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1.
Arq. bras. oftalmol ; 88(1): e2023, 2025. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1568845

RESUMEN

ABSTRACT Purpose: To characterize the extracellular vesicle protein cargo in the aqueous humor and plasma of patients with ocular toxoplasmosis. Methods: Aqueous humor and plasma were collected from six patients with active ocular toxoplasmosis and six patients with cataract. Extracellular vesicles were isolated, and western blotting and mass spectrometry were performed for protein analysis. Results: All plasma samples from patients with ocular toxoplasmosis and cataract were positive for the tetraspanins CD63 and TSG101. However, the aqueous humor from patients with ocular toxoplasmosis was positive only for CD63. Sixty-seven new unreported proteins were identified in the aqueous humor and plasma of patients with the ocular toxoplasmosis and cataract. Of the 67 proteins, 10 and 7 were found only in the cataract and ocular toxoplasmosis groups, respectively. In general, these proteins were involved in immune system activation and retina homeostasis and were related to infections and retina-associated diseases. Conclusion: The distinct protein signatures between ocular toxoplasmosis and cataract may be helpful in the differential diagnosis of ocular toxoplasmosis. However, more studies are needed to better understand the role of these proteins in the pathogenesis of ocular toxoplasmosis.

2.
Int J Environ Health Res ; : 1-8, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287148

RESUMEN

Our aim was to examine the relationship between Toxoplasma gondii (T. gondii) and Toxocara infection and patients with essential tremor (ET). This study comprised a total of 174 participants, consisting of 99 patients with ET and 75 healthy controls. The presence of anti-T. gondii IgG and anti-Toxocara IgG antibodies was investigated using ELISA. The relationship between the severity of the disease and the seropositivity of T. gondii and Toxocara were examined. The seropositivity rate for anti-T. gondii IgG antibodies among patients and control groups were 43.4% and 12%, respectively (odds ratio [OR]: 5.63; 95% CI: 2.53-12.56). The patient group exhibited a higher seroprevalence of anti-Toxocara IgG antibodies (32.3%) compared with the control group (13.3%; OR: 3.10; 95% CI: 1.41-6.83; p = 0.004). This study suggests that T. gondii and Toxocara infections can contribute to the pathogenic mechanisms underlying ET and could be risk factors for ET.

3.
Vet Parasitol ; 332: 110313, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39278072

RESUMEN

Toxoplasmosis caused by Toxoplasma gondii is a protozoal zoonosis with high sanitary risk for pregnant women and immunocompromised people. Felids, including domestic cats, are the only definitive hosts of T. gondii. They shed oocysts which, in the environment, become infectious for a wide range of animals, including humans, acting as intermediate hosts. This study evaluated the frequency of acute toxoplasmosis in domestic cats with compatible clinical signs and living in households with women of childbearing age. Individual serum samples were collected from 150 cats and analyzed for IgM and IgG against T. gondii. Statistical analyses were performed to evaluate associations between seropositivity and potential risk factors. Overall, 31 cats (20.7 %) were seropositive for anti-T. gondii antibodies, i.e. 9 (6.0 %) for IgM, 17 (11.3 %) for IgG and 5 (3.3 %) for both. The cats showed different combinations of clinical pictures. The following statistically significant associations were found: male sex and positivity for IgM and/or IgG (p=0.0248; OR= 0.3537; 95 % CI= 0.1528-0.8675), presence of 2 or more clinical signs and positivity to IgM only (p=0.0003; OR= +infinity; 95 % CI= 3.924 to +infinity), presence of either neurological signs (p=0.0025; OR= 13.30; 95 % CI= 3.409-61.39) or ocular signs (p=0.0228; OR= 5.835; 95 % CI= 1.631-22.37) and positivity to IgM only, presence of gastrointestinal signs and positivity to IgG only (p=0.0083; OR= 5.508; 95 % CI= 1.503-18.54). Male sex also resulted a possible risk factor in the binomial logistic regression (p= 0.011; OR= 3.336; 95 % CI= 1.131-8.44). These results indicate that cats living with women of childbearing age are at risk of infection with T. gondii. The presence of certain clinical signs can be helpful in identifying recent and/or current infections using laboratory analyses. Awareness on toxoplasmosis should be kept high to protect animal and public health.

4.
Animals (Basel) ; 14(17)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39272328

RESUMEN

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.

5.
Vet Anim Sci ; 25: 100389, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39263043

RESUMEN

Cats, being the definitive host of Toxoplasma gondii, have a significant impact on the spread and outbreaks of the parasite. An essential factor in comprehending the transmission pattern of this parasite is an analysis of the genetic diversity distribution in cats infected with T. gondii. This study was aimed at determining the prevalence rate and genotyping of T. gondii in stray cat feces from Khorramabad, West Iran. In the years 2016-2017, 200 cats were sampled to get fresh feces specimens. Parasitological methods were utilized for the identification of oocysts. The DNA was isolated from the feces using a commercially available Genomic Mini Kit. In order to identify the genetic composition of T. gondii, we employed PCR-RFLP, sequencing, and phylogenetic analysis of the GRA6 target gene. No one of the samples tested positive for parasitology techniques. A total of 6.5 % (13/200) samples were positive when using the GRA6-PCR method. Based on PCR-RFLP results, all 13 samples were of T. gondii type III genotype. The nucleotide sequences of two samples from this study were found to be 5 % different from those of 12 references of T. gondii and one strain of Hammondia hamondi that was used as an external control. Based on the findings, molecular tests are more sensitive than parasitological methods. The RFLP approach revealed that type III of T. gondii is the prevailing and important genotype in Khorramabad, West Iran.

6.
Front Immunol ; 15: 1429302, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39253089

RESUMEN

Toxoplasmosis is a worldwide parasitosis that is usually asymptomatic; cell-mediated immunity, particularly T cells, is a crucial mediator of the immune response against this parasite. Membrane protein expression has been studied for a long time in T lymphocytes, providing vital information to determine functional checkpoints. However, less is known about the role of post-translational modifications in T cell function. Glycosylation plays essential roles during maturation and function; particularly, sialic acid modulation is determinant for accurate T cell regulation of processes like adhesion, cell-cell communication, and apoptosis induction. Despite its importance, the role of T cell sialylation during infection remains unclear. Herein, we aimed to evaluate whether different membrane sialylation motifs are modified in T cells during acute Toxoplasma gondii infection using different lectins. To this end, BALB/c Foxp3EGFP mice were infected with T. gondii, and on days 3, 7, and 10 post-infection, splenocytes were obtained to analyze conventional (Foxp3-) CD4+ and CD8+ populations by flow cytometry. Among the different lectins used for analysis, only Sambucus nigra lectin, which detects sialic acid α2,6 linkages, revealed two distinctive populations (SNBright and SN-/Dim) after infection. Further characterization of CD4+ and CD8+ SN-/Dim lymphocytes showed that these are highly activated cells, with a TEf/EM or TCM phenotype that produce high IFN-γ levels, a previously undescribed cell state. This work demonstrates that glycan membrane analysis in T cells reveals previously overlooked functional states by evaluating only protein expression.


Asunto(s)
Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Ratones Endogámicos BALB C , Toxoplasma , Toxoplasmosis , Animales , Linfocitos T CD8-positivos/inmunología , Toxoplasma/inmunología , Ratones , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Toxoplasmosis/inmunología , Toxoplasmosis/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Femenino
7.
J Infect Dis ; 230(Supplement_2): S165-S172, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39255396

RESUMEN

BACKGROUND: Toxoplasma gondii infection of Alzheimer's disease model mice decreases amyloid ß plaques. We aimed to determine if there is a brain regional difference in amyloid ß reduction in the brains of T. gondii-infected compared to control mice. METHOD: Three-month-old 5xFAD (AD model) mice were injected with T. gondii or with phosphate-buffered saline as a control. Intact brains were harvested at 6 weeks postinfection, optically cleared using iDISCO+, and brain-wide amyloid burden was visualized using volumetric light-sheet imaging. Amyloid signal was quantified across each brain and computationally mapped to the Allen Institute Brain Reference Atlas to determine amyloid density in each region. RESULTS: A brain-wide analysis of amyloid in control and T. gondii-infected 5xFAD mice revealed that T. gondii infection decreased amyloid burden in the brain globally as well as in the cortex and hippocampus, and many daughter regions. Daughter regions that showed reduced amyloid burden included the prelimbic cortex, visual cortex, and retrosplenial cortex. The olfactory tubercle, a region known to have increased monocytes following T. gondii infection, also showed reduced amyloid after infection. CONCLUSIONS: T. gondii infection of AD mice reduces amyloid burden in a brain region-specific manner that overlaps with known regions of T. gondii infection and peripheral immune cell infiltration.


Asunto(s)
Enfermedad de Alzheimer , Encéfalo , Modelos Animales de Enfermedad , Ratones Transgénicos , Toxoplasma , Animales , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/parasitología , Enfermedad de Alzheimer/patología , Ratones , Encéfalo/parasitología , Encéfalo/metabolismo , Encéfalo/patología , Péptidos beta-Amiloides/metabolismo , Placa Amiloide/metabolismo , Placa Amiloide/patología , Toxoplasmosis/metabolismo , Femenino
8.
J Infect Public Health ; 17(10): 102539, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39270468

RESUMEN

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Vital organs like the heart are affected by the occlusion of blood vessels due to atherosclerotic plaque formation. However, the role of infectious agents has always been an essential subject of investigation. This study investigated the presence of microorganisms, including nanobacteria, in atherosclerotic plaques removed from human carotid arteries by microbiological and metagenomic examination. METHODS: Atheroma plaque samples were obtained from 20 patients with carotid artery stenosis who had atherectomy by surgery or percutaneous intervention. Nanobacteria were grown by culturing homogenates of the atheroma plaques. Whole genome sequencing was done for samples. Because of the high percentage of Toxoplasma gondii (T. gondii) DNA, PCR investigation was applied to detect T. gondii DNA in the samples. RESULTS: A molecular analysis of nanobacteria revealed them to be made of human proteins, supporting the theory that they are not living organisms. According to sequencing results, samples showed that more than 50 % of the metagenomic sequences belonged to Toxoplasma gondii. PCR investigation indicated that T. gondii DNA was positive in 8 (40 %) of 20 plaques. CONCLUSIONS: Further evidence regarding the role of T. gondii in the etiology of plaque formation may help determine the strategy for prevention and treatment of infections in preventing atheroma plaque formation in the future.

9.
Parasit Vectors ; 17(1): 377, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237959

RESUMEN

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.


Asunto(s)
Anticuerpos Antiprotozoarios , Proteínas Protozoarias , Vacunas Antiprotozoos , Toxoplasma , Toxoplasmosis Animal , Vacunas Atenuadas , Animales , Toxoplasma/inmunología , Toxoplasma/genética , Ratones , Vacunas Antiprotozoos/inmunología , Vacunas Antiprotozoos/administración & dosificación , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/administración & dosificación , Proteínas Protozoarias/inmunología , Proteínas Protozoarias/genética , Anticuerpos Antiprotozoarios/sangre , Femenino , Toxoplasmosis Animal/prevención & control , Toxoplasmosis Animal/inmunología , Citocinas/metabolismo , Virulencia , Carga de Parásitos , Modelos Animales de Enfermedad , Enfermedad Crónica , Toxoplasmosis/prevención & control , Toxoplasmosis/inmunología , Toxoplasmosis/parasitología
10.
Acta Parasitol ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225734

RESUMEN

BACKGROUND: Toxoplasma gondii (T. gondii) infects one third of the world's population with significant illness, mainly among immunocompromised individuals and pregnant women. Treatment options for toxoplasmosis are limited which signifies the need for novel, potent, and safe therapeutic options. The goal of this study was to assess the effectiveness of the ethanolic extract of Zingiber officinale (Z. officinale) in treating mice infected with the RH T. gondii strain. MATERIALS AND METHODS: Gas Chromatography/Mass Spectrometry (GC/MS) was used to identify components of ethanolic extract of Z. officinale. A total of 80 mice were randomly allocated into four experimental groups that contained 20 mice each. The first group was left uninfected (uninfected control), while three groups were infected with T. gondii RH virulent strain tachyzoites at 2500 tachyzoites/mouse. One infected group was left untreated (infected, untreated), whereas the other two groups were treated orally with either spiramycin (positive control) or Z. officinale ethanolic extract at doses of 200 mg/kg and 500 mg/kg, respectively for 5 days, starting the day of infection. Ten mice from each group were used to assess mice survival in different groups, whereas the other ten mice in each group were sacrificed on the 5th day post-infectin (dpi) to estimate the treatment efficacy by quantifying liver parasite load, liver function, nitric oxide (NO) production, and levels of antioxidant enzymes. Additionally, histopathological studies were performed to evaluate the therapeutic effect of Z. officinale treatment on toxoplasmosis-induced pathological alterations in liver, brain, and spleen. RESULTS: Treatment with Z. officinale ethanolic extract extended the survival of mice till 9th dpi compared to 7th dpi in infected untreated mice. Higher percentage of mice survived in Z. officinale-treated group compared to spiramycin-treatment group at different time points. Liver parasite loads were significantly lower in Z. officinale extract-treated mice and spiramycin-treated mice compared to infected untreated mice which correlated with significantly lower levels of serum liver enzymes (ALT, AST) and nitric oxide (NO), as well as significantly higher catalase (CAT) antioxidant enzyme activity. Scanning electron microscopy (SEM) examination of tachyzoites from the peritoneal fluid revealed marked damage in tachyzoites from Z. officinale-treated group compared to that from infected untreated mice. Moreover, treatment with Z. officinale ethanolic extract alleviated infection-induced pathological alterations and restored normal tissue morphology of liver, brain, and spleen. CONCLUSION: Our results demonstrated that Z. officinale treatment reduced parasite burden and reversed histopathological and biochemical alterations in acute murine toxoplasmosis. These findings support the potential utility of Z. officinale as a future effective natural therapeutic for toxoplasmosis. Further studies are needed to determine the effective active ingredient in Z. officinale extract that can be further optimized for treatment of toxoplasmosis.

11.
Comp Immunol Microbiol Infect Dis ; 113: 102231, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39232437

RESUMEN

Leptospirosis and toxoplasmosis are re-emerging zoonosis caused by infection with pathogenic spirochaetes of Leptospira and the protozoa Toxoplasma gondii, respectively. Wild boars (Sus scrofa), an exotic invasive species in Brazil, could play a role in the diseases' epidemiological cycles, but this issue is still unexplored. This study aimed to evaluate the Leptospira spp. and T. gondii seropositivity in wild boars in Rio Grande do Sul state, south Brazil. Of evaluated animals, 16% (13/80) and 85% (52/61) had antibodies to T. gondii and Leptospira spp., respectively. Sex, weight, age, hunt location and season of hunt were evaluated by their association with seropositivity for both pathogens, but none of them had statistical significance. This study revealed that wild boars should be considered as a potential source of Leptospira spp. and T. gondii dissemination for humans and animal species in shared environments in Rio Grande do Sul state.

12.
Parasites Hosts Dis ; 62(3): 294-301, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39218628

RESUMEN

Toxoplasma gondii, a common protozoan parasite, poses significant public health risks due to its potential to cause toxoplasmosis in humans and can be contracted from pigs, which are considered its critical intermediate host. The aim of this study is to evaluate the prevalence of T. gondii in slaughtered pigs for human consumption, emphasizing the zoonotic implications and the need for improved biosecurity and monitoring practices in pig farming. A total of 1,526 pig samples (1,051 whole blood samples and 384 lung tissue samples from the local slaughterhouse and 91 aborted fetus samples from local farms) were collected throughout the whole country of Korea in 2020. Among them, 6 (0.4%) were found to be infected with T. gondii by nested PCR. When compared by sample type, the prevalence of T. gondii was significantly higher in the aborted fetus samples (2.2%, 2/91) than in the blood (0.3%, 3/1,051) and lung tissue samples (0.3%, 1/384). The B1 gene sequence of T. gondii was similar (97.9-99.8%) to that of the other T. gondii isolates. This study represents the first molecular genotyping survey of T. gondii in the lung tissue of fattening pigs and aborted fetuses in Korea. Our findings indicated the importance of adopting preventive measures including the implementation of rigorous farm hygiene protocols and the promotion of public awareness about the risks of consuming undercooked pork. By addressing the gaps in current control strategies and encouraging the One Health approach, this study contributes to the development of more effective strategies to mitigate the transmission of T. gondii from pigs to humans, ultimately safeguarding public health.


Asunto(s)
Genotipo , Enfermedades de los Porcinos , Toxoplasma , Toxoplasmosis Animal , Animales , Toxoplasma/genética , Toxoplasma/aislamiento & purificación , República de Corea/epidemiología , Porcinos , Toxoplasmosis Animal/epidemiología , Toxoplasmosis Animal/parasitología , Enfermedades de los Porcinos/parasitología , Enfermedades de los Porcinos/epidemiología , Enfermedades de los Porcinos/transmisión , Prevalencia , Mataderos , Pulmón/parasitología , Reacción en Cadena de la Polimerasa , Humanos , ADN Protozoario/genética , Feto Abortado/parasitología
13.
Vet Parasitol Reg Stud Reports ; 54: 101093, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39237225

RESUMEN

Toxoplasmosis is one of the most common parasitic zoonoses and represents a significant health risk for humans, especially for immunodeficient patients. The main transmission route is by oral uptake of oocysts and consumption of undercooked meat of infected animals. Different species have been evaluated as possible reservoirs of the parasite, but few studies have been carried out to examine the role of horses in transmission of the disease. Given the proximity of these animals to humans and the widespread consumption of their meat in many countries, including the Mediterranean basin, it is important to determine the prevalence of T. gondii infection in this species. In this study, blood samples from 105 horses were collected and the presence of T. gondii was evaluated by serological and molecular methods. Antibodies against T. gondii of 12 horses (11.43%) were detected by enzyme-linked immunosorbent assay (ELISA), whereas 29 horses (27.62%) showed positive for PCR. Seroprevalence was related to use of the animals, being higher in horses used for dressage than in others. Purebreds had higher seroprevalence than crossbred animals. No differences between breed, sex or age were found. The results of this study confirm the presence of T. gondii infection in horses, highlighting the need to analyse the meat of this species before human consumption and to control of this infection in horses, as they could be an important reservoir of this zoonotic parasite.


Asunto(s)
Anticuerpos Antiprotozoarios , Ensayo de Inmunoadsorción Enzimática , Enfermedades de los Caballos , Toxoplasma , Toxoplasmosis Animal , Animales , Caballos/parasitología , Toxoplasmosis Animal/epidemiología , Toxoplasmosis Animal/diagnóstico , Toxoplasmosis Animal/parasitología , España/epidemiología , Enfermedades de los Caballos/parasitología , Enfermedades de los Caballos/epidemiología , Enfermedades de los Caballos/diagnóstico , Toxoplasma/aislamiento & purificación , Toxoplasma/genética , Estudios Seroepidemiológicos , Femenino , Anticuerpos Antiprotozoarios/sangre , Masculino , Ensayo de Inmunoadsorción Enzimática/veterinaria , Reacción en Cadena de la Polimerasa/veterinaria , Prevalencia
14.
Parasit Vectors ; 17(1): 376, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232817

RESUMEN

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.


Asunto(s)
Toxoplasma , Toxoplasma/efectos de los fármacos , Animales , Ratones , Femenino , Péptidos/farmacología , Toxoplasmosis/parasitología , Antiprotozoarios/farmacología , Hemólisis/efectos de los fármacos , Humanos
15.
Artículo en Inglés | MEDLINE | ID: mdl-39252165

RESUMEN

BACKGROUND: Toxoplasma gondii is a very common zoonotic parasite in humans and animals worldwide. Human seroprevalence is high in some regions of Canada's North and is thought to be associated with the consumption of traditionally prepared country foods, such as caribou, walrus, ringed seal and beluga. While numerous studies have reported on the prevalence of T. gondii in these animals, in the general absence of felid definitive hosts in the North there has been considerable debate regarding the source of infection, particularly in marine mammals. It has been proposed that fish could be involved in this transmission. AIMS: The objectives of the present study were to perform a targeted survey to determine the prevalence of T. gondii DNA in various tissues of anadromous Arctic charr sampled in Nunavik, Québec, and to investigate the possible role of this commonly consumed fish in the transmission of infection to humans and marine mammals in Canada's North. METHODS AND RESULTS: A total of 126 individual Arctic charr were sampled from several sites in Nunavik, and various tissues were tested for the presence of T. gondii DNA using PCR. Overall, 12 out of 126 (9.5%) Arctic charr tested in the present study were PCR-positive, as confirmed by DNA sequencing. Brain tissue was most commonly found to be positive, followed by heart tissue, while none of the dorsal muscle samples tested were positive. CONCLUSIONS: Although the presence of T. gondii DNA in brain and heart tissues of Arctic charr is very intriguing, infection in these fish, and their possible role in the transmission of this parasite to humans and marine mammals, will need to be confirmed using mouse bioassays. Arctic charr are likely exposed to T. gondii through the ingestion of oocysts transported by surface water and ocean currents from more southerly regions where the definitive felid hosts are more abundant. If infection in Arctic charr can be confirmed, it is possible that these fish could play an important role in the transmission of toxoplasmosis to Inuit, either directly through the consumption of raw fish or indirectly through the infection of fish-eating marine mammals harvested as country foods.

16.
Sci Rep ; 14(1): 20920, 2024 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251676

RESUMEN

Blood transfusion has a hazard of transmission of many pathogens, including Toxoplasma gondii (T. gondii) and other venereal infections. It is crucial to conduct epidemiological surveillance to detect the prevalence of these pathogens. The study aimed to assess the seroprevalence of T. gondii and common transfusable venereal infections among healthy blood donors in Menoufia Province, Egypt, and identify associated risk factors. Four hundred twenty individuals were recruited between January and April 2023 for cross-sectional descriptive research from the blood banks of Menoufia University medical hospitals. Collected blood samples were screened for anti-T. gondii IgM and IgG, HBsAg, anti-HCV antibodies, HIV p24 antigen and anti-HIV antibodies, and anti-Treponema pallidum antibodies. 46 (11.0%) and 22 donors (5.2%) individuals tested positive for anti-T. gondii IgG with a 95% CI (8.3-14.6) and IgM with a 95% CI (3.5-8.1), respectively, while one patient (0.2%) was positive for both antibodies. Regarding venereal infections, 12 (2.9%) were positive for HBV, 6 (1.4%) were positive for HCV, 7 (1.7%) were positive for HIV, and none of the tested population showed positivity for syphilis. Female gender, consumption of raw meat, agricultural environment, poor awareness about T. gondii, and blood group type (especially AB and O groups) were identified as independent risk factors for T. gondii infection. The study highlights the importance of testing blood donors for T. gondii and common transfusable venereal illnesses. Starting health education programs and preventative measures, such as suitable meat handling and cleanliness practices, is critical for minimizing the occurrence of these illnesses. Larger-scale additional study is advised to confirm these results and provide guidance for public health initiatives.


Asunto(s)
Donantes de Sangre , Enfermedades de Transmisión Sexual , Toxoplasma , Toxoplasmosis , Humanos , Egipto/epidemiología , Masculino , Toxoplasma/inmunología , Femenino , Toxoplasmosis/epidemiología , Toxoplasmosis/parasitología , Adulto , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/parasitología , Estudios Transversales , Estudios Seroepidemiológicos , Persona de Mediana Edad , Factores de Riesgo , Adulto Joven , Anticuerpos Antiprotozoarios/sangre , Prevalencia , Adolescente , Sífilis/epidemiología , Sífilis/sangre
17.
Vet Parasitol ; 332: 110306, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39265207

RESUMEN

Toxoplasma gondii is a globally distributed zoonotic protist, capable of infecting all warm-blooded animals. In Australia, cats (Felis catus) are the only definitive host capable of spreading T. gondii infection via oocysts. Free-roaming cats are widespread in Australia and can play a central role in the ecology of T. gondii. Therefore, understanding the epidemiology of this parasite in stray and feral cats is essential to understanding the potential risk of infection in animals and humans. Due to a lack of easily accessible commercial kits, an in-house modified agglutination test (MAT) was established to test for IgG antibodies against T. gondii, using cell culture-derived T. gondii tachyzoites, and compared with a commercial MAT. A total of 552 serum samples collected during 2018 - 2021 from stray (n = 456) and feral cats (n = 90) (samples with missing data n = 6) from four Australian states, representing different age groups of both sexes, were screened for antibodies against T. gondii. Risk factors for T. gondii infection were assessed using multivariable logistic regression analysis. The in-house MAT had excellent agreement with the commercial MAT and provided a reliable and economical serological tool for T. gondii screening in animals. The overall observed seroprevalence for T. gondii in cats was 40.4 % (223/552). Bodyweight (as a proxy for age), geographical location, season and whether cats were feral or stray, were factors associated with T. gondii seropositivity in cats. Sex was not found to be a risk factor for T. gondii infection in feral and stray cats. This study shows that Australian stray and feral cats have a high T. gondii seroprevalence, which may translate to significant health impacts for wildlife species, livestock and the public.

18.
Nervenarzt ; 2024 Sep 12.
Artículo en Alemán | MEDLINE | ID: mdl-39266688

RESUMEN

Pathogen-induced myelitis is an inflammatory disease of the spinal cord that can be caused by various pathogens including viruses, bacteria, fungi or parasites. The most frequent viral pathogens include herpes and enteroviruses, while bacterial myelitis can be caused by, e.g., Mycobacterium tuberculosis, Borrelia burgdorferi and Treponema pallidum. Fungi such as Candida and Aspergillus and parasites such as Toxoplasma gondii and schistosomes can also cause myelitis. The main symptom is subacute paraplegia with motor, sensory and autonomic deficits to varying degrees, often accompanied by fever and a general malaise. Following a thorough clinical examination and review of the medical history diagnostic imaging procedures, such as magnetic resonance imaging (MRI) along with cerebrospinal fluid analysis and blood tests that include antibody testing are warranted. The treatment is directed at the cause of the myelitis and mostly with anti-infective agents but for some viral pathogens no specific treatment is available and the only option is a symptomatic treatment. The prognosis is very variable and depends on the etiology and severity of the disease. A fast diagnosis and targeted treatment are crucial to achieve a good outcome.

19.
Artículo en Inglés | MEDLINE | ID: mdl-39253292

RESUMEN

This study aimed to evaluate the presence and viability of Toxoplasma gondii in chickens intended for human consumption in the Pernambuco State, Brazil. Blood and tissue samples were collected from 25 chickens sold in markets in Recife, Pernambuco. Samples were evaluated by indirect immunofluorescence assay (IFA) to detect antibodies to T. gondii. Pools of brain and heart of seropositive chickens were subjected to bioassay in two Swiss Webster mice, which were evaluated for 45 days then tested by IFA to detect seroconversion. The mice were euthanized, and their brains were evaluated for cysts. Peritoneal lavage was also conducted in mice that exhibited clinical signs. Brains containing cysts or peritoneal lavage with tachyzoites were inoculated into MA-104 cells. Brains of mice inoculated with the same tissue were pooled and analysed by ITS1-PCR. We obtained a frequency of antibodies to T. gondii of 68.00% (17/25) in chickens, and a seroconversion rate of 70.58% (24/34) in mice. Detection of Toxoplasma ITS1 DNA confirmed an isolation rate of 41.1% (7/17). Three isolates were characterized by mnPCR-RFLP as genotypes ToxoDB#36 and ToxoDB#114. We highlight the occurrence of ToxoDB#36 in chickens in Pernambuco State and the parasites' viability in chickens intended for human consumption.

20.
Front Chem ; 12: 1406307, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39104777

RESUMEN

Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii, an apicomplexan parasite that infects approximately a third of the world's human population. This disease can cause serious complications during pregnancy and can be fatal in immunocompromised hosts. The current treatment options for toxoplasmosis face several limitations. Thus, to address the urgent medical need for the discovery of novel anti-toxoplasma potential drug candidates, our research focused on exploring a series of monomeric and dimeric chalcones, polyphenolic molecules belonging to the class of flavonoids. Chalcones 1aa-1bg and axially chiral A-A'-connected bichalcones 2aa-2bg were evaluated in vitro against the proliferation of the parasite in a cell-based assay. A comparison of the efficacy demonstrated that, in several cases, bichalcones exhibited increased bioactivity compared to their corresponding monomeric counterparts. Among these compounds, a bichalcone with a phenyl substituent and a methyl moiety 2ab showed the most potent and selective inhibitory activity in the nanomolar range. Both enantiomers of this bichalcone were synthesized using an axially chiral biphenol building block. The biaryl bond was forged using Suzuki cross-coupling in water under micellar catalysis conditions. Separation of the atropisomers of this biphenol building block was conducted by chiral HPLC on a preparative scale. The biological evaluation of the enantiomers revealed that the (R a)-enantiomer (R a)-2ab is the eutomer. These studies suggest that bichalcones may be important drug candidates for further in vivo evaluations for the discovery of anti-toxoplasma drugs.

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