[Prevention of Recurrence of Ocular Toxoplasmosis - When? How? For Whom?] / Rezidivprophylaxe bei okulärer Toxoplasmose.

BACKGROUND: Ocular toxoplasmosis (OT) leads to permanent visual disturbances in a high proportion of patients. A combination of antibiotics and corticosteroids may reduce the risk of permanent visual impairment and may delay recurrence. In this overview, we summarise the current state of knowledge regarding the recurrence prophylaxis of OT. METHOD: The basis of this review is a literature search in PubMed with the key words (MeSH terms) "human ocular toxoplasmosis" or "retinochoroiditis" and "recurrence" and "prophylaxis" or "prevention". The resulting publications included case series with more than 20 patients, prospective clinical studies and meta-analyses published within the last 25 years, as well as other publications mentioned therein, and was evaluated on the basis of the experience of the authors. RESULTS: The frequency of recurrences does not differ between Latin America, North America and Europe, and is around 12 - 15% in the first two years and then decreases, with recurrences observed up to 49 years after an active infection. According to two placebo-controlled double-blind studies from Brazil, where particularly serious relapses occur, antibiotic prophylaxis with 160 mg trimethoprim combined with 800 mg sulfamethoxazole three times a week for 12 months can reduce the occurrence of relapses from 22 to 3% for up to three years. After that, the likelihood of recurrence is as high as in patients who have never received prophylaxis. CONCLUSION: Relapses can be effectively prevented, if this is medically indicated. Among other considerations are central location of the lesion, insufficient immune competence and frequent relapses. Prophylaxis should be carried out for at least 12 months, since the risk of recurrence is highest in the first two years.

Long-term Results of Trimethoprim-Sulfamethoxazole Versus Placebo to Reduce the Risk of Recurrent Toxoplasma gondii Retinochoroiditis.

PURPOSE: To compare the effects of 1 year of treatment with trimethoprim-sulfamethoxazole (TMP-SMZ) vs placebo in reducing the risk of recurrence of toxoplasmic retinochoroiditis during a 6-year follow-up period. DESIGN: Randomized, double-masked clinical trial. METHODS: This cohort included 141 subjects recruited in Campinas, Brazil. The inclusion criterion was unilateral active recurrent toxoplasmic retinochoroiditis. All subjects were treated with 1 dose of TMP-SMZ (160 mg/800 mg) twice daily for 45 days, and all lesions healed after this treatment. After this initial treatment, subjects were randomly assigned to group 1 (1 TMP-SMZ dose every other day for 311 days) or group 2 (1 identical placebo tablet containing starch with no active ingredients every other day for 311 days). Between the second and sixth years of follow-up appointments, none of the subjects received treatment unless a new recurrence episode had occurred. The primary outcomes were recurrent toxoplasmic retinochoroiditis within the first year of follow-up and recurrent toxoplasmic retinochoroiditis in the 6 years of follow-up. RESULTS: The cumulative probability of recurrence 1, 2, 3, 4, 5, and 6 years after the initial infection was, respectively, 13.0% (9/69), 17.4% (12/69), 20.3% (14/69), 23.2% (16/69), 26.1% (18/69), and 27.5% (19/69) in the placebo group and 0%, 0%, 0%, 0%, 0%, and 1.4% (1/72) in the TMP-SMZ group (P < .001; log-rank test). There were 3 cases (3/69; 4.3%) of multiple recurrences in the same individual in the placebo group. No treatment-limiting toxicity or side effects were observed in either group. New recurrences were more frequent among female subjects. CONCLUSIONS: TMP-SMZ may be used safely for prophylaxis of recurrent toxoplasmic retinochoroiditis and may provide long-term benefits.

Failure of systemic oral doxycycline in preventing ocular toxoplasmic retinochoroiditis in French military personnel.

This paper describes two cases of toxoplasmic chorioretinitis presenting in two French soldiers who had been receiving oral doxycycline for malaria prophylaxis. This is despite the proven effectiveness of oral doxycycline in treating Toxoplasma gondii, the most common cause of this infection. The lack of effectiveness of oral doxycycline in these two cases most likely reflected that the ocular concentration of 100 mg daily doxycycline is too low to treat or prevent Toxoplasmic retinochoroiditis (TC). Clinicians should therefore be aware that soldiers taking prophylactic oral doxycycline are still at risk of developing ocular TC with potentially sight-threatening consequences if not treated adequately.

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.

Trimethoprim-Sulfamethoxazole Versus Placebo in Reducing the Risk of Toxoplasmic Retinochoroiditis Recurrences: A Three-Year Follow-up.

PURPOSE: To compare the effects of 1 year of treatment with trimethoprim/sulfamethoxazole (TMP-SMZ) vs a placebo in reducing the risk of toxoplasmic retinochoroiditis recurrences during a 3-year follow-up period. DESIGN: Randomized, double-masked clinical trial. METHODS: This cohort included 141 volunteers recruited in Campinas, Brazil. Inclusion criterion was unilateral active recurrent toxoplasmic retinochoroiditis. All volunteers were treated with 1 tablet of TMP-SMZ (160 mg/800 mg) twice daily for 45 days, and all lesions healed after this treatment. After this initial treatment, the volunteers were randomly assigned to Group 1 (1 TMP-SMZ tablet every 2 days for 311 days) or Group 2 (1 identical placebo tablet containing starch with no active ingredients every 2 days for 311 days). At the second- and third-year follow-up appointments, none of the volunteers received treatment unless a new recurrence episode had occurred. The primary outcomes were recurrent toxoplasmic retinochoroiditis within the first year of follow-up and recurrent toxoplasmic retinochoroiditis within the third year of follow-up. RESULTS: The cumulative probability of recurrence at 1, 2, and 3 years of follow-up were, respectively, 13.0% (9/69), 17.4% (12/69), and 20.3% (14/69) in the placebo group and 0% (0/72) in the TMP-SMZ group (P < .001, log-rank test). There was no case of multiple recurrences in the same individual. No treatment-limiting toxicity or side effects were observed in either group. New recurrences were more frequent among female volunteers. CONCLUSIONS: TMP-SMZ may be used safely for prophylaxis of recurrent toxoplasmic retinochoroiditis, with long-term benefits.

Excretory-secretory antigens: a suitable candidate for immunization against ocular toxoplasmosis in a murine model.

Toxoplasmosis, responsible for ocular impairment, is caused by Toxoplasma gondii. We investigated the effect of Toxoplasma excretory-secretory antigens (ESA) on parasite load and distribution in the eye tissue of a murine model. Case and control groups were immunized with ESA and PBS, respectively. Two weeks after the second immunization, the mice were challenged intraperitoneally with virulent RH strain of Toxoplasma; eye tissue samples of both groups were collected daily (days 1, 2, 3, and the last day before death). Parasite load was determined using real-time quantitative PCR targeted at the B1 gene. Compared to the control group, infected mice that received ESA vaccine presented a considerable decrease in parasite load in the eye tissue, demonstrating the effect of ESA on parasite load and distribution. Diminution of parasite load in mouse eye tissue indicated that ESA might help control disease-related complications and could be a valuable immunization candidate against ocular toxoplasmosis.

Sitting at the window to the world--ocular parasites.

Parasitic infections cause significant ophthalmic disease, both in developing countries and in the Western world. The parasitic infections Acanthamoeba keratitis, ocular toxoplasmosis, and ocular toxocariasis are responsible for a significant proportion of ocular pathology. Especially in light of the recent increase of immunocompromised (i.e. using immunosuppressants or HIV) and aged populations, parasitic infections of the eye are rising in number. This reviews aims to describe the pathogenesis, symptoms, diagnosis and management of infection, as well as preventative measures for these three parasitic ocular diseases.

Ocular toxoplasmosis: recent aspects of pathophysiology and clinical implications.

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 understanding could be achieved in ocular toxoplasmosis, large gaps still exist on factors influencing the epidemiology and pathophysiology of this potentially blinding disease. We are only at the beginning of understanding the complex biology of this parasite and its mechanisms of invasion, virulence and interaction with the host's immune response. Since it is a preventable cause of blindness, it is necessary to assess factors that have the potential to control this disease in the future. This mini review will focus on recent advances in postnatal acquired ocular infection and the factors that may influence its prevalence and functional outcome.

Risk of reactivation of toxoplasmic retinitis following intraocular procedures without the use of prophylactic therapy.

BACKGROUND/AIMS: Toxoplasmic retinochoroiditis is the commonest known cause of posterior uveitis worldwide and reactivation is unpredictable. Based on results from one study, the authors proposed that antitoxoplasmic therapy should be initiated as prophylaxis for intraocular surgery in patients with toxoplasmic scars. The aim of this study is to analyse the risk of toxoplasmic retinochoroiditis reactivation following intraocular procedures. METHODS: Retrospective analysis of the medical records of a total of 69 patients who underwent intraocular surgery and presented with toxoplasmic retinochoroiditis scars. RESULTS: No patient received prophylactic antitoxoplasmic therapy. Reactivation following the surgical procedure occurred in four cases, with one at 3 months and the others respectively at 13, 14 and 17 months. CONCLUSIONS: Our study shows that intraocular surgery did not result in a significant reactivation rate of toxoplasmic retinochoroiditis in the absence of preoperative prophylactic antitoxoplasmic therapy.

Trimethoprim-sulfamethoxazole versus placebo to reduce the risk of recurrences of Toxoplasma gondii retinochoroiditis: randomized controlled clinical trial.

PURPOSE: To compare the effects of trimethoprim-sulfamethoxazole vs placebo in reducing the risk of recurrences of Toxoplasma gondii retinochoroiditis. DESIGN: Single-center, prospective randomized double-masked clinical trial. METHODS: A total of 95 patients from Campinas, Brazil, with active recurrent Toxoplasma gondii retinochoroiditis were included. The initially active toxoplasmosis lesions were successfully treated in all cases using trimethoprim-sulfamethoxazole (800 mg/160 mg) twice daily for 45 days. Subsequently, 5 patients dropped out of the study. The remaining patients were randomized to Group 1 (trimethoprim/sulfamethoxazole tablet every 2 days) or Group 2 (identical placebo tablet every 2 days). Randomization was 1:1, was stratified by sex, and used block sizes of 4. The primary outcome was recurrent toxoplasmosis retinochoroiditis within 1 year, and the secondary outcome was a 1-year change in best-corrected visual acuity (BCVA) (ETDRS chart). RESULTS: The incidence of recurrent toxoplasmosis retinochoroiditis within 12 months was 0 of 46 (0%) and 6 of 47 (12.80%) in the trimethoprim-sulfamethoxazole and placebo groups, respectively (P = .026). Visual acuity improvements in the 2 groups were similar. No treatment-limiting toxicity was observed. CONCLUSIONS: Trimethoprim/sulfamethoxazole therapy resulted in a 100% reduction in the recurrence of Toxoplasma gondii retinochoroiditis over 1 year of treatment.

Epidemiology of ocular toxoplasmosis.

Retinal infection with Toxoplasma gondii is the most important cause of posterior uveitis, whereby prevalence and incidence of ocular symptoms after infection depend on socio-economic factors and the circulating parasite genotypes. Ocular toxoplasmosis is more common in South America, Central America, and the Caribbean and parts of tropical Africa as compared to Europe and Northern America, and is quite rare in China. Ocular disease in South America is more severe than in other continents due to the presence of extremely virulent genotypes of the parasite. Drinking untreated water is considered the major source of Toxoplasma infection in developing countries, whereas in the Western world the consumption of raw or undercooked meat (products) is the most important cause. Since acquired infection with T. gondii is currently a more important cause of ocular toxoplasmosis compared to congenital infection, prevention should be directed not only toward pregnant women but toward the general population.

[Congenital toxoplasmosis: severe ocular and neurological complications]. / Congenitale toxoplasmose: ernstige oculaire en neurologische complicaties.

Two infants with congenital toxoplasmosis are presented. A girl born prematurely was treated postnatally after the mother had received antimicrobial treatment during pregnancy for acute toxoplasmosis. Apart from being small for gestational age, she remained without symptoms and treatment was ceased after 13 months. A 2-month-old boy presented with hydrocephalus and chorioretinitis, consistent with congenital toxoplasmosis. Despite antimicrobial treatment, at 12 months of age he suffered from epilepsy, cerebral palsy and vision impairment. Most infants with congenital toxoplasmosis (2 per 1000 live births in the Netherlands) are asymptomatic at birth. The education of pregnant women is crucial for the prevention of congenital toxoplasmosis. Awareness of antenatal and postnatal presenting signs and symptoms is important for clinicians, because early diagnosis and treatment may minimize sequelae. Untreated, the majority of affected infants will develop chorioretinitis, deafness and/or neurological symptoms.

Toxoplasmosis in Serbia: time for an action plan.

Known for a century, Toxoplasma gondii has been studied in Serbia half this time, ever since the introduction of the Sabin-Feldman test at the Institute for Medical Research (IMR) in 1959. However, despite 50 years of continuous efforts, exact data on the frequency of acute clinical disease, acute infections in pregnancy and congenital infection in the offspring are still lacking, due to the vague regulatory provision that toxoplasmosis is subject to reporting "in case of epidemiological indications". It is, however, clear that the major Toxoplasma-induced public health issue in Serbia, like elsewhere in Europe, is congenital toxoplasmosis (CT). Continuous monitoring of particular patient groups showed a dramatic decrease in the prevalence of infection over the past two decades, and a consequently increased proportion of women susceptible to infection in pregnancy, suggesting a potential increase in the incidence of CT. Studies of risk factors for infection transmission have provided data to guide national health education campaigns. It is expected that the recent appointment of the National Reference Laboratory for Toxoplasmosis as the focal point for the collection of data from the primary level, will provide the means for accurate assessment of the measure of the problem, which is a prerequisite of an evidence-based nation-wide prevention program. In the meantime, health education of all pregnant women, focused at risk factors of major local significance, is advocated as a sound and financially sustainable option to reduce congenital toxoplasmosis.

Toxoplasmosis ocular / Ocular toxoplasmosis

La toxoplasmosis ocular es una enfermedad producida por el parásito toxoplasma gondii. Es la causa más frecuente de uveítis posterior, es una enfermedad de distribución universal, al menos 500 millones de personas están infectadas en todo el mundo, ocasionando disminución de la visión y ceguera en muchas de ellas. Por tal motivo, realizamos una revisión actualizada sobre, la situación actual a nivel mundial, la historia de la enfermedad, la prevención, formas clínicas y el control de la toxoplasmosis. Se tratan otros aspectos de interés como el modo de transmisión, los hospederos (definitivos e intermediarios) y las manifestaciones clínicas más notables

The ocular toxoplasmosis is an illness caused by Toxoplasma gondii parasite. It is the most frequent cause in posterior uveitis, and it spreads worldwide since at least 500 million people are infected in the entire world, causing decrease of vision and blindness in many of them. This is the reason why we made a literature review, the current situation worldwide, the history, the prevention, the clinical forms and the control of toxoplasmosis. Other interesting aspects were the channel of transmission, the hosts (intermediary and final) and the most remarkable clinical manifestations

Toxoplasmosis ocular / Ocular toxoplasmosis

La toxoplasmosis ocular es una enfermedad producida por el parásito toxoplasma gondii. Es la causa más frecuente de uveítis posterior, es una enfermedad de distribución universal, al menos 500 millones de personas están infectadas en todo el mundo, ocasionando disminución de la visión y ceguera en muchas de ellas. Por tal motivo, realizamos una revisión actualizada sobre, la situación actual a nivel mundial, la historia de la enfermedad, la prevención, formas clínicas y el control de la toxoplasmosis. Se tratan otros aspectos de interés como el modo de transmisión, los hospederos (definitivos e intermediarios) y las manifestaciones clínicas más notables(AU)

The ocular toxoplasmosis is an illness caused by Toxoplasma gondii parasite. It is the most frequent cause in posterior uveitis, and it spreads worldwide since at least 500 million people are infected in the entire world, causing decrease of vision and blindness in many of them. This is the reason why we made a literature review, the current situation worldwide, the history, the prevention, the clinical forms and the control of toxoplasmosis. Other interesting aspects were the channel of transmission, the hosts (intermediary and final) and the most remarkable clinical manifestations(AU)

Azithromycin reduces ocular infection during congenital transmission of toxoplasmosis in the Calomys callosus model.

Toxoplasma gondii is a widely distributed obligatory intracellular parasite that causes severe disease to the fetus when transmitted during pregnancy. Drugs used to avoid congenital transmission have shown side effects, and their efficacy is controversial. The most widely used treatment for acute toxoplasmosis during pregnancy is pyrimethamine plus sulfadiazine, which has several side effects. In this work, we tested the efficacy of azithromycin in reducing congenital transmission of T. gondii in the large vesper mouse, Calomys callosus, a rodent. Females of C callosus were inoculated perorally with 20 cysts of ME49 strain of T. gondii on the day of fertilization, and fetuses were collected from the 15th to the 19th day of gestation. Azithromycin (300 mg/kg), in association with pyrimethamine (100 or 50 mg/kg) plus sulfadiazine (100 or 75 mg/kg) and folinic acid (15 mg/kg) (SPAf), or vehicle, were administered orally on different days after infection. Brain and ocular tissues were removed and processed for immunohistochemistry using a polyclonal antibody against T. gondii, or were processed for parasite DNA quantification. Toxoplasma gondii was detected in the brains of all females and in fetuses' eyes of C. callosus treated with SPAf. On the other hand, in females treated with azithromycin, there was a reduction of T. gondii in the brains of mothers, and no parasites were detected in eyes of fetuses, indicating that azithromycin may represent an alternative treatment for toxoplasmosis during pregnancy.

Effect of highly active antiretroviral therapy (HAART) on the natural history of ocular manifestations in HIV-infected children.

PURPOSE: To determine the effect of highly active antiretroviral therapy (HAART) on the natural history of ocular manifestations in HIV-infected children. METHODS: All of the HIV-infected children attending the Institute of Pediatrics, University of Milan, Milan, Italy, between 1982 and 2004 were studied. Every 3 months, they were physically examined and underwent indirect fundoscopy conducted by an experienced ophthalmologist; if diagnosed as having eye disease, they were evaluated by the ophthalmologist every week while on specific therapy and monthly thereafter. The clinical and laboratory findings before and after the introduction of HAART were compared. RESULTS: The cohort consisted of 117 HIV-infected children (61 males), with a follow-up ranging from 0.09 to 22.31 years (median, 16.33 years). A total of nine cases of ocular involvement (7.7%) were diagnosed between 1983 and 1994, before the introduction of HAART. All nine children died 4-24 months (median, 15 months) after the diagnosis of ophthalmic disease. No case of ocular involvement was observed after the introduction of HAART (P=0.011 vs. before HAART). CONCLUSION: The introduction of HAART has had a significant impact on the natural history of ocular manifestations in HIV-infected children, thus suggesting that a reduction in the frequency of ophthalmologic follow-up should be considered for HAART-treated HIV-infected children with immune reconstitution and no visual symptom.

Specific antibody levels in the aqueous humor and serum of two distinct populations of patients with ocular toxoplasmosis.

The population of Erechim, Southern Brazil, is characterized by a high incidence of ocular toxoplasmosis, which is presumed to be of acquired origin. We wished to compare the local specific humoral immune response of individuals from this region with that of Swiss patients suffering from the same disease. Paired samples of aqueous humor and serum were withdrawn from 27 Brazilian and 50 Swiss patients presenting consecutively with active ocular toxoplasmosis. The total and specific levels of IgG in each of these were determined. The populations did not differ with respect either to age or sex. The serum levels of total IgG in Brazilian (10.8 g/l) and Swiss patients (11.1 g/l) were similar (p = 0.499), but the aqueous humor ones were higher in the former group (95 vs. 20 mg/l; p = 0.0001). The systemic and local levels of specific IgG were likewise higher in Brazilian patients [206 i.u. vs. 72 i.u. (p = 0.001) and 14 i.u. vs. 4 i.u. (p = 0.005), respectively] and the number of individuals without detectable levels of local specific IgG was correspondingly lower (11% vs. 54%; p = 0.0005). The Goldmann-Witmer coefficient (an index of local specific antibody production) did not differ between Brazilian and Swiss patients (2.1 vs. 0.08, respectively; p = 0.107). Our findings are indicative of a more pronounced uveovascular barrier breakdown in Brazilians than in Swiss patients with active ocular toxoplasmosis. That the systemic and local specific immune response is weaker in Swiss than in Brazilian patients has not been hitherto documented. This finding may reflect differences in the immunological handling of the infection.