Search Results (68)

Congenital toxoplasmosis, caused by the obligatory intracellular apicomplexan protozoan Toxoplasma gondii, can lead to severe complications during pregnancy, including fetal malformations and spontaneous abortion. In the present study, the anti-T. gondii effects of the natural flavonoid quercetin were evaluated using in vitro, ex vivo, and in silico models. Cell viability and intracellular proliferation of the parasite were determined via colorimetric assays. The lipid droplet assay was analyzed using Nile Red staining, the antioxidant and oxidative stress parameters were determined by biochemical assays, and the cytokine levels were quantified by immunoassays. Our results demonstrated that non-cytotoxic concentrations of quercetin (CC₅₀ > 100 μM) significantly inhibited parasite proliferation (IC₅₀ = 14.10 ± 2.83 μM; SI > 7.09) in an irreversible manner. Quercetin impairs parasite adhesion, invasion, and reinfection capacity. In parallel, quercetin reduced lipid droplet accumulation, restored antioxidant balance by modulating redox biomarkers, and regulated cytokine production, notably increasing IL-4, IL-6, and IL-8 levels. Corroborating the in vitro findings, quercetin significantly reduced T. gondii proliferation in human placental villous explants while preserving tissue architecture and viability. In silico analyses revealed that quercetin binds to the active site of T. gondii hypoxanthine-guanine phosphoribosyltransferase (TgHGPRT) and exhibits favorable pharmacokinetic and drug-likeness properties. Full article

Toxoplasmosis remains one of the most common parasitic infections affecting humans, with significant implications for pregnancy and fetal health. Maternal primary infection during gestation can result in transplacental transmission of Toxoplasma gondii, leading to a wide spectrum of congenital disease. The risk of vertical transmission increases with gestational age, whereas disease severity is inversely related—early infections causing severe neurological and ocular damage, and late infections often resulting in subclinical forms. Advances in serological testing, including IgG avidity assays and molecular diagnostics such as PCR on amniotic fluid, have improved early detection and management. Prenatal treatment with spiramycin or pyrimethamine–sulfadiazine–folinic acid combinations has been associated with reduced transmission and less severe fetal disease in several studies, although the magnitude of benefit remains debated. Long-term follow-up is essential, as late-onset manifestations, particularly chorioretinitis and neurodevelopmental impairment, are common. This narrative review was based on a comprehensive literature search of major medical databases and summarizes current knowledge on the epidemiology, pathophysiology, diagnosis, treatment, and outcomes of toxoplasmosis in pregnancy. Particular emphasis is placed on high-prevalence countries, where greater parasite genetic diversity, distinct epidemiological patterns, and a higher burden of congenital disease pose unique clinical and public health challenges. Despite progress in understanding parasite biology, pathogenesis, and treatment efficacy, congenital toxoplasmosis continues to be underdiagnosed and underreported, especially in low-resource settings. Ongoing challenges include optimizing screening strategies, ensuring access to standardized therapies, and strengthening surveillance systems. Full article

Background: Toxoplasmosis is a prevalent zoonotic disease worldwide, affecting approximately one-third of the global human population. Primary infection with Toxoplasma gondii during pregnancy can induce miscarriage or congenital infection, leading to irreversible damage to the foetus. Moreover, reactivation of T. gondii infection in immunosuppressed individuals can result in fatal outcomes. No vaccine exists to prevent human disease caused by this parasite. Thus, a vaccine that could induce complete and lasting protection against human toxoplasmosis is an unmet need. Method: In this work, BALB/cByJ mice were intranasally immunised with a subunit vaccine consisting of T. gondii membrane proteins (TGMP) from the T. gondii Me49 strain plus CpG-oligodeoxynucleotide adjuvant (CpG). Antibody responses were analysed by ELISA, while T-cell responses were evaluated by flow cytometry. The immunogenic proteins present in TGMP were identified by mass spectrometry, and parasite burden was quantified by qPCR. Result: The results showed raised TGMP-specific serum IgG and intestinal IgA antibody levels, and parasite-specific IFN-γ-producing CD4⁺ and CD8⁺ memory T cells. Dense granule proteins (GRA) 2 and 7, surface antigen (SAG)-related sequences 25, 29B, and 34A, microneme protein (MIC) 10, toxofilin, nascent polypeptide-associated complex (NAC) domain-containing protein, and NAC subunit beta were identified as immunogenic proteins. Mice immunised with TGMP+CpG were challenged with T. gondii tachyzoites and showed a significant reduction in the parasitic burden in the peritoneal exudate, spleen, and lungs, compared to mice sham-immunised with CpG alone. Conclusions: Altogether, these results indicate that mucosal immunisation with TGMP plus CpG adjuvant is worth exploring as a vaccination approach to prevent toxoplasmosis. Full article

Objective: This study aimed to evaluate the association between T. gondii genotypes (types I, II, III) and cases of spontaneous abortion in humans. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. Databases (PubMed, Scopus, Web of Science, EMBASE, and ScienceDirect) were searched for studies published in the last 10 years. Observational studies evaluating T. gondii genotypes in abortion cases were included. Results: Eight cross-sectional studies were included. A pooled positivity proportion for T. gondii of approximately 20% was observed among abortion cases, with substantial heterogeneity (I² > 90%). Genotype distribution varied across studies, with types I and III being the most frequently reported. Conclusions: Available evidence suggests a possible association between T. gondii infection and spontaneous abortion; however, the role of specific genotypes remains uncertain due to limited and heterogeneous data. More multicenter studies are needed to robustly address the issue. Full article

Toxoplasmosis, caused by the obligate intracellular parasite T. gondii, is one of the most prevalent parasitic infections worldwide, affecting approximately one-third of the global population. Despite decades of intensive research, no effective human vaccine exists. The only commercially available vaccine, Toxovax, is restricted to veterinary use in sheep and is unsuitable for human application due to safety concerns. Beyond summarizing the literature, this review offers a critical appraisal of why translation has stalled and where the field should focus next. Live-attenuated vaccines remain the most immunogenic in preclinical models but face significant translational barriers for human use. Key antigenic targets include surface antigens (SAG), dense granule antigens (GRA), rhoptry proteins (ROP), and microneme proteins (MIC). Protective immunity relies critically on Th1-type immune responses characterized by interferon-gamma production. Major obstacles include the parasite’s complex life cycle, strain diversity, and difficulty achieving sterile immunity. Subunit and mRNA-based platforms offer more favorable safety profiles and established clinical precedents, representing the most viable pathway toward a human vaccine. Recent advances in CRISPR/Cas9 gene editing and emerging mRNA vaccine platforms offer promising new directions. This review advances the field in three ways. (i) It prioritizes mRNA and adjuvanted subunit formulations targeting multistage conserved antigens as the most realistic near-term human candidates. (ii) It identifies the limited targeting of bradyzoite-stage biology as a principal, under-addressed gap. (iii) It argues that future development must be differentiated into three complementary One Health goals—prevention of congenital disease in humans, reduction in tissue-cyst burden in livestock, and interruption of environmental transmission by vaccinating cats. In practice, a veterinary-first deployment strategy is the most immediate and impactful pathway to reducing the human and zoonotic burden of toxoplasmosis. Full article

Toxoplasmosis is a widely distributed zoonosis caused by the protozoan parasite Toxoplasma gondii. Infection during pregnancy is a major public health concern due to its potential impact on both maternal health and fetal development. Early detection of maternal infection is critical to prevent adverse outcomes; however, maternal signs are often subtle, non-specific or absent, complicating timely diagnosis. This scoping review aimed to map and synthesise existing evidence on early maternal signs, pregnancy and foetal outcomes, frequently assessed risk factors, and diagnostic approaches of toxoplasmosis in expectant mothers in Africa. The review was done in accordance with the PRISMA-ScR guidelines. A literature search of PubMed, Scopus, ResearchGate, and Google Scholar was performed to identify studies published between 2000 and 2025. Retrieved records were managed using Zotero (version 8.0.4) for deduplication and screening. Only English-language studies conducted in Africa and reporting relevant maternal or clinical data were included. A total of 28 cross-sectional studies were included. Lymphadenopathy (25.0%) was the most frequently reported maternal early sign, followed by flu-like illness, asymptomatic infection, low-grade or mild fever, and fatigue or malaise (each 10.7%). Congenital anomalies (50.0%) and miscarriage or spontaneous abortion (42.9%) were the most commonly reported foetal and pregnancy outcomes. Frequently reported risk factors were exposure to cat faeces (57.1%) and ingestion of undercooked or raw meat (42.9%). Diagnostic approaches were commonly enzyme-based immunoassays (78.6%), with limited use of RDTs and molecular methods. These findings suggest the need for improved early detection and prevention strategies in high-risk, low-resource African settings. Enhancing routine screening, health education, and access to appropriate diagnostics are considered. Future studies should consider adopting standardised reporting and integrating sensitive, affordable, rapid diagnostic approaches to enhance early detection and reduce the burden of congenital toxoplasmosis. Full article

Objective: To evaluate the diagnostic performance of an in-house-developed IgG Western blot (WB) for congenital toxoplasmosis and its complementary role with other serological markers. Methodology: For this purpose, the study utilized 42 mother–child pairs, evaluating the WB in comparison with a Composite Reference Standard (CRS). Cohen’s Kappa coefficient measured agreement, while McNemar’s test compared WB with Combined Serology (neonatal IgG titers higher than the mother’s (IgG↑), IgM, IgA). Results: The WB demonstrated a sensitivity of 75.0% and a specificity of 100.0%. Kappa indicated substantial agreement with the CRS (κ = 0.67; 95% CI: 0.44–0.89). McNemar’s test found no statistically significant difference between WB and Combined Serology (p = 0.7516). Crucially, WB detected 4 unique cases missed by Combined Serology, and Combined Serology detected 6 cases missed by WB. This complementarity increased the overall diagnostic rate from 82.14% to 96.43%. Conclusions: IgG-WB is a crucial complementary diagnostic tool, especially for asymptomatic newborns. Its integration significantly improves diagnostic certainty, allowing for more timely treatment for congenital toxoplasmosis. Full article

Background: Congenital toxoplasmosis remains a significant cause of fetal morbidity worldwide. This case–control study aimed to identify sociodemographic, dietary, and behavioral factors associated with Toxoplasma gondii infection during pregnancy in Italy by comparing infected women with seronegative controls, and to evaluate modifiable risk behaviors and treatment-related outcomes among affected patients. Methods: This case–control study included 201 pregnant women (100 with T. gondii infection and 101 seronegative controls). Participants completed a structured questionnaire on sociodemographic factors, diet, environmental exposures, and preventive behaviors. Clinical data were collected for infected women and analyzed using SPSS v27.0. Results: Sociodemographic and obstetric characteristics did not differ between groups. Infected women were more likely to live in rural areas (p < 0.001), have a lower educational level (p = 0.009), consume unpasteurized dairy products and cured meats (p < 0.05), purchase food from farmers or butchers (p = 0.01), and do not check food preparation practices when eating outside the home. High-risk animal-related behaviors were also more common among cases (p < 0.001). Despite similar baseline awareness, adherence to preventive measures was lower among cases; most infections were diagnosed in the first trimester and treated with spiramycin with good tolerability. Conclusions: Maternal toxoplasmosis is mainly associated with modifiable behavioral and environmental factors, underscoring the need for targeted, preconception counseling to reduce the risk of congenital infection. Full article

Congenital toxoplasmosis (CT) results from vertical transmission of Toxoplasma gondii during maternal infection in pregnancy. Early diagnosis in newborns is crucial to initiate timely therapy and prevent long-term sequelae. The IgM Immunosorbent Agglutination Assay (ISAGA) has historically been considered an important diagnostic tool for CT; however, its recent market withdrawal necessitates alternative approaches. We conducted a retrospective observational study at Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, including 44 newborns born to mothers with confirmed toxoplasmosis between 2019 and 2022. Newborns were classified as CT (n = 19) or non-CT (n = 25) based on serological follow-up, comparative Western blot (CWB) and Interferon Gamma Release Assay (IGRA). Sensitivity and specificity of CWB, IgM Chemiluminescent Immunoassay (CLIA), and IgM ISAGA were assessed at birth and at one month. At birth, CWB demonstrated 88.9% sensitivity, significantly higher than IgM CLIA (52.6%) and IgM ISAGA (57.9%). Specificity was 100% at birth and 92% at one month. CWB retained high sensitivity at one month (81.8%). IGRA complemented CWB in confirming or excluding infection in cases with equivocal or false-negative serology. Comparative Western blot thus represents a robust diagnostic alternative for CT, ensuring early detection and timely treatment, particularly in the absence of IgM ISAGA. Full article

Objective: To determine the prevalence of and risk factors for congenital toxoplasmosis in neonates treated in the public health network of the eastern region of the Brazilian Amazon, northern Tocantins state. Methods: A retrospective cohort study was conducted with neonates born to mothers with gestational toxoplasmosis who received care between 2017 and 2024. The outcome under analysis was positivity for immunoglobulin M in the electrochemiluminescence assay (CLIA). We estimated the prevalence of transplacental infection and respective 95% confidence intervals (95% CI) and its association with risk factors using the odds ratio (or) with a p-value < 0.05 in infected neonates before and after 16 gestational weeks at maternal infection diagnosis. Results: A total of 1142 neonates were surveyed, in which 496 were diagnosed with congenital toxoplasmosis (IgM positive), thus obtaining a prevalence of vertical transmission of 45.4%. The main risk factors for vertical transmission were the mother’s education level equal to or less than eight years, (OR = 1.5; 95% CI 1.2; 2.0) and having less than six prenatal consultations (OR = 22.8; 95% CI 3.0; 172.6). Conclusions: A high prevalence of congenital toxoplasmosis was observed, with higher rates of infection in neonates born to mothers with lower levels of education. Full article

Congenital toxoplasmosis presents with a wide clinical spectrum, ranging from asymptomatic infection to severe disease with multi-organ failure. We report a rare fatal case of disseminated congenital toxoplasmosis in a human neonate. The infant initially had thrombocytopenia and mild hepatitis, which rapidly progressed to fulminant liver failure. Despite initiation of standard therapy with pyrimethamine, sulfadiazine, and folinic acid on postnatal day 25, the infant died two days later. Autopsy revealed widespread involvement of the liver, spleen, brain, heart, lungs, urinary bladder, and skeletal muscle. To further characterize the infection, genomic sequencing of the isolate (TgHsUS2) was performed, which placed it within clade C (Haplogroup 9) and closely related to reference strains P89 and TgCatBr3. Variant analysis showed type III-like alleles in ROP18, ROP16, and GRA15. These alleles are known to modulate host immunity and may have influenced disease severity in this case. This report highlights the need for rapid recognition and targeted therapy as well as how strain genomics can inform disease mechanisms. Prevention through prenatal screening and maternal treatment during pregnancy may reduce infant mortality. Full article

Background: Toxoplasma gondii is a globally distributed apicomplexan parasite capable of causing congenital infections and spontaneous abortions in humans. While the parasite-secreted effector proteins TgGRA28 and TgGRA83 are known to mediate virulence or immune modulation, their potential as vaccine targets remains unexplored. Despite its immunomodulatory properties, the role of IL-28B (a type III interferon) in enhancing DNA vaccine efficacy against T. gondii infection remains unclear. Methods: In this study, we constructed eukaryotic expression plasmids pVAX-GRA28, pVAX- GRA83 and pVAX-IL-28B. After transfection into -293-T cell, protein expression encoding TgGRA28 and TgGRA83 was confirmed via indirect immunofluorescence assay (IFA), while IL-28B expression was analyzed by ELISA. Subsequently, C57BL/6J or IFNαR1 knockout mice were immunized with single or dual-antigen DNA vaccines, with or without the molecular adjuvant pVAX-IL-28B. Immune responses were assessed through Toxoplasma-specific antibody levels, cytotoxic T lymphocyte (CTL) activity, cytokine profiling (IFN-γ, IL-2, IL-12p40, IL-12p70), and flow cytometric analysis of lymphocyte subsets and dendritic cells (DCs). Protective efficacy was determined by survival rates and brain cyst burden following challenge with 100 or 10 ME49 T. gondii cysts, respectively. Results: Vaccination with pVAX-GRA28 and pVAX-GRA83 elicited robust humoral immune responses with increased T. gondii-specific IgG levels and also Th1-polarized immunity, characterized by elevated IgG2a/IgG1 ratio, IFN-γ-dominant cytokine responses, and enhanced DCs, CD4+ and CD8+ T-cell activation. The cocktail vaccine conferred superior protection compared to single-antigen formulations, significantly improving survival and reducing cyst formation. Co-administration of pVAX-IL-28B further augmented vaccine-induced immunity, enhancing both cellular and humoral responses. Moreover, these DNA immunization with pVAX-GRA28 and pVAX-GRA83 plus pVAX-IL-28B induced robust protective immunity that was largely independent of type I IFN signaling, consistent with type III IFN biology. Conclusions: Our findings demonstrate that TgGRA28 and TgGRA83 are promising vaccine candidates against toxoplasmosis, capable of inducing protective immunity against acute and chronic infection. Moreover, IL-28B serves as a potent genetic adjuvant, warranting further investigation for its broader application in vaccines targeting apicomplexan parasites. Full article

A systematic review of toxoplasmosis cases in patients receiving targeted immunotherapy with biologics or small molecules was performed. This systematic review searched for case reports, case series and observational studies in PubMed; last search was on 19 July 2025. The review identified 46 toxoplasmosis cases among patients receiving biologics (including CAR T-Cell Therapies) or small molecules for diverse autoimmune, oncologic and transplant conditions. These cases were reported from 18 countries, including the United States and several European countries. Most patients developed severe disease. Fifty percent (23/46) presented with cerebral toxoplasmosis, 33% (15/46) with ocular toxoplasmosis, 7% (3/46) with lymphadenopathy, 4% (2/46) with disseminated disease, 2% (1/46) with both cerebral and ocular disease, 2% (1/46) with pneumonic toxoplasmosis, and 2% (1/46) with severe fetal congenital toxoplasmosis. Among those were also four cases with fatal outcomes due to toxoplasmosis and eight cases with permanent ocular or neurological deficits. In addition, there was a case of fetal congenital toxoplasmosis that occurred despite maternal discontinuation of adalimumab five months before conception, resulting in elective pregnancy termination due to severe fetal cerebral disease. Overall, 44% (20/46) of cases were due to reactivation of chronic latent Toxoplasma infections and 39% (18/46) due to acute primary infections; 17% did not report this information. One case of disseminated acute toxoplasmosis was also identified after eating wild boar sausages, and two cases of severe acute ocular toxoplasmosis after eating undercooked venison meat, and undercooked unspecified type of meat respectively, while on small molecules or biologics. Details on the clinical presentations, management and clinical outcomes of these cases were reported. Recommendations for the management of toxoplasmosis in patients with targeted immunotherapies were also provided. Health care providers should consider toxoplasmosis in patients on biologics or small molecules who present with compatible clinical syndromes. Prompt diagnosis and treatment can be lifesaving. Full article

Background/Objectives: Toxoplasma gondii, an obligate intracellular parasite, poses a major global health concern owing to its potential for congenital transmission, particularly during pregnancy. Current pharmacological treatments, including spiramycin and pyrimethamine, exhibit limitations in both efficacy and safety, underscoring the need for novel therapeutic strategies. In this study, we investigated the antiparasitic potential of BthTX-II, an Asp49 phospholipase A₂ (PLA₂) isolated from Bothrops jararacussu venom, in human trophoblast cells (BeWo) and third-trimester human placental explants infected with T. gondii. Methods: In vitro assays were performed using BeWo cells infected with T. gondii tachyzoites and treated with non-cytotoxic concentrations of BthTX-II (3.125, 1.56, and 0.78 µg/mL). An ex vivo model employing third-trimester human placental villous explants was used under similar conditions. Parasite proliferation, adhesion, and invasion were assessed alongside host immune response modulation. Results: Our findings demonstrate that BthTX-II reduces T. gondii proliferation in BeWo cells at all tested non-cytotoxic concentrations. The toxin also significantly impaired parasite adhesion and invasion while modulating host immune response by upregulating interleukin (IL)-6, IL-8, and macrophage migration inhibitory factor (MIF), and downregulating vascular endothelial growth factor—potentially disrupting parasite proliferation. In placental villous explants, BthTX-II (1.56 μg/mL) reduced T. gondii proliferation and modulated IL-8, MIF, and tumour necrosis factor-alpha levels without compromising tissue viability. Conclusions: These findings highlight BthTX-II as a potential candidate in toxoplasmosis treatment. Further investigation should focus on its dual role in limiting parasite development and modulating immune responses at the maternal–fetal interface. Full article

Toxoplasma gondii is a globally distributed protozoan parasite and a major cause of congenital infections, particularly in South America. Current therapies for congenital toxoplasmosis are limited by toxicity, long treatment regimens, and suboptimal efficacy, highlighting the urgent need for safer and more effective alternatives. In this study, we evaluated the antiparasitic effects of crude ethanolic extract of Brazilian Red Propolis (BRP) and its isolated compounds, focusing on 7-O-methylvestitol, in human trophoblast (BeWo) cells and third-trimester placental explants. Both BRP and 7-O-methylvestitol significantly reduced T. gondii adhesion, invasion, and intracellular replication, without compromising host cell viability. Ultrastructural analyses revealed irreversible parasite damage, and cytokine profiling demonstrated immunomodulatory effects, with enhanced production of interleukin (IL)-6, IL-8, and macrophage migration inhibitory factor (MIF) in BeWo cells and downregulation of IL-6, MIF, and tumor Necrosis Factor (TNF) in infected placental villi. Notably, 7-O-methylvestitol reproduced and, in some assays, surpassed the antiparasitic activity of BRP, suggesting it as a key bioactive constituent responsible for the therapeutic potential of the extract. These findings support the identification of 7-O-methylvestitol as a promising lead compound for structure-based drug design and repositioning strategies, advancing the development of novel, safe, and targeted therapies against congenital toxoplasmosis. Full article