Research Article: Toxoplasmic retinochoroiditis: The influence of age, number of retinochoroidal lesions and genetic polymorphism for IFN-γ +874 T/A as risk factors for recurrence in a survival analysis

Date Published: February 12, 2019

Publisher: Public Library of Science

Author(s): Ana Luisa Quintella do Couto Aleixo, Raquel Vasconcelos C. de Oliveira, Maíra Cavalcanti Albuquerque, Ana Luiza Biancardi, André Luiz Land Curi, Eliezer Israel Benchimol, Maria Regina Reis Amendoeira, James T. Rosenbaum.


To analyze risk factors for recurrent toxoplasmic retinochoroiditis.

Single center prospective case series.

A total of 230 patients with toxoplasmic retinochoroiditis were prospectively followed to assess recurrences. All patients were treated with a specific drug regime for toxoplasmosis in each episode of active retinochoroiditis. Individuals with chronic diseases and pregnant women were excluded. Survival analysis by extended Cox regression model (Prentice-Williams-Peterson counting process model) was performed to evaluate the time between recurrences according to some potential risk factors: age, number of retinochoroidal lesions at initial evaluation, sex and interferon gamma +874 T/A gene polymorphism. Hazard Ratios (HR) and 95% confidence intervals (CI) were provided to interpret the risk effects.

One hundred sixty-two recurrence episodes were observed in 104 (45.2%) patients during follow-up that lasted from 269 to 1976 days. Mean age at presentation was 32.8 years (Standard deviation = 11.38). The risk of recurrence during follow up was influenced by age (HR = 1.02, 95% CI = 1.01–1.04) and number of retinochoroidal lesions at the beginning of the study (HR = 1.60, 95% CI = 1.07–2.40). Heterozygosis for IFN-γ gene polymorphism at position +874 T/A was also associated with recurrence (HR = 1.49, 95% CI = 1.04–2.14).

The risk of ocular toxoplasmosis recurrence after an active episode increased with age and was significantly higher in individuals with primary lesions, which suggests that individuals with this characteristic and the elderly could benefit from recurrence prophylactic strategies with antimicrobials. Results suggest an association between IFN-γ gene polymorphism at position +874T/A and recurrence.

Partial Text

Toxoplasmosis is widely distributed and has high prevalence around the world. In Brazil, the prevalence of ocular toxoplasmosis varies according to the area under study and can reach 17.7% of the population [1,2]. Individuals affected by toxoplasmic retinochoroiditis (TRC) are at risk of recurrent episodes throughout their lives, which may cause visual impairment. [3,4] Recurrence studies are extremely difficult to perform, mainly because they demand long follow-ups and also because recurrences may be influenced by an intricate network of possible and still unknown protection and risk factors. There are indications of a clustering pattern of recurrences and the course of the disease may be related to individual’s age, transmission form, whether congenital or acquired, virulence of T. gondii strain and host susceptibility. [5,6,7]

Patients with toxoplasmic retinochoroiditis were enrolled in the outpatient unit of Infectious Ophthalmology Laboratory of Evandro Chagas National Institute of Infectious Diseases (INI)- Fiocruz, from January 2010 to January 2014 and were followed until July 2015. The study was approved by the Evandro Chagas National Institute of Infectious Diseases (INI)Ethics Committee (CAAE 0075.0.009.00011) and all patients signed an informed consent form. Subjects between 14 and 18 years old who agreed to participate also signed an informed consent in conjunction with a parent or surrogate. Detailed description of the formation of this cohort and its characteristics have been previously published [16].

We analyzed 162 recurrence episodes in 104 out of 230 patients monitored over periods that varied from 269 to 1976 days, mean 1060 days. The main characteristics of the studied population are summarized in Table 1.

Studying the factors that influence recurrence of ocular toxoplasmosis is challenging due to multiple factors potentially involved. This study evaluated prospectively a large number of TRC patients, treated with a standardized drug regimen, selected with pre-determined diagnostic criteria and examined by the same ophthalmologists at every visit. This method, associated with the survival analyses for host risk factors performed, distinguishes it from the available scientific literature on this disease. In this cohort, recurrence risk after a TRC active episode was significantly higher in patients with primary lesion (defined as an active focal lesion in the absence of other retinochoroidal scars) and increased with patient’s age. This result is in agreement with previous literature data from retrospective studies, which indicates that the elderly and patients with a primary lesion have higher risk of recurrence. [21,22]

The analysis of this cohort showed that the risk of TRC recurrence during the first years after an active episode increased with age and was significantly greater in patients with primary lesion. This fact suggests that the elderly or individuals with primary lesions could benefit from prophylactic antimicrobials. In addition, this study suggests that the genetic polymorphism of IFN-γ +874T/A can be associated with TRC recurrence.




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