Recurrent Ocular Toxoplasmosis Research Articles

Ocular Toxoplasmosis: Advances in Toxoplasma gondii Biology, Clinical Manifestations, Diagnostics, and Therapy.

Toxoplasma gondii, an obligate intracellular parasite, is a globally prevalent pathogen capable of infecting a wide range of warm-blooded animals, including humans. Ocular toxoplasmosis (OT), a severe manifestation of T. gondii infection, can lead to potentially blinding complications. This comprehensive review delves into the current understanding of T. gondii biology, exploring its complex life cycle, diverse transmission routes, and strain diversity. This article provides an in-depth analysis of the clinical manifestations of OT, which can result from both congenital and acquired infections, presenting a spectrum of signs and symptoms. The review examines various diagnostic strategies employed for OT, including clinical examination, multimodal imaging techniques such as fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA), as well as laboratory tests including serology and molecular methods. Despite extensive research, the specific mechanisms underlying ocular involvement in T. gondii infection remain elusive, and current diagnostic options have limitations. Moreover, the treatment of active and recurrent OT remains a challenge. While existing therapies, such as antimicrobial agents and immunosuppressants, can control active infections, they do not offer a definitive cure or completely prevent recurrence. The clinical endpoints for the management of active and recurrent OT are also not yet well-established, and the available treatment methods carry the potential for adverse effects. This article highlights the need for future research to elucidate the pathogenesis of OT, investigate genetic factors influencing susceptibility to infection, and develop more sensitive and specific diagnostic tools. Enhancing global surveillance, implementing robust prevention strategies, and fostering multidisciplinary collaborations will be crucial in reducing the burden of OT and improving patient outcomes. This comprehensive review aims to provide a valuable resource for clinicians, researchers, and policymakers, contributing to a better understanding of T. gondii infection and its impact on ocular health.

Recurrent ocular toxoplasmosis is associated with interferon-gamma deficiency possibly due to genetic origin

ObjectiveOcular toxoplasmosis (OT) can cause posterior uveitis; causes of recurrent OT are not well understood. We explored clinical, immunological and genetic properties associated with recurrent OT.Methods and analysisA recurrent OT...

Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: A retrospective study in a Thai tertiary center.

Ocular toxoplasmosis (OT) is the most common cause of infectious uveitis worldwide, including Thailand. This study describes the clinical presentation, visual acuity (VA) outcomes, and factors associated with VA loss in patients with active OT following antiparasitic treatment. A retrospective chart review of patients with active OT treated with antiparasitic drugs between 2010 and 2020 was performed. Outcome measures included clinical characteristics, interval VA, and predictive factors associated with loss of VA ≤ 20/50 at 6 months post-treatment. Ninety-two patients (95 eyes) were enrolled. The median follow-up time was 10.9 months (IQR 4.9-31.8 months). The median age at presentation was 35.9 years, 51% were male, and 92.4% had unilateral OT. Eleven patients (12%) were immunocompromised (HIV infection, eight patients; receiving immunosuppressive agents, three patients). Patients mainly presented with primary retinitis without previous scar (62%), posterior pole lesion (56%), and lesion size of ≤ 2-disc area (75%). Immunocompromised patients showed a significantly larger size of retinitis than immunocompetent patients. Oral trimethoprim/sulfamethoxazole monotherapy was the primary short-term antiparasitic drug prescribed (85%). At the final visit, 21% of all affected eyes suffered VA ≤ 20/200. The cumulative incidence of recurrent OT at three years was 33.9% (95% CI, 19.7%-54.2%). Immunocompromised patients [adjusted odds ratio (aOR) 4.9, p = 0.041], macular lesion (aOR 5.4, p = 0.032), and initial VA ≤ 20/200 (aOR 9.1, p = 0.014) were predictive of having VA ≤ 20/50 at 6 months post-treatment. Ocular toxoplasmosis mainly presents as unilateral primary retinitis within the posterior pole. Severe VA loss was observed in one-fifth of eyes following treatment with lesion resolution. Immunocompromised patients, eyes with macular lesions, and poor initial VA were associated with poor VA outcomes.

Clinical and Serological Characteristics of Ocular Toxoplasmosis in the Democratic Republic of Congo

ABSTRACT Purpose To describe demographic data, clinical features, and serological profiles in a cohort of Congolese patients with ocular toxoplasmosis (OT). Method Cross-sectional study, carried out between March 2020 and July 2021 in two ophthalmic clinics in Kinshasa. Results The study comprised 95 participants with OT. Fifty-three patients were male (55.8%). The mean age at presentation was 35.6 ± 14.1 years (range 8–69 years); 71 had active OT (74.7%), among them, 33 had primary OT (46.5%), and 38 had recurrences (53.5%). At presentation, 51 patients (53.7%) had visual impairment (VA < 6/18). Retinochoroidal lesions were located in the central retina in 60 patients (63.1%). Patients with primary OT tend to have higher IgG levels than those with recurrent OT (P = .01). Conclusion We report the largest cohort of patients with OT in sub-Saharan Africa. In our setting, most patients had recurrent OT with multiple, extensive, and central retinochoroidal lesions.

CASE REPORT: REACTIVATION OF CONGENITAL OCULAR TOXOPLASMOSIS IN AN IMMUNOCOMPETENT PATIENT AFTER RECEIVING MEASLES

A case of recurrent ocular toxoplasmosis, presented through diagnostic imaging techniques and laboratory tests. To show the course and development of the clinical picture of ocular toxoplasmosis in a 19-year-old girl with good visual acuity in both eyes, which was accidentally detected during a routine ophthalmological examination for a driver's license. At the University Clinic for Eye Diseases in Skopje, several imaging diagnostic methods have been performed, such as: fundus photography, aurofluorescence, optical coherence tomography (OCT) and fundus fluorescence angiography (FFA). Imaging techniques, along with laboratory tests for specific anti-toxoplasmosis IgG and IgM antibodies, have helped to diagnose this not-so-common entity-ocular toxoplasmosis. The development of the disease was followed by a clinical picture, certain diagnostic methods in a period of seven years. Three recurrences of the parasitosis occurred during that period. The third attack of toxoplasmosis was associated with the occurrence of measles in an otherwise healthy young woman, a possible trigger for reactivation of the disease. Regular laboratory tests of anti-toxoplasma IgG and IgM antibody titers were performed with the help of ELISA at PHI UC for infectious diseases and febrile conditions in Skopje, during the entire process of monitoring. The lesion described by the diagnostic modalities corresponded to the data obtained from the literature and together with the elevated values ​​of anti-toxoplasma IgG and IgM antibodies confirmed the diagnosis of congenital ocular toxoplasmosis. Keywords: toxoplasmosis, ocular toxoplasmosis, therapy, laboratory tests, FFA, OCT &nbsp;

Immune Mediator Profile in Aqueous Humor Differs in Patients with Primary Acquired Ocular Toxoplasmosis and Recurrent Acute Ocular Toxoplasmosis

Purpose To compare the intraocular cytokine and chemokine profiles in patients with acute primary acquired ocular toxoplasmosis (pOT) or recurrent ocular toxoplasmosis (rOT) and to correlate them with their clinical characteristics. Methods Aqueous humor samples were collected from 62 consecutive patients (21 pOT, 30 rOT, and 11 noninfected controls) and analyzed by multiplex assay. Correlations were assessed between cytokine/chemokine levels, type of inflammatory response (Th1, Th2, and Th17), and clinical characteristics. In all OT patients, the clinical diagnosis of either pOT or rOT was confirmed by positive intraocular Goldmann/Witmer-Desmonts coefficient. Correlations were assessed between a preselected panel of immune mediators and the clinical characteristics of OT. Results In pOT patients, increased levels of IL-2, IFN-γ, TNF-α, IL-15, IL-4, IL-5, IL-9, IL-13, IL-17, IL-1Rα, IL-6, IL-1β, and chemokines MIP-1α, MIP-1β, IP-10, Eotaxin, IL-8, RANTES, PDGF-bb, GM-CSF, G-CSF, and MCP-1 were found in comparison to those in controls (p < 0.05). Patients with rOT showed elevated levels of IL-2, IFN-γ, TNF-α, IL-15, IL-4, IL-5, IL-9, IL-17, IL-1Rα, IL-6, IL-1β, and chemokines MIP-1α, IP-10, Eotaxin, IL-8, RANTES, PDGF-bb, G-CSF, and MCP-1 compared to controls (p < 0.05). In addition, IL-7 (p = 0.028) differed between pOT and rOT; IL-9 (p = 0.054) and IL-13 (p = 0.051) showed a tendency of higher concentration in pOT than in rOT. A negative correlation was found between IL-7 (p = 0.017) as well as IL-9 (p = 0.008) and the number of recurrences. Cytokine ratios showed no difference between pOT and rOT, indicating a dominant Th1-type response in both infectious groups. Moreover, a positive correlation was detected between IL-7, VEGF, IL-13 and age at aqueous humor sampling (p < 0.05). Conclusions This study for the first time shows subtle differences between the intraocular cytokine profiles in patients with either acute pOT or rOT.

Peptidyl-prolyl cis-trans isomerase A – A novel biomarker of multi-episodic (recurrent) ocular toxoplasmosis

Ocular toxoplasmosis (OT) is the most common etiology of posterior uveitis. The high incidence of macular scarring associated with OT is a leading cause of visual morbidity. Serum biomarkers of the disease would aid in its diagnosis. This study sought, for the first time, to elucidate serum biomarkers for OT by mass spectrometry. Blood samples were collected from four groups of nine patients each; toxoplasmosis IgG-with no history of uveitis, non-toxoplasmosis uveitis, first episode OT, and symptomatic recurrent OT. Serum was isolated and subjected to proteomics analysis using 2-dimensional gel electrophoresis (2D-GE) and surface-enhanced laser desorption ionization mass spectrometry (SELDI-MS). Selected proteins were further separated by SDS-PAGE and sequenced using tandem MS. Results were cross-validated with a T. gondii outbreak biomarker database that occurred in Brazil. Fifty markers of OT and 46 markers of recurrent disease were discovered by SELDI-MS of which 30 and 15, respectively, were cross-validated. 2D-GE analysis yielded 57 bands, selected based on the intensity of the bands, leading to the identification of 20 proteins. Eleven of those identified candidates were also found by SELDI-MS. Four candidates were chosen for immunoblotting. One serum protein, peptidyl-prolyl cis-trans isomerase A (PPIA), was confirmed as a biomarker of multi-episodic OT by immunoblotting in patients. PPIA can identify the patient with active recurrent OT from acute OT, other forms of uveitis and other parasitic infections. A validated PPIA assay may have a role in the diagnosis of the atypical OT patient before more invasive anterior chamber or vitreous tap is performed for PCR analysis or for Goldmann-Witner coefficient calculations. Base-line PPIA levels need to be studied to understand its possible use when deciding for prophylactic antibiotic use in the immunosuppressed sero-positive patient.

AB039. Peptidyl-prolyl cis-trans isomerase A (PPIA)—a novel biomarker of multi-episodic (recurrent) ocular toxoplasmosis

AB039. Peptidyl-prolyl cis-trans isomerase A (PPIA)—a novel biomarker of multi-episodic (recurrent) ocular toxoplasmosis

Aqueous humor cytokine profile of patients with primary or recurrent ocular toxoplasmosis

AbstractPurpose Toxoplasma gondii infection remains the most frequent cause of infectious posterior uveitis and a significant cause of visual impairment worldwide. Still, the immune mechanisms are largely unexplored. The aim of this study is to investigate the cytokine profiles of aqueous humor samples in patients with first or recurrent manifestation of ocular toxoplasmosis and to correlate findings with clinical characteristicsMethods Using the BioRad Multiplex immunoassay, we determined the concentrations of 27 cytokines/chemokines in aqueous humor specimens obtained from 16 patients with active (n=7) or recurrent (n=9) ocular toxoplasmosis. Results were compared to 5 matched control patients without intraocular infectionResults Using the Wilcoxon‐Mann‐Whitney‐Test significant changes could be identified in both groups affected by either initial or recurrent ocular toxoplasmosis compared to controls. Patients with initial manifestation revealed a significant increase (p &lt; 0.05) of IL‐1RA, IL‐7, MIP1a and IP‐10. In addition significant changes in individuals affected by recurrent disease also differed from controls and became significant (p&lt; 0.05) for TNF‐alpha, MIP‐1b and IP‐10. The cytokine/chemokine profiles however did not differ significantly between initial or recurrent ocular toxoplasmosis subgroups.Conclusion Our data suggests that MIP1 and IP‐10 are associated with both primary and recurrent ocular toxoplasmosis. These findings may support the important role of IP‐10 and MIP, as specific chemoattractants for activated T cells in parasitic disorders. In contrast to a recent report we were not able to correlate IL‐5 and VEGF with recurrences of the disease. A larger cohort is recruited to underline the results.

Clinical pattern of ocular toxoplasmosis treated in a referral centre in Serbia

To analyze the clinical pattern of ocular toxoplasmosis (OT) in a referral centre in Serbia. The medical records of consecutive patients admitted for OT to the single referral centre for uveitis in Serbia between 2006 and 2010 were retrospectively analyzed. OT was diagnosed on the basis of typical fundus lesions and positive serology for Toxoplasma. In a total of 457 uveitis patients, OT was the third leading cause, with 59 patients (12.9%). Most OT cases (73%) were monocular. An active primary retinal lesion was observed in 36% and recurrent OT in 64% patients. Localization of lesions was central/paracentral (44%), juxtapapillar (27%), peripheral (19%), and multifocal (10%). Other ocular manifestations of inflammation included vitritis (44%), anterior uveitis (19%), and retinal vasculitis (10%). Complications included choroidal neovascularization in two and exudative retinal detachment with cataract, glaucoma, and cystoid macular oedema in one patient each. The detection of Toxoplasma-specific IgM antibodies in a single patient indicates a low rate of OT concomitant with acute infection. After treatment, the mean best-corrected visual acuity (BCVA) increased significantly. However, 14 (24%) patients ended up legally blind in the affected eye, of which 2 (3%) with bilateral blindness, all with a very poor BCVA (0.047 ± 0.055) at presentation. Visual impairment and treatment outcome were both associated with central localization of lesions (P<0.0001 and P=0.006, respectively). OT is a significant cause of posterior uveitis in Serbia. Patients should be aware of the recurring nature of OT and react immediately if symptoms occur.

Immunopathology in ocular toxoplasmosis: facts and clues

Although parasite-mediated host cell lysis is deemed to be an important cause of tissue destruction in ocular toxoplasmosis (OT), the severity of the disease is probably correlated with hypersensitivity and inflammation. Notwithstanding, the mechanisms that regulate the inflammatory process in recurrent OT are poorly understood. Recent evidence has identified interleukin (IL) 17 as a marker for disease severity. The ocular and cerebral presence of this cytokine is generally associated with the induction of autoimmune responses in the brain and the eye. Indeed, there are indications that autoimmunity may contribute to clinical variability in the activity of OT. IL-23, which induces the proliferation of IL-17-producing cells and IL-27, which is a counterplayer to IL-17, may regulate T(H)-1-cell-mediated responses in OT. The importance of these cytokines in experimental models of uveitis and encephalitis has been recently reported. CD25(+) regulatory T-cells may control the local inflammatory response and protect the host against collateral inflammatory tissue damage. The responses of these cells to OT may be suitably tailored to cope with either an acquired or a congenital aetiology. Knowledge relating to immunoreactivity in OT has grown impressively during the past few years. Its characteristic and variable features have been identified and the potential relevance of autoimmunity has been assessed. In light of this knowledge, potential future treatment options have been considered.

Remote hypofluorescent dots in recurrent ocular toxoplasmosis on indocyanine green angiography

To report the findings of indocyanine green angiography performed in patients with recurrent ocular toxoplasmosis. Institutional prospective analysis of 23 eyes from 23 immunocompetent patients with recurrent ocular toxoplasmosis aged between 17 and 41 years. These patients underwent a complete ocular examination including indocyanine green angiography. Multiple hypofluorescent spots distant from the recurrent active lesion of retinochoroidal toxoplasmosis were found in 26.08% of the patients. We also found multiple hypofluorescent satellite dots in 69.56% of the patients. These remote dots seen suggest either a more widespread choroidal involvement in this disease and this can represent simply remote collections of inflammatory cells or subclinical infection.

Ocular toxoplasmosis after the fifth decade

PURPOSE: To describe the clinical features in patients presenting with ocular toxoplasmosis after the fifth decade and to analyze laboratory findings in comparison to uveitis history and clinical data. DESIGN: Prospective consecutive observational case series. METHODS: A prospective clinical analysis of 27 consecutive patients older than 50 years of age with primary or recurrent ocular toxoplasmosis was performed during a period of 8 years. These cases account for 12% of all ocular toxoplasmosis cases irrespective of age indexed in our institution during the same period. Paired serum and aqueous humor samples were tested for anti- Toxoplasma gondii IgG, IgM, and IgA antibodies. The presence of T. gondii DNA in aqueous humor was determined by polymerase chain reaction followed by DNA hydridization method. RESULTS: Although similar in age, two groups were distinguished clinically: 12 patients (44%) presented with usual forms of retinochoroiditis (mean ± SD, 1.6 ± 0.5 disk areas [DA] in size); 15 patients (56%) presented with atypical lesions, greater than 3 DA in size (mean ± SD, 5.0 ± 2.0 DA). The second group showed a higher rate of complications ( P = .028) and a poorer visual outcome ( P = .015). Twenty-four patients (89%) had intraocular IgG production, 17 (63%) had intraocular IgA production, 3 (11%) had intraocular IgM production, and 12 (44%) had a positive T. gondii DNA detection. CONCLUSIONS: After the fifth decade, ocular toxoplasmosis remains an important cause of posterior uveitis. The combination of antibody detection by immunocapture tests with T. gondii DNA detection, both in aqueous humor, allowed the diagnosis of toxoplasmic infection in the atypical cases with large ocular lesions.

SEROLOGIC EVALUATION OF PATIENTS WITH PRIMARY AND RECURRENT OCULAR TOXOPLASMOSIS FOR EVIDENCE OF RECENT INFECTION

Serologic evaluation of patients with primary and recurrent ocular toxoplasmosis for evidence of recent infection. Am J Ophthalmol 1999; 128:407–412.

Serologic evaluation of patients with primary and recurrent ocular toxoplasmosis for evidence of recent infection

PURPOSE: To identify the frequency of recently acquired vs chronic systemic Toxoplasma gondii infections in patients with ocular toxoplasmosis. METHODS: Serum samples from 22 patients with primary ocular toxoplasmosis (not from scars) and 42 patients with recurrent ocular toxoplasmosis were tested for the presence of anti– T. gondii IgM, IgG, and IgA antibodies and compared with samples from 24 patients with other causes of uveitis. Intraocular production of anti– T. gondii IgG and IgA, and the presence of T. gondii DNA was determined in patients and control subjects from whom ocular fluid was available. RESULTS: Serologic evidence of recently acquired infection was found for 11 (50%) of 22 patients with primary ocular toxoplasmosis and for one (2%) of 42 with recurrent ocular toxoplasmosis. In the uveitis control group, anti– T. gondii IgM antibodies could be detected in two (8%) of 24 patients, but anti– T. gondii IgA antibodies were not detectable. Patients with primary ocular toxoplasmosis and serologic markers of recently acquired systemic infection were significantly older than those with chronic infection ( P = .008). Intraocular production of anti– T. gondii IgG was more frequently noted in patients with recurrent than primary ocular toxoplasmosis (81% vs 41%; P < .001), but intraocular T. gondii DNA was more frequently found in patients with primary ocular toxoplasmosis than in those with recurrent ocular toxoplasmosis (37% vs 4%; P < .01). CONCLUSIONS: Primary ocular toxoplasmosis can be seen in either recently acquired or chronic T. gondii infection. Patients with ocular disease and recently acquired infection were older and more likely to have T. gondii DNA in intraocular fluids.

Differences between intraocular and serum antibody responses in patients with ocular toxoplasmosis

PURPOSE: To investigate the antigen specificity of the intraocular anti– Toxoplasma gondii antibody response in patients with ocular toxoplasmosis. METHODS: Paired ocular fluid and serum samples were collected from 13 patients with active ocular toxoplasmosis. Serum IgM anti– T. gondii antibodies were tested to distinguish recently-acquired from chronic infection. Anti– T. gondii IgG specificity was analyzed by immunoblotting using a crude T. gondii extract. RESULTS: Two of the 13 patients tested were IgM positive and considered to have acquired ocular toxoplasmosis. The antibody specificity in ocular fluid and serum of these two patients was similar, whereas in the patients with presumed chronic disease, marked differences could be observed. Most ocular fluid samples contained antibodies that stained a 28-kD antigen more intensely than did antibodies from paired serum samples. Using absorption and elution experiments, we demonstrated that this 28-kD protein was identical to the GRA-2 antigen, which is expressed in both the tachyzoite and the bradyzoite stages of the parasite. CONCLUSIONS: Our results show that the intraocular T. gondii antibody response of patients with recurrent ocular toxoplasmosis differs from the systemic response. This finding may have implications for our understanding of the immunopathogenesis of ocular toxoplasmosis and could be employed to improve diagnosis of the disease.

Recognition of a 28 and 45 kDa Toxoplasma gondii antigen by IgG from eyes of patients with active recurrent ocular toxoplasmosis

Recognition of a 28 and 45 kDa Toxoplasma gondii antigen by IgG from eyes of patients with active recurrent ocular toxoplasmosis

Recognition of a 28 and 45 kDa Toxoplasma gondii antigen by IgG from eyes of patients with active recurrent ocular toxoplasmosis

Recognition of a 28 and 45 kDa Toxoplasma gondii antigen by IgG from eyes of patients with active recurrent ocular toxoplasmosis

Quantitative Polymerase Chain Reaction in Diagnosing Ocular Toxoplasmosis

To determine if quantitative competitive polymerase chain reaction can be used to diagnose ocular toxoplasmosis with certainty. We examined the vitreous humor of a patient with recurrent ocular toxoplasmosis by using quantitative competitive polymerase chain reaction. The number of Toxoplasma gondii in the vitreous humor was quantified by quantitative competitive polymerase chain reaction. Quantitative competitive polymerase chain reaction was useful for diagnosing ocular toxoplasmosis.

1421 Toxoplasma gondii-specific T cell clones isolated from the vitreous fluid of patients with recurrent ocular toxoplasmosis

1421 Toxoplasma gondii-specific T cell clones isolated from the vitreous fluid of patients with recurrent ocular toxoplasmosis