Mapping the prevalence of Epstein-Barr virus and multiple sclerosis in Middle East and North Africa: a systematic review and meta-analysis

Multiple sclerosis (MS) prevalence has increased to medium-to-high levels in several countries of the Middle East and North Africa (MENA), while Epstein-Barr virus (EBV) exposure as one of the most consistently reported MS risk factors is common throughout the region. This systematic review and meta-analysis descriptively mapped published estimates of MS prevalence and EBV seroprevalence alongside each other in MENA countries. We searched MEDLINE, PubMed, Embase, Scopus, and Web of Science until 18 June 2022. Observational studies reporting MS prevalence or EBV seroprevalence among healthy MENA populations were eligible. For quantitative EBV synthesis, we restricted analyses to studies reporting VCA-IgG seroprevalence to improve comparability across studies. Studies reporting the prevalence of specific type of MS or those assessing EBV infection by IgA antibodies or non-serological tissues or without a control arm representing general population were excluded. The Joanna Briggs Institute (JBI) critical appraisal tools were used to determine the quality of the studies. The heterogeneity of studies was evaluated using I2 statistics. Results of the fix-effects meta-analysis were presented using prevalence and 95% confidence intervals. Of 4,323 records identified, 131 studies were included. The pooled MS prevalence was 51.02 per 100,000 population, and the pooled EBV VCA-IgG seroprevalence was 75%. In time-stratified analyses, pooled MS prevalence increased from 12 per 100,000 in studies conducted up to 2000 to 58 per 100,000 in studies conducted from 2011 to 2022. Pooled EBV seroprevalence increased from 71 to 75% across the same periods. These findings suggest that the prevalence of both MS and EBV has increased over time, with a more pronounced increase observed for MS. Between-study heterogeneity was extreme for both outcomes (I2 = 100%), reflecting substantial variation in geography, populations, study methods, diagnostic approaches, and study periods. Published MS prevalence estimates and EBV VCA-IgG seroprevalence estimates showed co-occurring uprising patterns in the available MENA literature. Based on a probable ecological correlation between the increasing prevalence of MS and EBV, the preventive measures against EBV infection may potentially yield favorable outcomes in terms of MS prevention. Future longitudinal, population-based studies with standardized MS ascertainment and age-specific EBV serology are needed.