RESUMO
Anti-Toxoplasma gondii antibodies were investigated in 125 Saimiri spp. kept at a research institute. A total of 12% of primates tested positive, all of which were Saimiri sciureus. These results highlight the need to minimize the possibility of this protozoan's circulation, which can lead to fulminant infection in these animals.
Assuntos
Anticorpos Antiprotozoários , Doenças dos Macacos , Saimiri , Toxoplasma , Toxoplasmose Animal , Animais , Brasil/epidemiologia , Anticorpos Antiprotozoários/sangue , Doenças dos Macacos/parasitologia , Feminino , Estudos Soroepidemiológicos , MasculinoRESUMO
BACKGROUND: Infection with the protozoan parasite Toxoplasma gondii leads to the formation of lifelong cysts in neurons that can have devastating consequences in the immunocompromised. In the immunocompetent individual, anti-parasitic effector mechanisms and a balanced immune response characterized by pro- and anti-inflammatory cytokine production establishes an asymptomatic infection that rarely leads to neurological symptoms. Several mechanisms are known to play a role in this successful immune response in the brain including T cell production of IFNγ and IL-10 and the involvement of CNS resident cells. This limitation of clinical neuropathology during chronic infection suggests a balance between immune response and neuroprotective mechanisms that collectively prevent clinical manifestations of disease. However, how these two vital mechanisms of protection interact during chronic Toxoplasma infection remains poorly understood. MAIN TEXT: This study demonstrates a previously undescribed connection between innate neutrophils found chronically in the brain, termed "chronic brain neutrophils" (CBNeuts), and neuroprotective mechanisms during Toxoplasma infection. Lack of CBNeuts during chronic infection, accomplished via systemic neutrophil depletion, led to enhanced infection and deleterious effects on neuronal regeneration and repair mechanisms in the brain. Phenotypic and transcriptomic analysis of CBNeuts identified them as distinct from peripheral neutrophils and revealed two main subsets of CBNeuts that display heterogeneity towards both classical effector and neuroprotective functions in an age-dependent manner. Further phenotypic profiling defined expression of the neuroprotective molecules NRG-1 andErbB4 by these cells, and the importance of this signaling pathway during chronic infection was demonstrated via NRG-1 treatment studies. CONCLUSIONS: In conclusion, this work identifies CBNeuts as a heterogenous population geared towards both classical immune responses and neuroprotection during chronic Toxoplasma infection and provides the foundation for future mechanistic studies of these cells.
Assuntos
Neutrófilos , Toxoplasmose , Animais , Neutrófilos/imunologia , Neutrófilos/metabolismo , Camundongos , Toxoplasmose/imunologia , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Neurônios/imunologia , Toxoplasma/imunologia , Feminino , Neuroproteção/fisiologia , Masculino , Encéfalo/imunologia , Encéfalo/patologia , Encéfalo/parasitologiaRESUMO
BACKGROUND: Road traffic injuries (RTIs) are among the most important issues worldwide. Several studies reported that infection with the neurotropic parasite Toxoplasma gondii (T. gondii) increased the risk of car accidents. In this study, our objective was to investigate the possible associations among latent T. gondii, Cytomegalovirus (CMV), and Herpes Simplex Virus (HSV) infections with the risk of motorcycle accidents in Jahrom (Fars Province), which is a county with a high rate of motorcycle accidents in Iran. METHODS: In the setting of a case-control study; 176 motorcyclist men, including 88 survivors of motorcycle accidents and 88 motorcyclist without accidents, were considered as case and control groups, respectively. Rates of latent infections with T. gondii, CMV, and HSV were assessed by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Eleven of 88 (12.5%) in the case group and 22 of 88 (25.0%) in controls were positive for anti-T. gondii IgG antibodies, this difference was statistically significant (OR = 0.42; CI: 0.19-0.95, p = 0.03). The general seroprevalence of CMV (94.3% in the case group vs. 87.5% in the control group, OR = 2.37; CI: 0.78-7.13, p = 0.12) and HSV (63.6% in the case group vs. 62.5% in the control group, OR = 1.05; CI: 0.57-1.94, p = 0.87) were not significantly different between the case and control groups. CONCLUSIONS: Although latent toxoplasmosis has been associated with traffic accidents in recent reports, we found a negative association between latent toxoplasmosis and motorcycle accidents among survivors of these accidents. As such, latent CMV and HSV infections did not differ significantly between the cases compared to the control groups.
Assuntos
Acidentes de Trânsito , Infecções por Citomegalovirus , Herpes Simples , Motocicletas , Toxoplasmose , Humanos , Irã (Geográfico)/epidemiologia , Acidentes de Trânsito/estatística & dados numéricos , Estudos de Casos e Controles , Masculino , Toxoplasmose/epidemiologia , Adulto , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/complicações , Herpes Simples/epidemiologia , Herpes Simples/complicações , Citomegalovirus , Adulto Jovem , Pessoa de Meia-Idade , Simplexvirus/patogenicidade , Toxoplasma , Fatores de Risco , Infecção Latente/epidemiologia , AdolescenteRESUMO
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.
Assuntos
Encéfalo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Nebivolol , Carga Parasitária , Toxoplasmose Animal , Animais , Nebivolol/farmacologia , Nebivolol/uso terapêutico , Camundongos , Toxoplasmose Animal/tratamento farmacológico , Toxoplasmose Animal/parasitologia , Encéfalo/parasitologia , Encéfalo/patologia , Encéfalo/efeitos dos fármacos , Feminino , Neurônios/efeitos dos fármacos , Neurônios/parasitologia , Etanolaminas/farmacologia , Etanolaminas/uso terapêutico , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Antiprotozoários/administração & dosagem , Benzopiranos/farmacologia , Benzopiranos/uso terapêutico , Resultado do Tratamento , Óxido Nítrico/metabolismo , Toxoplasma/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismoRESUMO
Toxoplasma gondii (T. gondii) is widely spread around the world, which can cause serious harm to immunosuppressed patients. Currently, the commercial test kits are poor at assessing T. gondii infection and vaccine effectiveness, making an urgent need to exploit effective enzyme-linked immunosorbent assay with great performance to compensate for this deficiency. Here, the TgIMP1 recombinant protein was expressed in E. coli BL(21) cells. The TgIMP1 was purified with affinity chromatography and the reactivity was retained with anti-TgIMP1 antibodies. The TgIMP1 was then used to develop an indirect ELISA (IMP1-iELISA) and the reaction conditions of IMP1-iELISA were optimized. As a result, the cut-off value was determined to be 0.2833 by analyzing the OD450nm values of forty T. gondii-negative sera. The coefficient of variation of 6 T. gondii-positive sera within and between runs were both less than 10%. The IMP1-iELISA was non-cross-reactive with the sera of cytomegalovirus, herpes virus, rubella virus, Cryptosporidium spp., Theileria spp., Neospora spp. and Plasmodium spp.. Furthermore, the sensitivity and specificity of IMP1-iELISA were 98.9% and 96.7%, respectively, based on testing 150 serum samples. The results suggest that this IMP1-iELISA is specific, sensitive, repeatable and can be applied to the detection of T. gondii infections in the medical and health industries.
Assuntos
Anticorpos Antiprotozoários , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Proteínas Recombinantes , Sensibilidade e Especificidade , Toxoplasma , Toxoplasmose , Toxoplasma/imunologia , Toxoplasma/genética , Ensaio de Imunoadsorção Enzimática/métodos , Anticorpos Antiprotozoários/sangue , Humanos , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/genética , Toxoplasmose/diagnóstico , Toxoplasmose/imunologia , Toxoplasmose/parasitologia , Imunoglobulina G/sangue , Animais , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/genética , Antígenos de Protozoários/imunologia , Antígenos de Protozoários/genética , Escherichia coli/genéticaRESUMO
BACKGROUND: Toxoplasmosis is potentially avoidable, treatable, and curable by simple and direct preventive measures. Knowledge, attitudes, and practices (KAP) assessments concerning gestational toxoplasmosis were evaluated in a cohort of pregnant women from Armenia-Quindío (Colombia, South America). METHODS: This cross-sectional descriptive KAP-type study was performed with informed consent between October 2021 and March 2022. The intervention involved a ten-minute talk administered by prenatal clinic nurses to pregnant women. This took place in the public health clinic RedSalud and the private clinic Happy Maternity with a post-KAP survey after pregnancy. RESULTS: The findings of the initial KAP survey revealed that approximately 42.8 % of the 250 mothers surveyed had IgG anti-T. gondii antibodies present. A strong correlation was observed between a lower frequency of antibodies and a higher level of education. Following an educational intervention, 73 seronegative women demonstrated a significant improvement in their knowledge and behavior. Among the 111 mothers who received the intervention, 42 (37 %) were followed until delivery. Unfortunately, their level of compliance with prenatal serological follow-up was lower compared to previous historical records of cohort of mothers in the same health center during pre-pandemic periods. No seroconversion occurred, although the small number of cases makes the outcome inconclusive with respect to statistical significance. CONCLUSIONS: Education plays a crucial role in imparting valuable knowledge and fostering effective practices. It holds significant potential to prevent toxoplasmosis in pregnant seronegative mothers. Prenatal check-ups have proven to be a critical determinant in leveraging the benefits of education for seronegative mothers. Reporting and observed behaviors differed, identifying areas for improvement.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Toxoplasmose , Humanos , Feminino , Gravidez , Estudos Transversais , Adulto , Toxoplasmose/prevenção & controle , Adulto Jovem , Colômbia , Anticorpos Antiprotozoários/sangue , Toxoplasma/imunologia , Inquéritos e Questionários , Complicações Parasitárias na Gravidez/prevenção & controle , Gestantes/psicologia , Cuidado Pré-Natal , Imunoglobulina G/sangue , AdolescenteRESUMO
Lung adenocarcinoma is the most prevalent subtype of lung cancer, which is the leading cause of cancer-related mortality worldwide. Toxoplasma gondii (T.gondii) Rhoptry protein 16 (ROP16) has been shown to quickly enter the nucleus, and through activate host cell signaling pathways by phosphorylation STAT3 and may affect the survival of tumor cells. This study constructed recombinant lentiviral expression vector of T. gondii ROP16 I/II/III and stably transfected them into A549 cells, and the effects of ROP16 on cell proliferation, cell cycle, apoptosis, invasion, and migration of A549 cells were explored by utilizing CCK-8, flow cytometry, qPCR, Western blotting, TUNEL, Transwell assay, and cell scratch assay, and these effects were confirmed in the primary human lung adenocarcinoma cells from postoperative cancer tissues of patients. The type I and III ROP16 activate STAT3 and inhibited A549 cell proliferation, regulated the expression of p21, CDK6, CyclinD1, and induced cell cycle arrest at the G1 phase. ROP16 also regulated the Bax, Bcl-2, p53, cleaved-Caspase3, and Caspase9, inducing cell apoptosis, and reduced the invasion and migration of A549 cells, while type II ROP16 protein had no such effect. Furthermore, in the regulation of ROP16 on primary lung adenocarcinoma cells, type I and III ROP16 showed the same anticancer potential. These findings confirmed the anti-lung adenocarcinoma effect of type I and III ROP16, offering fresh perspectives on the possible application of ROP16 as a target with adjuvant therapy for lung adenocarcinoma and propelling the field of precision therapy research toward parasite treatment of tumors.
Assuntos
Adenocarcinoma de Pulmão , Apoptose , Proliferação de Células , Neoplasias Pulmonares , Proteínas de Protozoários , Toxoplasma , Humanos , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/tratamento farmacológico , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Toxoplasma/genética , Toxoplasma/metabolismo , Movimento Celular , Células A549 , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Proteínas Tirosina QuinasesRESUMO
BACKGROUND: Chronic infection with the neurotropic parasite Toxoplasma gondii (T. gondii) can cause anxiety and gut microbiota dysbiosis in hosts. However, the potential role of gut microbiota in anxiety induced by the parasite remains unclear. METHODS: C57BL/6J mice were infected with 10 cysts of T. gondii. Antibiotic depletion of gut microbiota and fecal microbiota transplantation experiments were utilized to investigate the causal relationship between gut microbiota and anxiety. Anxiety-like behaviors were examined by the elevated plus maze test and the open field test; blood, feces, colon and amygdala were collected to evaluate the profiles of serum endotoxin (Lipopolysaccharide, LPS) and serotonin (5-hydroxytryptamine, 5-HT), gut microbiota composition, metabolomics, global transcriptome and neuroinflammation in the amygdala. Furthermore, the effects of Diethyl butylmalonate (DBM, an inhibitor of mitochondrial succinate transporter, which causes the accumulation of endogenous succinate) on the disorders of the gut-brain axis were evaluated. RESULTS: Here, we found that T. gondii chronic infection induced anxiety-like behaviors and disturbed the composition of the gut microbiota in mice. In the amygdala, T. gondii infection triggered the microglial activation and neuroinflammation. In the colon, T. gondii infection caused the intestinal dyshomeostasis including elevated colonic inflammation, enhanced bacterial endotoxin translocation to blood and compromised intestinal barrier. In the serum, T. gondii infection increased the LPS levels and decreased the 5-HT levels. Interestingly, antibiotics ablation of gut microbiota alleviated the anxiety-like behaviors induced by T. gondii infection. More importantly, transplantation of the fecal microbiota from T. gondii-infected mice resulted in anxiety and the transcriptomic alteration in the amygdala of the antibiotic-pretreated mice. Notably, the decreased abundance of succinate-producing bacteria and the decreased production of succinate were observed in the feces of the T. gondii-infected mice. Moreover, DBM administration ameliorated the anxiety and gut barrier impairment induced by T. gondii infection. CONCLUSIONS: The present study uncovers a novel role of gut microbiota in mediating the anxiety-like behaviors induced by chronic T. gondii infection. Moreover, we show that DBM supplementation has a beneficial effect on anxiety. Overall, these findings provide new insights into the treatment of T. gondii-related mental disorders.
Assuntos
Ansiedade , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Toxoplasma , Animais , Camundongos , Ansiedade/microbiologia , Toxoplasma/fisiologia , Masculino , Transplante de Microbiota Fecal , Disbiose/microbiologia , Tonsila do Cerebelo/metabolismo , Comportamento Animal , Toxoplasmose/fisiopatologia , Toxoplasmose/psicologia , Toxoplasmose/parasitologia , Toxoplasmose/microbiologia , Doença Crônica , Eixo Encéfalo-Intestino/fisiologia , Modelos Animais de Doenças , Colo/microbiologia , Colo/parasitologiaRESUMO
Toxoplasma gondii is a widely distributed apicomplexan parasite causing toxoplasmosis, a critical health issue for immunocompromised individuals and for congenitally infected foetuses. Current treatment options are limited in number and associated with severe side effects. Thus, novel anti-toxoplasma agents need to be identified and developed. 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) is considered the rate-limiting enzyme in the non-mevalonate pathway for the biosynthesis of the isoprenoid precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate in the parasite, and has been previously investigated for its key role as a novel drug target in some species, encompassing Plasmodia, Mycobacteria and Escherichia coli. In this study, we present the first crystal structure of T. gondii DXR (TgDXR) in a tertiary complex with the inhibitor fosmidomycin and the cofactor NADPH in dimeric conformation at 2.5â Å resolution revealing the inhibitor binding mode. In addition, we biologically characterize reverse α-phenyl-ß-thia and ß-oxa fosmidomycin analogues and show that some derivatives are strong inhibitors of TgDXR which also, in contrast with fosmidomycin, inhibit the growth of T. gondii in vitro. Here, ((3,4-dichlorophenyl)((2-(hydroxy(methyl)amino)-2-oxoethyl)thio)methyl)phosphonic acid was identified as the most potent anti T. gondii compound. These findings will enable the future design and development of more potent anti-toxoplasma DXR inhibitors.
Assuntos
Aldose-Cetose Isomerases , Fosfomicina , Complexos Multienzimáticos , Toxoplasma , Toxoplasma/enzimologia , Toxoplasma/efeitos dos fármacos , Aldose-Cetose Isomerases/antagonistas & inibidores , Aldose-Cetose Isomerases/química , Aldose-Cetose Isomerases/metabolismo , Aldose-Cetose Isomerases/genética , Fosfomicina/farmacologia , Fosfomicina/análogos & derivados , Fosfomicina/química , Cristalografia por Raios X , Complexos Multienzimáticos/antagonistas & inibidores , Complexos Multienzimáticos/química , Complexos Multienzimáticos/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , NADP/metabolismo , NADP/química , Humanos , Modelos Moleculares , Oxirredutases/antagonistas & inibidores , Oxirredutases/química , Oxirredutases/metabolismoRESUMO
Apicomplexan parasites balance proliferation, persistence, and spread in their metazoan hosts. AGC kinases, such as PKG, PKA, and the PDK1 ortholog SPARK, integrate environmental signals to toggle parasites between replicative and motile life stages. Recent studies have cataloged pathways downstream of apicomplexan PKG and PKA; however, less is known about the global integration of AGC kinase signaling cascades. Here, conditional genetics coupled to unbiased proteomics demonstrates that SPARK complexes with an elongin-like protein to regulate the stability of PKA and PKG in the model apicomplexan Toxoplasma gondii. Defects attributed to SPARK depletion develop after PKG and PKA are down-regulated. Parasites lacking SPARK differentiate into the chronic form of infection, which may arise from reduced activity of a coccidian-specific PKA ortholog. This work delineates the signaling topology of AGC kinases that together control transitions within the asexual cycle of this important family of parasites.
Assuntos
Proteínas de Protozoários , Toxoplasma , Toxoplasma/genética , Toxoplasma/enzimologia , Toxoplasma/fisiologia , Toxoplasma/crescimento & desenvolvimento , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Animais , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/genética , Transdução de Sinais , Reprodução AssexuadaRESUMO
Toxoplasma gondii and Toxocara spp. zoonotic infections may cause severe systemic and ocular illness in infected individuals. Cats play a significant role in environmental contamination and the transmission of parasites. The goal of the present study was to investigate the prevalence of Toxoplasma gondii (T. gondii) and Toxocara spp. infection among stray cats at Ahvaz Jundishapur University of Medical Sciences campus. The current descriptive study began with the collection of 170 fresh cat faecal samples from various sites in the Ahvaz Jundishapur University of Medical Sciences area. Sheather's sugar flotation method was applied to all specimens, and parasites were identified and examined microscopically. Next, a nested-PCR assay, sequencing, and real-time PCR with high-resolution melting curve (HRM) analysis were performed. In this study, out of 170 cat faecal samples microscopically evaluated, 8 (4.70%) and 37 (21.76%) were infected with T. gondii oocysts and Toxocara eggs, respectively. Using nested PCR, 8 out of 170 samples (4.70%) were found to be infected with T. gondii. HRM analysis showed that all isolates could be classified into three genetic lineages. Considerable prevalence, exceeding 50% for Toxocara and surpassing 25% for Toxoplasma in certain instances, along with genetic diversity, was observed in the present study. Hence, it is suggested that all individuals, including kindergarten children, students, employees, workers, and pregnant women who are in contact with their surroundings, take the necessary precautions.
Assuntos
Doenças do Gato , Fezes , Toxocara , Toxoplasma , Animais , Gatos , Toxoplasma/isolamento & purificação , Toxoplasma/genética , Toxocara/isolamento & purificação , Toxocara/genética , Fezes/parasitologia , Doenças do Gato/parasitologia , Doenças do Gato/epidemiologia , Universidades , Toxocaríase/epidemiologia , Toxocaríase/parasitologia , Toxoplasmose Animal/epidemiologia , Toxoplasmose Animal/parasitologia , Toxoplasmose/epidemiologia , Toxoplasmose/parasitologiaRESUMO
BACKGROUND: Toxoplasma gondii (T. gondii) is a ubiquitous protozoan parasite on our planet that causes toxoplasmosis. This study evaluated the seroprevalence and related risk factors for T. gondii infection in a population referred to healthcare centers in Meshkin-Shahr, Northwest Iran. METHODS: A total of 400 blood samples were randomly collected from the general population and assessed using the anti-Toxoplasma antibodies, Immunoglobulin G and M (IgG and IgM) Enzyme-linked immunosorbent assay (ELISA) Kits in two steps before and during the coronavirus disease 2019 (COVID-19) pandemic, 2019-2020. The results were analyzed through logistic regression via SPSS 26 software. RESULTS: Before the COVID-19 pandemic, anti-toxoplasma antibodies were detected in 39% of individuals (IgG: 38%, IgM: 0.5%, and IgG-IgM: 0.5%). Among the eleven risk factors evaluated, contact with soil and people awareness were significantly associated with T. gondii infection (p < 0.05). However, factors such as females, 20-39 age groups, junior high schools, housewives, rural areas, raw meat or vegetable consumption, vegetable or fruits washed by water, not detergent, and cat owners did not show a significant relationship with seropositivity (p > 0.05). After the outbreak of the COVID-19 pandemic, the overall seroprevalence for anti-T. gondii antibody increased to 49.7% (IgG: 47.7%, IgM: 0.5%, and IgG and IgM: 1.5%). Among these patients, 26% were positive for COVID-19. Additionally, before the COVID-19 pandemic, 40 samples were negative for anti-T. gondii antibodies but later became positive. The crude and adjusted models suggested that toxoplasmosis may be a possible risk factor for increased susceptibility to COVID-19, with an odds ratio (OR) of 1.28 (95% confidence interval (CI), 0.82-1.99; P < 0.05). Conversely, a non-significant protective effect against latent toxoplasmosis was observed in COVID-19-positive individuals (OR = 0.99; 95% CI, 0.51-1.92; P > 0.05), and COVID-19 positivity did not increase the levels of anti-T. gondii IgG antibodies. CONCLUSIONS: The general population in this region had a moderate seroprevalence of T. gondii. The increased number of COVID-19-positive patients with latent toxoplasmosis highlights the need to pay attention to the early diagnosis and proper treatment of toxoplasmosis in these patients and implement preventive programs in these areas for future possible viral infections.
Assuntos
Anticorpos Antiprotozoários , COVID-19 , Imunoglobulina G , Imunoglobulina M , SARS-CoV-2 , Toxoplasma , Toxoplasmose , Humanos , COVID-19/epidemiologia , COVID-19/imunologia , Irã (Geográfico)/epidemiologia , Estudos Soroepidemiológicos , Toxoplasmose/epidemiologia , Feminino , Masculino , Adulto , Toxoplasma/imunologia , Pessoa de Meia-Idade , Adulto Jovem , Imunoglobulina G/sangue , Fatores de Risco , Imunoglobulina M/sangue , Anticorpos Antiprotozoários/sangue , SARS-CoV-2/imunologia , Adolescente , Idoso , Criança , Prevalência , Ensaio de Imunoadsorção Enzimática , Pré-Escolar , PandemiasRESUMO
BACKGROUND: Toxoplasma gondii is a zoonotic protozoan parasite with a heteroxenus life cycle that involves felids as the definitive hosts and any warm-blooded animal, including humans, as intermediate hosts. Cats are key players in parasite transmission as they are capable of shedding high numbers of oocysts in their feces that contaminate the environment. METHODS: The study was performed on 31 domestic cats (31.23 ± 27.18 months old) originating from rural and urban areas (5.17:1) in the center and north-west Romania. Feces (n = 31), blood (n = 28), and heart samples (n = 27) were collected. Fecal samples were analyzed by flotation technique, and PCR (529 bp repetitive element). Fecal samples with T. gondii oocysts were bioassayed in mice. Serum samples were analyzed by modified agglutination test and ImmunoComb for the detection of specific anti-T. gondii IgG antibodies. Heart samples were bioassayed in mice, and analyzed by PCR. Toxoplasma gondii positive samples were genotyped by nPCR-RFLP targeting eleven genetic loci (SAG1, SAG2, alt-SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico). RESULTS: Toxoplasma gondii oocysts were found in 2 out of 31 fecal samples collected from a 3-months old stray kitten, and a 4-years old female. In total, 17 out of 27 sera were positive for T. gondii IgG antibodies. The antibody titers in MAT ranged from 1:6 to 1:384. Toxoplasma gondii DNA was detected in 7 out of 27 heart samples, and four of them were positive also by bioassay. Six T. gondii DNA samples from bioassayed mice could be assigned to ToxoDB PCR-RFLP genotype #1 or #3 (Type II) and one T. gondii DNA from heart digest to genotype #2 (Type III). Both of these genotypes are common in Europe. CONCLUSIONS: Our results revealed that the infection with T. gondii is still high in cats from Romania. The oocysts shedded by these cats represent an important source of infection for intermediate hosts, including humans. Further studies on a wider range of cases are necessary for a more exhaustive definition of the T. gondii genotypes circulating in Romania.
Assuntos
Doenças do Gato , Fezes , Genótipo , Toxoplasma , Toxoplasmose Animal , Animais , Gatos , Toxoplasma/genética , Toxoplasma/isolamento & purificação , Romênia/epidemiologia , Toxoplasmose Animal/epidemiologia , Toxoplasmose Animal/parasitologia , Doenças do Gato/parasitologia , Doenças do Gato/epidemiologia , Fezes/parasitologia , Camundongos , Feminino , Masculino , Anticorpos Antiprotozoários/sangueRESUMO
Rhoptries are specialized secretory organelles conserved across the Apicomplexa phylum, essential for host cell invasion and critical for subverting of host cellular and immune functions. They contain proteins and membranous materials injected directly into the host cells, participating in parasitophorous vacuole formation. Toxoplasma gondii tachyzoites harbor 8 to 12 rhoptries, 2 of which are docked to an apical vesicle (AV), a central element associated with a rhoptry secretory apparatus prior to injection into the host cell. This parasite is also equipped with 5 to 6 microtubule-associated vesicles, presumably serving as AV replenishment for iterative rhoptry discharge. Here, we characterized a rhoptry protein, rhoptry discharge factor 3 (RDF3), crucial for rhoptry discharge and invasion. RDF3 enters the secretory pathway, localizing near the AV and associated with the rhoptry bulb. Upon invasion, RDF3 dynamically delocalizes, suggesting a critical role at the time of rhoptry discharge. Cryo-electron tomography analysis of RDF3-depleted parasites reveals irregularity in microtubule-associated vesicles morphology, presumably impacting on their preparedness to function as an AV. Our findings suggest that RDF3 is priming the microtubule-associated vesicles for rhoptry discharge by a mechanism distinct from the rhoptry secretory apparatus contribution.
Assuntos
Microtúbulos , Proteínas de Protozoários , Toxoplasma , Toxoplasma/metabolismo , Toxoplasma/patogenicidade , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Microtúbulos/metabolismo , Animais , Camundongos , Interações Hospedeiro-Parasita , Humanos , Organelas/metabolismo , Tomografia com Microscopia Eletrônica , Toxoplasmose/parasitologia , Toxoplasmose/metabolismoRESUMO
Side effects and low efficacy of current anti-toxoplasmosis therapeutics against encysted bradyzoites necessitate research into alternative safe therapeutic options. The safety, immunostimulatory, and antimicrobial properties of alginate nanoparticle formulation (Alg-NP) highlight its potential as an oral therapy against acute toxoplasmosis. In the current study, Alg-NP was formulated and characterized and then assessed for its anti-Toxoplasma effects using parasitological, ultrastructural, immunological, and histopathological studies. Treatment with Alg-NP significantly prolonged mice survival and reduced the parasite burden in both peritoneal fluid and tissue impression smears. In addition, it altered parasite viability and caused severe tachyzoite deformities as evidenced by ultrastructural studies. Alg-NP induced high levels of serum IFN-γ in infected mice with significant amelioration in histopathological changes in both hepatic and splenic tissue sections. In conclusion, Alg-NP could be considered a promising therapeutic agent against acute murine toxoplasmosis, and owing to its safety, it could potentially be enlisted for human use.
Assuntos
Alginatos , Modelos Animais de Doenças , Nanopartículas , Toxoplasma , Toxoplasmose Animal , Animais , Alginatos/química , Camundongos , Administração Oral , Toxoplasma/efeitos dos fármacos , Toxoplasmose Animal/tratamento farmacológico , Antiprotozoários/farmacologia , Antiprotozoários/administração & dosagem , Antiprotozoários/uso terapêutico , Ácido Glucurônico , Feminino , Ácidos Hexurônicos , Fígado/parasitologia , Fígado/patologia , Fígado/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/parasitologia , Líquido Ascítico/parasitologia , Carga Parasitária , Análise de Sobrevida , Interferon gama/sangue , Camundongos Endogâmicos BALB C , Resultado do TratamentoRESUMO
INTRODUCTION: Since the Syrian Civil War began in 2011, the official number of refugees under temporary protection in Turkiye is reported to be 3,522,036 in 2023. Most of the Syrians living outside the refugee camps have worse conditions in terms of access to healthcare centers and social opportunities, compared to those living in camps. The Sanliurfa province hosts the third highest number of Syrians (370,291) in Turkiye. There are no data about the seroprevalence of Toxoplasma gondii (T. gondii), rubella (rub), or cytomegalovirus (CMV) among Syrian refugees in Sanliurfa. We aimed to investigate the seroprevalence of T. gondii, rub, and CMV infections among female Syrian refugees of reproductive age (15-49 years) living in Sanliurfa province. METHODOLOGY: A cross-sectional study was conducted in different districts of Sanliurfa. A total of 460 households were selected using the probability sampling method. One married female Syrian refugee aged between 15 and 49 years, was chosen in each household, leading to a sample size of 410 female Syrian refugees. The seropositivity of T. gondii, CMV, and rub IgM and IgG in blood samples were analyzed using enzyme immunoassays (Abbott Architect, Illinois, USA). RESULTS: The seropositivity rates of T. gondii, CMV, and rubella IgM and IgG were 4.4% and 59.8%; 3.9%; and 99%; and 1.9%, and 99.5%, respectively. CONCLUSIONS: A screening program should be implemented for T. gondii, CMV, and rub infections for Syrian refugees. Seronegative women should be vaccinated against rub and educated about the transmission and preventive routes of toxoplasmosis and CMV infection.
Assuntos
Infecções por Citomegalovirus , Refugiados , Rubéola (Sarampo Alemão) , Toxoplasmose , Humanos , Feminino , Refugiados/estatística & dados numéricos , Adulto , Estudos Soroepidemiológicos , Toxoplasmose/epidemiologia , Adolescente , Adulto Jovem , Rubéola (Sarampo Alemão)/epidemiologia , Síria/epidemiologia , Síria/etnologia , Pessoa de Meia-Idade , Estudos Transversais , Infecções por Citomegalovirus/epidemiologia , Turquia/epidemiologia , Toxoplasma/imunologia , Anticorpos Antivirais/sangue , Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Imunoglobulina M/sangueRESUMO
Toxoplasma gondii( T. gondii or Tg), is an obligatory intracellular parasite with humans as its intermediate hosts. In recent years, significant correlations between T. gondii infection and schizophrenia have been reported, including the possible mediating mechanisms. Currently, mechanisms and hypotheses focus on central neurotransmitters, immunity, neuroinflammation, and epigenetics; however, the exact underlying mechanisms remain unclear. In this article, we review the studies related to T. gondii infection and schizophrenia, particularly the latest research progress. Research on dopamine (DA) and other neurotransmitters, the blood-brain barrier, inflammatory factors, disease heterogeneity, and other confounders is also discussed. In addition, we also summarized the results of some new epidemiological investigations.
Assuntos
Esquizofrenia , Toxoplasma , Toxoplasmose , Esquizofrenia/parasitologia , Esquizofrenia/etiologia , Humanos , Toxoplasmose/complicações , Toxoplasmose/epidemiologia , Toxoplasmose/parasitologia , AnimaisRESUMO
In total, 901 dairy cow sera and data were collected from 51 farms in Nakhon Pathom, Ratchaburi and Kanchanaburi provinces (Western Region of Thailand). Serum samples were processed via the multispecies ELISA method to detect IgG antibodies against Toxoplasma gondii infection. The results demonstrated that the calculated true prevalence was 1.48% (95% CI, 0.64-2.75%) for the individual-level and 29.41% (95% CI, 18.71-43%) for the farm-level. The univariate risk factor analysis showed that the number of total owned cats, the presence of stray cats, and the frequency of cleaning per day were significant factors (p < 0.2). These three factors were subjected to logistic regression analysis, and the results revealed that the frequency of cleaning farms per day was a potential risk factor for T. gondii-seropositive farms (OR = 2.745, 95% CI, 1.15-8.69, p = 0.02). The frequency of cleaning might increase the T. gondii oocyst distribution within the barn area, thus increasing the possibility of infection. Our findings show that T. gondii continues to circulate in the dairy cow population in the western part of Thailand. The presence of cats on farms was not found to be associated with T. gondii infection, but the high frequency of cleaning the floor was, and contributed to the potential risk of infection.
Title: Prévalence et facteurs de risque de l'infection à Toxoplasma gondii chez les bovins laitiers de la région occidentale de la Thaïlande. Abstract: Au total, 901 sérums de vaches laitières et des données ont été collectés dans 51 fermes des provinces de Nakhon Pathom, Ratchaburi et Kanchanaburi (région occidentale de la Thaïlande). Les échantillons de sérum ont été traités via la méthode ELISA multi-espèces pour détecter les anticorps IgG contre l'infection à Toxoplasma gondii. Les résultats ont démontré que la prévalence réelle calculée était de 1,48 % (IC à 95 %, 0,642,75 %) au niveau individuel et de 29,41 % (IC à 95 %, 18,7143 %) au niveau des exploitations. L'analyse factorielle a montré que le nombre total de chats possédés, la présence de chats errants et la fréquence quotidienne de nettoyage étaient des facteurs significatifs (p < 0,2). Ces trois facteurs ont été soumis à une analyse de régression logistique et les résultats ont révélé que la fréquence quotidienne de nettoyage des exploitations était un facteur de risque potentiel pour les exploitations séropositives à T. gondii (OR = 2,745, IC à 95 % = 1,158,69, p = 0,02). La fréquence du nettoyage pourrait favoriser la répartition des oocystes de T. gondii dans les étables, augmentant ainsi le risque d'infection. Nos résultats indiquent que T. gondii continue de circuler dans la population de vaches laitières de l'ouest de la Thaïlande. La présence de chats dans les fermes n'a pas été associée à l'infection à T. gondii, mais la fréquence élevée du nettoyage du sol l'était et contribuait au risque potentiel d'infection.
Assuntos
Anticorpos Antiprotozoários , Doenças dos Bovinos , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G , Toxoplasma , Toxoplasmose Animal , Animais , Bovinos , Tailândia/epidemiologia , Toxoplasmose Animal/epidemiologia , Fatores de Risco , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/parasitologia , Toxoplasma/imunologia , Anticorpos Antiprotozoários/sangue , Feminino , Gatos , Estudos Soroepidemiológicos , Imunoglobulina G/sangue , Ensaio de Imunoadsorção Enzimática/veterinária , Indústria de Laticínios , Prevalência , Doenças do Gato/epidemiologia , Doenças do Gato/parasitologia , Modelos LogísticosRESUMO
BACKGROUND: Habitat modification and land use changes impact ecological interactions and alter the relationships between humans and nature. Mexico has experienced significant landscape modifications at the local and regional scales, with negative effects on forest cover and biological biodiversity, especially in the Yucatan peninsula in southeastern Mexico. Given the close relationship between landscape modification and the transmission of zoonotic and vector-borne diseases, it is essential to develop criteria for identifying priority zoonoses in the south of the country. METHODOLOGY/PRINCIPAL FINDINGS: We reviewed 165 published studies on zoonotic and vector-borne diseases in the region (2015-2024). We identified the most frequent vectors, reservoirs, and hosts, the most prevalent infections, and the factors associated with transmission risk and the anthropogenic landscape modification in urban, rural, ecotone, and sylvatic habitats. The most relevant pathogens of zoonotic risk included Trypanosoma cruzi, arboviruses, Leishmania, Rickettsia, Leptospira, and Toxoplasma gondii. Trypanosoma cruzi was the vector-borne agent with the largest number of infected vertebrate species across habitats, while Leishmania and arboviruses were the ones that affected the greatest number of people. Dogs, cats, backyard animals, and their hematophagous ectoparasites are the most likely species maintaining the transmission cycles in human settlements, while rodents, opossums, bats, and other synanthropic animals facilitate connection and transmission cycles between forested habitats with human-modified landscapes. Pathogens displayed different prevalences between the landscapes, T. cruzi, arbovirus, and Leptospira infections were the most prevalent in urban and rural settlements, whereas Leishmania and Rickettsia had similar prevalence across habitats, likely due to the diversity and abundance of the infected vectors involved. The prevalence of T. gondii and Leptospira spp. may reflect poor hygiene conditions. Additionally, results suggest that prevalence of zoonotic and vector-borne diseases is higher in deforested areas and agricultural aggregates, and in sites with precarious health and infrastructure services. CONCLUSIONS: Some hosts, vectors, and transmission trends of zoonotic and vector-borne diseases in the YP are well known but others remain poorly recognized. It is imperative to reinforce practices aimed at increasing the knowledge, monitoring, prevention, and control of these diseases at the regional level. We also emphasize the need to perform studies on a larger spatio-temporal scale under the socio-ecosystem perspective, to better elucidate the interactions between pathogens, hosts, vectors, environment, and sociocultural and economic aspects in this and many other tropical regions.
Assuntos
Doenças Transmitidas por Vetores , Zoonoses , Animais , Humanos , Zoonoses/transmissão , Zoonoses/epidemiologia , Doenças Transmitidas por Vetores/transmissão , Doenças Transmitidas por Vetores/epidemiologia , Prevalência , México/epidemiologia , Ecossistema , Trypanosoma cruzi/isolamento & purificação , Vetores de Doenças , Reservatórios de Doenças/microbiologia , Leptospira/isolamento & purificação , Leptospira/genética , Leptospira/classificação , Doença de Chagas/transmissão , Doença de Chagas/epidemiologia , Toxoplasma , Arbovírus/fisiologia , Leishmania/isolamento & purificação , Leishmaniose/transmissão , Leishmaniose/epidemiologiaRESUMO
In the decades since the discovery, Type I interferon (IFN-I) has been intensively studied for their antiviral activity. However, increasing evidences suggest that it may also play an important role in the infection of Toxoplasma gondii, a model organism for intracellular parasites. Recent studies demonstrated that the induction of IFN-I by the parasite depends on cell type, strain genotype, and mouse strain. IFN-I can inhibit the proliferation of T. gondii, but few studies showed that it is beneficial to the growth of the parasite. Meanwhile, T. gondii also can secrete proteins that impact the pathway of IFN-I production and downstream induced interferon-stimulated genes (ISGs) regulation, thereby escaping immune destruction by the host. This article reviews the major findings and progress in the production, function, and regulation of IFN-I during T. gondii infection, to thoroughly understand the innate immune mechanism of T. gondii infection, which provides a new target for subsequent intervention and treatment.