Parasitic diseases are a serious global health concern, causing many common and severe infections, including Chagas disease, leishmaniasis, and schistosomiasis. The NLRP3 inflammasome belongs to the NLR (nucleotide-binding domain leucine-rich-repeat-containing proteins) family, which are cytosolic proteins playing key roles in the detection of pathogens. NLRP3 inflammasomes are activated in immune responses to Plasmodium, Leishmania, Toxoplasma gondii, Entamoeba histolytica, Trypanosoma cruzi, and other parasites. The role of NLRP3 is not fully understood, but it is a crucial component of the innate immune response to parasitic infections and its functions as a sensor triggering the inflammatory response to the invasive parasites. However, while this response can limit the parasites\' growth, it can also result in potentially catastrophic host pathology. This makes it essential to understand how NLRP3 interacts with parasites to initiate the inflammatory response. Plasmodium hemozoin, Leishmania glycoconjugate lipophosphoglycan (LPG) and E. histolytica Gal/GalNAc lectin can stimulate NLRP3 activation, while the dense granule protein 9 (GRA9) of T. gondii has been shown to suppress it. Several other parasitic products also have diverse effects on NLRP3 activation. Understanding the mechanism of NLRP3 interaction with these products will help to develop advanced therapeutic approaches to treat parasitic diseases. This review summarizes current knowledge of the NLRP3 inflammasome\'s action on the immune response to parasitic infections and aims to determine the mechanisms through which parasitic molecules either activate or inhibit its action.

BACKGROUND: Timely diagnosis of Toxoplasma gondii infection is necessary to prevent and control toxoplasmosis transmission. The gold immunochromatographic assay (GICA) is a means of rapidly detecting pathogen in samples. GICA-based diagnostic methods have been developed to accurately detect pathogens with high sensitivity and specificity, and their application in T. gondii diagnosis is expected to yield good results.
METHODS: Colloidal gold test strips were produced using T. gondii C-terminal truncated apical membrane antigen 1 (AMA1C). Colloidal gold-AMA1C and colloidal gold-murine protein conjugate were synthesized under optimal conditions. A nitrocellulose membrane was treated with AMA1C and goat anti-mouse antibody as the test line and control line, respectively. In total, 90 cat serum samples were tested using AMA1C-GICA and a commercial enzyme linked immunosorbent assay (ELISA) kit. The GICA results were digitally displayed using a portable colloidal gold immunochromatographic test strip analyzer (HMREADER). The sensitivity, specificity, and stability of AMA1C-GICA were assessed, and this was then used to examine clinical samples, including 203 human sera, 266 cat sera, and 81 dog sera.
RESULTS: AMA1C-GICA had a detection threshold of 1:32 for T. gondii-positive serum. The GICA strips specifically detected T. gondii antibodies and exhibited no reactivity with Plasmodium vivax, Paragonimus kellicotti, Schistosoma japonicum, Clonorchis sinensis, and Schistosoma mansoni. Consequently, 15 (16.7%) positive samples were detected using the AMA1C-GICA and commercial ELISA kits for each of the assays. The receiver-operating characteristic curve showed that GICA had a relative sensitivity of 85.3% and specificity of 92%, with an area under the curve of 98%. After analyzing clinical samples using HMREADER, 1.2%-23.4% of these samples were found to be positive for T. gondii.
CONCLUSIONS: This study presents a novel assay that enables timely and efficient detection of serum antibodies against T. gondii, thereby allowing for its early clinical diagnosis. Furthermore, the integration of digital detection using HMREADER can enhance the implementation of GICA.

BACKGROUND: Toxoplasmosis is induced by Toxoplasma gondii, which affects 30 percent of the global population and is responsible for deaths related to foodborne pathogens. This study aimed to describe the seroprevalence of T. gondii infections in patients attending referral hospitals in the northwestern region of Saudi Arabia.
METHODS: The serology test results for T. gondii antibodies of 797 patients were retrospectively analyzed using the hospitals\' database. The enzyme-linked immunosorbent assay was used to detect anti-T. gondii antibodies (IgG and/or IgM).
RESULTS: Overall, the prevalence of anti-T. gondii antibodies was 8.3%. Higher (9.9%) prevalence of positive results among patients aged 30 years and above was observed. Statistically, the various age groups (P = 0.031) were found to be significant. Female was noted to have increased (8.1%) seroprevalence, and the incidence of infection occurred largely among participants living in rural areas (8.2%).
CONCLUSIONS: Toxoplasmosis remains a public health concern. The seroprevalence of T. gondii antibodies was relatively low in the study area. IgG antibodies to T. gondii were mainly detected. Increasing awareness on the mode of transmission, source of infection, and disease prevention through health education and dissemination is vital to reduce or eliminate toxoplasmosis.

The aim of our study was to evaluate the impact of T. gondii status on eosinophils count (EOS), the eosinophil-to-lymphocyte ratio (ELR), and the eosinophil-to-neutrophil-to-lymphocytes ratio (ENLR) before and after cannabis cessation in patients with psychiatric disorders. One hundred and eighty-eight patients were included in the study. T. gondii, EOS, ELR, ENLR, and urinary cannabis were measured at baseline and after 4 weeks of cannabis cessation. Highest levels and increase of PNE (p = 0.02), ENLR levels (p = 0.031) and highest level of ELR (p = 0.03) were found in patients after cannabis cessation only in patients positive for T. gondii serology (Toxo+ group). At four weeks, significant interactions between cannabis and T. gondii status for EOS (p = 0.038), and for ENLR (p = 0.043) levels were found, as well as for the evolution between baseline and 4 weeks for ENLR level (p = 0.049). After cannabis cessation, we found a positive correlation between negative symptoms and EOS levels at 4 weeks in the Toxo+ group. This study shows that the increase of inflammation after cannabis cessation might be modulated by T. gondii seropositivity status in patients after cannabis cessation.

Toxoplasma gondii is a cosmopolitan protozoan parasite that has a wide range of intermediate hosts. It infects all warm-blooded animals, including humans and birds. The latter typically pick up the infection by ground feeding, and people can contract the parasite from eating undercooked chicken meat. In recent years, investigations into T. gondii infection in poultry have been reported worldwide. However, there is no epidemiological data regarding the seroprevalence of anti-T. gondii antibodies in chicken in Lebanon. Thus, the current investigation was carried out to determine the seroprevalence and associated risk factors of T. gondii infection in chicken destined for human consumption in the Tripoli district of Lebanon. For this, a cross-sectional study was carried out between April 2021 and February 2022. Blood samples were collected from 400 chickens in four poultry abattoirs in Tripoli. The modified agglutination test (MAT) was used to test sera for T. gondii antibodies. The association of T. gondii seroprevalence with potential risk factors was assessed using the Chi-square test. Multivariate analysis was used to confirm the association. The seroprevalence of T. gondii antibodies reported in this study was 13% (52/400); it was higher in the free-range chicken group (19.3%, 29/150) than in the caged group (9.2%, 23/250) (OR = 2.365; 95% CI: 1.311-4.267) (P = 0.004). The wet season and the presence of cats in the poultry farms were significantly associated with an increased seropositivity to T. gondii infection (P ≤ 0.0001). Given the occurrence of T. gondii antibodies in slaughtered chicken in this area, the consumption of raw or undercooked chicken meats may pose a serious threat to public health and highlight the need to implement appropriate precautionary strategies to halt the spread of T. gondii to humans.

BACKGROUND: Immunocompromised patients may be at risk for reactivating the toxoplasmosis infection; therefore, early diagnosis would be highly desirable in these individuals. This study evaluated the possible association between coronavirus disease 2019 (COVID-19) and latent Toxoplasma gondii infection in Guilan province, Iran.
METHODS: The study was performed among 210 COVID-19 patients referred to Guilan University of Medical Sciences hospitals in 2022. Peripheral blood samples were taken for serum separation, collected into tubes, and kept at - 20 °C until use. Blood samples were obtained from COVID-19 patients. IgG antibody to Toxoplasma gondii was detected by a commercial ELISA kit. Accordingly, IgG absorbance levels <9 were considered harmful, 9-11 was considered borderline, and >11 was positive.
RESULTS: Toxoplasma IgG antibodies were found in 73.9 % of patients with COVID-19 in male patients. The seroprevalence of Toxoplasma in dead and lived COVID-19 male patients was 83.3 % and 66.7 %, respectively, and this difference was significant. A present study found a significant correlation between the rising titer of Toxoplasma IgG and the severity of COVID-19. There was no significant difference between the hospitalization duration factor and the seropositivity rate.
CONCLUSIONS: Regarding the significant association between the rising titer of Toxoplasma IgG and the severity of COVID-19. The findings demonstrated an association between the severity and mortality rate of COVID-19 with higher titer Anti-Toxoplasma IgG antibodies. Toxoplasmosis is currently considered a risk factor for COVID-19.

Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world\'s population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer 57Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT.

The hydrazones 3a-c, were synthesized from the reaction of indole-3-carbaldehyde and nicotinic acid hydrazide, isonicotinic acid hydrazide, and benzoic acid hydrazide, respectively. Their structures were confirmed using FTIR, 1HNMR, and 13CNMR spectroscopic techniques. Exclusively, hydrazones 3b and 3c were confirmed using single crystal X-ray crystallography to exist in the Eanti form. With the aid of DFT calculations, the most stable configuration of the hydrazones 3a-c in gas phase and in nonpolar solvents (CCl4 and cyclohexane) is the ESyn form. Interestingly, the DFT calculations indicated the extrastability of the EAnti in polar aprotic (DMSO) and polar protic (ethanol) solvents. Hirshfeld topology analysis revealed the importance of the N…H, O…H, H…C, and π…π intermolecular interactions in the molecular packing of the studied systems. Distribution of the atomic charges for the hydrazones 3a-c was presented. The hydrazones 3a-c showed a polar character where 3b has the highest polarity of 5.7234 Debye compared to the 3a (4.0533 Debye) and 3c (5.3099 Debye). Regarding the anti-toxoplasma activity, all the detected results verified that 3c had a powerful activity against chronic toxoplasma infection. Compound 3c showed a considerable significant reduction percent of cyst burden in brain homogenates of toxoplasma infected mice representing 49%.

Toxoplasma gondii (T. gondii) is a parasite that obtains the iron it needs for its own metabolism from the host-cell iron pool. In this work, we aimed to investigate if iron supplementation or deficiency affected the course of T. gondii infection. Eighty mice were divided into four groups, each with 20 animals: Group (I): Uninfected control group. Group (II): Infected control group: injected with Phosphate buffered saline. Group (III): Infected group: received iron sucrose treatment. Group (IV): Infected group: treated with deferoxamine. Quantitative PCR studies were performed on days 3 and 8 post-infection to detect the expression of iron metabolism genes (hamp and ferroprotin) and immune-histochemical analysis to study the percentage of TNF-α and TGF-β tissue expression. Iron supplementation induced progressions of infection evident by increased tissue expression of pro-inflammatory cytokine TNF-α and downregulation of TGF-β which is mostly linked to suppression of the inflammatory process caused by T. gondii. Increased expression of TGF-β and decreased expression of TNF-α was noticed when iron deprivation occurred. On day 3, we noticed increased expression in the hamp gene with iron supplementation while it decreases when the iron supply is low. On the contrary, iron deficiency increased ferroprotin gene expression whereas supplementing decreased it. On day 8, the level of expression of these genes returned to normal levels. These observations document the potential role of iron in controlling toxoplasmosis infection and indicate that the transcription of hamp and ferroprotin in T. gondii-infected cells appears to be regulated by a sophisticated indirect mechanism.

BACKGROUND: Toxoplasma gondii is an opportunistic protozoan that is ubiquitous in humans and animals. It can invade any human organ and cause severe diseases, including toxoplasma ophthalmopathy, meningoencephalitis, and liver necrosis. Porcine toxoplasmosis is prevalent in China. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and Cas (CRISPR-Associated Protein) systems are widely used for gene editing and pathogen detection. CRISPR-based diagnostics are molecular assays that have been developed to detect parasites with high sensitivity and specificity.
METHODS: This study aimed to establish a combined CRISPR/Cas12a and RPA rapid detection method for T. gondii by targeting the B1 gene and 529 bp repeat element (529 RE). The detection results could be visualized by the fluorescence or lateral flow strips (LFS). The sensitivity and specificity of the method were evaluated, and T. gondii-infected mouse blood was used for detection.
RESULTS: The results indicated that the established method for T. gondii detection was satisfactory, with a detection limit of 1.5 cp/μl for the two loci. Moreover, the B1 gene could detect 1 tachyzoite per reaction, and the 529 RE could detect 0.1 tachyzoite per reaction, consistently with the highly sensitive nested polymerase chain reaction (PCR) results. The method was suitable for strains, including RH, and did not cross-react with other protozoa DNA with similar habits. The T. gondii-infected mouse blood samples were all positive for T. gondii at 1, 3, and 5 days post infection (dpi).
CONCLUSIONS: This study established a rapid, sensitive, and time-saving DNA detection method for T. gondii that has the potential to be an alternative tool for T. gondii detection in the field.