Risk Of Infectious Mononucleosis Research Articles

Antimicrobials use and infection hospital contacts as proxies of infection exposure at ages 0–2 years and risk of infectious mononucleosis

Infectious mononucleosis (IM) often results from late primary infection with Epstein–Barr virus (EBV). Exposure to EBV at ages 0–2 years from, e.g., siblings therefore protects against IM. Using Danish registers, we therefore followed children born in 1997 through 2015 from age 3 years for a hospital contact with an IM diagnosis as outcome with the number of antimicrobial prescriptions filled before age 3 years as a proxy of infection pressure and the main exposure in stratified Cox regressions. The main analyses used sibships as strata primarily to adjust for health-seeking behaviour with further possible adjustments for age, sex, calendar period and sibship constellation. In these analyses we followed 7087 children, exposed on average to 3.76 antimicrobials prescriptions. We observed a crude hazard ratio for IM per unit increase in cumulative antimicrobial use of 1.00 (95% confidence interval 0.99, 1.02), with similar results in adjusted analyses. The hypothesis that children with the largest use of antimicrobials at ages 0–2 years would subsequently have the lowest risk of IM within a sibship was not corroborated by the data. Furthermore, sibship-matched analyses provided no support for some common early-life immune system characteristics being predictive of IM.

TLR4 896A/G and TLR9 1174G/A polymorphisms are associated with the risk of infectious mononucleosis

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and activate innate and adaptive immune responses. Single nucleotide polymorphisms (SNPs) within the TLR genes may influence host–pathogen interactions and can have an impact on the progression of infectious diseases. The present study aimed to investigate the genotype distribution of TLR2 (2029C/T, rs121917864; 2258G/A, rs5743708), TLR4 (896A/G, rs4986790), and TLR9 (− 1237T/C, rs5743836; − 1486T/C, rs187084; 1174G/A, rs352139; and 2848C/T, rs352140) polymorphisms in 149 children and adolescents with infectious mononucleosis (IM) and 140 healthy individuals. The potential association of TLR SNPs with the clinical manifestations of EBV infection was also studied. The presence of TLR2, TLR4, and TLR9 SNPs was identified by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). EBV DNA loads were detected by quantitative real-time PCR assay. The TLR4 896 GG and the TLR9 1174 GA genotypes were associated with an increased risk of EBV-related IM in examined patients (p = 0.014 and p = 0.001, respectively). The heterozygous genotype of the TLR4 896A/G SNP was associated with an increased risk of elevated liver enzyme levels and leukocytosis (p < 0.05). Our preliminary study revealed that the TLR4 896A/G and the TLR9 1174G/A polymorphisms seem to be related to the course of acute EBV infection in children and adolescents.

Risk of infectious mononucleosis among agonistic swimmers: a cross-sectional study.

The risk of infectious mononucleosis among athletes is quite debated. Some personal observations seem to suggest an increase risk of mononucleosis among athletes, because they attend always close settings with an high probability of respiratory pathogens transmission; overtraining has been also proposed as risk factor. Cross-sectional study in a group of swimmers (aged 11-14 years) of the University Sport Centre of Bari. 40 swimmers were interviewed by healthcare personnel at the end of training courses; demographic characteristics, personal habits, information about sport training and diagnosis of mononucleosis were analysed. The life-time incidence of mononucleosis was around 40%; multivariate analysis showed the association between mononucleosis and use of bottles of other persons (aOR=8.2; 95% CI=1.4-49.2; z=2.32; p=0.021) and average duration of training session was longer among subjects who reported mononucleosis than in subjects who did not indicate this disease. Future multi-centric studies are needed to better define the epidemiology of the mononucleosis in sport settings and to formulate appropriate recommendations to prevent the spreading of this disease.

Sibship structure and risk of infectious mononucleosis: a population-based cohort study.

Present understanding of increased risk of Epstein-Barr virus (EBV)-related infectious mononucleosis among children of low birth order or small sibships is mainly based on old and indirect evidence. Societal changes and methodological limitations of previous studies call for new data. We used data from the Danish Civil Registration System and the Danish National Hospital Discharge Register to study incidence rates of inpatient hospitalizations for infectious mononucleosis before the age of 20 years in a cohort of 2,543,225 Danes born between 1971 and 2008, taking individual sibship structure into account. A total of 12,872 cases of infectious mononucleosis were observed during 35.3 million person-years of follow-up. Statistical modelling showed that increasing sibship size was associated with a reduced risk of infectious mononucleosis and that younger siblings conferred more protection from infectious mononucleosis than older siblings. In addition to this general association with younger and older siblings, children aged less than 4 years transiently increased their siblings’ infectious mononucleosis risk. Our results were confirmed in an independent sample of blood donors followed up retrospectively for self-reported infectious mononucleosis. Younger siblings, and to a lesser degree older siblings, seem to be important in the transmission of EBV within families. Apparently the dogma of low birth order in a sibship as being at the highest risk of infectious mononucleosis is no longer valid.

Exposure to Infant Siblings During Early Life and Risk of Multiple Sclerosis

ContextThe “hygiene hypothesis” has implicated sibship as a marker of infection load during early life and suggests that exposure or reexposure to infections can influence the developing immune system. Viral infection has also been implicated in the pathogenesis of multiple sclerosis (MS).ObjectivesTo evaluate whether exposure to infant siblings in early life is associated with the risk of MS, and to explore the possible mechanism for any apparent protective effect, including altered Epstein-Barr virus (EBV) infection patterns.Design, Setting, and PatientsPopulation-based case-control study in Tasmania, Australia, from 1999 to 2001 based on 136 cases of magnetic resonance imaging–confirmed MS and 272 community controls, matched on sex and year of birth.Main Outcome MeasureRisk of MS by duration of contact with younger siblings aged less than 2 years in the first 6 years of life.ResultsIncreasing duration of contact with a younger sibling aged less than 2 years in the first 6 years of life was associated with reduced MS risk (adjusted odds ratios [AORs]: <1 infant-year, 1.00 [reference]; 1 to <3 infant-years, 0.57 [95% confidence interval {CI}, 0.33-0.98]; 3 to <5 infant-years, 0.40 [95% CI, 0.19-0.92]; ≥5 infant-years, 0.12 [95% CI, 0.02-0.88]; test for trend, P = .002). A history of exposure to infant siblings was associated with a reduced IgG response to EBV among controls. Controls with at least 1 infant-year contact had a reduced risk of infectious mononucleosis and a reduced risk of very high composite EBV IgG titers (AOR, 0.33; 95% CI, 0.11-0.98) compared with other controls. The inverse association between higher infant contact and MS was independent of EBV IgG titer.ConclusionHigher infant sibling exposure in the first 6 years of life was associated with a reduced risk of MS, possibly by altering childhood infection patterns and related immune responses.