Epstein–Barr virus, latitude and multiple sclerosis

Disanto, Giulio; Pakpoor, Julia; Morahan, Julia M.; Hall, Carolina; Meier, Ute‐Christiane; Giovannoni, Gavin; Ramagopalan, Sreeram

doi:10.1177/1352458512451942

Cited by 36 publications

(32 citation statements)

References 10 publications

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“…A meta-analysis of the association between EBV seroprevalence and latitude (of the studies, not individual participants) reported that EBV seroprevalence increased with distance from the equator, and suggested that as well as genetic, social and climactic factors, vitamin D may have a role in EBV-associated disease [99]. We did not identify any studies which looked at the association between vitamin D and EBV seroprevalence; this may merit further investigation.…”

Section: Discussionmentioning

confidence: 83%

Predictors of Epstein-Barr virus serostatus and implications for vaccine policy: A systematic review of the literature

Winter

Jackson

Lewis

et al. 2020

Journal of Global Health

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Background Epstein-Barr virus (EBV) is an important human pathogen; it infects >90% people globally and is linked to infectious mononucleosis and several types of cancer. Vaccines against EBV are in development. In this study we present the first systematic review of the literature on risk factors for EBV infection, and discuss how they differ between settings, in order to improve our understanding of EBV epidemiology and aid the design of effective vaccination strategies.Methods MEDLINE, Embase, and Web of Science were searched on 6 th March 2017 for observational studies of risk factors for EBV infection. Studies were excluded if they were published before 2008 to ensure relevance to the modern day, given the importance of influencing future vaccination policies. There were no language restrictions. After title, abstract and full text screening, followed by checking the reference lists of included studies to identify further studies, data were extracted into standardised spreadsheets and quality assessed. A narrative synthesis was undertaken.Results Seventy-seven papers met our inclusion criteria, including data from 31 countries. There was consistent evidence that EBV seroprevalence was associated with age, increasing throughout childhood and adolescence and remaining constant thereafter. EBV was generally acquired at younger ages in Asia than Europe/North America. There was also compelling evidence for an association between cytomegalovirus infection and EBV. Additional factors associated with EBV seroprevalence, albeit with less consistent evidence, included ethnicity, socioeconomic status, other chronic viral infections, and genetic variants of HLA and immune response genes. ConclusionsOur study is the first systematic review to draw together the global literature on the risk factors for EBV infection and includes an evaluation of the quality of the published evidence. Across the literature, the factors examined are diverse. In Asia, early vaccination of infants would be required to prevent EBV infection. In contrast, in Western countries a vaccine could be deployed later, particularly if it has only a short duration of protection and the intention was to protect against infectious mononucleosis. There is a lack of high-quality data on the prevalence and age of EBV infection outside of Europe, North America and South-East Asia, which are essential for informing effective vaccination policies in these settings.

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Section: Discussionmentioning

confidence: 83%

Predictors of Epstein-Barr virus serostatus and implications for vaccine policy: A systematic review of the literature

Winter

Jackson

Lewis

et al. 2020

Journal of Global Health

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“…A recent study by Disanto et al . [57] found that higher latitude was associated with higher prevalence of EBV exposure, independent from MS status.…”

Section: Discussionmentioning

confidence: 86%

Systematic Review and Meta-Analysis of the Sero-Epidemiological Association between Epstein Barr Virus and Multiple Sclerosis

et al. 2013

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BackgroundA role for Epstein Barr virus (EBV) in multiple sclerosis (MS) has been postulated. Previous systematic reviews found higher prevalences of anti-EBV antibodies in MS patients compared to controls, but many studies have since been published, and there is a need to apply more rigorous systematic review methods.Methodology/Principal FindingsWe examined the link between EBV and MS by conducting a systematic review and meta-analysis of case-control and cohort studies that examined the prevalence of anti-EBV antibodies in the serum of cases and controls. We searched Medline and Embase databases from 1960 to 2012, with no language restriction. The Mantel-Haenszel odds ratios (OR) for anti-EBV antibodies sero-positivity were calculated, and meta-analysis conducted. Quality assessment was performed using a modified version of the Newcastle Ottawa scale. Thirty-nine studies were included. Quality assessment found most studies reported acceptable selection and comparability of cases and controls. However the majority had poor reporting of ascertainment of exposure. Most studies found a higher sero-prevalence of anti-EBNA IgG and anti-VCA IgG in cases compared to controls. The results for anti-EA IgG were mixed with only half the studies finding a higher sero-prevalence in cases. The meta-analysis showed a significant OR for sero-positivity to anti-EBNA IgG and anti-VCA IgG in MS cases (4.5 [95% confidence interval (CI) 3.3 to 6.6, p<0.00001] and 4.5 [95% CI 2.8 to 7.2, p<0.00001] respectively). However, funnel plot examination suggested publication bias for the reporting of the anti-EBNA IgG. No significant difference in the OR for sero-positivity to anti-EA IgG was found (1.4 [95% CI 0.9 to 2.1, p = 0.09]).Conclusion/SignificanceThese findings support previous systematic reviews, however publication bias cannot be excluded. The methodological conduct of studies could be improved, particularly with regard to reporting and conduct of laboratory analyses.

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“…The latitudinal gradient of Epstein-Barr virus (EBV) infection prevalence may also partly explain the earlier onset at high latitudinal regions. A recent meta-analysis demonstrated that an increased rate of EBV infection in higher latitudinal areas occurred in both patients with MS and the general populations 6. Another study30 found a similar geographical distribution between infectious mononucleosis and MS that may also contribute to the latitudinal gradient in prevalence and also potentially AAO.…”

Section: Discussionmentioning

confidence: 97%

“…Indeed, we previously showed a positive association between latitude and MS prevalence with a 1.04 change in prevalence per degree-latitude (p<0.001),2 while Alonso and Hernán3 demonstrated that MS incidence increased 30% in women and 50% in men per each 10° increment of latitude. The explanations of this geographical variation have largely been considered to reflect changes in ambient ultraviolet radiation (UVR) and/or concomitant variations in vitamin D sufficiency5 although this is by no means the only potential explanation 6 7…”

Section: Introductionmentioning

confidence: 99%

Higher latitude is significantly associated with an earlier age of disease onset in multiple sclerosis

Tao

Simpson

Mei

et al. 2016

J Neurol Neurosurg Psychiatry

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Epstein–Barr virus, latitude and multiple sclerosis

Cited by 36 publications

References 10 publications

Predictors of Epstein-Barr virus serostatus and implications for vaccine policy: A systematic review of the literature

Predictors of Epstein-Barr virus serostatus and implications for vaccine policy: A systematic review of the literature

Systematic Review and Meta-Analysis of the Sero-Epidemiological Association between Epstein Barr Virus and Multiple Sclerosis

Higher latitude is significantly associated with an earlier age of disease onset in multiple sclerosis

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