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Central nervous system toxoplasmosis with an increased proportion of circulating gamma delta T cells in a patient with hyper-IgM syndrome.

Hyper-IgM syndrome represents a diverse group of immunodeficiencies characterized by normal or high serum IgM concentrations with decreased or absent IgG, IgA, and IgE. The X-linked form of hyper-IgM syndrome is caused by mutations in the CD40 ligand gene, preventing its expression on activated T cells. The CD40 ligand--CD40 interaction is critical for effective isotype switching and for initiating antigen-specific Tf cell responses. In addition to recurrent pyogenic infections, patients with the CD40L defect also have opportunistic infections. An increased proportion of circulating gamma-delta T cells, shown to be important early during primary infections, has been demonstrated in numerous infectious diseases including toxoplasmosis. Here, we report a patient with hyper-IgM syndrome and CNS toxoplasmosis, who showed a marked increase in gamma-delta T cells in his peripheral blood and who has responded well to treatment of his toxoplasmosis and to high-dose immunoglobulin replacement therapy.

Aging↗

Cerebral toxoplasmosis and Guillain-Barré syndrome after allogeneic peripheral stem cell transplantation.

We report an unusual case of cerebral toxoplasmosis associated with Guillain-Barré syndrome (GBS) in a 25-year-old patient diagnosed with chronic myelogenous leukaemia (CML), who underwent a mismatched allogeneic peripheral stem cell transplantation (PSCT). On day +83 he started with fever, and 7 days later tremor, muscular weakness, diplopia, dysarthria, respiratory difficulty, and universal arreflexia appeared, compatible with GBS. As the patient had a positive cytomegalovirus (CMV) antigenemia, this was the aetiology suspected for his neurologic findings, but specific treatment failed to improve his clinical situation, and he died on day +123. Necropsy demonstrated cerebral toxoplasmosis and axonal degeneration of nerve roots compatible with the axonal form of GBS. Interestingly, the polymerase chain reaction (PCR) signal for Toxoplasma gondii in two different cerebrospinal fluid (CSF) samples had been negative. In addition, this case showed unique magnetic resonance imaging (MRI) abnormalities. We conclude that a negative PCR on CSF cannot exclude toxoplasmosis in a transplant patient, and we emphasise the importance of considering Toxoplasma as an aetiology of fever and neurological symptoms in the transplant setting.

Adult↗

Cerebral toxoplasmosis - a late complication of allogeneic haematopoietic stem cell transplantation.

Toxoplasma gondii infection reactivation predominantly occurs among patients after allogeneic haematopoietic stem cell transplantation. Mostly, reactivation occurs during first 3 months after transplant, especially when risk factors are present. We report a case of late cerebral toxoplasmosis reactivation, which was probably triggered by a brief course of corticosteroids, administered for chronic graft-versus-host disease (cGVHD). In the presence of risk factors, such as cGVHD, prophylactic treatment for toxoplasmosis should be reinstituted; Trimethoprim-sulfamethoxasole most probably prevented earlier reactivation of toxoplasmosis in our patient.

Adrenal Cortex Hormones↗

Optic nerve changes in ocular toxoplasmosis.

PURPOSE: To determine the prevalence and features of the different types of involvement of the optic nerve in ocular toxoplasmosis. METHODS: Retrospective cross-sectional study. All patients with active ocular toxoplasmosis, consulting in the Uveitis Section of the Ophthalmology Department were selected. The involvement of the optic nerve was classified in the following categories: juxtapapillary retinochoroiditis, pure papillitis, neuroretinitis, distant lesion, and mixed lesion. RESULTS: The prevalence of involvement of the optic nerve found was 5.3%. The optic nerve involvement with the presence of a concurrent active distant lesion, occurred in 22 eyes (43.1%). A juxtapapillary lesion was found in 18 eyes (35.3%). Eight eyes (15.7%) presented lesions characterised as mixed. Isolated papillitis occurred in 3 eyes (5.9%). Forty-seven lesions (95.9%) were unilateral and two (4.1%) were bilateral. Twenty-eight eyes (54.9%) had pre-existing lesions and 23 (45%) were primary lesions. Visual acuity improved in 35 eyes (71.4%) and remained unchanged in 14 eyes (28.5%). CONCLUSION: The involvement of the optic nerve most frequently found in ocular toxoplasmosis was optic nerve oedema with a concurrent distant active lesion. The second type of lesion most often found was juxtapapillary retinochoroiditis. Involvement was monocular in most cases and the visual prognosis was favourable.

Adolescent↗

Protective immunity in the rat model of congenital toxoplasmosis and the potential of excreted-secreted antigens as vaccine components.

Toxoplasma infection is a major cause of severe foetal pathology both in humans and in domestic animals, particularly sheep. We have previously reported the development of an experimental model to study congenital toxoplasmosis in the rat. Here we demonstrate that, as in humans, total protection against congenital toxoplasmosis can be achieved regardless of the strain of Toxoplasma gondii used to infect rats, or when initial and challenge infections were carried out with different strains. Chronic infection is associated with a highly specific immunity that involves both B-and T-cell responses beginning at day 10 postinfection. The antibody isotype analysis revealed that whereas immunoglobulin (Ig)G2b is the major elicited isotype, no IgG1 antibodies are detected. T cell proliferation was assayed using crude Toxoplasma extracts or excretory-secretory antigens (ESA). The analysis of T cell supernatants showed the specific secretion of both interleukin-2 and interferon-gamma by activated T cells. Immunization of rats before pregnancy with either crude Toxoplasma extracts or with ESA elicited a B cell response that included antibodies of the IgG1 isotype and conferred on the newborns high levels of protection. Preliminary experiments of immunization using two HPLC-purified ESA, GRA2 and GRA5, conferred, a significant protection although to a lesser extent. This experimental model represents an attractive model for the identification of future vaccine candidates against congenital toxoplasmosis.

Animals↗

Central diabetes insipitus in a patient with congenital toxoplasmosis.

A 33-day-old male infant who developed central diabetes insipitus as a complication of congenital toxoplasmosis is presented. He had polyuria and hypernatremia on admission and responded to Intranasal desmopressin acetate with the normalization of above mentioned findings. Computed tomographic (CT) scan of the brain showed obstructive hydrocephaly with periventricular and right basal ganglion calcification. CT scan of the pituitary gland, thyroid function tests, and serum cortisol levels were all normal. This is the first report of isolated diabetes insipitus with congenital toxoplasmosis in literature and central diabetes insipitus should be remembered if polyuria and hypernatremia develops in a patient with congenital toxoplasmosis.

Diabetes Insipidus↗

[Sudden deafness and increased toxoplasmosis IgM titer].

BACKGROUND: Prenatal damage of the inner ear due to infection with toxoplasma gondii is documented. Nevertheless, there are only a few references about postnatal acquired toxoplasmosis as a cause of inner ear damage. PATIENTS: We report about a nine-year-old boy who suffered from unilateral hearing loss and tinnitus. RESULTS: Examinations did not show any other sign of a possible cause of hearing loss except for a very high toxoplasmosis titer of 1:102400. Besides our usual therapy regime for acute hearing loss, we treated the patient with pyrimethamine and sulphadiazine. Antibody titer decreased but the sensorineural hearing loss did not change substantially. Fortunately the patient lost the tinnitus. CONCLUSIONS: Acute Toxoplasmosis should be considered in the diagnostic process of sudden hearing loss, at least if there are appropriate clues in the medical history.

Animals↗

[Pyrimethamine-sulfadiazine resistant cerebral toxoplasmosis in AIDS].

A 48-year-old man with known HIV infection for 4 years was admitted with a 2-week history of increasing brachio-facial paraesthesiae of the left side of the body and pains in the head and neck. Physical examination also showed discrete slowing of mental activity and oral candidiasis. Toxoplasmosis serology showed a low titre with a borderline IgM titre. Cranial computer tomography showed two confluent contrast medium concentrating foci in the region of the head of the caudate nucleus and the right internal capsule. Because toxoplasmosis encephalitis was suspected, treatment was started with sulfadiazine (1 g four times daily), pyrimethamine (25 mg four times daily), folic acid (15 mg daily) and dexamethasone (8 mg three times daily). After 19 days of treatment there was no clinical improvement, and a check CT scan showed worsening with increased oedema of the cerebellar medulla, compression of the lateral ventricles and a mid-line shift of 5 mm. Since the Sabin-Feldman test titre had increased, and there was no evidence to suggest a lymphoma or a viral or fungal infection, toxoplasmosis resistant to standard therapy was postulated, and treatment was started with clindamycin (600 mg three times daily) and pyrimethamine (25 mg four times daily). The clinical features subsided within 4 days. A further check CT scan 14 days later showed almost complete resolution.

AIDS-Related Opportunistic Infections↗

[Enzyme-linked-immunosorbent assay (ELISA) for demonstrating antibodies against toxoplasmosis].

Serologic tests for specific antibodies are the primary method of diagnosis in suspected cases of toxoplasmosis. Available tests differ widely with regard to specificity and sensitivity. The enzyme-linked immunosorbent assay (ELISA) is specific for toxoplasmosis and has a sensitivity comparable to radio-immuno assays. The reproducibility of the CORDIA-T assay, tested by the authors in their laboratory, was excellent; the test itself was very easy to perform. When testing sera of 590 apparently normal subjects the authors found specific antibodies in 17.9% to 48.1% of all cases, depending on age. The ELISA-test seems to be useful in the diagnosis of ocular toxoplasmosis.

Adolescent↗

[Congenital toxoplasmosis with delayed immune response in children. Diagnostic problems].

A newborn, delivered at term, developed a rapidly increasing hydrocephalus with intracranial calcifications and seizures during the first week of life. Clinical suspicion of congenital toxoplasmosis was at first not confirmed serologically (serum titer in the immunofluorescence test [IFT] of 1:1024 and complement-fixation reaction [CFR] of 1:40 equalling those of the mother; IgM-IFT being negative and the IFT and CFR titers significantly falling within two weeks). But in the further course of the disease the diagnosis of congenital toxoplasmosis was confirmed: 1. Microscopic tachyzoits in CSF when aged six weeks; 2. positive IgM-IFT in serum and CSF from the seventh weeks onwards; 3. steep IFT titer rise in serum and CSF from the 16th week onwards. This case demonstrates that with delayed immune response in the infected child only serial serological tests will exclude or confirm the diagnosis of congenital toxoplasmosis.

Antibodies, Bacterial↗

[Toxoplasmosis encephalitis in patients with AIDS].

Toxoplasmosis encephalitis developed in three male homosexuals with AIDS. Clinical symptoms of encephalitis began with a nonspecific organic mental syndrome. In two cases there developed late focal symptoms. There were light to moderately severe generalized EEG changes with additional focal signs. CSF findings and toxoplasmosis titres were not diagnostically altered. Computed tomography demonstrated multiple areas of decreased density in cortex and cerebellum. Administration of pyrimethamine and sulfamethoxydiazine to the three patients brought about clinical improvement within a few days and regression of abnormal CT changes within a few weeks of onset of treatment. One patient died after an encephalitis recurrence: autopsy demonstrated toxoplasma pseudocysts in immediate proximity to small necrotic foci in the brain. The possibility of toxoplasma encephalitis should be considered in AIDS patients who develop an organic mental syndrome. Often the diagnosis can only be made after response to a trial of toxoplasmosis treatment.

Acquired Immunodeficiency Syndrome↗

Fuchs' heterochromic iridocyclitis following bilateral ocular toxoplasmosis.

PURPOSE: To describe the development of Fuchs' heterochromic iridocyclitis (FHI) following bilateral ocular toxoplasmosis in an Asian Indian female. METHODS: Case report of a patient with bilateral ocular toxoplasmosis who developed bilateral Fuchs' heterochromic iridocyclitis. RESULTS: Features characteristic of bilateral Fuchs' heterochromic iridocyclitis developed following several attacks of bilateral toxoplasmic retinochoroiditis in a 26-year-old Indian female patient. CONCLUSION: Fuchs' heterochromic iridocyclitis can develop over a period of time in patients with ocular toxoplasmosis.

Adult↗

Experimental ocular toxoplasmosis induced in naive and preinfected mice by intracameral inoculation.

We have developed a murine model to investigate the pathogenesis of acquired ocular toxoplasmosis. Tachyzoites of PLK strain of Toxoplasma gondii were intracamerally inoculated under anesthesia into the right eyes of naive or perorally preinfected C57BL/6 and MRL-MpJ mice. Clinical and histopathological observations of responses to intraocular infection were analyzed. Ocular inflammation from Toxoplasma gondii is dose-dependent in both strains of mice. After inoculation of fifty parasites, no evidence of inflammation was observed in the eyes of naive mice. The eyes of naive mice that received 500 or 5,000 parasites developed inflammatory changes by day 6 post challenge. By day 8, the changes progressed to moderate to severe intraocular inflammation. Histologic analysis of the ocular lesions demonstrated mononuclear cell infiltration and necrosis predominantly in the anterior segment of the eyes of the naive mice. Inoculation of 50,000 tachyzoites induced a destructive ocular inflammatory response and was uniformly lethal to the mice by approximately one week after challenge. In contrast, eyes from mice previously orally infected with Toxoplasma gondii and that received a 50 or 500 parasite intracameral challenge revealed no inflammation, but the eyes receiving 5,000 parasites demonstrated necrotic focal retinochoroiditis with vitreitis by day 8 after challenge. The murine model reproduces some features of ocular toxoplasmosis in humans and may be suitable for large-scale controlled studies of the pathogenesis and therapeutics of acquired ocular toxoplasmosis as well as for study of the mechanisms of immune privilege in the eye.

Animals↗

Use of murine subinoculation for the diagnosis and isolation of toxoplasmosis in HIV-infected patients with persistent lymphadenopathy.

A murine model was used to try to elucidate the importance of Toxoplasma gondii infection in HIV-positive patients. Laboratory mice were inoculated with lymph node homogenates or buffy coats from 30 HIV-infected individuals with persistent lymphadenopathy. Sabin and Feldman dye-tests, direct agglutination tests and indirect immunofluorescence assays (IFA) of serum samples taken from the mice six weeks after inoculation indicated, respectively, that 26.6%, 43.4% and 33.3% of the lymph node inocula and 13.3%, 30.0% and 16.7% of the buffy coat samples had been Toxoplasma-positive. Histological examination of the brains of the infected mice revealed Toxoplasma tachyzoites or bradyzoites in the mice given buffy coat samples from one patient (3.3%) and those given lymph node material from three patients (10%). No protozoa were found in the brains of the control mice, all of which were sero-negative. In contrast to the mouse results, other, concurrent tests failed to detect any signs of toxoplasmosis infection in the patients, except relatively low titres of anti-Toxoplasma antibodies in 11 patients, even though two patients developed brain toxoplasmosis, one 12 and the other 18 months after the study. It appears, therefore, that an animal model can be very useful in the diagnosis of toxoplasmosis in HIV patients.

AIDS-Related Complex↗

Magnetic resonance evaluation of cerebral toxoplasmosis in patients with the acquired immunodeficiency syndrome.

PURPOSE: To evaluate and delineate the characteristics of cerebral toxoplasmosis lesions using a combination of magnetic resonance (MR) spectroscopy, diffusion, and perfusion studies. MATERIAL AND METHODS: A total of 8 patients with 23 lesions were evaluated on a 1.5-T MR system. Diffusion-weighted imaging (DWI) was performed with three 'b' values of 50, 500, and 1000 s/mm2, and the apparent diffusion coefficient maps were calculated. The diffusion-weighted appearances and the T2-weighted MR appearances of the lesions were compared. MR spectroscopy was performed using the point-resolved single-voxel technique with two TE values of 135 ms and 270 ms. Perfusion studies were carried out using the dynamic contrast-enhanced technique, and the relative cerebral blood volume maps were qualitatively and quantitatively analyzed. RESULTS: DWI revealed the majority of the lesions as having increased diffusion within their necrotic centers, with the ADC ranging from 0.5 to 3.01 (mean +/- SD: 1.49 +/- 0.7). All the lesions revealed a predominant lipid peak on MR spectroscopy and were extremely hypovascular on perfusion MR studies. CONCLUSION: MR diffusion, spectroscopy, and perfusion studies help in characterizing toxoplasmosis lesions and, in most cases, can be used in combination to help establish the diagnosis of toxoplasmosis.

AIDS-Related Opportunistic Infections↗

A retrospective study about the use of cotrimoxazole as diagnostic support and treatment of suspected cerebral toxoplasmosis in AIDS.

The aim of this retrospective study was to define a diagnostic strategy and to evaluate the efficacy of cotrimoxazole (CTMX) for presumed cerebral toxoplasmosis in patients with AIDS. Twelve patients with toxoplasma encephalitis were reviewed. The best diagnostical signs of reactivated acute cerebral toxoplasmosis were the association of neurological symptoms indicative of focal cerebral lesions, and a radiological picture showing ring contrast enhanced hypodense mass-lesions; serology was unreliable for the diagnosis. Five patients out of twelve were treated without delay and until death with CTMX. Only these improved their clinical and radiological status obviously. Moreover, their median survival time was clearly longer (160 days, versus 9 days) and their autopsy demonstrated the absence of active necrotizing lesions of toxoplasma encephalitis. So, CTMX seems to be an efficient therapy for suspected cerebral toxoplasmosis in AIDS. Nevertheless, further prospective randomized therapeutic trials are required to confirm this impression.

Acquired Immunodeficiency Syndrome↗

Genotype of 86 Toxoplasma gondii isolates associated with human congenital toxoplasmosis, and correlation with clinical findings.

To study the influence of Toxoplasma gondii genotypes on the severity of human congenital toxoplasmosis (asymptomatic, benign, or severe infection or newborn or fetal death), 8 microsatellite markers were used to analyze 86 T. gondii isolates collected from patients with congenital toxoplasmosis. Seventy-four different genotypes were detected, some identical genotypes originating probably from the same source of contamination. The 3 less polymorphic microsatellite markers associated with 6 isoenzymatic markers allowed a classification of isolates into the 3 classical types and detected atypical genotypes. Whatever the clinical findings, type II isolates were largely predominant (84.88% in the whole collection and 96.49% in 57 consecutive cases). Type I and atypical isolates were not found in asymptomatic or benign congenital toxoplasmosis. However, in 4 cases in which children were not infected despite isolation of T. gondii from placenta, only type I isolates were found.

Animals↗

Toxoplasmosis in patients with cancer.

The unusual occurrence, protein manifestations, and often devastating consequences of toxoplasmosis in patients with cancer emphasize the need for clinical acumen in the diagnosis and management of this disorder. Toxoplasmosis in patients with cancer has most commonly been described in association with Hodgkin's disease. It has also been reported, usually in the setting of treatment with antineoplastic agents, in patients with other lymphoproliferative disorders, hematologic malignancies, and solid tumors. In this review, among patients for whom the diagnosis was made early enough to begin specific treatment, conditions of 68% improved; this finding was in marked contrast to the severe morbidity and mortality observed for untreated individuals. The high mortality in the untreated group reflects the general debilitation and severe immunocompromise of these patients. Therefore, although toxoplasmosis contributed to a poor prognosis, it was not necessarily always the proximate cause of death.

Encephalitis↗