Toxoplasma gondii is a single-celled parasite that infects nearly all warm-blooded animals, including humans (Montoya and Liesenfeld, 2004). It occurs worldwide and can persist for a lifetime in mammals. Humans get infected by eating undercooked meat of animals containing the tissue cysts of this parasite. In immune-competent individuals, T. gondii infection usually does not cause significant clinical symptoms, whereas in pregnant or immunocompromised individuals, T. gondii infection (toxoplasmosis) can cause more serious problems like abortion and even death (Dunn et al., 1999; Wang et al., 2017). A combination of pyrimethamine and sulfadiazine is usually used to treat toxoplasmosis, although it is generally inefficient and causes side effects (Alday and Doggett, 2017). Worse still, there is a lack of vaccines to prevent T. gondii infection in humans or animals.
Toxoplasma/enzymology* ; Animals ; Humans ; Toxoplasmosis ; Mitochondria/enzymology* ; Protozoan Proteins/metabolism*

The most common medications for the treatment of zoonotic toxoplasmosis are pyrimethamine and sulfadiazine, which may cause serious undesirable side effects. Thus, there is an urgent need to develop novel therapeutics. Baicalein (BAI, C₁₅H₁₀O₅) has been shown to perform well against protozoan parasites including Leishmania and Cryptosporidium. In this study, the inhibition efficacy of BAI on Toxoplasma gondii was evaluated using plaque, invasion, and intracellular proliferation assays. BAI effectively inhibited T. gondii (half-maximum inhibitory concentration (IC₅₀)=6.457×10^-5 mol/L), with a reduced invasion rate (33.56%) and intracellular proliferation, and exhibited low cytotoxicity (half-maximum toxicity concentration (TC₅₀)=5.929×10^-4 mol/L). Further investigation using a mouse model shed light on the inhibitory efficacy of BAI against T. gondii, as well as the potential mechanisms underlying its anti-parasitic effects. The survival time of T. gondii-infected ICR mice treated with BAI was remarkably extended, and their parasite burdens in the liver and spleen were greatly reduced compared with those of the negative control group. Histopathological examination of live sections revealed effective therapeutic outcomes in the treatment groups, with no notable pathological alterations observed. Furthermore, alterations in cytokine levels indicated that BAI not only effectively suppressed the growth of T. gondii but also prevented excessive inflammation in mice. Collectively, these findings underscore the significant inhibitory efficacy of BAI against T. gondii, positioning it as a promising alternative therapeutic agent for toxoplasmosis.
Animals ; Toxoplasma/drug effects* ; Flavanones/therapeutic use* ; Mice ; Antiparasitic Agents/therapeutic use* ; Mice, Inbred ICR ; Toxoplasmosis/drug therapy* ; Female

Child ; Humans ; Toxoplasmosis, Cerebral ; Hematopoietic Stem Cell Transplantation ; Thalassemia

Humans ; Toxoplasmosis ; Hematopoietic Stem Cell Transplantation ; Hematologic Diseases

OBJECTIVE: To analyze the RNA binding protein of Toxoplasma gondii (TgDDX39) using bioinformatics technology, and to evaluate the immunogenicity of TgDDX39, so as to provide insights into development of toxoplasmosis vaccines. METHODS: The amino acid sequences of TgDDX39 were retrieved from the ToxoDB database, and the physicochemical properties, transmembrane structure domain, signal peptide sites, post-translational modification sites, coils, secondary and tertiary structures, hydrophobicity, and antigenic epitopes of the TgDDX39 protein were predicted using online bioinformatics tools, incluiding ProtParam, TMHMM 2.0, SignalP 5.0, NetPhos 3.1, COILS, SOPMA, Phyre2, ProtScale, ABCpred, SYFPEITHI and DNA-STAR. RESULTS: TgDDX39 protein was predicted to be an unstable hydrophilic protein with the molecular formula of C₂₁₇₃H₃₄₅₈N₅₉₈O₆₆₁S₁₈, which contained 434 amino acids and had an estimated molecular weight of 49.1 kDa and a theoretical isoelectric point of 5.55. The protein was predicted to have an extremely low possibility of signal peptides, without transmembrane regions, and contain 27 phosphorylation sites. The β turn and random coils accounted for 39.63% of the secondary structure of the TgDDX39 protein, and a coiled helix tended to produce in one site. In addition, the TgDDX39 protein contained multiple B and T cell antigenic epitopes. CONCLUSIONS Bioinformatics analyses predict that TgDDX39 protein has high immunogenicity and contains multiple antigenic epitopes. TgDDX39 protein is a potential candidate antigen for vaccine development.
Humans ; Toxoplasma/metabolism* ; Toxoplasmosis/prevention & control* ; Vaccines ; Epitopes, T-Lymphocyte ; Computational Biology ; Protozoan Proteins/chemistry*

We report a literature review and a case of ocular toxoplasmosis in a patient with multiple drug allergies, who was successfully treated with regular intravitreal clindamycin and subconjunctival dexamethasone. A Malay lady in her twenties presented to us with right eye blurring of vision of 2 weeks duration, which she described as a central scotoma. Visual acuity at presentation was hand movements. Examination revealed intense ocular inflammation. The right eye had anterior segment inflammation of 3+ cells with fine keratic precipitates, whilst the posterior segment revealed papillitis, vitritis, retinitis, choroiditis, vasculitis and hyperpigmented chorioretinal scar inferotemporal to fovea. Ocular coherence tomography showed intraretinal fluid and retinal thickening. Fluorescein angiography showed early hypofluorescence of the lesion with progressive hyperfluorescence and leakage from the optic disc. Immunoglobulin G serology of Toxoplasma gondii was raised and immunoglobulin M levels were normal. The patient developed an allergic reaction with classical antibiotic and antifolate therapy. She was successfully treated with regular two-weekly intravitreal clindamycin and subconjunctival dexamethasone and her best corrected visual acuity was 6/18 at the end of her treatment. Intravitreal injection of clindamycin and subconjunctival dexamethasone is a good option in patients of ocular toxoplasmosis who are allergic to oral medications.
Toxoplasmosis, Ocular

Toxoplasma gondii is a worldwide parasite that can infect almost all kinds of mammals and cause fatal toxoplasmosis in immunocompromised patients. Apoptosis is one of the principal strategies of host cells to clear pathogens and maintain organismal homeostasis, but the mechanism of cell apoptosis induced by T. gondii remains obscure. To explore the apoptosis influenced by T. gondii, Vero cells infected or uninfected with the parasite were subjected to apoptosis detection and subsequent dual RNA sequencing (RNA-seq). Using high-throughput Illumina sequencing and bioinformatics analysis, we found that pro-apoptosis genes such as DNA damage-inducible transcript 3 (DDIT3), growth arrest and DNA damage-inducible α (GADD45A), caspase-3 (CASP3), and high-temperature requirement protease A2 (HtrA2) were upregulated, and anti-apoptosis genes such as poly(adenosine diphosphate (ADP)-ribose) polymerase family member 3 (PARP3), B-cell lymphoma 2 (Bcl-2), and baculoviral inhibitor of apoptosis protein (IAP) repeat containing 5 (BIRC5) were downregulated. Besides, tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1), TRAF2, TNF receptor superfamily member 10b (TNFRSF10b), disabled homolog 2 (DAB2)‍-interacting protein (DAB2IP), and inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) were enriched in the upstream of TNF, TNF-related apoptosis-inducing ligand (TRAIL), and endoplasmic reticulum (ER) stress pathways, and TRAIL-receptor 2 (TRAIL-R2) was regarded as an important membrane receptor influenced by T. gondii that had not been previously considered. In conclusion, the T. gondii RH strain could promote and mediate apoptosis through multiple pathways mentioned above in Vero cells. Our findings improve the understanding of the T. gondii infection process through providing new insights into the related cellular apoptosis mechanisms.
Animals ; Apoptosis ; Chlorocebus aethiops ; Gene Expression Profiling ; Humans ; Mammals/genetics* ; Toxoplasma/genetics* ; Toxoplasmosis/pathology* ; Vero Cells ; ras GTPase-Activating Proteins/genetics*

A 36-year-old-male was admitted complaining of headache, right sided weakness and numbness of upper and lower extremity, and multiple cranial nerve deficits. Cranial magnetic resonance imaging revealed an abscess in the pontomesencephalic junction. Patient was then diagnosed to have Human Immunodeficiency Virus with a CD 4 count of 32 cells/ uL, his CSF assay was positive for Toxoplasmosis IgG and was managed as a case of probable brainstem toxoplasmosis. Patient was treated with Co-Trimoxazole 800/160mg 2 tablets twice a day. Upon discharge the patient clinically improved and was tolerating oral feeding. A repeat cranial magnetic resonance imaging after 6 weeks of antibiotic treatment revealed a decrease of size in the previous lesion. To our knowledge, there are no reported cases in the Philippines that shows the documentation of CNS toxoplasmosis in the brainstem. In this paper, a case of CNS toxoplasmosis in the pons of a newly diagnosed HIV patient is presented and how its course led to a good outcome.
Toxoplasmosis ; Immunocompromised Host

We aimed to assess the risks of
China ; Cryptosporidiosis/microbiology* ; Cryptosporidium/isolation & purification* ; Giardia/isolation & purification* ; Giardiasis/microbiology* ; Humans ; Risk Assessment ; Water Microbiology ; Water Supply/statistics & numerical data*

PURPOSE: This study sought to describe the different clinical features and presentations of primary ocular toxoplasmosis in a setting not demonstrating an outbreak of disease.METHODS: This was a retrospective review of patients presenting to uveitis management services in Auckland and Hamilton, New Zealand between 2003 to 2018 with uveitis and positive toxoplasmosis immunoglobulin M serology.RESULTS: We identified 16 patients with primary acquired toxoplasmosis infection and ocular involvement. The mean age was 53 years. Systemic symptoms were reported in 56% (9 / 16). Visual acuity was reduced to 20 / 30 or less in 50% of patients (8 / 16). A single focus of retinitis without a pigmented scar was the salient clinical feature in 69% (11 / 16). Optic nerve inflammation was the sole clinical finding in 19% (3 / 16). Bilateral arterial vasculitis was the sole clinical finding in 13% (2 / 16). A delay in the diagnosis of toxoplasmosis of more than two weeks occurred in 38% (6 / 16) due to an initial alternative diagnosis. Antibiotic therapy was prescribed in all cases. Vision was maintained or improved in 69% (11 / 16) at the most recent follow-up visit (15 months to 10 years). Relapse occurred in 69% (11 / 16), typically within four years from the initial presentation.CONCLUSIONS: Primary ocular toxoplasmosis presenting in adulthood is a relatively uncommon cause of posterior uveitis in New Zealand. This condition should be considered in any patient presenting with retinitis or optic nerve inflammation without a retinochoroidal scar. This disease tends to relapse; thus, close follow-up is required.
Cicatrix ; Diagnosis ; Follow-Up Studies ; Humans ; Immunoglobulin M ; Inflammation ; New Zealand ; Optic Nerve ; Recurrence ; Retinitis ; Retrospective Studies ; Toxoplasmosis ; Toxoplasmosis, Ocular ; Uveitis ; Uveitis, Posterior ; Vasculitis ; Visual Acuity