Treatment Of Cerebral Toxoplasmosis Research Articles

Neuroimaging in the diagnosis and treatment of cerebral toxoplasmosis in children with severe β-thalassemia after allo-HSCT.

Children with severe β-thalassemia major (β-TM) are at high risk of developing toxoplasmosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of this study was to identify the neuroimaging findings of cerebral toxoplasmosis in pediatric patients with β-TM for early diagnosis and treatment of cerebral toxoplasmosis. We performed a retrospective assessment of clinical and neuroimaging data of children with severe β-TM who had cerebral toxoplasmosis after allo-HSCT. Additionally, we reviewed and summarized the literature on cerebral toxoplasmosis in patients with other underlying conditions. This case series identified three children who had severe β-TM and had subsequent cerebral toxoplasmosis after allo-HSCT. In addition, we identified 23 patients from literature who had toxoplasmosis and had underlying conditions other than β-TM. We found that the most common clinical symptom among the patients from our series and the patients from literature was fever upon presentation. We identified the typical neuroimaging findings including brain lesions with ring enhancement and eccentric/central nuclear target-like enhancement, which should facilitate early diagnosis and treatment of cerebral toxoplasmosis.

Iron-overload-induced ferroptosis in mouse cerebral toxoplasmosis promotes brain injury and could be inhibited by Deferiprone.

Iron is a trace metal element that is essential for the survival of cells and parasites. The role of iron in cerebral toxoplasmosis (CT) is still unclear. Deferiprone (DFP) is the orally active iron chelator that binds iron in a molar ratio of 3:1 (ligand:iron) and promotes urinary iron excretion to remove excess iron from the body. The aims of this experiment were to observe the alterations in iron in brains with Toxoplasma gondii (T. gondii) acute infections and to investigate the mechanism of ferroptosis in CT using DFP. We established a cerebral toxoplasmosis model in vivo using TgCtwh3, the dominant strains of which are prevalent in China, and treated the mice with DFP at a dose of 75 mg/kg/d. Meanwhile, we treated the HT-22 cells with 100 μM DFP for half an hour and then infected cells with TgCtwh3 in vitro. A qRT-PCR assay of TgSAG1 levels showed a response to the T. gondii burden. We used inductively coupled plasma mass spectrometry, an iron ion assay kit, Western blot analysis, glutathione and glutathione disulfide assay kits, a malonaldehyde assay kit, and immunofluorescence to detect the ferroptosis-related indexes in the mouse hippocampus and HT-22 cells. The inflammatory factors interferon-γ, tumor necrosis factor-α, transforming growth factor-β, and arginase 1 in the hippocampus and cells were detected using the Western blot assay. Hematoxylin and eosin staining, electron microscopy, and the Morris water maze experiment were used to evaluate the brain injuries of the mice. The results showed that TgCtwh3 infection is followed by the activation of ferroptosis-related signaling pathways and hippocampal pathological damage in mice. The use of DFP led to ferroptosis resistance and attenuated pathological changes, inflammatory reactions and T. gondii burden of the mice, prolonging their survival time. The HT-22 cells with TgCtwh3 activated the ferroptosis pathway and was inhibit by DFP in vitro. In TgCtwh3-infected cells, inflammatory response and mitochondrial damage were severe, but these effects could be reduced by DFP. Our study elucidates the mechanism by which T. gondii interferes with the host's iron metabolism and activates ferroptosis, complementing the pathogenic mechanism of CT and further demonstrating the potential value of DFP for the treatment of CT.

Detection and treatment of cerebral toxoplasmosis in an aplastic pediatric post-allogeneic hematopoietic cell transplant patient: a case report

BackgroundCerebral toxoplasmosis infection presents with non-specific neurologic symptoms in immunocompromised patients. With lack of measurable adaptive immune responses and reluctance to sample affected brain tissue, expedient diagnosis to guide directed treatment is often delayed.Case presentationWe describe the use of cerebrospinal fluid polymerase chain reaction and plasma cell-free DNA technologies to supplement neuroimaging in the diagnosis of cerebral toxoplasmosis in an immunocompromised pediatric patient following allogeneic hematopoietic cell transplantation for idiopathic severe aplastic anemia. Successful cerebral toxoplasmosis treatment included antibiotic therapy for 1 year following restoration of cellular immunity with an allogeneic stem cell boost.ConclusionsPlasma cell-free DNA technology provides a non-invasive method of rapid diagnosis, improving the likelihood of survival from often lethal opportunistic infection in a high risk, immunocompromised patient population.

USE OF MIDDLE-FIELD MRIWITH SPECIFIC SEQUENCIES COMPENSATING THE MOVEMENT ARTEFACTS FOR BRAIN STUDIES IN PATIENTS WITH HIV INFECTION

Nowadays of great importance is not only the issue of early diagnosis of HIV infection, but of early detection and effective treatment of AIDS complications. The annual increase in the incidence of HIV infection amounts to 4%. Unfortunately, a great number of patients ask for hospital care when their disease has the stage of secondary complications. Such situation requires a fast and affordable diagnostics together with verification of the nature of the affection. Purpose. To evaluate the diagnosis effectiveness of the secondary infectious cerebral affection in patients with HIV infection using the method of non-contrast MRI including the usage of the specially developed software. One hundred thirty three patients were recruited for the study, the main group of 108 persons (as old as 36,8±8,3), all referred to the brain MRI with suggestion of neurologic complications of HIV. The control group comprised 25 patients of the same age with focal damage of vascular nature. In everybody the MRI has been carried out using open middle-field scanner (Az-360, by AZ plc company, Moscow) with field induction 0,4 T, supplied with wireless four-channel quadratur coil for head studies, without contrast enhancement, but using in everybody the specially designed protocols for compensation of movement artifacts. All patients were re-examined in 2, 4 and 6 weeks. MRI images both in first admission and in follow-up studies were reported first qualitatively by type of contour of pathologic focus, by presence of multiple pattern of focal damage, by ultrastructure of foci, extent of perifocal oedema, interhaemispheric dislocation; also the dimensions of lateral ventriculi, of external subarachnoidal spaces and thickness of cortex in various regions were measured. Focal cerebral damage verified later as toxoplasmosis was revealed in the main group in 80% (86 of 108) of patients. False-negative and false-positive conclusions of MRI studies were not revealed also in prospective follow-up studies. Of these in 69 (80,2%) the pathologic foci were multiple and did localize periventricularly in particular in putamen, nucleus caudatus, equally frequent for both haemispherae, single foci were detected in thalami, concomitant with tendency to extensive cortical dystrophy. The putamen region was involved more frequently as compared to other basal ganglii (р=0,003). No significant differences were revealed between various cortical regions as regard to frequency of detection of pathologic foci. Four weeks period was detected as being the most effective time for the dynamic control in the course of treatment. Conclusion. Middle-field MRI of the brain with compensation of movement artifacts is a proper technique for both the diagnosis and follow-up control of treatment of cerebral toxoplasmosis in patients with HIV infection.

Cerebral Toxoplasmosis in a Treatment Naive HIV Patient with High CD4 Count Responding to Treatment with a Regime of Cotrimoxazole and Pyrimethamine: Do We Need to Start Prophylaxis for Toxoplasmosis at a Higher CD4 Count?

Cerebral toxoplasmosis is one of the commonest opportunistic infection of the nervous system in HIV patients. We present a case of gradual onset haemiparesis in an ART naive HIV patient with high CD4 count who was subsequently diagnosed to be a case of cerebral toxoplasmosis based on radiological and serological investigations. The patient responded to a regime of Cotrimoxazole and Pyrimethamine. His CD4 count at diagnosis was 299/μl. HAART was started after completion of treatment of cerebral toxoplasmosis. Prophylaxis against toxoplasmosis is recommended with cotrimoxazole if the CD4 count is below 200/μl. However, in this case as the patient had developed toxoplasmosis at a CD4 count value above the cut-off value for prophylaxis for cerebral toxoplasmosis, it may be worth considering to starting prophylaxis at a higher CD4 count than 200/μl and continuing for a longer time than the current guidelines.

Evolution of cytokine profile during the treatment of cerebral toxoplasmosis in HIV-infected patients

This study was to follow IFN-γ, TNF-α and IL-10 modulation of peripheral blood mononuclear cells (PBMC) from HIV/cerebral toxoplasmosis patients (CT) during specific treatment. The results were compared with two other groups: HIV patients that had CT at least one year before (P/CT) and individuals with chronic toxoplasmosis (CHR). Blood samples (63) collected from three groups were analyzed. CT, 15 patients (3 blood samples collected one day before Toxoplasma gondii treatment; 7 and 15days during the treatment). P/CT, 5 patients (one blood sample collected at least, one year after the treatment). CHR, 13 individuals with chronic toxoplasmosis (one blood sample). Cytokine levels were assessed by ELISA after PBMC stimulation with T. gondii antigen. CT patients had low IFN-γ; discrete increase at 7th and 15th days; and the levels were recovered in cured patients (P/CT). CT patients had high TNF-α in the beginning of the treatment. TNF-α levels decrease during the treatment (7th and 15th) and in those patients who were treated (P/CT). IL-10 levels were almost similar in CT and P/CT groups but low when compared with CHR individuals. The evolution of the infection was correlated to restoration of IFN-γ response and a decrease of the inflammation. The evaluation of the immune response can provide valuable information and better monitoring of patients during specific treatment.

Small Bowel Kaposiʼs Sarcoma: An Unusual Cause of GI Bleeding

Purpose: A 34-year-old previously healthy man presented with 1 week of melena and new right sided hemiplegia for 1 month. Initial hemoglobin was 6 g/dL from a baseline of 13.5 g/dL two years prior. Brain MRI showed two ring enhancing lesions in the left cortex and cerebellum suspicious for toxoplasmosis. An HIV antibody test was positive, with a CD4 count of 1. An upper endoscopy was performed and showed white adherent material in the esophagus (biopsy pathology positive for candidiasis), gastric erythema and normal duodenum without a bleeding source. Colonoscopy showed normal terminal ileal and colonic mucosa. A capsule endoscopy demonstrated a raised medium-sized submucosal erythematous mass in the mid-jejunum, suspicious for Kaposi's sarcoma (KS). A detailed skin exam yielded a violaceous plaque on the abdomen, with biopsy pathology diagnostic of KS. The patient was started on antiretroviral therapy (ART) and treatment for cerebral toxoplasmosis, with no further episodes of melena. KS is a vascular tumor that is associated with human herpesvirus 8 and is the most common tumor arising in HIV-infected persons. Its prevalence is increased with lower CD4 counts. KS was over 20,000 times more common in persons with AIDS than in the general population prior to the widespread use of highly active antiretroviral therapy (HAART), and the incidence has declined substantially since that time. Although KS can involve virtually any site in the body, cutaneous disease is most common and is the usual initial presentation for KS. The most frequent sites of noncutaneous disease are the oral cavity, gastrointestinal tract (most commonly the small intestine) and respiratory system. Prior to widespread ART, the gastrointestinal tract was involved in approximately 40% of patients with KS at initial diagnosis, and in up to 80% at autopsy. However, visceral involvement as the initial manifestation of KS in the HAART era is relatively uncommon. GI lesions may be asymptomatic or cause weight loss, abdominal pain, nausea and vomiting, upper or lower gastrointestinal bleeding, malabsorption, intestinal obstruction or diarrhea. On endoscopy, KS lesions are easily recognized as hemorrhagic nodules that can appear anywhere along the GI tract. In the HAART era the incidence of AIDS-related KS has dramatically decreased to less than 10% of the incidence reported in the pre-HAART era, but it is still recognized as a primary AIDS-defining illness that can lead to significant morbidity. Rarely, visceral KS can present as occult or gross GI bleeding. In persons with underlying AIDS presenting with anemia and/or GI bleeding, it is important for physicians to consider intestinal KS as a possible etiology.

Is it all cerebral toxoplasmosis?

A 43-year-old Nigerian man presented in April, 2010, with a 1 week history of progressive left leg weakness, urinary incontinence, and weight loss. Neurological examination showed left-sided neglect and hemiparesis. Physical examination was otherwise unremarkable. Blood test results were normal. MRI of the brain showed multiple bilateral ring-enhancing lesions; the largest was centred on the right basal ganglia with pronounced mass eff ect (fi gure A). Treatment for cerebral toxoplasmosis was initiated with sulfadiazine (15 mg/kg, four times daily), pyrimethamine (200 mg loading dose followed by 75 mg daily), and folinic acid (10 mg daily). IgG active against toxoplasma was detected and HIV-1 infection was confi rmed with a baseline viral load of 870 976 copies/mL and CD4 T-cell count of 68 cells/μL (11%). Left arm tone and power normalised after 24 h of treatment, but there was residual left leg weakness and over the next 2 weeks our patient developed a new rightsided hypertonia and he became progressively mute. Repeat MRI showed moderate improvement of the changes in the right hemisphere with reduction of vasogenic oedema (fi gure B). There was, however, a gradual progression of a solid mass in the left corona radiata on MRI; on fl uorine-18-labelled fl uorodeoxyglucose PET-CT (done 3 weeks after presentation) it showed signifi cantly higher uptake than the other lesions, which had lower uptake than normal cortex (see webappendix). These fi ndings suggested dual pathology, with lymphoma being the most likely secondary diagnosis. Despite initiation of highly active antiretroviral therapy and high-dose dexamethasone, our patient became less responsive and had generalised seizures necessitating ventilation 4 weeks after the initial presentation. A biopsy of the solid mass in the left hemisphere confi rmed primary cerebral diff use large B-cell lymphoma. We started our patient on high-dose methotrexate then cytarabine but there was no improvement. 8 weeks after initial presentation, treatment was withdrawn and the patient died on July 3, 2010. Cerebral toxoplasmosis is one of the commonest presenting diagnoses in advanced HIV disease. Primary cerebral lymphoma is uncommon, but over 30% of cases are associated with HIV infection. Diff erentiation of the two pathologies is diffi cult owing to the similar clinical and radiological presentation, but MRI and PET are the imaging modalities of choice, and tissue diagnosis is the gold standard. Prognosis in HIV-infected patients with primary cerebral lymphoma is poor, with median survival of 2 months, but antiretroviral therapy may improve life expectancy. The choice of chemotherapy tends to be a methotrexate-based regimen with a combination of other agents such as vincristine or cytarabine. This case serves as a reminder of the complexity of patients with late presentation of HIV infection in the UK, where the Health Protection Agency estimates that around 30% of individuals with HIV infection are undiagnosed and a similar percentage of those diagnosed present late. The HIV-infected population is predicted to reach 100 000 by 2012, therefore, the proportion of undiagnosed patients and late presenters must be reduced. Recent guidance from the Health Protection Agency recommends implementation of screening in health-care settings where the prevalence of HIV infection is higher than 2 per 1000, which may help to achieve this goal.

Penetration of clindamycin and its metabolite N-demethylclindamycin into cerebrospinal fluid following intravenous infusion of clindamycin phosphate in patients with AIDS.

Clindamycin, which is usually used in combination with pyrimethamine, has been proven effective in the treatment of cerebral toxoplasmosis in human immunodeficiency virus-infected patients. However, it is not known if clindamycin achieves inhibitory concentrations at the site of infection. Also, it has been hypothesized that the activity of clindamycin against Toxoplasma gondii may be due, at least in part, to a metabolite. We evaluated the penetration of clindamycin and its major metabolite, N-demethylclindamycin (NDC), into cerebrospinal fluid (CSF) of AIDS patients undergoing lumbar puncture for diagnostic purposes. A single, 1,200-mg dose of clindamycin was administered as a 45-min intravenous infusion beginning at 1.5 or 2.5 h before CSF sampling. The concentrations of clindamycin in CSF ranged from 0.091 to 0.429 mg/liter at 1.5 h and from 0.120 to 0.283 mg/liter at 2.5 h following the beginning of the infusion. The concentrations of clindamycin in CSF were well above the 50% inhibitory concentration of 0.001 mg/liter and the parasiticidal concentration of 0.006 mg/liter. NDC was undetectable both in plasma and in CSF. Our study provides a pharmacokinetic rationale for the clinical efficacy of clindamycin in the treatment of cerebral toxoplasmosis.

Failure of atovaquone in the treatment of cerebral toxoplasmosis

Durand, J-M.; Cretel, E; Bagneres, D.; Guillemot, E.; Kaplanski, G.; Soubeyrand, J. Author Information

Sulfadiazine desensitisation allows continued treatment of cerebral toxoplasmosis in allergic patients

Sulfadiazine desensitisation allows continued treatment of cerebral toxoplasmosis in allergic patients

Synthesis, characterization and in vitro evaluation of various sulfonamide chemical delivery systems

Abstract Dihydropyridine a3 pyridinium salt type chemical delivery systems were prepared for several sulfonamides found useful in the treatment of cerebral toxoplasmosis. Sulfadiazine, sulfamethoxazole, sulfamerazine and sulfamethazine were considered and both aniline (N4) and sulfamide (N1) derivatization were performed. The sulfamethoxazole derivative in which a reduced nicotinamide moiety was attached at the N1-site provided a compound which rapidly oxidized in various matrices and was highly lipophilic. In addition, studies in rat brain homogenates illustrated appropriate conversion of the chemical delivery system with ultimate release of the active sulfa drug.