Preprint

Brief Report

Environmental Risk Factors Associated with Retinochoroiditis Caused by Toxoplasma gondii

Altmetrics

Downloads

104

Views

Comments

Submitted:

01 November 2023

Posted:

02 November 2023

You are already at the latest version

Alerts

Abstract

Objective: To evaluate which risk factors contribute directly or indirectly to Toxoplasma gondii infection in patients with ocular toxoplasmosis. Methods: Between 2018-2020, a total of 306 patients were selected, and treated at the Retinology Outpatient Clinic of the Specialty Hospital of Sāo José do Rio Preto, in the state of São Paulo. After the fundoscopy test, the Enzyme Linked Fluorescent Assay (ELFA) was used to determine IgG and IgM class anti-Toxoplasma gondii antibodies. Results: The results showed that individuals aged 60 years or older, and women who had a previous pregnancy, (p=0.000, OR= 8.137 and 95 % CI = 2.562 – 25.844), (p=0.016, OR= 7.395 and CI 95 % = 1,449 – 37,725) respectively, were 48.6 % more likely to develop ocular toxoplasmosis. Conclusion: In this way, previous pregnancy is a risk factor for the reactivation of toxoplasma, as well as for the generation of retinochoroiditis in previously infected women.

Keywords:

Subject: Medicine and Pharmacology - Epidemiology and Infectious Diseases

Introduction

Toxoplasmosis is caused by the protozoan Toxoplasma gondii, which was first described in 1908 by Nicolle and Manceaux.[1] It is an obligate intracellular parasite, with worldwide distribution and capable of infecting warm-blooded animals, including mammals and birds.[2]

Its life cycle is heteroxenous, i.e., it occurs both sexually and asexually, with felines as definitive hosts, where sexual reproduction takes place, and vertebrates as intermediate hosts, where asexual reproduction occurs.[3,4]

Both animals and humans become infected from the consumption of raw or undercooked meat containing T. gondii cysts, by ingestion of food and water contaminated with oocysts of the parasite, or the transmission can be transplacental from mother to child during pregnancy.[5,6,7,8] There are reports of other transmission routes such as accidental inoculation, blood transfusion, and organ transplantation.[6,9,10]

Toxoplasmosis is asymptomatic in 80 % of cases due to the efficiency of the immune system, which is able to limit the spread of multiplying tachyzoites.[11] However, in immunocompromised patients (such as HIV+ and transplant recipients), the cysts can rupture, releasing bradyzoites, which can seriously compromise health status.[12,13,14,15]

Ocular toxoplasmosis (OT) is an infection caused by toxoplasma and is the most common cause of posterior uveitis that variety is directly related to the immune system of each individual. [16,17] Lesions caused by the parasite usually heal in two to four months in immunocompetent patients and a study reveals that in about 70 % of cases of patients who seek an ophthalmologist, the lesions resulting from OT that heal are associated with other lesions. [17,18] The study carried out by our research group revealed that OT represents 27 % of eye diseases affecting patients in the northwest region of the state of São Paulo, Brazil.[19]

Infection by the parasite is recognized as the most common zoonotic disease in the world, due to its worldwide distribution and the large number of intermediate hosts. Studies indicate that 25 to 30 % of the world population is infected by T. gondii. However, infection rates can vary significantly between and within countries, depending on socioeconomic, environmental, and cultural conditions such as living, eating, and housing habits.[1,7] The aim of this study was to evaluate which risk factors contribute directly or indirectly to T. gondii infection in patients with ocular toxoplasmosis.

Methods

Between the years 2018-2020, a total of 306 patients with positive and negative serology for toxoplasmosis were selected. These individuals were divided into four groups as follows: G1 = 53 patients with active lesion resulting from toxoplasmosis and positive serology; G2 = 29 patients who presented ocular scarring due to toxoplasmosis and positive serology; G3 = 135 patients without lesion or scar resulting from toxoplasmosis and with positive serology; and G4 = 89 patients without lesion or scar resulting from toxoplasmosis and with non-reactive serology. All individuals recruited in this study received care at the Retinology Outpatient Clinic of the Specialty Hospital of Sāo José do Rio Preto – SP, where they underwent clinical evaluation by fundoscopy.

Two skilled doctors evaluated patients clinically, using the previously mentioned indirect binocular ophthalmoscope (Binocular Ophthalmoscope ID10, Topcon Corporation, USA).[19,20] All patients underwent thorough eye exams that included measuring intraocular pressure using Goldmann applanation tonometry, measuring visual acuity using the logMAR Early Treatment Diabetic Retinopathy Study [ETDRS] chart with the best correction in accordance with ETDRS standards, performing biomicroscopy with a slit lamp, and performing stereoscopic biomicroscopy using a 78-diopter lens (Volk) and classifying the results in accordance with ETDRS.[21]

Patients who agreed to participate in the study signed the Free and Informed Consent Form (FICT) and after medical evaluation of these individuals, peripheral blood collection was performed to identify IgG and IgM anti-Toxoplasma gondii antibodies, using the ELFA method (Enzyme Linked Fluorescent Assay), according to the manufacturer's instructions (Biomeriux-France) and also answered a questionnaire with basic epidemiological data such as gender, age, eating habits (consumption of raw or undercooked meat, unpasteurized milk, adequate food hygiene); housing conditions (area in which they live, frequent presence of mechanical vectors and domestic animals); socioeconomic conditions; and history of blood transfusion.

Statistical analysis:

The collected data were analyzed using the Statistical Package For Social Sciences (SPSS, IBM, version 24.0), GraphPad Instat 3.10 (2009), and Prisma 6.07 (2015) statistical programs.

Descriptive statistical analysis was performed from the calculations of measures of central tendency, dispersion, and frequency counts. In univariate analysis, frequency comparisons were performed using Pearson's Chi-square test. Multivariate analysis of Binary Logistic Regression was used to verify the predictor variables of the outcome (Ocular Toxoplasmosis). Variables that presented P values ≤ 0.20 in the bivariate analysis were included in the regression model, which used the Backward Stepwise selection method (Likelihood Ratio).

In all analyses, a p value ≤ 0.05 was considered statistically significant.

Results

Binary logistic regression analysis was performed using the Backward Stepwise method (Likelihood Ratio), and only variables that presented p ≤ 0.20 in the univariate analysis were included in the model (Table 1). The percentage of correctness of the model was 70.1 %, with Nagelkerke's R² of 48.6 % and Hosmer and Lemeshow's Test with chi-square (X²) = 4.403, gl = 4, and p=0.3540. These values indicate that the model constructed has a high probability of being correct (70.1%) and a moderate association of the variables that remained in the model at the outcome (Nagelkerke's R² of 48.6 %).

The variables that remained in the model and presented p ≤ 0.05 were: age ≥ 60 years (p=0.000, OR= 8.137 and 95 % CI = 2.562 – 25.844) and previous pregnancy (p=0.016, OR= 7.395 and 95 % CI = 1.449 – 37.725). Based on the OR (Odds Ratio) values it was possible to verify the existence of a significant association between these variables present in the regression model, and the occurrence of ocular toxoplasmosis in the samples evaluated in the present study (Table 1).

Discussion

This study analyzed environmental risk factors for retinochoroiditis caused by T. gondii. The results of our analysis showed that individuals aged 60 or over had a risk factor for toxoplasma reactivation (p=0.000, OR= 8.137 and 95 % CI = 2.562 – 25.844). Studies show that extremes of age are considered a risk factor for increased severity of clinical manifestations; therefore, older patients appear to be in a more risky situation.[2] In the elderly, several clinical variations of ocular toxoplasmosis are likely to be present, such as atypical necrotizing disease.[22,23] The weakening of the immune system can impair the immune response to such an extent that it can trigger fulminant ocular toxoplasmosis. Possibly, the reduction of the immune response allows the large-scale proliferation of the parasite in the retinal cells, triggering severe lesions in atypical, extensive, or multiple areas of retinochoroiditis.[24] This information cited above is in agreement with our study on risk factors.

The idea that patients aged 60 years or older are more likely to develop toxoplasma retinochoroiditis is supported by Sadighi (2018)^.[25] In the elderly, a higher frequency of severe) manifestations related to toxoplasmosis is observed due to changes that occur in the innate and adaptive immune system in their senescent organisms,[25] which is in agreement with our study. When in contact with the organism, the toxoplasma triggers responses from macrophages, lymphocytes, and cytokines, all in association for the complete defense of the infected organism. As elderly individuals have a modified immune system that defense becomes deficient, allowing greater aggression of the parasite in target organs.

The hypothesis found in this study suggests that this increase in people aged 60 years or older is due to the decline of the immune system that occurs over the years, as well as that over the years, the patient is exposed to the parasite for a longer time, and over that time vision impairment occurs.

Likewise, associated with the results obtained from our study on a higher risk in women with previous pregnancy, the authors Florença Robert-Gangneux and Marie-Laure Dardéc agree in saying that when the primary infection occurs in the first trimester of pregnancy, the chance of the placental barrier protecting the fetus is ninety percent, so the mother remains with the parasitemia in her body, allowing more maternal cells to be affected by the parasite; as the eye is a target organ of toxoplasma, the chance of it being lodged in this site increases.[3] Thus, there is the possibility of re-acceleration of toxoplasmosis in these chronically infected patients, causing retinochoroiditis.[6,22,26] Our study shows that women who had a previous pregnancy are more likely to reactivate the infection (p=0.016, OR= 7.395 and 95 % CI = 1.449 – 37.725).

In addition, ocular toxoplasmosis, also called uveitis, is characterized by severe inflammation in the uvea, which can lead to visual impairment and blindness due to eye complications.^20,21 Studies have shown that the microglia present in the retina plays a key role in the onset of uveitis, and the activation of peripheral immune system cells results in apoptosis of retinal cells, promoting tissue inflammation. This indicates that microglia underlie the regulation of retinal inflammation as an immune response.²¹ Many studies corroborate that cytokines such as TNF-α, IL-1β, IL-6, and CCL2, and toxic mediators such as NO are directly involved in the regulation of the immune system in ocular toxoplasmosis, some of which act on vascular permeability, recruitment of leukocytes, and retinal inflammation.[27,28,29,30,31,32,33]

The reactivation of eye infection caused by T. gondii is frequent because it is an immunologically favorable environment [26,29,31,34,35,36] and pregnancy is a facilitating factor for its reactivation due to the immunotolerance that it confers on the host.[26,37,38,39] The T. gondii parasite, when penetrating the human cell, activates several cytokine genes such as IL-10, IL-1β, IFN-γ, which are associated with the development of ocular toxoplasmosis.[3,33,40,41,42] A study shows that the appearance of eye lesions is a consequence of the susceptibility of the host gene associated with exposure to more virulent strains.[43,44,45]

The studies by Kalogeropoulos and collaborators [46], as well as by Naranjo-Galvis and collaborators[47], describe the relationship of predisposition to susceptibility to the occurrence of ocular impairment, and indicate that the immune response triggered by genetic control is considerable for the pathogenesis of T. gondii retinochoroiditis. The patient's immunological status is decisive for the pathogenesis of ocular toxoplasmosis, as well as the status of the patient's immune system is closely related to the effectiveness of infection control, as its success is closely linked to the correct function of immune system T cells.[3,47,48,49,50,51]

The patients answered a questionnaire with basic epidemiological data such as gender, eating habits (consumption of raw or undercooked meat, unpasteurized milk, adequate food hygiene); housing conditions (area in which they live, frequent presence of mechanical vectors, and domestic animals); socioeconomic conditions; and history of blood transfusion, which did not present a statistically significant difference. Another study carried out by our research group, which evaluated the risk factors for the development of toxoplasmosis in Brazil, revealed that the presence of dogs and puppies and the consumption of raw or undercooked meat are associated with infection caused by the parasite T. gondii, but not with the development of ocular toxoplasmosis.[19,52]

Previous pregnancy and age over 60 years confer a risk factor for Toxoplasma reactivation.

Author Contributions

CCB: FBF, PMC were responsible for the concept and design of the study. RCS, FBF, GHP, AAACF, MP, GMFJ performed the inclusion of patients with ocular toxoplasmosis, sample collection, and developed the ophthalmological clinical evaluation and clinical analyses. GMFJ, APO, ALG, FHM performed the laboratorial tests. CGFG, GMFJ, LC, LCM, CCB performed the data analysis. CCB, LCM, GMFJ, CGFG, PMC wrote the manuscript. All authors read and approved the final manuscript.

Funding

This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (grants:2018/09448-8 to GMFJ) and by CNPq (305976/2022-2 to LCM). The opinions, assumptions, and conclusions or recommendations expressed in this material are the responsibility of the authors and do not necessarily reflect the views of FAPESP. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Ethical approval

Written informed consent was obtained from each enrolled patient. This study was approved by the Ethical in Human Research Committee of the Faculty of Medicine of Sāo José do Rio Preto (CAAE: 96386518.2.0000.5415).

Conflicts of interest

None declared.

References

Aguirre:, A.A.; Longcore, T.; Barbieri, M.; Dabritz, H.; Hill, D.; Klein, P.N.; Lepczyk, C.; Lilly, E.L.; McLeod, R.; Milcarsky, J.; et al. The One Health Approach to Toxoplasmosis: Epidemiology, Control, and Prevention Strategies. Ecohealth 2019, 16, 378–390. [Google Scholar] [CrossRef]
Holland, G.N. Ocular Toxoplasmosis: The Influence of Patient Age. Mem Inst Oswaldo Cruz 2009, 104, 351–357. [Google Scholar] [CrossRef]
Robert-Gangneux, F.; Dardé, M.L. Epidemiology of and Diagnostic Strategies for Toxoplasmosis. Clin Microbiol Rev 2012, 25, 264–296. [Google Scholar] [CrossRef] [PubMed]
Dubey, J.P. The History and Life Cycle of Toxoplasma Gondii. In Toxoplasma gondii; Elsevier, 2020; pp. 1–19 ISBN 9780128150412.
Shapiro, K.; Bahia-Oliveira, L.; Dixon, B.; Dumètre, A.; de Wit, L.A.; VanWormer, E.; Villena, I. Environmental Transmission of Toxoplasma Gondii: Oocysts in Water, Soil and Food. Food Waterborne Parasitol 2019, 15, e00049. [Google Scholar] [CrossRef] [PubMed]
Vargas-Villavicencio, J.A.; Cañedo-Solares, I.; Correa, D. Anti-Toxoplasma Gondii IgM Long Persistence: What Are the Underlying Mechanisms? Microorganisms 2022, 10, 1659. [Google Scholar] [CrossRef] [PubMed]
Djurković-Djaković, O.; Dupouy-Camet, J.; Van der Giessen, J.; Dubey, J.P. Toxoplasmosis: Overview from a One Health Perspective. Food Waterborne Parasitol 2019, 15, e00054. [Google Scholar] [CrossRef] [PubMed]
De Moura, L.; Garcia Bahia-Oliveira, L.M.; Wada, M.Y.; Jones, J.L.; Tuboi, S.H.; Carmo, E.H.; Ramalho, W.M.; Camargo, N.J.; Trevisan, R.; Graça, R.M.T.; et al. Waterborne Toxoplasmosis, Brazil, from Field to Gene. Emerg Infect Dis 2006, 12, 326–329. [Google Scholar] [CrossRef] [PubMed]
Zhu, Z.; Hua, X.; Yu, Y.; Zhu, P.; Hong, K.; Ke, Y. Effect of Red Blood Cell Transfusion on the Development of Retinopathy of Prematurity: A Systematic Review and Meta-Analysis. PLoS One 2020, 15. [Google Scholar] [CrossRef] [PubMed]
Foroutan-Rad, M.; Majidiani, H.; Dalvand, S.; Daryani, A.; Kooti, W.; Saki, J.; Hedayati-Rad, F.; Ahmadpour, E. Toxoplasmosis in Blood Donors: A Systematic Review and Meta-Analysis. Transfus Med Rev 2016, 30, 116–122. [Google Scholar] [CrossRef]
Murata, Y.; Sugi, T.; Weiss, L.M.; Kato, K. Identification of Compounds That Suppress Toxoplasma Gondii Tachyzoites & Bradyzoites. PLoS One 2017, 12. [Google Scholar] [CrossRef]
Vidal, J.E. HIV-Related Cerebral Toxoplasmosis Revisited: Current Concepts and Controversies of an Old Disease. J Int Assoc Provid AIDS Care 2019, 18, 232595821986731. [Google Scholar] [CrossRef]
Conrad, A.; Le Maréchal, M.; Dupont, D.; Ducastelle-Leprêtre, S.; Balsat, M.; Labussière-Wallet, H.; Barraco, F.; Nicolini, F.E.; Thomas, X.; Gilis, L.; et al. A Matched Case–Control Study of Toxoplasmosis after Allogeneic Haematopoietic Stem Cell Transplantation: Still a Devastating Complication. Clinical Microbiology and Infection 2016, 22, 636–641. [Google Scholar] [CrossRef]
La Hoz, R.M.; Morris, M.I. Tissue and Blood Protozoa Including Toxoplasmosis, Chagas Disease, Leishmaniasis, Babesia, Acanthamoeba, Balamuthia, and Naegleria in Solid Organ Transplant Recipients— Guidelines from the American Society of Transplantation Infectious Diseases Community. Clin Transplant 2019, 33, 1–20. [Google Scholar] [CrossRef]
Ramanan, P.; Scherger, S.; Benamu, E.; Bajrovic, V.; Jackson, W.; Hage, C.A.; Hakki, M.; Baddley, J.W.; Abidi, M.Z. Toxoplasmosis in Non-cardiac Solid Organ Transplant Recipients: A Case Series and Review of Literature. Transplant Infectious Disease 2020, 22, e13218. [Google Scholar] [CrossRef]
Kalogeropoulos, D.; Sakkas, H.; Mohammed, B.; Vartholomatos, G.; Malamos, K.; Sreekantam, S.; Kanavaros, P.; Kalogeropoulos, C. Ocular Toxoplasmosis: A Review of the Current Diagnostic and Therapeutic Approaches. Int Ophthalmol 2022, 42, 295–321. [Google Scholar] [CrossRef] [PubMed]
De-la-Torre, A.; Pfaff, A.W.; Grigg, M.E.; Villard, O.; Candolfi, E.; Gomez-Marin, J.E. Ocular Cytokinome Is Linked to Clinical Characteristics in Ocular Toxoplasmosis. Cytokine 2014, 68, 23–31. [Google Scholar] [CrossRef]
Rodriguez Fernandez, V.; Casini, G.; Bruschi, F. Ocular Toxoplasmosis: Mechanisms of Retinal Infection and Experimental Models. Parasitologia 2021, 1, 50–60. [Google Scholar] [CrossRef]
Ferreira, A.I.C.I.C.; De Mattos, C.C.B.C.B.; Frederico, F.B.B.; Meira, C.S.S.; Almeida, G.C.C.; Nakashima, F.; Bernardo, C.R.R.; Pereira-Chioccola, V.L.L.; De Mattos, L.C.C. Risk Factors for Ocular Toxoplasmosis in Brazil. Epidemiol Infect 2014, 142, 142–148. [Google Scholar] [CrossRef] [PubMed]
Previato, M.; Frederico, F.B.; Henrique Antunes Murata, F.; Siqueira, R.C.; Barbosa, A.P.; Silveira-Carvalho, A.P.; Da Silva Meira, C.; Pereira-Chioccola, V.L.; Gava, R.; Pereira Martins Neto, P.; et al. A Brazilian Report Using Serological and Molecular Diagnosis to Monitoring Acute Ocular Toxoplasmosis Infectious Diseases. BMC Res Notes 2015, 8, 746. [Google Scholar] [CrossRef]
Early Treatment Diabetic Retinopathy Study Design and Baseline Patient Characteristics: ETDRS Report Number 7. Ophthalmology 1991, 98, 741–756. [CrossRef]
Fabiani, S.; Caroselli, C.; Menchini, M.; Gabbriellini, G.; Falcone, M.; Bruschi, F. Ocular Toxoplasmosis, an Overview Focusing on Clinical Aspects. Acta Trop 2022, 225, 106180. [Google Scholar] [CrossRef] [PubMed]
Anvari, D.; Saberi, R.; Sharif, M.; Sarvi, S.; Hosseini, S.A.; Moosazadeh, M.; Hosseininejad, Z.; Chegeni, T.N.; Daryani, A. Seroprevalence of Neospora Caninum Infection in Dog Population Worldwide: A Systematic Review and Meta-Analysis. Acta Parasitol 2020, 65, 273–290. [Google Scholar] [CrossRef] [PubMed]
Johnson, M.W.; Greven, C.M.; Jaffe, G.J.; Sudhalkar, H.; Vine, A.K. Atypical, Severe Toxoplasmic Retinochoroiditis in Elderly Patients. Ophthalmology 1997, 104, 48–57. [Google Scholar] [CrossRef] [PubMed]
Sadighi Akha, A.A. Aging and the Immune System: An Overview. J Immunol Methods 2018, 463, 21–26. [Google Scholar] [CrossRef] [PubMed]
Boaventura Avelar, J.; Hállison Alves Rezende, H.; Ribeiro Storchilo, H.; Rassan de Lima Candido, R.; Naves do Amaral, W.; Martins Avelino, M.; Maria de Castro, A. Reativação Da Toxoplasmose Durante o Oitavo Mês de Gestação Reactivation of Toxoplasmosis during the Eighth Month of Pregnancy. Revista Norte Mineira de Enfermagem 2015, 4, 57–69. [Google Scholar]
Silverman, S.M.; Wong, W.T. Microglia in the Retina: Roles in Development, Maturity, and Disease. 2018, 4, 45–77. [CrossRef]
Hoogewoud, F.; Kowalczuk, L.; Bousquet, E.; Brézin, A.; Touchard, E.; Buggage, R.; Bordet, T.; Behar-Cohen, F. Les Anti-TNF-α Pour Le Traitement Des Uvéites Non Infectieuses. médecine/sciences 2020, 36, 893–899. [Google Scholar] [CrossRef]
Murenu, E.; Gerhardt, M.J.; Biel, M.; Michalakis, S. More than Meets the Eye: The Role of Microglia in Healthy and Diseased Retina. Front Immunol 2022, 13, 1006897. [Google Scholar] [CrossRef]
Wooff, Y.; Man, S.M.; Aggio-Bruce, R.; Natoli, R.; Fernando, N. IL-1 Family Members Mediate Cell Death, Inflammation and Angiogenesis in Retinal Degenerative Diseases. Front Immunol 2019, 10, 462812. [Google Scholar] [CrossRef]
Kumari, A.; Borooah, S. The Role of Microglia in Inherited Retinal Diseases. Adv Exp Med Biol 2023, 1415, 197–205. [Google Scholar]
Guo, L.; Choi, S.; Bikkannavar, P.; Cordeiro, M.F. Microglia: Key Players in Retinal Ageing and Neurodegeneration. Front Cell Neurosci 2022, 16, 804782. [Google Scholar] [CrossRef]
Araujo, W.M.R.; Ayo, C.M.; Previato, M.; de Faria, G.M.Jr.; Frederico, F.B.; Siqueira, R.C.; de Almeida, G.C.Jr.; Pereira-Chioccola, V.L.; de Mattos, L.C.; Brandão, C.C. Role of Interleukin 1β and Interleukin 10 Variants on Ocular Toxoplasmosis in Brazilian Individuals. Frontiers in Ophthalmology 2023, 3, 1183167. [Google Scholar] [CrossRef]
Bretagne, S.; Costa, J.M.; Foulet, F.; Jabot-Lestang, L.; Baud-Camus, F.; Cordonnier, C. Prospective Study of Toxoplasma Reactivation by Polymerase Chain Reaction in Allogeneic Stem-Cell Transplant Recipients. Transplant Infectious Disease 2000, 2, 127–132. [Google Scholar] [CrossRef]
Uğurlar, E. Uğurlar (2023) Reactivation of Latent Toxoplasmosis; Vol. 9;
Dick, A.D.; Forrester, J. V.; Liversidge, J.; Cope, A.P. The Role of Tumour Necrosis Factor (TNF-α) in Experimental Autoimmune Uveoretinitis (EAU). Prog Retin Eye Res 2004, 23, 617–637. [Google Scholar] [CrossRef]
Gómez-Chávez, F.; Cañedo-Solares, I.; Ortiz-Alegría, L.B.; Flores-García, Y.; Luna-Pastén, H.; Figueroa-Damián, R.; Mora-González, J.C.; Correa, D. Maternal Immune Response during Pregnancy and Vertical Transmission in Human Toxoplasmosis. Front Immunol 2019, 10, 285. [Google Scholar] [CrossRef]
Borges, M.; Magalhães Silva, T.; Brito, C.; Teixeira, N.; Roberts, C.W. How Does Toxoplasmosis Affect the Maternal-Foetal Immune Interface and Pregnancy? Parasite Immunol 2019, 41, e12606. [Google Scholar] [CrossRef]
Damar Çakırca, T.; Can, İ.N.; Deniz, M.; Torun, A.; Akçabay, Ç.; Güzelçiçek, A. Toxoplasmosis: A Timeless Challenge for Pregnancy. Trop Med Infect Dis 2023, 8. [Google Scholar] [CrossRef]
Sana, M.; Rashid, M.; Rashid, I.; Akbar, H.; Gomez-Marin, J.E.; Dimier-Poisson, I. Immune Response against Toxoplasmosis—Some Recent Updates RH: Toxoplasma Gondii Immune Response. Int J Immunopathol Pharmacol 2022, 36, 1–19. [Google Scholar] [CrossRef] [PubMed]
Stepp, M.A.; Menko, A.S. Immune Responses to Injury and Their Links to Eye Disease. Translational Research 2021, 1–20. [Google Scholar] [CrossRef] [PubMed]
Meira, C.S.; Pereira-Chioccola, V.L.; Vidal, J.E.; de Mattos, C.C.B.; Motoie, G.; Costa-Silva, T.A.; Gava, R.; Frederico, F.B.; de Mattos, L.C.; Dantas, D.S. de S.; et al. Cerebral and Ocular Toxoplasmosis Related with IFN-γ, TNF-α, and IL-10 Levels. Front Microbiol 2014, 5. [Google Scholar] [CrossRef]
Shwab, E.K.; Zhu, X.Q.; Majumdar, D.; Pena, H.F.J.; Gennari, S.M.; Dubey, J.P.; Su, C. Geographical Patterns of Toxoplasma Gondii Genetic Diversity Revealed by Multilocus PCR-RFLP Genotyping. Parasitology 2014, 141, 453–461. [Google Scholar] [CrossRef]
Meireles, L.R.; Bezerra, E.C.M.; Andrade, J.Q.; Cassiano, L.A.; Pena, H.F.J.; Alves, B.F.; Francisco, R.P.V.; de Andrade, H.F. Isolation and Characterization of Toxoplasma Gondii Isolates from Human Congenital Toxoplasmosis Cases Reveal a New Virulent Genotype in São Paulo, Brazil. Parasitol Res 2022, 121, 3223–3228. [Google Scholar] [CrossRef]
dos Santos, E.H.; Barreira, G.A.; Yamamoto, L.; Rocha, M.C.; Rodrigues, K.A.; Cruz, M.C.P.; Kanunfre, K.A.; Okay, T.S. New Allele-Specific Oligonucleotide (ASO) Amplifications for Toxoplasma Gondii Rop18 Allele Typing: Analysis of 86 Human Congenital Infections in Brazil. Acta Trop 2023, 247, 107011. [Google Scholar] [CrossRef]
Kalogeropoulos, D.; Kalogeropoulos, C.; Sakkas, H.; Mohammed, B.; Vartholomatos, G.; Malamos, K.; Sreekantam, S.; Kanavaros, P.; de-la-Torre, A. Pathophysiological Aspects of Ocular Toxoplasmosis: Host-Parasite Interactions. Ocul Immunol Inflamm 2021, 1–10. [Google Scholar] [CrossRef]
Naranjo-Galvis, C.A.; de-la-Torre, A.; Mantilla-Muriel, L.E.; Beltrán-Angarita, L.; Elcoroaristizabal-Martín, X.; McLeod, R.; Alliey-Rodriguez, N.; Begeman, I.J.; de Mesa, C.L.; Gómez-Marín, J.E.; et al. Genetic Polymorphisms in Cytokine Genes in Colombian Patients with Ocular Toxoplasmosis. Infect Immun 2018, 86. [Google Scholar] [CrossRef]
Cifuentes-González, C.; Zapata-Bravo, E.; Sierra-Cote, M.C.; Boada-Robayo, L.; Vargas-Largo, Á.P.; Reyes-Guanes, J.; de-la-Torre, A. Colombian Ocular Infectious Epidemiology Study (COIES): Ocular Toxoplasmosis Incidence and Sociodemographic Characterization, 2015-2019. International Journal of Infectious Diseases 2022, 117, 349–355. [Google Scholar] [CrossRef]
Ayo, C.M.; Frederico, F.B.; Siqueira, R.C.; Brandão De Mattos, C.D.C.; Previato, M.; Barbosa, A.P.; Murata, F.H.A.; Silveira-Carvalho, A.P.; De Mattos, L.C. Ocular Toxoplasmosis: Susceptibility in Respect to the Genes Encoding the KIR Receptors and Their HLA Class I Ligands. Sci Rep 2016, 6, 36632. [Google Scholar] [CrossRef] [PubMed]
de Faria Junior, G.M.; Ayo, C.M.; de Oliveira, A.P.; Lopes, A.G.; Frederico, F.B.; Silveira-Carvalho, A.P.; Previato, M.; Barbosa, A.P.; Murata, F.H.A.; de Almeida Junior, G.C.; et al. CCR5 Chemokine Receptor Gene Polymorphisms in Ocular Toxoplasmosis. Acta Trop 2018, 178, 276–280. [Google Scholar] [CrossRef] [PubMed]
Ayo, C.M.; Da Silveira Camargo, A.V.; Frederico, F.B.; Siqueira, R.C.; Previato, M.; Murata, F.H.A.; Silveira-Carvalho, A.P.; Barbosa, A.P.; De Mattos, C.D.C.B.; De Mattos, L.C. MHC Class i Chain-Related Gene A Polymorphisms and Linkage Disequilibrium with HLA-B and HLA-C Alleles in Ocular Toxoplasmosis. PLoS One 2015, 10, e0144534. [Google Scholar] [CrossRef] [PubMed]
Dubey, J.P.; Murata, F.H.A.; Cerqueira-Cézar, C.K.; Kwok, O.C.H.; Yang, Y.; Su, C. Toxoplasma Gondii Infections in Dogs: 2009-2020. Vet Parasitol 2020, 287, 109223. [Google Scholar] [CrossRef] [PubMed]

Table 1. Risk factors associated with Toxoplasma gondii infection in ocular toxoplasmosis patients by univariate logistic regression analysis, Sao Jose do Rio Preto, Sao Paulo state, 2022.

Variables		G1		G2		G3		G4		Univariate
Variables		N	%	N	%	N	%	N	%	p- value
Age	≥60 years	7	13.2	6	20.7	104	77	21	23.6	p = 0.000
Age	<60 years	46	86.7	23	79.3	31	23	68	76.4	p = 0.000
Gender	Male	36	67,9	18	62	77	57	53	59,5	p= 0.894
Gender	Female	17	32,1	11	38	58	43	36	40,5	p= 0.894
Blood transfusion	Yes	12	22.6	2	6.9	17	12.6	6	6.7	p = 0.000
Blood transfusion	No	41	77.3	27	93.1	118	87.4	83	93.3	p = 0.000
Domestic animal	Yes	45	84.9	22	75.8	86	63.7	69	77.5	p = 0.118
Domestic animal	No	8	15.1	7	24.2	49	36.3	20	22.5	p = 0.118
Have a cat at home	Yes	15	28.3	5	17.2	33	24.4	20	22.5	p = 0.716
Have a cat at home	No	38	71.7	24	82.8	102	75.6	69	77.5	p = 0.716
Go barefoot	Yes	20	37.7	15	51.7	44	32.6	39	43.8	p = 0.192
Go barefoot	No	33	62.3	14	48.3	91	67.4	50	56.2	p = 0.192
Drink unpasteurized milk	Yes	30	56.6	10	34.4	73	54	26	29.2	p = 0.000
Drink unpasteurized milk	No	23	43.4	19	65.6	62	46	63	70.8	p = 0.000
Eat raw or undercooked beef	Yes	26	49	6	20.7	38	28.1	23	25.8	p = 0.268
Eat raw or undercooked beef	No	27	51	23	79.3	97	71.9	66	74.2	p = 0.268
Eat raw or undercooked pork	Yes	5	9.4	2	6.9	12	8.9	2	2.2	p = 0.041
Eat raw or undercooked pork	No	48	90.6	27	93.1	123	91.1	87	97.3	p = 0.041
Wash the food	Yes	51	96.2	27	93.1	132	97.8	83	93.3	p = 0.181
Wash the food	No	2	3.8	2	6.9	3	2.2	6	6.7	p = 0.181
Had a previous pregnancy	Yes	13	24.5	10	34.4	54	40	22	24.7	p = 0.000
Had a previous pregnancy	No	40	75.5	19	65.6	81	60	67	75.3	p = 0.000
Had a premature child	Yes	5	9.4	3	10.3	8	6	5	5.6	p = 0.479
Had a premature child	No	48	90.6	26	89.7	127	94	84	94.4	p = 0.479
Had an abortion	Yes	5	9.4	1	3.4	24	17.8	4	4.5	p = 0.055
Had an abortion	No	48	90.6	28	96.6	111	82.2	85	95.5	p = 0.055
Housing area	Rural	4	7.5	3	10.3	14	10.4	4	4.5	p = 0.098
Housing area	Urban	49	92.5	26	89.7	121	89.6	85	95.5	p = 0.098
Type of housing	Masonry	47	88.6	29	100	132	97.8	87	97.3	p = 0.285
Type of housing	Wood	6	11.4	0	0	3	2.2	2	2.2	p = 0.285
Own home	Yes	35	66	20	69	105	77.8	65	73	p = 0.900
Own home	No	18	34	9	31	30	22.2	24	27	p = 0.900
Has a sewer network	Yes	51	96.2	25	86.2	124	91.9	87	97.3	p = 0.066
Has a sewer network	No	2	3.8	4	13.8	11	8.1	2	2.2	p = 0.066
Consume artesian well water	Yes	8	15	2	6.9	14	10.4	1	1.1	p = 0.004
Consume artesian well water	No	45	85	27	93.1	121	89.6	88	98.9	p = 0.004
Consume tap water	Yes	19	35.8	12	41.4	34	25.2	20	22.5	p = 0.184
Consume tap water	No	34	64.2	17	58.6	101	74.8	69	77.5	p = 0.184
Consume filtered water	Yes	23	43.4	15	51.7	86	63.7	68	76.4	p = 0.002
Consume filtered water	No	30	56.6	14	48.3	49	36.3	21	23.6	p = 0.002
Garbage destination	Burnt	1	1.8	1	3.4	4	3	3	3.4	p = 0.240
Garbage destination	Public collection	52	98.2	28	96.6	131	97	86	96.6	p = 0.240
There are rats where subject lives	Yes	7	13.2	10	34.4	9	6.7	8	9	p = 0.449
There are rats where subject lives	No	46	86.8	19	65.6	126	93.3	81	91	p = 0.449

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.