Primary Epstein-Barr virus infection with and without infectious mononucleosis

Autoři: Klaus Rostgaard aff001;  Henry H. Balfour, Jr. aff002;  Ruth Jarrett aff004;  Christian Erikstrup aff005;  Ole Pedersen aff006;  Henrik Ullum aff007;  Lars Peter Nielsen aff008;  Marianne Voldstedlund aff009;  Henrik Hjalgrim aff001
Působiště autorů: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark aff001;  Department of Laboratory Medicine and Pathology, University of Minnesota Medical Center, Minneapolis, MN, United States of America aff002;  Department of Pediatrics, University of Minnesota Medical Center, Minneapolis, MN, United States of America aff003;  MRC—University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom aff004;  Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark aff005;  Department of Clinical Immunology, Næstved Hospital, Næstved, Denmark aff006;  Department of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark aff007;  Danish National Biobank, Statens Serum Institut, Copenhagen, Denmark aff008;  Department of Infectious Epidemiology, Statens Serum Institut, Copenhagen, Denmark aff009;  Department of Haematology, Copenhagen University Hospital, Copenhagen, Denmark aff010
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226436



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.


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.

Klíčová slova:

Adolescents – Antibodies – Blood donors – Danish people – Epstein-Barr virus – General practitioners – Children – Immune response


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