Risk of infectious mononucleosis is not associated with prior infection morbidity

BackgroundThe probability of presenting with infectious mononucleosis (IM) upon primary Epstein–Barr virus infection increases dramatically at the start of puberty. Aiming to understand why that is, we assessed whether the number of infection-related health events during two specific time periods−ag...

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Main Authors: Klaus Rostgaard, Ragnar Kristjánsson, Olafur Davidsson, Jojo Biel-Nielsen Dietz, Signe Holst Søegaard, Lone Graff Stensballe, Henrik Hjalgrim
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Epidemiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fepid.2025.1518559/full
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author Klaus Rostgaard
Klaus Rostgaard
Ragnar Kristjánsson
Olafur Davidsson
Jojo Biel-Nielsen Dietz
Signe Holst Søegaard
Signe Holst Søegaard
Lone Graff Stensballe
Henrik Hjalgrim
Henrik Hjalgrim
Henrik Hjalgrim
Henrik Hjalgrim
author_facet Klaus Rostgaard
Klaus Rostgaard
Ragnar Kristjánsson
Olafur Davidsson
Jojo Biel-Nielsen Dietz
Signe Holst Søegaard
Signe Holst Søegaard
Lone Graff Stensballe
Henrik Hjalgrim
Henrik Hjalgrim
Henrik Hjalgrim
Henrik Hjalgrim
author_sort Klaus Rostgaard
collection DOAJ
description BackgroundThe probability of presenting with infectious mononucleosis (IM) upon primary Epstein–Barr virus infection increases dramatically at the start of puberty. Aiming to understand why that is, we assessed whether the number of infection-related health events during two specific time periods−ages 10–12 years (pre-teen window) and the three most recent years (recent window)−could predict the likelihood of individuals aged 13–19 years developing IM.MethodsWe used sibship-stratified Cox regression to mitigate socio-demographic confounding and bias. Consequently, we only followed members of IM-affected sibships aged 13–19 years between 1999 and 2021 for IM, based on information from complete nationwide Danish administrative and health registers. Estimates were further adjusted for sex, age, birth order (1, 2, 3+) and sibship constellation [number of siblings and their signed (older/younger) age difference to the index person]. Infection-related health events defining the exposures considered were either a category of antimicrobial prescription, or a hospital contact with an infectious disease diagnosis. We measured evidence/probability of the associations using asymptotic Bayes factors, rather than using p-value based testing.ResultsThe adjusted hazard ratio (HR) for IM with 95% confidence limits for an additional antimicrobial prescription in the pre-teen exposure window was [1.01; 0.98–1.04], and the corresponding adjusted HR for an additional antimicrobial prescription in the recent exposure window was [1.02; 0.99–1.06].ConclusionsIM was not preceded by unusual numbers of infections. Small effect sizes, together with small variation in exposure, did not render the assessed exposures useful for predicting IM for public health or the clinic.
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spelling doaj-art-651f2b80f2654566b0c8bdd7c8c16dc62025-08-20T02:47:52ZengFrontiers Media S.A.Frontiers in Epidemiology2674-11992025-03-01510.3389/fepid.2025.15185591518559Risk of infectious mononucleosis is not associated with prior infection morbidityKlaus Rostgaard0Klaus Rostgaard1Ragnar Kristjánsson2Olafur Davidsson3Jojo Biel-Nielsen Dietz4Signe Holst Søegaard5Signe Holst Søegaard6Lone Graff Stensballe7Henrik Hjalgrim8Henrik Hjalgrim9Henrik Hjalgrim10Henrik Hjalgrim11Danish Cancer Institute, Danish Cancer Society, Copenhagen, DenmarkDepartment of Epidemiology Research, Statens Serum Institut, Copenhagen, DenmarkDanish Cancer Institute, Danish Cancer Society, Copenhagen, DenmarkDanish Cancer Institute, Danish Cancer Society, Copenhagen, DenmarkDanish Cancer Institute, Danish Cancer Society, Copenhagen, DenmarkDanish Cancer Institute, Danish Cancer Society, Copenhagen, DenmarkDepartment of Congenital Disorders, Statens Serum Institut, Copenhagen, DenmarkDepartment of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DenmarkDanish Cancer Institute, Danish Cancer Society, Copenhagen, DenmarkDepartment of Epidemiology Research, Statens Serum Institut, Copenhagen, DenmarkDepartment of Hematology, Copenhagen University Hospital, Copenhagen, DenmarkDepartment of Clinical Medicine, Copenhagen University, Copenhagen, DenmarkBackgroundThe probability of presenting with infectious mononucleosis (IM) upon primary Epstein–Barr virus infection increases dramatically at the start of puberty. Aiming to understand why that is, we assessed whether the number of infection-related health events during two specific time periods−ages 10–12 years (pre-teen window) and the three most recent years (recent window)−could predict the likelihood of individuals aged 13–19 years developing IM.MethodsWe used sibship-stratified Cox regression to mitigate socio-demographic confounding and bias. Consequently, we only followed members of IM-affected sibships aged 13–19 years between 1999 and 2021 for IM, based on information from complete nationwide Danish administrative and health registers. Estimates were further adjusted for sex, age, birth order (1, 2, 3+) and sibship constellation [number of siblings and their signed (older/younger) age difference to the index person]. Infection-related health events defining the exposures considered were either a category of antimicrobial prescription, or a hospital contact with an infectious disease diagnosis. We measured evidence/probability of the associations using asymptotic Bayes factors, rather than using p-value based testing.ResultsThe adjusted hazard ratio (HR) for IM with 95% confidence limits for an additional antimicrobial prescription in the pre-teen exposure window was [1.01; 0.98–1.04], and the corresponding adjusted HR for an additional antimicrobial prescription in the recent exposure window was [1.02; 0.99–1.06].ConclusionsIM was not preceded by unusual numbers of infections. Small effect sizes, together with small variation in exposure, did not render the assessed exposures useful for predicting IM for public health or the clinic.https://www.frontiersin.org/articles/10.3389/fepid.2025.1518559/fullEpstein–Barr Virusimmune systeminfectionsinfectious mononucleosispubertyBayes factor
spellingShingle Klaus Rostgaard
Klaus Rostgaard
Ragnar Kristjánsson
Olafur Davidsson
Jojo Biel-Nielsen Dietz
Signe Holst Søegaard
Signe Holst Søegaard
Lone Graff Stensballe
Henrik Hjalgrim
Henrik Hjalgrim
Henrik Hjalgrim
Henrik Hjalgrim
Risk of infectious mononucleosis is not associated with prior infection morbidity
Frontiers in Epidemiology
Epstein–Barr Virus
immune system
infections
infectious mononucleosis
puberty
Bayes factor
title Risk of infectious mononucleosis is not associated with prior infection morbidity
title_full Risk of infectious mononucleosis is not associated with prior infection morbidity
title_fullStr Risk of infectious mononucleosis is not associated with prior infection morbidity
title_full_unstemmed Risk of infectious mononucleosis is not associated with prior infection morbidity
title_short Risk of infectious mononucleosis is not associated with prior infection morbidity
title_sort risk of infectious mononucleosis is not associated with prior infection morbidity
topic Epstein–Barr Virus
immune system
infections
infectious mononucleosis
puberty
Bayes factor
url https://www.frontiersin.org/articles/10.3389/fepid.2025.1518559/full
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