An ‘epidemic’ of multiple sclerosis and falling infection rates? Reflecting on comparisons made and the rising multiple sclerosis incidence in Bach's 2002 New England Journal of Medicine figure

Background and purpose: We set out to revisit and comment on the evidence surrounding a popular figure published in the New England Journal of Medicine (2002), which suggests that the incidence of immune-mediated diseases, including multiple sclerosis (MS), is increased by reduced exposure to infections. Methods: Commentary. Results: We found that, to date (May 2017), this influential article has been cited >2000 times. However, on close investigation of the figure, we noticed some problems. Specifically, we observed several challenges inherent in using ecological data from disparate studies and countries to make conclusions surrounding the temporal patterns and relationships between diseases. For example, the figure depicts incidence data for MS based solely on a limited group of individuals with MS (n = 637; 455 women and 182 men) living within the region of Sassari on the island of Sardinia, known for its unique genealogy and risk of MS. However, the infectious-related data were based primarily on large population studies from the USA, with one derived from army recruits in France. Conclusions: We encourage the scientific community to apply rigorous, consistent methods in order to confirm or refute whether a strong, direct relationship does or does not exist between the incidence of MS and infectious diseases. Further, our article highlights a major knowledge gap that would benefit from a thorough review of the temporal trends related to MS incidence. Collation of this wide body of knowledge may provide a balanced understanding of this important topic and would best serve the progress of MS research.