Gondii Infection Research Articles

The Potential Role of Toxoplasma Gondii Infection in Breast Cancer Through Affecting Programmed Death-1 Genes

Background: This study aimed to evaluate the possible effects of Toxoplasma gondii infection on breast cancer through affecting the serum and expression gene level of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in breast cancer patients from Thi-qar province, Iraq. Methods: This case-control study was involved 150 patients suffering from breast cancer (BC) who were referring to general hospitals of Thi-Qar province between July to September 2023 and 150 healthy patients (non-BC). Enzyme-linked immunosorbent test (ELISA) kit was used to evaluate the anti-Toxoplasma IgG and the serum level of PD-1 and PDL-1. Furthermore, the expression level of PD-1 and PDL-1 was measured through Real-time PCR. Results: Among 150 breast cancer patients, 71 patients (47.3%) and 25 (16.6%) of healthy subjects exhibited seropositivity for anti-T. gondii IgG antibodies, resepectively. We found that the serum level and the gene expression level of PD-1 and PDL-1 were significantly higher among BC patients seropositive for T. gondii compared with BC patients who were seronegative for T. gondii antibodies (p<0.05). Conclusion: These results indicated that T. gondii may play a role in the occurrence and even progression of cancer probably by elevating levels of PD-1 and PDL-1 genes. However, further studies are required to confirm these findings.

Caspase-1 in Cx3cr1-expressing cells drives an IL-18-dependent T cell response that promotes parasite control during acute Toxoplasma gondii infection.

Inflammasome activation is a robust innate immune mechanism that promotes inflammatory responses through the release of alarmins and leaderless cytokines, including IL-1α, IL-1β, and IL-18. Various stimuli, including infectious agents and cellular stress, cause inflammasomes to assemble and activate caspase-1. Then, caspase-1 cleaves targets that lead to pore formation and leaderless cytokine activation and release. Toxoplasma gondii has been shown to promote inflammasome formation, but the cell types utilizing caspase-1 and the downstream effects on immunological outcomes during acute in vivo infection have not been explored. Here, using knockout mice, we examine the role of caspase-1 responses during acute T. gondii infection globally and in Cx3cr1-positive populations. We provide in vivo evidence that caspase-1 expression is critical for, IL-18 release, optimal interferon-γ (IFN-γ) production, monocyte and neutrophil recruitment to the site of infection, and parasite control. Specifically, we find that caspase-1 expression in Cx3cr1-positive cells drives IL-18 release, which potentiates CD4+ T cell IFN-γ production and parasite control. Notably, our Cx3cr1-Casp1 knockouts exhibited a selective T cell defect, mirroring the phenotype observed in Il18 knockouts. In further support of this finding, treatment of Cx3cr1-Casp1 knockout mice with recombinant IL-18 restored CD4+ T cell IFN-γ responses and parasite control. Additionally, we show that neutrophil recruitment is dependent on IL-1 receptor accessory protein (IL-1RAP) signaling but is dispensable for parasite control. Overall, these experiments highlight the multifaceted role of caspase-1 in multiple cell populations contributing to specific pathways that collectively contribute to caspase-1 dependent immunity to T. gondii.

The Intestinal Barrier Protective Effect of Indole Aldehyde Derivatives on Acute Toxoplasma gondii Infection

The Intestinal Barrier Protective Effect of Indole Aldehyde Derivatives on Acute Toxoplasma gondii Infection

Toxoplasma gondii infection induces the expression of the chemokine CXCL16 in macrophages to promote chemoattraction of CXCR6+ cells.

CXCL16 is a multifaceted chemokine expressed by macrophages and other immune cells in response to viral and bacterial pathogens. However, few studies have investigated its role in parasitic infections. The obligate intracellular parasite Toxoplasma gondii (T. gondii) is the causative agent of toxoplasmosis, an infection with potentially deleterious consequences in immunocompromised individuals and the developing fetus of acutely infected pregnant women. Chemokines are critical mediators of host defense and, as such, dysregulation of their expression is a subversion strategy often employed by the parasite to ensure its survival. Herein, we report that types I and II T. gondii strains upregulated the expression of both transmembrane and soluble forms of CXCL16 in infected bone marrow-derived macrophages (BMDM). Exposure to soluble T. gondii antigens (STAg) and to excreted-secreted proteins (TgESP) led to the induction of CXCL16. Cxcl16 mRNA abundance and CXCL16 protein levels increased in a time-dependent manner upon T. gondii infection. Importantly, conditioned medium (CM) collected from T. gondii-infected wild-type (WT) macrophage cultures promoted the migration of RAW264.7 cells expressing CXCR6, the cognate receptor of CXCL16, an effect that was significantly reduced by a neutralizing anti-CXCL16 antibody or use of CM from CXCL16 knockout (KO) macrophages. Lastly, T. gondii-driven CXCL16 expression appeared to modulate cytokine-induced (IL-4 + IL-13) alternative macrophage activation and M2 phenotypic marker expression. Further investigation is required to determine whether this chemokine contributes to the pathogenesis of toxoplasmosis and to elucidate the underlying molecular mechanisms.

Toxoplasma gondii ROP5 Enhances Type I IFN Responses by Promoting Ubiquitination of STING.

Toxoplasma gondii is a widely spread opportunistic pathogen that can infect nearly all warm-blooded vertebrates and cause serious toxoplasmosis in immunosuppressed animals and patients. However, the relationship between the host's innate immune system and effector proteins is poorly understood, particularly with regard to how effectors antagonize cGAS-STING signaling during T. gondii infection. In this study, the ROP5 from the PRU strain of T. gondii was found to promote cGAS-STING-mediated immune responses. Mechanistically, ROP5 interacted with STING through predicted domain 2 and modulated cGAS-STING signaling in a predicted domain 3-dependent manner. Additionally, ROP5 strengthened cGAS-STING signaling by enhancing the K63-linked ubiquitination of STING. Consistently, ROP5 deficient PRU (PRUΔROP5) induced fewer type I IFN-related immune responses and replicated faster than the parental strain in RAW264.7 cells. Taken together, this study provides new insights into the mechanism by which ROP5 regulates T. gondii infection and provides new clues for strategies to prevent and control toxoplasmosis.

Study of Some Apoptotic Protein Expration in Human Mesenchymal Stem Cells During Toxoplasma Gondii Infection

Background: Toxoplasma gondii (T. gondii) infection is a significant health concern, particularly during pregnancy, as it can lead to fetal harm and birth abnormalities. Specific Background: The role of apoptosis in managing T. gondii infection remains poorly understood, particularly regarding its molecular mechanisms. Knowledge Gap: The impact of T. gondii infection on apoptosis in mesenchymal stem cells (MSCs) derived from human umbilical cords has not been thoroughly studied in existing literature. Aims: This study aimed to investigate the activation of apoptosis and its regulatory mechanisms in human Wharton’s Jelly mesenchymal stem cells (WJ-MSCs) during T. gondii infection. Results: Using non-enzymatic techniques, we isolated T. gondii from infected and aborted phase-specific placentas. Our findings demonstrated a significant increase in the expression of apoptosis-activating genes (CASP2, CASP3, Bak1) in WJ-MSCs following infection, with a marked decrease in cell viability observed within 2 to 4 hours of exposure to the parasite (P≤0.05). Novelty: This study provides novel insights into the relationship between T. gondii infection and apoptosis in WJ-MSCs, highlighting the specific gene expression changes that occur in response to infection. Implications: Research on T. gondii's apoptotic pathways is crucial for developing therapeutic strategies to mitigate pregnancy-related adverse effects and improve maternal and fetal health outcomes. Highlights: Increased Apoptosis: T. gondii enhances apoptosis in mesenchymal stem cells. Cell Viability Impact: Significant decrease in WJ-MSC viability after infection. Clinical Relevance: Insights can inform strategies to reduce fetal infection risks. Keywords: Toxoplasma gondii, apoptosis, Wharton’s Jelly mesenchymal stem cells, pregnancy, gene expression

Disseminated Toxoplasma Gondii Infection in a Deceased Donor Kidney Transplant Recipient: A Fatal Case Report

Abstract Introduction/Objective Post-transplant immunosuppression predisposes patients to severe complications from opportunistic infections, including Toxoplasma gondii. Typically asymptomatic and self-limited in immunocompetent individuals, Toxoplasma gondii can cause life-threatening disseminated disease in immunocompromised patients like solid organ transplant recipients. The challenge in diagnosing Toxoplasmosis is further exacerbated in patients receiving prophylactic therapy with agents such as Atovaquone, which may mask clinical suspicion. This case report describes a fatal presentation of disseminated Toxoplasmosis in a kidney transplant recipient. Methods/Case Report A 44-year-old male with a history of deceased donor kidney transplant presented to the emergency department two months post-transplant with symptoms of malaise, shortness of breath, hypoxemia, and hypotension. Despite medical interventions, the patient deteriorated rapidly, developing acute hypoxemic respiratory failure and septic shock requiring intubation. Subsequently, he succumbed to multisystem organ failure five days after admission. The autopsy revealed disseminated Toxoplasma gondii infection, with tachyzoites/bradyzoites identified in multiple organs, including the brain, bone marrow, and lymph nodes. Positive Toxoplasma immunohistochemical staining and PCR confirmed the diagnosis. Results (if a Case Study enter NA) NA Conclusion Toxoplasma infection in post-transplant patients can manifest as a severe and potentially fatal complication. Dissemination can arise from the reactivation of latent infection, donor transmission, or new acquisition. In this case, the infection likely resulted from the reactivation of latent infection in the donor, compounded by immunosuppression in the recipient. Notably, the patient received Atovaquone prophylaxis due to a sulfa allergy. Nonetheless, the case highlights the potential for delayed diagnosis due to atypical presentations in immunocompromised patients. Clinicians should maintain a high index of suspicion for Toxoplasma infection in post- transplant patients, particularly in those with unexplained clinical deterioration. This case emphasizes the importance of maintaining a high index of suspicion for T. gondii infection in post-transplant patients, even in those receiving prophylaxis.

Efficacy of Clindamycin in Preventing Abortion and Vertical Transmission of Toxoplasma gondii (PRU Strain) Infection in Pregnant BALB/c Mice

Background: Toxoplasma gondii transmission can occur during pregnancy if the mother contracts the infection for the first time. Treatment strategies include the use of antimicrobial medications and providing supportive care. Spiramycin is commonly used to treat toxoplasmosis in pregnant women and to hinder the disease's transmission. However, its ability to treat the fetus is questionable due to its limited capacity to cross the placental barrier. Additionally, economic constraints and sanctions may impede access to this medication. Objectives: Consequently, in search of an effective treatment, for the first time in Iran, the effectiveness of clindamycin in preventing abortion and vertical transmission of the PRU strain of T. gondii infection in pregnant mice was evaluated. Methods: On the twelfth day of gestation, pregnant mice were exposed to T. gondii and subsequently received treatment with either clindamycin or spiramycin. This resulted in the establishment of four distinct groups: A normal control group, an infected group without treatment, an infected group treated with clindamycin, and another infected group treated with spiramycin. Following these interventions, a series of parasitological evaluations (including microscopic examination and real-time PCR), histopathological evaluations, and immunological assessments were conducted. Results: The findings showed a significant reduction in the number of cysts in the eye and brain (ranging from 77.32% to 90.72%) among the groups treated with clindamycin and spiramycin compared to the control group. Furthermore, treatment with clindamycin, like treatment with spiramycin, was able to suppress inflammatory changes, prevent cell death, and reduce vascular cuffs in the brain, as well as decrease bleeding, placental thrombosis, and the accumulation of inflammatory cells in the placenta. Clindamycin was also effective in diminishing retinal folds, tiny retinal bleeds, and cell vacuolation in eye tissues. Immunologically, treatment in both the spiramycin and clindamycin groups resulted in a decrease in the level of the cytokine TNF-α, indicating an increase in the cellular immune response. In addition, increased levels of IL-10 in the treated infected groups could contribute to the reduction of TNF-α production. Conclusions: Typically, spiramycin is the first choice for treating congenital toxoplasmosis, but clindamycin can be a useful substitute or additional treatment when resistance to primary medications occurs, when there is intolerance, or when access to the main drugs is restricted.

Ocular Toxoplasmosis: Advances in Toxoplasma gondii Biology, Clinical Manifestations, Diagnostics, and Therapy.

Toxoplasma gondii, an obligate intracellular parasite, is a globally prevalent pathogen capable of infecting a wide range of warm-blooded animals, including humans. Ocular toxoplasmosis (OT), a severe manifestation of T. gondii infection, can lead to potentially blinding complications. This comprehensive review delves into the current understanding of T. gondii biology, exploring its complex life cycle, diverse transmission routes, and strain diversity. This article provides an in-depth analysis of the clinical manifestations of OT, which can result from both congenital and acquired infections, presenting a spectrum of signs and symptoms. The review examines various diagnostic strategies employed for OT, including clinical examination, multimodal imaging techniques such as fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA), as well as laboratory tests including serology and molecular methods. Despite extensive research, the specific mechanisms underlying ocular involvement in T. gondii infection remain elusive, and current diagnostic options have limitations. Moreover, the treatment of active and recurrent OT remains a challenge. While existing therapies, such as antimicrobial agents and immunosuppressants, can control active infections, they do not offer a definitive cure or completely prevent recurrence. The clinical endpoints for the management of active and recurrent OT are also not yet well-established, and the available treatment methods carry the potential for adverse effects. This article highlights the need for future research to elucidate the pathogenesis of OT, investigate genetic factors influencing susceptibility to infection, and develop more sensitive and specific diagnostic tools. Enhancing global surveillance, implementing robust prevention strategies, and fostering multidisciplinary collaborations will be crucial in reducing the burden of OT and improving patient outcomes. This comprehensive review aims to provide a valuable resource for clinicians, researchers, and policymakers, contributing to a better understanding of T. gondii infection and its impact on ocular health.

The Prevalence of Toxoplasma gondii in Saudi Arabia (1994-2023): A Systematic Review and Meta-Analysis.

Toxoplasmosis is one of the most common parasites affecting humans in diverse populations caused by T. gondii. This study aims to systematically review and analyze the prevalence of T. gondii infection among various population categories in Saudi Arabia. Our search was done in five databases: PubMed, Scopus, Cochrane Library, Embase, and Web of Science to find the relevant studies from inception to November 2023. The pooled prevalence of toxoplasmosis among the total population living in Saudi Arabia was estimated using a random-effect meta-analysis approach, and Comprehensive Meta-Analysis software was utilized for this analysis. Our study included 30 case-control and retrospective studies published from 1994 to 2023 involving 20,699 patients from different regions in the Kingdom of Saudi Arabia. Various cities were included, such as Al-Ahsa, Najran, Riyadh, Arar, Mecca, al Khobar, Mushait, Tabuk, jazan, Hail City, Almadinah Almunawwarah, AL-Ahsa, and Abha; 27 reported outcomes related to IgG seroprevalence, revealing an overall toxoplasmosis prevalence of 27.5% in Saudi Arabia. Fifteen studies that measured IgM seroprevalence found an overall toxoplasmosis prevalence of 2.2%. Specifically for pregnant women, IgG seroprevalence was 28%. Among different age categories, the highest toxoplasmosis prevalence was observed in the group aged 31-45years, reaching 32.5%, while the lowest prevalence was in the 10-20years category at 19.3%. Regarding gravidity, the grand multi-gravida group exhibited the highest prevalence at 32.9%, with an upper limit of 47.8%. Furthermore, individuals who consumed freshwater demonstrated a higher incidence than those drinking bottled water, with respective prevalence rates of 33.5% and 29.4%. In conclusion, the prevalence of toxoplasmosis in Saudi Arabia is lower than the global average, with significant variations across different age groups, water sources, and dietary habits. Targeted educational programs and public health interventions are essential to raise awareness and reduce the risk of T. gondii infection. Future research should focus on improving study quality and exploring the broader implications of toxoplasmosis on public health in Saudi Arabia.

Prevalence and genotyping of Toxoplasma gondii in questing Ixodes ricinus ticks from forest areas of Northern Poland.

Toxoplasma gondii occurs in a wide range of intermediate hosts, whose blood may be a meal for different tick species. A few studies have examined the role of ticks in the life cycle of T. gondii. This one includes the largest number and all stages of Ixodes ricinus collected from the widest area, covering seven recreational localities within a forest biotope in Northern Poland. This study aimed to determine the prevalence of T. gondii DNA in 2144 collected questing ticks to establish whether they may be involved in T. gondii life cycle. The additional goal was to genotype the detected T. gondii, as knowledge about its genotypes occurring in European ticks is insufficient. A further purpose was to detect coinfection with T. gondii and Borreliaceae in the collected ticks, as all of them have previously been tested for the presence of bacteria DNA. Nested PCR and sequencing of the obtained B1 gene fragment were conducted. T. gondii DNA was detected in 0.9% of all ticks (1.1% of nymphs and 0.7% of larvae). The presence of T. gondii in unfed larvae and nymphs may indicate the possibility of its vertical transmission. The prevalence of T. gondii DNA in ticks collected from individual sites was focal (0-4.3%) and seems to depend on local climatic conditions. Among all examined ticks, 0.3% were coinfected with T. gondii and Borreliella spp., vs. 0.6% of specimens with a single T. gondii infection. The obtained B1 sequences showed the greatest similarity (99.71-100%) to the sequence representing type III.

Seroprevalence and risk factors of Toxoplasmosis in HIV positive and negative patients attending the Bamenda Regional Hospital, North West Region, Cameroon

Background: Toxoplasmosis, caused by Toxoplasma gondii, can infect almost all warm-blooded animals including humans. T. gondii is regarded as an important opportunistic pathogen that can cause infection in HIV/AIDS patients associated with high mortality. The objective of this study is to determine the prevalence and risk factors of T. gondii infection in HIV-positive and negative patients and establish the relationship between HIV viral load and active toxoplasmosis in the Bamenda Regional Hospital Cameroon. Methodology: Three hundred and three (201 HIV-positive and 102 HIV-negative) participants attending the Bamenda Regional Hospital, Cameroon, were randomly recruited into the study. Well-structured questionnaires were used to obtain information on demographic characteristics and potential risk factors from each participant. Venous blood samples were collected for serological detection of toxoplasmosis using One-Step Toxo IgG/IgM rapid diagnostic test (RDT) kits, followed by confirmation of all positive samples by Toxoplasma IgM ELISA test. Data were analysed on SPSS version 23.0. Association of potential risk factors with seroprevalence of toxoplasmosis was done using Chi square test, and comparison of means HIV loads between participant categories was done using Mann-Whitney U-test and Kruskal-Wallis as applicable, with p<0.05 considered as significant level. Results: Of the 303 participants, 93 were positive for Toxoplasma IgG, giving latent toxoplasmosis seroprevalence rate of 30.7%, while 2 of the 303 participants were seropositive for Toxoplasma IgM, indicating active toxoplasmosis in 0.7%. The seroprevalence of latent toxoplasmosis was 28.9% (n=58/201) in HIV-positive compared to 34.3% (n=35/102) in HIV-negative participants (χ2=0.948, OR=0.775, p=0.330), while the seroprevalence of active toxoplasmosis was 1.0% (n=2/201) in HIV-positive compared to 0% (n=0/102) in HIV-negative participants (χ2=0.068, OR=2.568, p=0.552). Viral load was detectable (≥ 42 viral copies/ml) in 54 of the 201 HIV-positive participants, giving an overall detectable viral load rate of 26.9%. The sero-prevalence of latent toxoplasmosis was higher in HIV-positive participants with detectable viral load than those with non-detectable viral load, and the two HIV-positive patients with active toxoplasmosis had detectable viral loads. The risk factors significantly associated (p<0.05) with the latent toxoplasmosis were owning a cat, presence of stray cats, playing with cats, and eating soya. Conclusion: Latent toxoplasmosis is prevalent among HIV-positive and negative patients attending the Bamenda Regional Hospital in Cameroon, with active infection only among HIV-infected patients.

Investigation of Seropositivity of Anti-Toxoplasma gondii Antibodies and Possible Risk Factors in Pregnant Women with Diabetes at Risk.

Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii. Immunocompromised individuals and pregnant women are at risk, with the latter group being susceptible to miscarriages. This study aimed to determine the seropositivity of T. gondii antibodies and potential risk factors in pregnant women diagnosed with diabetes mellitus. The research was conducted at the Ankara City Hospital Perinatology Clinic between October 2021 and June 2022. The study included 277 pregnant women diagnosed with diabetes mellitus and 277 healthy pregnant women who had given birth. Retrospective analysis of anti-T. gondii immunoglobulin (Ig)G and IgM levels was performed for patients between January 2020 and February 2022. Participants were administered an informed consent form and a questionnaire. Data were analysed using SPSS 22. Among pregnant women with diabetes, IgG seropositivity was 18.4%, IgM was 0.0%, and IgG+IgM was 0.0%. In healthy pregnant women, IgG seropositivity was 12.3%, IgM was 0.4%, and IgG+IgM was 0.4%. Overall, seropositivity rates were 15.3% for IgG, 0.2% for IgM, and 0.2% for IgG+IgM. The difference between the two groups was statistically significant (p<0.05). Among pregnant women with diabetes, there was a significant statistical difference (p<0.05) in anti-T. gondii IgG seropositivity related to education, employment status, number of pregnancies and live births, history of toxoplasmosis diagnosis in children, previous toxoplasmosis diagnosis, hygiene, nutrition, and social habits. Among healthy pregnant women, significant statistical differences were found (p<0.05) in IgG seropositivity related to age, income, education level, number of pregnancies and live births, previous toxoplasmosis diagnosis, hygiene, nutrition, and social habits. No invasive interventions were performed on infants born to seropositive mothers, and perinatal data were not available. The seroprevalence of toxoplasmosis in Ankara appears to be decreasing, but T. gondii infections continue to pose a public health concern and are significant in pregnant women with diabetes mellitus.

Nanospheres as the delivery vehicle: novel application of Toxoplasma gondii ribosomal protein S2 in PLGA and chitosan nanospheres against acute toxoplasmosis.

Toxoplasma gondii (T. gondii) is a zoonotic disease that poses great harm to humans and animals. So far, no effective T. gondii vaccine has been developed to provide fully protection against such parasites. Recently, numerous researches have focused on the use of poly-lactic-co-glycolic acid (PLGA) and chitosan (CS) for the vaccines against T. gondii infections. In this study, we employed PLGA and CS as the vehicles for T. gondii ribosome protein (TgRPS2) delivery. TgRPS2-PLGA and TgRPS2-CS nanospheres were synthesized by double emulsion solvent evaporation and ionic gelation technique as the nano vaccines. Before immunization in animals, the release efficacy and toxicity of the synthesized nanospheres were evaluated in vitro. Then, ICR mice were immunized intramuscularly, and immune protections of the synthesized nanospheres were assessed. The results showed that TgRPS2-PLGA and TgRPS2-CS nanospheres could induce higher levels of IgG and cytokines, activate dendritic cells, and promote the expression of histocompatibility complexes. The splenic lymphocyte proliferation and the enhancement in the proportion of CD4+ and CD8+ T lymphocytes were also observed in immunized animals. In addition, two types of nanospheres could significantly inhabit the replications of T. gondii in cardiac muscles and spleen tissues. All these obtained results in this study demonstrated that the TgRPS2 protein delivered by PLGA or CS nanospheres provided satisfactory immunoprotective effects in resisting T. gondii, and such formulations illustrated potential as prospective preventive agents for toxoplasmosis.

Evaluation of Protective Efficacy of Recombinant Toxoplasma gondii DDX39 Protein Vaccine against Acute and Chronic T. gondii Infection in Mice

Toxoplasma gondii, a pervasive parasite responsible for toxoplasmosis, poses significant health risks to humans and animals. In this study, we investigated the immunogenicity and protective efficacy of the recombinant T. gondii DDX39 protein formulated with ISA201 adjuvant (rTgDDX39) as a candidate vaccine against toxoplasmosis. The full-length of TgDDX39 gene was successfully amplified, cloned into the pET-30a vector, and expressed in BL21 (DE3) competent cells, which was purified and identified as a 57.1 kDa protein via sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Western blot analysis confirmed that rTgDDX39 was specifically recognized by serum from T. gondii-infected mice. Furthermore, immunization of rats with rTgDDX39 generated antiserum that could specifically recognize the native TgDDX39 protein in T. gondii tachyzoite lysates. Immunofluorescence assay revealed that TgDDX39 was primarily located in the nucleus and perinuclear region of tachyzoites. Our vaccination strategy significantly increased T cell proliferation, with CD4+ T cells rising by 21.9% and CD8+ T cells by 57.8% by the sixth week compared to the adjuvant control group. Additionally, high titers of anti-rTgDDX39 IgG antibodies were detected in vaccinated mice, with a notable induction of IgG1 and IgG2a isotypes, and IgG1/IgG2a > 1 suggests a Th2-biased immune response.Furthermore, in vitro and in vivo assays demonstrated that polyclonal antibodies raised against rTgDDX39 could inhibit the proliferation of T. gondii RH tachyzoites, highlighting the potential of these antibodies to neutralize this parasite effectively. This study provides compelling evidence of the immunogenicity and protective efficacy of rTgDDX39, supporting its potential as a potential candidate vaccine against toxoplasmosis. The protective efficacy of the vaccine was evaluated in mice challenged with acute (RH) and chronic (PRU) strains of T. gondii, showing a survival time extended to 17 days in the acute model, compared to 13.5 and 14 days in the control groups, and a significant 34% reduction in cyst burden in the chronic model. Additionally, the survival rate in the PRU-infected mice increased from 15-20% in the control groups to 45% in the vaccinated group. In vitro and in vivo assays demonstrated that polyclonal antibodies raised against rTgDDX39 could inhibit the proliferation of T. gondii RH tachyzoites, highlighting the potential of these antibodies to neutralize the parasite effectively. This study provides compelling evidence of the immunogenicity and protective efficacy of rTgDDX39, supporting its potential as a candidate vaccine against toxoplasmosis.

Toxoplasma-induced behavior changes - is microbial dysbiosis the missing link?

Toxoplasma gondii (T. gondii) is one of the most successful intracellular protozoa in that it can infect the majority of mammalian cell types during the acute phase of infection. Furthermore, it is able to establish a chronic infection for the host's entire lifespan by developing an encysted parasite form, primarily in the muscles and brain of the host, to avoid the host immune system. The infection affects one third of the world population and poses an increased risk for people with a suppressed immune system. Despite the dormant characteristics of chronic T. gondii infection, there is much evidence suggesting that this infection leads to specific behavior changes in both humans and rodents. Although numerous hypotheses have been put forth, the exact mechanisms underlying these behavior changes have yet to be understood. In recent years, several studies revealed a strong connection between the gut microbiome and the different organ systems that are affected in T. gondii infection. While it is widely studied and accepted that acute T. gondii infection can lead to a dramatic disruption of the host's normal, well-balanced microbial ecosystem (microbial dysbiosis), changes in the gut microbiome during the chronic stage of infection has not been well characterized. This review is intended to briefly inspect the different hypotheses that attempt to explain the behavior changes during T. gondii infection. Furthermore, this review proposes to consider the potential link between gut microbial dysbiosis, and behavior changes in T. gondii infection as a novel way to describe the underlying mechanism.

SEROPREVALENCE OF TOXOPLASMA GONDII AMONG CANCER PATIENTS IN AL-AMAL CENTER FOR TREATMENT OF CANCER PATIENTS IN TAIZ CITY, YEMEN

The current study was done in Taiz city during the period from March 2019 to march 2020, this study aimed to determine the prevalence of Toxoplasma gondii infection among cancer patients and to determine the association of T. gondii seropositivity in cancer patients with gender, age and number of chemical doses in Al-Amal Center for Treatment of Cancer Patients in Taiz governorate, Yemen, using serological test by rapid devise Toxo-kits method. A total of 368 blood samples from cancer patients were collected and examined for anti-Toxoplasma gondii IgG and IgM antibodies. The overall T. gondii seroprevalence, including both Immunoglobulin G (IgG) and Immunoglobulin M (IgM) positive individuals was 42.12% (155/368). The seroprevalence rate of IgG and IgM antibodies was 41.58% (153/368) and 14.13% (52/368), respectively. Regarding sex, no statistically significant difference was found, with 65 seropositive out of 148 (43.92%) in males and 90 out of 220 (40.91%) in females (P&gt;0.05). The seroprevalence of T. gondii infection was high in all age groups, especially in younger and older cancer patients (aged from 1-10 and &gt;80 years old), (50.00%) in each; while the lower seroprevalence (25.81%) was detected in cancer patients aged 21 to 30 years old, but the differences were not significant (P&gt; 0.05). Moreover, the seroprevalence of toxoplasmosis was higher in individuals treated with chemotherapy (43.07%) than those not used chemotherapy (39.60%), with no significant difference (P&gt;0.05). T. gondii infection remains a major threat to cancer patients, and it needs proper screening, diagnosis and treatment.

BAFF as a Potential Marker for Toxoplasma Gondii Seroprevalence Among Cancer Patients on Chemotherapy

Background: Toxoplasmosis is a global zoonotic disease, that is mainly asymptomatic in healthy persons, but critical and life-threatening in immunocompromised patients. The infection is caused by an opportunistic obligate intracellular parasite protozoon “Toxoplasma gondii” (T. gondii) that can cause fatal complications in immunosuppressed patients. Cancer patients are being immunocompromised from the cancer itself and on the other hand cancer therapy they receive may reactive a latent T. gondii infection that leaves them at high risk. The B-cell activating Factor (BAFF) is a cytokine that plays an essential role in the activation, maturation, and survival of B cells. It is vital for the appropriate functioning of the immune system. Monitoring BAFF levels in cancer patients undergoing chemotherapy could be important for preventing or controlling infections in these vulnerable patients. Objectives: This study aimed to detect seroprevalence of T. gondii in cancer patients receiving chemotherapy and assess the levels of BAFF in those patients. Materials and Methods: 150 serum samples were collected from oncology patients having different types of cancer and receiving chemotherapy, from different ages. And 30 samples from healthy people for control. In this cross-sectional study, samples were collected from the 1st of October 2023 to the 1st of March 2024, at Kirkuk Oncology and Hematology center. The method used was the Sandwich Enzyme-Linked Immunosorbent Assay (Sandwich-ELISA) technique. Results: the overall anti-T. gondii IgG and IgM seropositive samples were found to be 67 (37.2%) in the total study population and 67(44.7%) in cancer patients. BAFF levels were elevated in cancer patients infected with T. gondii compared with the cancer patients with no infection and the healthy control group. A significant difference was indicated with (p-value 0.0004). Conclusions: A high rate of T. gondii seroprevalence was revealed among oncology patients receiving chemotherapy with elevated levels of BAFF associated with T. gondii infection in those patients.

Toxoplasma gondii infection affects the complete blood count and disturbs the markers of oxidative stress from the vital organs of wild rodents

Rodents are the synanthropic mammals that are existing in close proximity to humans and their belongings and have the potential to act as the reservoir for a variety of parasites having zoonotic potential. Present study was designed to report the molecular prevalence and phylogenetic evaluation of Toxoplasma gondii in the blood samples of four wild rodent species [Rattus rattus (N = 122), Mus musculus (N = 64), Rattus norvegicus (N = 57) and Dryomys nitedula (N = 1)] that were trapped during May 2022 till July 2023 from three districts in Punjab (Jampur, Dera Ghazi Khan and Multan) and three districts (Upper Dir, Mardan and Bunar) in Pakistan. Results revealed that 44/244 (18%) rodents amplified ITS-1 gene of Toxoplasma gondii through PCR. Parasite prevalence varied between the rodent species. Highest rate of infection was found in Rattus norvegicus followed by Rattus rattus and Mus musculus. For both rat species, Toxoplasma gondii infection significantly varies between the sampling districts. DNA sequencing and BLAST analysis confirmed the presence of Toxoplasma gondii in rodent blood samples. Phylogenetic analysis showed that Pakistani isolates were genetically diverse and clustered with the isolates that were reported from worldwide countries. Complete blood count analysis revealed that parasite infected rodents had disturbed lymphocyte, mean platelet volume, mean corpuscular volume (and mean corpuscular hemoglobin concentration. Markers of oxidative stress analysis revealed that infected rodent had elevated malondialdehyde levels in liver and kidney while disturb catalase concentrations in kidney and heart as compared to uninfected animals. In conclusion, we are reporting a relatively high prevalence of Toxoplasma gondii in Pakistani rodents. Infection leads to disturbed complete blood count and markers of oxidative stress in the vital organs. We recommend large scale studies in various geo-climatic regions of Pakistan to report the incidence and prevalence of this pathogen among the rodents in order to prevent their infections in local people as well as in livestock.

Toxoplasma Gondii infection and cardiovascular mortality: sex-specific differences in a United States population-based cohort study

BackgroundAlthough Toxoplasma gondii (T. gondii) infection has been linked to cardiac injury, the extent to which it increases the risk of cardiovascular disease (CVD) mortality remains unclear. We aimed to assess the association between T. gondii infection and CVD mortality in the United States population.MethodsThis study used data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2009 and 2014 to investigate the association between T. gondii infection and CVD mortality. The T. gondii infection status was determined by measuring serum T. gondii IgG antibody levels. CVD mortality outcomes were ascertained through linkage with the national mortality index records. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) of T. gondii infection on CVD mortality.ResultsA total of 10,237 (Male, n = 5010; Female, n = 5227) individuals aged ≥ 20 years were included in the analysis, of which 1,632 were positive for T. gondii serum IgG antibodies. After a median follow-up of eight years, there were 312 deaths due to CVD. In multivariable-adjusted analyses, the risk of death from CVD was 40% higher in T. gondii-seropositive men compared with seronegative men (HR: 1.40; 95%CI: 1.02–1.93), but not in women (HR: 0.87; 95% CI: 0.57–1.34). These results remained consistent in further stratified and sensitivity analyses.ConclusionIn this large population-based cohort study, T. gondii infection was associated with an increased risk of CVD mortality in men, but not in women. Further studies are required to elucidate the underlying mechanisms and potential sex-specific differences in the effects of T. gondii infection on CVD mortality. Future investigations should focus on validating these results and exploring the potential implications for cardiovascular risk assessment and management.