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Sararas Khongwirotphan, Sornjarod Oonsiri, Sarin Kitpanit, Anussara Prayongrat, Danita Kannarunimit, Chakkapong Chakkabat, Chawalit Lertbutsayanukul, Sira Sriswasdi, Yothin Rakvongthai
PLoS One Infectious Diseases, 12.02.2024
Tilføjet 12.02.2024
by Sararas Khongwirotphan, Sornjarod Oonsiri, Sarin Kitpanit, Anussara Prayongrat, Danita Kannarunimit, Chakkapong Chakkabat, Chawalit Lertbutsayanukul, Sira Sriswasdi, Yothin Rakvongthai Background The prognosis of nasopharyngeal carcinoma (NPC) is challenging due to late-stage identification and frequently undetectable Epstein-Barr virus (EBV) DNA. Incorporating radiomic features, which quantify tumor characteristics from imaging, may enhance prognosis assessment. Purpose To investigate the predictive power of radiomic features on overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) in NPC. Materials and methods A retrospective analysis of 183 NPC patients treated with chemoradiotherapy from 2010 to 2019 was conducted. All patients were followed for at least three years. The pretreatment CT images with contrast medium, MR images (T1W and T2W), as well as gross tumor volume (GTV) contours, were used to extract radiomic features using PyRadiomics v.2.0. Robust and efficient radiomic features were chosen using the intraclass correlation test and univariate Cox proportional hazard regression analysis. They were then combined with clinical data including age, gender, tumor stage, and EBV DNA level for prognostic evaluation using Cox proportional hazard regression models with recursive feature elimination (RFE) and were optimized using 20 repetitions of a five-fold cross-validation scheme. Results Integrating radiomics with clinical data significantly enhanced the predictive power, yielding a C-index of 0.788 ± 0.066 to 0.848 ± 0.079 for the combined model versus 0.745 ± 0.082 to 0.766 ± 0.083 for clinical data alone (p
Læs mere Tjek på PubMedMu Liu, Chenxu Huang, Xingchen Zhou, Congwei Jiang, Shuai Liu, Ying Gao, Linlin Kuang, Zhangmengxue Lei, Ran Jia, Jin Xu, Patrick Legembre, Xiaozhen Liang
Journal of Medical Virology, 2.02.2024
Tilføjet 2.02.2024
M. Lefebvre, L. Gross, R. Ollivier, S. Bailly, M. Coste‐Burel, J. Coutherut, J. Dina
Journal of Medical Virology, 19.12.2023
Tilføjet 19.12.2023
Journal of the American Medical Association, 29.11.2023
Tilføjet 29.11.2023
Due to a unique immune substrate consisting of abundant lymphocytic infiltration, high programmed death–ligand 1 (PD-L1) expression, and the presence of several immune targets (CD40, CD70, CD80, and CD86), there is a strong biological rationale for incorporating immunotherapy in the treatment of nasopharyngeal carcinoma (NPC). Nonkeratinizing histological subtypes encompass more than 95% of NPC cases in endemic areas, and NPC is largely linked to Epstein-Barr virus (EBV) infection, providing an additional immune-prone factor through the expression of EBV antigens and CD4+/CD8+ T-cell target proteins. In this issue of JAMA, Mai and colleagues report the prespecified definitive overall survival analysis of the phase 3 JUPITER-02 trial. The addition of the anti–PD-1 antibody toripalimab to platinum-gemcitabine as a first-line treatment for recurrent or metastatic NPC (RM-NPC) proved to reduce by 37% the risk of death at 3 years of follow-up.
Læs mere Tjek på PubMedHaihao Yan, Chenghua Zhu, Xiao Jin, Ganzhu Feng
PLoS One Infectious Diseases, 29.11.2023
Tilføjet 29.11.2023
by Haihao Yan, Chenghua Zhu, Xiao Jin, Ganzhu Feng Background Previous studies have found that the persistence of herpesvirus significantly increases the risk of idiopathic pulmonary fibrosis (IPF), but it is unclear whether this effect is causal. We conducted a two-sample Mendelian randomization (MR) study to evaluate the causal relationship between three herpesvirus infections and IPF. Methods We used genome-wide association studies (GWAS) data from three independent datasets, including FinnGen cohort, Milieu Intérieur cohort, and 23andMe cohort, to screen for instrumental variables (IVs) of herpesvirus infection or herpesvirus-related immunoglobulin G (IgG) levels. Outcome dataset came from the largest meta-analysis of IPF susceptibility currently available. Results In the FinnGen cohort, genetically predicted Epstein-Barr virus (EBV) (OR = 1.105, 95%CI: 0.897–1.149, p = 0.815), cytomegalovirus (CMV) (OR = 1.073, 95%CI: 0.926–1.244, p = 0.302) and herpes simplex (HSV) infection (OR = 0.906, 95%CI: 0.753–1.097, p = 0.298) were not associated with the risk of IPF. In the Milieu Intérieur cohort, we found no correlations between herpesvirus-related IgG EBV nuclear antigen-1 (EBNA1) (OR = 0.968, 95%CI: 0.782–1.198, p = 0.764), EBV viral capsid antigen (VCA) (OR = 1.061, 95CI%: 0.811–1.387, p = 0.665), CMV (OR = 1.108, 95CI%: 0.944–1.314, p = 0.240), HSV-1 (OR = 1.154, 95%CI: 0.684–1.945, p = 0.592) and HSV-2 (OR = 0.915, 95%CI: 0.793–1.056, p = 0.225) and IPF risk. Moreover, in the 23andMe cohort, no evidence of associations between mononucleosis (OR = 1.042, 95%CI: 0.709–1.532, p = 0.832) and cold scores (OR = 0.906, 95%CI: 0.603–1.362, p = 0.635) and IPF were found. Sensitivity analysis confirmed the robustness of our results. Conclusions This study provides preliminary evidence that EBV, CMV, and HSV herpesviruses, and herpesviruses-related IgG levels, are not causally linked to IPF. Further MR analysis will be necessary when stronger instrument variables and GWAS with larger sample sizes become available.
Læs mere Tjek på PubMedBMC Infectious Diseases, 17.11.2023
Tilføjet 17.11.2023
Abstract Purpose Post-COVID-19-Syndrome (PCS) frequently occurs after an infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the understanding of causative mechanisms is still limited. Aim of this study was to determine the PCS rate among SARS-CoV-2 seropositive blood donors as representatives of supposedly healthy adults, who had experienced an asymptomatic or mild COVID-19 disease course, and to examine whether Epstein-Barr virus (EBV) is reactivated in individuals reporting PCS. Methods The PCS rate was determined using questionnaires that included questions about infection and persistent symptoms. Pre-pandemic blood samples and samples collected at regular, pre-defined times after a SARS-CoV-2 infection were analysed for neopterin, a marker for antiviral immune responses, by an enzyme-linked immunosorbent assay (ELISA). Additionally, we determined the rate of SARS-CoV-2 anti-N total antibodies using an electrochemiluminescence immunoassay (ECLIA). Furthermore, quantitative real-time polymerase chain reaction (qPCR) to detect EBV DNA and ECLIA screening for EBV viral capsid-antigen (VCA) IgM, IgG and EBV nuclear antigen 1 (EBNA) IgG were performed. Results Our data reveal that 18% of all infections result in PCS, with symptoms lasting for up to one year. In individuals reporting PCS, no elevated levels of neopterin were detected, indicating no persisting pro-inflammatory, antiviral immune response. SARS-CoV-2 antibody levels were declining in all participants in comparable manner over time, pointing to a successful virus clearance. In individuals with PCS, no EBV DNA could be detected. Furthermore, no differences in EBV specific antibody levels could be shown in PCS groups compared to non-PCS groups. Conclusion Our data suggest that PCS in per se healthy, immunocompetent adults cannot be ascribed to a reactivation of EBV.
Læs mere Tjek på PubMedTrunfio, Mattia; Sacchi, Alessandra; Vai, Daniela; Pittaluga, Fabrizia; Croce, Michele; Cavallo, Rossana; Imperiale, Daniele; Bonora, Stefano; Di Perri, Giovanni; Letendre, Scott Lee; Calcagno, Andrea
AIDS, 15.11.2023
Tilføjet 15.11.2023
Objective: HIV and EBV co-infection has been linked to increased immune activation and larger HIV reservoir. We assessed whether anti-EBV humoral responses are associated with increased cerebrospinal fluid (CSF) inflammation and with neurocognitive impairment (NCI) in people with HIV (PWH). Design: Cross-sectional analysis in 123 EBV-seropositive PWH either on antiretroviral therapy (n = 70) or not. Methods: Serum and CSF anti-EBV Viral Capsid Antigen Immunoglobulin G (anti-EVI) and CSF EBV DNA were measured by commercial immunoassay and RT-PCR. Seventy-eight participants without neurological confounding factors underwent neurocognitive assessment (Global Deficit Score, GDS). CSF total tau and 181-phosphorylated-tau (ptau) were measured by immunoassays together with biomarkers of blood-brain barrier (BBB) integrity, immune activation, astrocytosis, and intrathecal synthesis. Logistic and linear regressions and moderation analysis were used to investigate the relationships between CSF anti-EVI, GDS, and biomarkers. Results: Twenty-one (17.1%) and twenty-two participants (17.9%) had detectable CSF anti-EVI (10.5–416.0 U/mL) and CSF EBV DNA (25–971 cp/mL). After adjusting for BBB integrity, age, and clinical factors, the presence of CSF anti-EVI was only associated with serum levels of anti-EVI, and not with CSF EBV DNA. CSF anti-EVI and tau and ptau showed reciprocal interactions affecting their associations with GDS. After adjusting for demographics and clinical parameters, higher CSF anti-EVI levels were associated with worse GDS (aβ 0.45, p
Læs mere Tjek på PubMedClinical & Experimental Immunology, 13.11.2023
Tilføjet 13.11.2023
AbstractCD8 T cells recognize infected and cancerous cells via their T cell receptor (TCR), which binds peptide-MHC complexes on the target cell. The affinity of the interaction between the TCR and peptide-MHC contributes to the antigen sensitivity, or functional avidity, of the CD8 T cell. In response to peptide-MHC stimulation, the TCR-CD3 complex and CD8 co-receptor are downmodulated. We quantified CD3 and CD8 downmodulation following stimulation of human CD8 T cells with CMV, EBV, and HIV peptides spanning eight MHC restrictions, observing a strong correlation between the levels of CD3 and CD8 downmodulation and functional avidity, regardless of peptide viral origin. In TCR-transduced T cells targeting a tumor-associated antigen, changes in TCR-peptide affinity were sufficient to modify CD3 and CD8 downmodulation. Correlation analysis and generalized linear modelling indicated that CD3 downmodulation was the stronger correlate of avidity. CD3 downmodulation, simply measured using flow cytometry, can be used to identify high-avidity CD8 T cells in a clinical context.
Læs mere Tjek på PubMedRushil Harryparsad, Bahiah Meyer, Ongeziwe Taku, Myrna Serrano, Pai Lien Chen, Xiaoming Gao, Anna-Lise Williamson, Celia Mehou-Loko, Florence Lefebvre d’Hellencourt, Jennifer Smit, Jerome Strauss, Kavita Nanda, Khatija Ahmed, Mags Beksinska, Gregory Buck, Charles Morrison, Jennifer Deese, Lindi Masson
PLoS One Infectious Diseases, 10.11.2023
Tilføjet 10.11.2023
by Rushil Harryparsad, Bahiah Meyer, Ongeziwe Taku, Myrna Serrano, Pai Lien Chen, Xiaoming Gao, Anna-Lise Williamson, Celia Mehou-Loko, Florence Lefebvre d’Hellencourt, Jennifer Smit, Jerome Strauss, Kavita Nanda, Khatija Ahmed, Mags Beksinska, Gregory Buck, Charles Morrison, Jennifer Deese, Lindi Masson Background South Africa is among the countries with the highest prevalence of sexually transmitted infections (STIs), including Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). In 2017, there were an estimated 6 million new CT, 4.5 million NG and 71 000 Treponema pallidum infections among South African men and women of reproductive age. Methods We evaluated STI prevalence and incidence and associated risk factors in 162 women aged 18–33 years old, residing in eThekwini and Tshwane, South Africa who were part of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. Women were randomised to use depot medroxyprogesterone acetate (n = 53), copper intrauterine device (n = 51), or levonorgestrel (n = 58) implant. Lateral vaginal wall swab samples were collected prior to contraceptive initiation and at months one and three following contraceptive initiation for STI testing. Results There were no significant differences in STI incidence and prevalence across contraceptive groups. At baseline, 40% had active STIs (CT, NG, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) or herpes simplex virus-2 shedding across all age groups– 18–21 years (46%), 22–25 years (42%) and 26–33 years (29%). The incidence of STIs during follow-up was exceptionally high (107.9/100 women-years [wy]), with younger women (18–21 years) more likely to acquire CT (75.9/100 wy) compared to 26–33 year olds (17.4/100 wy; p = 0.049). TV incidence was higher in the 26–33 year old group (82.7/100 wy) compared to the 18–21 year olds (8.4/100 wy; p = 0.01). Conclusions Although the study participants received extensive counselling on the importance of condom use, this study highlights the high prevalence and incidence of STIs in South African women, especially amongst young women, emphasising the need for better STI screening and management strategies.
Læs mere Tjek på PubMedBoczar, K. E., Shin, S., deKemp, R. A., Dowlatshahi, D., Tavoosi, A., Wiefels, C., Liu, P., Lochnan, H., MacPherson, P. A., Chong, A. Y., Torres, C., Leung, E., Tawakol, A., Ahmadi, A., Garrard, L., Lefebvre, C., Kelly, C., MacPhee, P., Tilokee, E., Raggi, P., Wells, G. A., Beanlands, R.
BMJ Open, 10.11.2023
Tilføjet 10.11.2023
BackgroundInflammation is a key mediator in the development and progression of the atherosclerotic disease process as well as its resultant complications, like myocardial infarction (MI), stroke and cardiovascular (CV) death, and is emerging as a novel treatment target. Trials involving anti-inflammatory medications have demonstrated outcome benefit in patients with known CV disease. In this regard, colchicine appears to hold great promise. However, there are potential drawbacks to colchicine use, as some studies have identified an increased risk of infection, and a non-significant trend for increased all-cause mortality. Thus, a more thorough understanding of the underlying mechanism of action of colchicine is needed to enable a better patient selection for this novel CV therapy. ObjectiveThe primary objective of the Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE) trial is to assess the effect of colchicine on vascular inflammation in the carotid arteries and ascending aorta measured with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with type 2 diabetes mellitus (T2DM) or pre-diabetes who have experienced a recent vascular event (acute coronary syndrome (ACS)/MI, transient ischaemic attack (TIA) or stroke). Secondary objectives include determining colchicine’s effect on inflammatory biomarkers (high-sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6)). Additionally, we will assess if baseline inflammation imaging or biomarkers are associated with a treatment response to colchicine determined by imaging. Exploratory objectives will look at: (1) the difference in the inflammatory response to colchicine in patients with coronary events compared with patients with cerebral events; (2) the difference in the inflammatory response to colchicine in different vascular beds; (3) the relationship of FDG-PET imaging markers with serum biomarkers and (4) assessment of quality-of-life changes. Methods and designCADENCE is a multicentre, prospective, randomised, double-blinded, placebo-controlled study to determine the effect of colchicine on arterial inflammation as assessed with imaging and circulatory biomarkers, specifically carotid arteries and aortic FDG uptake as well as hs-CRP and IL-6 among others. Patients with T2DM or pre-diabetes who have recently experienced a CV event (within 30–120 days after an ACS (ie, ST-elevation MI (STEMI) or non-STEMI)) or TIA/stroke with documented large vessel atherosclerotic disease will be randomised to treatment with either colchicine 0.6 mg oral daily or placebo. Participants will undergo baseline clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan of the ascending aorta and left and right carotid arteries. Patients will undergo treatment for 6 months and have repeat clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan at the conclusion of the study. The primary outcome will be the change in the maximum target to background ratio (TBRmax) in the ascending aorta (or carotid arteries) from baseline to follow-up on FDG PET/CT imaging. DiscussionColchicine is an exciting potential new therapy for CV risk reduction. However, its use is associated with side effects and greater understanding of its underlying mechanism of action is needed. Importantly, the current study will determine whether its anti-inflammatory action is an indirect systemic effect, or a more local plaque action that decreases inflammation. The results will also help identify patients who will benefit most from such therapy. Trial registration numberNCT04181996.
Læs mere Tjek på PubMedInfection, 5.11.2023
Tilføjet 5.11.2023
Abstract Background Infection-associated secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially life-threatening hyperinflammatory condition caused by various infectious diseases. Malaria has rarely been described as trigger. The aim of this study is to collect data on frequency, clinical spectrum, and outcome of sHLH induced by malaria. Methods We collected case numbers on malaria and malaria-associated sHLH from specialized centers in Germany from 2015 to 2022. In addition, we conducted a literature search on published cases of malaria-associated sHLH and systematically analyzed the literature regarding clinical and diagnostic criteria. Results We obtained data from 13 centers treating 1461 malaria cases with different Plasmodium species, of which 5 patients (0.34%) also were diagnosed with sHLH. The literature search revealed detailed case reports from further 51 patients and case series comprising the description of further 24 patients with malaria-associated sHLH. Most cases (48/80; 60%) were reported from Asia. The median time interval between onset of malaria symptoms and hospital admission was 7 days. Severe complications of sHLH were documented in 36% (20/56) of patients, including two patients with multiple organ failure in our case series. Only 41% (23/56) of patients received specific treatment for sHLH, nevertheless the mortality rate (CFR) of 5% is lower compared to the CFR reported for sHLH triggered by other infectious diseases (e.g., 25% in sHLH due to EBV infection). Conclusion Malaria-associated sHLH appears to have a comparatively good prognosis but may still represent an underdiagnosed and potentially fatal complication of malaria, especially in resource-poor settings.
Læs mere Tjek på PubMedBMC Infectious Diseases, 26.10.2023
Tilføjet 26.10.2023
Abstract Background and aim Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and infectious mononucleosis (EBV-IM) share mimic symptoms in the early stages of childhood development. We aimed to examine the clinical features and laboratory indices of these two diseases in children and uncover unique indicators to assist pediatricians in identifying these diseases early. Methods We collected clinical data from 791 pediatric patients diagnosed with EBV-IM or EBV-HLH, compared the clinical traits and laboratory biomarkers presented in the two groups, and constructed predictive models based on them. Results Patients with EBV-IM had greater ratios of cervical lymphadenopathy, eyelid edema, and tonsillitis, whereas individuals with EBV-HLH were more likely to have hepatomegaly and splenomegaly. When using the criteria of interleukin (IL)-10 > 89.6 pg/mL, interferon (IFN)-γ > 45.6 pg/mL, ferritin > 429 μg/L, D-dimer > 3.15 mg/L and triglycerides > 2.1 mmol/L, the sensitivity was 87.9%, 90.7%, 98.1%, 91.1% and 81.5% to predict EBV-HLH, while the specificity was 98.4%, 96.3%, 96.5%, 94.1% and 80.6%, respectively. A logistic regression model based on four parameters (IL-10, ferritin, D-dimer, and triglycerides) was established to distinguish EBV-HLH patients from EBV-IM patients, with a sensitivity of 98.0% and a specificity of 98.2%. Conclusions IL-10, IFN-γ, ferritin and D-dimer levels are significantly different between EBV-HLH and EBV-IM. Predictive models based on clinical signs and laboratory findings provide simple tools to distinguish the two situations.
Læs mere Tjek på PubMedInfection, 25.10.2023
Tilføjet 25.10.2023
Abstract Background Infection-associated secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially life-threatening hyperinflammatory condition caused by various infectious diseases. Malaria has rarely been described as trigger. The aim of this study is to collect data on frequency, clinical spectrum, and outcome of sHLH induced by malaria. Methods We collected case numbers on malaria and malaria-associated sHLH from specialized centers in Germany from 2015 to 2022. In addition, we conducted a literature search on published cases of malaria-associated sHLH and systematically analyzed the literature regarding clinical and diagnostic criteria. Results We obtained data from 13 centers treating 1461 malaria cases with different Plasmodium species, of which 5 patients (0.34%) also were diagnosed with sHLH. The literature search revealed detailed case reports from further 51 patients and case series comprising the description of further 24 patients with malaria-associated sHLH. Most cases (48/80; 60%) were reported from Asia. The median time interval between onset of malaria symptoms and hospital admission was 7 days. Severe complications of sHLH were documented in 36% (20/56) of patients, including two patients with multiple organ failure in our case series. Only 41% (23/56) of patients received specific treatment for sHLH, nevertheless the mortality rate (CFR) of 5% is lower compared to the CFR reported for sHLH triggered by other infectious diseases (e.g., 25% in sHLH due to EBV infection). Conclusion Malaria-associated sHLH appears to have a comparatively good prognosis but may still represent an underdiagnosed and potentially fatal complication of malaria, especially in resource-poor settings.
Læs mere Tjek på PubMedOffor, U. T., Hollis, P., Ognjanovic, M., Parry, G., Khushnood, A., Long, H. M., Gennery, A. R., Bacon, C. M., Simmonds, J., Reinhardt, Z., Bomken, S.
BMJ Open, 21.10.2023
Tilføjet 21.10.2023
IntroductionPaediatric heart transplant patients are disproportionately affected by Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) compared with other childhood solid organ recipients. The drivers for this disparity remain poorly understood. A potential risk factor within this cohort is the routine surgical removal of the thymus—a gland critical for the normal development of T-lymphocyte-mediated antiviral immunity—in early life, which does not occur in other solid organ transplant recipients. Our study aims to describe the key immunological differences associated with early thymectomy, its impact on the temporal immune response to EBV infection and subsequent risk of PTLD. Methods and analysisProspective and sequential immune monitoring will be performed for 34 heart transplant recipients and 6 renal transplant patients (aged 0–18 years), stratified into early (1 year) and non-thymectomy groups. Peripheral blood samples and clinical data will be taken before transplant and at 3, 6, 12 and 24 months post-transplant. Single cell analysis of circulating immune cells and enumeration of EBV-specific T-lymphocytes will be performed using high-dimensional spectral flow cytometry with peptide-Major Histocompatibilty Complex (pMHC) I/II tetramer assay, respectively. The functional status of EBV-specific T-lymphocytes, along with EBV antibodies and viral load will be monitored at each of the predefined study time points. Ethics and disseminationEthical approval for this study has been obtained from the North of Scotland Research Ethics Committee. The results will be disseminated through publications in peer-reviewed journals, presentations at scientific conferences and patient-centred forums, including social media. Trial registration numberISRCTN10096625.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 5.10.2023
Tilføjet 5.10.2023
AbstractPurposeTo analyze the clinical characteristics of peripheral Epstein-Barr virus(EBV)-infected lymphocyte subtypes in children with chronic active EBV infection(CAEBV).MethodsThe levels of peripheral EBV infection of CD4 + T cells, CD8 + T cells, and CD56 + NK cells were determined by flow cytometry and qPCR in patients with CAEBV from July 2017 to July 2022.ResultsA total of 112 children with CAEBV were evaluated in the study. Of them, CD4 + type, CD8 + type, and CD56 + type were defined in 44, 21, and 47 patients, respectively. Patients with CD8 + T-cell type had a significantly higher frequency of rash, while hepatomegaly was more common in patients with CD4 + T-cell type. Generally, patients with CD8 + T-cell type had the lowest overall survival(OS) rate(P = 0.017). As for treatment, patients treated with chemotherapy and hematopoietic stem cell transplantation had a better prognosis(P = 0.001). In multivariate analysis, rash, HLH, CD8 + T-cell type, and no decrease of plasma EBV-DNA after treatment were indicated as independent factors of poor prognosis(P = 0.002, 0.024, 0.022, and 0.012, respectively).ConclusionIn children with CAEBV, the rash was more frequent in patients with CD8 + T-cell type, whereas patients with CD4 + T-cell type were more likely to develop hepatomegaly. Patients with CD8 + T-cell type had a poor prognosis despite receiving chemotherapy or further HSCT.
Læs mere Tjek på PubMedStarnes, J. R., Rogers, A., Wamae, J., Okoth, V., Mudhune, S. A., Omondi, A., Were, V., Baraza Awino, D., Lefebvre, C. H., Yap, S., Otieno Odhong, T., Vill, B., Were, L., Wamai, R.
BMJ Open, 22.08.2023
Tilføjet 22.08.2023
ObjectivesThe under-five mortality (U5M) rate in Kenya (41 per 1000 live births) remains significantly above international goals (25 per 1000 live births). This is further exacerbated by regional inequalities in mortality. We aimed to describe U5M in Migori County, Kenya, and identify associated factors that can serve as programming targets. DesignCross-sectional observational survey. SettingAreas served by the Lwala Community Alliance and control areas in Migori County, Kenya. ParticipantsThis study included 15 199 children born to respondents during the 18 years preceding the survey. Primary and secondary outcome measuresThe primary outcome was mortality in the first 5 years of life. The survey was powered to detect a 10% change in various health metrics over time with 80% power. ResultsA total of 15 199 children were included in the primary analyses, and 230 (1.5%) were deceased before the fifth birthday. The U5M rate from 2016 to 2021 was 32.2 per 1000 live births. Factors associated with U5M included year of birth (HR 0.926, p
Læs mere Tjek på PubMedDeborah Schönegger, Armelle Marais, Bisola Mercy Babalola, Chantal Faure, Marie Lefebvre, Laurence Svanella-Dumas, Sára Brázdová, Thierry Candresse
PLoS One Infectious Diseases, 17.08.2023
Tilføjet 17.08.2023
by Deborah Schönegger, Armelle Marais, Bisola Mercy Babalola, Chantal Faure, Marie Lefebvre, Laurence Svanella-Dumas, Sára Brázdová, Thierry Candresse High-throughput sequencing (HTS) has proven a powerful tool to uncover the virome of cultivated and wild plants and offers the opportunity to study virus movements across the agroecological interface. The carrot model consisting of cultivated (Daucus carota ssp. sativus) and wild carrot (Daucus carota ssp. carota) populations, is particularly interesting with respect to comparisons of virus communities due to the low genetic barrier to virus flow since both population types belong to the same plant species. Using a highly purified double-stranded RNA-based HTS approach, we analyzed on a large scale the virome of 45 carrot populations including cultivated, wild and off-type carrots (carrots growing within the field and likely representing hybrids between cultivated and wild carrots) in France and six additional carrot populations from central Spain. Globally, we identified a very rich virome comprising 45 viruses of which 25 are novel or tentatively novel. Most of the identified novel viruses showed preferential associations with wild carrots, either occurring exclusively in wild populations or infecting only a small proportion of cultivated populations, indicating the role of wild carrots as reservoir of viral diversity. The carrot virome proved particularly rich in viruses involved in complex mutual interdependencies for aphid transmission such as poleroviruses, umbraviruses and associated satellites, which can be the basis for further investigations of synergistic or antagonistic virus-vector-host relationships.
Læs mere Tjek på PubMedMaria Pena-FranceschLiliana Danusia VanoaicaGao-Feng ZhuMichael StumpeDevanarayanan Siva SankarHeike NowagAlma Delia Valencia-CamargoWolfgang HammerschmidtJörn DengjelLaure-Anne LigeonChristian MünzaViral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich 8057, SwitzerlandbDepartment of Biology, University of Fribourg, Fribourg 1700, SwitzerlandcResearch Unit Gene Vectors, Helmholtz Zentrum München, German Research Center for Environmental Health and German Center for Infection Research, D-81377 Munich, Germany
Proceedings of the National Academy of Sciences, 16.08.2023
Tilføjet 16.08.2023
Proceedings of the National Academy of Sciences, Volume 120, Issue 34, August 2023.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 11.08.2023
Tilføjet 11.08.2023
AbstractThe use of soluble recombinant ACE2 (rACE2) as a decoy capable of blocking SARS-CoV-2 entry into cells has been envisaged as a therapeutic strategy to reduce viral loads in patients suffering from severe COVID-19. We engineered a novel form of rACE2, fused to the Epstein-Barr virus (EBV) antigen P18F3 (rACE2-P18F3), to reorient a pre-existing humoral response towards EBV against SARS-CoV-2 particles. Recombinant ACE2-P18F3 was able to bind to the SARS-CoV-2 spike protein, neutralized viral entry into cells and promoted the phagocytosis of spheres coated with different spike variants by monocytic cells. The results position rACE2-P18F3 as a promising therapeutic candidate to universally block coronaviruses cell entry and clear viral particles.
Læs mere Tjek på PubMedBlouin, K., Lefebvre, B., Trudelle, A., Defay, F., Perrault Sullivan, G., Ezin Aloffan, L. N. D., Labbe, A.-C.
BMJ Open, 4.08.2023
Tilføjet 4.08.2023
ObjectivesTo examine correlates of Neisseria gonorrhoeae antimicrobial resistance (AMR) to first-line antimicrobials (azithromycin, cefixime and ceftriaxone). Design and settingThe sentinel surveillance network is an open cohort of gonococcal infection cases from Québec, Canada. Cross-sectional results are reported herein. ParticipantsBetween 1 January 2016 and 31 December 2019, data from 886 individuals accounting for 941 gonorrhoea cases were included. MethodsEpidemiological and clinical data were collected using an auto-administered questionnaire, direct case interviews and chart reviews. Antimicrobial susceptibility testing was performed using the agar dilution method. Generalised estimating equations were used for regression. ResultsThe prevalence of azithromycin resistance with a minimal inhibitory concentration (MIC) of ≥2 mg/L was 21.3%. In 2016, men who have sex with men were more likely to be infected with an azithromycin-resistant N. gonorrhoeae isolate (adjusted prevalence ratio (aPR)=4.73, 95% CI 1.48 to 15.19) or with an isolate with increased third-generation cephalosporin (3GC) MIC (aPR=5.32, 95% CI 1.17 to 24.11 for cefixime (MIC≥0.06 mg/L) and aPR=4.38, 95% CI 1.53 to 12.54 for ceftriaxone (MIC≥0.03 mg/L)). However, these associations were not maintained between 2017 and 2019, with increased MIC observed in men who have sex exclusively with women and women. Overall, azithromycin resistance was significantly more likely in cases who self-reported HIV infection (aPR=1.65, 95% CI 1.00 to 2.71). Cefixime increased MIC were more likely in individuals 25–34 years old (aPR=2.23, 95% CI 1.18 to 4.21). Cefixime and ceftriaxone increased MIC were both more likely in cases who reported ≥5 sexual partners (cefixime: aPR=2.10, 95% CI 1.34 to 3.27 and ceftriaxone: aPR=1.62, 95% CI 1.14 to 2.30). ConclusionSignificant correlates of N. gonorrhoeae AMR to first-line antimicrobials were observed. Antimicrobial stewardship may be particularly important for 3GC. Active monitoring and interventions are critical for 3GC non-susceptible strains, especially considering the very low prevalence in Québec.
Læs mere Tjek på PubMedBMC Infectious Diseases, 21.07.2023
Tilføjet 21.07.2023
Abstract Introduction Haemophagocytic lymphohistiocytosis is a rare and life-threatening condition caused by uncontrolled immune activation leading to excessive inflammation and tissue destruction. It could either be due to a primary genetic defect or be triggered by secondary causes such as infections, autoimmune diseases, rheumatological diseases or post-transplant immunosuppression. We here report the case of a 4-year-old child with a recent AIDS diagnosis who developed a severe systemic inflammation. Case report We here report the case of a 4-year-old child with a recent AIDS diagnosis who was admitted to the ER with acute respiratory failure due to Pneumocystis jiroveci infection and Aspergillosis; the following microbiological assessment also showed a CMV, HSV, EBV and HHV-7 coinfection. On the 51st day after she’d started antiretroviral therapy, 39th after she’d followed a course of Bactrim and Caspofungin for PJI and Ambisome for pulmonary Aspergillosis, she started presenting fever, unresponsive to broad-spectrum antibiotic therapy. She also presented worsening of her clinical conditions, with evidence at the laboratory assessments of progressive raise in inflammatory indexes, coagulopathy, trilinear cytopenia and hyperferritinemia. To perform the differential diagnosis between IRIS and HLH, HLA-DR on T cells was studied, turning out negative for IRIS. Therefore, in the suspicion of HLH, a bone marrow aspirate and biopsy were performed with evidence of trilinear cytopenia, prevalence of T-cells and macrophages with signs of phagocytosis. She was started on high-dose steroids and Anakinra for a total of 29 days, resulting in prompt apyrexia and progressive improvement of her clinical conditions and laboratory results. Conclusion To the best of our knowledge there is poor literature available about the differential diagnosis of HLH and IRIS, therefore medical management in the concurrence of these two conditions needs to be further investigated, especially in a setting where immunological testing is not quickly available. The clinical differences between these pathologies are blurred and the bone marrow biopsy within marker for IRIS helped us to distinguish these two entities.
Læs mere Tjek på PubMedBMC Infectious Diseases, 19.07.2023
Tilføjet 19.07.2023
Abstract Introduction Haemophagocytic lymphohistiocytosis is a rare and life-threatening condition caused by uncontrolled immune activation leading to excessive inflammation and tissue destruction. It could either be due to a primary genetic defect or be triggered by secondary causes such as infections, autoimmune diseases, rheumatological diseases or post-transplant immunosuppression. We here report the case of a 4-year-old child with a recent AIDS diagnosis who developed a severe systemic inflammation. Case report We here report the case of a 4-year-old child with a recent AIDS diagnosis who was admitted to the ER with acute respiratory failure due to Pneumocystis jiroveci infection and Aspergillosis; the following microbiological assessment also showed a CMV, HSV, EBV and HHV-7 coinfection. On the 51st day after she’d started antiretroviral therapy, 39th after she’d followed a course of Bactrim and Caspofungin for PJI and Ambisome for pulmonary Aspergillosis, she started presenting fever, unresponsive to broad-spectrum antibiotic therapy. She also presented worsening of her clinical conditions, with evidence at the laboratory assessments of progressive raise in inflammatory indexes, coagulopathy, trilinear cytopenia and hyperferritinemia. To perform the differential diagnosis between IRIS and HLH, HLA-DR on T cells was studied, turning out negative for IRIS. Therefore, in the suspicion of HLH, a bone marrow aspirate and biopsy were performed with evidence of trilinear cytopenia, prevalence of T-cells and macrophages with signs of phagocytosis. She was started on high-dose steroids and Anakinra for a total of 29 days, resulting in prompt apyrexia and progressive improvement of her clinical conditions and laboratory results. Conclusion To the best of our knowledge there is poor literature available about the differential diagnosis of HLH and IRIS, therefore medical management in the concurrence of these two conditions needs to be further investigated, especially in a setting where immunological testing is not quickly available. The clinical differences between these pathologies are blurred and the bone marrow biopsy within marker for IRIS helped us to distinguish these two entities.
Læs mere Tjek på PubMedBaptiste HOELLINGER, Charlotte KAEUFFER, Pierre BOYER, Nicolas LEFEBVRE, Yves HANSMANN, Amandine ROBERT, François SEVERAC, Alain GRAVET, François DANION, Yvon RUCH, Axel URSENBACH
International Journal of Infectious Diseases, 14.07.2023
Tilføjet 14.07.2023
Enterobacterales bloodstream infections (BSI) are common life-threatening conditions. Prompt and appropriate antimicrobial therapy is an essential part of the treatment and has demonstrated a significant reduction in mortality [1, 2]. AmpC β-lactamase-hyperproducing Enterobacterales (ABLHE) are frequently isolated in healthcare-associated infections, which leads to the prescription of carbapenems. ABLHE refers to Enterobacterales that have derepressed AmpC and are therefore third-generation cephalosporin (3GC)-resistant.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 13.07.2023
Tilføjet 13.07.2023
AbstractObjectiveThe two co-factors in the etiology of Burkitt lymphoma (BL) are Epstein Barr virus (EBV) and repeated Plasmodium falciparum malaria infections. This study evaluated EBV loads in mucosal and systemic compartments of children with malaria and in community controls. Age was analyzed as a covariate as immunity to malaria in endemic regions is age dependent.MethodsChildren (2-10 years) with clinical malaria from Western Kenya and community controls without malaria were enrolled. Saliva and blood samples were collected, EBV viral load was assessed by quantitative-PCR and EpiTYPER MassARRAY was used to assess methylation of 3 different EBV genes.ResultsRegardless of the compartment, we detected EBV more frequently in malaria cases compared to controls although not significant. When EBV was detected, there were no differences in viral load between cases and controls. However, EBV methylation was significantly lower in the malaria group compared to controls in both plasma and saliva (p-value
Læs mere Tjek på PubMedBMC Infectious Diseases, 12.07.2023
Tilføjet 12.07.2023
Abstract Background Chronic active Epstein-Barr virus infection (CAEBV) is a systemic EBV-positive lymphoproliferative disorder (EBV-LPD) considered to be associated with a genetic immunological abnormality, although its cause is still unclear. EBV is usually detected in T cells or NK cells in CAEBV patients with only a few cases involving B cells described in East Asia, which may be due to differences in genetic and environmental factors. Case description A 16-year-old boy who seemed to be diagnosed as CAEBV of B cell type was studied. The patient had IM-like symptoms persisting for more than 3 months, high levels of EBV DNA in the PB, and positive EBER in situ hybridization in B cells. In addition, to exclude underlying genetic disorders, we performed next-generation sequencing (NGS) and whole-exome sequencing (WES), which identified the missense mutation in PIK3CD (E1021K), ADA (S85L) and CD3D (Q140K) in the patient while no same genetic mutation was detected in his parents and sister. However, there is no diagnosis of CAEBV of B cell type in the most recent World Health Organization classification of tumors of hematopoietic and lymphoid tissues, therefore we finally diagnosed this patient as EBV-B-LPD. Conclusions This study shows a rare case of a patient meeting the definition of CAEBV B-cell disease in East Asia. Meanwhile, the case indicates that the missense mutation and the disease are related.
Læs mere Tjek på PubMedXing Zhang; Yan Zhang; Wen Liu; Bing Luo;
Reviews in Medical Virology, 10.07.2023
Tilføjet 10.07.2023
Protein post‐translational modifications (PTMs) are reversible processes that regulate the function of target proteins without altering their sequences. High‐throughput sequencing surveys have provided insights into the patterns of PTMs, such as ubiquitination, SUMOylation, and phosphorylation. After primary infection, the Epstein‐Barr virus (EBV), a ubiquitous herpesvirus, establishes a life‐long latent infection. EBV can establish a delicate balance to regulate its proliferation and host cell survival. Owing to the limited gene products of EBV, interfering with the host PTM machinery is an effective way to alter host immune responses and physiological status and establish infection. In this review, we focus on the current knowledge of the mechanisms by which EBV products manipulate host ubiquitination, SUMOylation, and phosphorylation to establish a latent infection or favour viral replication and pathogenesis.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.07.2023
Tilføjet 8.07.2023
Abstract Background Chronic active Epstein-Barr virus infection (CAEBV) is a systemic EBV-positive lymphoproliferative disorder (EBV-LPD) considered to be associated with a genetic immunological abnormality, although its cause is still unclear. EBV is usually detected in T cells or NK cells in CAEBV patients with only a few cases involving B cells described in East Asia, which may be due to differences in genetic and environmental factors. Case description A 16-year-old boy who seemed to be diagnosed as CAEBV of B cell type was studied. The patient had IM-like symptoms persisting for more than 3 months, high levels of EBV DNA in the PB, and positive EBER in situ hybridization in B cells. In addition, to exclude underlying genetic disorders, we performed next-generation sequencing (NGS) and whole-exome sequencing (WES), which identified the missense mutation in PIK3CD (E1021K), ADA (S85L) and CD3D (Q140K) in the patient while no same genetic mutation was detected in his parents and sister. However, there is no diagnosis of CAEBV of B cell type in the most recent World Health Organization classification of tumors of hematopoietic and lymphoid tissues, therefore we finally diagnosed this patient as EBV-B-LPD. Conclusions This study shows a rare case of a patient meeting the definition of CAEBV B-cell disease in East Asia. Meanwhile, the case indicates that the missense mutation and the disease are related.
Læs mere Tjek på PubMedClinical & Experimental Immunology, 7.07.2023
Tilføjet 7.07.2023
AbstractMultiple sclerosis is characterised by the chronic inflammatory destruction of myelinated axons in the central nervous system. Several ideas have been put foward to clarify the roles of the peripheral immune system and neurodegenerative events in such destruction. Yet, none of the resulting models appears to be consistent with all the experimental evidence. They also do not answer the question why MS is exclusively seen in humans, how Epstein-Barr virus contributes to its development but does not immediately trigger it, and why optic neuritis is such a frequent early manifestation in MS.Here we describe a scenario for the development of MS that unifies existing experimental evidence as well as answer the above questions. We propose that all manifestions of MS are caused by a series of unfortunate events that usually unfold over a longer period of time after a primary EBV infection and involves periodic weakening of the blood-brain barrier, antibody-mediated CNS disturbances, accumulation of the oligodendrocyte stress protein αB-crystallin and self-sustaining inflammatory damage.
Læs mere Tjek på PubMedChu Xie, Lan‐Yi Zhong, Guo‐Long Bu, Ge‐Xin Zhao, Bo‐Yu Yuan, Yuan‐Tao Liu, Cong Sun, Mu‐Sheng Zeng
Journal of Medical Virology, 21.05.2023
Tilføjet 21.05.2023
Arman Shafiee; Mohammad Mobin Teymouri Athar; Mohammad Javad Amini; Hamed Hajishah; Sepehr Siahvoshi; Mehrsa Jalali; Bahar Jahanbakhshi; Sayed‐Hamidreza Mozhgani;
Reviews in Medical Virology, 10.05.2023
Tilføjet 10.05.2023
To provide a comprehensive systematic review and meta‐analysis regarding the cumulative incidence (incidence proportion) of human herpesvirus (HHV) reactivation among patients with coronavirus disease 2019 (COVID‐19), we searched PubMed/MEDLINE, Web of Science, and EMBASE up to 25 September 2022, with no language restrictions. All interventional and observational studies enrolling patients with confirmed COVID‐19 and providing data regarding HHV reactivation were included. The random‐effects model was used in the meta‐analyses. We included information from 32 studies. HHV reactivation was considered a positive polymerase chain reaction result taken at the time of COVID‐19 infection. Most of the included patients were severe COVID‐19 cases. The pooled cumulative incidence estimate was 38% (95% Confidence Intervals [CI], 28%–50%, = 86%) for herpes simplex virus (HSV), 19% (95% CI, 13%–28%, = 87%) for cytomegalovirus (CMV), 45% (95% CI, 28%–63%, = 96%) for Epstein‐Barr virus (EBV), 18% (95% CI, 8%–35%) for human herpesvirus 6 (HHV‐6), 44% (95% CI, 32%–56%) for human herpesvirus 7 (HHV‐7), and 19% (95% CI, 14%–26%) for human herpesvirus 8 (HHV‐8). There was no evidence of funnel plot asymmetry based on visual inspection and Egger\'s regression test for the results of HSV ( = 0.84), CMV ( = 0.82), and EBV ( = 0.27) reactivation. In conclusion, the identification of HHV reactivation in severe COVID‐19 patients is helpful in the management of patients as well as the prevention of complications. Further research is required to elucidate the interaction between HHVs and COVID‐19. Systematic review registration: PROSPERO CRD42022321973.
Læs mere Tjek på PubMedBMC Infectious Diseases, 27.04.2023
Tilføjet 27.04.2023
Abstract Background Viral reactivations and co-infections have been reported among COVID-19 patients. However, studies on the clinical outcomes of different viral reactivations and co-infections are currently in limit. Thus, the primary purpose of this review is to perform an overarching investigation on the cases of latent virus reactivation and co-infection in COVID-19 patients to build collective evidence contributing to improving patient health. The aim of the study was to conduct a literature review to compare the patient characteristics and outcomes of reactivations and co-infections of different viruses. Methods Our population of interest included confirmed COVID-19 patients who were diagnosed with a viral infection either concurrently or following their COVID-19 diagnosis. We extracted the relevant literature through a systematic search using the key terms in the online databases including the EMBASE, MEDLINE, Latin American Caribbean Health Sciences Literature (LILACS), from inception onwards up to June 2022. The authors independently extracted data from eligible studies and assessed the risk of bias using the Consensus-based Clinical Case Reporting (CARE) guidelines and the Newcastle–Ottawa Scale (NOS). Main patient characteristics, frequency of each manifestation, and diagnostic criteria used in studies were summarized in tables. Results In total, 53 articles were included in this review. We identified 40 reactivation studies, 8 coinfection studies, and 5 studies where concomitant infection in COVID-19 patients was not distinguished as either reactivation or coinfection. Data were extracted for 12 viruses including IAV, IBV, EBV, CMV, VZV, HHV-1, HHV-2, HHV-6, HHV-7, HHV-8, HBV, and Parvovirus B19. EBV, HHV-1, and CMV were most frequently observed within the reactivation cohort, whereas IAV and EBV within the coinfection cohort. In both reactivation and coinfection groups, patients reported cardiovascular disease, diabetes, and immunosuppression as comorbidities, acute kidney injury as complication, and lymphopenia and elevated D-dimer and CRP levels from blood tests. Common pharmaceutical interventions in two groups included steroids and antivirals. Conclusion Overall, these findings expand our knowledge on the characteristics of COVID-19 patients with viral reactivations and co-infections. Our experience with current review indicates a need for further investigations on virus reactivation and coinfection among COVID-19 patients.
Læs mere Tjek på PubMedLorenzo Zaffiri, Joshua E. Messinger, Erika J. Bush, Janet S. Staats, Prekshaben Patel, Scott M. Palmer, Kent J. Weinhold, Laurie D. Snyder, Micah A. Luftig
Journal of Medical Virology, 19.04.2023
Tilføjet 19.04.2023
Journal of Medical Virology, 13.04.2023
Tilføjet 14.04.2023
Trends in Microbiology, 24.03.2023
Tilføjet 25.03.2023
There are nine HHVs, including three alpha-herpesviruses [herpes simplex viruses type 1 (HSV-1; HHV-1) and 2 (HSV-2; HHV-2) and VZV (HHV-3)]; four beta-herpesviruses [HHV-6A, HHV-6B, HHV-7, and human cytomegalovirus (HCMV; HHV-5)]; and two gamma-herpesviruses [Kaposi’s sarcoma-associated herpesviruses (KSHV; HHV-8) and Epstein–Barr virus (EBV; HHV-4)]. HHVs are ubiquitous in human populations and their latent or lytic infections cause various diseases [1]. In addition to known HHV pathologies, recent studies linked HSV-1 and VZV with Alzheimer’s disease, and EBV with multiple sclerosis [2–5].
Læs mere Tjek på PubMedJournal of Medical Virology, 13.03.2023
Tilføjet 15.03.2023
Clinical Infectious Diseases, 9.03.2023
Tilføjet 9.03.2023
AbstractWe report sustained remission of chronic active EBV infection in a 27-year-old female patient treated with third-party EBV-specific T-cells followed by allogeneic HSCT. The viremia cleared after administration of anti-T-lymphocyte globulin for GvHD prophylaxis. Subsequent expansion of EBV-infected host T-cells was controlled by transfusion of donor-derived EBV-specific T-cells.
Læs mere Tjek på PubMed