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Therapy for ocular toxoplasmosis.

We conducted a prospective multicenter study of the efficacy of current therapeutic strategies for ocular toxoplasmosis in 149 patients. Treatment consisted of the following three triple-drug combinations: group 1, pyrimethamine, sulfadiazine, and corticosteroids; group 2, clindamycin, sulfadiazine, and corticosteroids; and group 3, trimethoprim, sulfamethoxazole and corticosteroids. Patients with peripheral retinal lesions were not treated systemically. No difference in the duration of inflammatory activity was observed between treated and untreated patients (P = .5). The most important factor predicting the duration of inflammatory activity was the size of the retinal lesion itself, independent of the treatment (P < .001). We found a reduction in size of the retinal inflammatory lesion for 49% of the pyrimethamine-treated patients (17 of 35) compared to 20% of the untreated patients (eight of 41) (P < .01). However, the most frequent occurrence of side effects was also associated with pyrimethamine medication (26%, nine of 35). The mean recurrence rate after three years of follow-up was 49% for all patients (60 of 122 patients), with no differences between treated and untreated patients (P = .6).

Adult↗

Use of fluorescence resonance energy transfer hybridization probes to evaluate quantitative real-time PCR for diagnosis of ocular toxoplasmosis.

Toxoplasma gondii infection is an important cause of chorioretinitis in Europe and the United States. Ophthalmological examination and a good clinical response to adequate therapy mainly support ocular toxoplasmosis diagnosis. However, clinical diagnostic may be difficult in some atypical cases. In these cases, laboratory confirmation, based on detection of local specific antibodies and parasite DNA by conventional PCR, is therefore important to confirm the disease etiology. More recently, real-time PCR has been developed to improve prenatal congenital toxoplasmosis diagnosis. We therefore examined the diagnostic value of quantitative real-time PCR for the detection of T. gondii in aqueous humor samples, associated with quantification of human beta-globin to control sample quantitative quality, by using a double fluorescence resonance energy transfer hybridization probes system with a double fluorescence reading. Of the 23 the clinically toxoplasmosis suspect patients, 22 showed serological evidence of exposure to Toxoplasma; one had a serological profile indicative of active infection. The analysis of paired aqueous humor and serum samples revealed an intraocular antibody production in 9 of 23 cases (39.1%). The quantitative real-time PCR revealed positive and high parasite numbers and high Toxoplasma/human genome ratios in three cases. Furthermore, PCR was the only positive confirmatory test in two cases (11.1%). None of the patients included in the control group (n = 7) had evidence of either local specific antibody production or T. gondii DNA detection, suggesting a good relative assay specificity. On the whole, quantitative real-time PCR appears to be useful for diagnosing atypical ocular toxoplasmosis presentations.

Adolescent↗

Ocular toxoplasmosis: the role of cellular immune defense in the development of recurrences. Results from animal experiments.

Five toxoplasmosis-free animals and ten animals that had been immunized intraocularly against toxoplasma organisms were used in a rabbit model of ocular toxoplasmosis. Five of the ten immune animals were immunosuppressed by cyclosporin A at a cellular level. Experimental toxoplasmic retinochoroiditis occurred in all animals, a process that in complete contradiction to experience reported previously. In the rabbit model, immunity after a past history of toxoplasma infection has thus far appeared to be a safe form of protection from experimental ocular toxoplasmosis. The concept of "immunological privilege of the eye" is discussed as the cause for the unexpected results.

Animals↗

[Research on antibodies anti toxoplasma gondii in intraocular fluids (Aqueous and vitreous humor) from patients with ocular toxoplasmosis, in the City of Belém, Pará State].

Tests were performed for antibodies IgG, IgM and IgA anti-Toxoplasma gondii antibodies in serum and intraocular fluids (Aqueous and vitreous humor) from patients with ocular toxoplasmosis. By the results obtained, it was verified that intraocular IgG and IgA anti-Toxoplasma gondii antibodies can be important markers for the diagnosis of ocular toxoplasmosis.

Adult↗

Frequency of specific anti-Toxoplasma gondii IgM, IgA and IgE in colombian patients with acute and chronic ocular toxoplasmosis.

We studied the frequency of specific anti-Toxoplasma IgM, IgA and IgE antibodies in serum of 28 immunocompetent Colombian patients, selected by ophthalmologists and with lesions that were compatible with ocular toxoplasmosis. Patients were classified in three groups: (i) group 1 consisted of ten patients with a first episode; (ii) group 2, with seven patients with a recurrence and (iii) group 3, consisted of eleven patients with chronic chorioretinal lesion without uveitis. We found that 10/28 (35%) of Colombian patients with ocular toxoplasmosis possessed at least one serological marker for Toxoplasma infection different from IgG. In group 1 (first episode), we found simultaneous presence of specific IgM plus IgA plus IgE in 1/10 (10%). In group 2 (recurrences) in 1/7 (14%) we found IgM and IgA test positives and in 1/7 (14%) we found IgM and IgE tests positives. In group 3 (toxoplasmic chorioretinal scar) the IgA serological test was positive in 2/11 (18%). These results show that serum IgM or IgA or IgE can be present during recurrences.

Acute Disease↗

Ocular toxoplasmosis in the fetus. Immunohistochemistry analysis and DNA amplification.

PURPOSE: Ocular toxoplasmosis is often the result of a congenital infection. However, the earlier stages of the ocular lesions in the fetus have not been well studied. The purpose of the present study is to analyze the ocular findings in four aborted fetuses that were infected congenitally with Toxoplasma gondii. METHODS: Eight eyes from four fetuses of 22 to 27.5 weeks with T. gondii infection were studied by routine and immunohistochemical techniques. Two of the four were also examined by polymerase chain reaction (PCR). RESULTS: In two cases, the results of gross and histopathologic of the eyes were normal; marked retinal necrosis was present in the other two cases. Although no toxoplasmic cysts were identified by routine histopathologic examination, antigens of the tachyzoite were detected by immunohistochemistry analysis in the areas of retinal necrosis. In one of the cases with ocular lesions, the presence of T. gondii was confirmed by PCR. The presence of ocular lesions correlated with the severity of pathologic changes in the central nervous system. Large numbers of T cells were observed in the retinal lesions and in the choroid. CONCLUSION: Retinal necrosis, neovascularization, and marked chorioretinal inflammations despite the absence of bradyzoites are characteristic findings in the fetal eyes infected with T. gondii, and infiltrating T lymphocytes play a role in early recognition of the toxoplasma organism.

Adult↗

Clinical ocular toxoplasmosis in neonatal kittens.

OBJECTIVE: To describe ocular findings in kittens with congenital or early neonatal infection by Toxoplasma gondii and to determine if there are detectable differences in disease caused by three strains. ANIMALS STUDIED: Six adult female cats and the offspring from seven litters. METHODS: Four kittens from uninfected specific pathogen-free (SPF) queens and 21 kittens from SPF queens inoculated at various times late in gestation with Mozart, Maggie, or ME-49 strain of T. gondii were used. Ocular examinations were performed on queens prior to and after delivery, and on kittens weekly to bi-weekly for up to 27 weeks. Whole blood for serology was collected from all kittens at 5(1/2) to 8 weeks of age and again at 12 weeks of age or later. RESULTS: No kittens from noninfected queens developed ocular lesions or antibody to T. gondii. Three of the 24 kittens from infected queens died or were euthanized early in the study. Chorioretinitis was detected in 15 of 21 living kittens from infected queens. Two developed concurrent anterior uveitis that resolved within 1 week. Posterior segment lesions varied ophthalmoscopically between strains. Of 21 kittens from T. gondii-infected queens, six developed positive antibody titers to T. gondii during the study. All seropositive kittens were born to queens infected with Mozart strain of T. gondii. CONCLUSION: Results of this study suggest that ocular toxoplasmosis can occur without other evidence of clinical illness in kittens infected in utero or in the neonatal period, and that T. gondii strains may have varying degrees of ocular pathogenicity in cats.

Animals↗

[Ocular Toxoplasmosis: Case report.].

Toxoplasma gondii is one of the most frequently encountered infectious agents in uveitis. Ocular toxoplasmosis may develop as a result of congenital or acquired infection. In this study, a patient with acquired acute ocular toxoplasmosis has been presented.

English Abstract↗

[Ocular toxoplasmosis. Utilization of immunohistochemical reaction for diagnosis].

The diagnosis of ocular toxoplasmosis is based primarily on clinical presentation and laboratory tests described else where. Eventually, unusual clinical presentation, as well unusual pathologic findings occur, mainly in immunosuppressed individuals. The authors report a case of a female patient from Paraná with a progressive ocular disease, for at least three years, without definite diagnosis. After an exhaustive clinical and laboratory investigation, as well empiric medical treatment, without success, it was decided to enucleate the atrofic organ and to proceed to a histologic examination. It revealed a cronic and inspecific inflammatory process without any specific agent. However the immunohistochemical technique was able to detect Toxoplasma gondii antigens in the ocular tissue. This technique provides an alternative method for the diagnosis of unusual forms of toxoplasmosis.

Female↗

Therapy of ocular toxoplasmosis.

We performed a prospective multicentre study to evaluate the efficacy of therapeutic strategies currently used for ocular toxoplasmosis in a large number of patients (n = 106). Treatment was given for at least four weeks and consisted of three triple drug combinations: group 1, pyrimethamine, sulphadiazine and corticosteroids (n = 29); group 2. clindamycin, sulphadiazine and corticosteroids (n = 37); and group 3. cotrimoxazole (trimethoprim and sulphamethoxazole) and corticosteroids (n = 8). Patients with peripheral retinal lesions remained without systemic therapy (group 4, n = 32). Patients from group 1 received leucovorin 5 mg twice a week. No difference in the duration of inflammatory activity was observed between the treated and untreated patients or between the separate groups of patients. The most important factor predicting the duration of inflammatory activity was the size of the retinal focus itself, independently of the therapy given (P less than 0.05). We showed a reduction in size of the retinal inflammatory focus in 52% of the pyrimethamine patients as compared to 25% of untreated cases. However the most frequent side effects were also associated with pyrimethamine medication and included hematologic complications as thrombocytopenia and leucopenia despite leucovorin medication.

Chorioretinitis↗

Effects of sulfamethoxazole on murine ocular toxoplasmosis in interferon-gamma knockout mice.

PURPOSE: To evaluate the effects of sulfamethoxazole (SMX) on experimental ocular toxoplasmosis by quantitative competitive polymerase chain reaction (QC-PCR) assay. METHODS: Wild-type (WT) C57BL/6 and WT BALB/c mice and interferon-gamma knockout (GKO) mice were infected orally with Toxoplasma gondii of the Fukaya strain. Mice were classified into groups. The first group (G1) remained untreated, the second group (G2) had a short SMX treatment period, and the third group (G3) received treatment continuously. WT and GKO mice were divided into G1 and G3, and G1, G2, and G3, respectively. T. gondii burdens were evaluated by QC-PCR assay. The effect on stage distribution was analyzed by reverse transcription-PCR. RESULTS: SMX significantly decreased mortality among the infected WT C57BL/6 and GKO mice. In WT G1 mice, T. gondii DNA was detected in all organs and tissues, although in G3 mice it was detected only in the brain. In GKO C57BL/6 G1 mice, the protozoan proliferated much more actively than in the WT mice. In the GKO C57BL/6 G2 mice, the number of T. gondii was less than in G1 during the treatment, although the protozoan reappeared after cessation of treatment. In GKO C57BL/6 G3 mice, T. gondii DNA was detected in the brain, optic nerve, and retina, but not in the iris, choroid, sclera, and blood. In GKO BALB/c mice, the patterns of the kinetics of protozoan abundance in various organs were similar or were milder than those in GKO C57BL/6 mice. In SMX-treated GKO mice, the percentage of bradyzoites increased and that of tachyzoites decreased in the organs and tissues. CONCLUSIONS: SMX decreased the parasitic load in both WT and GKO mice. SMX decreased the tachyzoite load but did not completely eliminate bradyzoites in GKO mice. The present mouse model was used successfully to assess treatment effects in a quantitative fashion.

Animals↗

[Ocular toxoplasmosis in AIDS].

Since 1983, we have seen 11 cases of toxoplasmic retinochoroiditis in patients with AIDS. Ocular toxoplasmosis appears to be a growing concern in AIDS: 3.3% in 1983, 6.1% in 1988 and 5.9% during the first trimester of 1989. Anti-Toxoplasma gondii antibody titers in the aqueous humour were not conclusive, therefore the diagnosis was based on ophthalmoscopic criteria and on a rapid response to specific therapy. As for brain toxoplasmosis, treatment must be continued indefinitely to prevent relapse. Seven out of 11 patients had cerebral toxoplasmosis, which was diagnosed by computerized tomography (CT) scan. This suggests that a neurological evaluation and a brain CT scan should be performed in all AIDS patients with toxoplasmic retinochoroiditis.

Acquired Immunodeficiency Syndrome↗

Evidence for a compartmentalized B cell response as characterized by IgG epitope specificity in human ocular toxoplasmosis.

Infectious agents in the eye induce both a local and a systemic humoral immune response. Previously, differences in Ag recognition were observed between systemic and ocular derived IgG of patients with ocular toxoplasmosis. This finding implied a nonrandom distribution of IgG-producing B cells in the inflamed eye. In the present study, we compared the intraocular and systemic B cell responses of patients with ocular toxoplasmosis to a single Toxoplasma gondii Ag. Two series of C-terminally deleted recombinant T. gondii GRA-2 proteins were constructed to delineate IgG B cell epitopes of paired ocular and serum samples. Differences in epitope region recognition between the ocular and systemic compartment were detected in 9 of 13 patients. The difference in distribution of GRA-2 epitopes between paired samples is indicative of a local GRA-2 specific B cell population functionally different from the systemic GRA-2-specific B cell population. Our results suggest a selective activation of a subset of B cells locally in nonlymphoid tissue.

Adolescent↗

Immunological studies of chronic ocular toxoplasmosis: up-regulation of major histocompatibility complex class I and transforming growth factor beta and a protective role for interleukin-6.

A murine model was used to characterize the local immune and inflammatory response during ocular toxoplasmosis. Major histocompatibility complex (MHC) class I, normally expressed at low levels in immune-privileged sites such as the eye, was up-regulated during infection as determined by competitive reverse transcriptase (RT)-PCR and immunocytochemistry for both beta2-microglobulin and the MHC class I heavy chain. However, the eyes of chronically infected mice also had increased levels of mRNA transcripts for transforming growth factor beta, a cytokine associated with immune privilege and constitutively expressed in normal eyes. Transcripts for a number of inflammatory mediators, including interleukin-6 (IL-6), were increased during chronic infection. The role of IL-6 was further investigated by comparing disease progression and the development of the local immune response in wild-type (WT) and IL-6-deficient mice (IL-6(-/-) mice). Following infection, IL-6(-/-) mice developed more severe inflammation in the retina and vitreous humor compared with WT mice. This increased severity of disease was associated with reduced ocular IL-1alpha and increased tumor necrosis factor alpha mRNA production compared with WT mice. Moreover, the increased severity of disease in IL-6(-/-) mice correlated with increased eye parasite burden as determined by RT-PCR for the Toxoplasma gondii bradyzoite-specific LDH2 gene. These results demonstrate alterations to components of immune privilege as a result of ocular toxoplasmosis and a role for IL-6 in controlling parasite numbers and inflammation in the eye.

Animals↗

Ocular toxoplasmosis in mice: comparison of two routes of infection.

This paper aims to test the influence of route of infection (intravitreal and instillation) on the course of ocular toxoplasmosis in mice, using the Toxoplasma gondii Me-49 strain. All mice inoculated intravitreally or by instillation presented the same pattern of infection. Using either route, parasites were observed in the retinal vessel with the formation of a glial reaction in the inner plexiforme layer and discontinuity of the pigmented epithelium of the retina 7 days after infection. However, when the intravitreal route was used a more intense inflammatory infiltrate was observed in the retina. The results suggest that inoculation route remarkably influences the inflammatory pattern in ocular toxoplasmosis and that the instillation route should be preferentially used in experimental infections in the murine ocular model of infection by T. gondii, specially with small animals where there is extensive needle damage, which is not observed in the instillation route.

Animals↗

Inhibition of nitric oxide production exacerbates chronic ocular toxoplasmosis.

There is considerable controversy as to the roles of parasite proliferation and the inflammatory response in destruction of the retina during Toxoplasma gondii infection. A murine model was used to investigate the role of nitric oxide in pathogenesis of chronic ocular toxoplasmosis. Increased quantities of messenger RNA (mRNA) transcripts for iNOS were detected in the eyes of chronically infected C57BL/6 mice compared with noninfected control mice. Inhibition of nitric oxide (NO) by the addition of Lomega-nitro-L-arginine methyl ester (L-NAME) to the drinking water of infected mice between weeks 4-6 of infection, exacerbated ocular inflammation. The amount of inflammation was assessed semiquantitatively in histological sections of the eye. Eyes from L-NAME treated mice showed a significant increase in inflammation of the retina (P = 0.02), choroid (P = 0.03), and vitreous (P = 0.02) compared with control mice. These results demonstrate a protective role for NO in the control of chronic, ocular toxoplasmosis.

Animals↗

Ocular toxoplasmosis; common and rare symptoms and signs.

The common and rare symptoms and signs of congenital, childhood and adult ocular toxoplasmosis are discussed together with the differential diagnosis of the retinal lesions. A choroidal coloboma in connection with congenital toxoplasmosis is described. The occurrence of an optic pit with congenital macular toxoplasmosis, growth of subretinal new vessels as well as disappearance of arteriolar and venular sheathing is demonstrated.

Adult↗