Search Results (450)

Resistance formation and considerable toxicities limit the application of currently available antiparasitic drugs. Thus, new drug candidates are required. Piperlongumine-based cinnamides are promising antiparasitic compounds. In this study, new synthetic cinnamide derivatives with variable halogen substituents (F, Cl, and Br) were prepared and analyzed. They were tested for activity against Toxoplasma gondii and Leishmania major parasites. Considerable activities against T. gondii parasites were observed for certain chloro- and bromo-substituted cinnamides (IC₅₀ = 1.88–2.72 µM), while activities against L. major were less pronounced. Structure–activity relationships were investigated, which revealed notable relations of anti-toxoplasmal activity with the nature of the applied halogen substituents and a preference for chloro- and bromo-substituents in active compounds. In contrast to piperlongumine, the new active compounds have no methoxy substituents anymore and appear to be suitable for advanced antiparasitic studies. Successful docking of selected derivatives into the colchicine binding site of tubulin provided a strong hint at a possible mode of action for these cinnamides (S-scores of −6.075 and −5.993 kcal/mol). In addition, considerable drug-like properties were determined by ADME-T calculations. Thus, in conclusion, new halo-substituted cinnamides with promising activity against Toxoplasma gondii were identified. The selectivity for Toxoplasma parasites can lead to better drugs for the therapy of 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

Background: Neglected diseases caused by protozoan parasites remain a major public health burden, particularly in low- and middle-income countries. Among the chemical motifs explored in antiparasitic drug discovery, guanidine-containing compounds have attracted considerable attention due to their strong cationic character, high capacity for hydrogen bonding, and versatility in interacting with biological targets. Methodology: This review summarizes advances reported in the last decade regarding guanidine derivatives with activity against pathogens associated with Chagas disease, human African trypanosomiasis, Leishmaniasis, tuberculosis, toxoplasmosis, dengue and schistosomiasis. Results: Evidence gathered from synthetic, natural, and drug-repurposing studies indicates that the guanidine, guanidine-containing and guanidine-related compounds contribute to modulating biological activity by changing electrostatic interactions, hydrogen-bonding networks, and physicochemical properties, with enzymes, nucleic acids, and membrane-associated targets essential for parasite survival. Across the analyzed studies, several emerging structure–activity relationship trends were identified, including the contribution of polycationic or dicationic architectures, the influence of halogenated or lipophilic substituents, and the dependence of biological activity on the complete molecular framework, including heterocyclic systems, macrocycles, peptide conjugates, hybrid scaffolds, and repurposed drugs. In addition to direct antiparasitic effects, certain guanidine-containing and guanidine-related compounds demonstrate immunomodulatory or host-protective properties, expanding the therapeutic relevance of this class. Despite promising in vitro results, protonation trapping, efflux pump susceptibility, and pharmacokinetic limitations such as poor oral absorption, high polarity, plasma protein binding and limited membrane permeability remain significant challenges for clinical translation. Nonetheless, the integration of medicinal chemistry, computational modeling, and biological screening continues to accelerate the identification of optimized scaffolds. Conclusions: Overall, guanidine-based compounds constitute a promising scaffold for the development of new therapeutic strategies targeting neglected parasitic diseases, and further structural optimization may enable the emergence of candidates with improved efficacy, selectivity, and drug-like properties. Full article

Toxoplasma gondii (T. gondi) is a widespread zoonotic parasite that poses a significant threat to global public health, yet effective therapeutic options remain limited. In this study, we found that the flavonoid compound myricetin (MYR) can significantly inhibit the proliferation of T. gondii. This effect is associated with the inhibition of dihydroorotase (TgDHO) activity in the de novo pyrimidine biosynthesis pathway, and this inhibition can be partially reversed by exogenous supplementation with uracil. Further studies revealed that MYR treatment can induce cell cycle arrest in tachyzoites and impair bradyzoite proliferation, concurrently disrupting the UDP-GlcNAc glycosylation of the cyst wall. In mouse models, MYR demonstrated significant efficacy, achieving an 80% survival rate in acute infection and inducing morphological abnormalities in intracerebral cysts during chronic infection. Collectively, these findings elucidate the anti-Toxoplasma activity and multifaceted mechanisms of MYR, providing valuable insights for developing novel therapeutics against toxoplasmosis. Full article

Different protozoan parasites are the causative agents of tropical diseases, including malaria, toxoplasmosis, leishmaniasis, and Chagas disease (CD), which, altogether, affect over 300 million people throughout the world. Except for two recently approved malaria vaccines, individuals affected by or at risk of contracting any of these four diseases still experience a lack of effective treatments and vaccines. Many vaccine studies, including those that have reached clinical trials, are based on inactivated parasites, adjuvanted recombinant proteins, or viral vector vaccines. Here, we review the current advances towards the development of vaccines based on genetically modified live-attenuated parasites (GMLAP) as well as RNA formulations encoding parasite antigens. Because these are diseases caused by intracellular pathogens that depend on efficient T-cell responses for parasite control, these two new vaccine platforms have generated great expectations, since they are known to induce a robust cellular immune response. Although preclinical studies aimed at developing new malaria, toxoplasmosis, and leishmaniasis vaccines have led to significant progress that may soon result in clinical trials, advances in next-generation vaccines against CD are lagging behind. Increased collaborative efforts between research groups, governments, and the pharmaceutical industry, particularly in Africa, Asia, and Latin American countries, are urgently needed to accelerate the development of vaccines for all neglected and less-studied diseases. Full article

Toxoplasma gondii is an obligate intracellular parasite of the phylum Apicomplexa and the causative agent of toxoplasmosis, a disease with a worldwide distribution that causes serious consequences in immunocompromised patients and during pregnancy. Current pharmacological treatments have significant limitations, including their toxicity, lack of efficacy against the chronic phase of the parasite, and low selectivity, highlighting the need to develop new therapeutic targets. One of the most promising targets is the fatty acid synthesis pathway II (FASII), a metabolic pathway located in the parasite’s apicoplast and absent in mammalian hosts. This review synthesizes the available evidence on FASII pathway inhibitors described to date, as well as their potential impact on the viability and development of T. gondii. Overall, the reviewed studies support the FASII pathway as an attractive therapeutic target for the development of more selective and effective treatments against toxoplasmosis. Full article

Background/Objectives: Toxoplasmosis is a globally distributed parasitic zoonosis caused by Toxoplasma gondii (Apicomplexa, Sarcocystidae), an obligate intracellular protozoan with an indirect life cycle in which domestic cats and wild felids serve as definitive hosts, whereas humans and a broad range of domestic and wild animals act as intermediate hosts. The objective of the study was to document the seroprevalence of anti-Toxoplasma gondii antibodies in professionals and students of Veterinary Medicine in Aguascalientes, Mexico. Methods: The study included 153 clinically healthy individuals from two population segments: Veterinarians (70) and Veterinary Medicine Students (83). Serum samples were analyzed using a commercial ELISA test to determine the presence of T. gondii-specific IgG. A questionnaire was applied to collect sociodemographic information and information about contact with cats. Results: The overall prevalence of anti-T. gondii antibodies in the study population was 7.8% (12/153; CI 95% 4.3–13.6). In the group of Veterinarians, the seroprevalence was 11.4% (8/70; CI 95% 5.4–21.8), while in the group of students it was 4.8% (4/83; CI 95% 1.5–12.5), with no differences observed between them (p = 0.22). Association was found with those who consume raw/undercooked meat (p = 0.002). Conclusions: In this cross-sectional sample of veterinary professionals and students in Aguascalientes, anti-T. gondii IgG seroprevalence was 7.8%, with no statistically significant difference between occupational groups. Consumption of raw or undercooked meat was the only exposure significantly associated with seropositivity. 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

Toxoplasma gondii is an obligate intracellular protozoan parasite that causes toxoplasmosis, posing a significant threat to human health and livestock production worldwide. Although monovalent DNA or mRNA vaccines often confer only partial protection, whether these platforms can be effectively integrated into a heterologous prime–boost regimen against T. gondii remains to be fully elucidated. Here, we constructed GRA35-encoding DNA and mRNA vaccines and evaluated their immunogenicity and protective efficacy, administered either alone or in heterologous prime–boost combinations, in C57BL/6 and BALB/c mice. Both vaccines induced strong antigen-specific immune responses, with the heterologous prime–boost regimen eliciting the strongest effects and conferring the most robust and consistent protection across both mouse strains. Immunization triggered a predominantly Th1-skewed response characterized by significantly elevated IFN-γ production, accompanied by balanced antigen-specific IgG responses. Moreover, vaccinated mice developed rapid and potent cytotoxic T lymphocyte (CTL) responses. Following challenge with the RH and PRU strains, vaccinated mice exhibited prolonged survival and significantly reduced brain cyst burdens following PRU challenge compared with control groups. Collectively, these findings indicate that GRA35-based nucleic acid vaccines, particularly when administered in a heterologous prime–boost regimen, elicit multifaceted protective immune responses and represent promising vaccine candidates against T. gondii infection. Full article

Toxoplasma gondii, the causative agent of toxoplasmosis, a disease widely distributed, is an intracellular parasite that invades host cells of different tissues using specialized endocytic activity. Recent studies suggest that tunneling nanotubes (TNTs), thin cell-surface projections, may participate in the parasite–host cell interaction. Here we report results that suggest the involvement of host-cell TNTs in the adhesion of T. gondii tachyzoites to epithelial LLC-MK² cells. Microscopy analysis showed that incubating cells in a medium containing 0.45 M sucrose induces reversible assembly of TNTs without affecting cell viability. The presence of extended TNTs correlated with increased parasite adhesion and reduced parasite entry, thus suggesting a structural or signaling role in mediating adhesion. TNTs assembled following sucrose incubation contain both actin and tubulin components as determined by immunofluorescence microscopy. These results highlight a possible functional relevance of TNTs in T. gondii host cell interaction, especially in parasite adhesion, opening new perspectives for understanding T. gondii-host cell interaction. 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

Ocular toxoplasmosis is a relapsing infectious eye disease that carries an increasing risk of vision loss with each reactivation episode. Antimicrobial drug prophylaxis has been used to reduce the rate of recurrence. This review aims to summarize the current literature regarding expert clinician preferences, as well as the effectiveness and safety of prophylaxis. A literature search was conducted using the PubMed platform of the National Library of Medicine of the National Center for Biotechnology Information and relevant pre-specified search terms. Four professional surveys indicated that approximately three-quarters of experts gave antimicrobial drug prophylaxis for recurrent ocular toxoplasmosis, and that trimethoprim-sulfamethoxazole was the most popular approach. Clinical studies of prophylaxis varied in multiple parameters, including drug, dosing and duration, plus time of follow-up. Considering the four studies with at least 50 participants, the rate of recurrence of ocular toxoplasmosis within 5 years was up to 9.1% of patients taking prophylaxis, and treatment-limiting side effects occurred in up to 7.9% of patients. The available literature demonstrates that antimicrobial drug prophylaxis can reduce the recurrence rate of ocular toxoplasmosis; however, further research on drug dosing and duration of treatment is required to assist decision-making in clinical practice. Full article

Toxoplasma gondii is a protozoan parasite with high zoonotic potential. Currently, no information is available on natural toxoplasmosis in domestic rabbits in Romania; therefore, the aim of the present study was to evaluate the seroprevalence of T. gondii IgG antibodies and to determine the prevalence of T. gondii DNA in domestic rabbits in our country. In total, 372 domestic rabbits were tested. Blood samples were obtained from 352 animals and tissue samples were obtained from 49 animals, of which 29 animals provided paired blood–tissue samples. Samples were collected from pet rabbits and from rabbits raised in household settings, hereafter referred to as farm rabbits. Sera samples were analyzed using a modified agglutination test (MAT), with a cut-off of 1:24, for anti-T. gondii antibody IgG-type detection, and the tissue specimens were tested by nested polymerase chain reaction (nested PCR) targeting the B1 gene for T. gondii DNA detection. A seropositivity of 16.5% (58/352) was obtained by MAT, while the prevalence of T. gondii DNA was 4.1% (2/49). The present study highlighted the presence of T. gondii in domestic rabbits in Romania, which suggests that rabbit meat consumption may represent a potential risk to human health and therefore warrants further attention. Moreover, to the best of our knowledge, this is the first study to report data on the prevalence of T. gondii in domestic rabbits from Romania. Full article

Toxoplasmosis is a cosmopolitan zoonosis that particularly threatens pregnant women, their fetuses and immunocompromised individuals. Among people living with HIV, Toxoplasma gondii may invade the central nervous system, producing neuropathological effects associated with mental and psychiatric disorders. We assessed the seroprevalence of anti-T. gondii IgG in HIV-infected and HIV-uninfected residents of Iquitos, Peru, and evaluated an in-house ELISA based on total lysate antigen (TLA) and recombinant GRA1 (rGRA1), with ELISA-TLA compared against a commercial kit. In this observational cross-sectional study, 151 participants were enrolled: 92 HIV-positive and 59 HIV-negative. ELISA-TLA showed a seroprevalence of 88.08% (133/151), reaching 91.30% (84/92) in the HIV-positive group and 83.05% (49/59) in the HIV-negative group. ELISA-rGRA1 showed a similar epidemiological pattern but lower overall seroprevalence, 81.46% (123/151), with 84.78% (78/92) in HIV-positive and 74.58% (44/59) in HIV-negative participants. Taken together, both TLA and rGRA1-based ELISAs showed similar epidemiological patterns, supporting the consistency of the serological findings. These results also indicate very high exposure to T. gondii in Iquitos, particularly among HIV-positive individuals, in whom prior exposure is clinically relevant because of the risk of reactivation under immunosuppression. Serological screening and preventive counseling may therefore be warranted in high-burden Amazonian communities. Full article

Toxoplasma gondii establishes latent infection in a substantial proportion of the global population, yet the long-term health consequences of this infection remain incompletely characterized. We conducted a retrospective observational matched cohort study using longitudinal electronic health record data from a nationwide integrated healthcare provider, including members aged 18–45 years who underwent routine Toxoplasma serologic screening, typically performed in obstetric evaluation, excluding patients with clinical toxoplasmosis, immunosuppression, or HIV. Seropositive individuals were matched 1:1 without replacement to seronegative controls to align demographic, temporal, and socioeconomic variables. Time-to-event associations with predefined medical conditions were evaluated using Cox proportional hazards models with false discovery rate correction. The final cohort included 19,443 seropositive individuals and 19,443 matched controls (96.7% female), with a tight baseline balance of demographic and temporal characteristics. During follow-up, seropositivity was associated with increased risks of tobacco dependence (aHR 1.65), alcohol dependence (2.32), suicide attempt (1.82), motor vehicle accidents (1.22), and work accidents (1.27), as well as multiple infectious conditions, including hepatitis B (1.55), hepatitis C (2.15), and syphilis (2.43), with an overall trend toward increased all-cause mortality (1.32, 95% CI [1.00–1.74]). These findings suggest that asymptomatic Toxoplasma infection in young adults is associated with increased long-term behavioral and medical comorbidity. Full article