Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Association between multiple sclerosis and Candida species: evidence from a case-control study

Abstract

Candida infection among multiple sclerosis (MS) patients has not been studied in depth. We determined whether there is an association between serological evidence of Candida infection and MS. Blood specimens were obtained from 80 MS patients and 240 matched controls. Immunofluorescence analysis and ELISA were used to detect Candida species antibodies and slot-blot to detect antigens. Using immunofluorescence analysis, moderate to high concentrations of serum antibodies to Candida famata were present in 30 (37.5%) MS patients vs. 30 (12.5%) controls (p < 0.001). Results for Candida albicans were 47.5% (38/80) in MS patients vs. 21.3% (51/240) in controls (p < 0.001), for Candida parapsilosis 37% (28/80) vs. 17.1% (41/240) (p < 0.001) and for Candida glabrata 46.3% (37/80) vs. 17.5% (42/240) (p < 0.001), respectively. After adjusting for age and gender, the odds ratios (95% confidence intervals) for MS, according to the presence of Candida antigens were: 2.8 (0.3–23.1, p = 0.337) for Candida famata; 1.5 (0.7–3.4, p = 0.290) for Candida albicans; 7.3 (3.2–16.6, p < 0.001) for Candida parapsilosis; and 3.0 (1.5–6.1, p = 0.002) for Candida glabrata. The results were similar after excluding ten patients on immunosuppressants. The results of this single study suggest that Candida species infection may be associated with increased odds of MS.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Pugliatti M, Sotgiu S, Rosati G (2002) The worldwide prevalence of multiple sclerosis. Clin Neurol Neurosurg 104:182–191

  2. 2.

    Benito-León J, Morales JM, Rivera-Navarro J (2002) Health-related quality of life and its relationship to cognitive and emotional functioning in multiple sclerosis patients. Eur J Neurol 9:497–502

  3. 3.

    Benito-León J, Morales JM, Rivera-Navarro J, Mitchell A (2003) A review about the impact of multiple sclerosis on health-related quality of life. Disabil Rehabil 25:1291–1303

  4. 4.

    Mitchell AJ, Benito-León J, Gonzalez JM, Rivera-Navarro J (2005) Quality of life and its assessment in multiple sclerosis: integrating physical and psychological components of well-being. Lancet Neurol 4:556–566

  5. 5.

    Morales-Gonzalez JM, Benito-León J, Rivera-Navarro J, Mitchell AJ; GEDMA Study Group (2004) A systematic approach to analyse health-related quality of life in multiple sclerosis: the GEDMA study. Mult Scler 10:47–54

  6. 6.

    Rivera-Navarro J, Morales-González JM, Benito-León J; Madrid Demyelinating Diseases Group (GEDMA) (2003) Informal caregiving in multiple sclerosis patients: data from the Madrid demyelinating disease group study. Disabil Rehabil 25:1057–1064

  7. 7.

    Ascherio A, Munger K (2008) Epidemiology of multiple sclerosis: from risk factors to prevention. Semin Neurol 28:17–28

  8. 8.

    Gilden DH (2005) Infectious causes of multiple sclerosis. Lancet Neurol 4:195–202

  9. 9.

    Contini C, Seraceni S, Cultrera R, Castellazzi M, Granieri E, Fainardi E (2008) Molecular detection of Parachlamydia-like organisms in cerebrospinal fluid of patients with multiple sclerosis. Mult Scler 14:564–566

  10. 10.

    Ascherio A (2008) Epstein-Barr virus in the development of multiple sclerosis. Expert Rev Neurother 8:331–333

  11. 11.

    Butcher J (1976) The distribution of multiple sclerosis in relation to the dairy industry and milk consumption. NZ Med J 83:427–430

  12. 12.

    Malosse D, Perron H, Sasco A, Seigneurin JM (1992) Correlation between milk and dairy product consumption and multiple sclerosis prevalence: a worldwide study. Neuroepidemiology 11:304–312

  13. 13.

    Lagneau PE, Lebtahi K, Swinne D (1996) Isolation of yeasts from bovine milk in Belgium. Mycopathologia 135:99–102

  14. 14.

    Gass JD (1993) Acute zonal occult outer retinopathy. Donders lecture: the Netherlands Ophthalmological Society, Maastricht, Holland, June 19, 1992. J Clin Neuroophthalmol 13:79–97

  15. 15.

    Gass JD, Agarwal A, Scott IU (2002) Acute zonal occult outer retinopathy: a long-term follow-up study. Am J Ophthalmol 134:329–339

  16. 16.

    Hintzen RQ, van den Born LI (2006) Acute zonal occult outer retinopathy and multiple sclerosis. J Neurol Neurosurg Psychiatry 77:1373–1375

  17. 17.

    Carrasco L, Ramos M, Galisteo R, Pisa D, Fresno M, González ME (2005) Isolation of Candida famata from a patient with acute zonal occult outer retinopathy. J Clin Microbiol 43:635–640

  18. 18.

    Pisa D, Ramos M, Molina S, García P, Carrasco L (2007) Evolution of antibody response and fungal antigens in the serum of a patient infected with Candida famata. J Med Microbiol 56:571–578

  19. 19.

    Pisa D, Ramos M, García P, Escoto R, Barraquer R, Molina S, Carrasco L (2008) Fungal infection in patients with serpiginous choroiditis or acute zonal occult outer retinopathy. J Clin Microbiol 46:130–135

  20. 20.

    Trick WE, Fridkin SK, Edwards JR, Hajjeh RA, Gaynes RP, Hospitals National Nosocomial Infections Surveillance System (2002) Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989-1999. Clin Infect Dis 35:627–630

  21. 21.

    Pfaller MA, Diekema DJ (2002) Role of sentinel surveillance of candidemia: trends in species distribution and antifungal susceptibility. J Clin Microbiol 40:3551–3557

  22. 22.

    Lipton SA, Hickey WF, Morris JH, Loscalzo J (1984) Candidal infection in the central nervous system. Am J Med 76:101–108

  23. 23.

    Laín A, Elguezabal N, Moragues MD, García-Ruiz JC, del Palacio A, Pontón J (2008) Contribution of serum biomarkers to the diagnosis of invasive candidiasis. Expert Rev Mol Diagn 8:315–325

  24. 24.

    McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD et al (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127

  25. 25.

    Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452

  26. 26.

    Ellepola AN, Morrison CJ (2005) Laboratory diagnosis of invasive candidiasis. J Microbiol 43:65–84

  27. 27.

    Southern P, Horbul J, Maher D, Davis DA (2008) C. albicans colonization of human mucosal surfaces. PLoS ONE 3:e2067

  28. 28.

    Yang YL (1993) Virulence factors of Candida species. J Microbiol Immunol Infect 36:223–228

  29. 29.

    Kurtzke JF (1993) Epidemiologic evidence for multiple sclerosis as an infection. Clin Microbiol Rev 6:382–427

  30. 30.

    Belgi G, Friedmann PS (2002) Traditional therapies: glucocorticoids, azathioprine, methotrexate, hydroxyurea. Clin Exp Dermatol 27:546–554

Download references

Acknowledgments

We wish to express our sincere thanks to Dr. Nancy Grajales Hernández and Gerardo García Perales, as well as other members of the Multiple Sclerosis association of Madrid (Spain). We also thank Drs. Mari Luz Borbolla and Manuel Algora (Transfusion Center of the Community of Madrid) for providing the control samples. Fátima Palomares is also acknowledged for her involvement during the early stages of this study. Finally, we also acknowledge the contribution provided by Dr. Elan D. Louis who critiqued late stage drafts of the paper. The study was supported by grants from the Fundación de Investigación Médica Mútua Madrileña and Fundación Ramón Areces. Dr. Benito-León is supported by NIH R01 NS024859 from the National Institutes of Health, Bethesda, MD, USA.

Competing interests

The authors declare that they have no competing interests.

Author information

Correspondence to J. Benito-León.

Additional information

Authors’ contributions

JB-L and LC conceived, coordinated and designed the original study. JB-L conducted the analysis of data and drafted the manuscript. JBL, DP, RA, PC, and MDS collected data and samples. DP and RA conducted the serological testing. All authors offered critical input into the manuscript and all have read and approved the final version.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Benito-León, J., Pisa, D., Alonso, R. et al. Association between multiple sclerosis and Candida species: evidence from a case-control study. Eur J Clin Microbiol Infect Dis 29, 1139–1145 (2010). https://doi.org/10.1007/s10096-010-0979-y

Download citation

Keywords

  • Multiple Sclerosis
  • Multiple Sclerosis Patient
  • Candida Species
  • Glatiramer Acetate
  • Candida Glabrata