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Redox Biology Nov 2023Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is...
Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT.
Topics: Animals; Mice; Humans; Toxoplasmosis, Ocular; Ferroptosis; Toxoplasma; Chorioretinitis; Retina; Iron
PubMed: 37738924
DOI: 10.1016/j.redox.2023.102890 -
Le Infezioni in Medicina 2023cytomegalovirus (CMV) retinitis, cerebral and ocular toxoplasmosis are common infections in patients with acquired immunodeficiency syndrome (AIDS). Material and...
BACKGROUND
cytomegalovirus (CMV) retinitis, cerebral and ocular toxoplasmosis are common infections in patients with acquired immunodeficiency syndrome (AIDS). Material and methods: this is a case of a 46-year-old female with previous Kaposi's sarcoma, diagnosed with an HIV infection two weeks prior to hospitalization. Blood test at diagnosis showed a CD4+ count of 77 cell/μL and HIV-RNA 3.758.745 copies/mL. Therapy with bictegravir/emtricitabine/tenofovir alafenamide fumarate was started and clinical, viroimmunological and microbiological investigations were performed.
RESULTS
the patient went to our hospital for the onset of left occipito-parietal headache and blurred vision. Brain CT and MRI were performed which did not show focal lesions or vascular alterations. Syphilis serology was negative, serology showed positive IgG and negative IgM, serum CMV-DNA was 31.184 IU/mL. Eye fundus evidenced intraretinal hemorrhages, fluorescein angiography and computed optical tomography documented cottony exudates, retinal hemorrhages and vitreous involvement. Therapy with valganciclovir was initiated for suspicion of CMV retinitis. About a month later, the patient reported blurred vision for which she was re-admitted. Ocular fundus showed a cottony lesion near the macula. Molecular test on vitreous body was positive for , while on cerebrospinal fluid it was negative; in addition, an MRI of the brain with contrast medium was performed which showed an area of altered hyperintense signal compatible with a diagnosis of uveitis and neurotoxoplasmosis. Therapy with pyrimethamine and clindamycin (allergy for sulfonamide reported by the patient) was started. Allergy counseling was performed with the execution of allergy tests (patch test) with negative result; therefore the administration of clindamycin was replaced with sulfadiazine. A month following the start of anti-toxoplasma therapy, there was a clinical and radiological improvement.
CONCLUSIONS
despite progressive developments in the management of PLWH, in this case two different kind of opportunistic infection are found in a late-presenter patient. In particular, two aspects can be highlighted. The first one is that, in the setting of an highly impaired immune system, clinical presentation can be deceptive and more than one opportunistic infection can be observed together in the same patient. The second aspect is that after starting antiretroviral therapy, a rapid improvement of viro-immunologic parameters has been documented, probably leading to an immune reconstitution inflammatory syndrome (IRIS).
PubMed: 37701378
DOI: 10.53854/liim-3103-15 -
Parasites, Hosts and Diseases Aug 2023In elderly patients, ocular toxoplasmosis is one of the most common etiologies of uveitis, which should be differentially diagnosed from ocular lymphoma, another common...
In elderly patients, ocular toxoplasmosis is one of the most common etiologies of uveitis, which should be differentially diagnosed from ocular lymphoma, another common pathology of uveitis in older adults. The high level of interleukin (IL)-10 and an IL-10/IL-6 ratio higher than 1 (>1.0) are helpful parameters to diagnose ocular lymphoma. In this study, we used aqueous humor samples to detect 4 cases of ocular toxoplasmosis in patients with high levels of IL-10 and an IL-10/IL-6 ratio higher than 1. Our results show that ocular toxoplasmosis may be associated with increased cytokine levels in aqueous humor.
Topics: Aged; Humans; Interleukin-10; Toxoplasmosis, Ocular; Interleukin-6; Cytokines; Lymphoma, Non-Hodgkin; Eye Neoplasms
PubMed: 37648237
DOI: 10.3347/PHD.22172 -
Research Square Aug 2023Studies 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 and herpetic viruses and HIV, and chest radiographs.
RESULTS
We recruited 128 patients. The mean age was 36 ± 14 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: 37609303
DOI: 10.21203/rs.3.rs-3222203/v1 -
Cureus Jul 2023This report describes the optical coherence tomography angiography (OCTA) findings detected at the choriocapillaris slab before the clinical picture of acute...
This report describes the optical coherence tomography angiography (OCTA) findings detected at the choriocapillaris slab before the clinical picture of acute toxoplasmosis choroiretinitis (TCR) by following up a patient with serial images of OCT and OCTA from the quiescent to the active stage of the disease. In this case, the increased thickness of the choroid in the OCT B-scan and the prominent flow void at the choriocapillaris slab of the OCTA were detected early in the course of the disease. OCTA is a useful imaging technique in TCR and might help in predicting the TCR lesion at the subclinical stage.
PubMed: 37554609
DOI: 10.7759/cureus.41543 -
Frontiers in Cellular Neuroscience 2023Toxoplasmosis affects one third of the world population and has the protozoan as etiological agent. Congenital toxoplasmosis (CT) can cause severe damage to the fetus,...
BACKGROUND
Toxoplasmosis affects one third of the world population and has the protozoan as etiological agent. Congenital toxoplasmosis (CT) can cause severe damage to the fetus, including miscarriages, intracranial calcification, hydrocephalus and retinochoroiditis. Severity of CT depends on the gestational period in which infection occurs, and alterations at the cellular level during retinal development have been reported. In this study, we proposed a mouse CT model to investigate the impact of infection on retinal development.
METHODS
Pregnant females of pigmented C57BL/6 strain mice were infected intragastrically with two cysts (ME49 strain) at embryonic day 10 (E10), and the offspring were analyzed at E18.
RESULTS
Infected embryos had significantly smaller body sizes and weights than the PBS-treated controls, indicating that embryonic development was affected. In the retina, a significant increase in the number of Ki-67-positive cells (marker of proliferating cells) was found in the apical region of the NBL of infected mice compared to the control. Supporting this, cell cycle proteins Cyclin D3, Cdk6 and pChK2 were significantly altered in infected retinas. Interestingly, the immunohistochemical analysis showed a significant increase in the population of β-III-tubulin-positive cells, one of the earliest markers of neuronal differentiation.
CONCLUSIONS
Our data suggests that CT affects cell cycle progression in retinal progenitor cells, possibly inducing the arrest of these cells at G2/M phase. Such alterations could influence the differentiation, anticipating/increasing neuronal maturation, and therefore leading to abnormal retinal formation. Our model mimics important events observed in ocular CT.
PubMed: 37545879
DOI: 10.3389/fncel.2023.1211446 -
Case Reports in Infectious Diseases 2023, an obligate intracellular parasitic protozoon, usually causes a mild, acute infection followed by a latent asymptomatic phase with tissue cysts or a chronic form with...
, an obligate intracellular parasitic protozoon, usually causes a mild, acute infection followed by a latent asymptomatic phase with tissue cysts or a chronic form with recurrent retinochoroiditis. However, immunocompromised patients can cause disseminated disease due to the reactivation of the latent tissue cysts or due to a primary infection. Here, we present a rare case of bilateral ocular toxoplasmosis and concurrent subacute toxoplasma encephalitis in a 70-year-old patient on anti-CD40 treatment following his liver transplant. The diagnosis was confirmed by PCR of anterior chamber fluid and brain biopsy, and no other sites of disseminated disease were detected on PET-CT. The patient has been treated with sulfamethoxazole-trimethoprim 800/160 mg with virtually complete resolution of the neurological and ocular symptoms. Iatrogenic blockade of the CD40 pathway may elicit a particular susceptibility for CNS reactivation of .
PubMed: 37545749
DOI: 10.1155/2023/5565575 -
International Ophthalmology Oct 2023To analyse the demography, etiology, and classification of uveitis at a tertiary academic referral center. (Observational Study)
Observational Study
PURPOSE
To analyse the demography, etiology, and classification of uveitis at a tertiary academic referral center.
METHODS
An observational study was conducted on the archives of uveitic patients at the Ocular Inflammation Service of the Department of Ophthalmology at the University Hospital of Ioannina (Greece) from 1991 to 2020. This study aimed to investigate the epidemiological profile of patients, including their demographics and the main etiologic factors of uveitis.
RESULTS
Out of 6191 cases with uveitis, 1925 were infectious, 4125 were non-infectious, and an overall of 141 masquerade syndromes were recorded. Among these cases, 5950 patients were adults, with a slight female predominance, while 241 were children (< 18 years old). Interestingly, 24.2% of cases (1500 patients) were associated with 4 specific microorganisms. Herpetic uveitis (HSV-1 and VZV/HZV) was the most common cause of infectious uveitis (14.87%), followed by toxoplasmosis (6.6%) and tuberculosis (2.74%). In 49.2% of non-infectious uveitis cases, no systematic correlation was found. The most frequent causes of non-infectious uveitis included sarcoidosis, white dot syndromes, ankylosing spondylitis, lens-induced uveitis, Adamantiades-Behçet disease, and idiopathic juvenile arthritis. Infectious uveitis was more common in the rural population, whereas non-infectious uveitis was more frequently recorded in the urban population CONCLUSIONS: Although our study was conducted on a predominantly white Caucasian population, it also reflects the effect of increasing immigration, improvements of diagnostic techniques, changes in referral patterns, and various actual changes in disease incidence.
Topics: Adult; Child; Humans; Female; Adolescent; Male; Uveitis; Behcet Syndrome; Tertiary Care Centers; Morbidity; Referral and Consultation; Retrospective Studies
PubMed: 37428299
DOI: 10.1007/s10792-023-02772-5 -
PloS One 2023Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii, affects about one-third of the world's population and can cause severe congenital,...
Repurposing the Medicines for Malaria Venture's COVID Box to discover potent inhibitors of Toxoplasma gondii, and in vivo efficacy evaluation of almitrine bismesylate (MMV1804175) in chronically infected mice.
Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii, affects about one-third of the world's population and can cause severe congenital, neurological and ocular issues. Current treatment options are limited, and there are no human vaccines available to prevent transmission. Drug repurposing has been effective in identifying anti-T. gondii drugs. In this study, the screening of the COVID Box, a compilation of 160 compounds provided by the "Medicines for Malaria Venture" organization, was conducted to explore its potential for repurposing drugs to combat toxoplasmosis. The objective of the present work was to evaluate the compounds' ability to inhibit T. gondii tachyzoite growth, assess their cytotoxicity against human cells, examine their absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, and investigate the potential of one candidate drug through an experimental chronic model of toxoplasmosis. Early screening identified 29 compounds that could inhibit T. gondii survival by over 80% while keeping human cell survival up to 50% at a concentration of 1 μM. The Half Effective Concentrations (EC50) of these compounds ranged from 0.04 to 0.92 μM, while the Half Cytotoxic Concentrations (CC50) ranged from 2.48 to over 50 μM. Almitrine was chosen for further evaluation due to its favorable characteristics, including anti-T. gondii activity at nanomolar concentrations, low cytotoxicity, and ADMET properties. Administering almitrine bismesylate (Vectarion®) orally at dose of 25 mg/kg/day for ten consecutive days resulted in a statistically significant (p < 0.001) reduction in parasite burden in the brains of mice chronically infected with T. gondii (ME49 strain). This was determined by quantifying the RNA of living parasites using real-time PCR. The presented results suggest that almitrine may be a promising drug candidate for additional experimental studies on toxoplasmosis and provide further evidence of the potential of the MMV collections as a valuable source of drugs to be repositioned for infectious diseases.
Topics: Animals; Mice; Toxoplasma; Almitrine; Drug Repositioning; COVID-19; Toxoplasmosis; Malaria
PubMed: 37418497
DOI: 10.1371/journal.pone.0288335