Season of infectious mononucleosis and risk of multiple sclerosis at different latitudes; the EnvIMS Study

Background: Seasonal fluctuations in solar radiation and vitamin D levels could modulate the immune response against Epstein-Barr virus (EBV) infection and influence the subsequent risk of multiple sclerosis (MS). Methods: Altogether 1660 MS patients and 3050 controls from Norway and Italy participating in the multinational casecontrol study of Environmental Factors In Multiple Sclerosis (EnvIMS) reported season of past infectious mononucleosis (IM). Results: IM was generally reported more frequently in Norway (p=0.002), but was associated with MS to a similar degree in Norway (odds ratio (OR) 2.12, 95% confidence interval (CI) 1.64–2.73) and Italy (OR 1.72, 95% CI 1.17–2.52). For all participants, there was a higher reported frequency of IM during spring compared to fall (p<0.0005). Stratified by season of IM, the ORs for MS were 1.58 in spring (95% CI 1.08–2.31), 2.26 in summer (95% CI 1.46–3.51), 2.86 in fall (95% CI 1.69–4.85) and 2.30 in winter (95% CI 1.45–3.66). Conclusions: IM is associated with MS independently of season, and the association is not stronger for IM during spring, when vitamin D levels reach nadir. The distribution of IM may point towards a correlation with solar radiation or other factors with a similar latitudinal and seasonal variation.