[Ocular toxoplasmosis developed after liver transplantation]. / Karaciger Transplantasyonu Sonrasi Gelisen Oküler Toksoplazmoz.

Ocular toxoplasmosis after solid organ transplantation occurs usually within the first three months of primary infection or reactivation of latent infection. There are a few reports of ocular toxoplasmosis following liver transplantation in the literature, however, no reports were detected in the national data. In this report a 35-year-old female patient diagnosed as ocular toxoplasmosis following reactivation in the second year after liver transplantation, was presented. The case was successfully treated with trimethoprim/sulfamethoxazole and clindamycin. This case was presented to emphasize late presentation of toxoplasmosis in transplantation patients and to withdraw attention to the importance of serological investigations done before transplantation.

Ocular Toxoplasmosis after Exposure to Wild Game.

PURPOSE: To describe eight patients with toxoplasma retinochoroiditis following exposure to wild game. METHODS: Retrospective, multicenter case series. RESULTS: Eight men, aged 29 to 71 (mean, 56 years), developed toxoplasmic retinochoroiditis after hunting and/or consuming wild game in the United States, including seven deer and one bear. Five patients developed the disease after eating undercooked game meat, while three developed ocular findings after cleaning hunted animals. Seven patients were healthy prior to exposure. LogMAR visual acuity at presentation was 0.697 ± 0.745, improving to 0.256 ± 0.335 by last follow-up. Disease complications developed in five (62.5%) patients, of which recurrence of retinochoroiditis was the most common. CONCLUSIONS: Contact with wild game is a potential source of primary ocular toxoplasmosis in immunocompetent adults. Hunters and consumers of rare game are at risk of serious ocular disease and appropriate contact precautions and cooking may reduce this complication.

Pathogenesis of ocular toxoplasmosis.

Ocular toxoplasmosis is a retinitis -almost always accompanied by vitritis and choroiditis- caused by intraocular infection with Toxoplasma gondii. Depending on retinal location, this condition may cause substantial vision impairment. T. gondii is an obligate intracellular protozoan parasite, with both sexual and asexual life cycles, and infection is typically contracted orally by consuming encysted bradyzoites in undercooked meat, or oocysts on unwashed garden produce or in contaminated water. Presently available anti-parasitic drugs cannot eliminate T. gondii from the body. In vitro studies using T. gondii tachyzoites, and human retinal cells and tissue have provided important insights into the pathogenesis of ocular toxoplasmosis. T. gondii may cross the vascular endothelium to access human retina by at least three routes: in leukocyte taxis; as a transmigrating tachyzoite; and after infecting endothelial cells. The parasite is capable of navigating the human neuroretina, gaining access to a range of cell populations. Retinal Müller glial cells are preferred initial host cells. T. gondii infection of the retinal pigment epithelial cells alters the secretion of growth factors and induces proliferation of adjacent uninfected epithelial cells. This increases susceptibility of the cells to parasite infection, and may be the basis of the characteristic hyperpigmented toxoplasmic retinal lesion. Infected epithelial cells also generate a vigorous immunologic response, and influence the activity of leukocytes that infiltrate the retina. A range of T. gondii genotypes are associated with human ocular toxoplasmosis, and individual immunogenetics -including polymorphisms in genes encoding innate immune receptors, human leukocyte antigens and cytokines- impacts the clinical manifestations. Research into basic pathogenic mechanisms of ocular toxoplasmosis highlights the importance of prevention and suggests new biological drug targets for established disease.

Long-term outcome of children with congenital toxoplasmosis.

OBJECTIVE: Maternal toxoplasmosis infection acquired during pregnancy carries significant risk of fetal damage. We aimed to assess the long-term outcome of children and young adults with congenital toxoplasmosis diagnosed and treated in utero. STUDY DESIGN: This was a 20 year prospective study (1985-2005). All mothers received spiramycin, alone or associated with pyrimethamine-sulfadoxine, and underwent amniocentesis and monthly ultrasound screening. Infected children were followed every 3-6 months. RESULTS: Of 666 liveborn children (676 mothers), 112 (17%) had congenital toxoplasmosis. Among these, 107 were followed up for 12-250 months: 79 were asymptomatic (74%) and 28 had chorioretinitis (26%). Only 1 child had a serious neurological involvement. CONCLUSION: The percentage of chorioretinitis in treated children depends on length of follow-up, but this complication occurs mainly before the age of 5 years and almost always before the age of 10 years. Visual impairment was infrequently severe, and outcome appears consistently good. Long-term follow-up is recommended to monitor ocular and neurological prognosis, whatever the practical difficulties.

Disease of the Year 2019: Ocular Toxoplasmosis in HIV-infected Patients.

Ocular toxoplasmosis (OT) may be an initial manifestation of acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV)-infected patients. OT has different clinical manifestations and can mimic other intraocular infections. Clinical findings may show single or multifocal retinochoroidal lesions or panuveitis. Atypical presentations are associated with extensive uni- or bilateral areas of retinal necrosis. OT lesions not associated with preexisting retinochoroidal scars are usually due to acquired rather than congenital infection. When CD4+ T cell counts are <100 c/uL, vitritis is frequently mild. Isolated anterior uveitis has been reported in single cases. Positive immunoglobulin M (IgM) antibodies are rare but their presence can support the diagnosis. As atypical presentations of OT are common, anterior chamber puncture for multiplex polymerase chain reaction amplification of infectious DNA should be considered, as early diagnosis and treatment can prevent massive tissue destruction and preserve vision. This review provides an overview of OT in HIV-infected patients.

Analysis of recurrence patterns associated with toxoplasmic retinochoroiditis.

PURPOSE: Toxoplasmic retinochoroiditis is thought to recur randomly. We sought to determine whether there is, instead, a longitudinal pattern of recurrences and to identify risk factors for recurrence. DESIGN: Longitudinal cohort study. METHODS: We collected the following data for 143 patients with toxoplasmic retinochoroiditis in The Netherlands: gender, first affected eye, age at first episode, mode of Toxoplasma gondii infection (congenital vs postnatal), treatment history, and presence of retinal scars at initial examination. For each episode, we determined age, duration since first episode, and interval since previous episode. We estimated the relationship between disease-free interval after an episode and recurrence risk. The influence of host and disease factors on recurrence risk was analyzed using Cox regression with frailty modeling for correlated intrapatient recurrence times. We performed a Monte Carlo test for occurrence of clusters after prolonged disease-free intervals. RESULTS: Follow-up ranged from 0.3 to 41 years (323 episodes in first-affected eyes). Recurrence risk was highest immediately after an episode, then decreased with increasing disease-free intervals, a pattern consistent with clustering. Relative risk (RR) of recurrence declined 72% (RR, 0.28; 95% confidence interval [CI], 0.22 to 0.36; P < .001) with each 10-year interval since first episode, and declined 15% (RR, 0.85; 95% CI, 0.71 to 1.01; P = .06) for each 10-year increase in age at first episode. Patients more than 40 years of age were at higher risk of recurrence than younger patients (RR, 1.74; 95% CI, 1.06 to 2.86; P = .03). Clusters of episodes occurred after prolonged disease-free intervals. CONCLUSIONS: Toxoplasmic retinochoroiditis occurs in clusters over time. Recurrence risk is influenced by patient age and duration of infection.

[Uveitis treated with biotherapy and/or DMARD: Analysis from the French Pharmacovigilance Study Base]. / Uvéites sous biothérapies et/ou DMARDs en rhumatologie : analyse de la base de données déclarative de la pharmacovigilance nationale française.

PURPOSE: To report the characteristics of uveitis cases occurring while on biologic therapy or disease-modifying antirheumatic drugs (DMARDs) reported to the French national pharmacovigilance database. METHODS: All the uveitis cases occurring in patients with chronic rheumatologic diseases, chronic inflammatory intestinal diseases or connective tissue diseases, while treated with DMARDs and/or biologic therapies between 2000 and 2015 and reported to the French National Pharmacovigilance Database were collected. RESULTS: During the study period, 32 cases of uveitis were reported (15 men, 17 women). Two patients were treated with one DMARD alone, 24 with biologic therapy alone, and six with both treatments. Anterior uveitis was diagnosed in 19 patients (8 cases were bilateral); intermediate uveitis was found (unilaterally) in one patient; posterior and diffuse uveitis occurred in 5 and 2 cases respectively. Five cases were inconclusive with regard to the anatomical type of uveitis. The uveitis was of infectious origin in 5 cases: 2 toxoplasmosis, 2 herpes virus and 1 tuberculosis. In the 27 other cases, it was not possible to state whether the uveitis was associated with the underlying disease (uncontrolled) or a side effect of the biologic/DMARD treatments. The occurrence of the uveitis led to 9 switches in biologic therapy and 13 discontinuations of treatment (8 complete discontinuations, 5 discontinuations only until uveitis remission was obtained). In 4 cases, the treatments were not modified. The database does not specify the ultimate course or rheumatologic disease activity at the time of the uveitis. CONCLUSIONS: The presence of uveitis while on biologic therapy must not be taken to indicate a therapeutic failure, especially if the ocular manifestation is isolated. In the case of uveitis occurring in patients treated with biologic therapies and/or DMARDs, infectious complications should be ruled out.

Toxoplasma retinitis following intravitreal injection of triamcinolone acetonide: A case report and review of literature.

The aim of this study was to report a case of atypical toxoplasma retinochoroiditis following intravitreal triamcinolone acetonide (IVTA) injection and to review the literature pertaining to toxoplasma retinochoroiditis following intravitreal injection of corticosteroid. Clinical data were collected from a 64-year-old male who developed toxoplasma retinitis 2 months after IVTA. A review of the literature was conducted to identify additional reports on similar cases. A 64-year-old male, known diabetic with nonproliferative diabetic retinopathy in both the eyes and optic atrophy in the left eye, presented with atypical retinitis inferior to the disc following IVTA. Real-time polymerase chain reaction and serology confirmed the toxoplasma etiology, and the patient was started on anti-toxoplasma therapy along with oral corticosteroid leading to regression of the lesion by 3 months. A high index of suspicion and proper microbiological diagnosis with appropriate antimicrobial therapy can aid in the management of toxoplasma retinochoroiditis following intravitreal injection of corticosteroid.

Toxoplasmosis retinochoroiditis after photodynamic therapy and intravitreal triamcinolone for a supposed choroidal neovascularization: a case report.

The purpose is to report a complication after photodynamic therapy (PDT) and intravitreal triamcinolone for a presumed choroidal neovascularization in age-related macular degeneration. Photodynamic therapy and intravitreal triamcinolone were used in an 84-year-old man with choroidal neovascularization in the left eye. Forty-five days after therapy, the patient returned with a severe necrotizing uveitis in the posterior pole and vitritis. Laboratory investigation disclosed a high anti-Toxoplasma IgG titer. Therapy with pyrimethamine, sulfadiazine and folinic acid resulted in total lesion healing although central vision was lost. Intravitreal triamcinolone may have had an influence on the exacerbation of retinochoroiditis in the posterior pole of the patient. Although rare, this complication may not be disregarded in the cases that require intraocular corticosteroids for treatment of several conditions, especially in patients who had previously suffered from toxoplasmosis infection.

The Impact of Short-Term, Intensive Antifolate Treatment (with Pyrimethamine and Sulfadoxine) and Antibiotics Followed by Long-Term, Secondary Antifolate Prophylaxis on the Rate of Toxoplasmic Retinochoroiditis Recurrence.

PURPOSE: To assess the impact of intensive antifolate treatment, followed by secondary antifolate prophylaxis (A-SP) on the recurrence rate of toxoplasmic retinochoroiditis (TRC). To investigate whether there are any other factors potentially predisposing for recurrence. MATERIAL AND METHODS: A total of 637 medical records of TRC patients, who had been treated in the years 1994-2013 were reviewed. All patients were treated with pyrimethamine /sulfadoxine one 25mg/500mg tablet daily (P/S 25/500mg) for 21 days with a double loading dose for the first two days. From Day 2 the patients also received prednisone at a starting dose of 40mg and spiramycine 3 million IU three times daily, given for 10 days followed by azithromycin 500mg once daily for another 6 days. The analysis of the recurrence rate involved 352 patients who had completed 6-month secondary prophylaxis (P/S one 25 mg/500mg tablet twice a week). RESULTS: When secondary antifolate prophylaxis (A-SP) was instituted immediately after the treatment for TRC, the probability of 3-year recurrence-free survival after the first course of A-SP was 90.9%. A recurrence was most likely approximately 3.5 years after the first treatment. A univariate Cox regression model demonstrated that a risk for recurrence was 2.82 times higher (p = 0.02) in patients with retinal scars. In the multivariate analysis, the risk for recurrence was 2.41 higher (p = 0.06). In patients with haemorrhagic lesions the risk for recurrence was lower, aRR = 0.17 (approaching borderline statistical significance p = 0.08). CONCLUSIONS: With the institution of A-SP of immediately after the intensive treatment for TRC, i.e. when a reactivation was most likely, there was no recurrence during A-SP. Following A-SP the recurrence rates were low and recurrence-free periods tended to be longer. The treatment regimen employed had a beneficial effect on the recurrence interval as it reduced and delayed the highest probability of recurrence.

Reactivation of ocular toxoplasmosis after LASIK.

PURPOSE: To report a reactivation of ocular toxoplasmosis after LASIK. METHODS: Case report of a 34-year-old man who underwent bilateral LASIK. The posterior segment examination revealed an old toxoplasmosis scar in the retinal periphery of the right eye. RESULTS: Uncorrected visual acuity improved postoperatively, and the patient was satisfied. However, 52 days after the procedure, he complained of loss of visual acuity in his right eye. Examination revealed signs of anterior uveitis, vitreitis, and active chorioretinal lesion satellite of the old toxoplasmosis scar. The patient was treated with a multidrug regiment with resolution of the vitreous and lesion activity. CONCLUSIONS: Toxoplasmosis reactivation may develop after LASIK.

[Postnatal follow-up of infants born to mothers with certain Toxoplasma gondii infection: evaluation of prenatal management]. / Follow-up post-natale in nati da madre con infezione certa da Toxoplasma gondii: considerazioni sul management prenatale.

UNLABELLED: The clinical management of perinatal toxoplasmosis involves a gynaecologist during pregnancy and a neonatologist after delivery. Then, in the absence of a uniform approach, early evaluation of infected infants requires a thorough long-term follow-up also in asymptomatic children, who have to be observed for at least one year due to unpredictable sequelae in later life. We retrospectively analyzed pregnancy management of 54 women with certain infection from Toxoplasma gondii (TG) and prospectively enrolled their infants to compare prenatal management with postnatal clinical outcome. All mothers with seroconversion for TG infection were from the Palermo area and were retrospectively analyzed, whereas their newborns referred to G. Di Cristina Children Clinical Hospital between 1999-2004 were prospectively enrolled in a 48-month follow-up. Timing of infection was dated for 24 women (45%) to the first trimester, 18 (33%) to the second and 12 (22%) the third. The maternal-fetal transmission rate was 17.2%. Prenatal diagnosis from amniotic fluid was performed in 25/54 pregnant subjects and showed positive results in 6. Despite diagnosis of TG infection, 9 women were untreated and only 2 with positive amniocentesis received combined therapy. 10/55 enrolled infants were infected and half of them were preterm and/or SGA at birth. None showed peculiar signs of TG at birth but 4 had abnormalities during the follow-up. 9/10 infected children were born to mothers who had undergone neither amniocentesis nor combined therapy. CONCLUSIONS: Our work confirms the difficulty of applying standardized therapeutic protocol for TG infection during pregnancy. The asymptomatic course of TG infection at birth confirms the importance of an instrumental long-term follow-up to identify typical TG lesion to prevent sequelae.

Differential diagnosis of retinitis and choroiditis in patients with acquired immunodeficiency syndrome.

Patients with acquired immunodeficiency syndrome (AIDS) are at high risk for developing retinitis. The most common forms of retinitis in such patients are those caused by cytomegalovirus (CMV) and Toxoplasma; however, retinitis or choroiditis can also be caused by other viral, protozoal, bacterial, and fungal agents. Differential diagnosis of these infections is based on a number of factors, including ophthalmoscopic appearance, underlying disease, clinical history, and severity of underlying immunosuppression. Rapid and accurate diagnosis is essential in preserving functional vision, as some forms of retinitis are rapidly progressive and since appropriate treatment varies by diagnosis.

Acquired retinochoroiditis in hamsters inoculated with ME 49 strain Toxoplasma.

PURPOSE: These studies were undertaken to establish an animal model for use in studies of ocular toxoplasmosis. An animal model is needed to examine the development, progression, and resolution of ocular Toxoplasma infections and to study the effects on the disease of currently used and experimental therapies. METHODS: Cysts of the ME 49 strain of Toxoplasma gondii were injected intraperitoneally into each of 60 golden hamsters. The hamsters' eyes were examined before inoculation and at intervals after inoculation, and fundus photographs were taken. Histologic sections were analyzed and photographed to document the ocular effects of the infection. RESULTS: Retinochoroiditis was found in both eyes of all hamsters within 2 to 3 weeks of inoculation. The disease resolved spontaneously without treatment and was quiescent in most cases at 12 weeks after inoculation. The animals remained in good general health, and those tested had high antibody titers to Toxoplasma (1:256 to 1:32,000) at 6 months after the infection. The discovery of cysts and lesions in the retina confirmed the diagnosis. CONCLUSIONS: Although the lesions were not identical to those of human disease, this animal model of ocular toxoplasmosis offers several advantages: reproducibility, short incubation time, spontaneous resolution without treatment, consistent production of cysts, and ease of inoculation intraperitoneally without intraocular injection.

Involvement of apoptosis and interferon-gamma in murine toxoplasmosis.

PURPOSE: A murine toxoplasmosis model has been developed that results in central nervous system (CNS) and ocular inflammation characterized by encephalitis with numerous brain tissue cysts and milder inflammation with rare tissue cysts in the eye after 4 weeks of Toxoplasma gondii infection. In this model IFN gamma and inducible nitric oxide (iNO) are protective against T. gondii infection. In this study, the role of apoptosis in the pathogenesis of toxoplasmosis was investigated. METHODS: C57BL/6 (wild-type mice), B6MRL/lpr, and B6MRL/gld (defective Fas or FasL expression, respectively) mice were infected intraperitoneally with 20 to 30 tissue cysts of the ME-49 strain of T. gondii. Mice were killed at days 0, 14, or 28 after infection. The eyes and brains were harvested for histologic, immunohistochemical, and molecular studies. Analysis included immunostaining for Fas, FasL, Bcl-2, and Bax; in situ apoptosis detection (TUNEL assay); RT-PCR amplification for IFN gamma; and measurement of ocular nitrite levels. The control mice were naïve mice of each strain that received no inoculation or injection. RESULTS: Wild-type mice appeared to constitutively express apoptotic molecules at higher levels in the eye than in the brain. Consequently, during T. gondii infection, apoptosis was greater in the eyes than in the brain. Untreated naïve lpr and gld mice showed no expression of Fas and FasL, respectively. After infection, a slightly higher number of tissue cysts (lpr, 11.8 +/- 2.4; gld, 10.3 +/- 3.4) were found in the brains of the mutants than in the control animals (8.8 +/- 2.9). However, no significant differences between the number of apoptotic cells, inflammatory scores, or number of tissue cysts were noted in the eyes. IFN gamma mRNA in control mice was detected at day 28 after infection, whereas in both mutants, mRNA production occurred earlier, at day 14. Ocular nitrite levels were higher in lpr and gld mice than in wild-type mice. CONCLUSIONS: No significant difference in the degree of ocular inflammation and apoptosis was detected between the wild-type and Fas or FasL mutant mice. However, there was an earlier and subjectively greater expression of IFN gamma in the brain and eye and a higher level of nitrite in the ocular tissue of mutant strains than in the wild type. Multiple factors are likely to be involved in the pathogenesis of ocular toxoplasmosis.

Toxoplasma retinitis/encephalitis 9 months after allogeneic bone marrow transplantation.

In a 34-year-old patient toxoplasma retinitis/encephalitis developed 9 months after bone marrow transplantation. The BMT was complicated with a serious GVHD. Although she initially responded well to antibiotic therapy she died 2 years after BMT due to progressive infection.

Reactivation toxoplasmic retinochoroiditis in patients undergoing bone marrow transplantation: is there a role for chemoprophylaxis?

The objective of this study was to report the occurrence of reactivation ocular toxoplasmosis in bone marrow transplant (BMT) recipients and to propose guidelines for identification and chemoprophylaxis of high-risk patients. The study design was a series of cases from the tertiary care university hospital which has an active BMT program. The patients were two recipients of autologous BMTs with past histories of toxoplasma retinochoroiditis who developed symptomatic reactivation of ocular toxoplasmosis as documented by formal opthalmologic examination in the early post-transplant period. Opthalmoscopic examinations in the two patients with non-Hodgkin's lymphoma who received autologous transplants and then developed decreased visual acuity in the first week after transplant revealed recurrent retinochoroiditis adjacent to old toxoplasma lesions. Pre-transplant eye examinations in both patients had demonstrated only inactive chorioretinal scars. Therapy with sulfadiazine, pyrimethamine and prednisone ultimately led to resolution of retinitis in both patients. BMT recipients who are seropositive for antibody to T. gondii and have findings consistent with previous toxoplasma retinochoroiditis on pre-transplant ophthalmologic examination appear to be at risk for reactivation of ocular toxoplasmosis in the early post-transplant period and may warrant preventive chemoprophylaxis for toxoplasmosis.