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 6th 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.
Conclusions Our 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.