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

Toxoplasmosis is a cosmopolitan zoonotic infection, caused by a unicellular protozoan parasite known as Toxoplasma gondii that belongs to the phylum Apicomplexa. It is estimated that over one-third of the world's population has been exposed and are latently infected with the parasite. In humans, toxoplasmosis is predominantly asymptomatic in immunocompetent persons, while among immunocompromised individuals may be cause severe and progressive complications with poor prognosis. Moreover, seronegative pregnant mothers are other risk groups for acquiring the infection. The life cycle of T. gondii is very complex, indicating the presence of a plurality of antigenic epitopes. Despite of great advances, recognize and construct novel vaccines for prevent and control of toxoplasmosis in both humans and animals is still remains a great challenge for researchers to select potential protein sequences as the ideal antigens. Notably, in several past years, constant efforts of researchers have made considerable advances to elucidate the different aspects of the cell and molecular biology of T. gondii mainly on microneme antigens, dense granule antigens, surface antigens, and rhoptry proteins (ROP). These attempts thereby provided great impetus to the present focus on vaccine development, according to the defined subcellular components of the parasite. Although, currently there is no commercial vaccine for use in humans. Among the main identified T. gondii antigens, ROPs appear as a putative vaccine candidate that are vital for invasion procedure as well as survival within host cells. Overall, it is estimated that they occupy about 1%–30% of the total parasite cell volume. In this review, we have summarized the recent progress of ROP-based vaccine development through various strategies from DNA vaccines, epitope or multi epitope-based vaccines, recombinant protein vaccines to vaccines based on live-attenuated vectors and prime-boost strategies in different mouse models.
Animals ; Antigens, Surface ; Apicomplexa ; Cell Size ; Epitopes ; Humans ; Immunization ; Life Cycle Stages ; Mice ; Molecular Biology ; Mothers ; Parasites ; Prognosis ; Toxoplasma* ; Toxoplasmosis ; Vaccines ; Vaccines, DNA ; Vaccines, Synthetic ; Zoonoses

Adult ; Hematopoietic Stem Cell Transplantation ; Humans ; Magnetic Resonance Imaging ; Male ; Toxoplasma ; Toxoplasmosis, Cerebral ; diagnosis ; therapy ; Young Adult

OBJECTIVE: To investigate the infection rate of Toxoplasma gondii in patients with hematological diseases. METHODS: The Toxoplasma gondii IgM antibody in 200 patients with hematological diseases were tested, at the same time, IgM antibody in the persons received physical examination and other patients with common clinical diseases also were test, and their detection results were compared. RESULTS: The positive rate of Toxoplasma gondii IgM antibody in patients with hematological diseases was 7.50%, the positive rate in persons received physical examination was 0.67%, and the positive rate in patients with other common clinical diseases was 1.20%. The positive rate of IgM antibody in patients with hematological diseases was statistically significantly higher than that in the latter two kinds of persons(P<0.05). Among the patients with hematological diseases, the positive rate of Toxoplasma gondii IgM antibody in patients with bone marrow neoplastic diseases was 10.32%, which was statistically significantly higher than that in patients with bone marrow non-neoplastic diseases (2.70%). CONCLUSION Patients with hematological diseases are susceptible to Toxoplasma gondii, and to whom enough attention should be paid.
Antibodies, Protozoan ; Hematologic Diseases ; complications ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Toxoplasmosis ; complications

Both Plasmodium spp. and Toxoplasma gondii are important apicomplexan parasites, which infect humans worldwide. Genetic analyses have revealed that 33% of amino acid sequences of inner membrane complex from the malaria parasite Plasmodium berghei is similar to that of Toxoplasma gondii. Inner membrane complex is known to be involved in cell invasion and replication. In this study, we investigated the resistance against T. gondii (ME49) infection induced by previously infected P. berghei (ANKA) in mice. Levels of T. gondii-specific IgG, IgG1, IgG2a, and IgG2b antibody responses, CD4+ and CD8+ T cell populations were found higher in the mice infected with P. berghei (ANKA) and challenged with T. gondii (ME49) compared to that in control mice infected with T. gondii alone (ME49). P. berghei (ANKA) + T. gondii (ME49) group showed significantly reduced the number and size of T. gondii (ME49) cysts in the brains of mice, resulting in lower body weight loss compared to ME49 control group. These results indicate that previous exposure to P. berghei (ANKA) induce resistance to subsequent T. gondii (ME49) infection.
Amino Acid Sequence ; Animals ; Antibody Formation ; Body Weight ; Brain ; Humans ; Immunoglobulin G ; Malaria ; Membranes ; Mice ; Parasites ; Plasmodium berghei ; Plasmodium ; Toxoplasma ; Toxoplasmosis