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Vol. 21, No. 4, 2002
Issue release date: July–August 2002
Neuroepidemiology 2002;21:180–186

Hepatitis B Vaccination and First Central Nervous System Demyelinating Event: A Case-Control Study

Touzé E. · Fourrier A. · Rue-Fenouche C. · Rondé-Oustau V. · Jeantaud I. · Bégaud B. · Alpérovitch A.
aINSERM U360, Hôpital de la Salpêtrière, Paris, et bDépartement de Pharmacologie Clinique, Université Victor Segalen Bordeaux 2, Bordeaux, France

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Objective: To investigate the relationship between hepatitis B (HB) vaccination and a first central nervous system (CNS) demyelinating event in adults. Methods: In 1998, we conducted a multicentre, hospital-based case-control study which enrolled 402 cases of first CNS demyelinating event occurring between 1994 and 1995 and 722 controls matched for centre, age, sex and date of admission. An independent expert committee validated the diagnoses of cases and controls. Data on vaccinations were obtained from a standardized phone interview. Forty percent of eligible cases and 50% of eligible controls could not be localized or were excluded because they did not satisfy inclusion or matching criteria. Results: Conditional logistic regression performed on 236 and 355 matched controls showed that adjusted odds ratios for the first CNS demyelinating event within 2 months following an injection of HB vaccine were 1.8 [95% confidence interval (CI), 0.7–4.6] in the whole group and 1.4 (95% CI, 0.4–4.5) in the subgroup of cases (n = 152) and controls (n = 253) referring to vaccination certificates during the phone interview. Restricting the analyses to the cases with definite or probable multiple sclerosis, these odds ratios were 2.0 (95% CI, 0.8–5.4) and 1.6 (95% CI, 0.4–5.6), respectively. Odds ratios tend towards 1 for a longer interval between HB vaccine and demyelinating event. Conclusions: This study was sufficiently powerful to rule out a strong association between HB vaccine exposure and a subsequent demyelinating event. However, it could not provide a clear indication of a moderately increased risk of a CNS demyelinating event shortly after HB vaccination in adults.

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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  1. Poser CM, Paty DW, Scheinberg L, et al: New diagnostic criteria for multiple sclerosis: Guidelines for research protocols. Ann Neurol 1983;13:227–231.
  2. Miller AE: Diagnosis of multiple sclerosis. Semin Neurol 1998;18:309–316.
  3. Poser CM: The epidemiology of multiple sclerosis: A general overview. Ann Neurol 1994;36:S180–S193.

    External Resources

  4. Sadovnick AD, Ebers GC, Dyment DA, Risch NJ: Evidence for genetic basis of multiple sclerosis. The Canadian Collaborative Study Group. Lancet 1996;347:1728–1730.
  5. Compston A: Genetic epidemiology of multiple sclerosis. J Neurol Neurosurg Psychiatry 1997;62:553–561.
  6. Pender MP: Genetically determined failure of activation-induced apoptosis of autoreactive T cells as a cause of multiple sclerosis. Lancet 1998;351:978–981.
  7. Alter M, Zhang ZX, Davanipour Z, et al: Multiple sclerosis and childhood infections. Neurology 1986;36:1386–1389.
  8. Gronning M, et al: Infections in childhood and adolescence in multiple sclerosis. A case-control study. Neuroepidemiology 1993;12:61–69.
  9. Granieri E, Casetta I: Selected reviews common childhood and adolescent infections and multiple sclerosis. Neurology 1997;49(suppl 2):S42–S54.
  10. Garson JA, Tuke PW, Giraud P, Paranhos-Baccala G, Perron H: Detection of virion-associated MSRV-RNA in serum of patients with multiple sclerosis. Lancet 1998;351:33.
  11. Monteyne P, Bureau JF, Brahic M: Viruses and multiple sclerosis. Curr Opin Neurol 1998;11:287–291.
  12. Fenichel GM: Neurological complications of immunization. Ann Neurol 1982;12:119–128.

    External Resources

  13. Miller H, Cendrowski W, Schapira K: Multiple sclerosis and vaccination. Br Med J 1967;2:210–213.

    External Resources

  14. Kesselring J, Miller DH, Robb SA, et al: Acute disseminated encephalomyelitis. MRI findings and the distinction from multiple sclerosis. Brain 1990;113:291–302.

    External Resources

  15. Herroelen L, de Keyser J, Ebinger G: Central-nervous-system demyelination after immunisation with recombinant hepatitis B vaccine. Lancet 1991;338:1174–1175.
  16. Hopkins RS, Indian RW, Pinnow E, Conomy J: Multiple sclerosis in Galion, Ohio: Prevalence and results of a case-control study. Neuroepidemiology 1991;10:192–199.
  17. Poser CM: Multiple sclerosis. Observations and reflections – a personal memoir. J Neurol Sci 1992;107:127–140.
  18. Nadler JP: Multiple sclerosis and hepatitis B vaccination. Clin Infect Dis 1993;17:928–929.
  19. Kaplanski G, Retornaz F, Durand JM, Soubeyrand J: Central-nervous-system demyelination after vaccination against hepatitis B and HLA haplotype. J Neurol Neurosurg Psychiatry 1995;58:758–759.
  20. Tourbah A, Gout O, Liblau R, et al: Encephalitis after hepatitis B vaccination: Recurrent disseminated encephalitis or MS? Neurology 1999;53:396–401.
  21. Myers LW, Ellison GW, Lucia M, Novom S: Swine-influenza vaccination in multiple sclerosis. N Engl J Med 1976;295:1204.
  22. Bamford CR, Sibley WA, Laguna JF: Swine influenza vaccination in patients with multiple sclerosis. Arch Neurol 1978;35:242–243.

    External Resources

  23. Quast U, Herder C, Zwisler O: Vaccination of patients with encephalomyelitis disseminata. Vaccine 1991;9:228–230.
  24. Kurland LT, Molgaard CA, Kurland EM, Wiederholt WC, Kirkpatrick JW: Swine flu vaccine and multiple sclerosis. JAMA 1984;251:2672–2675.
  25. Miller AE, Morgante LA, Buchwald LY, et al: A multicenter, randomized, double-blind, placebo-controlled trial of influenza immunization in multiple sclerosis. Neurology 1997;48:312–314.
  26. Anonymous: Expanded programme on immunization (EPI). Lack of evidence that hepatitis B vaccine causes multiple sclerosis. Wkly Epidemiol Rec 1997;72:149–152.
  27. Sadovnick AD, Scheifele DW: School-based hepatitis B vaccination programme and adolescent multiple sclerosis. Lancet 2000;355:549–550.
  28. Guérin N, Nicolas L, Aufère A: Impact des recommandations sur la couverture vaccinale contre l’hépatite B. Bull Epidem Hebdom (Ministère du Travail et des Affaires Sociales, Direction Générale de la Santé) 27/1996.
  29. Touzé E, Gout O, Verdier-Taillefer MH, Lyon-Caen O, Alpérovitch A: Premier épisode de démyélinisation du système nerveux central et vaccination contre l’hépatite B: Etude cas-témoins pilote. Rev Neurol (Paris). 2000;156:242–246.
  30. SAS Institute: SAS User’s Guide: Statistics, ed 6. Cary, SAS Institute, 1990.
  31. Zipp F, Weil JG, Einhaupl KM: No increase in demyelinating diseases after hepatitis B vaccination. Nat Med 1999;5:964–965.
  32. Ascherio A, Zhang SM, Hernan MA, Olek MJ, Coplan PM, Brodovicz K, Walker AM: Hepatitis B vaccination and the risk of multiple sclerosis. N Engl J Med 2001;344:327–332.
  33. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG: Multiple sclerosis. N Engl J Med 2000;343:938–952.
  34. Sturckemboom MCJM, Fourrier A: Serious doubts on the recent proof that vaccination against hepatitis B would not cause multiple sclerosis. N Engl J Med 2001;344:1794.

    External Resources

  35. Fourrier A, Bégaud B, Alpérovitch A, Verdier-Taillefer MH, Touzé E, Decker N, Imbs JL: Hepatitis B vaccine and primary episodes of central nervous system demyelinating disorders: A comparison between reported and expected number of cases. Br J Clin Pharmacol 2001;51:489–490.

    External Resources

  36. Wacholder S, McLaughlin JK, Silverman DT, Mandel JS: Selection of controls in case-control studies. II. Types of controls. Am J Epidemiol 1992;135:1029–1041.
  37. IPSOS: Taux de vaccination contre l’hépatite B en France en 1993–1994. Internal report, September 1995.
  38. Lhermitte F, Alpérovitch A, Lyon-Caen O: Note préliminaire concernant une enquête sur la sclérose en plaques lançée par la télévision française. Rev Neurol 1988;144:135–136.
  39. Weinshenker BG, Rodriguez M: Epidemiology of multiple sclerosis; in Gorelick PB, Alter M (eds): Handbook of Neuroepidemiology. New York, Marcel Dekker, 1994, pp 533–568.
  40. Fujinami RS, Oldstone MBA: Amino acid homology between the encephalitogenic site of myelin basic protein and virus: Mechanism for autoimmunity. Science 1985;230:1043–1045.
  41. Garcia KC, Degano M, Pease LR, et al: Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen. Science 1998;279:1166–1172.
  42. Wucherpfenning KW, Catz I, Hausmann S, Strominger JL, Steinman L, Warren KG: Recognition of the immunodominant myelin basic protein peptide by autoantibodies and HLA-DR2-restricted T cell clones from multiple sclerosis patients. Identity of key contact residues in the B-cell and T-cell epitopes. J Clin Invest 1997;100:1114–1122.
  43. Hemmer B, Fleckenstein BT, Vergelli M, et al: Identification of high potency microbial and self ligands for a human autoreactive class II-restricted T cell clone. J Exp Med 1997;185:1651–1659.
  44. Talbot PJ, Paquette JS, Ciurli C, Antel JP, Ouellet F: Myelin basic protein and human coronavirus 229E cross-reactive T cells in multiple sclerosis. Ann Neurol 1996;39:233–240.
  45. Zhao ZS, Granucci F, Yeh L, Schafer PA, Cantor H: Molecular mimicry by herpes simplex virus-type 1: Autoimmune disease after viral infection. Science 1998;279:1344–1347.
  46. Evans CF, Horwitz MS, Hobbs MV, Oldstone MBA: Viral infection of transgenic mice expressing a viral protein in oligodendrocytes leads to chronic central nervous system autoimmune diseases. J Exp Med 1996;184:2371–2384.

    External Resources

  47. Segal BM, Klinman DM, Shevach EM: Microbial products induce autoimmune disease by an IL12-dependent pathway. J Immunol 1997;159:5087–5090.

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