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Epstein–Barr virus (EBV) is a well-known risk factor for the development of nasopharyngeal carcinoma, Hodgkin's lymphoma (HL), and Non-Hodgkin's lymphoma (NHL). People with HIV infection (PWH) are at increased risk for EBV-associated malignancies such as HL and NHL. Nevertheless, there are limited data on the burden of EBV among this population group in Ethiopia. Hence, this study aimed to determine the burden of EBV infection among adult HIV-positive individuals in Ethiopia and assess the determinants of EBV DNA positivity. We conducted a cross-sectional study at the Tikur Anbessa Specialised Hospital from March 2020 to March 2021. Two hundred and sixty individuals were enrolled in this study, including 179 HIV-positive and 81 HIV-negative individuals. A structured questionnaire was used to capture demographic and individual attributes. In addition, the clinical data of patients were also retrieved from clinical records. EBV viral capsid antigen (VCA) IgG antibody was measured by multiplex flow immunoassay, and EBV DNA levels were tested by quantitative real-time polymerase chain reaction (q-PCR) assays targeting the EBNA-1 open reading frame (ORF). Descriptive statistics were conducted to assess each study variable. A multivariable logistic regression model was applied to evaluate the determinants of EBV infection. Statistical significance was determined at a p-value < 0.05. Two hundred and fifty-three (97.7%) study participants were seropositive for the EBV VCA IgG antibody. Disaggregated by HIV status, 99.4% of HIV-positive and 93.8% of HIV-negative participants were EBV seropositive. In this study, 49.7% of HIV-positive and 24.7% of HIV-negative individuals were EBV DNA positive. PWH had a higher risk of EBV DNA positivity at 3.05 times (AOR: 3.05, 95% CI: 1.40–6.67). Moreover, among PWH, those with an HIV viral load greater than 1000 RNA copies/mL (AOR = 5.81, 95% CI = 1.40, 24.13) had a higher likelihood of EBV DNA positivity. The prevalence of EBV among PWH was significantly higher than among HIV-negative individuals. Higher HIV viral loads in PWH were associated with an increased risk of EBV DNA positivity. Since the increases in the viral load of EBV DNA among PWH could be related to the risk of developing EBV-associated cancers, it is necessary for more research on the role of EBV in EBV-associated cancer in this population group to be carried out. [ABSTRACT FROM AUTHOR]

Background: Epstein–Barr virus (EBV) seronegative solid organ transplant recipients (SOTRs) are at increased risk for post‐transplant lymphoproliferative disorder (PTLD). Assays for EBV serostatus assess antibody to both EBV viral capsid antigen (VCA) and Epstein–Barr nuclear antigen‐1 (EBNA‐1), but PTLD risk among SOT recipients with discordant VCA and EBNA‐1 results is unknown. Methods: We performed a retrospective, single‐center cohort study to determine the risk of PTLD among adult (≥ 18 years) SOTRs with discordant pre‐transplant VCA and EBNA‐1 IgG compared to that of SOTRs with concordantly negative or concordantly positive serology using univariable and multivariable Cox‐proportional hazards models. Results: Of 4106 SOTRs, the number (%) who were concordantly positive, concordantly negative, and discordant was 3787 (92.2%), 149 (3.6%), and 170 (4.2%), respectively. The adjusted hazard of PTLD was significantly higher among discordant SOTRs compared to concordantly positive SOTRs (aHR 2.6, 95% CI 1.04–6.6, p =.04) and lower compared to concordantly negative SOTRs (aHR 0.27, 95% CI 0.10–0.76, p <.001). The adjusted hazard of EBV+ PTLD among those with discordant serology was also significantly higher compared to the concordantly positive cohort (aHR 3.53, 95% CI 1.04–12.0, p =.04) and significantly lower compared to the concordantly negative cohort (aHR 0.23, 95% CI 0.06–0.82, p =.02). Conclusions: Risk of PTLD among SOTRs with discordant VCA and EBNA‐1 may be intermediate between those with concordantly positive and negative serology. If confirmed in future studies, revision of national EBV serology reporting to include both VCA and EBNA results may be needed to optimize PTLD risk stratification. [ABSTRACT FROM AUTHOR]

Epstein–Barr virus (EBV) is a well-known risk factor for the development of nasopharyngeal carcinoma, Hodgkin’s lymphoma (HL), and Non-Hodgkin’s lymphoma (NHL). People with HIV infection (PWH) are at increased risk for EBV-associated malignancies such as HL and NHL. Nevertheless, there are limited data on the burden of EBV among this population group in Ethiopia. Hence, this study aimed to determine the burden of EBV infection among adult HIV-positive individuals in Ethiopia and assess the determinants of EBV DNA positivity. We conducted a cross-sectional study at the Tikur Anbessa Specialised Hospital from March 2020 to March 2021. Two hundred and sixty individuals were enrolled in this study, including 179 HIV-positive and 81 HIV-negative individuals. A structured questionnaire was used to capture demographic and individual attributes. In addition, the clinical data of patients were also retrieved from clinical records. EBV viral capsid antigen (VCA) IgG antibody was measured by multiplex flow immunoassay, and EBV DNA levels were tested by quantitative real-time polymerase chain reaction (q-PCR) assays targeting the EBNA-1 open reading frame (ORF). Descriptive statistics were conducted to assess each study variable. A multivariable logistic regression model was applied to evaluate the determinants of EBV infection. Statistical significance was determined at a p-value < 0.05. Two hundred and fifty-three (97.7%) study participants were seropositive for the EBV VCA IgG antibody. Disaggregated by HIV status, 99.4% of HIV-positive and 93.8% of HIV-negative participants were EBV seropositive. In this study, 49.7% of HIV-positive and 24.7% of HIV-negative individuals were EBV DNA positive. PWH had a higher risk of EBV DNA positivity at 3.05 times (AOR: 3.05, 95% CI: 1.40–6.67). Moreover, among PWH, those with an HIV viral load greater than 1000 RNA copies/mL (AOR = 5.81, 95% CI = 1.40, 24.13) had a higher likelihood of EBV DNA positivity. The prevalence of EBV among PWH was significantly higher than among HIV-negative individuals. Higher HIV viral loads in PWH were associated with an increased risk of EBV DNA positivity. Since the increases in the viral load of EBV DNA among PWH could be related to the risk of developing EBV-associated cancers, it is necessary for more research on the role of EBV in EBV-associated cancer in this population group to be carried out.

Epstein-Barr virus ( EBV) is closely associated with nasopharyngeal carcinoma ( NPC). Serum IgA antibodies against early antigen ( EA-IgA) and viral capsid antigen ( VCA-IgA) are the most commonly used to screen for NPC in endemic areas. However, the prognostic value of serum EA-IgA and VCA-IgA in patients with NPC is less clear. We hypothesize that serum EA-IgA and VCA-IgA levels have prognostic impact for survival outcomes in NPC patients with undetectable pretreatment EBV ( pEBV) DNA. In this series, 334 patients with non-metastatic NPC and undetectable pEBV DNA were included. Serum EA-IgA and VCA-IgA were determined by ELISA. After analysis, serum EA-IgA and VCA-IgA loads correlated positively with T, N, and overall stage (all P < 0.05). Serum EA-IgA was not associated with survival outcome in univariable analyses. But patients with serum VCA-IgA >1:120 had significantly inferior 5-year progression-free survival (80.4% vs 89.6%, P = 0.025), distant metastasis-free survival (88.4% vs 94.8%, P = 0.050), and locoregional relapse-free survival (88.4% vs 95.6%, P = 0.023; log-rank test). Multivariable analyses revealed that N stage was the only independent prognostic factor (all P < 0.05), but the VCA-IgA became insignificant. Further analyses revealed that serum VCA-IgA was not an independent prognostic factor in early N (N0-1) or advanced N (N2-3) stage NPC. In summary, although both EA-IgA and VCA-IgA correlate strongly with TNM stage, our analyses do not suggest that these antibodies are prognostic biomarkers in patients with NPC and undetectable pEBV DNA. [ABSTRACT FROM AUTHOR]

Objectives This study was designed to establish an ELISA method, as well as the cut-off value, for IgA against Epstein-Barr virus (EBV) viral capsid antigen (VCA), as a screening assay for nasopharyngeal carcinoma (NPC) in southern China. In addition, the correlation between relative optical density (rOD) values from ELISA and titers from the immunoenzymatic assay (IEA) was also evaluated. Methods Two hundred and fifty-eight NPC cases, 33 non-NPC head and neck cancer patients, and 1156 healthy controls were recruited for this study. VCA-IgA and early antigen (EA)-IgA were measured by ELISA kits and IEA in parallel. Results The total precision of the VCA-IgA ELISA achieved a level of <13.0% coefficient of variation. An rOD value of 1.60 for the VCA-IgA ELISA was determined as the cut-off point for southern China, and the sensitivity and specificity for NPC diagnosis when using this cut-off value were 93.0% and 92.4%, respectively. The area under the receiver operating characteristic curve (ROC-AUC) value was 0.969. The correlation coefficient between titers and rOD values was 0.957. rOD values were correlated with NPC overall stage and lymph node involvement. Conclusions The cut-off level established in our study could be used to facilitate more accurate diagnosis of NPC in southern China. The rOD value might be an index for NPC prognosis, since it shows a good correlation with the titer from IEA. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system. Many diseases are associated with Epstein-Barr virus (EBV) infection, such as infectious mononucleosis and many types of malignancies, and it is thought to be related to some diseases of autoimmune origin, such as rheumatoid arthritis, systemic lupus erythematosis, and others. The present study aimed to assess EBV in patients with MS.This case-control study was conducted from October 2012 to September 2013 on 75 MS patients and non-MS controls. Both were tested quantitatively for immunoglobulin G (IgG) antibodies against Epstein-Barr nuclear antigen-1 (EBNA1) and viral capsid antigen (VCA) using the enzyme linked immunosorbent assay technique.Seventy MS patients (93.3%) were positive for EBNA1 IgG compared with 68 controls (90.7%). In MS patients, the mean EBNA1 IgG serum level was 310.91 (±131.05) U/ml; meanwhile, among controls the mean serum EBNA IgG level was 177.81 (±104.98) U/ml.All patients with MS were positive for VCA IgG, whereas only 60 (80.0%) controls were positive. In the MS group, the VCA IgG mean level was 302.19 (±152.11) U/ml compared with 167.94 (±111.79) U/ml in controls. The differences in the serum levels of both markers between the two groups were statistically significant (P<0.001).EBV proved to have a unique immunological pattern in MS patients when compared with non-MS controls. Further studies for more confirmation of the relation between EBV and MS on a large scale are recommended. [ABSTRACT FROM AUTHOR]

[Objective] To explore inhibiting effect of 12 heat-clearing and detoxicating drugs originated in Guangdong on the expression of EBV viral capsid antigen in cells in vitro and the cytotoxic effect of which on B95-8 cell. [Methods] Study the inhibiting effect of 12 traditional Chinese medicines on the expression of capsid antigen in B95-8 cell by indirect immunoenzyme technique Observe the cytotoxic effect of tradition- al Chinese medicines on B95-8 cell cultured under stimulating circumstances by trypan blue exclusion test. [Results] The expression of VCA in B95-8 cells cultured under stimulating circumstances could be significantly inhibited by 12 heat-clearing and detoxicating drugs originated in Guangdong. Most of the medicines were dose-dependent. The dose of corresponding drug increased 1000 times, the 12 traditional Chinese medicines had significant cytotoxic effect on B95-8 cells and their effects were concentration-dependent. [Conclusions] The inhibiting effect of 12 heat-clearing and detoxicating drugs originated in Guangdong on the expression of EBV viral capsid antigen was significant and with high concentrations, they all had cytotoxic effect on B95-8cells. [ABSTRACT FROM AUTHOR]

Abstract: Background: In recent years a number of Epstein–Barr virus (EBV) proteins were defined as being immunodominant for either IgM, IgG or IgA immune responses, yielding promising markers for diagnostic serology. Specific reactivity patterns to these proteins have been described for infectious mononucleosis (IM), nasopharyngeal carcinoma (NPC), various types of lymphoma, and healthy EBV carriers. Objectives: To compare the NPC-related diagnostic value of EBV RecombLine test (Mikrogen, Germany) with a standardized immunoblot assay [Fachiroh J, Schouten T, Hariwiyanto B, Paramita DK, Harijadi A, Haryana SM, et al. Molecular diversity of Epstein–Barr virus IgG and IgA antibody responses in nasopharyngeal carcinoma: a comparison of Indonesian, Chinese, and European subjects. J Infect Dis 2004;190:53–62] and to define the diagnostic value of individual EBV marker proteins in a population with high incidence of NPC. Result: Sera from Indonesian NPC patients taken at primary diagnosis (n =108) were analyzed for IgG and IgA reactivity and compared with regional healthy blood donors (n =62), non-NPC patient controls (n =10) and IM patients (n =10). Most NPC patients and controls showed strong IgG reactivity to VCA-p18, -p23, and EBNA1, limiting their diagnostic use. Few (<20%) healthy donors and patient controls showed IgG reactivity to EA proteins p47/54 and p138, yielding combined sensitivity/specificity and PPV/NPV values of 92.6%/98.3% and 99.0%/88.1%, for diagnosing NPC. NPC sera showed significantly more EBV reactive IgA antibody (>80% positive) than controls (<10% positive), although being less broadly reactive and significantly less strong compared to IgG. For IgA best results were observed for RecombLine EBNA1 with sensitivity/specificity and PPV/NPV values of 92%/89% and 93.4%/85.9%, respectively. Conclusion: In high incidence NPC regions with low incidence IM yet high prevalence of EBV infection, both RecombLine IgG and IgA tests provide a useful alternative to the more complex cell-extract based immunoblot assay as confirmation test for NPC diagnosis in particular when using EA and EBNA1 as discriminators in IgG and IgA testing, respectively. [Copyright &y& Elsevier]

Epstein–Barr virus (EBV) is the causative agent of infectious mononucleosis and some malignancies including EBV-associated-lymphomas. A large portion of adults all over the world are infected with EBV. In children, however, there are geographic variations. Most of the children in Asia and in other developing countries are infected in their early life, before 1 year of age (>90% of 5–9-year-old children are infected), while the age of primary infection is delayed in Western countries (approx. 50% of 5–9-year-old children are infected). The purpose of the present paper was to investigate the recent time trend of the EBV seropositivity among 5–7-year-old children living in Tokyo and its neighboring prefectures. Indirect immunofluorescein study for IgG antibody to viral capsid antigen was performed on 442 archival sera. Before the early 1990s, >80% of 5–7-year-old children were found to be seropositive, while the positivity rate decreased to 59% ( P < 0.001) for the years 1995–1999. These results also showed that the delay in the age of primary infection is continuing and that the rate is estimated to be <50% in 2006. This result suggests that the delay will affect the incidence of EBV-associated disorders in Japan. [ABSTRACT FROM AUTHOR]

Context: Acute undifferentiated febrile illness (AUFI) is characterized by a sudden onset of raised body temperature and is a common cause of hospital admission though not recognized as a disease state by the World Health Organization. Epstein-Barr virus (EBV) is reported to account for a significant occurrence of AUFI cases., Aim: To know the role of EBV infection as a cause of acute undifferentiated febrile illness (AUFI)., Settings and Design: We have used the combination of EBV serological assays to establish the role of the Epstein-Barr virus as the cause of acute undifferentiated febrile illness., Methods and Material: A total of 721 suspected cases of acute undifferentiated febrile illness which were tested negative for other common causes of acute febrile illness were selected for the study. Serum samples collected from these cases were tested for the presence of the EBV viral capsid antigen (VCA) IgM antibody. All positive serum samples were tested for the presence of EBV Epstein-Barr nuclear antigen (EBNA) IgG., Statistical Analysis Used:  Statistical analysis was performed with the help of Microsoft Excel software (Microsoft Corporation, Redmond, USA).  Results: Out of 721 suspected AUFI cases tested for EBV VCA IgM antibodies, 117 samples were positive and 604 were negative. All these 117 samples were tested for EBV EBNA IgG antibodies in which 88 were positive and 29 were negative. In our study, we found that around 4% (positive for VCA IgM and negative for EBNA IgG) of AUFI cases can be attributed to primary acute EBV infection., Conclusions: EBV infection should be considered particularly in AUFI cases of less than five years of age even in those who do not meet the typical presentation of fever, lymphadenopathy and sore throat. Our study should help to raise awareness regarding the possibility of EBV infection particularly in AUFI cases. A high index of suspicion and timely diagnosis will definitely help clinicians to avoid a battery of investigations and misuse of antibiotics in cases of AUFI., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Dhodapkar et al.)