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PLoS Neglected Tropical Diseases Jun 2024Ocular toxoplasmosis (OT) is the most common cause of infectious uveitis worldwide, including Thailand. This study describes the clinical presentation, visual acuity...
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.
BACKGROUND
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.
METHODOLOGY/PRINCIPAL FINDINGS
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.
CONCLUSIONS
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.
Topics: Humans; Toxoplasmosis, Ocular; Male; Retrospective Studies; Adult; Female; Thailand; Visual Acuity; Middle Aged; Tertiary Care Centers; Young Adult; Immunocompromised Host; Antiparasitic Agents; Trimethoprim, Sulfamethoxazole Drug Combination; Adolescent; Treatment Outcome; Southeast Asian People
PubMed: 38843299
DOI: 10.1371/journal.pntd.0012232 -
Ocular Immunology and Inflammation Jan 2024Uveitis and scleritis may be caused by local or systemic infection, or associated with noninfectious systemic inflammatory autoimmune disease. This study explored the...
PURPOSE
Uveitis and scleritis may be caused by local or systemic infection, or associated with noninfectious systemic inflammatory autoimmune disease. This study explored the all-cause mortality following an individual's first presentation with uveitis/scleritis.
METHODS
A cross-sectional study was conducted on all uveitis/scleritis patients diagnosed by uveitis specialists and treated in a single tertiary referral center in New Zealand between 2006 and 2020(15y). Masquerade syndromes including intraocular lymphoma were excluded. Outcome measures: demographics, etiology of uveitis/scleritis, anatomical location and all-cause mortality.
RESULTS
2723 subjects were identified. Median age of onset of uveitis/scleritis was 44.9 years (Range:1.5-99.5 years). 49.6% were female. Median follow-up from diagnosis of uveitis/scleritis was 8.0 years (IQR 4.1-11.6 years) with a total follow-up of 24 443.3 subject-years. The most frequent diagnosis was idiopathic disease (30.9%), HLA-B27-positive uveitis (20.0%), and sarcoidosis (4.7%). Infectious etiologies (24.1%) were most commonly from herpes zoster virus (9.3%) and toxoplasmosis (4.3%). The age-adjusted mortality rate was higher in subjects with idiopathic disease, sarcoidosis, Fuchs' uveitis syndrome, granulomatosis with polyangiitis/ANCA-associated vasculitis, toxoplasmosis, and herpes zoster virus, when compared to HLA-B27-positive uveitis. Hazard of mortality peaked in the first seven years following diagnosis, then subsequently declined. Patients with uveitis/scleritis had a significantly higher rate of mortality compared to the general New Zealand population (IRR 1.656 = 0.017).
CONCLUSION
Infectious etiologies of uveitis/scleritis in this cohort were high when compared to other developed nations, attributable to data from a tertiary referral center treating inpatients. Potential shared inflammatory mechanisms in the eye and other organs can lead to concurrent non-ocular disease requiring systemic treatment, impacting an individual's longevity.
PubMed: 38833275
DOI: 10.1080/09273948.2023.2296033 -
Indian Journal of Ophthalmology Jun 2024A 33-year-old male presented with unilateral painless vision loss with a history of sub-tenon steroid for the same. The fundus showed an elevated focus of...
A 33-year-old male presented with unilateral painless vision loss with a history of sub-tenon steroid for the same. The fundus showed an elevated focus of retinochoroiditis with vitritis. On investigating for the cause, polymerase chain reaction test on the anterior chamber tap was found to be positive for Toxoplasma. Such confusing and atypical cases usually produce a clinical dilemma and should be managed in a stepwise manner. Ancillary investigations usually provide a clue to the clinician and should be performed without any hesitation.
Topics: Humans; Male; Adult; Toxoplasmosis, Ocular; Toxoplasma; Polymerase Chain Reaction; Chorioretinitis; Fundus Oculi; Eye Infections, Parasitic; DNA, Protozoan; Diagnosis, Differential; Fluorescein Angiography
PubMed: 38804796
DOI: 10.4103/IJO.IJO_3341_23 -
Frontiers in Immunology 2024Ocular toxoplasmosis (OT) is an intraocular infection caused by the parasite OT is manifested as retinal choroiditis and is the most common infectious cause of... (Review)
Review
Ocular toxoplasmosis (OT) is an intraocular infection caused by the parasite OT is manifested as retinal choroiditis and is the most common infectious cause of posterior uveitis. Invasion of the retina by leads to disruption of the blood-ocular barrier and promotes the migration of immune cells to the ocular tissues. Cytokines such as IFN-γ and IL-1β are effective for controlling parasite growth, but excessive inflammatory responses can cause damage to the host. In this review, we will discuss in detail the latest advances in the immunopathology and treatment of OT.
Topics: Humans; Toxoplasmosis, Ocular; Toxoplasma; Animals; Cytokines
PubMed: 38799473
DOI: 10.3389/fimmu.2024.1403025 -
Parasite Immunology May 2024Ocular toxoplasmosis (OT) is characterised by intraocular inflammation due to Toxoplasma gondii infection. Studies have found that interleukin 17 (IL-17) plays a central...
Ocular toxoplasmosis (OT) is characterised by intraocular inflammation due to Toxoplasma gondii infection. Studies have found that interleukin 17 (IL-17) plays a central role in the pathology of OT. However, nucleotide variability in IL17 and interleukin 17 receptor (IL17R) genes has not been characterised in OT. As cytokine gene polymorphisms may influence the expression of these molecules, the aim of this study was to verify whether IL17A (rs2275913), IL17F (rs763780), IL17RA (rs4819554) and IL17RC (rs708567) polymorphisms are associated with OT in a Brazilian population. This study enrolled 214 patients seropositive for T. gondii (110 with OT and 104 without) and 107 controls. Polymorphisms were identified by PCR-restriction fragment length polymorphism analysis, validated by DNA sequencing with chi-square and multivariate analyses being used to assess possible associations between polymorphisms and OT. Logistic regression under the dominant model revealed a protection factor against OT of the C mutant allele of the IL17F (rs763780) polymorphism. The T/C-C/C genotypes were significantly more common in patients without OT compared to those with OT (p value = 0.0066) and controls (p value = 0.014). Findings from this study suggest that the IL17F polymorphism may have an influence in the immunopathology of OT in Brazilian individuals.
Topics: Humans; Toxoplasmosis, Ocular; Male; Female; Interleukin-17; Adult; Brazil; Middle Aged; Young Adult; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Polymorphism, Restriction Fragment Length; Protective Factors; Adolescent; Genotype; Polymorphism, Genetic; Polymerase Chain Reaction; Aged
PubMed: 38767154
DOI: 10.1111/pim.13038 -
Eye (London, England) May 2024Studies on uveitis in Sierra Leone were conducted prior to the Ebola Virus Disease epidemic of 2013-16, which was associated with uveitis in 20% of survivors. They did...
BACKGROUND/OBJECTIVES
Studies on uveitis in Sierra Leone were conducted prior to the Ebola Virus Disease epidemic of 2013-16, which was associated with uveitis in 20% of survivors. They did not include imaging or investigation of tuberculosis and used laboratory services outside the country. We performed a cross-sectional study on patients presenting with uveitis to establish their clinical characteristics and identify the impact of in-country laboratory diagnoses.
METHODS
We invited uveitis cases presenting to Eye Clinics in Sierra Leone from March to September 2022 to participate in the study. They underwent a diagnostic work-up, including fundus and ocular coherence tomography imaging. Active uveitis cases underwent further investigations including serology and immunological tests for syphilis, tuberculosis, herpetic viruses and HIV and chest radiographs.
RESULTS
We recruited 128 patients. The median age was 34 (IQR 19) years and there was an equal gender split. Panuveitis was the predominant anatomical uveitis type (n = 51, 40%), followed by posterior uveitis (n = 36, 28%). Bilateral disease affected 40 patients (31%). Active uveitis was identified in 75 (59%) cases. ICD 11 definition of blindness with VA < 3/60 occurred in 55 (33%) uveitis eyes. Aetiology of uveitis from clinical and laboratory assessment demonstrated that most cases were of undifferentiated aetiology (n = 66, 52%), followed by toxoplasmosis (n = 46, 36%). Trauma contributed to eight (6%) cases, syphilis to 5 (4%) cases and Ebola to 2 (2%).
CONCLUSIONS
Uveitis was associated with high levels of visual impairment. Posterior and panuveitis contributed to the highest proportion of uveitis cases. Laboratory studies helped differentiate syphilis as a significant aetiology of uveitis.
PubMed: 38750125
DOI: 10.1038/s41433-024-03009-0 -
BMC Infectious Diseases May 2024Toxoplasma gondii (T. gondii) is capable of infecting nearly all warm-blooded animals and approximately 30% of the global population. Though most infections are...
BACKGROUND
Toxoplasma gondii (T. gondii) is capable of infecting nearly all warm-blooded animals and approximately 30% of the global population. Though most infections are subclinical in immunocompetent individuals, congenital contraction can lead to severe consequences such as spontaneous abortion, stillbirth, and a range of cranio-cerebral and/or ocular abnormalities. Previous studies reported that T. gondii-infected pregnancy mice unveiled a deficit in both the amount and suppressive functions of regulatory T (Treg) cells, accompanied with reduced levels of forkhead box p3 (Foxp3). Recently, accumulative studies have demonstrated that microRNAs (miRNAs) are, to some extent, relevant to T. gondii infection. However, the link between alterations in miRNAs and downregulation of Foxp3 triggered by T. gondii has been only sporadically studied.
METHODS
Quantitative reverse transcription polymerase chain reaction (RT-qPCR), protein blotting and immunofluorescence were employed to evaluate the impact of T. gondii infection and antigens on miRNA transcription and Foxp3 expression. Dual-luciferase reporter gene assays were performed to examine the fluorescence activity in EL4 cells, which were transfected with recombinant plasmids containing full-length/truncated/mutant microRNA-142a-3p (miR-142a) promoter sequence or wild type/mutant of Foxp3 3' untranslated region (3' UTR).
RESULTS
We found a pronounced increase in miR-142a transcription, concurrent with a decrease in Foxp3 expression in T. gondii-infected mouse placental tissue. Similarly, comparable findings have been experimentally confirmed through the treatment of EL4 cells with T. gondii antigens (TgAg) in vitro. Simultaneously, miR-142a mimics attenuated Foxp3 expression, whereas its inhibitors markedly augmented Foxp3 expression. miR-142a promoter activity was elevated upon the stimulation of T. gondii antigens, which mitigated co-transfection of mutant miR-142a promoter lacking P53 target sites. miR-142a mimics deceased the fluorescence activity of Foxp3 3' untranslated region (3' UTR), but it did not affect the fluorescence activity upon the co-transfection of mutant Foxp3 3' UTR lacking miR-142a target site.
CONCLUSION
In both in vivo and in vitro studies, a negative correlation was discovered between Foxp3 expression and miR-142a transcription. TgAg enhanced miR-142a promoter activity to facilitate miR-142a transcription through a P53-dependent mechanism. Furthermore, miR-142a directly targeted Foxp3 3' UTR, resulting in the downregulation of Foxp3 expression. Therefore, harnessing miR-142a may be a possible therapeutic approach for adverse pregnancy caused by immune imbalances, particularly those induced by T. gondii infection.
Topics: MicroRNAs; Female; Animals; Pregnancy; Forkhead Transcription Factors; Mice; Down-Regulation; Toxoplasma; Toxoplasmosis; Pregnancy Outcome; T-Lymphocytes, Regulatory; Mice, Inbred C57BL; 3' Untranslated Regions
PubMed: 38741041
DOI: 10.1186/s12879-024-09375-0 -
BMJ Case Reports May 2024A woman in her late 30s presented with sudden diminution of vision, redness and pain in the right eye (OD) of 10 days' duration. Best corrected visual acuity (BCVA) was...
A woman in her late 30s presented with sudden diminution of vision, redness and pain in the right eye (OD) of 10 days' duration. Best corrected visual acuity (BCVA) was 20/160 in OD and 20/20 in the left eye (OS). Anterior segment of OD showed keratic precipitates, flare 3+, cells 2+ and a festooned pupil. Vitreous haze and cells were seen in OD. Frosted branch angiitis (FBA) was seen in all quadrants in OD and old scar was seen in both eyes. Serum toxoplasma immunoglobulin G (IgG) was positive and IgM negative, and PCR of an aqueous humour sample was negative for She was diagnosed with toxoplasa retinochoroiditis in OD and treated with intravitreal clindamycin injections, oral anti- antibiotics and steroids. Three months later, her BCVA in OD was 20/40 with resolving inflammation. She presented 2 months later with a new focus of retinochoroiditis without FBA and an old scar.
Topics: Humans; Female; Chorioretinitis; Toxoplasmosis, Ocular; Toxoplasma; Adult; Multimodal Imaging; Vasculitis; Visual Acuity; Clindamycin; Tomography, Optical Coherence; Anti-Bacterial Agents
PubMed: 38740445
DOI: 10.1136/bcr-2022-253286 -
Life Science Alliance Jul 2024Toxoplasmosis is the most prevalent parasitic zoonosis worldwide, causing ocular and neurological diseases. No vaccine has been approved for human use. We evaluated the...
Toxoplasmosis is the most prevalent parasitic zoonosis worldwide, causing ocular and neurological diseases. No vaccine has been approved for human use. We evaluated the response of peripheral blood mononuclear cells (PBMCs) to a novel construct of total antigen in maltodextrin nanoparticles (NP/TE) in individuals with varying infectious statuses (uninfected, chronic asymptomatic, or ocular toxoplasmosis). We analyzed the concentration of IFN-γ after NP/TE ex vivo stimulation using ELISA and the immunophenotypes of CD4 and CD8 cell populations using flow cytometry. In addition, serotyping of individuals with toxoplasmosis was performed by ELISA using GRA6-derived polypeptides. Low doses of NP/TE stimulation (0.9 μg NP/0.3 μg TE) achieved IFN-γ-specific production in previously exposed human PBMCs without significant differences in the infecting serotype. Increased IFN-γ expression in CD4 effector memory cell subsets was found in patients with ocular toxoplasmosis with NP/TE but not with TE alone. This is the first study to show how T-cell subsets respond to ex vivo stimulation with a vaccine candidate for human toxoplasmosis, providing crucial insights for future clinical trials.
Topics: Humans; Nanoparticles; Polysaccharides; Toxoplasma; Antigens, Protozoan; Toxoplasmosis; Interferon-gamma; Lymphocyte Activation; Female; Adult; Leukocytes, Mononuclear; CD4-Positive T-Lymphocytes; Male; CD8-Positive T-Lymphocytes; T-Lymphocytes; Middle Aged
PubMed: 38724195
DOI: 10.26508/lsa.202302486 -
International Journal of Ophthalmology 2024Multiple evanescent white dot syndrome (MEWDS) is a rare fundus disease, characterized by acute vision loss and visual field defects. Many previous studies have... (Review)
Review
Multiple evanescent white dot syndrome (MEWDS) is a rare fundus disease, characterized by acute vision loss and visual field defects. Many previous studies have explained the possible pathogenesis and clinical features of primary MEWDS. However, as the number of reported cases increases, secondary MEWDS occurs in other related retinal diseases and injuries, exhibiting some special characteristics. The associated retinal diseases include multifocal choroiditis/punctate inner choroidopathy (MFC/PIC), acute zonal occult outer retinopathy, best vitelliform macular dystrophy, pseudoxanthoma elasticum, and ocular toxoplasmosis. The related retinal injury is laser photocoagulation, surgery, and trauma. Although primary MEWDS often have a self-limiting course, secondary MEWDS may require treatment in some cases, according to the severity of concomitant diseases and complications. Notably, MEWDS secondary to MFC/PIC that is prone to forming choroidal neovascularization and focal choroidal excavation, needs positive treatment with corticosteroids. The possible underlying pathogenesis of secondary MEWDS is the exposure of choroidal antigen after the disruption of Bruch's membrane. The MEWDS-related features in secondary MEWDS are still evanescent under most circumstances. Its prognosis and treatment depend on the severity of complications. Current studies propose that the etiology is associated with immune factors, including viral infection, inflammation in choroid and Bruch's membrane, and antigen exposure caused by retinal and/or choroidal insults. More pathogenic studies should be conducted in the future. Accurate diagnosis for secondary MEWDS could benefit patients in aspects of management and prognosis.
PubMed: 38721509
DOI: 10.18240/ijo.2024.03.23