Associations between Toxoplasma gondii Infection and Multiple Sclerosis: A Case-Control Seroprevalence Study
-
Masoumeh Shahra
,
Hossein Keshavarz
,
Mohammad Ali Sahraeian
,
Saeedeh Shojaee
,
Aliehsan Heidari
,
Rasoul Alimi
,
Aref Teimouri
Abstract
Background: Currently, there are conflicting reports on the associations between Toxoplasma gondii infection and multiple sclerosis (MS) in humans. In the present study, a case–control study was carried out to assess associations between seropositivity to T. gondii infection and MS.
Methods: This case-control study was carried out on 200 MS patients (cases) attended in Sina Hospital affiliated to Tehran University of Medical Sciences, Tehran, Iran, and 200 healthy subjects from the general population of the same city, March to July 2017. Blood samples were collected from individuals and were examined using Enzyme-linked immunosorbent assay (ELISA) for the presence of T. gondii IgG antibodies and the IgG-positive samples were further analyzed for specific anti-T. gondii IgM.
Results: The overall seroprevalence of anti-T. gondii IgG was 44.2% (177/400) in 121 (60.5%) sera of the 200 MS patients (cases) and 56 (28.0%) sera of the 200 controls (OR = 3.94; 95% CI: 2.59–5.99; P < 0.001). Seroprevalence of T. gondii infection in MS patients increased significantly with increasing of age (P < 0.001). In the control group, no statistically significant differences were seen between the seroprevalence of T. gondii infection in various age groups (P = 0.858). Moreover, no statistically significant relationships were reported between the seropositivity to T. gondii and the sex for the cases and controls (P>0.05). Anti-T. gondii IgM antibodies were not detected in anti-T. gondii IgG positive patients.
Conclusion: T. gondii infection might be a probability risk factor for MS. However, further studies are necessary to describe clearly the roles of T. gondii infection in MS.
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13. Mahmoudvand H, Sheibani V, Shojaee S, et al. Toxoplasma gondii Infection Potentiates Cognitive Impairments of Alzheimer's Disease in the BALB/c Mice. J Parasitol. 2016;102(6):629–635. https://doi.org/10.1645/16-28
14. Matta SK, Rinkenberger N, Dunay IR, Sibley LD. Toxoplasma gondii infection and its implications within the central nervous system. Nat Rev Microbiol. 2021;19(7): 467–480.
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17. Sadeghi M, Riahi SM, Mohammadi M, et al. An updated meta-analysis of the association between Toxoplasma gondii infection and risk of epilepsy, Trans R Soc Trop Med Hyg. 2019; 113(8): 453–462.
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19. Koskderelioglu A, Afsar I, Pektas B, Gedizlioglu M. Is Toxoplasma gondii infection protective against multiple sclerosis risk? Mult Scler Relat Disord. 2017; 15:7–10. https://doi.org/10.1016/j.msard.2017.04.004
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22. Sabzevari M, Tavalla M. Seroepidemiolog-ical Study of Toxoplasma gondii in patients with multiple sclerosis in Ahvaz, Southeastern Iran. Med Laboratory J .2017; 11(3):6–9.
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24. Pestehchian N, Etemadifarr M, Yousefi HA, Chiani M, Aslani N, Nasr Z. Frequency of blood-tissue parasitic infections in patients with multiple sclerosis, as compared to their family members. Int J Prev Med. 2014;5(12):1578–81.
25. Saberi R, Sharif M, Sarvi S, et al. Is Toxoplasma gondii playing a positive role in multiple sclerosis risk? A systematic review and meta-analysis. J Neuroimmunol. 2018; 322:57–62.
26. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292–302. https://doi.org/10.1002/ana.22366
27. Teunissen C, Menge T, Altintas A, et al. Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis. Mult Scler. 2013;19(13):1802–9.
28. Hillyer GV, Soler de Galanes M, Rodriguez-Perez J, et al. Use of the falcon assay screening test– enzyme-linked immunosorbent assay (FAST-ELISA) and the enzyme-linked immunoelectrotransfer blot (EITB) to determine the prevalence of human fascioliasis in the Bolivian Altiplano. Am J Trop Med Hyg. 1992; 46(5): 603–609.
29. Teimouri A, Modarressi MH, Shojaee S, et al. Detection of Toxoplasma-specific immunoglobulin G in human sera: performance comparison of in house Dot-ELISA with ECLIA and ELISA. Eur J Clin Microbiol Infect Dis. 2018;37(8):1421-1429. https://doi.org/10.1007/s10096-018-3266-y.
30. Corp Released IBM. IBM SPSS statistics for windows, version 21.0. Armonk, NY: IBM Corp; 2012.
31. Méndez-Hernández EM, Hernández-Tinoco J, Salas Pacheco JM, et al. Toxoplasma gondii infection and multiple sclerosis: an age- and a gender-matched case-control seroprevalence study. Eur J Microbiol Immunol (Bp). 2020; 10(2):76–79. https://doi.org/10.1556/1886.2019.00020
32. Nicoletti A, Cicero CE, Giuliano L, et al. Toxoplasma gondii and multiple sclerosis: a population-based case-control study. Sci Rep. 2020;10(1):18855. https://doi.org/10.1038/s41598-020-75830-y
33. Shapira Y, Agmon-Levin N, Selmi C, et al. Prevalence of anti-Toxoplasma antibodies in patients with autoimmune diseases. J Autoimmun. 2012;39(1-2):112-116. https://doi.org/10.1016/j.jaut.2012.01.001
34. Walker ER, Druss BG. Mental and addictive disorders and medical comorbidities. Curr Psychiatry Rep. 2018; 20(10):86. doi: 10.1007/s11920-018-0956-1
35. Nakamura Y, Koh M, Miyoshi E, et al. High prevalence of the hepatitis C virus infection among the inpatients of schizophrenia and psychoactive substance abuse in Japan. Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28(3):591–7. doi: 10.1016/j.pnpbp. 2004.01.018
36. Seminog OO, Goldacre MJ. Risk of pneumonia and pneumococcal disease in people with severe mental illness: English record linkage studies. Thorax. 2013; 68(2):171–6. doi: 10.1136/thoraxjnl-2012-202480
37. Krause D, Matz J, Weidinger E, et al. The association of infectious agents and schizophrenia. World J Biol Psychiatry. 2010;11(5):739–43.
38. Fleming J, Fabry Z. The hygiene hypothesis and multiple sclerosis. Ann Neurol. 2007;61(2):85–9.
39. Fallon PG, Alcami A. Pathogen-derived immunomodulatory molecules: future immunotherapeutics? Trends Immunol. 2006;27(10):470–476.
2. Global, regional, and national burden of neurological disorders during 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol. 2017; 16(11): 877–897.
3. Oksenberg JR, Baranzini, SE, Sawcer S, Hauser SL. The genetics of multiple sclerosis: SNPs to pathways to pathogenesis. Nat Rev Genet. 2008; 9(7): 516–26.
4. Correale J, Gaitán MI. Multiple sclerosis and environmental factors: the role of vitamin D, parasites, and Epstein-Barr virus infection. Acta Neurol Scand. 2015; 132(199):46–55. https://doi.org/10.1111/ane.12431
5. Ascherio A. Munger K. Environmental risk factors for multiple sclerosis. Part I: the role of infection. Ann Neurol. 2007; 61(4): 288-99.
6. Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet. 2004; 363(9425):1965–76. doi:10.1016/S0140-6736(04)16412-X
7. Dubey JP. Toxoplasmosis of Animals and Humans. 2nd ed. Boca Raton, FL: CRC Press LLC; 2010.
8. Tenter AM, Heckeroth AR, Weiss LM. Toxoplasma gondii: from animals to humans. Int J Parasitol. 2000; 30(12-13):1217–58. doi: 10.1016/s0020-7519(00)00124-7
9. Teimouri A, Mohtasebi S, Kazemirad E, Keshavarz H. Role of Toxoplasma gondii IgG avidity testing in discriminating between acute and chronic toxoplasmosis in pregnancy. J Clin Microbiol. 2020;58(9):e00505–20. doi: 10.1128/JCM.00505-20
10. Shojaee S, Teimouri A, Keshavarz H, Azami SJ, Nouri S. The relation of secondary sex ratio and miscarriage history with Toxoplasma gondii infection. BMC Infect Dis. 2018;18(1):307. doi: 10.1186/s12879-018-3228-0
11. Alipour A, Shojaee S, Mohebali M, Tehranidoost M, Abdi Masoleh F, Keshavarz H. Toxoplasma infection in schizophrenia patients: a comparative study with control group. Iran J Parasitol. 2011; 6(2):31–37.
12. Mahmoudvand H, Ziaali N, Aghaei I, et al. The possible association between Toxoplasma gondii infection and risk of anxiety and cognitive disorders in BALB/c mice. Pathog Glob Health. 2015; 109(8):369–76. doi: 10.1080/20477724.2015.1117742. PMID: 26924347; PMCID: PMC4809231.
13. Mahmoudvand H, Sheibani V, Shojaee S, et al. Toxoplasma gondii Infection Potentiates Cognitive Impairments of Alzheimer's Disease in the BALB/c Mice. J Parasitol. 2016;102(6):629–635. https://doi.org/10.1645/16-28
14. Matta SK, Rinkenberger N, Dunay IR, Sibley LD. Toxoplasma gondii infection and its implications within the central nervous system. Nat Rev Microbiol. 2021;19(7): 467–480.
15. McConkey GA, Martin HL, Bristow GC, Webster JP. Toxoplasma gondii infection and behaviour–location, location, location? J Exp Biol. 2013; 216(Pt 1):113–119.
16. Bayani M, Riahi SM, Bazrafshan N, Gamble HR, Rostami A. Toxoplasma gondii infection and risk of Parkinson and Alzheimer diseases: a systematic review and meta-analysis on observational studies, Acta Trop. 2019;196:165–171.
17. Sadeghi M, Riahi SM, Mohammadi M, et al. An updated meta-analysis of the association between Toxoplasma gondii infection and risk of epilepsy, Trans R Soc Trop Med Hyg. 2019; 113(8): 453–462.
18. Cicero CE, Allibrio FE, Giuliano L, Luna J, Preux PM, Nicoletti A. Toxoplasma gondii and multiple sclerosis: A systematic review and meta-analysis. Eur J Neurol. 2021; 28(12):4251–4257.
19. Koskderelioglu A, Afsar I, Pektas B, Gedizlioglu M. Is Toxoplasma gondii infection protective against multiple sclerosis risk? Mult Scler Relat Disord. 2017; 15:7–10. https://doi.org/10.1016/j.msard.2017.04.004
20. Stascheit F, Paul F, Harms L, Rosche B. Toxoplasma gondii seropositivity is negatively associated with multiple sclerosis. J Neur immunol. 2015;285:119–24. https://doi.org/10.1016/j.jneuroim.2015.05.011.
21. Oruc S, Karakaya F, Demirbas H, et al. Relationship of Toxoplasma gondii Exposure with Multiple Sclerosis. European Journal of General Medicine. 2016; 13(1):58–63. doi:10.15197/ejgm.01429.
22. Sabzevari M, Tavalla M. Seroepidemiolog-ical Study of Toxoplasma gondii in patients with multiple sclerosis in Ahvaz, Southeastern Iran. Med Laboratory J .2017; 11(3):6–9.
23. Rahnama M, Asgari Q, Petramfar P, Tasa D, Hemati V, Solgi R. The Role of Toxoplasma gondii Infection among Multiple Sclerosis Patient Compared to Ordinary People in South of Iran: A Case-Control Study. Mod Care J. 2020; 17(3). doi: 10.5812/modernc.105090.
24. Pestehchian N, Etemadifarr M, Yousefi HA, Chiani M, Aslani N, Nasr Z. Frequency of blood-tissue parasitic infections in patients with multiple sclerosis, as compared to their family members. Int J Prev Med. 2014;5(12):1578–81.
25. Saberi R, Sharif M, Sarvi S, et al. Is Toxoplasma gondii playing a positive role in multiple sclerosis risk? A systematic review and meta-analysis. J Neuroimmunol. 2018; 322:57–62.
26. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292–302. https://doi.org/10.1002/ana.22366
27. Teunissen C, Menge T, Altintas A, et al. Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis. Mult Scler. 2013;19(13):1802–9.
28. Hillyer GV, Soler de Galanes M, Rodriguez-Perez J, et al. Use of the falcon assay screening test– enzyme-linked immunosorbent assay (FAST-ELISA) and the enzyme-linked immunoelectrotransfer blot (EITB) to determine the prevalence of human fascioliasis in the Bolivian Altiplano. Am J Trop Med Hyg. 1992; 46(5): 603–609.
29. Teimouri A, Modarressi MH, Shojaee S, et al. Detection of Toxoplasma-specific immunoglobulin G in human sera: performance comparison of in house Dot-ELISA with ECLIA and ELISA. Eur J Clin Microbiol Infect Dis. 2018;37(8):1421-1429. https://doi.org/10.1007/s10096-018-3266-y.
30. Corp Released IBM. IBM SPSS statistics for windows, version 21.0. Armonk, NY: IBM Corp; 2012.
31. Méndez-Hernández EM, Hernández-Tinoco J, Salas Pacheco JM, et al. Toxoplasma gondii infection and multiple sclerosis: an age- and a gender-matched case-control seroprevalence study. Eur J Microbiol Immunol (Bp). 2020; 10(2):76–79. https://doi.org/10.1556/1886.2019.00020
32. Nicoletti A, Cicero CE, Giuliano L, et al. Toxoplasma gondii and multiple sclerosis: a population-based case-control study. Sci Rep. 2020;10(1):18855. https://doi.org/10.1038/s41598-020-75830-y
33. Shapira Y, Agmon-Levin N, Selmi C, et al. Prevalence of anti-Toxoplasma antibodies in patients with autoimmune diseases. J Autoimmun. 2012;39(1-2):112-116. https://doi.org/10.1016/j.jaut.2012.01.001
34. Walker ER, Druss BG. Mental and addictive disorders and medical comorbidities. Curr Psychiatry Rep. 2018; 20(10):86. doi: 10.1007/s11920-018-0956-1
35. Nakamura Y, Koh M, Miyoshi E, et al. High prevalence of the hepatitis C virus infection among the inpatients of schizophrenia and psychoactive substance abuse in Japan. Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28(3):591–7. doi: 10.1016/j.pnpbp. 2004.01.018
36. Seminog OO, Goldacre MJ. Risk of pneumonia and pneumococcal disease in people with severe mental illness: English record linkage studies. Thorax. 2013; 68(2):171–6. doi: 10.1136/thoraxjnl-2012-202480
37. Krause D, Matz J, Weidinger E, et al. The association of infectious agents and schizophrenia. World J Biol Psychiatry. 2010;11(5):739–43.
38. Fleming J, Fabry Z. The hygiene hypothesis and multiple sclerosis. Ann Neurol. 2007;61(2):85–9.
39. Fallon PG, Alcami A. Pathogen-derived immunomodulatory molecules: future immunotherapeutics? Trends Immunol. 2006;27(10):470–476.
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| Issue | Vol 18 No 2 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijpa.v18i2.13182 | |
| Keywords | ||
| Toxoplasma gondii Multiple sclerosis Seroprevalence Case-control study Iran | ||
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How to Cite
1.
Shahra M, Keshavarz H, Sahraeian MA, Shojaee S, Heidari A, Alimi R, Teimouri A. Associations between Toxoplasma gondii Infection and Multiple Sclerosis: A Case-Control Seroprevalence Study. Iran J Parasitol. 2023;18(2):165-171.
