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Simplified world map of global seroprevalence for T. gondii. Colour code: dark red: >60%; red: 40e60%; yellow: 20e40%; blue: 10e20%; green: <10%; grey: no data available; striated areas represent strong regional differences. Note to the reader: In several cases seroprevalences depicted may not be a true representative for an individual country since small regional data sets have been used and extrapolated country wide. Furthermore, samples were frequently drawn from populations strongly biased towards pregnant women. Data combined from Pappas et al. (2009); Tenter et al. (2000) and individual sources: (Asatova et al., 1993; Ashrafunnessa et al., 1998; Jacquier et al., 1995; Kamani et al., 2009; Kistiah et al., 2012; Lopes et al., 2012; Minbaeva et al., 2013; Pal et al., 1996; Sadaruddin et al., 1991; Sakikawa et al., 2012; Swai and Schoonman, 2009).

Simplified world map of global seroprevalence for T. gondii. Colour code: dark red: >60%; red: 40e60%; yellow: 20e40%; blue: 10e20%; green: <10%; grey: no data available; striated areas represent strong regional differences. Note to the reader: In several cases seroprevalences depicted may not be a true representative for an individual country since small regional data sets have been used and extrapolated country wide. Furthermore, samples were frequently drawn from populations strongly biased towards pregnant women. Data combined from Pappas et al. (2009); Tenter et al. (2000) and individual sources: (Asatova et al., 1993; Ashrafunnessa et al., 1998; Jacquier et al., 1995; Kamani et al., 2009; Kistiah et al., 2012; Lopes et al., 2012; Minbaeva et al., 2013; Pal et al., 1996; Sadaruddin et al., 1991; Sakikawa et al., 2012; Swai and Schoonman, 2009).

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Toxoplasma gondii is an extremely successful opportunistic parasite which infects approximately one third of the human population worldwide. The impact of this parasite on human health becomes particularly manifest in congenital damage with infection and subsequent inflammation of neuronal tissues including the retina. Although advances in our unde...

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... 10 to 80%) and even within countries. Low seroprevalence has been re- ported from South East Asia, North America ( Dubey and Jones, 2008) and Northern Europe (10e30%). Prevalences between 30 and 50% have been reported for Central and Southern Europe, whereas high seroprevalences are observed in Latin America and in tropical African countries (Fig. 3) (Robert-Gangneux and Darde, 2012). In countries with low and moderate seroprevalence, the seropositivity rates increase with age due to the lifelong but relative low risk of infection (Table 1). Interestingly, in countries with high seroprevalence, seropositivity rates plateau at relative young age (e.g. in Brazil at the age of 20e29 ...

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... Among the clinical manifestations of CT, the retinochoroiditis is one of the most common disease outcomes reported in Brazil [12]. The consequences for the infants that may result in partial or total loss of vision depend on the location where the lesions develop and the extent of the affected tissue [13]. New retinochoroidal lesions developed after the first year of life is common even in patients treated, which indicates the importance of long-term follow-up of patients with CT [14]. ...
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Changes on immune response of children with congenital toxoplasmosis (CT) regarding infection evolution and therapeutic intervention was addressed. Infants with CT presented increased counts of monocytes, CD3-CD16-CD56High, CD3+CD56+ and CD4+ T-cells 1-year after treatment onset (TOXO1-yearAT). Smaller numbers of CD3-CD16-CD56+ and TCRγδ+ T-cells were specifically observed in infants with retinochoroidal lesions (L(+)). When infants were classified based on the baseline status, expansion of CD3-CD16-CD56High and CD4+ T-cells were observed in L(+) who had active, active/cicatricial or cicatricial lesions. Infants who had active or active/cicatricial lesions display augmented numbers of monocytes, CD3-CD16+CD56+, CD3+CD56+, CD8+DR+ and TCRγδ+ T-cells and those with active/cicatricial or cicatricial at baseline displayed increase in CD14+CD64+ monocytes. Moreover, all L(+) had increased IFN-γ+ and IL-10+ CD4+ T-cells, while L(-) had increased ratios of TNF+, IFN-γ+ and IL-4+ NK-cells upon antigen-specific stimulation. Persistent alterations in leukocytes in TOXO1-yearAT suggest long-term sequels in the immune system of infants with CT.
... Interestingly, the cysts contain hundreds of bradyzoites and their size may reach up to 60 lm. However, in most cases, they do not cause host reaction and remain inactive [7]. ...
Article
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PurposeThis review aims to summarize the current knowledge concerning the clinical features, diagnostic work-up and therapeutic approach of ocular toxoplasmosis focusing mainly on the postnatally acquired form of the disease.MethodsA meticulous literature search was performed in the PubMed database. A supplementary search was made in Google Scholar to complete the collected items.ResultsOcular toxoplasmosis is one of the most frequent infectious etiologies of posterior uveitis. It typically presents with retinochoroiditis. Setting an accurate diagnosis depends to a considerable degree on detecting characteristic clinical characteristics. In addition to the evaluation of clinical features, the diagnosis of toxoplasmosis relies at a large degree on serologic testing. The detection of the parasite DNA in the aqueous or vitreous humor can provide evidence for a definitive diagnosis. The current mainstay for the treatment, if necessary, is the use of oral antibiotic with systemic corticosteroids. Recent evidence suggests other therapeutic approaches, such as intravitreal antibiotics can be used.Conclusion Recent developments in the diagnostic and therapeutic approach have contributed to preventing or limiting vision loss of patients suffering from ocular toxoplasmosis. Further studies are required to provide a better understanding of epidemiology, pathogenesis, diagnosis, and treatment with a significant impact on the management of this challenging clinical entity.
... Toxoplasma gondii is a highly successful opportunistic parasite, which can be successfully treated upon detection, despite infecting approximately one-third of the world's population [1]. Most primary infections in humans remain asymptomatic; however, target organs such as the eyes and brain are prone to sequelae which may affect daily function. ...
Article
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Purpose Studies on the occurrence of ocular toxoplasmosis (OT) in a general population are rare. Therefore, we conducted this pilot study to assess whether a nonmydriatic ultra-wide-field (UWF) scanning laser ophthalmoscope (SLO) is suitable for a simple, rapid screening procedure. Methods The population of this cross-sectional study was randomly recruited from a cohort of hospital-based patients in an urban geriatric hospital. Ophthalmologic evaluation was performed on 201 eyes from 101 participants through nonmydriatic UWF-SLO (Optos Daytona) and assessed for suspicious lesions and other relevant ocular findings. All images were evaluated by two independent examiners. Individuals who presented lesions with a morphological appearance suggestive of OT underwent fundoscopy and serological analysis of Toxoplasma gondii -specific antibodies. Results The mean age of the study group was 76 years, and 63 (62%) were female. Despite many health restrictions, the SLO examination was carried out easily in this geriatric population. Three participants presented findings by SLO suspicious for T. gondii -related injury. Further clinical examination and serological investigation confirmed the diagnosis, with funduscopic evaluation and positive T. gondii ELISA testing. In addition, a high rate of arterial hypertension and dyslipidemias within the cohort led to a high incidence of vascular changes and age-related fundus findings. Conclusion In our study, we confirm that UWF-SLO technology is helpful in the rapid detection of peripheral retinal injuries in elderly patients such as OT and may be used as a routine screening tool.
... Severe life-threatening toxoplasmosis may develop in immunosuppressed patients due to reactivation of latent infection (Bessieres et al., 2009). During pregnancy, T. gondii is transmitted congenitally, mother-to-foetus, to which infection can cause severe damage including brain calcification, hydro-encephalitis, vision disorders and still birth or abortion (Roberts et al., 2001;Pleyer et al., 2014;Brasil et al., 2017;Jones et al., 2017). The prevalence of congenital toxoplasmosis in different communities ranges from 0.1 to 1.0 cases per 1,000 live births (Yıldız et al., 2015), and ophthalmological and neurological disabilities are the most important consequences of congenital toxoplasmosis (Blader et al., 2015). ...
... Approximately 70 to 90% of patients with CT and 10 to 12% of patients with postnatal toxoplasmosis develop ocular toxoplasmosis (OT), which is the most common cause of retinitis (Dardé, 2008). OT is either acquired or caused by reactivation of congenital infection (Pleyer et al., 2014). Toxoplasmic encephalitis (TE) is the leading cause of mortality in HIV-infected patients (Rothova, 2003). ...
... 1,2 Old retinal scars are hallmarks of OT, and the presence of pigmented old scars near the active lesion in the retina strongly suggests that an active lesion is from a congenital infection recurrence. However, OT is known to develop not only from recurrences of congenital infection but also from postnatally acquired primary infections, [3][4][5][6][7][8] which account for the majority of OT cases. 4,9,10 Additionally, evidence of OT followed by an outbreak of toxoplasmosis, that is, the detection of both immunoglobulin (Ig) G and IgM, has confirmed that primary acquired OT may be more frequent than previously thought. ...
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Purpose: To establish a murine model of primary acquired ocular toxoplasmosis (OT) and to investigate the immune mediator profiles in the aqueous humor (AH). Methods: C57BL/6 mice were perorally infected with Toxoplasma gondii. The ocular fundus was observed, and fluorescein angiography (FA) was performed. The AH, cerebrospinal fluid (CSF), and serum were collected before infection and at 28 days post-infection (dpi); the immune mediator levels in these samples were analyzed using multiplex bead assay. Results: Fundus imaging revealed soft retinochoroidal lesions at 14 dpi; many of these lesions became harder by 28 dpi. FA abnormalities, such as leakage from retinal vessels and dilation and tortuosity of the retinal veins, were observed at 14 dpi. Nearly all these abnormalities resolved spontaneously at 28 dpi. In the AH, interferon-γ, interleukin (IL)-1α, IL-1β, IL-6, IL-10, IL-12(p40), IL-12(p70), CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, and CXCL1/KC levels increased after infection. All these molecules except IL-1α, IL-4, and IL-13 showed almost the same postinfection patterns in the CSF as they did in the AH. The tumor necrosis factor α, IL-4, and IL-5 levels in the AH and CSF of the T. gondii-infected mice were lower than those in the serum. The postinfection IL-1α, IL-6, CCL2/MCP-1, CCL4/MIP-1β, and granulocyte colony-stimulating factor levels in the AH were significantly higher than those in the CSF and serum. Conclusions: A murine model of primary acquired OT induced via the natural infection route was established. This OT model allows detailed ophthalmologic, histopathologic, and immunologic evaluations of human OT. Investigation of AH immune modulators provides new insight into OT immunopathogenesis.
... Although there was no statistically significant association between occupation and POT/OT, middlemen who were directly involved in bulk purchase and retail sellers showed a near significant association (P=0.056). Possible causes of ocular manifestations of toxoplasmosis have not been fully elucidated, but it is believed that factors related to both the parasite and the host (genetic, age, immune status, inoculum) contribute to the development of this disease (19). ...
Article
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BACKGROUND፡ Toxoplasmosis is the commonest cause of infectious posterior uveitis in humans and can lead to blindness and low vision in both immune-competent and immune-compromised persons worldwide. The aim of this study was to determine the prevalence of Ocular Toxoplasmosis (OT) and potential risk factors among livestock farmers and raw meat handlers in Uyo. METHODS: This was a descriptive cross-sectional community-based study involving clinical eye examination, laboratory detection of anti-Toxoplasma gondiiIgG antibody There were 339 participants aged 15-78 (mean 34.8±11.6) years,283 (83.5%)were males 56(16.5%) were females; 189 (55.8%) tested seropositive for anti-Toxo. gondiiIgG antibodies.and HIV testing. Participants’ other information was obtained using interviewer-administered questionnaire. RESULTS: Eight (2.4%) had presumed ocular toxoplasmosis (POT); 6 of the 8 were seropositive for anti-T.gondiiIgG antibody; and 2 of the 8 POT (25%) were HIV-seropositive. Of the 189 who were anti-T.gondiiIgG antibody seropositive, 6 (3.2%) had OT. Factors associated with OT were age (31-50 years) and female gender (P = 0.049 and 0.001, respectively). HIV infection was associated with POT (P=0.033). Most of the ocular lesions (87.5%) were unilateral and located at the posterior pole (77.7%). CONCLUSION: The prevalence of presumed ocular toxoplasmosis (POT) and ocular toxoplasmosis (OT) among livestock farmers and raw meat handlers in Uyo are 2.4% and 1.8%, respectively. Potential risk factors are being female, and persons between fourth and fifth decades of life. Awareness creation on toxoplasmosis among this occupational group is advocated. KEYWORDS: Ocular toxoplasmosis, occupationally exposed, anti-T. gondiiIgG antibody
... OT typically presents as retinochoroiditis, sometimes associated with anterior uveitis or vasculitis [4]. It is often asymptomatic, especially when lesions are located at the outer edge of the retina, but can cause blurred vision and floaters [5]. In case of extensive lesions or particular location, such as macular or papillary involvement, the visual prognosis of the infected eye can be severe. ...
... The pathophysiological basis of this phenomenon is poorly understood. It may be the consequence of the active liberation of tachyzoites from resident cysts [5]. Other studies suggested the rupture of senescent cysts, traumas, hormonal fluctuations, decrease in humoral or cellular immunity, pregnancy, or even eye surgery [40][41][42]. ...
Article
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Infections with the protozoan parasite Toxoplasma gondii are frequent, but one of its main consequences, ocular toxoplasmosis (OT), remains poorly understood. While its clinical description has recently attracted more attention and publications, the underlying pathophysiological mechanisms are only sparsely elucidated, which is partly due to the inherent difficulties to establish relevant animal models. Furthermore, the particularities of the ocular environment explain why the abundant knowledge on systemic toxoplasmosis cannot be just transferred to the ocular situation. However, studies undertaken in mouse models have revealed a central role of interferon gamma (IFNγ) and, more surprisingly, interleukin 17 (IL17), in ocular pathology and parasite control. These studies also show the importance of the genetic background of the infective Toxoplasma strain. Indeed, infections due to exotic strains show a completely different pathophysiology, which translates in a different clinical outcome. These elements should lead to more individualized therapy. Furthermore, the recent advance in understanding the immune response during OT paved the way to new research leads, involving immune pathways poorly studied in this particular setting, such as type I and type III interferons. In any case, deeper knowledge of the mechanisms of this pathology is needed to establish new, more targeted treatment schemes.
... Humans can become infected with T. gondii when they ingest food contaminated with oocysts shed in the feces of cats (where the sexual cycle occurs) or tissue cysts present in undercooked meat (4). T. gondii infection is generally transient and presents with no or mild symptoms, except in immunocompromised individuals and in fetuses; in these cases severe ocular and neurologic disease may occur (5,6). Because it is difficult to prevent T. gondii infection, congenital transmission remains a significant problem in the US and around the world, together with encephalitis caused by reactivation of the parasite in immunosuppressed individuals (7,8). ...
Article
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Once considered unusual, nucleocytoplasmic glycosylation is now recognized as a conserved feature of eukaryotes. While in animals O -GlcNAc transferase (OGT) modifies thousands of intracellular proteins, the human pathogen Toxoplasma gondii transfers a different sugar, fucose, to proteins involved in transcription, mRNA processing and signaling. Knockout experiments showed that Tg SPY, an ortholog of plant SPINDLY and paralog of host OGT, is required for nuclear O -fucosylation. Here we verify that Tg SPY is the nucleocytoplasmic O -fucosyltransferase (OFT) by 1) complementation with Tg SPY-MYC 3 , 2) its functional dependence on amino acids critical for OGT activity, and 3) its ability to O -fucosylate itself and a model substrate and to specifically hydrolyze GDP-Fuc. While many of the endogenous proteins modified by O -Fuc are important for tachyzoite fitness, O -fucosylation by Tg SPY is not essential. Growth of Δ spy tachyzoites in fibroblasts is modestly affected, despite marked reductions in the levels of ectopically-expressed proteins normally modified with O -fucose. Intact Tg SPY-MYC 3 localizes to the nucleus and cytoplasm, whereas catalytic mutants often displayed reduced abundance. Δ spy tachyzoites of a luciferase-expressing type II strain exhibited infection kinetics in mice similar to wild type but increased persistence in the chronic brain phase, potentially due to an imbalance of regulatory protein levels. The modest changes in parasite fitness in vitro and in mice, despite profound effects on reporter protein accumulation, and the characteristic punctate localization of O -fucosylated proteins, suggest that Tg SPY controls the levels of proteins to be held in reserve for response to novel stresses.
... • Responsible of 85% of posterior uveitis in immunocompetent patients. 22 • In Europe and United States, toxoplasmosis was found as etiology of uveitis in 4-8% of patients. 5,23 • OT causes permanent visual impairment in more than 25% of patients. ...
Article
Purpose: To present a narrative review about ocular toxoplasmosis epidemiology, disease burden and prevalent African parasitic strains. Methods: An initial search for MeSH terms was conducted with a posterior advanced search in two electronic databases. Full text reading was performed. Results: Animal African studies have identified Toxoplasma gondii type II, type III, Africa 1, and Africa 3 strains. Seroprevalence varies from 6.4% to 74.5%. Nevertheless, there is a scarcity of epidemiology and serotyping information about ocular toxoplasmosis. African studies have demonstrated that uveitis patients present high frequencies of ocular toxoplasmosis. There is a lack of studies describing specific clinical characteristics, which can be related, to environmental and socioeconomic factors, parasite serotype and genotype, and genetic susceptibility of the host. Conclusion: As Toxoplasma gondii has more virulent strains in the Southern hemisphere, it is relevant to determine African strain types and the correlation between the infecting strains and the clinical manifestations.
... While infections of immunocompetent hosts are commonly asymptomatic to benign, they can be severe to even life-threatening in immunocompromised hosts or after transmission to fetuses during pregnancy (1). T. gondii is also a significant cause of posterior uveitis after infection of immunocompetent adults (2), particularly in South America where hypervirulent strains of the parasite are common (3). In the U.S.A., toxoplasmosis has recently been recognized as a leading food-borne infectious disease based on annual costs and loss of quality-adjusted life years (4). ...
Article
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Host defense against the human pathogen Toxoplasma gondii depends on secretion of interferon (IFN)-γ and subsequent activation of monocytic cells to combat intracellular parasites. Previous studies have shown that T. gondii evades IFN-γ-mediated immunity by secreting the effector TgIST into the host cell where it binds to STAT1, strengthens its DNA binding activity and recruits the Mi-2/NuRD complex to STAT1-responsive promoters. Here we investigated the impact of the host chromatin environment on parasite interference with IFN-γ-induced gene expression. Luciferase reporters under control of primary and secondary IFN-γ response promoters were only inhibited by T. gondii when they were stably integrated into the host genome but not when expressed from a plasmid vector. Absence of CpG islands upstream and/or downstream of the transcriptional start site allowed more vigorous up-regulation by IFN-γ as compared to CpG-rich promoters. Remarkably, it also favored parasite interference with IFN-γ-induced gene expression indicating that nucleosome occupancy at IFN-γ-responsive promoters is important. Promoter DNA of IFN-γ-responsive genes remained largely non-methylated in T. gondii-infected cells, and inhibition of DNA methylation did not impact parasite interference with host responses. IFN-γ up-regulated histone marks H4ac, H3K9ac, and H3K4me3 but down-regulated H3S10p at primary and secondary response promoters. Infection with T. gondii abolished histone modification, whereas total nuclear activities of histone acetyl transferases and histone deacetylases were not altered. Taken together, our study reveals a critical impact of the host chromatin landscape at IFN-γ-activated promoters on their inhibition by T. gondii with a comprehensive blockade of histone modifications at parasite-inactivated promoters.