Nyt fra tidsskrifterne

by Arthur Daniel Rocha Alves, Jéssica Vasques Raposo, Rafaela Moraes Pereira de Sousa, Claudete Aparecida Araújo Cardoso, Pâmela Karla Simões de Freitas Costa, Julienne Martins Araújo, Sabrina Teresinha Alvim Barreiro, Clarisse da Silveira Bressan, Guilherme Amaral Calvet, Rogério Valls de Souza, Patrícia Brasil, Rita de Cássia Nasser Cubel Garcia, Marcelo Alves Pinto, Vanessa Salete de Paula, Luciane Almeida Amado

Introduction A wide variety of viruses can cause rash diseases (RDs) or acute febrile illness (AFIs) in children, adolescents and adults; however, approximately 19% of RD cases and 40% of AFI cases remain without a defined etiology. Parvovirus B19 (B19V) and herpesvirus infection can also cause RD and/or AFI, and in some risk groups, these infections can become persistent (or latent) and may require hospital treatment. Since these infections do not have mandatory reporting, they can be hidden by other diseases, such as those caused by arboviruses (e.g., dengue virus). In this context, the aim of this study was to pursue the differential laboratory diagnoses of B19V and herpesvirus infections in patients with RD and AFI, without a defined etiology, seen in hospitals and/or reference centers for infectious diseases in Rio de Janeiro. Methods A total of 114 participants were enrolled in the study, including 54 children and 60 adults. B19V infection was assessed by real-time PCR (qPCR) and ELISA (anti-B19V IgM and IgG). EBV was assessed through qPCR, and betaherpesviruses (HCMV, HHV-6 and HHV-7) were assessed through multiplex qPCR. Sociodemographic and clinical data were obtained from the medical record data of these participants. Results The median age of children with RD was 2 years (interquartile range (IQR): 5), and 55.6% were male. Among adults with AFI, the median age was 38 years (IQR: 21), and 56.7% were female. Regarding RD patients, viral prevalence (and load) were 5.5%(104IU/mL), 3.4%(104IU/mL), 5.5%(104IU/mL) and 11.1%(105IU/mL) for B19V, EBV, HCMV and HHV-6 infection, respectively, and in AFI patients they were 6.6%(105IU/mL), 1.6%(103IU/mL), 3.3%(104IU/mL) for B19V, HCMV and HHV-6, respectively. HHV-7 was not detected in RD or AFI patients. Conclusion These results suggest the importance of including B19V and herpesviruses in the differential laboratory diagnoses for patients with RD and AFI, not only for epidemiological purposes but also for the proper management of the patient.…

Journal of Medical Virology, Accepted Article.

The diffusion of the SARS-CoV-2 delta (B.1.617.2) variant and the waning of immune response after primary Covid-19 vaccination favoured the breakthrough SARS-CoV-2 infections in vaccinated subjects. To assess the impact of vaccination, we determined the severity of infection in hospitalised patients according to vaccine status.

Emergency departments (EDs) were on the front line for the diagnostic workup of patients with COVID-19 like symptoms during the first wave. Chest imaging was the key to rapidly identifying COVID-19 before administering RT-PCR which was time-consuming.The objective of our study was to compare the costs and organizational benefits of triage strategies in ED during the first wave of the COVID-19 pandemic.

AbstractHPV-related oropharyngeal cancer (OPC) incidence is increasing among men. Biomarkers that can identify oral HPV 16/18 infections likely to persist, the obligate precursor for HPV-OPC, are needed. Control of oral co-infections, including Epstein-Barr virus (EBV), could serve as a biomarker of immune competence and the ability to control oral HPV. We assessed the association between oral EBV and oral HPV 16/18 persistence among 63 men in the HIM Study who tested HPV16/18 positive. Detection of oral EBV was significantly associated with oral HPV 16/18 ≥ 12-month persistence and deserves evaluation as a biomarker for oral HPV persistence and related OPC.

Nature Medicine, Published online: 19 May 2022; doi:10.1038/d41591-022-00061-9Nanoparticle vaccines show promise in preclinical models; clinical evaluation is warranted to assess whether they could help reduce the burden of disease associated with EBV in humans.

Background:

There is a need for a specific atherosclerotic risk assessment for people living with HIV (PLWH).

Setting:

A machine learning classification model was applied to PLWH and control subjects with low-to-intermediate cardiovascular risks to identify associative predictors of diagnosed carotid artery plaques. Associations with plaques were made using strain elastography in normal sections of the common carotid artery (CCA) and traditional cardiovascular risk factors.

Methods:

One hundred and two PLWH and 84 control subjects were recruited from the prospective Canadian HIV and Aging Cohort Study (57±8 years; 159 men). Plaque presence was based on clinical ultrasound scans of left and right CCA and internal carotid arteries (ICA). A classification task for identifying subjects with plaque was defined using random forests and logistic regression models. Receiver operating characteristic curves (AUC-ROC) were applied to select 5 among 50 combinations of 4 or less features yielding the highest AUC-ROCs.

Results:

To retrospectively classify individuals with and without plaques, the 5 most discriminant combinations of features had AUC-ROCs between 0.76 and 0.79. AUC-ROCs from random forests were statistically significantly higher than those obtained with logistic regressions (p=0.0001). The most discriminant features of random forests classifications in PLWH were age, smoking status, maximum axial strain and pulse pressure (equal weights), and sex and antiretroviral therapy exposure (equal weights). When considering the whole population, the HIV status was identified as a co-factor associated with carotid artery plaques.

Conclusion:

Strain elastography adds to traditional cardiovascular risk factors for identifying individuals with carotid artery plaques.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

The microbiological anorectal cure rate was significantly lower among women who received a single dose of azithromycin than among those who received a 1-week course of doxycycline. This finding suggests that doxycycline should be the first-line therapy for C trachomatis infection in women.

Nature Medicine, Published online: 05 May 2022; doi:10.1038/s41591-022-01785-4A comparison of Sars-Cov-2 vaccine platforms: the CoviCompare project…

by Jonathan Poh, Kao Chin Ngeow, Michelle Pek, Kian-Hin Tan, Jing Shan Lim, Hao Chen, Choon Kiat Ong, Jing Quan Lim, Soon Thye Lim, Chwee Ming Lim, Boon Cher Goh, Yukti Choudhury

Next-generation sequencing of circulating tumor DNA presents a promising approach to cancer diagnostics, complementing conventional tissue-based diagnostic testing by enabling minimally invasive serial testing and broad genomic coverage through a simple blood draw to maximize therapeutic benefit to patients. LiquidHALLMARK® is an amplicon-based next-generation sequencing assay developed for the genomic profiling of plasma-derived cell-free DNA (cfDNA). The comprehensive 80-gene panel profiles point mutations, insertions/deletions, copy number alterations, and gene fusions, and further detects oncogenic viruses (Epstein-Barr virus (EBV) and hepatitis B virus (HBV)) and microsatellite instability (MSI). Here, the analytical and clinical validation of the assay is reported. Analytical validation using reference genetic materials demonstrated a sensitivity of 99.38% for point mutations and 95.83% for insertions/deletions at 0.1% variant allele frequency (VAF), and a sensitivity of 91.67% for gene fusions at 0.5% VAF. In non-cancer samples, a high specificity (≥99.9999% per-base) was observed. The limit of detection for copy number alterations, EBV, HBV, and MSI were also empirically determined. Orthogonal comparison of epidermal growth factor receptor (EGFR) variant calls made by LiquidHALLMARK and a reference allele-specific polymerase chain reaction (AS-PCR) method for 355 lung cancer specimens revealed an overall concordance of 93.80%, while external validation with cobas® EGFR Mutation Test v2 for 50 lung cancer specimens demonstrated an overall concordance of 84.00%, with a 100% concordance rate for EGFR variants above 0.4% VAF. Clinical application of LiquidHALLMARK in 1,592 consecutive patients demonstrated a high detection rate (74.8% circulating tumor DNA (ctDNA)-positive in cancer samples) and broad actionability (50.0% of cancer samples harboring alterations with biological evidence for actionability). Among ctDNA-positive lung cancers, 72.5% harbored at least one biomarker with a guideline-approved drug indication. These results establish the high sensitivity, specificity, accuracy, and precision of the LiquidHALLMARK assay and supports its clinical application for blood-based genomic testing.

Science Advances, <a href='https://www.science.org/toc/sciadv/8/17'>Volume 8, Issue 17</a>, April 2022. …

Nature Reviews Microbiology, Published online: 26 April 2022; doi:10.1038/s41579-022-00741-wAn in vitro study shows that the nuclear lamina regulates Epstein–Barr virus latency and viral gene expression.

by Mai Abdel Haleem Abusalah, Ahmad Adebayo Irekeola, Rafidah Hanim Shueb, Mu’taman Jarrar, Chan Yean Yean

Background The EBV-associated epithelial tumours consist 80% of all EBV-associated cancer, where the nasopharyngeal cancer (NPC) and EBV-associated gastric carcinoma (EBVaGC) are considered as the most frequent EBV-associated epithelial tumours. It has been shown that the BART-encoded miRNAs are abundantly expressed in EBV-associated epithelial tumours, hence, these miRNAs may serve as diagnostic and prognostic biomarkers for EBV-associated epithelial tumours. Therefore, the purpose of this systematic review and meta-analysis is to assess these EBV miRNAs as prognostic biomarkers for NPC and GC. Method This systematic review was developed based on PRISMA guidelines and utilizing PubMed, Web of Science, Scopus, Cochrane, and Google scholar databases. The retrieved articles were thoroughly screened in accordance with the selection criteria. The hazard ratio (HR) and 95% confidence interval (CI) for patient survival outcomes were used to evaluate EBV miRNA expression levels. To assess the risk of bias, funnel plot symmetry and Egger’s bias test were employed. Result Eleven studies met the selection criteria for inclusion, and four were included in the meta-analysis. Most of the articles considered in this study were from China, with one study from South Korea. The overall pooled effect size estimation (HR) for upregulated EBV miRNAs was 3.168 (95% CI: 2.020–4.969), demonstrating that upregulated EBV miRNA expression enhanced the mortality risk in NPC and GC patients by three times. Conclusion To the best of our knowledge, this is the first meta-analysis that investigates the significance of EBV miRNAs as prognostic biomarkers in NPC and GC patients. The pooled effect estimates of HR of the various studies revealed that higher EBV miRNA expression in NPC and GC may result in a worse survival outcome. To assess the clinical significance of EBV miRNAs as prognostic biomarkers, larger-scale prospective studies are needed.…

Journal of Medical Virology, Accepted Article.

Objective:

Widespread use of the measles vaccine should lead to the elimination of this disease. Here we study the seroprevalence of measles in a cohort of adults living with HIV born after the introduction of measles vaccine in France and attempt to identify risk factors for the absence of serum measles antibody.

Design:

In this multicenter cross-sectional study, adult outpatients born after 1980 were screened for the presence of measles IgG antibody. Demographic and clinical data were obtained from the standardised electronic medical record system. Univariate and multivariate logistic regressions were performed to identify factors associated with the absence of measles antibodies.

Results:

Between April 2019 and April 2020, 648 participants were enrolled. The median age was 33 years, 53.6% were born outside of France, and 74% were considered as socially deprived. Plasma HIV RNA was undetectable in 86% of patients. Among 603 evaluable patients, measles serology was positive in 87.2%. Only 81.8% of the patients with documented vaccination tested positive for measles IgG. Younger age was significantly associated with the absence of measles serum antibodies (P = 0.004 for each 10-year lower), as was birth in France (P …

Abstract

Background

Epstein-Barr virus (EBV) infects more than 90% of the population worldwide. However, chronic active EBV infection (CAEBV) is one of the EBV-positive T- or NK-lymphoproliferative diseases with high morbidity and mortality. Here, we report a case of a 9-year girl with CAEBV, successively presenting with polymyositis and coronary artery dilation (CAD).

Case presentation

The girl complained of fatigue for more than 1 month. Muscle strength examinations had no abnormal findings. Blood chemistries showed elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK). Magnetic resonance imaging (MRI) showed spotty high-intensity signals in thigh muscles, and electromyogram suggested myogenic damage. The significant findings were positive EBV antibodies (EBVEA-IgG, EBVCA-IgG, and EBVNA-IgG), increased EBV DNA copies in B, T, and NK cells, and positive EBV-encoded small RNA in biopsy muscle specimen. The girl received ganciclovir, intravenous immunoglobulin, and methylprednisolone, and her symptoms improved. On the 45th day of hospitalization, echocardiograph revealed CAD. She received additional anticoagulants and Tocilizumab. Her condition improved and continued to be followed up at the clinic preparing for hematopoietic stem cell transplantation.

Conclusions

This is the first reported case of CAEBV successively with polymyositis and CAD. This case makes the diagnoses of autoimmune diseases in children more complicated. Careful investigation of hidden CAEBV should be recommended in children with atypical polymyositis or CAD.

…

Abstract

Background

Epstein-Barr virus (EBV) infects more than 90% of the population worldwide. However, chronic active EBV infection (CAEBV) is one of the EBV-positive T- or NK-lymphoproliferative diseases with high morbidity and mortality. Here, we report a case of a 9-year girl with CAEBV, successively presenting with polymyositis and coronary artery dilation (CAD).

Case presentation

The girl complained of fatigue for more than 1 month. Muscle strength examinations had no abnormal findings. Blood chemistries showed elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK). Magnetic resonance imaging (MRI) showed spotty high-intensity signals in thigh muscles, and electromyogram suggested myogenic damage. The significant findings were positive EBV antibodies (EBVEA-IgG, EBVCA-IgG, and EBVNA-IgG), increased EBV DNA copies in B, T, and NK cells, and positive EBV-encoded small RNA in biopsy muscle specimen. The girl received ganciclovir, intravenous immunoglobulin, and methylprednisolone, and her symptoms improved. On the 45th day of hospitalization, echocardiograph revealed CAD. She received additional anticoagulants and Tocilizumab. Her condition improved and continued to be followed up at the clinic preparing for hematopoietic stem cell transplantation.

Conclusions

This is the first reported case of CAEBV successively with polymyositis and CAD. This case makes the diagnoses of autoimmune diseases in children more complicated. Careful investigation of hidden CAEBV should be recommended in children with atypical polymyositis or CAD.

…

AbstractBackgroundHIV-exposed, uninfected (HEU) children have a higher risk of severe infection than HIV-unexposed children, though the causes are poorly understood. Emerging data point to altered antibody transfer in women with HIV (WHIV), however, specific perturbations and the influence of ART and viremia remain unclear.MethodsWe evaluated antigen-specific transplacental antibody transfer across 14 antigens in paired maternal and umbilical cord plasma from 352 Ugandan women; 176 were WHIV taking ART. We measured antigen-specific IgG subclass (IgG1, 2, 3, 4) levels and antibody Fcγ receptor (FcγRn, 2a, 2b, 3a, 3b) binding profiles. We used Partial Least Squares Discriminant Analysis to define antigen-specific transplacental antibody transfer features.ResultsGlobal antibody transfer patterns were similar by maternal HIV serostatus, pointing to effective placental function in WHIV on ART. However, HEU umbilical cord antibody profiles were altered, driven by perturbed maternal seroprofiles. WHIV and paired HIV-exposed umbilical cord plasma had higher levels of chronic herpesvirus antibodies (P<0.01 for EBV, HSV) and lower levels of classic vaccine-induced antibodies (P<0.01 for tetanus, polio, HiB), suggesting that umbilical cord antibody profile differences arise from imbalanced WHIV immunity. Multivariate regression analysis demonstrated abnormal WHIV antibody profiles were associated with HIV viremia, lower CD4 count and post-conception ART initiation (P=0.01).ConclusionsPreserved placental antibody transfer and perturbed immune-dominance profiles in WHIV shift the balance of immunity delivered to neonates, pointing to HIV-associated changes in maternal antibody profiles as a key determinant of compromised neonatal immunity. Maternal vaccination interventions may promote transfer of relevant, effective antibodies to protect HEU children against early-life infections.

Abstract

Background

Infectious mononucleosis, a common disease in children and young adults, is often accompanied by elevated transaminase levels and rarely, liver failure. This study aimed to determine whether adenosine deaminase is a marker of severity in children with infectious mononucleosis, especially those with elevated alanine transaminase levels.

Methods

This case-control study was conducted at the Children’s Hospital of Soochow University. A total of 104 children with infectious mononucleosis and 50 controls with other acute infections and fever, tonsillitis, or lymphadenitis, were enrolled in the study. Among the 104 children with infectious mononucleosis, 54 had normal alanine transaminase levels and 50 had elevated alanine transaminase levels. The children’s clinical and laboratory data were analyzed to assess the diagnostic value of adenosine deaminase in the three groups.

Results

The adenosine deaminase level in the infectious mononucleosis group was significantly higher than that in the control group (P < 0.001). The adenosine deaminase levels were highly correlated with lymphocyte count, CD3+CD8+ T cells (%), CD4+/CD8+ ratio, and CD3−CD19+ (%) (r > 0.7, P < 0.01). The sensitivity and specificity of adenosine deaminase in predicting children with infectious mononucleosis were 97.1% and 94.0%, respectively. Furthermore, multivariate regression analysis revealed that adenosine deaminase level was a risk factor for elevated alanine transaminase in children with infectious mononucleosis.

Conclusions

Adenosine deaminase may be a marker of the severity of infectious mononucleosis in children, and a predictor of elevated alanine transaminase in children with infectious mononucleosis.

…

Abstract

Background

Infectious mononucleosis, a common disease in children and young adults, is often accompanied by elevated transaminase levels and rarely, liver failure. This study aimed to determine whether adenosine deaminase is a marker of severity in children with infectious mononucleosis, especially those with elevated alanine transaminase levels.

Methods

This case-control study was conducted at the Children’s Hospital of Soochow University. A total of 104 children with infectious mononucleosis and 50 controls with other acute infections and fever, tonsillitis, or lymphadenitis, were enrolled in the study. Among the 104 children with infectious mononucleosis, 54 had normal alanine transaminase levels and 50 had elevated alanine transaminase levels. The children’s clinical and laboratory data were analyzed to assess the diagnostic value of adenosine deaminase in the three groups.

Results

The adenosine deaminase level in the infectious mononucleosis group was significantly higher than that in the control group (P < 0.001). The adenosine deaminase levels were highly correlated with lymphocyte count, CD3+CD8+ T cells (%), CD4+/CD8+ ratio, and CD3−CD19+ (%) (r > 0.7, P < 0.01). The sensitivity and specificity of adenosine deaminase in predicting children with infectious mononucleosis were 97.1% and 94.0%, respectively. Furthermore, multivariate regression analysis revealed that adenosine deaminase level was a risk factor for elevated alanine transaminase in children with infectious mononucleosis.

Conclusions

Adenosine deaminase may be a marker of the severity of infectious mononucleosis in children, and a predictor of elevated alanine transaminase in children with infectious mononucleosis.

…

by Marine Ballutaud, Morgane Travers-Trolet, Paul Marchal, Stanislas F. Dubois, Carolina Giraldo, Andrew C. Parnell, M. Teresa Nuche-Pascual, Sébastien Lefebvre

Stable isotope ratios are used to reconstruct animal diet in trophic ecology via mixing models. Several assumptions of stable isotope mixing models are critical, i.e., constant trophic discrimination factor and isotopic equilibrium between the consumer and its diet. The isotopic turnover rate (λ and its counterpart the half-life) affects the dynamics of isotopic incorporation for an organism and the isotopic equilibrium assumption: λ involves a time lag between the real assimilated diet and the diet estimated by mixing models at the individual scale. Current stable isotope mixing model studies consider neither this time lag nor even the dynamics of isotopic ratios in general. We developed a mechanistic framework using a dynamic mixing model (DMM) to assess the contribution of λ to the dynamics of isotopic incorporation and to estimate the bias induced by neglecting the time lag in diet reconstruction in conventional static mixing models (SMMs). The DMM includes isotope dynamics of sources (denoted δs), λ and frequency of diet-switch (ω). The results showed a significant bias generated by the SMM compared to the DMM (up to 50% of differences). This bias can be strongly reduced in SMMs by averaging the isotopic variations of the food sources over a time window equal to twice the isotopic half-life. However, the bias will persist (∼15%) for intermediate values of the ω/λ ratio. The inferences generated using a case study highlighted that DMM enhanced estimates of consumer’s diet, and this could avoid misinterpretation in ecosystem functioning, food-web structure analysis and underlying biological processes.

Nature Reviews Microbiology, Published online: 02 February 2022; doi:10.1038/s41579-022-00701-4Two recent papers implicate Epstein–Barr virus (EBV) as a trigger for the development of multiple sclerosis and provide mechanistic insights into EBV-mediated development of the disease.

Antimicrobial Agents and Chemotherapy, <a href='https://journals.asm.org/toc/aac/0/ja'>Volume 0, Issue ja</a>, -Not available-. …

Abstract

Background

Acute fibrinous and organizing pneumonia (AFOP) is a rare lung condition that is associated with acute lung injury. Its etiology may be idiopathic or secondary to a series of conditions, including immune-related diseases, unclassified connective tissue diseases, hematopoietic stem cell transplantation, infections, hematological diseases and drug induced lung toxicity. We report for the first time a case of AFOP complicated with hemophagocytic lymphohistiocytosis (HLH) caused by chronic active Epstein-Barr virus (CAEBV) infection.

Case presentation

A 64-year-old man was admitted with a complaint of fever and dyspnea for 2 weeks. The patient presented with elevated serum aminotransferase levels, splenomegaly, progressive decrease of red blood cells and platelets, hyperferritinemia, hypofibrinogenemia, and elevated of Soluble interleukin-2 receptor (sCD25). His chest computed tomography (CT) scan revealed multiple patchy consolidation in both lungs and multiple lymphadenopathy in the mediastinum and hilum. The serology for antibodies of VCA-IgG was positive, EBV-DNA in peripheral blood was elevated, and EBV nucleic acid was detected in the alveolar lavage fluid. Histopathology of the lung tissue showed a dominant of intra-alveolar fibrin and organizing pneumonia. Hemophagocytic cells was found in the bone marrow smear and biopsy. EBV-DNA was detected in lung tissue and bone marrow using in situ hybridization with an EBV-encoded RNA (EBER) probe. After 50 days of hospitalization, he was improved in lung and hemogram.

Conclusion

We report a case of AFOP with HLH caused by CAEBV in an immunocompetent adult, suggesting that AFOP may be a rare but serious complication caused by CAEBV, and glucocorticoid therapy may improve short-term prognosis.

Journal of Medical Virology, Accepted Article.

Malaria parasites replicate within the liver shortly after infection. This stage can be controlled by CD8 T cells, but which subsets undertake this function is unclear. Lefebvre et al. now elegantly show that effector memory T (TEM) cells are avid participants, working as a dynamic duo with liver tissue-resident memory T (TRM) cells to combat infection.

Purpose of review

Management of Epstein–Barr virus posttransplant lymphoproliferative disorder (EBV PTLD) is complex, involving risk stratification, prevention and/or preemptive measures involving monitoring EBV DNAemia and balancing treatment options, using a combination of reduction of immune suppression, anti-B cell therapy, and cytotoxic T lymphocytes (CTLs).

Recent findings

The highest risk factor for the development of EBV PTLD in hematopoietic cell transplant (HCT) remains T cell depletion, with increasing use of antithymocyte globulin (ATG) or alemtuzumab in conditioning. In solid organ transplantation (SOT), the incidence of PTLD is highest among EBV seronegative recipients who are at risk for primary EBV infection following transplant in the first 12 months. Prevention is a critical component of the management of EBV PTLD. Although preemptive therapy remains standard of care, there continues to be heterogenicity and debate over the optimal choice of EBV DNA quantification and the threshold to use. Novel therapies such as donor-derived multipathogen and EBV specific CTLs for the prevention and third party CTLs for the treatment of EBV PTLD are promising, with rapidly expanding evidence, including large scale Phase III trials currently underway.

Summary

With an increasing number of risk groups for developing EBV PTLD in HCT and SOT, management strategies using prophylaxis or preemptive therapy remain standard of care, however the use of prophylactic or preemptive EBV specific or multipathogen CTLs show promising results and safety profiles.

Journal of Medical Virology, Accepted Article.

AbstractBackgroundThe arrival of highly effective, well-tolerated, direct-acting antiviral agents (DAA) led to a dramatic decrease in hepatitis C virus (HCV) prevalence. Human immunodeficiency virus (HIV)-HCV–coinfected patients are deemed a priority population for HCV elimination, while a rise in recently acquired HCV infections in men who have sex with men (MSM) has been described. We describe the variations in HIV-HCV epidemiology in the French Dat’AIDS cohort.MethodsThis was a retrospective analysis of a prospective cohort of persons living with HIV (PLWH) from 2012 to 2018. We determined HCV prevalence, HCV incidence, proportion of viremic patients, treatment uptake, and mortality rate in the full cohort and by HIV risk factors.ResultsFrom 2012 to 2018, 50 861 PLWH with a known HCV status were followed up. During the period, HCV prevalence decreased from 15.4% to 13.5%. HCV prevalence among new HIV cases increased from 1.9% to 3.5% in MSM but remained stable in other groups. Recently acquired HCV incidence increased from 0.36/100 person-years to 1.25/100 person-years in MSM. The proportion of viremic patients decreased from 67.0% to 8.9%. MSM became the first group of viremic patients in 2018 (37.9%). Recently acquired hepatitis represented 59.2% of viremic MSM in 2018. DAA treatment uptake increased from 11.4% to 61.5%. More treatments were initiated in MSM in 2018 (41.2%) than in intravenous drug users (35.6%). In MSM, treatment at the acute phase represented 30.0% of treatments in 2018.ConclusionsA major shift in HCV epidemiology was observed in PLWH in France from 2012 to 2018, leading to a unique situation in which the major group of HCV transmission in 2018 was MSM.Clinical Trials Registration. NCT02898987.

We are writing this Comment out of concern over the alarming number of publications describing endotracheal tube occlusions in patients with COVID-19 receiving mechanical ventilation.1–3 This potentially fatal complication had become rare, but high rates of occlusions (up to 72%) have been described in patients with COVID-19.4 This increase in prevalence has prompted questionable recommendations, such as the systematic change of endotracheal tubes every week in this patient group,2 or the routine use of tube cleaning devices.

Author Summary. We utilized a virome-wide protein array to better understand whether (1) different segments of a given Epstein-Barr virus (EBV) protein and/or (2) different variants of select EBV protein sequences (i.e., amino acid changes in a protein segment) elicited differential IgG antibody reactivity in health adults. We posited that this approach would help identify EBV protein regionss containing immunodominant epitopes for eliciting antibody mediated B-cell immunity. Using this approach, we identified eight EBV proteins with at least one sequence associated with differential IgG antibody response, including three proteins with segments that were differentially reactive (BALF5, LMP1, LMP2A), and five proteins with specific amino acid changes that altered IgG antibody response (BLF4, EBNA3A, EBNA3B, EBNA-LP, LF1) in two independent populations.

Antimicrobial Agents and Chemotherapy, <a href="https://journals.asm.org/toc/aac/0/ja">Volume 0, Issue ja</a>, -Not available-.

Abstract

Background

Our goal is to further elucidate the clinical condition and prognosis of patients with severe acute COVID-19 with EBV reactivation.

Method

This is a retrospective single-center study of COVID-19 patients admitted to the intensive care unit of Wuhan No. 3 Hospital (January 31 to March 27, 2020). According to whether Epstein-Barr virus reactivation was detected, the patients were divided into an EBV group and a Non-EBV group. Baseline data were collected including epidemiological, larithmics, clinical and imaging characteristics, and laboratory examination data.

Results

Of the 128 patients with COVID-19, 17 (13.3%) were infected with Epstein-Barr virus reactivation. In the symptoms,the rate of tachypnoea in the EBV group was apparently higher than that in the Non-EBV group. In lab tests, the lymphocyte and albumin of EBV group decreased more significantly than Non-EBV group, and the D-dimer and serum calcium of EBV group was higher than Non-EBV group. Regarding the infection index, CRP of EBV group was apparently above the Non-EBV group, and no significant difference was found in procalcitonin of the two groups. The incidence of respiratory failure, ARDS, and hypoproteinaemia of EBV group had more incidence than Non-EBV group. The 28-day and 14-day mortality rates of EBV group was significantly higher than that of Non-EBV group.

Conclusions

In the COVID-19 patients, patients with EBV reactivation had higher 28-day and 14-day mortality rates and received more immuno-supportive treatment than patients of Non-EBV group.

Immune checkpoint blockade using programed cell death 1 (PD-1) antibody is an effective approach to enhance T cell activity against cancers, while it is an emerging cause of hemophagocytic lymphohistiocytosis (HLH)[1]. Recent studies report that PD-1 antibody nivolumab could cure Epstein-Barr virus-associated HLH (EBV-HLH) by restoring the defective anti-EBV response without severe adverse events[2,3]. Herein, we report on a pediatric patient with relapsed/refractory (r/r) EBV-HLH who developed fulminant cytokine release syndrome after receiving nivolumab treatment.

Introduction

Acute viral hepatitis is a disease of great clinical importance. This study proposes actions to better characterise cases of acute hepatitis in Brazil and to provide relevant information to institutionalised health policies within the Unified Health System. Available data on acute hepatitis in Brazil need to be re-evaluated regarding the different hepatotropic agent (hepatitis A to E virus) frequencies, as well as other agents that can cause similar clinical conditions, such as Herpes Simplex Virus 1 and 2(HSV1, HSV2), Varicella Zoster Virus (VZV), Cytomegalovirus (CMV), Epstein Barr Virus (EBV), Human Herpes Virus 6 and 7 (HHV6, HHV7), arbovirus (yellow fever, dengue, chikungunya, Zika), parvovirus B19, adenovirus, parechovirus, enterovirus, HIV, leptospirosis, toxoplasmosis and syphilis, in addition to autoimmune hepatitis. In this context, the primary aim of this study is the clinical-epidemiological and molecular characterisation of acute viral hepatitis in Brazilian health services from all geographical regions of the country. The present article describes the study protocol.

Methods and analysis

This study will evaluate 2280 patients with symptoms and/or signs suggestive of acute liver disease in Brazilian health institutions in all five geographic Brazilian regions. Demographic, epidemiological and clinical data will be collected, as well as blood samples to be analysed at Hospital Israelita Albert Einstein Clinical Laboratory.

Ethics and dissemination

Ethics approval was obtained at the national research ethics committee (Conselho Nacional de Ética em Pesquisa— CONEP–CAAE 00952818.4.1001.0071) and at all participating sites. Results will be published in journals and presented at scientific meetings.

Journal of Medical Virology, Accepted Article.

by Shams Rahman, Deanna Wathington, Tim Waterboer, Michael Pawlita, Luisa L. Villa, Eduardo Lazcano-Ponce, Martina Willhauck-Fleckenstein, Nicole Brenner, Anna R. Giuliano

Objectives To estimate the seroprevalence of Chlamydia trachomatis (CT), herpes simplex type-2 (HSV2), hepatitis C (HCV), Epstein-Barr virus (EBV) and nine human papilloma virus (HPV) types, and investigated factors associated with the seropositivity among men from three countries (Brazil, Mexico and U.S).

Methods Archived serum specimens collected at enrollment for n = 600 men were tested for antibodies against CT, HSV2, HCV, EBV, and 9-valent HPV vaccine types (6/11/16/18/31/33/45/52/58) using multiplex serologic assays. Socio-demographic, lifestyle and sexual behavior data at enrollment were collected through a questionnaire.

Results Overall, 39.3% of the men were seropositive for CT, 25.4% for HSV2, 1.3% for HCV, 97.3% for EBV, 14.0% for at least one of the seven oncogenic HPV (types: 16/18/31/33/45/52/58), and 17.4% for HPV 6/11. In the unadjusted models, age, race, smoking, sexual behavior variables, and seropositivity for high-risk HPV were significantly associated with the seropositivity for CT. In multivariable analyses, self-reported black race, higher numbers of lifetime female/male sexual partners, current smoking, and seropositivity to high-risk HPV were significantly associated with increased odds of CT seropositivity. Odds of HSV2 seroprevalence were elevated among older men and those seropositive for high risk HPV.

Conclusion Exposure to STIs is common among men. Prevention and screening programs should target high-risk groups to reduce the disease burden among men, and to interrupt the disease transmission to sexual partners.

Clinical & Experimental Immunology, Accepted Article.

Background.

Persistent inflammation in HIV infection is associated with elevated cardiovascular disease risk, even with viral suppression. Identification of novel surrogate biomarkers can enhance cardiovascular disease risk stratification and suggest novel therapies. We investigated the potential of IL-32, a proinflammatory multi-isoform cytokine, as a biomarker for subclinical carotid artery atherosclerosis in virologically-suppressed women living with HIV (WLWH).

Methods and Results.

Nested within the Women’s Interagency HIV Study (WIHS), we conducted a cross-sectional comparison of IL-32 between 399 WLWH and 100 women without HIV, followed by a case-control study of 72 WLWH (36 carotid artery plaque cases vs. 36 age-matched controls without plaque). Plasma IL-32 protein was measured by ELISA, and mRNA of IL-32 isoforms (IL-32α, β, γ, D, ε, θ) was quantified by RT-PCR from peripheral blood mononuclear cells (PBMCs). Plasma IL-32 protein levels were higher in WLWH compared to women without HIV (p=0.02). Among WLWH, while plasma IL-32 levels did not differ significantly between plaque cases and controls, expression of IL-32 isoforms α, β and ε mRNA was significantly higher in PBMCs from cases (p=0.01, p=0.005, and p=0.018, respectively). Upregulation of IL-32β and IL-32ε among WLWH with carotid artery plaque persisted after adjustment for age, race/ethnicity, smoking, systolic blood pressure, body mass index, and history of hepatitis C virus (p=0.04 and p=0.045); the adjusted association for IL-32α was marginally significant (p=0.07).

Conclusion.

IL-32 isoforms should be studied further as potential cardiovascular disease biomarkers. This is of particular interest in WLWH by virtue of altered IL-32 levels in this population.

Correspondence : Cécile L. Tremblay, MD, FRCPC, Département de Microbiologie, Immunologie et Infectiologie, Université de Montréal, Centre Hospitalier de l’Université de Montréal, 1000, rue Saint-Denis, Montréal (Québec) H2X 0C1, Tel: +1-514-890-8148, FAX: +1-514-412-7234, 10.1097/QAI.0000000000002746, Email: c.tremblay@umontreal.ca

# Equal contribution.

The authors report no conflicts of interest related to this work.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Journal of Medical Virology, Volume 93, Issue 6, Page 3824-3834, June 2021.