Epstein-Barr Virus VCA Research Articles

Investigation of atypical serological profiles for Epstein-Barr virus (EBV)

BackgroundCommercial immunoassays that detect IgG and IgM directed toward VCA and IgG EBNA are used in combination to assess EBV immune status. However, this strategy does not always confirm/exclude recent/past EBV infection or absence of immunity. ObjectivesThe aim of our study was to perform complementary investigations on samples with atypical EBV serological profiles, in order to identify the clinical situation they correspond to. Study designEBV serology was performed using EBV VCA IgM/IgG and EBNA IgG LXL® DiaSorin assay. Complementary investigations included ELISA IgM VCA, immunoblots, CMV IgM/IgG and CMV IgG avidity, and EBV PCR. ResultsIn our study, 12810 EBV serological results were analyzed, and 3580 atypical profiles were detected (28 %). Among these latter, isolated VCA IgG represented 42.9 %, the three positive markers accounted for 29.1 %, isolated EBNA IgG represented 18.5 %, isolated VCA IgM accounted for 6.4 % and positive VCA IgM & positive EBNA IgG represented 3.1 %. VCA IgG detected alone were specific in 100 % cases and EBNA IgG detected alone were specific in 91.7 % cases. VCA IgM detected alone were false positive or due to a cross reaction with CMV in 52.8 % cases. The pattern positive VCA IgM and positive EBNA IgG correspond to a false positive in VCA IgM, EBNA IgG or both in 83.4 % cases. Positive EBV VCA IgM/IgG and EBNA IgG were unreliable to detect active EBV infection in 66.7 % cases. DiscussionAtypical EBV serological profiles may correspond to several clinical situations and complementary investigations allow to determine the immune status in more than 98.5 % cases.

P309 Impact of EBV Status on decision making for advanced therapies in IBD Patients

Abstract Background The CESAME study suggested that Thiopurines confer increased risk of lymphomas in IBD patients who are naïve to Epstein - Barr virus (EBV) particularly in young males. European Crohn’s and Colitis Organisation (ECCO) guidelines recommend considering EBV screening in individuals prior to initiating immunomodulator therapy. The impact of EBV serology status on decision-making processes regarding advanced therapies in IBD patients is not studied before. Methods Consecutive patients initiated on advanced therapies (biologics or small molecules). EBV nuclear and vca IgG status were recorded. The first advanced therapy of the positive and negative patients were compared. Proportion of the negative patients who seroconverted and the time to seroconversion were analysed. Results We included 491 patients (M: F 1:14). Median age of patients who had EBV serology done prior to initiating on advanced therapies was 31.5 years (range 5-84 years) .In 41 (8.35%) patients, neither nuclear nor vca IgG antibody were detected at initial screening. The median age of EBV negative patients was 26 years (range 13-51 years).30 of the EBV negative patients were males. Azathioprine/6MP was not initiated in 37 (90.24%) of the EBV negative patients. Re-testing of EBV negative patients were done at a median interval of 28 months (range 3-90 months). 5 of these retested patients (12.2%), seroconverted and in three of this patients Azathioprine was used following seroconversion. Conclusion A significant minority of IBD patients are EBV negative when tested as part of pre biologic screening, including in male patients above the age of 25. Thiopurine therapy was avoided in these patients. Only a fraction of EBV negative patient seroconverted on re-testing. The impact of EBV testing in treatment decision, as well as the attributable costs needs to be evaluated further.

High Epstein-Barr virus capsid antigen IgG level associates with the carriership of CD8+ T cell somatic mutations in the STAT3 SH2 domain

High carrier prevalence of STAT3 SH2 domain somatic mutations was recently discovered in CD8+ T cells. We found these low-allele-fraction clones in 26% of donors, without difference between multiple sclerosis (MS) patients and controls. Here we tested whether anti-viral antibodies associate with the carriership of these mutant clones. We compared antibody responses against common viruses in mutation carriers vs. non-carriers. Plasma samples of 152 donors (92 MS patients, 60 controls) were analyzed for antibodies against cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6A and parvovirus B19. The mutation carrier status associated with EBV VCA IgG level (p = 0.005) and remained significant after logistic regression (p = 0.036). This association was contributed similarly by MS patients and controls. These results suggest that EBV contributes to the generation or growth of these clones. The pathogenic role of the STAT3 mutant clones in MS is presently unclear, but their detailed characterization warrants further study.

Cigarette smoking is associated with Herpesviruses in persons with and without serious mental illness.

Herpesviruses are recognized as major causes of human diseases. Following initial infection, Herpesviruses can undergo cycles of reactivation controlled largely by the immune system. Cigarette smoking is an important modulator of the immune system particularly in individuals with serious mental illness where smoking is associated with increased rates of cardiopulmonary diseases and mortality. However, the effect of smoking on Herpesviruses has not been extensively studied. In this nested cohort study, cigarette smoking was assessed in 1323 persons with serious mental illness or without a psychiatric disorder ascertained in a psychiatric health care system and the adjacent community. Participants provided a blood sample from which were measured IgG class antibodies to five human Herpesviruses: Cytomegalovirus (CMV), Epstein Barr Virus (EBV), Herpes Simplex Virus-Type 1 (HSV-1); Varicella Zoster Virus (VZV); and Human Herpes Virus-Type 6 (HHV-6). The associations between smoking variables and antibody levels to the Herpesviruses were analyzed among diagnostic groups in multiple regression models adjusted for age, sex, and race. Current smoking was significantly associated with higher levels of antibodies to CMV (coefficient .183, 95% CI .049, .317, p<.001, q<.007) and the three EBV proteins (EBV NA -(coefficient .088, 95% CI .032, .143, p = .002, q<.014; EBV Virion - coefficient .100, 95% CI .037, .163, p = .002, q<.014; and EBV VCA - coefficient .119, 95% CI .061, .177, p = .00004, q<.0016). The amount of cigarettes smoked was also correlated with higher levels of antibodies to the three EBV proteins. Interaction analyses indicated that the association between cigarette smoking and levels of antibodies to CMV and EBV was independent of diagnostic group. Cigarette smoking was not significantly associated with the level of antibodies to HSV-1, VZV, or HHV-6. Individuals who smoke cigarettes have increased levels of IgG antibodies to CMV and EBV. Cigarette smoking may be a contributory factor in the relationship between CMV, EBV and chronic somatic disorders associated with these viruses.

Epstein-Barr virus dynamics and its prognostic impact on nasopharyngeal cancers in a non-endemic region.

Epstein-Barr virus (EBV) DNA quantification in nasopharyngeal cancer (NPC) is an indicator of the tumour burden, stage and survival. Although EBV dynamics in endemic regions has been extensively studied and reported, the data from non-endemic regions is sparse. This study attempts to investigate the EBV dynamics in NPC patients from a non-endemic region and also to identify the factors impacting the outcomes. This was a prospective observational study conducted at a tertiary care centre in South India and enrolled patients with non-metastatic, biopsy proven NPC, who were suitable for radical chemo-radiotherapy with or without induction chemotherapy. Two blood samples, one prior to initiation of any anticancer treatment, and second at 6 weeks post treatment, were collected to quantify EBV DNA using real-time quantitative polymerase chain reaction. Antibodies against EBV viral capsid antigen (EBV VCA IgM), EBV Early Antigen (EBV EA IgG) and EBV Nuclear Antigen (EBV EBNA IgG) were also measured in the sample. The impact of EBV dynamics on the outcomes was then analysed. The study included a total of 35 patients. Thirty-three had identifiable EBV DNA (94.3%) and a histological diagnosis of non-keratinising undifferentiated type of squamous cell carcinoma. There was no correlation between the EBV DNA and anti-EBV antibodies. There was a significant association between composite stage and pre-treatment DNA titre (p = 0.030). The mean EBV DNA titre was lower for patients with no clinically demonstrable disease at last follow-up and the reduction in EBV DNA titres was significant (p = 0.020) for those patients who remained disease free. Plasma EBV DNA is an accurate and reliable biomarker for NPC for WHO type 2 and 3 tumours even in non-endemic regions.

Epstein-Barr virus-associated acute pancreatitis: a clinical report and review of literature

BackgroundAcute pancreatitis is a disorder of reversible inflammation of the pancreas. Only a few cases are related to infections and the most common pathogens are the viruses responsible for mumps, parotitis, and influenza. Epstein-Barr virus (EBV)-associated acute pancreatitis is a rare condition and it may occur in children and adults.Case presentationA 3-year-old female was admitted to the “G. Di Cristina” Children's Hospital in Palermo for vomiting and abdominal pain. Laboratory investigations revealed elevated amylase and lipase, with normal liver function tests. Abdominal ultrasound demonstrated an enlarged pancreas, with hypoechogenic areas; no biliary lithiasis was observed. Infectious disease serology was positive for the presence of EBV VCA IgM and IgG. A diagnosis of EBV-associated acute pancreatitis was made. The patient was treated conservatively and recovered.ConclusionsAcute pancreatitis is rarely associated with EBV infection; a review of the English literature revealed only 10 pediatric and 6 adult cases. Patients with pancreatitis should always be evaluated for EBV serology, even in the absence of the typical clinical and hematological features of infectious mononucleosis. For these patients, good prognosis is generally expected.

Declining Epstein-Barr Virus Antibody Prevalence in College Freshmen Strengthens the Rationale for a Prophylactic EBV Vaccine

Background: To better understand the epidemiology of primary Epstein-Barr virus (EBV) infection and to identify EBV-naïve candidates eligible to receive a prophylactic EBV vaccine, we screened freshmen from the University of Minnesota Class of 2025 for circulating EBV antibody, which is indicative of previous infection. This permitted us to compare their EBV antibody prevalence with that of 4 other freshman classes (Classes of 2010, 2011, 2016, 2021) that have been previously published. Methods: Freshman students were recruited during screening sessions in the residence halls. Venous blood was collected and the serum fraction tested for IgG antibody against EBV viral capsid antigen (VCA IgG) using commercial enzyme immunoassays. Results: All classes combined, 1196 participants were tested (female, 677; male, 513; did not identify gender, 6) who were 18–23 years old (median, 18; mean, 18.37). The EBV VCA IgG antibody prevalence was 58% (689/1196) and was higher in women than men. The EBV antibody prevalence of 64% (170/267) in the 2010 freshman class versus 52% (78/150) in the Class of 2025 was statistically significantly different (p = 0.0223, Fisher exact test).” Conclusions: Sufficient participants are available for a prophylactic vaccine trial. Antibody prevalence decreased over 15 years from 64% to 52%. If this trend continues, the number of EBV-naïve adolescents and young adults who are in the age group most susceptible to infectious mononucleosis will increase, strengthening the rationale to develop an effective prophylactic EBV vaccine.

Application of magnetic immunofluorescence assay based on microfluidic technology to detection of Epstein-Barr virus

EB病毒(Epstein-Barr virus, EBV)的早期诊断能够降低患者发生重大疾病的风险。临床上常用的EBV抗体的检测方法存在耗时长、试剂消耗大和效率低等缺点。相比于传统的检测方法,微流控(microfluidics)技术具有高通量、试剂消耗少,污染少和自动化程度高等优点,磁免疫荧光技术具有检测效率高、信号强等优点,将两者的优势结合,能够弥补传统方法的不足。鉴于此,采用聚甲基丙烯酸甲酯(PMMA)作为芯片原材料,经过激光切割及真空热压加工工艺能够快速获得芯片。将包被抗原的磁珠及包被抗人抗体的荧光微球经过冷冻干燥工艺快速冻干成小球并嵌入芯片内,经过孵育和清洗后,进行检测。通过图像分析快速得到检测结果。通过精密度、特异性、剂量-反应曲线及检出限测试,进行性能验证。通过与化学发光免疫分析法(CLIA)检测的临床样本比对,进行方法学与临床应用评价。结果显示相对标准偏差(RSD)均小于10%。与多种常见的病原体抗体均无交叉反应。EB病毒衣壳抗原(Epstein-Barr viral capsid antigen, EB VCA)IgG项目的检出限为1.92 U/mL,线性范围为1.92~200 U/mL,阳性符合率为95.77%(68/71),阴性符合率为86%(43/50); EB VCA IgA项目的检出限为2.79 U/mL,线性范围为2.79~200 U/mL,阳性符合率为92%(46/50),阴性符合率为92.96%(66/71); EB病毒核心抗原1(Epstein-Barr nuclear antigen 1, EB NA1)IgG项目的检出限为3.13 U/mL,线性范围为3.13~200 U/mL,阳性符合率为92.96%(66/71),阴性符合率为92%(46/50); EB NA1 IgA项目的检出限为1.53 U/mL,线性范围为1.53~200 U/mL,阳性符合率为90%(45/50),阴性符合率为91.55%(65/71)。4个项目能在20 min内快速完成检测,且与临床上使用CLIA方法测试的结果具有良好的相关性,可以为临床提供一种快速、灵敏、简便、自动化程度高和易于基层推广的检测方法。

An Unusual Presentation of Glandular Fever

Epstein-Barr virus (EBV) is an ubiquitous DNA herpesvirus with >90% of adults >40 years of age showing a serological response. While in their youth, primary EBV infection may pass unnoticed, young adults have a high incidence of infectious mononucleosis (IM). This is characterized by a triad of pharyngitis, cervical lymphadenopathy, and fever because of a self-limiting lymphoproliferative disease. Common complications include but are not limited to hepatitis, splenomegaly, encephalitis, and haemophagocytic lymphohistiocytosis (HLH) with evidence that Caucasian males and smokers are more likely to suffer severe disease. Here we present a 21-year-old male who presented with a 2-week history of fever, dry cough, and a 4-week history of pharyngitis. He had no exposure to unwell contacts and denied any new sexual partners. Examination revealed general pallor with tender bilateral cervical lymphadenopathy and pharyngeal erythema. Admission bloods revealed pancytopenia (WCC 1.5 × 109/L, Plt 84 × 109/L, and Hb 82 g/L) with normal reticulocyte count and raised mean corpuscular volume (114 fL). Serum vitamin B12 and folate were low with serum ferritin raised (1027 µg/L) suggesting a proinflammatory state. Admission liver function tests, coeliac serology, autoimmune panel (ANA, ANCA, and anti-dsDNA), hepatitic (hepatitis A, B, and E), human immunodeficiency virus (HIV), toxoplasmosis, parvovirus, and CMV serology were normal. The monospot test on day 1 of the presentation was negative. Ultrasound (US) of the abdomen on day 3 of the presentation revealed isolated splenomegaly (16.8 cm). Day 4 EBV serology (VCA IgM, VCA IgG, and EBNA IgG) was negative as such haematological investigations including JAK2, serum free light chains, and BCR-ABL were undertaken alongside cervical lymph node core biopsy. Repeat Monospot testing on day 7 came back positive. Repeat EBV serology now showed equivocal EBV VCA IgG (0.77 OD) and positive VCA IgM (9.04 OD) with concurrent new hepatitis. Histopathology of the core biopsy revealed Sternberg-reed cells and a mixed immunoblastic reaction in keeping with resolving IM. This case highlights the need for physicians to have a strong clinical suspicion of IM and understand the multiple ways in which IM may be present as well as the time lag to positivity in serological testing.

S2703 A Rare Case of EBV Reactivation in an Immunocompetent Patient

Introduction: Hepatic involvement during an active primary Epstein-Barr virus (EBV) infection often results in mild, self-resolving elevation of transaminases and is associated with infectious mononucleosis (IM). EBV rarely reactivates, and most cases occur in immunocompromised individuals. We present a rare case of EBV reactivation in an immunocompetent patient only presenting with cholestatic liver injury. Case Description/Methods: A 19-year-old female with a history of resolved EBV IM one year prior presented with dark urine and jaundice. She had no fever, abdominal pain, nausea, vomiting, weight changes or night sweats. She had no history of illicit drug, tobacco or alcohol use, recent travel, or sick contacts. Her medications were loratadine and an OCP;she denied use of acetaminophen or herbal supplements. Family history was unrevealing. On exam she was jaundiced but otherwise normal. Initial laboratory tests showed AST 97 U/L, ALT 75 U/L, ALP 165 U/L, T-BILI 8.1 mg/dL, D-BILI 5.7 mg/dL. CT abdomen revealed splenomegaly. Work up revealed ASMA titer (1:40), but otherwise negative/ normal ANA, IgG, AMA, HCV Ab, HBV serologies, HAV IgM, CMV PCR, iron studies, tick borne serologies, SARS CoV-2 PCR, A1AT and ceruloplasmin. On the second day, the T-BILI peaked to 12.4 mg/dL, AST 151 U/L, ALT 131 U/L, ALP 237 U/L. (Fig.1) EBV serologies were positive (EBV VCA IgG >750.0 U/ml, EBV VCA IgM >160.0 U/ml), EBV viral load of 23,500 copy/ ml and negative monospot test. On day four, the LFTs improved and she was discharged. One month later LFTs had normalized, and she was asymptomatic. Discussion: EBV reactivation causing cholestatic liver injury is extremely rare in immunocompetent individuals. Furthermore, EBV-induced hepatitis is usually associated with IM but our patient's sole complaint was jaundice and dark urine. Interestingly, she had mononucleosis due to EBV one year prior with unremarkable LFTs. The fact that the hepatitis was caused by the reactivation of the virus instead of a primary infection may be the reason for lack of other symptoms. It is unclear whether EBV reactivation increases the risk of hepatitis. The diagnosis can be made without a liver biopsy if thorough work up for hepatitis is negative and the EBV serologies are positive. The disease is often self-limited and the use of antivirals is controversial and thus there is no clear indication. Our case demonstrates that EBV reactivation presenting without the 'classic' IM symptoms may be under-recognized as a cause of cholestatic liver injury. (Figure Presented).

Клинический случай и литературный обзор патогенетических аспектов комбинированной инфекции вируса Эпштейна — Барр и кандидоза полости рта

Актуальность. Лечение пациентов с рецидивирующей инфекцией, которая устойчива к традиционной терапии, является сложной клинической задачей в педиатрии. Цель работы: проанализировать существующую литературу о клинических особенностях кандидоза полости рта и инфекционного мононуклеоза. Материалы и методы. Представлен случай комбинированной вирусной инфекции Эпштейна — Барр в форме инфекционного мононуклеоза и кандидоза ротовой полости рта у 4-летнего мальчика. Результаты. Исследована бактериальная флора горла и рта, в культурах из горла были изолированы Str.viridans 103 КОЕ/мл, S.aureus 105 КОЕ/мл, Candida albicans 106 КОЕ/мл. Иммуноферментный анализ показал, что индекс антител EBV VCA IgM составлял 2,63 (более 0,8 — положительный результат). Выводы. При инфекционном мононуклеозе в сочетании с кандидозом полости рта наблюдаются следующие общие симптомы: длительная лихорадка, лимфаденопатия и синдром экзантемы. Обычно они возникают после приема антибактериальных средств широкого спектра действия. В случае заболевания с такими симптомами, как длительная лихорадка, лимфаденопатия, тонзиллит и синдром экзантемы, которые являются общими для кандидоза полости рта и инфекционного мононуклеоза, требуется дифференциальная диагностика. Необходимо изучить микробиоту ротоглотки у пациентов с инфекционным мононуклеозом для выявления флоры, которая может обусловливать осложненное течение заболевания и трудности диагностики. В таком случае данный вид исследования является важным диагностическим методом обнаружения кандидоза.

Performance of Plasma HSP90α, Serum EBV VCA IgA Antibody and Plasma EBV DNA for the Diagnosis and Prognosis Prediction of Nasopharyngeal Carcinoma.

ObjectiveThe aim of this study was to evaluate the effectiveness of Epstein–Barr virus (EBV) VCA-IgA antibody, EBV DNA and HSP90α alone or in combinations for the diagnosis and prognostic prediction of nasopharyngeal carcinoma (NPC).MethodsA total of 113 treatment-naïve patients with NPC and 40 healthy controls were enrolled. Plasma HSP90α and serum EBV VCA IgA antibody were detected using ELISA, and plasma EBV DNA was quantified using qPCR assay. The effectiveness of plasma HSP90α level, serum EBV VCA IgA antibody and plasma EBV DNA was examined in the diagnosis and prognosis prediction of NPC.ResultsHigher plasma HSP90α, serum EBV VCA IgA antibody and plasma viral load of EBV DNA were detected in NPC patients than in healthy controls (P < 0.001). The plasma HSP90α levels, serum EBV VCA IgA antibody titers and plasma viral load of EBV DNA were significantly greater in NPC patients with stages III and IV than in those with stages I and II (P < 0.001), and significantly lower plasma HSP90α levels, serum EBV VCA IgA antibody titers and plasma viral load of EBV DNA were found in the good prognosis group than in the poor prognosis group post-treatment (P < 0.05). The area under representative operating curves (AUCs) of plasma HSP90α, serum EBV VCA IgA antibody and plasma EBV DNA alone and in combination were 0.884, 0.841, 0.934 and 0.954 for the diagnosis of NPC, respectively. Univariate and multivariate Cox proportional hazards regression analyses identified HSP90α as an independent prognostic factor for NPC.ConclusionThe combination of plasma HSP90α, serum EBV VCA IgA antibody and plasma EBV DNA shows high diagnostic performance for NPC, and plasma HSP90α may be a potential marker for diagnosis and prognosis prediction of NPC.

Analytical performance evaluation of the Elecsys Epstein-Barr virus immunoassay panel

We evaluated the analytical performance of the Elecsys® Epstein-Barr virus (EBV) immunoassay panel for the in vitro detection of EBV immunoglobulin M (IgM), EBV viral capsid antigen immunoglobulin G (VCA IgG), and EBV nuclear antigen immunoglobulin G (EBNA IgG). Relative sensitivity/specificity were assessed using 1,734 human blood samples (1,068 residual samples from routine EBV testing; 467 presumed acute infection; 199 presumed seronegative) tested with the Elecsys EBV and 2 comparator panels (ARCHITECT EBV; Liaison EBV). EBV infection status was defined by majority approach. The three panels demonstrated comparable relative sensitivities/specificities, ranging between values (%) of 98.3−99.5 / 96.9−97.4 (EBV IgM); 96.3−98.4 / 98.4−98.7 (EBV VCA IgG); and 98.1−99.5 / 99.1−99.5 (EBV EBNA IgG). The Elecsys EBV IgM assay demonstrated superior analytical specificity in samples containing potential interferents. Utilizing the Elecsys EBV panel for the EBNA-first approach showed 97.5% overall agreement versus the majority approach in samples with clear EBV status.

Lower CMV and EBV Exposure in Children With Kawasaki Disease Suggests an Under-Challenged Immune System.

Background: Kawasaki Disease (KD) is a pediatric vasculitis of which the pathogenesis is unclear. The hypothesis is that genetically pre-disposed children develop KD when they encounter a pathogen which remains most often unidentified or pathogen derived factors. Since age is a dominant factor, prior immune status in children could influence their reactivity and hence the acquisition of KD. We hypothesized that systemic immune responses early in life could protect against developing KD. With this study we tested whether the incidence of previous systemic cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection is lower in children with KD compared to healthy age-matched controls.Methods and Results: We compared 86 KD patients with an age-matched control group regarding CMV and EBV VCA IgG measurements (taken before or 9 months after IVIG treatment). We found that both CMV and EBV had an almost 2-fold lower seroprevalence in the KD population than in the control group.Conclusions: We suggest that an under-challenged immune system causes an altered immune reactivity which may affect the response to a pathological trigger causing KD in susceptible children.

The positivity rate of Epstein-Barr virus anti-viral capsid antigen IgG among children with infectious mononucleosis in Diyala-Iraq

Background: Epstein-Barr virus (EBV) is a double-stranded linear DNA human herpesvirus that is transmitted primarily through saliva during childhood. Although the majority of primary EBV infections are clinically asymptomatic, clinical cases are presented as infectious mononucleosis (IMN) syndrome. Objectives: This study was conducted to explore the rate of EBV anti-VCA IgG among children who were clinically suspected as having IMN in Diyala province. Subjects and methods: This is a cross sectional study that was carried out during 2018 in Diyala province- Iraq. A total of 370 blood samples were collected from 190 children under 15 years of age who were clinically suspected as having IMN, and 180 apparently healthy children as controls. The anti EBV VCA IgG antibodies were detected in serum using the VCA IgG ELISA kit (from Dia.Pro Diagnostic Bioprobes srl - Italy). Statistical analysis was carried out using the SPSS- version 25. A statistical significance was considered whenever the P value was ≤ 0.05. Results: The results showed that the IgG positivity rate among suspected IMN patients was insignificantly higher in the age group 10-14 years old children (80.8%, P = 0.364). In control subjects the highest positivity rate was in the age group of 1-4 years with a statistically significant difference (79.5%, P = 0.002). In suspected IMN patients, the age group of 10-14 years had the highest mean concentration ± SD of anti-VCA IgG (44.018 ± 38.644 arbitrary units per milliliter (arbU/ml)), while in controls, the highest value (38.018 ± 34.908 arbU/ml) was in the age group of 1-4 years, with insignificant difference in either group (P = 0.257 and 0.072, respectively). The results also showed that in both suspected IMN patients and control subjects, females showed higher IgG positivity rate (70.6%, and 75.5%) compared to males (64.8%, and 65.1%) with insignificant difference in both groups (P = 0.392 and 0.126, respectively). Similarly, the IgG mean concentration ± SD was insignificantly higher in females in both suspected IMN patients and control subjects (P = 0.447 and 0.256, respectively). 21 (87.5%) IgM positive suspected IMN patients were also IgG positive with a statistically significant association (P = 0.028). Conclusion: The positivity rate of anti-EBV VCA IgG among apparently healthy subjects in Diyala province was 70.6%, and the rate increases with age, with slight association with clinical suspicion of infectious mononucleosis.

Evaluation of Clinical and Laboratory Data of Pediatric Patients Diagnosed with Infectious Mononucleosis

Aim: In childhood, infectious mononucleosis cases caused by Epstein-Barr virus (EBV) are seen with high frequency. The signs and symptoms of acute EBV infection can manifest with different clinical pictures. Care should be taken in differential diagnosis for correct treatment. In our study, it was aimed to examine the clinical presentation of acute EBV infections by age and high-risk age groups among children. Patients and Methods: A total of 337 pediatric patients with infectious mononucleosis who applied to our tertiary hospital in 2013-2020 were included in the study. EBV VCA IgM and IgG antibodies were studied by ELISA method (quantitative microplate ELISA, Euroimmun®, Germany) in accordance with company recommendations. Patient information and results were evaluated retrospectively. Results: The mean age of the patients was 5.1 ± 3.4 years. 22.8% of the patients were in the group of 0-2, 43.0% of them were 3-5, 29.7% of them were 6-12, and 4.5% of them were 12 years old and above. The most common signs or symptoms in children diagnosed with acute EBV infection were lymphadenopathy (59.6%), lymphocytosis (45.1%), fever (40.9%), swelling in the throat (39.2%) and pharyngitis (30.0%). Fever complaints were significantly higher between the ages of 3-5 compared to other age groups. The seasonal distribution of the cases was similar. It was determined that the cases increased over the years and the most cases were seen in 2019 (23.4%). It was observed that the time between the start of complaints and the application to the hospital increased directly proportional to age groups. Conclusion: In our study, it was concluded that there was no difference in acute EBV infection in childhood age groups in terms of signs and symptoms, and the number of cases increased slightly over the years, especially in children with lymphadenopathy, splenomegaly and hepatomegaly.

Non-invasive detection of IgG antibodies from common pathogenic viruses using oral flocked swabs

Salivary antibodies are useful in surveillance and vaccination studies. However, low antibody levels and degradation by endonucleases are problematic. Oral flocked swabs are a potential non-invasive alternative for detecting viral antibodies. Seroprevalence for Cytomegalovirus (CMV), Varicella-Zoster virus (VZV), Epstein–Barr virus (EBV), Measles and Mumps IgG antibodies were determined from 50 matched serum, saliva and swabs samples from healthy volunteers using commercial ELISAs. CMV IgG, VZV IgG, and EBV EBNA-1 IgG, VCA IgG, and Measles IgG swab versus serum sensitivities were 95.8%, 96.0%, 92.1%, 95.5%, 84.5%, respectively, and swabs correlated well with saliva. Sensitivity of Mumps IgG in swabs and saliva was poor at 60.5%, and 68.2%, respectively. Specificities for IgG antibodies were 100% for CMV, EBV and Mumps, but could not be determined for VZV and Measles due to exclusively seropositive volunteers. Except for Mumps IgG, swabs correlate well with serum, are easy to self-collect and are stable at room temperature.

The Positivity Rate of Epstein-Barr Virus Anti-Viral Capsid Antigen IgG among Children with Infectious Mononucleosis in Diyala-Iraq

Background: Epstein-Barr virus (EBV) is a double-stranded linear DNA human herpesvirus that is transmitted primarily through saliva during childhood. Although the majority of primary EBV infections are clinically asymptomatic, clinical cases are presented as infectious mononucleosis (IMN) syndrome. Objectives: This study was conducted to explore the rate of EBV anti-VCA IgG among children who were clinically suspected as having IMNin Diyala province. Subjects and Methods: This is a cross sectional study that was carried out during 2018 in Diyala province-Iraq. A total of 370 blood samples were collected from 190 children under 15 years of age who were clinically suspected as having IMN, and 180 apparently healthy children as controls. The anti EBV VCA IgG antibodies were detected in serum using the VCA IgG ELISA kit (from Dia.Pro Diagnostic Bioprobessrl-Italy). Statistical analysis was carried out using the SPSS-version 25. A statistical significance was considered whenever the P value was ≤ 0.05. Results: The results showed that the IgG positivity rate among suspected IMN patients was insignificantly higher in the age group 10 - 14 years old children (80.8%, P = 0.364). In control subjects the highest positivity rate was in the age group of 1 - 4 years with a statistically significant difference (79.5%, P = 0.002). In suspected IMN patients, the age group of 10 - 14 years had the highest mean concentration ± SD of anti-VCA IgG 44.018 ± 38.644 arbitrary units per milliliter (arbU/ml), while in controls, the highest value 38.018 ± 34.908 (arbU/ml) was in the age group of 1 - 4 years, with insignificant difference in either group (P = 0.257 and 0.072, respectively). The results also showed that in both suspected IMN patients and control subjects, females showed higher IgG positivity rate (70.6%, and 75.5%) compared to males (64.8%, and 65.1%) with insignificant difference in both groups (P = 0.392 and 0.126) respectively. Similarly, the IgG mean concentration ± SD was insignificantly higher in females in both suspected IMN patients and control subjects (P = 0.447 and 0.256) respectively. 21 (87.5%) of IgM positive suspected IMN patients were also IgG positive with a statistically significant association (P = 0.028). Conclusion: The positivity rate of anti-EBV VCA IgG among apparently healthy subjects in Diyala province was 70.6%, which increases by age with slight association with clinical suspicion of infectious mononucleosis.

2325 Severe Cholestatic Hepatitis: An Atypical Presentation of Epstein-Barr Virus Infection

INTRODUCTION: Infectious mononucleosis (IM) is a benign lymphoproliferative disease caused by Epstein-Barr Virus (EBV). In adults, EBV infection can cause an acute hepatitis with elevation of transaminases, usually resolving spontaneously. We report a rare case of a severe cholestatic hepatitis following an acute EBV infection. CASE DESCRIPTION/METHODS: A 24-year-old previously healthy Caucasian woman presented with fever, body aches, headache, odynophagia and dry cough for 5 days. Initially CBC was normal but she had significant liver test abnormalities: aspartate transaminase (AST) 723 IU/L, alanine transaminase (ALT) 647 IU/L, alkaline phosphatase (ALP) 708 IU/L, and normal total bilirubin (TB) 1.2 mg/dl (Figure 1). Patient took acetaminophen (&lt;2 g/day) at home for fever for 5 days. She had no prior history of hepatitis, blood transfusions, intravenous drug use, high-risk sexual activity, or significant alcohol use. Monospot test was positive. Chest x-ray showed left lower lobe pneumonia, azithromycin was prescribed for 5 days. The fever subsided, but she became jaundiced (TB 9.2 mg/dl) on day 11 and the patient was admitted. RUQ ultrasound showed no evidence of biliary obstruction, masses or gallstones. CBC showed profound lymphocytosis. Hepatitis A, B, C and E serologies were negative. EBV VCA IgM Ab was positive, CMV and EBV PCR were negative. Autoimmune markers revealed mildly elevated ANA (1:160). Liver biopsy was done revealing sinusoidal lymphocytic infiltration typical of EBV hepatitis (Figure 2). Cholestasis worsened after admission with peak TB of 9.6 mg/dl and ALP 2080 IU/L. Follow-up lab work a month later showed a normal TB with mild elevation of ALP, GGT, AST and ALT. At 4-month follow up, all liver tests normalized with positive EBV serology (VCA IgG and EBNA), which confirmed the patient’s recent EBV infection. DISCUSSION: Acute cholestatic hepatitis is an extremely rare presentation of EBV infection, with few cases reported in the medical literature. To the best of our knowledge, our patient had the highest ALP elevation reported in association with EBV infection. It is essential for physicians to recognize this unusual EBV infection presentation in patients with fever and progressive cholestasis in the absence of biliary obstruction, to avoid prolonged hospitalization and invasive procedures.

The Association between Epstein-Barr virus (EBV) Past Infection with the Risk of Oral Squamous Cell Carcinoma (OSCC)

The association of Epstein-Barr virus (EBV) with oral cancer has been widely reported in the past. However, previous studies mainly focused on the current infection of EBV without acknowledging the possibility of past infection in patients which may lead to oral cancer development. The present study aims to investigate the correlation between past EBV infections with Oral Squamous Cell Carcinoma (OSCC). Both Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibodies against EBV were screened to detect the presence of EBV in sera of OSCC patients using Enzyme-Linked Immunosorbent Assay (ELISA). The use of IgM antibody against EBV confirms current infection in patients, whereas IgG antibody would predict past infection throughout patients’ lifetime. Through the present study, we would be able to confirm whether patients with past EBV infection have a significant risk in developing oral cancer. ELISA tests were carried out to detect the presence of EBV IgG and IgM in 206 OSCC and control serum samples. Statistical analysis was performed using SPSS 12.0.1. Our results had shown that 96.6% (n = 199) of OSCC samples and 97.2% (n = 130) control were positive with EBV VCA IgG, however, none of the OSCC and control samples was positive for EBV VCA IgM. The presence of EBV VCA IgG in both OSCC and control suggest that past EBV infection does not play a significant role as a risk indicator for OSCC. Therefore, the association between EBV and OSCC was not well demonstrated in this study.