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Association of Infectious Mononucleosis with Multiple Sclerosis

A Population-Based Study

Ramagopalan S.V.a, b · Valdar W.a · Dyment D.A.a, b · DeLuca G.C.a, b · Yee I.M.c · Giovannoni G.e · Ebers G.C.a, b · Sadovnick A.D.c, d
aWellcome Trust Centre for Human Genetics, and bDepartment of Clinical Neurology, University of Oxford, Oxford, UK; cDepartment of Medical Genetics and dFaculty of Medicine, Division of Neurology, University of British Columbia, Vancouver, B.C., Canada; eInstitute of Cell and Molecular Science, Queen Mary University, and the Department of Neurology, Barts and The London NHS Trust, The Royal London Hospital, London, UK Neuroepidemiology 2009;32:257–262 (DOI:10.1159/000201564)


Background: Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. Several studies have attempted to correlate exposure to viral illness with the subsequent development of MS. Here in a population-based Canadian cohort, we investigate the relationship between prior clinical infection or vaccination and the risk of MS. Methods: Using the longitudinal Canadian database, 14,362 MS index cases and 7,671 spouse controls were asked about history of measles, mumps, rubella, varicella and infectious mononucleosis as well as details about vaccination with measles, mumps, rubella, hepatitis B and influenza vaccines. Comparisons were made between cases and spouse controls. Results: Spouse controls and stratification by sex appear to correct for ascertainment bias because with a single exception we found no significant differences between cases and controls for all viral exposures and vaccinations. However, 699 cases and 165 controls reported a history of infectious mononucleosis (p < 0.001, corrected odds ratio 2.06, 95% confidence interval 1.71–2.48). Females were more aware of disease history than males (p < 0.001). Conclusions: The data further confirms a reporting distortion between males and females. Historically reported measles, mumps, rubella, varicella and vaccination for hepatitis B, influenza, measles, mumps and rubella are not associated with increased risk of MS later in life. A clinical history of infectious mononucleosis is conspicuously associated with increased MS susceptibility. These findings support studies implicating Epstein-Barr virus in MS disease susceptibility, but a co-association between MS susceptibility and clinically apparent infectious mononucleosis cannot be excluded.


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