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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]

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]

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]

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]

Toxoplasma gondii is a zoonotic parasite with global distribution capable of infecting homeothermic animals. Transmission of protozoan to humans includes ingestion of water and raw food contaminated with sporulated oocysts, ingestion of raw or undercooked meat with tissue cysts, and tachyzoites' transplacental transmission. Fresh goat milk intake has already been linked to human toxoplasmosis outbreaks, but little is known about the infectious potential of this biological sample. Accordingly, the aim of the present study is to assess the survival and infectivity of T. gondii tachyzoites in fresh goat milk samples through an experimental protocol to detect this parasite via bioassay carried out with a murine model, DNA amplification, and serology. Swiss Webster mice were inoculated with fresh goat milk samples contaminated with different T. gondii RH strain tachyzoite concentrations per milliliter and stored for different refrigeration times. Animals showing clinical signs compatible to toxoplasmosis were euthanized. Milk samples contaminated with high parasitic loads and kept for a shorter refrigeration time were the most lethal ones. No significant differences were observed between mean death rates recorded for different goat milk contamination concentrations (p = 0.1888), and for the refrigeration time, contaminated milk samples were kept under (p = 0.9440). T. gondii DNA was amplified in all contaminated milk samples, but only one of the surviving mice was serologically positive. Results of the present study have shown T. gondii survival and infectivity in fresh goat milk samples, and it highlights its significant risk for public health. Therefore, molecular methods must be the tests of choice when milk samples are used to assess infection caused by protozoan in goats' dairy products. [ABSTRACT FROM AUTHOR]

Background: Ocular toxoplasmosis (OT) is the most common cause of infectious uveitis worldwide, including Thailand. This study describes the clinical presentation, visual acuity (VA) outcomes, and factors associated with VA loss in patients with active OT following antiparasitic treatment. Methodology/Principal findings: A retrospective chart review of patients with active OT treated with antiparasitic drugs between 2010 and 2020 was performed. Outcome measures included clinical characteristics, interval VA, and predictive factors associated with loss of VA ≤ 20/50 at 6 months post-treatment. Ninety-two patients (95 eyes) were enrolled. The median follow-up time was 10.9 months (IQR 4.9–31.8 months). The median age at presentation was 35.9 years, 51% were male, and 92.4% had unilateral OT. Eleven patients (12%) were immunocompromised (HIV infection, eight patients; receiving immunosuppressive agents, three patients). Patients mainly presented with primary retinitis without previous scar (62%), posterior pole lesion (56%), and lesion size of ≤ 2–disc area (75%). Immunocompromised patients showed a significantly larger size of retinitis than immunocompetent patients. Oral trimethoprim/sulfamethoxazole monotherapy was the primary short-term antiparasitic drug prescribed (85%). At the final visit, 21% of all affected eyes suffered VA ≤ 20/200. The cumulative incidence of recurrent OT at three years was 33.9% (95% CI, 19.7%–54.2%). Immunocompromised patients [adjusted odds ratio (aOR) 4.9, p = 0.041], macular lesion (aOR 5.4, p = 0.032), and initial VA ≤ 20/200 (aOR 9.1, p = 0.014) were predictive of having VA ≤ 20/50 at 6 months post-treatment. Conclusions: Ocular toxoplasmosis mainly presents as unilateral primary retinitis within the posterior pole. Severe VA loss was observed in one-fifth of eyes following treatment with lesion resolution. Immunocompromised patients, eyes with macular lesions, and poor initial VA were associated with poor VA outcomes. Author summary: Ocular toxoplasmosis (OT) is the most common cause of infectious uveitis worldwide, including Thailand. Vision loss is common despite receiving antiparasitic treatment because of the development of ocular complications. Little is known about the Thai population's demographics, clinical presentations, and visual outcomes. We conducted a retrospective cohort study to examine the clinical presentation and visual acuity outcomes of this group of patients, including both immunocompetent and immunocompromised patients, at the largest tertiary center in southern Thailand. Patients with active OT in our cohort mainly presented with unilateral, focal retinitis without associated scar, and central lesions. Our findings support those of previous studies, in which immunocompromised patients exhibited significantly larger lesion sizes with poorer visual acuity recovery than immunocompetent patients. A significant proportion (21%) of all affected eyes showed severe vision loss following antiparasitic treatment, in which oral trimethoprim/sulfamethoxazole monotherapy was mainly used. Education on Toxoplasma gondii infection and transmission should be provided to communities to decrease the risk of infection and ocular toxoplasmosis disease burden. [ABSTRACT FROM AUTHOR]

Objectives: This study was conducted to evaluate the relationship between toxoplasmosis and cryptogenic epilepsy (CE) by comparing the rate of Toxoplasma gondii seropositivity identified in CE patients with those without any neurological disorder. Methods: The study included 200 cryptogenic patients and 164 individuals without neurological disorders. T. gondii seropositivity was studied in individuals included in the study using the T. gondii-IgG ELISA kit. Results: The study found T. gondii IgG in 15.50% of CE patients and 28.66% of individuals without any neurological disorder. The difference between the two groups was determined to be statistically significant. Conclusion: Toxoplasmosis did not increase the risk of epilepsy in the region where this study was conducted. However, for a better understanding of the CE-T. gondii relationship, we believe that seroprevalence studies should be conducted in larger populations. [ABSTRACT FROM AUTHOR]

Toxoplasma infection in humans is considered due to direct contact with infected cats. Toxoplasma infection (an endemic disease) has the potential to affect various organs and systems (brain, eyes, heart, lungs, liver, and lymph nodes). Bilinear incidence rate and constant population (birth rate is equal to death rate) are used in the literature to explain the dynamics of Toxoplasmosis disease transmission in humans and cats. The goal of this study is to consider the mathematical model of Toxoplasma disease with harmonic mean type incident rate and also consider that the population of humans and cats is not equal (birth rate and the death rate are not equal). In examining Toxoplasma transmission dynamics in humans and cats, harmonic mean incidence rates are better than bilinear incidence rates. The disease dynamics are first schematically illustrated, and then the law of mass action is applied to obtain nonlinear ordinary differential equations (ODEs). Analysis of the boundedness, positivity, and equilibrium points of the system has been analyzed. The reproduction number is calculated using the next-generation matrix technique. The stability of disease-free and endemic equilibrium are analyzed. Sensitivity analysis is also done for reproduction number. Numerical simulation shows that the infection is spread in the population when the contact rate β h and β c increases while the infection is reduced when the recovery rate δ h increases. This study investigates the impact of various optimal control strategies, such as vaccinations for the control of disease and the awareness of disease awareness, on the management of disease. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cytokines play an essential role in regulating the interaction of immune cells in diabetes and infections such as toxoplasmosis. This study was conducted to investigate the serum levels of Interleukin-6 (IL-6) and Transforming Growth Factor-Beta (TGF-P) in diabetic patients with toxoplasmosis. Materials and Methods: This study was conducted in Zabol City on patients with type I and type II diabetes, both with and without toxoplasmosis. The serum levels of target cytokines were measured using the ELISA method. Data analysis was performed using oneway ANOVA, and chi-square test was utilized to examine demographic indices. Results: A significant increase in TGF-β levels was observed in the group with type II diabetes and toxoplasmosis. Additionally, a slight rise in serum IL-6 levels was noted in the group with type I diabetes. However, the level of TGF-β was decreased in this group. Conclusions: The present study revealed that an increase in TGF-β and a decrease in IL-6 in patients with type II diabetes and toxoplasmosis may indicate a reduction in inflammation within this specific group. [ABSTRACT FROM AUTHOR]

Objective: Toxoplasma gondii, rubella, and cytomegalovirus (CMV) are among the TORCH (Toxoplasma, Others, Rubella, Cytomegalovirus, Herpes simplex virus) group microorganisms. Knowing regional epidemiological data on TORCH group infections is important, especially when deciding whether to perform routine screening at the regional and national levels. Our study aimed to evaluate the frequency of T. gondii, rubella, and CMV IgM and/or IgG antibodies in female patients admitted to a state hospital in İstanbul. Method: T. gondii, rubella, and CMV IgG and IgM antibody results tested in patient sera between January 2017 and December 2020 were evaluated retrospectively. Results: The results of 33 636 samples were evaluated. The highest rate of seropositivity was detected in the 20-29 age group (n=4626, 26.72%). The highest of antibody positivity was reported in 2019 (33.29%). The IgG seropositivity rate was 24.1% for T. gondii, 93.5% for rubella, and 98.3% for CMV. Conclusion: Except for the differences in T. gondii seroprevalence, the results of our study seem to be similar to those of other studies both in our country and globally. The seronegativity rate (74.9%) for T. gondii was high in our research, which indicates that pregnant women should be carefully monitored for T. gondii infection in our region. We conclude that more comprehensive studies are needed to establish national screening programs for TORCH group agents. [ABSTRACT FROM AUTHOR]

Objectives: Toxoplasma gondii (T. gondii) is a zoonotic and opportunistic protozoan, accountable for infecting about a third of the world's population. It has serious effects on immunocompromised individuals. Patients receiving hemodialysis are more vulnerable to toxoplasmosis due to their impaired immunity. Investigating the prevalence of anti-T. gondii antibodies (IgG and IgM) in hemodialysis patients compared to a control group was the purpose of this case-control study. Methods: Using the conventional enzyme-linked immunosorbent assay (ELISA) method, anti-T. gondii (IgG and IgM) antibodies were assessed in 82 patients undergoing hemodialysis and 50 control individuals. Besides, collecting data regarding possible risk factors for infection. Results: In 57.31% (47/82) of the cases in the hemodialysis group and 22% (11/50) of participants in the control group, the anti-T.gondii IgG antibody was found. Even though, 2.43% (2/82) of the hemodialysis group proved seropositive for the anti-T. gondii IgM antibodies and no positive cases were detected in the control group. Regarding anti-T. gondii IgG antibody, there is a highly statistically significant difference (P=0.000) between both groups. Besides, a significant correlation between cats' contact and undercooked meat consumption and positive anti-T. gondii IgG antibodies in both hemodialysis and control groups. Conclusion: Hemodialysis patients had a higher seroprevalence of anti-T. gondii IgG antibody than controls (P=0.000) indicating their vulnerability. Thus, it is imperative to establish strategies for T. gondii infection prevention and control in hemodialysis patients and to plan for routine screening for toxoplasmosis among those patients. [ABSTRACT FROM AUTHOR]

Background: Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide. Objectives: We asked whether high performance of an Immunochromatographic-test (ICT) could enable accurate, rapid diagnosis/treatment, establishing new, improved care-paradigms at point-of-care and clinical laboratory. Methods: Data were obtained in 12 studies/analyses addressing: 1-feasibility/efficacy; 2-false-positives; 3-acceptability; 4-pink/black-line/all studies; 5-time/cost; 6-Quick-Information/Limit-of-detection; 7, 8-acute;-chronic; 9-epidemiology; 10-ADBio; 11,12-Commentary/Cases/Chronology. Findings: ICT was compared with gold-standard or predicate-tests. Overall, ICT performance for 1093 blood/4967 sera was 99.2%/97.5% sensitive and 99.0%/99.7% specific. However, in clinical trial, FDA-cleared-predicate tests initially caused practical, costly problems due to false-positive-IgM results. For 58 persons, 3/43 seronegative and 2/15 chronically infected persons had false positive IgM predicate tests. This caused substantial anxiety, concerns, and required costly, delayed confirmation in reference centers. Absence of false positive ICT results contributes to solutions: Lyon and Paris France and USA Reference laboratories frequently receive sera with erroneously positive local laboratory IgM results impeding patient care. Therefore, thirty-two such sera referred to Lyon's Reference laboratory were ICT-tested. We collated these with other earlier/ongoing results: 132 of 137 USA or French persons had false-positive local laboratory IgM results identified correctly as negative by ICT. Five false positive ICT results in Tunisia and Marseille, France, emphasize need to confirm positive ICT results with Sabin-Feldman-Dye-test or western blot. Separate studies demonstrated high performance in detecting acute infections, meeting FDA, CLIA, WHO REASSURED, CEMark criteria and patient and physician satisfaction with monthly-gestational-ICT-screening. Conclusions/significance: This novel paradigm using ICT identifies likely false positives or raises suspicion that a result is truly positive, rapidly needing prompt follow up and treatment. Thus, ICT enables well-accepted gestational screening programs that facilitate rapid treatment saving lives, sight, cognition and motor function. This reduces anxiety, delays, work, and cost at point-of-care and clinical laboratories. Trial registration: NCT04474132, https://clinicaltrials.gov/study/NCT04474132ClinicalTrials.gov Author summary: Toxoplasmosis is a major health burden for developed and developing countries, causing damage to eyes and brain, loss of life and substantial societal costs. Prompt diagnosis in gestational screening programs enables treatment, thereby relieving suffering, and leading to > 14-fold cost savings for care. Herein, we demonstrate that using an ICT that meets WHO REASSURED-criteria identifying persons with/without antibody to Toxoplasma gondii in sera and whole blood with high sensitivity and specificity, is feasible to use in USA clinical practice. We find this new approach can help to obviate the problem of detection of false positive anti-T. gondii IgM results for those without IgG antibodies to T. gondii when this occurs in present, standard of care, predicate USA FDA cleared available assays. Thus, this accurate test facilitates gestational screening programs and a global initiative to diagnose and thereby prevent and treat T. gondii infection. This minimizes likelihood of false positives (IgG and/or IgM) while maintaining maximum sensitivity. When isolated IgM antibodies are detected, it is necessary to confirm and when indicated continue follow up testing in ~2 weeks to establish seroconversion. Presence of a positive ICT makes it likely that IgM is truly positive and a negative ICT makes it likely that IgM will be a false positive without infection. These results create a new, enthusiastically-accepted, precise paradigm for rapid diagnosis and validation of results with a second-line test. This helps eliminate alarm and anxiety about false-positive results, while expediting needed treatment for true positive results and providing back up distinguishing false positive tests. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system that affects mainly young people. It is believed that the autoimmune process observed in the pathogenesis of MS is influenced by a complex interaction between genetic and environmental factors, including infectious agents. The results of this study suggest the protective role of Toxoplasma gondii infections in MS. Interestingly, high Toxoplasma IgM seropositivity in MS patients receiving immunomodulatory drugs (IMDs) was identified. On the other hand, Borrelia infections seem to be positively associated with MS. Although the interpretation of our results is limited by the retrospective nature of the studies, the results strongly indicate that further experimental and clinical studies are needed to explain the role of infectious agents in the development and pathophysiological mechanisms of MS. [ABSTRACT FROM AUTHOR]

Zoonotic abortive diseases represent a significant health and economic risk for national public health. This cross-sectional survey was conducted from April to October 2021 among 200 selected small ruminant farmers in the three northern regions of Cameroon. Data collection was done through questionnaires administered by exchange with the herder, and responses were coded and recorded on an Excel spreadsheet. The data were then analyzed with R software, version 2.13.0. An ANOVA test was used to assess significant differences in mean of Knowledge, Attitudes, Practices, and Perception of zoonotic risks (KAPP) scores between regions. Pearson correlations were used to calculate the association between KAPP scores within regions. Small ruminant farmers surveyed had low mean scores for knowledge of abortive toxoplasmosis and chlamydophilosis (0.1 ± 0.2), desirable attitude (0.32 ± 0.07), appropriate practice (0.36 ± 0.13) in managing abortion, and positive perception of zoonotic risks of toxoplasmosis and chlamydophilosis in small ruminants (0.12 ± 0.33), respectively. KAPP was significantly (P < 0.01) and positively associated with knowledge (r = 0.98) and risk perception (r = 0.99). However, attitudes (r = 0.06), practices (r = 0.05), and risk perception of toxoplasmosis (r = 0.07) and chlamydophilosis (r = 0.08) were not associated with farmers' knowledge. This study revealed significant knowledge gaps, low levels of desired attitudes, and high-risk behavioral practices. These results therefore call for capacity building of health professionals and farmers to better integrate the One Health concept in the management of neglected zoonotic diseases. [ABSTRACT FROM AUTHOR]

A mortality event involving 23 allied rock‐wallabies (Petrogale assimilis) displaying neurological signs and sudden death occurred in late April to May 2021 in a suburban residential area directly adjacent to Magnetic Island National Park, on Magnetic Island (Yunbenun), North Queensland, Australia. Three allied rock‐wallabies were submitted for necropsy, and in all three cases, the cause of death was disseminated toxoplasmosis. This mortality event was unusual because only a small, localised population of native wallabies inhabiting a periurban area on a tropical island in the Great Barrier Reef World Heritage Area were affected. A disease investigation determined the outbreak was likely linked to the presence of free‐ranging feral and domesticated cats inhabiting the area. There were no significant deaths of other wallabies or wildlife in the same or other parts of Magnetic Island (Yunbenun) at the time of the outbreak. This is the first reported case of toxoplasmosis in allied rock‐wallabies (Petrogale assimilis), and this investigation highlights the importance of protecting native wildlife species from an infectious and potentially fatal parasitic disease. [ABSTRACT FROM AUTHOR]

The article focuses on updated guidelines for managing opportunistic infections in Human Immunodeficiency Virus (HIV)-positive individuals, specifically addressing considerations during pregnancy. Topics discussed include recommendations for healthcare providers regarding the management of opportunistic infections, particularly focusing on the unique challenges and considerations related to pregnancy in individuals living with HIV.

Simple Summary: Toxoplasmosis is a globally distributed zoonosis caused by Toxoplasma gondii. This protozoan is capable of infecting mammals and birds and can cause significant impacts on human and animal health. Much of what is known about the parasite's biology, the immune mechanisms involved in toxoplasmosis, and the development of diagnostic tests for this protozoan disease is due to the maintenance of the parasite in laboratory mice. However, the increasing debate on the use of biomodels in scientific research has brought about the need to implement the principles of the 3Rs in laboratory protocols, such as experimental infections with T. gondii in murine models. Therefore, this study aimed to establish the humane endpoints for experimental infection with the T. gondii RH strain in Swiss Webster mice. The results presented here seek to disseminate the method we have proposed for the humane finalization of these animals in experimental protocols using this highly virulent strain as a method of refinement that seeks to enhance animal welfare. The highly virulent Toxoplasma gondii RH strain is maintained through successive passages in mice, but there is still a lack of studies that refine these procedures from a 3Rs perspective, where humanitarian ideals aim to minimize the stress, pain, or suffering of the animals used in the research without the loss of results. The aim of this study was to establish humane endpoints in Swiss Webster mice inoculated with the T. gondii RH strain. A total of 52 mice were infected with 5 × 106 tachyzoites/mL and monitored for periods of up to 5 days. The parameters body weight; hair condition; higher than normal body temperature; hypothermia; respiratory function; pain; soft stools or diarrhea; bloody diarrhea; tense, nervous, or in distress during handling; and ascites were recorded daily in score tables. The results showed that prominent piloerection, respiratory function, pain parameters, and ascites are important clinical signs to be used as a cut-off point for implementing euthanasia. The application of this refinement method helped to avoid animal suffering and pain without compromising the number of parasites recovered. We therefore suggest adopting these parameters in research protocols that require the maintenance of the T. gondii RH strain in murine models to avoid and reduce animal suffering. [ABSTRACT FROM AUTHOR]

The lipid profile and adipokines of an adolescent may be affected by some parasite infections. Recently, it has been discovered that these parasites are connected to body mass index (BMI), lipids and adipokines. The current study, therefore, aimed to specify how Toxoplasma gondii (T. gondii) affect BMI, lipid profile and adipokines. This study was conducted in Al Madain hospital, Baghdad from October to December 2022. An ELISA test was performed to examine the antiT. gondii IgG and IgM for a group of adolescents attending the hospital. Based on this examination ninety adolescents were chosen to be involved in the study. They were separated in to two groups: individuals who tested positive for the parasite (n=45) and those who tested negative for the parasite, control group (n=45). All participating adolescents were subjected to some measurements which included body mass index (BMI), lipid profile parameters (cholesterol, triglycerides, HDL, LDL, and VLD) and adipokines (adiponectin and chemerin). Significant high BMI was noticed in T. gondii positive group (29.65±0.6 Kg/m²) compared to control. The results also indicated that there was a significant increase in all tests of the lipid profile among T. gondii positive group compared to the control. However, the matter reversed in HDL examination as its level increased significantly in the control compared to the T. gondii positive group. Finally, both adiponectin (78.6±0.037 ng/ml) and chemerin (3.43±0.1 ng/ml) raised up significantly in T. gondii positive group versus control group. [ABSTRACT FROM AUTHOR]

Ocular toxoplasmosis (OT) is characterised by intraocular inflammation due to Toxoplasma gondii infection. Studies have found that interleukin 17 (IL‐17) plays a central role in the pathology of OT. However, nucleotide variability in IL17 and interleukin 17 receptor (IL17R) genes has not been characterised in OT. As cytokine gene polymorphisms may influence the expression of these molecules, the aim of this study was to verify whether IL17A (rs2275913), IL17F (rs763780), IL17RA (rs4819554) and IL17RC (rs708567) polymorphisms are associated with OT in a Brazilian population. This study enrolled 214 patients seropositive for T. gondii (110 with OT and 104 without) and 107 controls. Polymorphisms were identified by PCR‐restriction fragment length polymorphism analysis, validated by DNA sequencing with chi‐square and multivariate analyses being used to assess possible associations between polymorphisms and OT. Logistic regression under the dominant model revealed a protection factor against OT of the C mutant allele of the IL17F (rs763780) polymorphism. The T/C‐C/C genotypes were significantly more common in patients without OT compared to those with OT (p value = 0.0066) and controls (p value = 0.014). Findings from this study suggest that the IL17F polymorphism may have an influence in the immunopathology of OT in Brazilian individuals. [ABSTRACT FROM AUTHOR]

Pyrimethamine (PYM) is an antiparasitic drug used in the treatment of congenital toxoplasmosis, available only as tablets. Therefore, preparing extemporaneous formulations and their quality control is essential for safe pediatric treatment. This study aimed to develop and validate a stability-indicating method by ultra-performance liquid chromatography (UPLC) to quantify PYM and methylparaben (MP) in extemporaneous oral suspension and evaluate its applicability to the tablets assay. The analytical conditions included RP-C18 column, mobile phase composed of 0.05 M acetate buffer pH 4.5 and organic mixture (acetonitrile:methanol), at 60:40 (v/v), flow rate of 0.2 mL/min, injection volume of 2 µL and detection at 272 nm. PYM was detected at 3.9 min and MP at 4.7 min, without interference of the degradation products or other excipients. Linearity was observed in the range of 0.5 to 25 μg/mL. The method showed accuracy (mean recovery between 98.0 and 102.0%) and precision (RSD < 2%) for suspension and tablets; the method was robust regarding the variations in the analytical conditions. The developed method met the requirements of current guidelines, was indicative of stability, and was suitable for PYM determination in extemporaneous preparations and tablets. [ABSTRACT FROM AUTHOR]

Toxoplasmosis is a worldwide zoonosis that affects warm-blooded animals, including humans. Wild animals can act as intermediate hosts of this pathogen; thus, this study aims to detect Toxoplasma gondii infection in invasive European brown hares in Brazil. For this, 72 wild European brown hares were captured from July 2020 to June 2022 in three Brazilian states: São Paulo, Paraná, and Rio Grande do Sul. The diagnostic of Toxoplasma gondii infection was performed by bioassay in mouse, histopathology in Hematoxylin-Eosin-stained tissue sections (brain, liver, lungs, kidneys, and small intestine), serology by IFAT, and molecular techniques by conventional PCR and qPCR. The combined prevalence of the different diagnostic methods was 51.4% (37/72, CI= 40.1 - 62.6 %), and there was no statistical difference between sexes, age range, or geographical region of the hosts. Mouse bioassay was the technique that detected more positive hares. To our knowledge, this is the first confirmation of Toxoplasma gondii infection in invasive European brown hares in Brazil. These animals act as reservoirs and potential infection source for carnivores and other wild and domestic animals, including humans, thus contributing to perpetuate the disease cycle in São Paulo, Paraná, and Rio Grande do Sul States. Research such as the present study is necessary to raise awareness about the role of animals in the disease cycle. [ABSTRACT FROM AUTHOR]

Toxoplasmosis poses a global health threat, ranging from asymptomatic cases to severe, potentially fatal manifestations, especially in immunocompromised individuals and congenital transmission. Prior research suggests that oregano essential oil (OEO) exhibits diverse biological effects, including antiparasitic activity against Toxoplasma gondii. Given concerns about current treatments, exploring new compounds is important. This study was to assess the toxicity of OEO on BeWo cells and T. gondii tachyzoites, as well as to evaluate its effectiveness in in vitro infection models and determine its direct action on free tachyzoites. OEO toxicity on BeWo cells and T. gondii tachyzoites was assessed by MTT and trypan blue methods, determining cytotoxic concentration (CC50), inhibitory concentration (IC50), and selectivity index (SI). Infection and proliferation indices were analyzed. Direct assessments of the parasite included reactive oxygen species (ROS) levels, mitochondrial membrane potential, necrosis, and apoptosis, as well as electron microscopy. Oregano oil exhibited low cytotoxicity on BeWo cells (CC50: 114.8 µg/mL ± 0.01) and reduced parasite viability (IC50 12.5 ± 0.06 µg/mL), demonstrating 9.18 times greater selectivity for parasites than BeWo cells. OEO treatment significantly decreased intracellular proliferation in infected cells by 84% after 24 h with 50 μg/mL. Mechanistic investigations revealed increased ROS levels, mitochondrial depolarization, and lipid droplet formation, linked to autophagy induction and plasma membrane permeabilization. These alterations, observed through electron microscopy, suggested a necrotic process confirmed by propidium iodide labeling. OEO treatment demonstrated anti-T. gondii action through cellular and metabolic change while maintaining low toxicity to trophoblastic cells. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is a highly prevalent pathogen, reported from almost all geographical regions of the world. Current anti‐T. gondii drugs are not effective enough in immunocompromised patients, encephalitis, chorioretinitis, and congenital toxoplasmosis. Therefore, the prescription of these drugs has been limited. Rose hip oil (RhO) is a natural plant compound, which shows antibacterial, anticancer, and anti‐inflammatory activities. In the current study, the anti‐T. gondii and cell toxicity effects of solid lipid nanoparticles (SLNs) loaded by RhO (RhO‐SLNs) were evaluated. Emulsification sonicated‐homogenization method was used to prepare SLNs. RhO‐SLNs were characterized, and their anti‐T. gondii and cell toxicity effects were evaluated using in vitro analyses. The particle size and the zeta potential of the nanoparticles were 152.09 nm and −15.3 mV nm, respectively. The entrapment efficiency percentage was 79.1%. In the present study, the inhibitory concentration (IC)50 against T. gondii was >1 μg/mL (p‐value <.0001). The cell toxicity assay showed cytotoxicity concentration (CC)50 >10 mg/mL (p‐value =.017). In addition, at least 75% of T. gondii‐infected Vero cells remained alive at concentrations >10 mg/mL. The concentration of 1 mg/mL showed highest anti‐Toxoplasma activity and lowest cell toxicity against the Vero cell. Our findings suggest that carrying natural plant compounds with SLNs could be considered an effective option for treatment strategies against T. gondii infections. [ABSTRACT FROM AUTHOR]

PurposeMaterials and MethodsResultsConclusionTo report a rare case of a toxoplasma chorioretinitis in one eye and peripheral ocular toxocariasis granuloma in the fellow eye of the same patient.Retrospective case report.A 44-year-old male presented with gradual loss of vision over the past weeks. The patient was diagnosed with ocular toxoplasma chorioretinitis recurrence in his right eye and an inactive peripheral granuloma of ocular toxocariasis was found in the left eye. The patient was a farmer who had been involved in animal husbandry throughout his life. The patient was treated with antibiotics for toxoplasma chorioretinitis and kept under follow-up for ocular toxocariasis.Coinfections of zoonoses are related to socioeconomic environment and individual characteristics of the host. Ocular toxoplasmosis and ocular toxocariasis may present with different scenarios. To our knowledge, this is the first case of a coinfection of ocular toxoplasmosis and ocular toxocariasis in the same patient. A thorough ophthalmological examination and detailed anamnesis are important for diagnosis. [ABSTRACT FROM AUTHOR]

This study presents an evaluation of seventeen newly produced recombinant trivalent chimeric proteins (containing the same immunodominant fragment of SAG1 and SAG2 of Toxoplasma gondii antigens, and an additional immunodominant fragment of one of the parasite antigens, such as AMA1, GRA1, GRA2, GRA5, GRA6, GRA7, GRA9, LDH2, MAG1, MIC1, MIC3, P35, and ROP1) as a potential alternative to the whole-cell tachyzoite lysate (TLA) used in the detection of infection in small ruminants. These recombinant proteins, obtained by genetic engineering and molecular biology methods, were tested for their reactivity with specific anti-Toxoplasma IgG antibodies contained in serum samples of small ruminants (192 samples of sheep serum and 95 samples of goat serum) using an enzyme-linked immunosorbent assay (ELISA). The reactivity of six recombinant trivalent chimeric proteins (SAG1-SAG2-GRA5, SAG1-SAG2-GRA9, SAG1-SAG2-MIC1, SAG1-SAG2-MIC3, SAG1-SAG2-P35, and SAG1-SAG2-ROP1) with IgG antibodies generated during T. gondii invasion was comparable to the sensitivity of TLA-based IgG ELISA (100%). The obtained results show a strong correlation with the results obtained for TLA. This suggests that these protein preparations may be a potential alternative to TLA used in commercial tests and could be used to develop a cheaper test for the detection of parasite infection in small ruminants. [ABSTRACT FROM AUTHOR]