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Multiple Sclerosis (Houndmills,... Oct 2020Epstein-Barr virus (EBV) infection is thought to play a central role in the development of multiple sclerosis (MS). If causal, it represents a target for interventions... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epstein-Barr virus (EBV) infection is thought to play a central role in the development of multiple sclerosis (MS). If causal, it represents a target for interventions to reduce MS risk.
OBJECTIVE
To examine the evidence for interaction between EBV and other risk factors, and explore mechanisms via which EBV infection may influence MS risk.
METHODS
Pubmed was searched using the terms 'multiple sclerosis' AND 'Epstein Barr virus', 'multiple sclerosis' AND EBV, 'clinically isolated syndrome' AND 'Epstein Barr virus' and 'clinically isolated syndrome' AND EBV. All abstracts were reviewed for possible inclusion.
RESULTS
A total of 262 full-text papers were reviewed. There was evidence of interaction on the additive scale between anti-EBV antibody titre and HLA genotype (attributable proportion due to interaction (AP) = 0.48, < 1 × 10). Previous infectious mononucleosis (IM) was associated with increased odds ratio (OR) of MS in HLA-DRB1*1501 positive but not HLA-DRB1*1501 negative persons. Smoking was associated with a greater risk of MS in those with high anti-EBV antibodies (OR = 2.76) but not low anti-EBV antibodies (OR = 1.16). No interaction between EBV and risk factors was found on a multiplicative scale.
CONCLUSION
EBV appears to interact with at least some established MS risk factors. The mechanism via which EBV influences MS risk remains unknown.
Topics: Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Infectious Mononucleosis; Multiple Sclerosis; Risk Factors
PubMed: 32202208
DOI: 10.1177/1352458520907901 -
Journal of Clinical Virology : the... Jun 2017Textbooks and reviews do not mention the association of symptomatic primary Epstein-Barr virus infectious mononucleosis with acute kidney injury in subjects without... (Review)
Review
BACKGROUND AND OBJECTIVES
Textbooks and reviews do not mention the association of symptomatic primary Epstein-Barr virus infectious mononucleosis with acute kidney injury in subjects without immunodeficiency or autoimmunity.
STUDY DESIGN
Stimulated by our experience with two cases, we performed a review of the literature.
RESULTS
The literature documents 38 cases (26 male and 12 female individuals ranging in age from 0.3 to 51, median 18 years) of symptomatic primary Epstein-Barr virus infectious mononucleosis complicated by acute kidney injury: 27 acute interstitial nephritides, 1 jaundice-associated nephropathy, 7 myositides and 3 hemolytic uremic syndromes. Acute kidney injury requiring renal replacement therapy was observed in 18 (47%) cases. Acute kidney injury did not resolve in one patient with acute interstitial nephritis. Two patients died because of systemic complications. The remaining 35 cases fully recovered.
CONCLUSIONS
In individuals with acute symptomatic Epstein-Barr virus infectious mononucleosis, a relevant kidney injury is rare but the outcome potentially fatal. It results from interstitial nephritis, myositis-associated acute kidney injury, hemolytic uremic syndrome or jaundice-associated nephropathy.
Topics: Acute Kidney Injury; Adult; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Infectious Mononucleosis; Male; Myositis; Nephritis, Interstitial
PubMed: 28410496
DOI: 10.1016/j.jcv.2017.03.016 -
The Cochrane Database of Systematic... Dec 2016Infectious mononucleosis (IM) is a clinical syndrome, usually caused by the Epstein Barr virus (EPV), characterised by lymphadenopathy, fever and sore throat. Most cases... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Infectious mononucleosis (IM) is a clinical syndrome, usually caused by the Epstein Barr virus (EPV), characterised by lymphadenopathy, fever and sore throat. Most cases of symptomatic IM occur in older teenagers or young adults. Usually IM is a benign self-limiting illness and requires only symptomatic treatment. However, occasionally the disease course can be complicated or prolonged and lead to decreased productivity in terms of school or work. Antiviral medications have been used to treat IM, but the use of antivirals for IM is controversial. They may be effective by preventing viral replication which helps to keep the virus inactive. However, there are no guidelines for antivirals in IM.
OBJECTIVES
To assess the effects of antiviral therapy for infectious mononucleosis (IM).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, March 2016), which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, MEDLINE (1946 to 15 April 2016), Embase (1974 to 15 April 2016), CINAHL (1981 to 15 April 2016), LILACS (1982 to 15 April 2016) and Web of Science (1955 to 15 April 2016). We searched the World Health Organization (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov for completed and ongoing trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing antivirals versus placebo or no treatment in IM. We included trials of immunocompetent participants of any age or sex with clinical and laboratory-confirmed diagnosis of IM, who had symptoms for up to 14 days. Our primary outcomes were time to clinical recovery and adverse events and side effects of medication. Secondary outcomes included duration of abnormal clinical examination, complications, viral shedding, health-related quality of life, days missing from school or work and economic outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, assessed the included studies' risk of bias and extracted data using a customised data extraction sheet. We used the GRADE criteria to rate the quality of the evidence. We pooled heterogeneous data where possible, and presented the results narratively where we could not statistically combine data.
MAIN RESULTS
We included seven RCTs with a total of 333 participants in our review. Three trials studied hospitalised patients, two trials were conducted in an outpatient setting, while the trial setting was unclear in two studies. Participants' ages ranged from two years to young adults. The type of antiviral, administration route, and treatment duration varied between the trials. The antivirals in the included studies were acyclovir, valomaciclovir and valacyclovir. Follow-up varied from 20 days to six months. The diagnosis of IM was based on clinical symptoms and laboratory parameters.The risk of bias for all included studies was either unclear or high risk of bias. The quality of evidence was graded as very low for all outcomes and so the results should be interpreted with caution. There were statistically significant improvements in the treatment group for two of the 12 outcomes. These improvements may be of limited clinical significance.There was a mean reduction in 'time to clinical recovery as assessed by physician' of five days in the treatment group but with wide confidence intervals (CIs) (95% CI -8.04 to -1.08; two studies, 87 participants). Prospective studies indicate that clinical signs and symptoms may take one month or more to resolve and that fatigue may be persistent in approximately 10% of patients at six-month follow-up, so this may not be a clinically meaningful result.Trial results for the outcome 'adverse events and side effects of medication' were reported narratively in only five studies. In some reports authors were unsure whether an adverse event was related to medication or complication of disease. These results could not be pooled due to the potential for double counting results but overall, the majority of trials reporting this outcome did not find any significant difference between treatment and control groups.There was a mean reduction in 'duration of lymphadenopathy' of nine days (95% CI -11.75 to -6.14, two studies, 61 participants) in favour of the treatment group.In terms of viral shedding, the overall effect from six studies was that viral shedding was suppressed while on antiviral treatment, but this effect was not sustained when treatment stopped.For all other outcomes there was no statistically significant difference between antiviral treatment and control groups.
AUTHORS' CONCLUSIONS
The effectiveness of antiviral agents (acyclovir, valomaciclovir and valacyclovir) in acute IM is uncertain. The quality of the evidence is very low. The majority of included studies were at unclear or high risk of bias and so questions remain about the effectiveness of this intervention. Although two of the 12 outcomes have results that favour treatment over control, the quality of the evidence of these results is very low and may not be clinically meaningful. Alongside the lack of evidence of effectiveness, decision makers need to consider the potential adverse events and possible associated costs, and antiviral resistance. Further research in this area is warranted.
Topics: Acute Disease; Acyclovir; Adolescent; Adult; Antiviral Agents; Child; Child, Preschool; Female; Guanine; Humans; Infectious Mononucleosis; Male; Randomized Controlled Trials as Topic; Valacyclovir; Valine; Young Adult
PubMed: 27933614
DOI: 10.1002/14651858.CD011487.pub2 -
Journal of Clinical Virology : the... Sep 2016Acute pancreatitis and acalculous cholecystitis have been occasionally reported in primary acute symptomatic Epstein-Barr virus infection. We completed a review of the... (Review)
Review
Acute pancreatitis and acalculous cholecystitis have been occasionally reported in primary acute symptomatic Epstein-Barr virus infection. We completed a review of the literature and retained 48 scientific reports published between 1966 and 2016 for the final analysis. Acute pancreatitis was recognized in 14 and acalculous cholecystitis in 37 patients with primary acute symptomatic Epstein-Barr virus infection. In all patients, the features of acute pancreatitis or acalculous cholecystitis concurrently developed with those of primary acute symptomatic Epstein-Barr virus infection. Acute pancreatitis and acalculous cholecystitis resolved following a hospital stay of 25days or less. Acalculous cholecystitis was associated with Gilbert-Meulengracht syndrome in two cases. In conclusion, this thorough analysis indicates that acute pancreatitis and acalculous cholecystitis are unusual but plausible complications of primary acute symptomatic Epstein-Barr virus infection. Pancreatitis and cholecystitis deserve consideration in cases with severe abdominal pain. These complications are usually rather mild and resolve spontaneously without sequelae.
Topics: Acalculous Cholecystitis; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Pancreatitis; Treatment Outcome
PubMed: 27434148
DOI: 10.1016/j.jcv.2016.06.017 -
Journal of Medical Virology Feb 2017The purpose of this study was to report a case of a previously healthy 20-year-old woman diagnosed with splenic infarction following infectious mononucleosis (IM) by... (Review)
Review
The purpose of this study was to report a case of a previously healthy 20-year-old woman diagnosed with splenic infarction following infectious mononucleosis (IM) by Epstein-Barr virus (EBV) infection and to perform the first systematic review of the clinical characteristics of splenic infarction associated with IM. A systematic review was conducted using English, French, and Japanese literatures of splenic infarction associated with IM due to EBV infection published between 1961 and 2015 in PubMed Medline. A total of 19 cases were extracted from the collected articles. Left upper quadrant (LUQ) pain was observed in 15 (79%) patients. Splenectomy was performed in five (26%) cases, among which four patients presented with stable vital signs. Splenic rupture was accompanied in two (10%) patients. The median time from the onset of IM symptoms to the diagnosis of splenic infarction was 5 days (range, 1-25 days). Fourteen (74%) of 19 patients experienced improvement through medical treatment, and there were no deaths. Splenic infarction associated with IM due to EBV infection can show a favorable clinical outcome after medical treatment. Clinicians should consider the possibility of splenic infarction when patients with IM experience LUQ pain. J. Med. Virol. 89:332-336, 2017. © 2016 Wiley Periodicals, Inc.
Topics: Adolescent; Adult; Child; Female; Herpesvirus 4, Human; Humans; Infectious Mononucleosis; Male; Middle Aged; Splenic Infarction; Young Adult
PubMed: 27357912
DOI: 10.1002/jmv.24618 -
JAMA Apr 2016Early, accurate diagnosis of infectious mononucleosis can help clinicians target treatment, avoid antibiotics, and provide an accurate prognosis. (Review)
Review
IMPORTANCE
Early, accurate diagnosis of infectious mononucleosis can help clinicians target treatment, avoid antibiotics, and provide an accurate prognosis.
OBJECTIVE
To systematically review the literature regarding the value of the clinical examination and white blood cell count for the diagnosis of mononucleosis.
DATA SOURCES
The databases of PubMed (from 1966-2016) and EMBASE (from 1947-2015) were searched and a total of 670 articles and abstracts were reviewed for eligibility.
STUDY SELECTION
Eleven studies were included that reported data sufficient to calculate sensitivity, specificity, or both for clinical examination findings and white blood cell count parameters compared with a valid reference standard.
DATA EXTRACTION AND SYNTHESIS
Data were abstracted from each article by at least 2 reviewers, with discrepancies reconciled by consensus. Clinical findings evaluated in only 1 study are reported with sensitivity, specificity, likelihood ratio (LR), and 95% confidence interval, which were calculated from the available data. Findings evaluated in only 2 studies were summarized with their range, findings evaluated in 3 studies were summarized with a univariate random-effects summary, and findings evaluated in 4 or more studies were summarized with a bivariate random-effects meta-analysis.
MAIN OUTCOMES AND MEASURES
Sensitivity, specificity, and LRs for the diagnosis of mononucleosis.
RESULTS
Mononucleosis is most commonly present among patients aged 5 to 25 years (especially those aged 16-20 years, among whom approximately 1 in 13 patients presenting with sore throat has mononucleosis). The likelihood of mononucleosis is reduced with the absence of any lymphadenopathy (summary sensitivity, 0.91; positive LR range, 0.23-0.44), whereas the likelihood increases with the presence of posterior cervical adenopathy (summary specificity, 0.87; positive LR, 3.1 [95% CI, 1.6-5.9]), inguinal or axillary adenopathy (specificity range, 0.82-0.91; positive LR range, 3.0-3.1), palatine petechiae (specificity, 0.95; positive LR, 5.3 [95% CI, 2.1-13]), and splenomegaly (specificity range, 0.71-0.99; positive LR range, 1.9-6.6). Symptoms are of limited value for the diagnosis of mononucleosis; sore throat and fatigue are sensitive (range, 0.81-0.83) but nonspecific. The presence of atypical lymphocytosis significantly increases the likelihood of mononucleosis (summary LR, 11.4 [95% CI, 2.7-35] for atypical lymphocytes ≥10%, 26 [95% CI, 9.6-68] for those with 20%, and 50 [95% CI, 38-64] for those with 40%). The combination of a patient having greater than 50% lymphocytes and greater than 10% atypical lymphocytes also is useful (specificity, 0.99; positive LR, 54 [95% CI, 8.4-189]).
CONCLUSIONS AND RELEVANCE
In adolescent and adult patients presenting with sore throat, the presence of posterior cervical, inguinal or axillary adenopathy, palatine petechiae, splenomegaly, or atypical lymphocytosis is associated with an increased likelihood of mononucleosis.
Topics: Adolescent; Adult; Axilla; Fatigue; Humans; Infectious Mononucleosis; Leukocyte Count; Lymphatic Diseases; Lymphocyte Count; Neck; Pharyngitis; Physical Examination; Purpura; Sensitivity and Specificity; Splenomegaly; Symptom Assessment; Young Adult
PubMed: 27115266
DOI: 10.1001/jama.2016.2111 -
Neurotoxicology Jul 2017Multiple sclerosis (MS) is a chronic disease of the central nervous system with an unidentified etiology. We systematically reviewed the literature on the possible risk... (Review)
Review
Multiple sclerosis (MS) is a chronic disease of the central nervous system with an unidentified etiology. We systematically reviewed the literature on the possible risk factors associated with MS disease onset, relapses and progression from 1960 to 2012 by accessing six databases and including relevant systematic reviews, meta-analyses, case-control or cohort studies. The focus was on identifying modifiable risk factors. Fifteen systematic reviews and 169 original articles were quality assessed and integrated into a descriptive review. Best evidence, which included one or more prospective studies, suggested that lower exposure to sunlight and/or lower serum vitamin D levels were associated with an increased risk of developing MS onset and subsequent relapses, but a similar quality of evidence was lacking for disease progression. Prospective studies indicated that cigarette smoking may increase the risk of MS as well as accelerate disease progression, but whether smoking altered the risk of a relapse was largely unknown. Infections were implicated in both risk of developing MS and relapses, but data for progression were lacking. Specifically, exposure to the Epstein-Barr virus, particularly if this manifested as infectious mononucleosis during adolescence, was associated with increased MS risk. Upper respiratory tract infections were most commonly associated with an increase in relapses. Relapse rates typically dropped during pregnancy, but there was no strong evidence to suggest that pregnancy itself altered the risk of MS or affected long-term progression. Emerging research with the greatest potential to impact public health was the suggestion that obesity during adolescence may increase the risk of MS; if confirmed, this would be of major significance.
Topics: Cohort Studies; Disease Progression; Humans; Multiple Sclerosis; Recurrence; Respiratory Tract Infections; Risk Factors
PubMed: 27045883
DOI: 10.1016/j.neuro.2016.03.020 -
Injury Mar 2016Infectious mononucleosis (IM) is a common viral illness that predominantly causes sore throat, fever and cervical lymphadenopathy in adolescents and young adults.... (Review)
Review
INTRODUCTION
Infectious mononucleosis (IM) is a common viral illness that predominantly causes sore throat, fever and cervical lymphadenopathy in adolescents and young adults. Although usually a benign, self-limiting disease, it is associated with a small risk of splenic rupture, which can be life-threatening. It is common practice therefore to advise avoiding vigorous physical activity for at least 4-6 weeks, however this is not based on controlled trials or national guidelines. We reviewed published case reports of splenic rupture occurring in the context of IM in an attempt to ascertain common factors that may predict who is at risk.
METHOD
A search of MEDLINE and EMBASE databases was performed for case reports or series published between 1984 and 2014. In total, 52 articles or abstracts reported 85 cases. Data was extracted and compiled into a Microsoft Excel(®) spreadsheet.
RESULTS
The average patient age was 22 years, the majority (70%) being male. The average time between onset of IM symptoms and splenic rupture was 14 days, with a range up to 8 weeks. There was a preceding history of trauma reported in only 14%. Abdominal pain was the commonest presenting complaint of splenic rupture, being present in 88%. 32% were successfully managed non-operatively, whereas 67% underwent splenectomy. Overall mortality was 9%.
CONCLUSIONS AND RECOMMENDATIONS
From our data, it appears that men under 30 within 4 weeks of symptom onset are at highest risk of splenic rupture, therefore particular vigilance in this group is required. As cases have occurred up to 8 weeks after the onset of illness, we would recommend avoidance of sports, heavy lifting and vigorous activity for 8 weeks. Should the patient wish to return to high risk activities prior to this, an USS should be performed to ensure resolution of splenomegaly. The majority of cases reviewed had no preceding trauma, although previous studies have suggested this may be so minor as to go unnoticed by the patient. It is therefore prudent to warn patients about the symptoms of splenic rupture to ensure prompt presentation and minimise treatment delay rather than focusing purely on activity limitation.
Topics: Humans; Infectious Mononucleosis; Rupture, Spontaneous; Splenectomy; Splenic Rupture; Splenomegaly
PubMed: 26563483
DOI: 10.1016/j.injury.2015.10.071 -
The Cochrane Database of Systematic... Nov 2015Infectious mononucleosis, also known as glandular fever or the kissing disease, is a benign lymphoproliferative disorder. It is a viral infection caused by the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Infectious mononucleosis, also known as glandular fever or the kissing disease, is a benign lymphoproliferative disorder. It is a viral infection caused by the Epstein-Barr virus (EBV), a ubiquitous herpes virus that is found in all human societies and cultures. Epidemiological studies show that over 95% of adults worldwide have been infected with EBV. Most cases of symptomatic infectious mononucleosis occur between the ages of 15 and 24 years. It is transmitted through close contact with an EBV shedder, contact with infected saliva or, less commonly, through sexual contact, blood transfusions or by sharing utensils; however, transmission actually occurs less than 10% of the time. Precautions are not needed to prevent transmission because of the high percentage of seropositivity for EBV. Infectious mononucleosis is self-limiting and typically lasts for two to three weeks. Nevertheless, symptoms can last for weeks and occasionally months.Symptoms include fever, lymphadenopathy, pharyngitis, hepatosplenomegaly and fatigue. Symptom relief and rest are commonly recommended treatments. Steroids have been used for their anti-inflammatory effects, but there are no universal criteria for their use.
OBJECTIVES
The objectives of the review were to determine the efficacy and safety of steroid therapy versus placebo, usual care or different drug therapies for symptom control in infectious mononucleosis.
SEARCH METHODS
For this 2015 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (January 1966 to August 2015) and EMBASE (January 1974 to August 2015). We also searched trials registries, however we did not identify any new relevant completed or ongoing trials for inclusion. We combined the MEDLINE search with the Cochrane search strategy for identifying randomised controlled trials (RCTs). We adapted the search terms when searching EMBASE.
SELECTION CRITERIA
RCTs comparing the effectiveness of steroids with placebo, usual care, or other interventions for symptom control for people with documented infectious mononucleosis.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane.
MAIN RESULTS
For this 2015 update, we did not identify any new RCTs for inclusion. The previous version of the review included seven trials with a total of 362 participants. Four trials compared the effectiveness of a steroid to placebo for short-term symptom control in glandular fever, one to aspirin, and two trials explored the effects of steroids in conjunction with an antiviral. Heterogeneity between trials prevented a combined analysis.Trials under-reported methodological design features. Three trials did not adequately describe sequence generation for randomisation. Four trials provided adequate details of allocation concealment. All trials were double-blind but four were not specific as to who was blinded. Loss to follow-up was under-reported in four trials, making it difficult to exclude attrition bias. The risk of selective reporting in the included trials was unclear.Across the trials, no benefit was found in 8/10 assessments of health improvement. Two trials found benefit of steroid therapy over placebo in reducing sore throat at 12 hours (eight-day course odds ratio (OR) 21.00, 95% confidence interval (CI) 1.94 to 227.20; one-dose OR 4.20, 95% CI 1.08 to 16.32), but the benefit was not maintained.In combination with an antiviral drug, participants in the steroid group had less pharyngeal discomfort between days two to four (OR 0.31, 95% CI 0.09 to 1.08) compared to placebo. Across the trials the effects on other common symptoms were less clear. Two trials set out to measure safety; they documented no major adverse effects. In two other trials adverse events were reported, including respiratory distress and acute onset of diabetes. However, the association of the events with the steroid is not definite.
AUTHORS' CONCLUSIONS
There is insufficient evidence to the efficacy of steroids for symptom control in infectious mononucleosis. There is a lack of research on the side effects and long-term complications.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Humans; Infectious Mononucleosis; Randomized Controlled Trials as Topic; Young Adult
PubMed: 26558642
DOI: 10.1002/14651858.CD004402.pub3 -
Journal of Medical Virology May 2016In this meta-analysis, we evaluated the diagnostic role of Epstein-Barr virus deoxyribonucleic acid detection and quantitation in the serum of pediatric and young adult... (Meta-Analysis)
Meta-Analysis Review
In this meta-analysis, we evaluated the diagnostic role of Epstein-Barr virus deoxyribonucleic acid detection and quantitation in the serum of pediatric and young adult patients with infectious mononucleosis. The primary outcome of this meta-analysis was the sensitivity and specificity of Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) detection and quantitation using polymerase chain reaction (PCR). A systematic review and meta-analysis was performed by searching for articles that were published through September 24, 2014 in the following databases: Medline, Cochrane, EMBASE, and Google Scholar. The following keywords were used for the search: "Epstein-Barr virus," "infectious mononucleosis," "children/young adults/infant/pediatric," and "polymerase chain reaction or PCR." Three were included in this analysis. We found that for detection by PCR, the pooled sensitivity for detecting EBV DNA was 77% (95%CI, 66-86%) and the pooled specificity for was 98% (95%CI, 93-100%). Our findings indicate that this PCR-based assay has high specificity and good sensitivity for detecting of EBV DNA, indicating it may useful for identifying patients with infectious mononucleosis. This assay may also be helpful to identify young athletic patients or highly physically active pediatric patients who are at risk for a splenic rupture due to acute infectious mononucleosis.
Topics: Adolescent; Adult; Child; Child, Preschool; DNA, Viral; Female; Herpesvirus 4, Human; Humans; Infant; Infectious Mononucleosis; Male; Molecular Diagnostic Techniques; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity; Viral Load; Young Adult
PubMed: 26455510
DOI: 10.1002/jmv.24402