplasmosis were excluded. Risk factors for toxoplasmosis were analyzed using conditional logistic regression. Results: A total of 269/9576 (2.8%) PLWH were diagnosed with toxoplasmosis in 19 TAHOD sites. Of these, 227 (84%) were reported retrospectively and 42 (16%) were prospective diagnoses after cohort enrollment. At the time of toxoplasmosis diagnosis, the median age was 33 years (interquartile range 28–38), and 80% participants were male, 75% were not on antiretroviral therapy (ART). Excluding 63 out of 269 people without CD4 values, 192 (93.2%) had CD4 ≤200 cells/μL and 162 (78.6%) had CD4 ≤100 cells/μL. By employing 538 matched controls, we found that factors associated with toxoplasmosis included abstaining from ART (odds ratio [OR] 3.62, 95% CI 1.81–7.24), in comparison to receiving nucleoside reverse transcriptase inhibitors plus non-nucleoside reverse transcriptase inhibitors, HIV exposure through injection drug use (OR 2.27, 95% CI 1.15–4.47) as opposed to engaging in heterosexual intercourse and testing positive for hepatitis B virus surface antigen (OR 3.19, 95% CI 1.41–7.21). Toxoplasmosis was less likely with increasing CD4 counts (51–100 cells/μL: OR 0.41, 95% CI 0.18–0.96; 101–200 cells/μL: OR 0.14, 95% CI 0.06–0.34; >200 cells/μL: OR 0.02, 95% CI 0.01–0.06), when compared to CD4 ≤50 cells/μL. Moreover, the use of prophylactic cotrimoxazole was not associated with toxoplasmosis. Conclusions: Symptomatic toxoplasmosis is rare but still occurs in PLWH in the Asia-Pacific region, especially in the context of delayed diagnosis, causing advanced HIV disease. Immune reconstitution through early diagnosis and ART administration remains a priority in Asian PLWH. [ABSTRACT FROM AUTHOR]

Purpose: To study the role of Toxoplasma IgG avidity in evaluating the stage of systemic infection during manifestation as toxoplasma retinochoroiditis and its clinical implications in eastern India. Methods: Retrospective chart review of Toxoplasma retinochoroiditis cases with Toxoplasma serology for IgG, IgM, and IgG avidity. Results: Included in this study were 17 eyes of 17 patients who had active retinitis located in the macula (14), mid-periphery (2), or periphery (1). They were either primary lesions (12) or reactivations (5). All the cases had Toxoplasma IgG positive; one case had IgM positivity, while all the cases had high IgG avidity values. IgG avidity had a positive correlation with the duration of symptoms. Conclusion: We observed high IgG avidity values in active retinochoroiditis in both primary ocular Toxoplasmosis and reactivation subgroups. These results indicate a late ocular manifestation after initial systemic infection with a possible incubation period ranging from 5 weeks to 5 months. [ABSTRACT FROM AUTHOR]

Toxoplasmosis as a zoonotic disease has a worldwide distribution and can infect a wide range of animal hosts, as well as at least one third of the world's human population. The disease is usually mild or asymptomatic in immunocompetent individuals, but dormant tissue cysts survive especially in the brain for the host lifespan, known as latent toxoplasmosis (LT). Recent studies suggest that LT can have certain neurological, immunological psychological and behavioural effects on human including schizophrenia, bipolar disorder, Alzheimer's disease, depression, suicide anxiety and sleeping disorders. LT effects are controversial, and their exact mechanisms of action is not yet fully understood. This review aims to provide an overview of the potential effects, their basic mechanisms including alteration of neurotransmitter levels, immune activation in the central nervous system and induction of oxidative stress. Additionally, beneficial effects of LT, and an explanation of the effects within the framework of manipulation hypothesis, and finally, the challenges and limitations of the current research are discussed. [ABSTRACT FROM AUTHOR]

Background: Bone defects, resulting from substantial bone loss that exceeds the natural self-healing capacity, pose significant challenges to current therapeutic approaches due to various limitations. In the quest for alternative therapeutic strategies, bone tissue engineering has emerged as a promising avenue. Notably, excretory proteins from Toxoplasma gondii (TgEP), recognized for their immunogenicity and broad spectrum of biological activities secreted or excreted during the parasite's lifecycle, have been identified as potential facilitators of osteogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs). Building on our previous findings that TgEP can enhance osteogenic differentiation, this study investigated the molecular mechanisms underlying this effect and assessed its therapeutic potential in vivo. Methods: We determined the optimum concentration of TgEP through cell cytotoxicity and cell proliferation assays. Subsequently, hBMSCs were treated with the appropriate concentration of TgEP. We assessed osteogenic protein markers, including alkaline phosphatase (ALP), Runx2, and Osx, as well as components of the BMP/Smad signaling pathway using quantitative real-time PCR (qRT-PCR), siRNA interference of hBMSCs, Western blot analysis, and other methods. Furthermore, we created a bone defect model in Sprague-Dawley (SD) male rats and filled the defect areas with the GelMa hydrogel, with or without TgEP. Microcomputed tomography (micro-CT) was employed to analyze the bone parameters of defect sites. H&E, Masson and immunohistochemical staining were used to assess the repair conditions of the defect area. Results: Our results indicate that TgEP promotes the expression of key osteogenic markers, including ALP, Runx2, and Osx, as well as the activation of Smad1, BMP2, and phosphorylated Smad1/5—crucial elements of the BMP/Smad signaling pathway. Furthermore, in vivo experiments using a bone defect model in rats demonstrated that TgEP markedly promoted bone defect repair. Conclusion: Our results provide compelling evidence that TgEP facilitates hBMSC osteogenic differentiation through the BMP/Smad signaling pathway, highlighting its potential as a therapeutic approach for bone tissue engineering for bone defect healing. [ABSTRACT FROM AUTHOR]

Despite being the initial choice for treating toxoplasmosis, sulfadiazine and pyrimethamine have limited effectiveness in eliminating the infection and were linked to a variety of adverse effects. Therefore, the search for new effective therapeutic strategies against toxoplasmosis is still required. The current work is the first research to assess the efficacy of spiramycin-loaded maltodextrin nanoparticles (SPM-loaded MNPs) as a novel alternative drug therapy against toxoplasmosis in a murine model. Fifty laboratory-bred Swiss albino mice were divided into five groups: normal control group (GI, n = 10), positive control group (GII, n = 10), orally treated with spiramycin (SPM) alone (GIII, n = 10), intranasal treated with SPM-loaded MNPs (GIV, n = 10), and orally treated with SPM-loaded MNPs (GV, n = 10). Cysts of Toxoplasma gondii ME-49 strain were used to infect the mice. Tested drugs were administered 2 months after the infection. Drug efficacy was assessed by counting brain cysts, histopathological examination, and measures of serum CD19 by flow cytometer. The orally treated group with SPM-loaded MNPs (GV) showed a marked reduction of brain cyst count (88.7%), histopathological improvement changes, and an increasing mean level of CD19 (80.2%) with significant differences. SPM-loaded MNPs showed potent therapeutic effects against chronic toxoplasmosis. Further research should be conducted to assess it in the treatment of human toxoplasmosis, especially during pregnancy. [ABSTRACT FROM AUTHOR]

The diagnosis of a congenital infection leads to feeling of anxiety and fear not only the pregnant woman but also in the medical practitioner caring for the woman. This is not surprising given that these conditions are rare events and so each clinician may only see a handful in their career. This article gives practical advice for when to suspect congenital infection, and to provide a framework for investigation, counselling and management of seven important congenital infections: toxoplasmosis, cytomegalovirus (CMV), zika virus, parvovirus B19, rubella, syphilis, and varicella zoster. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii (T. gondii) is the causal agent of toxoplasmosis. It may produce severe damage in immunocompromised individuals, as well as congenital infection and intrauterine growth restriction (IUGR). Previous reports have associated interleukin IL-33 with miscarriage, fetal damage, and premature delivery due to infections with various microorganisms. However, IL-33 has not been associated with congenital toxoplasmosis. The sST2 receptor has been reported in patients who have had recurrent miscarriages. On the other hand, IL-1β was not found in acute Toxoplasma infection. Our aim was to analyze the associations between the serum levels of IL-33 and IL-1β in IUGR and toxoplasmosis during pregnancy. Eighty-four serum samples from pregnant women who had undergone 26 weeks of gestation were grouped as follows: with anti-Toxoplasma antibodies, without anti-Toxoplasma antibodies, IUGR, and the control group. IgG and IgM anti-T. gondii antibodies, as well as IL-33, ST2, and IL-1β, were determined using an ELISA assay. Statistical analyses were performed using the Pearson and Chi-square correlation coefficients, as well as the risk factors and Odds Ratios (ORs), with a confidence interval of 95% (CI 95). The results showed that 15/84 (17.8%) of cases were positive for IgG anti-Toxoplasma antibodies and 2/84 (2.38%) of cases were positive for IgM. A statistically significant difference was found between IUGR and IL-33 (p < 0.001), as well as between ST2 and IUGR (p < 0.001). In conclusion, IUGR was significantly associated with IL-33 and ST2 positivity based on the overall IUGR grade. No significant association was found between IUGR and the presence of anti-Toxoplasma antibodies. There was no association between IL-1β and IUGR. More research is needed to strengthen the utility of IL-33 and ST2 as biomarkers of IUGR. [ABSTRACT FROM AUTHOR]

Toxoplasmosis is an important health concern for people and farm animals, leading to many studies on its effects on these populations. Despite this, there is a lack of research on the prevalence of Toxoplasma gondii infection among horses in Iran. This study aims to determine the seroprevalence of toxoplasmosis using the Modified Agglutination Test (MAT) in northwest Iran horses. In this study, blood samples were taken from 385 horses in Ardabil, East Azerbaijan, and West Azerbaijan provinces. Data regarding the age, gender, and location of each horse was documented to assess their impact on the prevalence of toxoplasmosis. The data was analyzed using the chi-square test, with a significance level of p < 0.05. Of the 385 samples, 34 (8.8%) were positive for Toxoplasma gondii. Among the 271 male and 114 female horses, 24 (8.9%) and 10 (8.8%) were seropositive, respectively. Of the 116 horses under and 269 over five years old, 15 (12.9%) and 19 (7.1%) were seropositive, respectively. The prevalence rates in Ardabil, East Azerbaijan, and West Azerbaijan were 11.7% (18 out of 154), 5.1% (7 out of 136), and 9.5% (9 out of 95), respectively. According to the statistical analysis, there were no significant differences in the prevalence of Toxoplasma gondii infection based on age, gender, or sampling location. This study is the first extensive report on the toxoplasmosis seroprevalence among horses in northwest Iran. The results provide important information that can help control and prevent the spread of toxoplasmosis. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is a zoonotic parasite that can cause severe morbidity and mortality in warm-blooded animals, including marine mammals such as sea otters. Free-ranging cats can shed environmentally resistant T. gondii oocysts in their feces, which are transported through rain-driven runoff from land to sea. Despite their large population sizes and ability to contribute to environmental oocyst contamination, there are limited studies on T. gondii oocyst shedding by free-ranging cats. We aimed to determine the frequency and genotypes of T. gondii oocysts shed by free-ranging domestic cats in central coastal California and evaluate whether genotypes present in feces are similar to those identified in sea otters that died from fatal toxoplasmosis. We utilized a longitudinal field study of four free-ranging cat colonies to assess oocyst shedding prevalence using microscopy and molecular testing with polymerase chain reaction (PCR). T. gondii DNA was confirmed with primers targeting the ITS1 locus and positive samples were genotyped at the B1 locus. While oocysts were not visualized using microscopy (0/404), we detected T. gondii DNA in 25.9% (94/362) of fecal samples. We genotyped 27 samples at the B1 locus and characterized 13 of these samples at one to three additional loci using multi locus sequence typing (MLST). Parasite DNA detection was significantly higher during the wet season (16.3%, 59/362) compared to the dry season (9.7%; 35/362), suggesting seasonal variation in T. gondii DNA presence in feces. High diversity of T. gondii strains was characterized at the B1 locus, including non-archetypal strains previously associated with sea otter mortalities. Free-ranging cats may thus play an important role in the transmission of virulent T. gondii genotypes that cause morbidity and mortality in marine wildlife. Management of free-ranging cat colonies could reduce environmental contamination with oocysts and subsequent T. gondii infection in endangered marine mammals and people.

Abstract Background Toxoplasmosis, caused by Toxoplasma gondii , poses serious health issues for humans and animals. Individuals with impaired immune systems are more susceptible to severe toxoplasmosis. Pregnant women infected by T. gondii can face the possibility of birth defects and miscarriages. While pyrimethamine and sulfadiazine are commonly used drugs in clinical practice, concerns over their side effects and resistance are on the rise. A spider peptide XYP1 isolated from Lycosa coelestis had potent anti-T. gondii effects, but it had a high synthesis cost and strong cytotoxicity. Methods This study intended to modify XYP1 for producing derived peptides via amino acid truncation and substitution. The anti-T. gondii effect was evaluated by trypan blue staining assay and killing experiment of RH strain tachyzoites. The CCK8 and hemolysis assays were used to compare their safeties. The morphological changes of T. gondii were observed by scanning electron microscope and transmission electron microscope. In addition, the mechanism of XYP1 against T. gondii through RNA-sequencing was further explored. Results In vivo and in vitro experiments revealed that XYP1-18 and XYP1-18-1 had excellent anti-T. gondii activity with lower cytotoxicity and hemolysis activity than XYP1. XYP1, XYP1-18, and XYP1-18-1 were able to disrupt the surface membrane integrity of T. gondii tachyzoites, forming pores and causing the disruption of organelles. Furthermore, RNA-sequencing analysis indicated that XYP1 could stimulate the host immune response to effectively eliminate T. gondii and lessen the host’s inflammatory reaction. Conclusions XYP1-18 had lower cytotoxicity and hemolysis activity than XYP1, as well as significantly extending the survival time of the mice. XYP1 played a role in host inflammation and immune responses, revealing its potential mechanism. Our research provided valuable insights into the development and application of peptide-based drugs, offering novel strategies and directions for treating toxoplasmosis. Graphical Abstract

Abstract Background Alongside affective episodes, cognitive dysfunction is a core symptom of bipolar disorder. The intracellular parasite T. gondii has been positively associated with both, the diagnosis of bipolar disorder and poorer cognitive performance, across diagnostic boundaries. This study aims to investigate the association between T. gondii seropositivity, serointensity, and cognitive function in an euthymic sample of bipolar disorder. Methods A total of 76 participants with bipolar disorder in remission were tested for T. gondii-specific IgG and IgM antibodies and for cognitive performance using neuropsychological test battery. Cognitive parameters were categorized into three cognitive domains (attention and processing speed, verbal memory, and executive function). Statistical analysis of associations between continuous indicators of cognitive function as dependent variables in relationship to T. gondii, included multivariate analyses of co-variance for seropositivity, and partial correlations with IgG serointensity in IgG seropositives. All analyses were controlled for age and premorbid IQ. Results In seropositives (n = 27), verbal memory showed significant inverse partial correlations with IgG antibody levels (short delay free recall (r=–0.539, p = 0.005), long delay free recall (r=–0.423, p = 0.035), and immediate recall sum trial 1–5 (r=–0.399, p = 0.048)). Cognitive function did not differ between IgG seropositive and seronegative individuals in any of the cognitive domains (F (3,70) = 0.327, p = 0.806, n = 76). IgM positives (n = 7) were too few to be analyzed. Conclusions This investigation is the first to show an association between T. gondii IgG serointensity and memory function in a well-diagnosed bipolar disorder sample. It adds to the existing literature on associations between latent T. gondii infection and cognition in bipolar disorder, while further research is needed to confirm and expand our findings, eliminate potential sources of bias, and establish cause-effect relationships.