Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
4,125
result(s) for
"Mononucleosis"
Sort by:
The short seller
While seventh-grader Lindy Sachs is recovering from mononucleosis, her father gives her access to his etrading account as a way to pass the time and she discovers that she has a knack for buying and selling stocks.
Book
Epidemiology of Epstein-Barr virus infection and infectious mononucleosis in the United Kingdom
Background
Epstein-Barr Virus (EBV) is a ubiquitous gamma-herpesvirus with which ~ 95% of the healthy population is infected. EBV infection has been implicated in a range of haematological malignancies and autoimmune diseases. Delayed primary EBV infection increases the risk of subsequent complications. Contemporaneous seroepidemiological data is needed to establish best approaches for successful vaccination strategies in the future.
Methods
We conducted a sero-epidemiological survey using serum samples from 2325 individuals between 0 and 25 years old to assess prevalence of detectable anti-EBV antibodies. Second, we conducted a retrospective review of Hospital Episode Statistics to examine changes in Infectious Mononucleosis (IM) incidence over time. We then conducted a large case-control study of 6306 prevalent IM cases and 1,009,971 unmatched controls extracted from an East London GP database to determine exposures associated with IM.
Results
1982/2325 individuals (85.3%) were EBV seropositive. EBV seropositivity increased more rapidly in females than males during adolescence (age 10–15). Between 2002 and 2013, the incidence of IM (derived from hospital admissions data) increased. Exposures associated with an increased risk of IM were lower BMI, White ethnicity, and not smoking.
Conclusions
We report that overall EBV seroprevalence in the UK appears to have increased, and that a sharp increase in EBV seropositivity is seen in adolescent females, but not males. The incidence of IM requiring hospitalisation is increasing. Exposures associated with prevalent IM in a diverse population include white ethnicity, lower BMI, and never-smoking, and these exposures interact with each other. Lastly, we provide pilot evidence suggesting that antibody responses to vaccine and commonly encountered pathogens do not appear to be diminished among EBV-seronegative individuals. Our findings could help to inform vaccine study designs in efforts to prevent IM and late complications of EBV infection, such as Multiple Sclerosis.
Journal Article
Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue
Epstein-Barr virus (EBV) causes infectious mononucleosis (IM) that can lead to chronic fatigue syndrome. The CEBA-project (Chronic fatigue following acute EBV infection in Adolescents) has followed 200 patients with IM and here we present an immunological profiling of adolescents with IM related to clinical characteristics.
Patients were sampled within 6 weeks of debut of symptoms and after 6 months. Peripheral blood mononuclear cells (PBMC) were cultured and stimulated
(n=68), and supernatants analyzed for cytokine release. Plasma was analyzed for inflammatory markers (n=200). The Chalder Fatigue Questionnaire diagnosed patients with and without chronic fatigue at 6 months (CF+ and CF- group, respectively) (n=32 and n=91,
and plasma cohorts, respectively.
Broad activation of PBMC at baseline, with high levels of RANTES (Regulated on activation, normal T-cell expressed and secreted) in the CF+ group, and broad inflammatory response in plasma with high levels of T-cell markers was obeserved. At 6 months, there was an increased β-agonist response and RANTES was still elevated in cultures from the CF+ group. Plasma showed decrease of inflammatory markers except for CRP which was consistently elevated in the CF+ group.
Patients developing chronic fatigue after IM have signs of T-cell activation and low-grade chronic inflammation at baseline and after 6 months.
https://clinicaltrials.gov/, identifier NCT02335437.
Journal Article
Stratifying Multiple Sclerosis Susceptibility Risk: The Role of HLA‐E01 and Infectious Mononucleosis in a Population Cohort
Background Epstein–Barr Virus (EBV) and its clinical manifestation, infectious mononucleosis (IM), are strongly linked to MS risk. A recent in vitro study suggests that HLA‐E*01:03, in contrast to HLA‐E*01:01, may protect against MS through more effective immune responses against EBV‐infected B cells. However, the role of HLA‐E*01 in MS remains unclear. Methods We investigated if HLA‐E*01:01 was significantly associated with higher MS risk in individuals with a history of IM diagnosis, using 487,144 individuals from the UK Biobank's cohort. We estimated the interaction between HLA‐E*01:01 and IM using Cox proportional hazard models, adjusting for demographics, smoking, childhood body size, older siblings, and MS‐related HLA alleles (e.g., HLA‐DRB1*15:01). Results HLA‐E*01:01 allele alone was not significantly associated with IM or MS (p > 0.05). However, a significant interaction between HLA‐E*01:01 and IM history was observed in relation to MS risk (p < 0.001). Specifically, MS risk was significantly higher in both HLA‐E*01:01 heterozygotes (HR = 1.74 [95% CI: 1.36, 1.97], p < 0.001) and homozygotes (HR = 3.01 [95% CI: 1.81, 3.88], p < 0.001) with IM history, compared to HLA‐E*01:03 homozygotes. Conversely, these associations were non‐significant in individuals without IM history (p > 0.05). The estimated proportion of the combined risk attributable to interaction effects was 40% in HLA‐E*01:01 heterozygotes and 65% in HLA‐E*01:01 homozygotes. Conclusions HLA‐E*01:01 carriers diagnosed with IM are at significantly increased risk of MS, independently from other MS‐related HLA alleles. This supports the hypothesis that HLA‐E*01:01 may contribute to MS susceptibility due to weaker immune control over EBV infection. Incorporating HLA‐E*01:01 into existing MHC‐based MS risk models could then enhance personalized risk assessments in individuals with IM history.
Journal Article
Recombinant gp350 Vaccine for Infectious Mononucleosis: A Phase 2, Randomized, Double- Blind, Placebo-Controlled Trial to Evaluate the Safety, Immunogenicity, and Efficacy of an Epstein- Barr Virus Vaccine in Healthy Young Adults
Background. To date, there is no commercially available vaccine to prevent infectious mononucleosis, a disease frequently induced by Epstein-Barr virus (EBV) infection in adolescents or adults devoid of preexisting immunity to the virus. Methods. A total of 181 EBV-seronegative, healthy, young adult volunteers were randomized in a double-blind fashion to receive either placebo or a recombinant EBV subunit glycoprotein 350 (gp350)/aluminum hydroxide and 3-O-desacyl-4′-monophosphoryl lipid A (AS04) candidate vaccine in a 3-dose regimen. Results. The vaccine had demonstrable efficacy (mean efficacy rate, 78.0% [95% confidence interval {CI}, 1.0%–96.0%]) in preventing the development of infectious mononucleosis induced by EBV infection, but it had no efficacy in preventing asymptomatic EBV infection. One month after receipt of the final dose of gp350 vaccine, 98.7% of subjects showed seroconversion to anti-gp350 antibodies (95% CI, 85.5%–97.9%), and they remained anti-gp350 antibody positive for >18 months. Furthermore, there were no concerns regarding the safety or reactogenicity of the gp350/AS04 vaccine. Conclusion. These data support the clinical feasibility of using an EBV vaccine to prevent infectious mononucleosis. Trial registration. ClinicalTrials.gov identifier: NCT00430534.
Journal Article
Behavioral, Virologic, and Immunologic Factors Associated With Acquisition and Severity of Primary Epstein-Barr Virus Infection in University Students
Background. University students were studied prospectively to determine the incidence of and risk factors for acquisition of primary Epstein-Barr virus (EBV) infection and the virologic and immune correlates of disease severity. Methods. EBV antibody-negative freshmen participated in monthly surveillance until graduation. If antibodies developed, proximate samples were assayed for viral load by polymerase chain reaction. Lymphocyte and natural killer (NK) cell numbers and activation were measured by flow cytometry, and plasma cytokine levels were measured by a multiplex assay. Results. Of 546 students screened, 202 (37%) were antibody negative; 143 antibody-negative students were enrolled. During a median of 3 years of observation, 66 subjects experienced primary infection. Of these, 77% had infectious mononucleosis, 12% had atypical symptoms, and 11% were asymptomatic. Subjects reporting deep kissing with or without coitus had the same higher risk of infection than those reporting no kissing (< .01). Viremia was transient, but median oral shedding was 175 days. Increases were observed in numbers of NK cells and CD8⁺ T-cells but not in numbers of CD4⁺ T-cells during acute infection. Severity of illness correlated positively with both blood EBV load (P = .015) and CD8⁺ lymphocytosis (P = .0003). Conclusions. Kissing was a significant risk for primary EBV infection. A total of 89% of infections were symptomatic, and blood viral load and CD8⁺ lymphocytosis correlated with disease severity.
Journal Article
A predictive model for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis
Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a severe hyperinflammatory disorder induced by overactivation of macrophages and T cells. This study aims to identify the risk factors for the progression from infectious mononucleosis (EBV-IM) to EBV-HLH, by analyzing the laboratory parameters of patients with EBV-IM and EBV-HLH and constructing a clinical prediction model. The outcome of this study carries important clinical value for early diagnosis and treatment of EBV-HLH.
A retrospective analysis was conducted on 60 patients diagnosed with EBV-HLH and 221 patients diagnosed with EBV-IM at our hospital between November 2018 and January 2024. Participants were randomly assigned to derivation and internal validation cohorts in a 7:3 ratio. LASSO regression and logistic regression analyses were employed to identify risk factors and construct the nomogram.
Ferritin (OR, 213.139; 95% CI, 8.604-5279.703; P=0.001), CD3
CD16
CD56
% (OR, 0.011; 95% CI, 0-0.467; P=0.011), anti-EBV-NA-IgG (OR, 57.370; 95%CI, 2.976-1106.049; P=0.007), IL-6 (OR, 71.505; 95%CI, 2.118-2414.288; P=0.017), IL-10 (OR, 213.139; 95% CI, 8.604-5279.703; P=0.001) were identified as independent predictors of EBV-HLH. The prediction model demonstrated excellent discriminatory capability evidenced by an AUC of 0.997 (95% CI,0.993-1.000). When visualized using a nomogram, the ROC curves for the derivation and validation cohorts exhibited AUCs of 0.997 and 0.993, respectively. These results suggested that the model was highly stable and accurate. Furthermore, calibration curves and clinical decision curves indicated that the model possessed good calibration and offered significant clinical benefits.
The nomogram, which was based on these five predictors, exhibited robust predictive value and stability, thereby can be used to aid clinicians in the early detection of EBV-HLH.
Journal Article
Role of IL-27 in Epstein–Barr virus infection revealed by IL-27RA deficiency
Epstein–Barr virus (EBV) infection can engender severe B cell lymphoproliferative diseases
1
,
2
. The primary infection is often asymptomatic or causes infectious mononucleosis (IM), a self-limiting lymphoproliferative disorder
3
. Selective vulnerability to EBV has been reported in association with inherited mutations impairing T cell immunity to EBV
4
. Here we report biallelic loss-of-function variants in
IL27RA
that underlie an acute and severe primary EBV infection with a nevertheless favourable outcome requiring a minimal treatment. One mutant allele (rs201107107) was enriched in the Finnish population (minor allele frequency = 0.0068) and carried a high risk of severe infectious mononucleosis when homozygous.
IL27RA
encodes the IL-27 receptor alpha subunit
5
,
6
. In the absence of IL-27RA, phosphorylation of STAT1 and STAT3 by IL-27 is abolished in T cells. In in vitro studies, IL-27 exerts a synergistic effect on T-cell-receptor-dependent T cell proliferation
7
that is deficient in cells from the patients, leading to impaired expansion of potent anti-EBV effector cytotoxic CD8
+
T cells. IL-27 is produced by EBV-infected B lymphocytes and an IL-27RA–IL-27 autocrine loop is required for the maintenance of EBV-transformed B cells. This potentially explains the eventual favourable outcome of the EBV-induced viral disease in patients with IL-27RA deficiency. Furthermore, we identified neutralizing anti-IL-27 autoantibodies in most individuals who developed sporadic infectious mononucleosis and chronic EBV infection. These results demonstrate the critical role of IL-27RA–IL-27 in immunity to EBV, but also the hijacking of this defence by EBV to promote the expansion of infected transformed B cells.
IL-27RA–IL-27 has a critical role in the immunity to EBV, and this defence is hijacked by Epstein–Barr virus to promote the expansion of infected transformed B cells
Journal Article
Primary Epstein-Barr virus infection with and without infectious mononucleosis
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.
Journal Article
Common Questions About Infectious Mononucleosis
Epstein-Barr is a ubiquitous virus that infects 95% of the world population at some point in life. Although Epstein-Barr virus (EBV) infections are often asymptomatic, some patients present with the clinical syndrome of infectious mononucleosis (IM). The syndrome most commonly occurs between 15 and 24 years of age. It should be suspected in patients presenting with sore throat, fever, tonsillar enlargement, fatigue, lymphadenopathy, pharyngeal inflammation, and palatal petechiae. A heterophile antibody test is the best initial test for diagnosis of EBV infection, with 71% to 90% accuracy for diagnosing IM. However, the test has a 25% false-negative rate in the first week of illness. IM is unlikely if the lymphocyte count is less than 4,000 mm . The presence of EBV-specific immunoglobulin M antibodies confirms infection, but the test is more costly and results take longer than the heterophile antibody test. Symptomatic relief is the mainstay of treatment. Glucocorticoids and antivirals do not reduce the length or severity of illness. Splenic rupture is an uncommon complication of IM. Because physical activity within the first three weeks of illness may increase the risk of splenic rupture, athletic participation is not recommended during this time. Children are at the highest risk of airway obstruction, which is the most common cause of hospitalization from IM. Patients with immunosuppression are more likely to have fulminant EBV infection.
Journal Article