Epidemiology of Epstein-Barr Virus infection and Infectious Mononucleosis in the United Kingdom
Authors: Kuri Ashvin , Jacobs Benjamin Meir , Vickaryous Nicola , Pakpoor Julia , Middeldorp Jaap , Giovannoni Gavin , Dobson Ruth 
Published: January 2020

Background

Epstein-Barr Virus (EBV) is a ubiquitous gamma-herpesvirus with which ∼95% of the healthy population is infected. EBV infection has been implicated in a range of haematological malignancies and autoimmune diseases. Delayed primary EBV infection increases the risk of subsequent complications. Over recent decades, the age of primary EBV infection has become later, largely due to improved sanitation and living conditions.

Methods and findings

First, we conducted a sero-epidemiological survey of healthy volunteers between 0 and 25 years old to assess prevalence of detectable anti-EBV antibodies. 1982 of 2325 individuals (85.3%) were EBV seropositive. EBV seropositivity increased monotonically with age, and increased more among females than males during adolescence (ages 10 – 15). Second, we conducted a retrospective review of Hospital Episode Statistics to determine changes in Infectious Mononucleosis (IM) incidence over time. Between 2002 and 2013, the incidence of IM (derived from hospital admissions data) increased. We then conducted a large case-control study of 6306 prevalent IM cases and 1,009,971 unmatched controls extracted from an East London GP database to determine exposures associated with IM. Exposures associated with lower risk of IM were elevated BMI (Overweight OR 0.80 [0.75 to 0.86], obese OR 0.63 [0.57 to 0.70]), non-white ethnicity (Black OR 0.21 [0.18 to 0.23], Asian OR 0.14 [0.13 to 0.16], Other ethnicity OR 0.22 [0.19 to 0.25]), and a history of smoking (OR 0.87 [0.83 to 0.92]), whereas affluence was associated with a higher risk of IM (per increase in IMD decile OR 1.15 [1.13 to 1.17]. Finally, we used ELISA to determine antibody responses to common pathogens and vaccine antigens among EBV-seronegative individuals. EBV-seronegative donors did not display diminished serum antibody responses to pertussis, rubella, or varicella compared to EBV-seropositive donors.

Conclusions

In this study we make several important observations on the epidemiology of EBV infection in the UK. We find that overall EBV seroprevalence in the UK appears to have increased, and that the sharp increase in EBV seropositivity takes places earlier among females than males. We find that the incidence of IM requiring hospitalisation is increasing. We find that exposures associated with prevalent IM in a diverse population include white ethnicity, affluence, lower BMI, and never-smoking, and these exposures interact with each other. Lastly, we provide pilot evidence suggesting that antibody responses to vaccine and encountered pathogens do not seem to be diminished among EBV-seronegative individuals, which is a theoretical counter-argument to developing EBV vaccines. Our findings could help to inform vaccine study designs in efforts to prevent IM and late complications of EBV infection, such as Multiple Sclerosis.

Key messages

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Epstein-Barr Virus (EBV) is a ubiquitous virus which infects over 95% of the world’s population. The majority of infection is silent and without consequence. In a subset of individuals, EBV is thought to play a role in the pathogenesis of autoimmune disease and haematological cancers.

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During childhood and adolescence, EBV seroprevalence increased monotonically with age from 0-5 (67.8% females, 72.0% males) to 20-25 (96.4% females, 95.5% males)

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The incidence of Infectious Mononucleosis (IM) leading to hospital admission has increased over the past decade

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Exposure associated with IM in a large, diverse East London cohort (n>1,000,000) were low BMI, never-smoking, white ethnicity, and affluence.