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.     

Ocular toxoplasmosis I: parasitology,epidemiology and public health

Ocular toxoplasmosis results from retinal infection with the protozoan, Toxoplasma gondii. This parasite, which exists as multiple clonal subpopulations and in three stages, is capable of replication in any nucleated cell of its primary feline or multiple paratenic hosts. Human seroprevalence of toxoplasmosis is high across the globe, but with geographic variation. While prevalence of ocular toxoplasmosis is not well documented, toxoplasmic retinochoroiditis is the commonest form of posterior uveitis in many countries. Correlation of parasite genotype with disease is an important area of new research. Ocular infection with T. gondii often follows ingestion of bradyzoites in undercooked infected meat. Oocysts may survive for an extended period in the environment, and water contaminated with oocysts is an important source in toxoplasmosis epidemics. Ocular toxoplasmosis is preventable by a combination of community activities and personal measures. Public health action is well justified by the considerable burden of congenital and postnatal infections.     

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.     

Review of the Series “Disease of the Year 2011: Toxoplasmosis” Pathophysiology of Toxoplasmosis

Toxoplasma gondii is a major cause of chronic parasitic infection in the world. This protozoan can cause retino-choroiditis in newborns and in adults, both immunocompetent and immunodeficient. This disease tends to be recurrent and can lead to severe visual impairment. The authors review current knowledge on the role of parasite genetics in influencing susceptibility to ocular toxoplasmosis and on the immuno-pathogenesis of this disease.     

Ocular toxoplasmosis II: clinical features,pathology and management

The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this disease, characterized by unilateral, necrotizing retinitis with secondary choroiditis, occurring adjacent to a pigmented retinochoroidal scar and associated with retinal vasculitis and vitritis. Multiple atypical presentations are also described, and severe inflammation is observed in immunocompromised patients. Histopathological correlations demonstrate focal coagulative retinal necrosis, and early in the course of the disease, this inflammation is based in the inner retina. For typical ocular toxoplasmosis, a diagnosis is easily made on clinical examination. In atypical cases, ocular fluid testing to detect parasite DNA by polymerase chain reaction or to determine intraocular production of specific antibody may be extremely helpful for establishing aetiology. Given the high seroprevalence of toxoplasmosis in most communities, serological testing for T. gondii antibodies is generally not useful. Despite a lack of published evidence for effectiveness of current therapies, most ophthalmologists elect to treat patients with ocular toxoplasmosis that reduces or threatens to impact vision. Classic therapy consists of oral pyrimethamine and sulfadiazine, plus systemic corticosteroid. Substantial toxicity of this drug combination has spurred interest in alternative antimicrobials, as well as local forms of drug delivery. At this time, however, no therapeutic approach is curative of ocular toxoplasmosis.     

Management Dilemmas of Atypical Ocular Toxoplasmosis Aided by Wide-Field Fluorescein Angiography

Purpose: To report an atypical presentation of ocular toxoplasmosis and to demonstrate the utility of wide-field angiography in delineating peripheral retinal pathology.

Methods: Case Report.

Results: A 17-year-old male presented with acute unilateral papillitis and retinochoroiditis. Laboratory testing supported reactivation of congenitally acquired Toxoplasma gondii infection. Wide-field fluorescein angiography showed extensive retinal vasculitis. The patient was treated with sulfamethoxazole/trimethoprim. Ocular inflammation resolved over a two-week period. There was no documented visual loss.

Conclusion: Wide-field fluorescein angiography details ocular pathology otherwise unnoticed on traditional posterior pole fluorescein angiography. Documentation of extensive vasculitis associated with ocular toxoplasmosis can assist with management decisions.     

A presentation of longstanding toxoplasmosis chorioretinitis

BackgroundToxoplasmosis gondii is the most common cause of focal necrotizing retinitis in healthy individuals. This case report describes a presentation of toxoplasmosis chorioretintis and reviews the current management options.Case ReportA 10-year-old Hispanic girl presented with complaints of decreased vision in her right eye for 3 weeks. The patient had presumed ocular toxoplasmosis chorioretinitis with secondary granulomatous panuveitis. She was treated successfully with Bactrim^® (Roche Laboratories, Nutley, New Jersey) and topical steroids and cylcoplegics.ConclusionOcular toxoplasmosis is a self-limiting disease in immunocompetent individuals; however, proper diagnosis and early intervention improves visual outcome.     

Ocular toxoplasmosis in the immunocompromised host

Disseminated toxoplasmosis is a well-known complication of immunodeficiency states, including those induced by malignancies, steroid and cytotoxic drug therapy, and AIDS. In immunodeficient patients, toxoplasmic infections of the eye are less common than toxoplasmic infections of other organs for unknown reasons. When ocular toxoplasmosis does occur in the immunodeficient host, or if immunosuppressive therapy is administered to patients with active disease, widespread tissue destruction by proliferating organisms may result. Immunodeficiency alone may not be sufficient, however, to cause reactivation of encysted organisms in retinochoroidal scars.Ocular toxoplasmosis in the immunocompromised host presents difficult problems in diagnosis and management. There may be a variety of clinical lesions, including single foci of retinochoroiditis in one or both eyes, multifocal lesions, or diffuse areas of retinal necrosis. The majority of lesions do not arise from the borders of preexisting scars, which suggests that they result from acquired infection or dissemination of organisms from nonocular sites of disease.Toxoplasma gondii may infect iris, choroid, and vitreous-tissues that are not usually infected in the immunocompetent host. Ocular lesions appear to respond to standard antiparasitic drug therapies, but continued treatment is probably necessary to prevent reactivation of disease in the most immunocompromised patients. The best treatment regimens have yet to be determined. Histopathologic studies show little retinal inflammation; therefore anti-inflammatory drugs, such as oral steroids, probably have no role in the management of infection.     

Toxoplasmosis

Toxoplasmosis is the most common cause of posterior uveitis in immunocompetent subjects. The infection can be congenital or acquired. Ocular symptoms are variable according to the age of the subject. For instance, young children present with reduced visual acuity, strabismus, nystagmus, and leucocoria, while teenagers and adults complain of decreased vision, floaters, photophobia, pain, and hyperemia. Toxoplasmic retinochoroiditis typically affects the posterior pole, and the lesions can be solitary, multiple or satellite to a pigmented retinal scar. Active lesions present as grey-white focus of retinal necrosis with adjacent choroiditis, vasculitis, hemorrhage and vitreitis. Cicatrization occurs from the periphery towards the center, with variable pigmentary hyperplasia. Anterior uveitis is a common finding, with mutton-fat keratic precipitates, fibrine, cells and flare, iris nodules and posterior synechiae. Atypical presentations include punctate outer retinitis, neuroretinitis, papillitis, pseudo-multiple retinochoroiditis, intraocular inflammation without retinochoroiditis, unilateral pigmentary retinopathy, Fuchs'-like anterior uveitis, scleritis and multifocal or diffuse necrotizing retinitis. The laboratory diagnosis of toxoplasmosis is based on detection of antibodies and T. gondii DNA using polymerase chain reaction (PCR). Toxoplasmosis therapy includes specific medication and corticosteroids. There are several regimens, with different drug combinations. Medications include pirimetamine, sulfadiazine, clindamycin, trimethoprime-sulphamethoxazol, spiramycin, azithromycin, atovaquone, tetracycline and minocycline. The prognosis of ocular toxoplasmosis is usually good in immunocompetent individuals, as long as the central macula is not directly involved.     

Epidemiology,Pathophysiology, and the Future of Ocular Toxoplasmosis

Abstract

Despite large advances in the field of ocular toxoplasmosis, large gaps still exist in our knowledge concerning the epidemiology and pathophysiology of this potentially blinding infectious disease. Although ocular toxoplasmosis is considered to have a high health burden, still little is known about its exact prevalence and how it affects the quality of life. The epidemiology of toxoplasmosis depends on local habits throughout the globe, and changes are likely in view of increased meat consumption in developing countries and demands for higher animal welfare in the Western world. Water is increasingly seen as an important risk factor and more studies are needed to quantitate and control the role of water exposure (drinking, swimming). Tools are now becoming available to study both the human host as well as parasite genetic factors in the development of ocular toxoplasmosis. Further research on the role of Toxoplasma strains as well as basic studies on parasite virulence is needed to explain why Toxoplasma associated eye disease is so severe in some countries, such as Brazil. Although genetic analysis of the parasite represents the gold standard, further developments in serotyping using peptide arrays may offer practical solutions to study the role of parasite strains in the pathogenesis of Toxoplasma retinochoroiditis. More research is needed concerning the pathways whereby the parasite can infect the retina. Once in the retina further tissue damage may be due to parasite virulence factors or could be caused by an aberrant host immune response. Local intraocular immune responses are nowadays used for diagnostic procedures. Future developments may include the use of Raman technology or the direct visualization of a Toxoplasma cyst by optical coherence tomography (OCT). With the availability of ocular fluid specimens obtained for diagnostic purposes and the development of advanced proteomic techniques, a biomarker fingerprint that is unique for an eye with toxoplasmosis may become available. It is hoped that such a biomarker analysis may also be able to distinguish between acquired versus congenital disease. Recently developed mouse models of congenital ocular toxoplasmosis are extremely promising with regard to disease pathogenesis, diagnosis, and treatment.     

The prevalence of Toxoplasma antibody in patients with various ocular diseases in central Japan

Background: Ocular toxoplasmosis has been considered to be a largely asymptomatic infection because of the high seroprevalence of Toxoplasma antibodies and the low rate of clinical diagnosis. On the other hand, Toxoplasma infection has been reported to be associated with the other ocular disease. To investigate the association of Toxoplasma infection with the development of various ocular diseases, we studied Toxoplasma seroprevalence in patients with various ocular diseases. Methods: We investigated Toxoplasma seroprevalence in 982 patients with various ocular diseases in central Japan. Then we compared the seroprevalence of anti-Toxoplasma antibodies. Results: Of 982 patients with various ocular diseases, 122 (12.4%) had serological evidence of previous exposure to Toxoplasma gondii. There were no statistically significant differences among the patients with various ocular diseases. However, the seroprevalence in patients aged 40 to 99 years with macular degenerative lesions was significantly higher than that in patients without these lesions (P<0.05, Yates' correction). Conclusion: This result suggests that Toxoplasma infection could play some role in the development of a type of macular degenerative lesion.     

Detection of Toxoplasma gondii in aqueous humour by the polymerase chain reaction.

Ocular toxoplasmosis is the most frequent infectious cause of chorioretinal inflammation in immunocompetent patients. Nowadays, the biological diagnosis of ocular toxoplasmosis requires serological tests and anterior chamber puncture to detect the local production of specific antibodies. A new technique is described to detect Toxoplasma in aqueous humour by a polymerase chain reaction in which the target is a specific ribosomal DNA segment. Sixty eight patients (71 eyes) were included; 59 (83%) eyes were suspected of having ocular toxoplasmosis. Of these 59 eyes, 15 (25.4%) had characteristic fundus lesions with obvious intraocular inflammation signs and 44 (75%) had retinal scar of ocular toxoplasmosis without clinically detectable inflammation. Twelve (17%) eyes had uveitis of non-Toxoplasma origin and constituted the control group. The parasite was present in aqueous humour in 20 (33.8%) cases. No false positives were detected. The sensitivity of the test is reduced by the low numbers of the sample. The combination of this technique with Witmer-Desmonts coefficient increases the probability of making a biological diagnosis of ocular toxoplasmosis. The physiopathological value of this technique is emphasised and the presence of tachyzoites in the anterior chamber is suggested. This should be a very promising technique for the diagnosis of ocular toxoplasmosis.     

Ocular toxoplasmosis: a global reassessment. Part I: epidemiology and course of disease

PURPOSE: To update clinical information about ocular toxoplasmosis. Part I reviews information about prevalence of disease, sources of infection, relation of ocular disease to time of Toxoplasma gondii infection (congenital vs. postnatally acquired), and course of disease. DESIGN: Literature review. METHODS: Selected articles from the medical literature, information from recent scientific meetings, and the author's personal experiences were reviewed critically in preparation for the LX Edward Jackson Memorial Lecture. RESULTS: The prevalence of T. gondii infection varies geographically and increases with age; in the United States, the overall proportion is 22.5%. The proportion of infected individuals in the United States who have had episodes of ocular toxoplasmosis is unknown, but may be approximately 2%. Prevalence of ocular involvement is substantially greater in other parts of the world, including southern Brazil. In addition to undercooked meat and unwashed vegetables, drinking water contaminated with oocysts may be an important source of infection in some settings. In contrast to traditional teaching, evidence suggests that most individuals with ocular toxoplasmosis were infected postnatally. Ocular lesions may first develop many years after T. gondii infection. The risk of recurrent ocular disease appears to be greater during the first year after an episode of toxoplasmic retinochoroiditis than during subsequent years. CONCLUSIONS: Reassessment of older publications in the light of recent observations provides a richer understanding of ocular toxoplasmosis, although knowledge about the disease remains incomplete. A better understanding of the clinical characteristics and course of ocular toxoplasmosis will have important implications for developing more effective prevention and treatment strategies.     

Diagnostic and therapeutic dilemmas in ocular toxoplasmosis

Ocular toxoplasmosis, a leading cause of visual handicaps in young people, represents a late manifestation of congenital infection in the majority of cases. Ocular involvement in acquired toxoplasmosis has been repeatedly reported and shows that toxoplasmic retinitis may develop in the wake of acquired infection. The diagnosis of ocular toxoplasmosis is mainly clinical since serologic tests are positive for a considerable percentage of the general population and are not indicative for ocular involvement. The demonstration of local synthesis of toxoplasma antibodies in the eye by intraocular fluid analysis is a valuable diagnostic tool. The application of the polymerase chain reaction, in which the parasite's DNA is detected, may be expected to change the diagnostic repertoire drastically in the future. The need for appropriate therapy for patients with ocular toxoplasmosis is a matter of continued debate: the majority of the medications used for treatment have potentially serious side effects and the efficacy of treatments has not been clarified in previous studies. Recently, a prospective multicenter study to evaluate the efficacy of current therapeutic strategies for ocular toxoplasmosis was performed in The Netherlands and included 106 patients with active ocular toxoplasmosis. The principal conclusion of this study is that only drug therapy with pyrimethamine had any perceptible influence on any aspect of ocular toxoplasmosis, but this effect may not be worth the risk of side effects except in fovea threatening lesions.     

Ocular toxoplasmosis past,present and new aspects of an old disease

Ocular toxoplasmosis (OT) is considered the most frequent form of infectious posterior uveitis and is caused by the protozoan parasite Toxoplasma gondii. The resulting vision loss frequently incapacitates patients and places a considerable socio-economic burden on societies in particular in developing countries. Although, toxoplasmic retinochoroiditis is a world-wide phenomenon stark regional differences with regard to prevalence and presumably route of infection exist. This review will discuss our current clinical understanding of OT including typical and atypical manifestations, patient characteristics which influence the course of disease and treatment options. Even though, congenital and acquired OT are not regarded as separate entities, certain differences exist, which will be assessed and evaluated in detail. A strong focus is laid on the disease causing parasite T. gondii, since solving the mystery of OT aetiology and the development of improved therapies will not be possibly with clinical science alone, but rather requires a precise understanding of parasitological and immunological pathomechanisms. Additionally, the biology and genetics of T. gondii form the foundation for novel and sophisticated diagnostic methods. Scientific advances in the recent years have shed some light on the different role of T. gondii strains with regard to OT manifestation and severity of disease. Genetic and environmental factors influencing OT will be presented and commonalities between OT and toxoplasmic encephalitis will be briefly discussed. Furthermore, the laboratory tools to study OT are crucial in our understanding of OT. In vivo and in vitro experimental approaches will be summarised and evaluated extensively. Finally, a brief outlook is given in which direction OT research should be headed in the future.     

Toxoplasmosis,old stories and new facts

In this introductory paper some general opinions are presented regarding the parasiteToxoplasma gondii, toxoplasma infection and toxoplasmosis. The transmission of the parasite through oocysts and/or infected meat is discussed with regard to possible prevention. Old stories have been replaced by new facts in the epidemiology of toxoplasma infection. Veterinary measurements in the field of prevention are not likely to be accepted in the near future. It is stressed that laboratory diagnosticians should clearly differentiate between diagnostic support in suspected cases of clinical toxoplasmosis or screening for certain characteristics such as IgG antibodies to toxoplasma in a healthy population.     

Infectious causes of uveitis in the developing world

Infectious causes of uveitis are common in the developing world and include some causes that are rarely encountered in industrialized nations, such as tuberculosis, leptospirosis, leprosy, onchocerciasis, and cystercicosis. Ocular toxoplasmosis occurs in all countries but is more common in Central and South America, the South Pacific, and western Europe. AIDS-related opportunistic infections occur wherever HIV infection is prevalent, including North and South America, western and eastern Europe, the former Soviet Union, sub-Saharan Africa, and South and Southeast Asia. Physicians who care for patients in the developing world should consider these infectious possibilities whenever their patients develop uveitis.     

Socioeconomic conditions as determining factors in the prevalence of systemic and ocular toxoplasmosis in Northeastern Brazil

OBJECTIVE To determine the prevalence of systemic and ocular toxoplasmosis among 1024 students in the city of Natal, Northeastern Brazil, and correlate it with demographic, socioeconomic and epidemiological risk factors. METHODS The study population was randomly selected, asked to fill out a questionnaire, provide a blood sample for IgG and IgM (MEIA) serology and a hemogram, and undergo an eye examination. RESULTS The seroprevalence for IgG was 46% (95% CI = 42.9-49.2%) and that for IgM was 1.4% (95% CI = 0.8-2.4%). The prevalence of ocular lesions was 1.15% (95% CI = 0.6-2.0%). In the univariate analyses, confirmed by multivariate analysis, the socioeconomic conditions were determinants in the prevalence of systemic and ocular toxoplasmosis (mother's schooling = literacy/OR = 2.9 and p &lt; 0.001). CONCLUSIONS The prevalence of systemic toxoplasmosis, although high, was lower than that found in studies performed in the South and Southeast of Brazil, and the incidence of ocular lesions was totally different, being lower by a factor varying from 5 to 17. Although important epidemiological variables, such as owning a cat, drinking unfiltered water or having had contact with lakes or rivers, were found to be correlated with toxoplasmosis in the preliminary analysis, they lost their influence when included in the logistic model. However, further studies must be undertaken to identify the reasons for these findings, including the determination of the strains of Toxoplasma gondii encountered in different regions of the country and the sources of the water utilized by these populations.     

Branch retinal arterial occlusion associated with toxoplasmic chorioretinitis

Background:Ocular toxoplasmosis can cause a variety of retinal vascular changes including branch retinal arterial occlusion, which is a rare complication of the disease. Patient and methods:We report a case of toxoplasmic chorioretinitis in a pregnant woman, who developed branch retinal arterial obstruction adjacent to the active chorioretinitis lesion. Results:The patient received an appropriate steroid and antibiotic treatment and the retinitis lesion resolved over a six-week period. At two months after diagnosis, visual acuity in her right eye was 20/30 and there was a hyperpigmented scar at the site where active retinitis had been observed. Conclusion:Especially in young patients with branch retinal vascular occlusion associated with posterior uveitis, the diagnosis of ocular toxoplasmosis should be kept in mind and serologic test results should be obtained.     

Decline in Ocular Toxoplasmosis over 40 Years at a Tertiary Referral Practice in the United States

Purpose: To identify whether there has been a decline in ocular toxoplasmosis at a tertiary uveitis practice.

Methods: Retrospective review of new patients at the University of Illinois Uveitis Service from 1973 to 2012.

Results: There were 6820 patients with adequate records for inclusion; 323 (4.7%) were diagnosed with ocular toxoplasmosis. There was a 78.0% decline in prevalence of ocular toxoplasmosis from 2008 to 2012 compared with 1973 to 1977. Compared with the aggregate uveitis population, toxoplasmosis patients were more likely to be Hispanic (p<0.0001) and less likely to be African American (p<0.0001). Ocular toxoplasmosis in Hispanics commonly occurred in foreign-born patients (85.3%).

Conclusions: The diagnosis of ocular toxoplasmosis at our clinic declined, with Hispanics accounting for an increasing proportion of cases. These trends are consistent with the decreasing toxoplasmosis seropositivity in the United States, but may also reflect decreased referrals due to improved management of ocular toxoplasmosis in primary clinics.