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.