Prevalence of Toxoplasmic Retinochoroiditis in an Australian Adult Population: a Community-Based Study

Toxoplasmic retinochoroiditis is common in Australian adults. Efforts to quantify and address risk factors for human infection with T. gondii are justified.

Eight participants (0.16%) had retinal lesions that were considered to have the characteristic appearance of toxoplasmic retinochoroiditis, plus detectable serum T. gondii IgG, consistent with the diagnosis of toxoplasmic retinochoroiditis. On the assumption that 23.81% of retinal lesions occur at the posterior pole, as reported in a community-based survey conducted in Brazil (Sci Rep. 2021;11:3420), the prevalence of toxoplasmic retinochoroiditis was estimated at 0.67% or 1 per 149 persons.

Retinal color photographs centered on the optic disc and macula were captured on a digital retinal camera following dilation of the pupils. Three uveitis-subspecialized ophthalmologists assessed each pigmented retinal lesion, and complete concordance of opinion was required to assign a toxoplasmic etiology. Serum T. gondii immunoglobulin (Ig)G levels were measured for those participants with retinal lesions judged to be toxoplasmic retinochoroiditis.

Toxoplasmic retinochoroiditis is the most common clinical manifestation of an infection with the protozoan parasite, Toxoplasma gondii. Up to 50% of the human population is estimated to be infected with T. gondii. However, the epidemiology of toxoplasmic retinochoroiditis is not widely reported. We sought to estimate the prevalence of toxoplasmic retinochoroiditis in Australia using data collected as part of the Busselton Healthy Ageing Study.

In the study reported here, we sought to address the epidemiologic knowledge gap in toxoplasmic retinochoroiditis, by using data collected as part of the Busselton Healthy Ageing Study.Retinal color photographs of approximately 5,000 individuals living in urban Western Australia were obtained during this project, to evaluate the prevalence of glaucoma and age-related macular degeneration. Three uveitis-subspecialized ophthalmologists reviewed these photographs, and serum was tested for T. gondii IgG, to provide an estimate of the prevalence of toxoplasmic retinochoroiditis in an Australian cohort.

Rationale, design and methods for a community-based study of clustering and cumulative effects of chronic disease processes and their effects on ageing: the Busselton healthy ageing study.

It is widely stated that between 30% and 50% of the human population is infected with T. gondii.This estimate is based on prevalence of serum anti-T. gondii immunoglobulin (Ig), and studies from around the world have provided seroprevalence rates that range widely from 0.5% to 87.7%, with regional differences.Arguably the more important statistic is the prevalence of the clinical disease, but there are no national population-based and few community-based observational studies of toxoplasmic retinochoroiditis with serological confirmation of T. gondii infection.A major challenge for studying the epidemiology of this condition is that unless an individual suffers an attack of inflammation, they are unlikely to present for medical care. Moreover, screening for the disease requires pharmacological dilation of the pupils and examination of the retina, which are not routine procedures outside an ophthalmology clinic.

Toxoplasma gondii is an Apicomplexan protozoan parasite that causes the infectious disease known as toxoplasmosis.Globally, a wide spectrum of mammals and birds are infected with T. gondii, which is contracted in environments soiled by primary feline hosts, or by consuming the carcass of other infected animals.Humans, in particular, develop toxoplasmosis most commonly after eating undercooked meat sourced from infected livestock.Manifestations of the disease depend on the age, health and genetics of the infected individual, and the parasite strain, load and form, as well as environmental factors.The most common clinical manifestation is a recurrent unilateral inflammatory retinal disease – or posterior uveitis – termed ocular toxoplasmosis or, more specifically, toxoplasmic retinochoroiditis.Cohort studies demonstrate that approximately 60% of inflamed eyes suffer reduced vision, and up to 25% become irreversibly blind.On resolution of any attack of inflammation, the individual is left with a pigmented retinal scar that has a highly typical clinical appearance.

Molecular basis of the retinal pigment epithelial changes that characterize the ocular lesion in toxoplasmosis.

The Busselton Healthy Ageing Study is approved by the University of Western Australia Human Research Ethics Committee (approval number: RA/4/1/2203). The study adheres to the Declaration of Helsinki, and all study participants have provided written informed consent. The use of retinal photographs from the Busselton Healthy Ageing Study for the purpose of this work specifically was approved by the Busselton Population Medical Research Institute Scientific Committee (approval number: BSN20/02). A literature search conducted using the National Library of Medicine, National Center for Biotechnology Information PubMed database with multiple search terms (i.e., population AND ocular toxoplasmosis; population AND toxoplasmic retinochoroiditis; community AND ocular toxoplasmosis; community AND toxoplasmic retinochoroiditis; epidemiology AND toxoplasmic retinochoroiditis; epidemiology AND ocular toxoplasmosis, last updated on 11 April, 2022) identified no national population-based studies of the epidemiology of serologically confirmed ocular toxoplasmosis.

The diagnosis of toxoplasmic retinochoroiditis was based primarily on the clinical appearance of the retinal lesion, which is standard practice.Three uveitis-subspecialized ophthalmologists (LBF, JMF, JRS) assessed each pigmented retinal lesion by virtual conference chaired by a fourth ophthalmologist (DM) (Zoom Video Conferencing, San Jose, CA).As noted by Stanford et al.,the intraclass correlation coefficient for diagnosis of toxoplasmic retinochoroiditis from retinal photographs by experts is moderate to good, and complete concordance of opinion was required to establish the diagnosis. Given the high infection rate with T. gondii in the human population, a negative T. gondii serological test is used to exclude the diagnosis.Thus, for participants who had retinal lesions that were judged to be toxoplasmic retinochoroiditis, serum T. gondii immunoglobulin (Ig)G levels were measured at PathWest Laboratory Medicine WA (Nedlands, Australia) using the Alinity i Toxo IgG Reagent Kit, which is a chemiluminescent microparticle immunoassay (Abbott Laboratories, Wiesbaden, Germany).

The ophthalmic assessment included retinal color photography, with the stated purpose of assessment for glaucoma and age-related macular degeneration. Unless they declined, participants had dilation of the pupil of each eye with tropicamide 1% eye drops. Between 15 and 20 minutes later, retinal photographs were taken using a digital retinal camera (Canon CR-1, Japan). Two images were obtained, centered on the optic disc and on the macula. These images were saved in JPG format with 300 pixels/inch resolution of a 15.84 x 10.56 inchphotograph. Retinal images were available for 5,020 participants. These images were screened to identify participants with pigmented retinal lesions in one or both eyes.

This study made use of clinical data that were collected in the course of the Busselton Healthy Ageing Study. The design and methods of this study have been described in detail previously.In summary, this is a community-based, prospective cohort study involving 5,107 ‘baby boomers’ (i.e., born between 1946 and 1964), who reside within the local government electoral boundary of the City of Busselton in Western Australia. All persons listed on the compulsory Western Australian Electoral Commission Electoral Roll were eligible to participate: 82% of those on the electoral register were contacted and confirmed eligible; and 76% of those contacted were recruited between May 2010 and December 2015. The overall goal of the project is ‘to identify the cumulative effects of disparate illnesses that constitute the burden of disease that impacts on healthy ageing.’Baseline data collection included a health- and lifestyle- focused questionnaire, blood sampling, anthropometric measurements and body imaging, cardiovascular and respiratory monitoring, tests of physical function and balance, cognitive assessment, sleep studies, and auditory and ophthalmic examinations.

Rationale, design and methods for a community-based study of clustering and cumulative effects of chronic disease processes and their effects on ageing: the Busselton healthy ageing study.

Rationale, design and methods for a community-based study of clustering and cumulative effects of chronic disease processes and their effects on ageing: the Busselton healthy ageing study.

Toxoplasmic retinochoroiditis may occur at any location across the retina although there is a tendency for the lesions to occur in the central retina, i.e., in the region of the macula and optic disc. A recent community-based survey conducted in Cássia dos Coqueiros, Sao Paulo, Brazil (721 adult participants) used our definition of toxoplasmic retinochoroiditis, and described the disease by location across the retina, distinguishing ‘central’ and ‘peripheral’ lesions located within or outside the posterior pole, respectively; the work showed that toxoplasmic retinal lesions were located in the central retina in 23.81% of affected individuals.By applying this figure to our findings from the photographs centered on the macula and on the optic disc, the prevalence of toxoplasmic retinochoroiditis at any location across the retina may be estimated at 0.67% of the Busselton Healthy Ageing Study population, or 1 per 149 persons.

A total of 5,020 participants in the Busselton Healthy Ageing Study (2,264 men and 2,756 women aged 45 to 69 years, with a median age of 58 years) provided retinal color photographs. Among this group of adults, 4909 (97.8%) were meat eaters, including 4808 (95.8%) who ate red meat, and 963 (19.2%) were cat owners. Overall, 306 participants had pigmented retinal lesions around the macula or optic nerve. Twelve participants had retinal lesions (0.24%) that were judged by all three uveitis-subspecialized ophthalmologists to have the characteristic appearance of toxoplasmic retinochoroiditis. Serum tested from 8 of these 12 participants (0.16%) returned a positive result for T. gondii IgG, indicating the diagnosis of toxoplasmic retinochoroiditis. Retinal photographs from these 8 participants are presented in Figure 1 ; given that the retinal photographs were obtained for the purpose of visualizing the macula or optic nerve, for several of the images, the lesions are located at the end of the field of photography.

Color photographs of the retina from participants of the Busselton Health Ageing Study, who were diagnosed with toxoplasmic retinochoroiditis on the basis of the clinical appearance and serum Toxoplasma gondii immunoglobulin G. Images were centered on the optic disc (A-C, H) or macula (D-G), and for some images (A, D, H), the lesions are located at the end of the photographic field.

Figure 1 Color photographs of the retina from participants of the Busselton Health Ageing Study, who were diagnosed with toxoplasmic retinochoroiditis on the basis of the clinical appearance and serum Toxoplasma gondii immunoglobulin G. Images were centered on the optic disc (A-C, H) or macula (D-G), and for some images (A, D, H), the lesions are located at the end of the photographic field.

Discussion

17 De Angelis R.E.

Veronese Rodrigues M.L.

Passos A.D.C.

et al. Frequency and visual outcomes of ocular toxoplasmosis in an adult Brazilian population. 18 Jones J.L.

Kruszon-Moran D.

Elder S.

et al. Toxoplasma gondii infection in the United States, 2011-2014. Despite the high rates of T. gondii infection in human and diverse animal populations across the world, the prevalence of the clinical disease remains poorly described. The most common manifestation of the infection is toxoplasmic retinochoroiditis, but because toxoplasmosis is a neglected disease, it is difficult to gain traction for dedicated studies to describe its epidemiology. To estimate the prevalence of toxoplasmic retinochoroiditis, we applied standard diagnostic method to retinal photographs based at the macula and at the optic disc that were collected as part of an Australian community-based health survey with independent goals. We drew from a smaller community-based study conducted in Brazil that involved retinal examinations, with assessment of both posterior pole and periphery;although parasite strains may differ between these countries, this factor is not known to influence lesion location. We found that toxoplasmic retinochoroiditis was common in Australian adults – approximately 1 in 150 adults suffers from this condition – based on a population of baby boomers aged from 45 to 69 years at the time of the study. The rate of T. gondii infection increases with age,and thus the prevalence is expected to be lower than this figure in children and young adults, and higher than this figure in aged adults.

19 Glasner P.D.

Silveira C.

Kruszon-Moran D.

et al. An unusually high prevalence of ocular toxoplasmosis in southern Brazil. 20 de Amorim Garcia C.A.

Orefice F.

de Oliveira Lyra C.

et al. Socioeconomic conditions as determining factors in the prevalence of systemic and ocular toxoplasmosis in Northeastern Brazil. 21 Aleixo A.L.Q.

Benchimol E.I.

Neves Ede S.

et al. Frequency of lesions suggestive of ocular toxoplasmosis among a rural population in the State of Rio de Janeiro. 17 De Angelis R.E.

Veronese Rodrigues M.L.

Passos A.D.C.

et al. Frequency and visual outcomes of ocular toxoplasmosis in an adult Brazilian population. 22 de-la-Torre A.

Gonzalez G.

Diaz-Ramirez J.

Gomez-Marin J.E. Screening by ophthalmoscopy for Toxoplasma retinochoroiditis in Colombia. 23 Abu E.K.

Boampong J.N.

Amoabeng J.K.

et al. Epidemiology of ocular toxoplasmosis in three community surveys in the central region of Ghana, West Africa. There are no national population-based studies of the epidemiology of serologically confirmed ocular toxoplasmosis, but community-based surveys have been conducted in the Americas and Africa. An early survey, undertaken in Erechim, Rio Grande do Sul, alerted the field to a potentially high prevalence of the disease in Brazil,and several surveys have been conducted in different regions of the country over the past two decades. Applying the same criteria that we employed to identify toxoplasmic retinochoroiditis: De Amorim Garcia et al.described a prevalence of 0.94% in 959 students studying in Natal, Rio Grande do Norte in 2001; Aleixo et al.reported a prevalence of 3.8% in 1,071 residents of Santa Rita de Cássia, Rio de Janeiro in 2004; and De Angelis et al.measured a prevalence of 5.8% in 721 adults living in Cássia dos Coqueiros, Sao Paulo in 2016 and 2017. Surveys in 2005 of 200 staff and students at the University of Quindío, Colombia,and in 2013 of 390 children and adults across households in the Central Region, Ghana,indicated a prevalence of toxoplasmic retinochoroiditis by clinical and serological markers of 4.5% and 2.6%, respectively.

24 Holland G.N. Ocular toxoplasmosis: a global reassessment. Part I: epidemiology and course of disease. 18 Jones J.L.

Kruszon-Moran D.

Elder S.

et al. Toxoplasma gondii infection in the United States, 2011-2014. This work represents the first effort to quantify the rate of ocular toxoplasmosis in the Western Pacific Region of the world. The prevalence of toxoplasmic retinochoroiditis that we have estimated is lower than those reported in the South American and West African surveys. While it may be relevant that our study included a considerably higher number of participants than any of the other surveys, regional environmental factors are likely to impact prevalence of the condition. Interestingly, in 2003, Hollandpredicted the prevalence of toxoplasmic retinochoroiditis in the United States at 2% of the infected population, which most recently was measured at 11.14% of persons aged over 5 years;his prediction suggests a prevalence that also is lower than the previously reported figures, and indeed is lower than our result in the Busselton community cohort.

25 Johnson A.M. The incidence of anti-toxoplasma antibody in the Australian population. 26 Adriaanse K.

Firestone S.M.

Lynch M.

et al. Comparison of the modified agglutination test and real-time PCR for detection of Toxoplasma gondii exposure in feral cats from Phillip Island, Australia, and risk factors associated with infection. 3 Dawson A.C.

Ashander L.M.

Appukuttan B.

et al. Lamb as a potential source of Toxoplasma gondii infection for Australians. 27 Belluco S.

Mancin M.

Conficoni D.

et al. Investigating the determinants of Toxoplasma gondii prevalence in meat: a systematic review and meta-regression. 1 Smith J.R.

Ashander L.M.

Arruda S.L.

et al. Pathogenesis of ocular toxoplasmosis. 28 Parameswaran N.

Thompson R.C.

Sundar N.

et al. Non-archetypal Type II-like and atypical strains of Toxoplasma gondii infecting marsupials of Australia. 29 Pan S.

Thompson R.C.

Grigg M.E.

et al. Western Australian marsupials are multiply infected with genetically diverse strains of Toxoplasma gondii. 30 Donahoe S.L.

Slapeta J.

Knowles G.

et al. Clinical and pathological features of toxoplasmosis in free-ranging common wombats (Vombatus ursinus) with multilocus genotyping of Toxoplasma gondii type II-like strains. 31 Brennan A.

Donahoe S.L.

Beatty J.A.

et al. Comparison of genotypes of Toxoplasma gondii in domestic cats from Australia with latent infection or clinical toxoplasmosis. 29 Pan S.

Thompson R.C.

Grigg M.E.

et al. Western Australian marsupials are multiply infected with genetically diverse strains of Toxoplasma gondii. A summary of serological studies conducted at antenatal clinics and blood banks across Australia, published in 1979, suggested that 24% to 44% of the population was infected with T. gondii.Treatment of drinking water by filtration, and regulated farming and food processing in Australia are likely to reduce the risk of contamination of food with T. gondii. On the other hand, Australia has substantial feral cat populations that are highly infected,which, together with high levels of free-range and organic livestock farming, may promote infection with the parasite. We recently detected frequent contamination of Australian lamb with T. gondii.There is a vogue for eating a wide range of meats undercooked or raw, which overall is considered the most common route for becoming infected,and over 95% of the study group were meat eaters. Parasite genetics may also impact the likelihood of developing ocular toxoplasmosis, although review of 19 parasite genotyping studies in patients with ocular toxoplasmosis shows that strains across all genotypes may cause toxoplasmic retinochoroiditis.There have been several reports of T. gondii genotypes in Australia, each involving the study of a small number of animals, including 12 kangaroos and bettongs,16 kangaroos and wallaroos,8 wombats,and 8 domestic cats.The study of macropods was conducted in the state of Western Australia, approximately 450 miles from Busselton.These studies showed marked genotypic diversity across the strains, with a majority having nonarchetypal clonal or atypical genetics.

32 Jeroudi A.

Yeh S. Diagnostic vitrectomy for infectious uveitis. 33 Anwar Z.

Galor A.

Albini T.A.

et al. The diagnostic utility of anterior chamber paracentesis with polymerase chain reaction in anterior uveitis. 15 Yogeswaran K.

Furtado J.M.

Bodaghi B.

et al. Current practice in the management of ocular toxoplasmosis. 34 Rajput R.

Denniston A.K.

Murray P.I. False negative toxoplasma serology in an immunocompromised patient with PCR positive ocular toxoplasmosis. , 35 Sigle M.

El Atrouni W.

Ajlan R.S. Seronegative ocular toxoplasma panuveitis in an immunocompetent patient. 14 Standardization of Uveitis Nomenclature Working Group

Classification criteria for toxoplasmic retinitis. 36 Karason K.T.

Vo D.

Grauslund J.

Rasmussen M.L. Comparison of different methods of retinal imaging for the screening of diabetic retinopathy: a systematic review. As applies to all clinical research on toxoplasmic retinochoroiditis, not only epidemiological studies, one limitation of our work relates to diagnostic accuracy. It is not possible to recover an organism to confirm the diagnosis, given that T. gondii resides in the retina and retinal biopsy is inherently damaging to the intraocular tissues. Polymerase chain reaction amplification of parasite DNA in ocular fluid is used clinically,but only in ambiguous cases since there is risk to the sampling procedure,and not in epidemiology studies. Thus, the diagnostic standard is clinical appearance – which was judged by three uveitis-subspecialized ophthalmologists in this study – along with positive T. gondii serology.Negative serology is possible in patients with ocular toxoplasmosis, specifically in immunocompromised or aged persons.Like other investigators, we observed lesions that were typical of toxoplasmic retinochoroiditis, but had to be discounted as serology was negative. Recently reported diagnostic criteria apply to active disease only,and must be modified for epidemiological surveys, in which most or all toxoplasmic lesions are expected to be inactive. Another limitation of our work relates to the ocular imaging; with the advent of wide field photography and non-mydriatic cameras,there exists the opportunity for a broader retinal coverage and increased participation in future studies in this area.

In summary, this work represents the first effort to estimate the prevalence of toxoplasmic retinochoroiditis in an Australian population. Our findings indicate that this condition is common. Further, these results imply that efforts to quantify and address risk factors are justified, including infections in domesticated and feral cats, contamination of meat, and preparation of meat and meat products for human consumption.