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Rodents are considered as reservoir hosts for various pathogens (such as Toxoplasma gondii) and have been revealed to play an important role in the spread of several infectious diseases to humans and other animals. The aim of this investigation was to survey the prevalence of anti-T. gondii IgG antibodies in wild rats in Northern Iran. One hundred rats were caught using rat traps set in different areas in Northern Iran (September 2017). The thoracic cavity of each rat was opened, and then the blood sample was collected from the heart. IgG anti-Toxoplasma gondii antibodies were detected using the modified agglutination test (MAT) with a cutoff value equal to 1 : 40. Overall, 56% of rats were infected by T. gondii. Considering the sex of rats, 45% of male and 55% of female rats were seropositive, but the differences were not statistically significant. There was a significant difference between seropositivity and habitat types and age of rodents. Our findings have public health implications and confirm the high seroprevalence of T. gondii infection in northern Iran. The study established that wild rats represent an important and persistent wildlife intermediate host reservoir for T. gondii. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is an intracellular parasite infecting almost all warm-blooded animals. Many studies on vaccination have been performed previously, and micronemal proteins (MICs) have crucial importance in this regard. The current review aims to reveal the efficiency of MICs as target antigen, adjuvants, animal models (species/strain), T. gondii strains for challenge infection, and routes of vaccine to prevent Toxoplasma infection. A comprehensive literature search was performed on April 18, 2018, in several known databases. Studies were included when evaluating vaccines based on MIC against T. gondii compared to that of a control group. Two independent researchers done the search process, study choice, and data extraction. A total of 28 articles published were selected for further analysis. Among them, 57.03% of the studies focused on MIC3 and its epitopes. SAG1 was further used in cocktail vaccines compared to other antigens. GM-CSF and Freund's complete were the predominant adjuvants used. BALB/c mice have been introduced as a proper model for lethal challenge. Virulent T. gondii (RH) was utilized more than other strains for challenge. Among MICs, the results of vaccination with MIC1-4, MIC6, and PLP1 demonstrated significantly strong humoral and cellular immunity, increased survival time, and reduced cyst burden in the mice. This review summarizes the latest results on MIC-based vaccines and presents that the most effective vaccination procedure is the administration of the cocktail vaccines. Our survey can serve as a basis for further studies to develop more efficient novel vaccines against T. gondii for animals and humans. [ABSTRACT FROM AUTHOR]

Abstract At present, there is not any available accepted vaccine for prevention of Toxoplasma gondii (T. gondii) in human and animals. We conducted literature search through English (Google Scholar, PubMed, Science Direct, Scopus, EBSCO, ISI Web of Science) scientific paper databases to find the best vaccine candidates against toxoplasmosis among T. gondii antigens. Articles with information on infective stage, pathogenicity, immunogenicity and characterization of antigens were selected. We considered that the ideal and significant vaccines should include different antigens and been expressed in all infective stages of the parasite with a high pathogenicity and immunogenicity. Evaluation within this systematic review indicates that MIC 3, 4, 13, ROP 2, RON 5, GRA 1, 6, 8, 14 are expressed in all three infective stages and have pathogenicity and immunogenicity. MIC 5, ROM 4, GRA 2, 4, 15, ROP 5, 16, 17, 38, RON 4, MIC 1, GRA 10, 12, 16, SAG 3 are expressed in only tachyzoites and bradyzoites stages of T. gondii with pathogenicity/immunogenicity. Some antigens appeared to be expressed in a single stage (tachyzoites) but have high pathogenicity and induce immune response. They include enolase2 (ENO2), SAG 1, SAG5D, HSP 70, ROM 1, ROM 5, AMA 1, ROP 18, RON2 and GRA 24. In conclusion, current vaccination against T. gondii infection is not satisfactory, and with the increasing number of high-risk individuals, the development of an effective and safe specific vaccine is greatly valuable for toxoplasmosis prevention. This systematic review reveals prepare candidates for immunization studies. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is a ubiquitous and infectious parasite that multiplies in any nucleated cell of warm-blooded animals and humans worldwide. This parasite has intricate mechanisms to reciprocate host-cell apoptosis to exist in the host cell. So far, the details of the parasite interactions with host cells are not well known. MicroRNAs (miRNAs) are one of the small noncoding RNAs that are now considered as a key mechanism of gene regulation. They are important in physiological and pathological processes such as apoptosis. In this study a Real Time quantitative PCR technique was used to evaluate the levels of miR-20a of miRNAs family in human macrophage during T. gondii infection to determine the role of miR-20a in apoptosis. Then, the inhibition of miR-20a function through interaction with transfection of Locked Nucleic Acid (LNA) antisense oligomer was studied. Furthermore, it was examined whether miR-20a is involved in apoptosis of human macrophages with T. gondii infected cells using flow cytometry. We found that miR-20a expression is up-regulated in human macrophages following T. gondii infection. After LNA anti miR-20a oligomer transfection, miR-20a inhibition was evaluated by quantitative reverse transcriptase polymerase chain reaction. Flow cytometry results showed that LNA anti-miR20a oligomer increased apoptosis. In agreement with this result, we found that specific LNA oligonucleotides prevent the functional activity of miR-20a and promotion of human macrophages apoptosis with T. gondii infection by inhibition of this miRNAs gene. Also, the results support the concept that LNA oligomer antisense may be used as a therapeutic implement for blocking detrimental miRNAs overexpressed in infections. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is a widespread obligatory intracellular parasite infecting humans and most of all other warm-blooded animals. Currently there is no any accepted vaccine for prevention of T. gondii infection. Many studies are focused on using of various excretory secretory antigens (ESA); and among them dense granule antigens (GRAs) being involved in parasite survival, virulence and replication processes, are considered as one of the predominant vaccine candidates. The aim of this systematic review is to prepare more comprehensive understanding of these antigens to reduce T. gondii infection in humans and animals. English databases, including PubMed, Science Direct, Google Scholar, Scopus, ISI Web of Science were systematically searched and papers evaluating GRA antigens published until June 2019 were selected. Evaluation of selected publications revealed that GRA4 and GRA7 substantially increased survival time of the experimental animals. It is noticeable that the maximum reduction in cyst burden was observed in BALB/c mice vaccinated with combination of GRA3, GRA7 and M2AP antigens (93.5%). GRA6 and GRA10 have shown high immunogenicity and GRA1 and 2 are important for virulence and induction of immune responses. This review will be helpful for researchers to conduct more effective studies in the field of immunization against T. gondii infection. [ABSTRACT FROM AUTHOR]

As current toxoplasmosis chemotherapies have many side effects along with toxicity on patients, we examined the anti- Toxoplasma effect of a biologically important natural antibiotic, kojic acid, in vitro and in vivo. Vero cells were incubated with different concentrations of kojic acid or pyrimethamine (positive control), and the cellular viability was determined. Next, Vero cells were infected with T. gondii (RH strain) and treated with drugs. Then, we calculated the infection index, T. gondii intracellular proliferation and the number and measure of plaque. Moreover, the effect of kojic acid on survival times, serum levels of IFN-γ and TNF-α and histopathological changes in the liver and spleen of Balb/c mice infected with T. gondii were determined. Kojic acid reduced the infection index, intracellular proliferation, the number and measure of plaque in vitro when compared to untreated infected cells. Kojic acid (100 mg/kg/day) also showed a better survival rate than infected untreated control mice (P < 0.05). IFN-γ and TNF-α secretions were significantly increased by kojic acid treatment in comparison to untreated groups (P < 0.05). In addition, its inhibitory effects on inflammatory alterations, apoptosis, and necrosis have been shown in sections of liver and spleen. We conclude that kojic acid exhibit potent anti- Toxoplasma activity with direct and indirect effects on the parasite, although further studies are needed before consideration of clinical trials. Image 1 • Kojic acid is firstly proved to has anti- T. gondii activity in vitro and in vivo. • Kojic acid may be a novel drug candidate for treating T. gondii infection. [ABSTRACT FROM AUTHOR]

Background and purpose: Toxoplasma gondii is a protozoon with worldwide distribution. In spite of increasing information about its biology, treatment of toxoplasmosis is restricted to a few drugs and unfortunately using of each of drugs is associated with significant side effects in patients. It seems that investigation on alternative drugs is necessary. Materials and methods: In case group, concentrations of 1, 5 and 10 μg/ml of ketotifen were prepared and added to RPMI (Roswell Park Memorial Institute) medium containing peritoneal macrophages. After 60 minutes, incubation and adding Toxoplasma gondii tachyzoites to medium, the inhibitory rate of different concentrations of ketotifen on entrance of Toxoplasma tachyzoites into macrophages in 30 and 60 minutes were evaluated. Control group did not receive ketotifen. Results: The best efficacy of ketotifen in inhibition of entrance of Toxoplasma tachyzoites into macrophages was observed in 10 μg/ml and in 60 minutes (72.90 ± 1.70) (P < 0.05). Conclusion: The findings of this research show that ketotifen is a suitable drug for inhibiting the entrance of Toxoplasma gondii tachyzoites into nucleated cells in vitro. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is an obligate intracellular protozoan parasite that can cause serious public health problems. The development of a safe and effective vaccine against T. gondii is urgently needed to prevent and control the spread of toxoplasmosis. The aim of this study was to evaluate the immune responses induced by a pcGRA14 + pcROP13 vaccine cocktail in BALB/c mice. All groups were immunized intramuscularly three times at two-week intervals. The production of anti- Toxoplasma gondii lysate antigen (TLA) antibodies, lymphocyte proliferation, serum levels of IFN-γ and IL-4 cytokines and the survival time were monitored after vaccination and challenged with the virulent RH strain of T. gondii. The results showed that immunization with the pcGRA14 + pcROP13 DNA vaccine significantly increased the production of specific IgG antibodies and cytokines against toxoplasmosis. Interestingly, high levels of IgG2a and IFN-γ were found in animals vaccinated with DNA vaccine cocktail. Furthermore, immunized mice challenged with the RH strain of T. gondii showed prolonged survival time when compared to control groups (P < 0.05). The present study demonstrates the potential of a DNA cocktail vaccine expressing pcGRA14 and pcROP13 in developing specific immune responses and providing effective protection against T. gondii infection. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii , the etiological agent of toxoplasmosis, can cause serious public health problems. Although Toxoplasma gondii tends more to neurotropic and ocular organs, some existing evidence suggest that this disease might induce serious pathological effects on liver. Hence, this study aimed to evaluate the relationship between chronic liver diseases and toxoplasmosis. Meanwhile, it attempted to assess whether patients with toxoplasmosis are susceptible to chronic liver diseases. To achieve this aim, the published studies related to the subject were systematically searched in five major electronic databases between the January 1, 1950 and October 1, 2019. The meta-analysis was carried out using the StatsDirect statistical software and a p-value less than 0.05 was considered significant for any test. Out of 691 identified studies, 10 studies met our inclusion criteria and entered this systematic review. The pooled prevalence rates of Toxoplasma gondii in patients with liver diseases (35.97%; 95% CI: 28.38–43.93) were higher than those in the control group (18.24%; 95% CI: 13.85–23.09). The meta-analysis indicated that the common Odd Ratio by a random effect model was 2.7 (95% CI: 2.30–3.24), revealing a significant association between chronic liver diseases and anti- Toxoplasma IgG antibody. The results of this systematic review confirmed the positive connection between toxoplasmosis and chronic liver diseases. Nonetheless, more studies are needed to clarify the detailed association between these diseases. • The pooled prevalence rate of T. gondii in the patients with chronic liver diseases (CLDs) was 35.97%. • The positive relationship was demonstrated between toxoplasmosis and CLDs. • There was no significant difference between toxoplasmosis and types of liver diseases. • Incidence of toxoplasmosis in the patients with CLDs was associated with the country and year. [ABSTRACT FROM AUTHOR]

• Toxoplasma SAG1 as the main surface antigen of the tachyzoite, is involved in the process of the recognition, adhesion and invasion of host cells. • The result of study showed experimental SAG1 vaccines enhanced both humoral and cellular immune responses against toxoplasmosis. • The highest survival rates using live attenuated vectors were obtained after immunization with adenovirus-SAG1. • Combination of SAG1 with SAG2, MIC3, MIC4, ROP2, ROP4, GRA1, and GRA4 induced more effective protection against T. gondii infection. Toxoplasma gondii is an intracellular parasite that infects a broad range of animal species and humans. As the main surface antigen of the tachyzoite, SAG1 is involved in the process of recognition, adhesion and invasion of host cells. The aim of the current systematic review study is to clarify the latest status of studies in the literature regarding SAG1-associated recombinant proteins or SAG1-associated recombinant DNAs as potential vaccines against toxoplasmosis. Data were systematically collected from six databases including PubMed, Science Direct, Web of Science, Google Scholar, EBSCO and Scopus, up to 1st of January 2019. A total of 87 articles were eligible for inclusion criteria in the current systematic review. The most common antigens used for experimental cocktail vaccines together with SAG1 were ROP2 and SAG2. In addition, the most parasite strains used were RH and ME49. Freund's adjuvant and cholera toxin have been predominantly utilized. Furthermore, regarding the animal models, route and dose of vaccination, challenge methods, measurement of immune responses and cyst burden have been discussed in the text. Most of these experimental vaccines induce immune responses and have a high degree of protection against parasite infections, increase survival rates and duration and reduce cyst burdens. The data demonstrated that SAG1 antigen has a high potential for use as a vaccine and provided a promising approach for protecting humans and animals against toxoplasmosis. [ABSTRACT FROM AUTHOR]