A large population-based study finds that individuals who had Epstein-Barr virus–positive infectious mononucleosis (mono) in adolescence or adulthood have about a threefold higher risk of developing multiple sclerosis (MS) later in life compared to those who did not have mono.

Mono, caused by EBV and spread through saliva, is common, but MS remains relatively rare; EBV is likely a trigger in genetically susceptible individuals rather than a sole cause of MS.

Researchers stress that although mono increases risk, most people with mono do not develop MS, indicating MS likely results from multiple interacting triggers beyond EBV alone.

The study supports the potential benefit of EBV-targeted vaccines in reducing MS burden, a point highlighted by investigators and Moderna TX, Inc., which funded the research and is developing such vaccines.

The study tracked 4,721 EBV-confirmed mono cases and 14,163 controls over about six to eight years, observing MS diagnoses despite overall rarity in both groups.

Neurologists note EBV is widespread in India and that MS results from a mix of genetic, environmental, and immune factors; EBV may act as a trigger but is not the sole cause.

The association appears stronger for earlier onset of MS among those infected with EBV, though experts caution that the link is not proven causal and may reflect diagnostic and awareness changes.

The authors advocate urgent development of vaccines to prevent EBV infection or the specific form that could lead to MS, arguing preventive strategies against EBV-positive IM are essential based on their findings and prior research.

Findings bolster interest in preventive strategies, including an EBV vaccine to reduce MS risk.

Medical experts advise against long-term monitoring after mono due to low absolute risk, while urging awareness of early neurological symptoms (vision changes, tingling, numbness, fatigue, imbalance, or shock-like spine sensations lasting over 24 hours) that warrant evaluation.

Among the studied cohort, 8 exposed individuals (0.17%) developed MS versus 10 controls (0.07%), equating to 2.25 vs 0.77 MS cases per 10,000 person-years respectively.

Methodology notes: the study used laboratory-confirmed EBV infection and MS diagnoses, with incident cases validated by blinded expert chart review and Cox proportional hazards models to estimate risk.