Vaccines and multiple sclerosis: a systematic review

Journal of Neurology volume 264, pages 1035–1050 (2017)Cite this article

Abstract

Vaccinations are often the most effective tool against some disease known to mankind. This study offers a literature review on the role of vaccines regarding the risk of developing multiple sclerosis (MS) and MS relapse. The method used in this study is a systematic literature review on the database PubMed. The study found no change in risk of developing multiple sclerosis (MS) after vaccination against hepatitis B virus, human papillomavirus, seasonal influenza, measles–mumps–rubella, variola, tetanus, Bacillus Calmette-Guérin (BCG), polio, or diphtheria. No change in risk of relapse was found for influenza. Further research is needed for the potential therapeutic use of the BCG vaccine in patients in risk of developing MS and for the preventive potential of the tetanus and diphtheria vaccine.

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References

  1. 1.

    Denis F, Levy-Bruhl D (2006) Mass vaccination against hepatitis B: the French example. Curr Top Microbiol Immunol 304:115–129

    CAS  PubMed  Google Scholar 

  2. 2.

    Williamson EM, Berger JR (2015) Infection risk in patients on multiple sclerosis therapeutics. CNS Drugs 29(3):229–244

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Demicheli V et al (2003) Hepatitis B vaccination and multiple sclerosis: evidence from a systematic review. J Viral Hepat 10(5):343–344

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    DeStefano F, Verstraeten T, Chen RT (2002) Hepatitis B vaccine and risk of multiple sclerosis. Expert Rev Vaccines 1(4):461–466

    Article  PubMed  Google Scholar 

  5. 5.

    Farez MF, Correale J (2011) Immunizations and risk of multiple sclerosis: systematic review and meta-analysis. J Neurol 258(7):1197–1206

    Article  PubMed  Google Scholar 

  6. 6.

    Gout O (2001) Vaccinations and multiple sclerosis. Neurol Sci 22(2):151–154

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Jefferson T, Heijbel H (2001) Demyelinating disease and hepatitis B vaccination: is there a link? Drug Saf 24(4):249–254

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Loebermann M et al (2011) Vaccination against infection in patients with multiple sclerosis. Nat Rev Neurol 8(3):143–151

    Article  Google Scholar 

  9. 9.

    Merelli E, Casoni F (2000) Prognostic factors in multiple sclerosis: role of intercurrent infections and vaccinations against influenza and hepatitis B. Neurol Sci 21(4 Suppl 2):S853–S856

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Sievers EJ, Heyneman CA (2002) Relationship between vaccinations and multiple sclerosis. Ann Pharmacother 36(1):160–162

    Article  PubMed  Google Scholar 

  11. 11.

    Ascherio A et al (2001) Hepatitis B vaccination and the risk of multiple sclerosis. N Engl J Med 344(5):327–332

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    DeStefano F et al (2003) Vaccinations and risk of central nervous system demyelinating diseases in adults. Arch Neurol 60(4):504–509

    Article  PubMed  Google Scholar 

  13. 13.

    Eftekharian MM et al (2014) Multiple sclerosis and immunological-related risk factors: results from a case-control study. Hum Antibodies 23(1–2):31–36

    PubMed  Google Scholar 

  14. 14.

    Geier DA, Geier MR (2005) A case-control study of serious autoimmune adverse events following hepatitis B immunization. Autoimmunity 38(4):295–301

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Hernan MA et al (2004) Recombinant hepatitis B vaccine and the risk of multiple sclerosis: a prospective study. Neurology 63(5):838–842

    Article  PubMed  Google Scholar 

  16. 16.

    Hocine MN et al (2007) Hepatitis B vaccination and first central nervous system demyelinating events: reanalysis of a case-control study using the self-controlled case series method. Vaccine 25(31):5938–5943

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Langer-Gould A et al (2014) Vaccines and the risk of multiple sclerosis and other central nervous system demyelinating diseases. JAMA Neurol 71(12):1506–1513

    Article  PubMed  Google Scholar 

  18. 18.

    Mikaeloff Y et al (2007) Hepatitis B vaccine and risk of relapse after a first childhood episode of CNS inflammatory demyelination. Brain 130(Pt 4):1105–1110

    PubMed  Google Scholar 

  19. 19.

    Mikaeloff Y et al (2007) Hepatitis B vaccination and the risk of childhood-onset multiple sclerosis. Arch Pediatr Adolesc Med 161(12):1176–1182

    Article  PubMed  Google Scholar 

  20. 20.

    Mikaeloff Y et al (2009) Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood. Neurology 72(10):873–880

    Article  PubMed  Google Scholar 

  21. 21.

    Ozakbas S et al (2006) Development of multiple sclerosis after vaccination against hepatitis B: a study based on human leucocyte antigen haplotypes. Tissue Antigens 68(3):235–238

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Ramagopalan SV et al (2009) Association of infectious mononucleosis with multiple sclerosis. A population-based study. Neuroepidemiology 32(4):257–262

    Article  PubMed  Google Scholar 

  23. 23.

    Sadovnick AD, Scheifele DW (2000) School-based hepatitis B vaccination programme and adolescent multiple sclerosis. Lancet 355(9203):549–550

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Touze E et al (2002) Hepatitis B vaccination and first central nervous system demyelinating event: a case-control study. Neuroepidemiology 21(4):180–186

    Article  PubMed  Google Scholar 

  25. 25.

    Zipp F, Weil JG, Einhaupl KM (1999) No increase in demyelinating diseases after hepatitis B vaccination. Nat Med 5(9):964–965

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Confavreux C et al (2001) Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group. N Engl J Med 344(5):319–326

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Chao C et al (2012) Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J Intern Med 271(2):193–203

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Grimaldi-Bensouda L et al (2014) Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects. J Intern Med 275(4):398–408

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Pellegrino P et al (2013) No evidence of a link between multiple sclerosis and the vaccine against the human papillomavirus. Eur J Epidemiol 28(8):705–707

    Article  PubMed  Google Scholar 

  30. 30.

    Scheller NM et al (2015) Quadrivalent HPV vaccination and risk of multiple sclerosis and other demyelinating diseases of the central nervous system. JAMA 313(1):54–61

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Alter M, Speer J (1968) Clinical evaluation of possible etiologic factors in multiple sclerosis. Neurology 18(2):109–116

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Bardage C et al (2011) Neurological and autoimmune disorders after vaccination against pandemic influenza A (H1N1) with a monovalent adjuvanted vaccine: population based cohort study in Stockholm, Sweden. Bmj 343:d5956

    Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Zorzon M et al (2003) Risk factors of multiple sclerosis: a case-control study. Neurol Sci 24(4):242–247

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Auriel E et al (2012) Seasonal and H1N1v influenza vaccines in MS: safety and compliance. J Neurol Sci 314(1–2):102–103

    Article  PubMed  Google Scholar 

  35. 35.

    Bamford CR, Sibley WA, Laguna JF (1978) Swine influenza vaccination in patients with multiple sclerosis. Arch Neurol 35(4):242–243

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    De Keyser J, Zwanikken C, Boon M (1998) Effects of influenza vaccination and influenza illness on exacerbations in multiple sclerosis. J Neurol Sci 159(1):51–53

    Article  PubMed  Google Scholar 

  37. 37.

    Farez MF et al (2012) H1N1 vaccination does not increase risk of relapse in multiple sclerosis: a self-controlled case-series study. Mult Scler 18(2):254–256

    Article  PubMed  Google Scholar 

  38. 38.

    McNicholas N, Chataway J (2011) Relapse risk in patients with multiple sclerosis after H1N1 vaccination, with or without seasonal influenza vaccination. J Neurol 258(8):1545–1547

    Article  PubMed  Google Scholar 

  39. 39.

    Michielsens B et al (1990) Serial magnetic resonance imaging studies with paramagnetic contrast medium: assessment of disease activity in patients with multiple sclerosis before and after influenza vaccination. Eur Neurol 30(5):258–259

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Miller AE et al (1997) A multicenter, randomized, double-blind, placebo-controlled trial of influenza immunization in multiple sclerosis. Neurology 48(2):312–314

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Mokhtarian F et al (1997) Influenza virus vaccination of patients with multiple sclerosis. Mult Scler 3(4):243–247

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Moriabadi NF et al (2001) Influenza vaccination in MS: absence of T-cell response against white matter proteins. Neurology 56(7):938–943

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Myers LW et al (1977) Swine influenza virus vaccination in patients with multiple sclerosis. J Infect Dis 136(Suppl):S546–S554

    Article  PubMed  Google Scholar 

  44. 44.

    Salvetti M et al (1995) Clinical and MRI assessment of disease activity in patients with multiple sclerosis after influenza vaccination. J Neurol 242(3):143–146

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Sibley WA, Bamford CR, Laguna JF (1976) Influenza vaccination in patients with multiple sclerosis. JAMA 236(17):1965–1966

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Sibley WA, Foley JM (1965) Infection and immunization in multiple sclerosis. Ann N Y Acad Sci 122:457–466

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Ahlgren C et al (2009) A population-based case-control study on viral infections and vaccinations and subsequent multiple sclerosis risk. Eur J Epidemiol 24(9):541–552

    Article  PubMed  Google Scholar 

  48. 48.

    Bansil S et al (1997) Multiple sclerosis in India: a case-control study of environmental exposures. Acta Neurol Scand 95(2):90–95

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Kurtzke JF et al (1997) Multiple sclerosis in the Faroe Islands. 7. Results of a case control questionnaire with multiple controls. Acta Neurol Scand 96(3):149–157

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Pekmezovic T, Jarebinski M, Drulovic J (2004) Childhood infections as risk factors for multiple sclerosis: Belgrade case-control study. Neuroepidemiology 23(6):285–288

    Article  PubMed  Google Scholar 

  51. 51.

    Zilber N, Kahana E (1996) Risk factors for multiple sclerosis: a case-control study in Israel. Acta Neurol Scand 94(6):395–403

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Ahlgren C et al (2009) Multiple sclerosis incidence in the era of measles-mumps-rubella mass vaccinations. Acta Neurol Scand 119(5):313–320

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Andersen E, Isager H, Hyllested K (1981) Risk factors in multiple sclerosis: tuberculin reactivity, age at measles infection, tonsillectomy and appendectomy. Acta Neurol Scand 63(2):131–135

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Casetta I et al (1994) Environmental risk factors and multiple sclerosis: a community-based, case-control study in the province of Ferrara, Italy. Neuroepidemiology 13(3):120–128

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Compston DA et al (1986) Viral infection in patients with multiple sclerosis and HLA-DR matched controls. Brain 109(Pt 2):325–344

    Article  PubMed  Google Scholar 

  56. 56.

    Berr C et al (1989) Risk factors in multiple sclerosis: a population-based case-control study in Hautes-Pyrenees, France. Acta Neurol Scand 80(1):46–50

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Ristori G et al (1999) Use of Bacille Calmette–Guerin (BCG) in multiple sclerosis. Neurology 53(7):1588–1589

    CAS  Article  PubMed  Google Scholar 

  58. 58.

    Farez MF, Correale J (2011) Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis. Arch Neurol 68(10):1267–1271

    Article  PubMed  Google Scholar 

  59. 59.

    Baumhackl U et al (2003) A controlled trial of tick-borne encephalitis vaccination in patients with multiple sclerosis. Vaccine 21(Suppl 1):S56–S61

    Article  PubMed  Google Scholar 

  60. 60.

    Quast U, Herder C, Zwisler O (1991) Vaccination of patients with encephalomyelitis disseminata. Vaccine 9(4):228–230

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Ristori G et al (2014) Effects of Bacille Calmette-Guerin after the first demyelinating event in the CNS. Neurology 82(1):41–48

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Pool V, Gordon DM, Decker M (2012) Methodological issues with the risk of relapse study in patients with multiple sclerosis after yellow fever vaccination. Arch Neurol 69(1):144 (author reply 144-5)

    Article  PubMed  Google Scholar 

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Affiliations

  1. University of Copenhagen, Copenhagen, Denmark

    Mia Topsøe Mailand

  2. Department of Neurology, University of Copenhagen, Rigshospitalet Glostrup, Nordre Ringvej 57, 2600, Glostrup, Denmark

    Jette Lautrup Frederiksen

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  1. Mia Topsøe Mailand
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  2. Jette Lautrup Frederiksen
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Correspondence to Jette Lautrup Frederiksen.

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Mailand, M.T., Frederiksen, J.L. Vaccines and multiple sclerosis: a systematic review. J Neurol 264, 1035–1050 (2017). https://doi.org/10.1007/s00415-016-8263-4

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Keywords

  • Multiple sclerosis
  • Vaccination
  • Immunization