Primary Epstein-Barr virus infection with and without infectious mononucleosis

Rostgaard, K., Balfour, H. H., Jarrett, R. , Erikstrup, C., Pedersen, O., Ullum, H., Nielsen, L. P., Voldstedlund, M. and Hjalgrim, H. (2019) Primary Epstein-Barr virus infection with and without infectious mononucleosis. PLoS ONE, 14(12), e0226436. (doi: 10.1371/journal.pone.0226436) (PMID:31846480) (PMCID:PMC6917282)

Abstract

Background: Infectious mononucleosis (IM) is a common adverse presentation of primary infection with Epstein-Barr virus (EBV) in adolescence and later, but is rarely recognized in early childhood where primary EBV infection commonly occurs. It is not known what triggers IM, and also not why IM risk upon primary EBV infection (IM attack rate) seemingly varies between children and adolescents. IM symptoms may be severe and persist for a long time. IM also markedly elevates the risk of Hodgkin lymphoma and multiple sclerosis for unknown reasons. The way IM occurrence depends on age and sex is incompletely described and hard to interpret etiologically, because it depends on three quantities that are not readily observable: the prevalence of EBV-naϊve persons, the hazard rate of seroconverting and the attack rate, i.e. the fraction of primary EBV infections that is accompanied by IM. We therefore aimed to provide these quantities indirectly, to obtain epidemiologically interpretable measures of the dynamics of IM occurrence to provide etiological clues. Methods and findings: We used joint modeling of EBV prevalence and IM occurrence data to provide detailed sex- and age-specific EBV infection rates and IM attack rates and derivatives thereof for a target population of all Danes age 0–29 years in 2006–2011. We demonstrate for the first time that IM attack rates increase dramatically rather precisely in conjunction to typical ages of puberty onset. The shape of the seroconversion hazard rate for children and teenagers confirmed a priori expectations and underlined the importance of what happens at age 0–2 years. The cumulative risk of IM before age 30 years was 13.3% for males and 22.4% for females. IM is likely to become more common through delaying EBV infection in years to come. Conclusions: The change in attack rate at typical ages of puberty onset suggests that the immunologic response to EBV drastically changes over a relatively short age-span. We speculate that these changes are an integrated part of normal sexual maturation. Our findings may inform further etiologic research into EBV-related diseases and vaccine design. Our methodology is applicable to the epidemiological study of any infectious agent that establishes a persistent infection in the host and the sequelae thereof.

• Item Type: Articles
• Additional Information: Funding: The study was supported by Ulla og Mogens Folmer Andersen’s Foundation (grant number 100041-1 to HH), Helsefonden (https://helsefonden.dk; grant number 19-B-0352 to KR), and the University of Minnesota Foundation (https://give.umn.edu; grant number 20707 to HB).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jarrett, Professor Ruth

Creator Roles

Jarrett, R.: Investigation, Writing – original draft, Writing – review and editing

• Authors: Rostgaard, K., Balfour, H. H., Jarrett, R., Erikstrup, C., Pedersen, O., Ullum, H., Nielsen, L. P., Voldstedlund, M., and Hjalgrim, H.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Copyright Holders: Copyright © 2019 Rostgaard et al.
• First Published: First published in PLoS ONE
• Publisher Policy: Reproduced under a Creative Commons license