Primary Epstein-Barr virus infection with and without infectious mononucleosis.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
09
09
2019
accepted:
26
11
2019
entrez:
18
12
2019
pubmed:
18
12
2019
medline:
28
3
2020
Statut:
epublish
Résumé
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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31846480
doi: 10.1371/journal.pone.0226436
pii: PONE-D-19-25327
pmc: PMC6917282
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0226436Subventions
Organisme : Medical Research Council
ID : MC_UU_12014/3
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
PLoS Pathog. 2015 Dec 01;11(12):e1005286
pubmed: 26624012
Scand J Infect Dis. 1983;15(4):335-8
pubmed: 6318303
Int J Epidemiol. 2014 Oct;43(5):1607-14
pubmed: 25436250
Clin Immunol. 2015 May;158(1):59-66
pubmed: 25805657
Am J Epidemiol. 2014 Oct 1;180(7):687-95
pubmed: 25167864
Pediatr Infect Dis J. 2003 Nov;22(11):974-8
pubmed: 14614370
Clin Transl Immunology. 2015 Feb 27;4(2):e33
pubmed: 25774295
Clin Infect Dis. 2014 Jun;58(12):1684-9
pubmed: 24696238
J Infect Dis. 2013 Oct 15;208(8):1286-93
pubmed: 23868878
J Infect Dis. 2013 Jan 1;207(1):80-8
pubmed: 23100562
Trends Immunol. 2014 Apr;35(4):159-69
pubmed: 24589417
Math Med Biol. 2012 Sep;29(3):245-61
pubmed: 21700566
J Infect Dis. 1996 May;173(5):1248-51
pubmed: 8627079
Lancet. 2012 Dec 15;380(9859):2095-128
pubmed: 23245604
Ann Epidemiol. 2013 May;23(5):275-80
pubmed: 23621993
Vox Sang. 2012 Apr;102(3):271
pubmed: 21967299
Cancer Res. 2007 Mar 1;67(5):2382-8
pubmed: 17332371
Reprod Toxicol. 2006 May;21(4):436-45
pubmed: 16580943
Clin Diagn Lab Immunol. 2003 Jan;10(1):78-82
pubmed: 12522043
N Engl J Med. 2003 Oct 2;349(14):1324-32
pubmed: 14523140
Am J Med. 2007 Oct;120(10):911.e1-8
pubmed: 17904463
J Virol. 2017 Oct 13;91(21):
pubmed: 28835490
BMC Infect Dis. 2017 Mar 21;17(1):220
pubmed: 28320319
PLoS Pathog. 2015 Mar 27;11(3):e1004746
pubmed: 25816224
Arch Neurol. 2007 Jan;64(1):72-5
pubmed: 17210811
Int J Epidemiol. 2016 Jun;45(3):825-34
pubmed: 25925268
J Clin Microbiol. 2004 Aug;42(8):3381-7
pubmed: 15297472
J R Stat Soc Ser A Stat Soc. 2012 Oct;175(4):831-861
pubmed: 23193356
Clin Infect Dis. 2001 Jul 1;33(1):83-8
pubmed: 11389499
Can J Infect Dis Med Microbiol. 2014 Sep;25(5):277-80
pubmed: 25371691
PLoS One. 2017 Apr 17;12(4):e0175574
pubmed: 28414725
World J Pediatr. 2011 Feb;7(1):45-9
pubmed: 21191775
Clin Transl Immunology. 2016 Aug 12;5(8):e94
pubmed: 27588199
BMC Res Notes. 2012 Jul 20;5:361
pubmed: 22818256
J Infect Dis. 2004 Jul 1;190(1):63-71
pubmed: 15195244
Clin Infect Dis. 2006 Aug 1;43(3):276-82
pubmed: 16804839
Clin Epidemiol. 2015 Nov 17;7:449-90
pubmed: 26604824
Eur J Epidemiol. 2014 Aug;29(8):541-9
pubmed: 24965263
Annu Rev Immunol. 2007;25:587-617
pubmed: 17378764
Sci Transl Med. 2011 Nov 2;3(107):107fs7
pubmed: 22049067
Am J Trop Med Hyg. 1990 Apr;42(4):380-5
pubmed: 2158753
Clin Transl Immunology. 2015 Jan 23;4(1):e32
pubmed: 25671130
Infect Dis (Lond). 2015;47(12):908-14
pubmed: 26308113
J Infect Dis. 2001 Sep 15;184(6):777-80
pubmed: 11517440
Curr Top Microbiol Immunol. 2015;390(Pt 1):211-40
pubmed: 26424648
Acta Neurol Scand. 2004 Apr;109(4):270-5
pubmed: 15016009
Dan Med J. 2012 Jul;59(7):B4485
pubmed: 22759852
Clin Epigenetics. 2018 May 9;10:62
pubmed: 29760811
Perspect Sex Reprod Health. 2002 Nov-Dec;34(6):304-9
pubmed: 12558093
PLoS One. 2017 Feb 9;12(2):e0169112
pubmed: 28182624
BMC Infect Dis. 2014 Mar 20;14:151
pubmed: 24650116
Clin Diagn Lab Immunol. 2000 May;7(3):451-6
pubmed: 10799460
Med Mal Infect. 2017 Dec;47(8):540-545
pubmed: 28987291
Mult Scler. 2007 Apr;13(3):420-3
pubmed: 17439912
Clin Microbiol Rev. 2011 Jan;24(1):193-209
pubmed: 21233512
Curr Opin Virol. 2016 Oct;20:34-39
pubmed: 27591678
J Clin Microbiol. 2006 May;44(5):1873-4
pubmed: 16672427