Brain Toxoplasmosis Research Articles

THU440 A Case Of Osteomalacia In A Young Adult Female With Premature Ovarian Insufficiency

Abstract Disclosure: I.H. Kasimoglu: None. T. Vu: None. J.Q. Dai-Ju: None. Background: Osteomalacia is a condition due to inadequate mineralization during the bone-remodeling process. Common causes of bone demineralization include Vitamin D deficiency and low calcium intake. Consequently, the treatment often involves both Vitamin D and calcium supplementation, corresponding dietary modifications, and adequate exposure to sunlight. Clinical Case: 34-year-old female with past medical history of sickle cell disease s/p allogenic bone marrow transplant in 11/2020, brain toxoplasmosis infection 3/2021, secondary amenorrhea due to premature ovarian insufficiency diagnosed in 12/2021, was referred to endocrinology for management of osteomalacia. Dexa Scan from 11/2021 reported lower bone density than expected compared with the same age/gender group (Z-Scores: Left Hip – 0.3, Neck –1.4, and L1-L4 –3.6). Vitamin D 25-OH level was 8.3 (n>30) ng/mL and serum calcium level as low as 5.8 (n8.6-10.3) mg/dL in 3/2021, PTH-I elevated to 459 (n10-68) pg/mL, alkaline phosphatase elevated to 166 (n34-104) U/L. The patient was encouraged to increase Vitamin D3 to 4000 iu daily and calcium intake to 1200 mg daily. After discussion with patient of benefits and risks of hormone replacement, patient was started on very low dose of estradiol patch (0.025mg/day) for concern of prior history of pulmonary embolism, and progesterone 100 mg oral daily 3/2022. Vitamin D 25-OH, PTH, serum and 24 hr urine calcium have been within normal range since 9/2022. Dexa Scan from 11/2022 showed significant improvement of bone density (32.0% increase of lumbar spine, 11.2% increase of left hip). This case of osteomalacia resulting from Vitamin D deficiency and subsequent secondary hyperparathyroidism demonstrates that it is imperative to recognize and treat Vitamin D deficiency because it restores bone strength and prevents fractures while simultaneously correcting biochemical abnormalities (1). This case is also interesting as the patient still carries an increased risk of bone density loss complicated by underlying premature ovarian insufficiency and hypoestrogenic state. Thus, by providing patients with the appropriate Vitamin D and calcium supplementation recommendations along with hormone replacement therapy in young adults, it is possible to rehabilitate their overall bone health as well as reduce future risks of fractures. Conclusion: Adequate Vitamin D and calcium supplementation is important for the management of osteomalacia. In patients with premature ovarian insufficiency, it is even more imperative to promote supplementations, dietary modifications, and sunlight exposure in conjunction with traditional agents of hormonal therapy to promote overall bone health. Reference: 1) Bhan A., et al. Osteomalacia as a result of vitamin D deficiency. Endocrinol Metab Clin North Am. 2010;39(2):321–331. 10.1016/j.ecl.2010.02.001 Presentation: Thursday, June 15, 2023

Myasthenia gravis treatment in the elderly presents with a significant iatrogenic risk: a multicentric retrospective study.

Myasthenia gravis (MG) is an autoimmune disease treated with acetylcholinesterase inhibitors and immunosuppressant/immunomodulatory drugs. MG is frequently diagnosed in elderly patients, a fragile population in which treatment adverse effects (TAE) have not been evaluated until now. We retrospectively analysed the files of all MG patients with disease onset after age 70years in four French University Hospitals, including clinical, electrophysiological, biological, and treatment data, with an emphasis on TAE. MG outcomes were assessed using the Myasthenia Gravis Foundation of America (MGFA) status scale. We included 138 patients (59% of men) with a mean follow-up of 4.5years (range 1-19). Mean age at diagnosis was 78years (70-93). Anti-acetylcholine receptor antibodies were found in 87% of cases, electrophysiological abnormalities in 82%, and thymoma in 10%. MG outcome was good in a majority of cases, with 76% of treated patients presenting with alleviated symptoms at follow-up. TAE were observed in 41% of patients, including severe TAE in 14% of cases. Seven patients (5.1%) died, including four (2.9%) from MG-related respiratory failure, and three (2.2%) from MG treatment-related complications, i.e., sepsis in 2 cases and brain toxoplasmosis in 1 case. TAE were observed in 53% of patients treated with azathioprine, 23% of patients treated with corticosteroids, and 15% of patients treated with mycophenolate mofetil. This retrospective study demonstrates MG in the elderly presents with a significant iatrogenic risk, including fatal immunosuppressant-related infections.

UPR-mediated modulation of dendritic cell responses during Toxoplasma gondii infection

The modulation of dendritic cell (DC) functions by intracellular parasites remains poorly investigated. Toxoplasma gondii (Tg) infects a wide range of warm-blooded animals including humans. In immune-competent individuals, acute Tg infection is mostly asymptomatic but the parasite chronically persists in the brain and cerebral chronic toxoplasmosis has recently emerged as an underestimated cause of mental disorders and neurodegenerative pathologies. Tg infection induces a robust Th1 immune response that is initiated by type I conventional DC (cDC1). cDC1-mediated T cell activation is critical to restrict parasite growth during acute toxoplasmosis and T cells play a major role in keeping chronic cerebral infection under control. The induction of the Unfolded Protein Response (UPR) in immune cells has recently emerged as a central response, not only to the accumulation of misfolded proteins in the Endoplasmic Reticulum (ER) but also to cellular metabolic variations and infections. In particular, TLR stimulation in macrophages and DC induces the expression of the XBP1s and CHOP transcription factors, which directly activate inflammatory cytokine production. The UPR also modulates MHC class I antigen presentation in cDC1. We found that Tg infection of Bone Marrow Derived DC (BMDC) triggers the IRE1α/XBP1 branch of the UPR and that parasite replication is not required to induce this pathway. Using BMDC deleted for XBP1, we demonstrated that the Tg-induced UPR promotes a unique set of pro-inflammatory cytokines in a MyD88-dependent manner. In addition, our in vitro results suggest that the UPR modulates MHC-I presentation of OVA peptides from OVA-expressing parasites. Finally, using reporter mice, XBP1 activation was confirmed in infected mice and specifically detected in splenic cDC1 during the acute phase of the infection. Mice deleted for IRE1α and XBP1 in CD11c+-DC display a severe susceptibility to infection demonstrating the protective role of DC specific activation of the UPR during Tg infection.

Impact of Plant-Based Foods and Nutraceuticals on Toxoplasma gondii Cysts: Nutritional Therapy as a Viable Approach for Managing Chronic Brain Toxoplasmosis.

Toxoplasma gondii is an obligate intracellular parasite that mainly infects warm-blooded animals including humans. T. gondii can encyst and persist chronically in the brain, leading to a broad spectrum of neurological sequelae. Despite the associated health threats, no clinical drug is currently available to eliminate T. gondii cysts. In a continuous effort to uncover novel therapeutic agents for these cysts, the potential of nutritional products has been explored. Herein, we describe findings from in vitro and in vivo studies that support the efficacy of plant-based foods and nutraceuticals against brain cyst burden and cerebral pathologies associated with chronic toxoplasmosis. Finally, we discuss strategies to increase the translatability of preclinical studies and nutritional products to address whether nutritional therapy can be beneficial for coping with chronic T. gondii infections in humans.

Зміни імунологічного статусу у ВІЛ-інфікованих осіб із хронічною токсоплазмозною інвазією та токсоплазмозним енцефалітом

Актуальність. Інвазія Toxoplasma gondii у ВІЛ-інфікованих осіб може призвести до поглибленої імунопатології, що сприяє реактивації брадизоїтів та розвитку тяжких опортуністичних захворювань. Мета дослідження: вивчити особливості імунологічного статусу ВІЛ-інфікованих пацієнтів, які інвазовані токсоплазмами, та визначити предиктори розвитку токсоплазмозу мозку. Матеріали та методи. Обстежено 61 ВІЛ-інфіковану особу (33 особи серопозитивні на токсоплазмоз і 28 — серонегативні). Застосовували імуноферментний метод для визначення титрів специфічних протитоксоплазмозних IgG та IgМ; загальних IgM, IgA, IgG, а також IL-2, -4, -10, INF-γ, TNF-2α. Статистичну обробку здійснювали в статистичному пакеті програми Exсel з використанням t-критерію Стьюдента, а також z-критерію Фішера. Методом Байєса та послідовного статистичного аналізу А. Вальда визначали діагностичну цінність окремих лабораторних показників. Результати. У ВІЛ-інфікованих осіб виявлено дисбаланс цитокінів порівняно зі здоровими особами. У серонегативних на токсоплазмоз пацієнтів були підвищені рівні IL-4 (1,57 ± 0,30 пг/мл проти 0,81 ± 0,09 пг/мл, р < 0,001), IL-10 (9,81 ± 0,17 пг/мл проти 6,70 ± 0,13 пг/мл, р < 0,001), ТNF-2α (2,89 ± 0,08 пг/мл проти 1,90 ± 0,04 пг/мл, р < 0,001), INF-γ (9,30 ± 0,47 пг/мл проти 4,13 ± 0,12 пг/мл, р < 0,001), а також загальний IgG (20,63 ± 0,65 г/л проти 16,30 ± 0,94 г/л, р < 0,001). На відміну від серонегативних осіб у серопозитивних були вищими показники IL-10 (11,88 ± 0,50 пг/мл проти 9,81 ± 0,17 пг/мл, р < 0,05) та INF-γ (10,75 ± 0,44 пг/мл проти 9,30 ± 0,47 пг/мл, р < 0,05). Поєднання 2 ознак — INF-γ < 8,8 пг/мл та IL-4 < 0,77 пг/мл чи INF-γ < 8,8 пг/мл та IL-10 > 11,8 пг/мл або 3 ознак — IL-4 < 0,77 пг/мл, IL-10 > 11,8 пг/мл та IL-2 < 1,5 пг/мл є предиктором розвитку токсоплазмозного енцефаліту. Висновки. Установлено, що у ВІЛ-інфікованих осіб відмічаються підвищені рівні деяких прозапальних (TNF-α, INF-γ) та протизапальних (IL-4, -10) цитокінів, але порівняно із серонегативними в серопозитивних на токсоплазмоз осіб переважають показники INF-γ і IL-10. Проявом поглибленої імунопатології та предиктором розвитку токсоплазмозного енцефаліту є зниження рівня INF-γ, IL-4, -2 із підвищенням рівня IL-10 у контингенті серопозитивних на токсоплазмоз осіб.

Brain Toxoplasmosis and Bacterial Infection after Liver Transplantation.

Brain Toxoplasmosis and Bacterial Infection after Liver Transplantation.

Brain Toxoplasmosis Comorbid with Autoimmune Disease: Complicated Immune Response And Case Demonstration

Toxoplasmosis is an opportunistic infection caused by Toxoplasma gondii (TG), commonly involving the brain. Symptomatic clinical disease of TG infection is much more commonly associated with immunodeficiency; clinicopathological manifestations of brain toxoplasmosis are linked to individual immune responses including brain infiltration of T-cells that are thought to fight against toxoplasmosis. In patients with autoimmune diseases, immune status is typically characterized by T-cell infiltration and complicated mainly by immunosuppressant and/or immunomodulatory treatment. In this study, we demonstrate clinical and radiological features correlated with pathological features of brain toxoplasmosis at different disease stages in a patient with coexisting autoimmune diseases, including systemic lupus erythematosus and autoimmune hepatitis. The infiltration of CD8+ T-cells in toxoplasma immunostaining-positive acute lesions was greater than that in toxoplasma immunostaining-negative chronic lesions. We also review previously reported cases of brain toxoplasmosis with comorbid autoimmune diseases. Our present case and literature review suggest that brain toxoplasmosis in patients with autoimmune diseases may be asymptomatic unless disease complications occur; it may present as an incidental finding at postmortem examination of rapidly developed lesions. T-cell infiltration in patients with autoimmune diseases and coexisting toxoplasmosis may be at least partially reduced; ultimately, the roles of T-cell infiltration in brain toxoplasmosis deserve further investigation.Learning ObjectivesDiscuss complicated immune response to toxoplasmosis in patients with autoimmune diseases.Describe clinical, radiological, and pathological features of brain toxoplasmosis in patients with autoimmune diseases.

CLINICAL FEATURES OF THE HIV INFECTION COURSE AND THE DEPENDENCE OF CHANGES IN LABORATORY PARAMETERS ON THE CLINICAL STAGE AND ON THE CD4 LYMPHOCYTES LEVEL

The aim: Is to determine the features of the HIV infection and changes in indicators of endogenous intoxication and immunoreactivity depending on the clinical stage and the level of CD4 lymphocytes. Materials and methods: 72 HIV-patients were examined. Comparison group included 40 healthy blood donors. Clinical and laboratory examination was performed. Indicators of endogenous intoxication, nonspecific reactivity and inflammatory activity were calculated. Results:Main opportunistic infections were: oropharyngeal candidiasis; tuberculosis of different localization, more often pulmonary tuberculosis; and brain toxoplasmosis (p<0,05). Indices of endogenous intoxication and immunoreactivity are important objective criteria for diagnosis. In groups where the distribution of patients depended on the level of CD4 cells - HIV (CD4≥500) and HIV (CD4≤499-200), index changes were more pronounced than in the HIV I and HIV III groups. The most significant changes in indexes were in the HIV IV clinical group and the HIV (CD4≤199) group: endogenous intoxication indexes were increased by 1,2-7,5 and 1,9-13,7 times in both groups respectively. Non-specific reactivity indexes were decreased by 1,2-1,6 and 1,3-1,6 times, respectively; nuclear index (NI) in groups was 3 and 3,4 times higher (p<0,05-0,001). Changes in indexes of inflammatory activity were observed (p<0,05-0,001). Conclusions: Main diagnosed opportunistic infections were: oropharyngeal candidiasis; tuberculosis of different localization; and brain toxoplasmosis (p<0,05). Indices of endogenous intoxication and immunoreactivity are important objective criteria for diagnosis. The most significant changes in indexes were in the HIV IV clinical group and the HIV (CD4≤199) group (p<0,05-0,001).

Encephalic Toxoplasm in a White-Eared Possum (Didelphis albiventris)

Background: Toxoplasmosis is caused by Toxoplasma gondii, an obligate intracellular protozoan that belongs to the Aplicomplexa phylum, coccidian subclass, and affects all warm-blooded animals. The role of opossums in the epidemiology of toxoplasmosis in Brazil is not fully understood, and there are very few descriptions of toxoplasmosis lesions in these animals. This report describes the anatomopathological, molecular and immunohistochemical findings of a case of encephalic toxoplasmosis in free-living white-eared possum (Didelphis albiventris).Case: A young male opossum (D. albiventris), was treated at the Veterinary Hospital of Wild Animals of the University of Brasília, Federal District. The animal was apathetic, uncoordinated, reluctant to move, and had an exposed proximal fracture in the left radius and ulna with laceration of muscles and adjacent tendinous structures. Amputation on the left thoracic limb was performed followed by analgesia and antibiotic therapy. The environment is frequented by other wild animals, and stray cats have access to the patio of the building. Twenty-five days after arriving at the hospital, the animal was found dead in its cage. After death, a necropsy was performed. Organ fragments from the abdominal cavity, thoracic and central nervous system were collected, processed routinely for histology and stained with hematoxylin and eosin. Macroscopic lesions in the central nervous system were not observed. On microscopy, the brain showed moderate random glial nodules throughout the neuropil associated with the presence of spherical to elongated parasitic cysts of about 20 µm, with a thin wall and with its interior full of bradyzoites, consistent with Toxoplasma gondii. There was also moderate fibrinoid necrosis and moderate multifocal lymphoplasmacytic infiltrate surrounding the blood vessels (perivascular cuffs) To investigate the etiology of the brain injury, brain sections were subjected to immunohistochemistry (IHC) and real-time polymerase chain reaction (qPCR) technique for detection of T. gondii and Neospora caninum. Immunostaining for T. gondii in the cyst wall and in bradyzoites and negative immunostaining for N. caninum. qPCR was positive for T. gondii and negative for N. caninum.Discussion: Diagnosis of encephalic toxoplasmosis in a Didelphis albiventris was possible based on histopathological, immunohistochemical and molecular findings. The morphological classification of the brain lesion was important for the diagnosis. Brain toxoplasmosis in opossums usually results in focal areas of malacia on macroscopy and focally extensive necrosis on microscopy, neutrophil infiltrate, calcified necrotic material, and perivascular cuffs of lymphocytes and plasma cells. In the present case, similar histopathological lesions were noted, but no significant macroscopic changes were observed. The etiology here was defined by immunohistochemistry and qPCR, techniques proven to be useful and with good specificity for diagnosing toxoplasmosis in mammals. It is believed that the positive immunohistochemical and molecular result for Toxoplasma gondii together with the negative result for Neospora caninum were conclusive for the diagnosis. Thus, we demonstrate here a post mortem diagnosis of toxoplasmosis in a free-living synanthropic opossum and the use of anatomopathology, immunohistochemistry and real-time polymerase chain reaction as a diagnostic option for this disease in opossums. Keywords: Toxoplasma gondii, marsupial, immunohistochemistry, Real time PCR, protozoal encephalitis.Título: Toxoplasmose encefálica em um gambá-de-orelha-branca (Didelphis albiventris)Descritores: Toxoplasma gondii, marsupial, imuno-histoquímica, Real time PCR, encefalite protozoal.

Investigation the Prevalence of Common Parasitic Infections in Farmed Quails in Upper Egypt

The present study was conducted to investigate the prevalence and identification of most common parasitic infections of quails and to determine their seasonal variation. One hundred diseased quails (60 quails in summer and 40 quails in winter) were obtained from quail farms in different localities of Assiut and El-menia Governorates and were examined for the presence of ectoparasites, endoparasites, intestinal protozoa, blood protozoa and parasites of other organs (lungs, brain and liver). Results revealed that neither ectoparasites nor macroscopic parasites were observed in the examined quails. Mainly, the encountered parasites were intestinal protozoa (44%), blood protozoa (25%) and parasites of other organs (28%). The overall parasitic infection rate in the examined quails was higher in cold season (57%) than warm season (53%). The intestinal protozoa were identified including Eimeria spp. (30%), Cryptosporidium spp. (19%), Tetratrichomonas galinarum (15%), Cyclospora spp. (4%), Isospora spp. (3%) and Microsporidia spp. (3%). The prevalence rate of intestinal protozoal infection was higher in warm season 46.6% (28 out of 60 examined birds) than cold seasons 40% (16 out of 40 examined birds). The incidence rate of mixed intestinal protozoal infection was higher (24.8%) than the single infection (18.8%). The blood protozoa were reported including Leucocytozoon spp. (9%), Babesiosoma spp. (8%), Aegyptianella spp. (7%), Plasmodium gallinaceum (4%), Haemoproteus spp. (4%), Atoxoplasma spp. (1%) and Ehrlichia spp. (1%). The prevalence of parasitic infection in other organs showed that respiratory tract (trachea and lung) infection with Cryptosporidium spp. (24%), hepatic histomoniasis (3%) and brain toxoplasmosis (7%).

Incidence of epilepsy and brain toxoplasmosis in hospital Mario Rivas, Honduras

The presence of neurological alterations is a frequent manifestation in patients with HIV, especially focal onset epilepsy. The cerebral toxoplasmosis represents the main cause of occupational injury in an immunological patient for HIV related to a CD4 T lymphocyte count less than 100/uL. A descriptive, cross-sectional study was carried out in which the clinical characteristics associated with cerebral toxoplasmosis were determined, as well as the alterations in the main encephalographic alterations and the findings in neuroimaging studies (cranial tomography or cerebral magnetic resonance). All patients underwent a complete medical history including history of neurological diseases. A total of 26 patients with a diagnosis of HIV-AIDS infection and cerebral toxoplasmosis were evaluated, of which 15 (57.7%) were women. The age of the patients ranged between 23 and 65 years (standard deviation 11,081). The manifestation by which the patients were admitted (main symptom) were altered state of consciousness (2, 7.7%), acute psychotic outbreak (4, 15.3%), headache (1, 3.8%), seizures (10, 38.5 %), focal motor deficit (5, 19.2%), vertigo (1, 3.8%), diarrhea (1, 3.8%), fever (1, 3.8%) and alteration of cranial nerves (1, 3.8%). Differents findings was found in patients: slow-wave, spike-slow wave complex, polymorphic slow wave. Toxoplasmosis is a frequent opportunistic infection in patients with HIV, with epilepsy being one of the main manifestations of this. Neuroimaging studies (brain CT or brain MRI) allow diagnosis. The encephalogram study is frequently associated with alterations in patients with toxoplasmosis. Timely diagnosis is associated with a good prognosis in our patients.

Resveratrol as a Therapy to Restore Neurogliogenesis of Neural Progenitor Cells Infected by Toxoplasma gondii.

The intracellular protozoan Toxoplasma gondii may cause congenital toxoplasmosis and serious brain damage in fetus. However, the underlying mechanism of neuropathogenesis in brain toxoplasmosis remains unclear. For this study, neural progenitor cells (NPCs) were obtained from embryo telencephalons (embryonic day 13) and induced to proliferation in the presence of growth factors (GFs). For gathering insights into the biological effects of resveratrol (RSV) on neurogenesis, this study aimed to investigate effects of RSV concentrations (0.1 to 100μM) on proliferation, migration and differentiation of NPCs infected by T. gondii. T. gondii infection increased the presence of cells in Sub G1 phase, reducing the global frequency of undifferentiated cells in S and G2/M phases of cell cycle and reduced cell viability/mithochondrial activity of infected NPCs. Moreover T. gondii stimulated neural migration and gliogenesis during neutral differentation. However, the treatment with RSV stimulated cell proliferation, restored cellular viability of infected NPCs and exerted an inhibitory effect on gliogenesis of infected NPCs favorecing neuronal maturation during toxoplasmosis infection. Thus, we have successfully to demonstrated that RSV is promising as therapeutic for congenital toxoplasmosis.

Comparative transcriptome analysis of zebrafish (Danio rerio) brain and spleen infected with Spring Viremia of Carp Virus (Abstract)

SVCV is the pathogen of spring viremia of carp (SVC) and often causes acute hemorrhagic symptoms in various kinds of cyprinids and induces serious environmental and economic losses. However, the molecular mechanisms of infection remain poorly understood, especially at the individual level. In this study, zebrafish was employed as the infection model to explore the pathogenesis of SVCV. 4 groups of zebrafish tissues were set and RNA sequencing (RNA-Seq) technology was employed to analyze the differentially expressed genes (DEGs) after SVCV-infection. A total of 360,971,498 clean reads were obtained from 12 samples, 382 DEGs in the brain and 926 DEGs in the spleen were identified. These DEGs were annotated into three ontologies after gene ontology (GO) enrichment analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEGs were primarily related to Influenza A pathway and Herpes simplex infection pathway in brain and Tuberculosis and Toxoplasmosis pathways in spleen, and all of these pathways may be involved in response to pathogen invasion. At the same time, 3’ and 5’ alternative splicing (AS) events were significantly up-regulated in the spleen. The transcriptome analysis results demonstrated changes and tissue-specific influences caused by SVCV in vivo, which provided us with more information to understand the complex relationships between SVCV and its host.

THE EVALUATION OF DELAYED ENHANCEMENT METHOD AS A TOOL FOR MAGNETIC RESONANCE DIFFERENTIATION BETWEEN THE METASTASES AND NEUROTOXOPLASMOSIS

The aimof this study was to evaluate delayed enhancement as the tool for differentiation between metastatic brain lesions and neurotoxoplasmosis.Materials and methods.38 patients with multiple brain lesions with mass-effect and ring-type of contrast enhancement based on CT/MRI have been enrolled in the study. All cases were associated with metastatic brain lesions or toxoplasmosis. For every patient we performed contrast enhanced brain MRI and achieved axial T1WI immediately after contrast injection, in 15, 30 and 45 min. Acquired images were evaluated for the presence of contrast accumulation at delayed images in the central part of the lesions. Overall, we analyzed data for 153 lesions with 64 toxoplasmosis lesions and 89 metastatic.Results.Among 153 lesions with ring-type contrast enhancement central contrast enhancement at delayed images was determined for 83 lesions. Among 89 metastatic lesions 81 demonstrated delayed central enhancement. Among 64 neurotoxoplasmosis lesions only 2 demonstrated delayed central enhancement. The sensitivity of the sign was 88%, specificity 95%.Conclusions.The presence of central contrast enhancement at delayed images significantly increases the probability of metastatic nature of the lesions (specificity 95%). Consequently that sign might be effectively used for the differential between the metastases and neurotoxoplasmosis.

Acute confusional state and holocranial headaches as symptoms of previously asymptomatic HIV positive patient with brain toxoplasmosis

Background: Even when considering previously healthy individuals, the combination of fever, headache, and neurological deficits should immediately strike as a possible immunossupressed patient.

Comparative transcriptome analysis of zebrafish (Danio rerio) brain and spleen infected with spring viremia of carp virus (SVCV)

Spring viremia of carp virus (SVCV) is the pathogen of spring viremia of carp (SVC) and often causes acute hemorrhagic symptoms in various kinds of cyprinids and induces serious environmental and economic losses. However, the molecular mechanisms of infection remain poorly understood, especially at the individual level. In this study, zebrafish was employed as the infection model to explore the pathogenesis of SVCV. 4 groups of zebrafish tissues were set and RNA sequencing (RNA-Seq) technology was employed to analyze the differentially expressed genes (DEGs) after SVCV-infection. A total of 360,971,498 clean reads were obtained from 12 samples, 382 DEGs in the brain and 926 DEGs in the spleen were identified. These DEGs were annotated into three ontologies after gene ontology (GO) enrichment analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEGs were primarily related to Influenza A pathway and Herpes simplex infection pathway in brain and Tuberculosis and Toxoplasmosis pathways in spleen, and all of these pathways may be involved in response to pathogen invasion. At the same time, 3′ and 5′ alternative splicing (AS) events were significantly up-regulated in the spleen. The transcriptome analysis results demonstrated changes and tissue-specific influences caused by SVCV in vivo, which provided us with more information to understand the complex relationships between SVCV and its host.

Application of diffusion tensor imaging in AIDS patients with brain opportunistic diseases: A comparative study of tuberculosis and toxoplasmosis

ObjectiveThis paper aims to discuss the diagnostic value of quantitative DTI on AIDS patients with brain tuberculosis or toxoplasmosis. Materials and methods22 subjects (12 with brain tuberculosis and 10 with toxoplasmosis) were recruited, who underwent routine MRI, T1WI-CE and DTI imaging sequence. The morphological characteristics of lesions were observed, and FA and ADC values of the solid areas, edematous areas and the contralateral normal areas of the lesions were calculated. Results were compared by one-way ANOVA and independent sample t-test. The TB diagnosis efficiency of these two values was analyzed by ROC curve. ResultsADC and FA values were detected with significant differences among the three regions between subjects with brain tuberculosis and subjects with toxoplasmosis (P < 0.05). Statistically significant difference was recorded between solid and edematous areas and contralateral areas in ADC and FA values (P < 0.05). And so was between the solid areas and edema areas in either group. Moreover, the FA values of the solid areas between two groups also presented statistically significant difference (P < 0.01). ROC curve of TB showed the AUC of FA value was larger than that of ADC value (0.914 vs. 0.715, respectively, P < 0.05). DTT imaging showed infiltrative changes of white matter fibers in the lesion areas. ConclusionsQuantitative DTI is valuable for diagnosis and differential diagnosis of patients with AIDS-associated infections, and also could provide references for clinical physicians for proper medications. The quantitative FA value could help better reveal different changes of microstructural integrity between different opportunistic infections.

Optimización de la Reacción en Cadena de la Polimerasa para la Detección del gen B1 de T. gondii

Optimizar las condiciones de amplificación del gen B1 (35 copias en el genoma) para la detección de ADN de T.gondii en casos probables de toxoplasmosis cerebral. Materiales y métodos: Se realizó extracción de ADN a partir de exudado peritoneal de ratones inoculados con la cepa RH de T. gondii obteniendo 17 mL con una concentración inicial de 1x107 parásitos/mL. Se optimizaron las condiciones de PCR del gen B1. Resultados: Se obtuvo amplificación de un fragmento de 132 pb a partir de ADN obtenido de diluciones seriadas desde 1x106 a 1x10-1 parásitos por mL, estableciéndose un límite de detección de 1 taquizoíto de T. gondii.

Review of Toxoplasmic Encephalitis in HIV Infection; a Case Study

Introduction: Infection with Human Immunodeficiency Virus (HIV) causes a spectrum of clinical problems in multiple organs. It may affect the nervous system directly, producing distinct neurological syndromes, or indirectly, by causing immunodeficiency with a resultant susceptibility to opportunistic infections such as Toxoplasma gondii. Case Presentation: In this case study, we described a 47-year-old man who admitted to our emergency department with fever and confusion progressing from two days before the admission. He was candidate for biopsy 20 days before due to acute onset left-side hemiplegia and right-side ptosis and imaging findings consistent with a brain mass. Due to these findings and positive histories of lung tuberculosis and esophageal diffuse mucosal candidiasis, rapid HIV antibody test was requested, which had a positive result. Then we performed Magnetic Resonance Imaging (MRI) with intravenous contrast showing a ring enhancement lesion in the right basal ganglia suggestive of brain toxoplasmosis. It was confirmed with significant raising of anti-toxoplasmosis IgG. Conclusions: Toxoplasma gondii infection is usually diagnosed by serologic tests. Although, brain imaging is necessary for proper diagnosis and management, its findings are not pathognomonic. Patients with toxoplasmic encephalitis typically experience rapid clinical and even radiologic improvement after initiation of appropriate therapy.

Toxoplasma gondiiinduce apoptosis of neural stem cells via endoplasmic reticulum stress pathway

Toxoplasma gondii is a major cause of congenital brain disease; however, the underlying mechanism of neuropathogenesis in brain toxoplasmosis remains elusive. To explore the role of T. gondii in the development of neural stem cells (NSCs), NSCs were isolated from GD14 embryos of ICR mice and were co-cultured with tachyzoites of T. gondii RH strain. We found that apoptosis levels of the NSCs co-cultured with 1×106 RH tachyzoites for 24 and 48 h significantly increased in a dose-dependent manner, as compared with the control. Western blotting analysis displayed that the protein level of C/EBP homologous protein (CHOP) was up-regulated, and caspase-12 and c-Jun N-terminal kinase (JNK) were activated in the NSCs co-cultured with the parasites. Pretreatment with endoplasmic reticulum stress (ERS) inhibitor (TUDCA) and caspase-12 inhibitor (Z-ATAD-FMK) inhibited the expression or activation of the key molecules involved in the ERS-mediated apoptotic pathway, and subsequently decreased the apoptosis levels of the NSCs induced by the T. gondii. The findings here highlight that T. gondii induced apoptosis of the NSCs through the ERS signal pathway via activation of CHOP, caspase-12 and JNK, which may constitute a potential molecular mechanism responsible for the cognitive disturbance in neurological disorders of T. gondii.