Journal of Clinical Virology最新文献_第4页

Syndromic approach for rapid detection and differentiation of human pathogenic alphaviruses 快速检测和鉴别人致病性甲病毒的证候法。

IF 3.4 3区医学 Q2 VIROLOGY

Journal of Clinical Virology

Pub Date : 2025-12-01 Epub Date: 2025-09-19 DOI: 10.1016/j.jcv.2025.105872

Carlo Fischer , Anges Yadouleton , Miguel Mauricio Cabada , Miladi Gatty Nogueira , Marta Piche-Ovares , Stephane Sohou , César Augusto Cabezas Sánchez , Patricia T. Bozza , María Paquita García Mendoza , Eduardo Gotuzzo , Fernando Augusto Bozza , Jan Felix Drexler

Background

Knowledge of epidemiology, pathogenesis, and public health burden is scarce for many arthropod-borne viruses (arboviruses). Insufficient knowledge is partly attributable to the lack of exhaustive laboratory diagnostics due to resource limitations. Among arboviruses, arthritogenic and encephalitogenic alphaviruses are globally widespread, can cause severe disease, and can co-occur regionally.

Objectives

We developed and validated a multiplexed real-time reverse transcription-PCR assay for the detection of all alphaviruses commonly causing human disease except Barmah Forest virus.

Study design

The assay combines five antigenic complex-specific assays and one Chikungunya virus (CHIKV)-specific assay in a single parallelized reaction.

Results

Comparisons with previously published PCR-based protocols for broad alphavirus detection using 20 different human-pathogenic alphaviruses revealed a significantly higher sensitivity of the new multiplexed assay (Fisher’s exact test, p < 0.0001). Detection limits with the new assay ranged from 0.83 cps/μl of extracted O’nyong-nyong virus to 33.05 cps/μl of extracted Western equine encephalitis virus. Antigenic complexes could be clearly differentiated by reactivity, Ct values (t-test, p < 0.0025) and signal intensities (t-test, p < 0.0001), even when testing high alphavirus concentrations potentially capable of causing false-positive PCR results. Testing of high-titred cell culture supernatants of eight important non-alphaviral arboviruses, of 4308 serum samples collected from febrile patients in Benin and Peru, of seven CHIKV-positive diagnostic samples from Brazil, and of non-targeted alphaviruses confirmed excellent diagnostic performance by the new assay, including improved detection of CHIKV, Mayaro and Venezuelan equine encephalitis virus in clinical specimens.

Conclusions

Short turn-around time, applicability in resource-limited settings, antigenic complex determination, and higher sensitivity compared to previously available tests make the new assay a useful tool for alphavirus surveillance and routine patient diagnostics.

背景：关于许多节肢动物传播的病毒（虫媒病毒）的流行病学、发病机制和公共卫生负担的知识很少。知识不足的部分原因是由于资源限制而缺乏详尽的实验室诊断。在虫媒病毒中，致关节炎和致脑甲病毒在全球广泛传播，可引起严重疾病，并可在区域内同时发生。目的：我们开发并验证了一种多重实时逆转录pcr检测方法，用于检测除Barmah森林病毒外所有常见的人类疾病的甲病毒。研究设计：该试验在单一平行反应中结合了五种抗原复合物特异性测定和一种基孔肯雅病毒（CHIKV）特异性测定。结果：与先前发表的基于pcr的方案进行比较，使用20种不同的人类致病性甲病毒进行广泛的甲病毒检测，发现新的多重检测方法的灵敏度显着提高（Fisher精确测试，p ）。与以前可用的检测方法相比，新的检测方法周转时间短、适用于资源有限的环境、抗原复合体的测定以及更高的灵敏度，使其成为甲病毒监测和常规患者诊断的有用工具。

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引用次数: 0

Performance of the Alinity m HR HPV assay on self-collected vaginal samples compared to clinician-collected cervical samples Alinity m HR HPV检测在自体阴道样本和临床采集宫颈样本上的表现。

IF 3.4 3区医学 Q2 VIROLOGY

Journal of Clinical Virology

Pub Date : 2025-12-01 Epub Date: 2025-10-20 DOI: 10.1016/j.jcv.2025.105883

Adino Tesfahun Tsegaye , Megan A. Clarke , Beverly Long , Nicole P. Chappell , Sarah A. Phillips , Megan A. Swiger , Anna BuAbbud , Priya Sathyanarayan , Nicolas Wentzensen

Background

Human papillomavirus (HPV) testing using self-collected samples could increase cervical cancer screening among never screened or underscreened populations. This study aimed to evaluate the concordance between self-collected and clinician-collected samples using the Alinity m high risk (HR) HPV extended genotyping assay.

Methods

Self-collected vaginal samples and clinician-collected cervical samples were obtained from 25 to 69-year-old women who had visits for cervical cancer screening, colposcopy, follow up pap test, and/or treatment of cervical dysplasia at the George Washington University Hospital in Washington DC and Sarasota Memorial Health Care System and their affiliates in Florida. Extended genotyping based on the Alinity m HR HPV assay was performed on stored residual samples and the agreement between clinician- and self-collected HPV test results was assessed using positive percent agreement and Cohen’s kappa values.

Results

There were 294 participants who provided paired self and clinician-collected samples. The overall prevalence of any HR-HPV was 26 %(76/293) for clinician-collected samples and 27 %(79/291) for self-collected samples. The positive percent agreement between clinician- and self-collected samples for any HR-HPV was 78 %, and the Cohen’s Kappa value was 0.83(95 %CI:0.76,0.91). For specific HPV genotypes, the positive percent agreement ranged from 72 % for HPV16–79 % for other HR-HPV group A (HPV31/33/52/58); and the Kappa value ranged from 0.83(95 %CI:0.68,0.98) for HPV16–0.87(95 %CI:0.77,0.97) for other HR-HPV group A.

Conclusion

There was a strong test concordance between self-collected and clinician-collected samples using the Alinity m HR HPV assay. Self-collected samples tested with the Alinity m HR HPV assays can be considered an alternative to clinician-collected primary HPV testing.

背景：人乳头瘤病毒（HPV）检测使用自我收集的样本可以增加宫颈癌筛查从未筛查或筛查不足的人群。本研究旨在评估使用Alinity m高风险（HR） HPV扩展基因分型检测的自我采集和临床采集样本之间的一致性。方法：在华盛顿特区的乔治华盛顿大学医院和佛罗里达州的萨拉索塔纪念医疗保健系统及其附属机构进行宫颈癌筛查、阴道镜检查、随访巴氏试验和/或宫颈发育不良治疗的25至69岁妇女中，收集自阴道样本和临床收集的宫颈样本。对储存的剩余样本进行基于Alinity m HR HPV检测的扩展基因分型，并使用阳性一致性百分比和Cohen’s kappa值评估临床医生和自己收集的HPV检测结果之间的一致性。结果：有294名参与者提供了配对的自我和临床收集的样本。临床采集样本的HR-HPV总患病率为26 %(76/293)，自行采集样本的HR-HPV总患病率为27 %（79/291）。临床医生和自己收集的任何HR-HPV样本的阳性率为78 %，Cohen's Kappa值为0.83（95 %CI:0.76,0.91）。对于特定的HPV基因型，HPV16-79的阳性率为72% %，其他HR-HPV A组（HPV31/33/52/58）的阳性率为 %；hpv16组的Kappa值为0.83(95 %CI:0.68,0.98)，其他HR-HPV a组的Kappa值为0.87（95 %CI:0.77,0.97）。结论：使用Alinity m HR HPV检测方法自行采集的样本与临床采集的样本具有很强的一致性。用Alinity m HR HPV检测检测的自收集样本可以被认为是临床收集的原发性HPV检测的替代方法。

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引用次数: 0

Detection of HIV-1 drug resistance in RNA and proviral DNA genotyping is variable both longitudinally and during repeat testing HIV-1耐药的RNA和前病毒DNA基因分型检测在纵向和重复检测中都是可变的

IF 3.4 3区医学 Q2 VIROLOGY

Journal of Clinical Virology

Pub Date : 2025-12-01 Epub Date: 2025-09-10 DOI: 10.1016/j.jcv.2025.105870

Michelle L. D'Antoni , Kristen Andreatta , Silvia Chang , Kirsten White , Hui Liu , Yongwu Shao , Jason T. Hindman , Laurie A. VanderVeen , Christian Callebaut

Background

HIV-1 variants harboring resistance-associated mutations (RAMs) can be archived in viral reservoirs and then re-emerge. Given the dynamic properties of the latent reservoir and detection limits of genotypic assays, RAM persistence over time is incompletely understood.

Objective

This retrospective analysis investigated RAM detection in adults with HIV.

Study design

Genotyping of protease, reverse transcriptase, and integrase from 3 bictegravir/emtricitabine/tenofovir alafenamide switch studies was included. Longitudinal analyses were performed for participants with combinations of RNA and proviral DNA genotype reports from ≥2 pre-switch timepoints. Reported RAMs assessed at 2 timepoints were categorized as 100 % or 50 % detection, and those assessed at ≥3 timepoints as persistent, lost, gained, or inconsistent detection. From each whole blood sample, reproducibility (%) of proviral RAM reporting was the number of times the mutation was detected per number of assays run (2–4 replicates).

Results

In 223 participants, of 262 RAMs tracked longitudinally over 2 timepoints, 39 % (103/262) had 100 % detection and 61 % (159/262) had 50 % detection, with 64 % (101/159) detected at timepoint 2. In 25 participants with ≥3 timepoints, detection of 57 RAMs was categorized as persistent (19 %; 11/57), lost (12 %; 7/57), gained (26 %; 15/57), or inconsistent (42 %; 24/57). Mean (standard deviation) reproducibility of proviral RAM detection at 1 timepoint was 80.9 % (27.2 %) (336 RAMs from 70 participants).

Conclusions

No consistent pattern of longitudinal RAM detection was observed. Reproducibility of proviral genotyping was high but variable. Since RAMs were not always consistently detected, an individual’s cumulative resistance history should be considered for optimal treatment management.

hiv -1变异含有耐药性相关突变（RAMs），可以储存在病毒储存库中，然后重新出现。鉴于潜伏库的动态特性和基因型分析的检测极限，RAM随时间的持久性尚不完全清楚。目的回顾性分析成人HIV感染者RAM的检测情况。研究设计纳入了3个比替格拉韦/恩曲他滨/替诺福韦阿拉那胺转换研究的蛋白酶、逆转录酶和整合酶基因分型。对来自≥2个开关前时间点的RNA和前病毒DNA基因型组合报告的参与者进行纵向分析。在2个时间点评估的ram被分类为100 %或50 %的检出率，在≥3个时间点评估的ram被分类为持续、丢失、获得或不一致的检出率。从每个全血样本中，前病毒RAM报告的再现性（%）是每次检测（2-4个重复）中检测到突变的次数。结果223名受试者中，2个时间点纵向追踪的262只RAMs中，39只 %（103/262）的检出率为100 %，61只 %（159/262）的检出率为50 %，64只 %（101/159）的检出率为2个时间点。在25名≥3个时间点的参与者中，57个ram的检测分为持续（19 %;11/57）、丢失（12 %;7/57）、获得（26 %;15/57）或不一致（42 %;24/57）。前病毒RAM检测在1个时间点的平均（标准差）重复性为80.9 %(27.2 %)（来自70名参与者的336只RAM）。结论纵向RAM检测模式不一致。原病毒基因分型的重复性高，但存在差异。由于ram并不总是被一致检测到，因此应考虑个体的累积耐药史以进行最佳治疗管理。

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引用次数: 0

Evaluation of a diagnostic metagenomic sequencing assay: Virus detection sensitivity and background nucleic acids in three different sample materials 诊断性宏基因组测序测定的评价：三种不同样品材料中的病毒检测敏感性和背景核酸。

IF 3.4 3区医学 Q2 VIROLOGY

Journal of Clinical Virology

Pub Date : 2025-12-01 Epub Date: 2025-10-20 DOI: 10.1016/j.jcv.2025.105882

Martin Ekman , Amir Nematollahi Mahani , Shambhu Ganeshappa Aralaguppe , Tanja Normark , Sofia Stamouli , Lili Andersson-Li , Dan Sun , Sandra Broddesson , Valtteri Wirta , Niklas K. Björkström , Jan Albert , Tobias Allander

Background

Metagenomic sequencing has emerged as an attractive, general, and agnostic diagnostic method, in particular for detection of viruses. However, its application faces limitations, including reduced sensitivity due to background nucleic acid content of samples, and the search for an optimized protocol is still ongoing.

Methods

We report the development of a metagenomic sequencing protocol for diagnostic use and its performance in detecting DNA and RNA viruses in three different sample materials: serum, cerebrospinal fluid (CSF) and nasopharyngeal swabs (NPS).

Results

Sensitivity was higher for RNA viruses than for DNA viruses, and also higher in CSF than in serum and lowest in NPS. We characterized the background nucleic acids and found higher DNA than RNA levels in CSF and serum and overall highest nucleic acid levels in NPS, intermediate in serum and lowest in CSF. These differences largely explained the observed variability in sensitivity between sample preparations and sample materials.

Conclusions

Our results highlight the need to consider sample-type specific characteristics in efforts to improve the sensitivity of metagenomic assays e.g. via host depletion protocols.

背景：宏基因组测序已成为一种有吸引力的、通用的、不确定的诊断方法，特别是在病毒检测方面。然而，它的应用面临着局限性，包括样品的背景核酸含量降低了灵敏度，并且寻找优化的方案仍在进行中。方法：我们报告了用于诊断的宏基因组测序方案的发展及其在三种不同样品材料（血清、脑脊液（CSF）和鼻咽拭子（NPS））中检测DNA和RNA病毒的性能。结果：RNA病毒敏感性高于DNA病毒敏感性，脑脊液敏感性高于血清敏感性，NPS敏感性最低。我们鉴定了背景核酸，发现脑脊液和血清中DNA水平高于RNA水平，NPS中核酸水平最高，血清中居中，脑脊液中最低。这些差异在很大程度上解释了在样品制备和样品材料之间观察到的灵敏度差异。结论：我们的结果强调了在努力提高宏基因组分析的敏感性时需要考虑样品类型的特定特征，例如通过宿主耗尽方案。

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引用次数: 0

Prevalence and epidemiology of enterovirus species in a pediatric oncology patient population 儿科肿瘤患者肠道病毒种类的流行病学研究

IF 3.4 3区医学 Q2 VIROLOGY

Journal of Clinical Virology

Pub Date : 2025-12-01 Epub Date: 2025-10-15 DOI: 10.1016/j.jcv.2025.105881

Osaretin Emmanuel Asowata , Tracy McMillen , Krupa Jani , Brenden Clark , Sejal Morjaria , Mini Kamboj , N.Esther Babady

Background

Enteroviruses (EV) are associated with a range of syndromes including respiratory infections. Non-polio enteroviruses like EV-D68 can cause more severe symptoms in children, and immunocompromised individuals. The goal of this study was to determine the prevalence and genotypes of EV in a pediatric oncology patient population.

Methods

Pediatric patients (<18 years old) testing positive for Rhinovirus/Enterovirus (RV/EV) by multiplexed respiratory pathogens panels between September and December 2022 and 2023 were included in the study. RV/EV positive nasopharyngeal swabs (NPS) specimens were further characterized using pan-enterovirus RT-PCR, EV-D68 RT-PCR and Whole genome sequencing (WGS). Clinical characteristics of EV positive patients and matched controls were extracted from the clinical information system.

Results

Across the two study periods, 3.8 % (9/238) and 3.6 % (8/225) EV were identified in RV/EV positives NPS in 2022 and 2023 respectively. The most prevalent EV species were EV-D68 (3/9, 33 %) and Coxsackievirus A6 (3/9, 33 %). All three patients with EV-D68 were male with an underlying diagnosis of acute lymphoblastic lymphoma or neuroblastoma. Besides, the EV-D68 detections were only from the 2022 NPS samples. There were no differences in symptoms severity between patients with or without EV infections.

Conclusions

The prevalence of EV during the study periods was low in this patient population and not associated with severe symptoms. However, further exploration is required to understand the relationship between EV infection and patient symptoms since this study was limited by the low EV detection. Larger studies are needed to further characterize EV infections in this patient population.

背景肠病毒（EV）与包括呼吸道感染在内的一系列综合征相关。像EV-D68这样的非脊髓灰质炎肠道病毒可在儿童和免疫功能低下的个体中引起更严重的症状。本研究的目的是确定EV在儿科肿瘤患者群体中的患病率和基因型。方法选取2022年9月至12月至2023年12月间经多重呼吸道病原体检测鼻病毒/肠道病毒（RV/EV）阳性的18岁儿科患者为研究对象。采用泛肠道病毒RT-PCR、EV- d68 RT-PCR和全基因组测序（WGS）对RV/EV阳性鼻咽拭子（NPS）标本进行进一步鉴定。从临床信息系统中提取EV阳性患者和匹配对照的临床特征。结果在两个研究期间，2022年和2023年在RV/EV阳性的NPS中分别鉴定出3.8 %（9/238）和3.6 %（8/225）的EV。最流行的病毒种为EV- d68（3/ 9,33 %）和柯萨奇病毒A6（3/ 9,33 %）。所有3例EV-D68患者均为男性，诊断基础为急性淋巴母细胞淋巴瘤或神经母细胞瘤。此外，EV-D68仅在2022年NPS样品中检测到。有无肠病毒感染的患者在症状严重程度上没有差异。结论在研究期间，该患者人群的EV患病率较低，且与严重症状无关。然而，由于本研究受到低EV检出率的限制，需要进一步探索EV感染与患者症状之间的关系。需要更大规模的研究来进一步表征这一患者群体中的EV感染。

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引用次数: 0

Evaluation of cytomegalovirus cell-mediated immunity assays in the healthy Singapore cohort and challenges of test validation 巨细胞病毒细胞介导免疫试验在新加坡健康人群中的评价和试验验证的挑战

IF 3.4 3区医学 Q2 VIROLOGY

Journal of Clinical Virology

Pub Date : 2025-12-01 Epub Date: 2025-08-29 DOI: 10.1016/j.jcv.2025.105858

Soon Hwee Ng , Shireen Yan Ling Tan , Su Ming Thean , Poi Wah Kwek , Qirong Yang , Ya Yun Lim , Wee Ching Ng , Terrence Yi Shern Kee , Ian Tatt Liew , Shimin Jasmine Chung , Wei Yee Wan

Background

Cytomegalovirus (CMV) is a major cause of morbidity and mortality for transplant and immunocompromised patients. While cell-mediated immunity (CMI) is crucial for control of CMV and can influence the management of patients, commercial kits to measure CMI responses have only recently become available. In this study, we evaluated 2 different test kit platforms to determine their performance with the aim of implementing CMV-CMI testing to serve local needs.

Materials

Fresh blood samples from healthy volunteers (27 CMV-IgG positives and 10 CMV-IgG negatives) were used to evaluate the performance of CMV Interferon-gamma assays, an ELISA and an ELISpot-assay (ES-a).

Results

Specificity was 100 % for both assays, while sensitivity was 66.67 % and 88.89 % respectively for ELISA and ES-a. For the ELISA, the mean coefficient of variations (CV) for within-run and between-run precisions were 3.8 % (1.4–7.3 %) and 15.5 % (5.6–24.7 %), respectively. The mean CV for ES-a’s within-run precisions was 14 % (7.9–21.8 %), though it was not feasible to evaluate between-run precision as blood samples collected on different days from healthy volunteers may have variable results. For ES-a, both delayed blood processing and seeding of peripheral blood mononuclear cells (PBMCs) at lower densities resulted in reduced spot counts but did not affect the qualitative interpretations.

Conclusions

ES-a had better sensitivity compared to ELISA in our healthy cohort. Challenges faced in evaluating these assays comprised of the need for fresh blood sample and large blood volume, particularly for ES-a. Such challenges need to be considered during the implementation of similar tests for diagnostic use.

巨细胞病毒（CMV）是移植和免疫功能低下患者发病和死亡的主要原因。虽然细胞介导免疫（CMI）对巨细胞病毒的控制至关重要，并且可以影响患者的管理，但用于测量CMI反应的商业试剂盒直到最近才出现。在本研究中，我们评估了两种不同的检测试剂盒平台，以确定其性能，目的是实施CMV-CMI测试，以满足当地的需求。材料健康志愿者的新鲜血液样本（27例CMV- igg阳性和10例CMV- igg阴性）用于评估CMV干扰素- γ检测、ELISA和ELISA -检测（ES-a）的性能。结果两种方法的特异性均为100 %，ELISA和ES-a的敏感性分别为66.67 %和88.89 %。ELISA的组内精密度和组间精密度的平均变异系数（CV）分别为3.8 %（1.4 ~ 7.3 %）和15.5 %（5.6 ~ 24.7 %）。ES-a的运行内精密度的平均CV值为14 %(7.9-21.8 %)，但由于健康志愿者在不同日期采集的血液样本可能有不同的结果，因此无法评估运行间精密度。对于ES-a，延迟的血液处理和低密度的外周血单个核细胞（PBMCs）播种导致斑点计数减少，但不影响定性解释。结论与ELISA相比，es -a在健康人群中具有更好的敏感性。评估这些检测方法所面临的挑战包括需要新鲜血液样本和大血容量，特别是ES-a。在实施用于诊断用途的类似测试时，需要考虑到这些挑战。

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引用次数: 0

Identifying people with chronic hepatitis B virus who are lost to clinical follow up: A retrospective case finding and re-engagement service improvement exercise 确定失去临床随访的慢性乙型肝炎病毒感染者：回顾性病例发现和再参与服务改进工作

IF 3.4 3区医学 Q2 VIROLOGY

Journal of Clinical Virology

Pub Date : 2025-12-01 Epub Date: 2025-10-01 DOI: 10.1016/j.jcv.2025.105876

Rachel Jackson , Adinah Marks , William L. Irving , Kathryn Jack

Background

Hepatitis B virus (HBV) infection is an important cause of liver disease-related mortality and morbidity. The World Health Organisation aims to eliminate this as a public health concern by 2030 and as such the key international guidelines recommend that all patients are reviewed regularly to observe for preventable signs of disease progression. This requires life-long engagement with specialist services, but some patients fall out of the care pathway and become lost to follow-up.

Objectives

This study sought to identify and re-engage patients with HBV who were lost to follow up (LTFU), defined as any HBsAg positive patient who had not been seen in the hepatology outpatient service since 31st December 2021, excluding those with acute infection.

Study design

A retrospective case finding and re-engagement healthcare service improvement exercise was conducted to identify and contact individuals with HBV diagnosed between June 2007 and the end of December 2021 who were lost-to-follow-up.

Results

One third of the HBsAg positive cohort were lost to follow-up (32.9 %, n = 506/1539). Of this group, 145 people were still living in the hospital’s catchment area, yet only 60 people could be contacted by telephone of whom 50 returned to clinic. More than 12 % of patients were HBeAg positive at their last clinic visit, and almost one quarter (23.2 %) had an abnormally raised ALT. There was extensive ethnic heterogeneity with 65 languages spoken among 474 people. We successfully re-engaged 10.07 % (51/506) back into care.

Conclusions

Patients with potentially progressive HBV-related liver disease are falling out of the care pathway with the attendant long-term problems that failure to control their infection may have.

背景乙型肝炎病毒（HBV）感染是肝脏疾病相关死亡率和发病率的重要原因。世界卫生组织的目标是到2030年消除这一公共卫生问题，因此，主要的国际指南建议定期对所有患者进行检查，以观察可预防的疾病进展迹象。这需要终生接受专业服务，但有些患者脱离了护理途径，无法随访。本研究旨在确定并重新参与失访（LTFU）的HBV患者，定义为自2021年12月31日以来未在肝病科门诊就诊的任何HBsAg阳性患者，不包括急性感染患者。研究设计进行了一项回顾性病例发现和再参与医疗保健服务改进活动，以确定和联系2007年6月至2021年12月底期间诊断为乙型肝炎病毒的失踪者。结果1 / 3的HBsAg阳性队列失访（32.9% %,n = 506/1539）。在这一群体中，145人仍然住在医院的集水区，但只有60人可以通过电话联系，其中50人返回诊所。超过12% %的患者在最后一次就诊时HBeAg呈阳性，几乎四分之一（23.2% %）的患者ALT异常升高。474人中有65种语言，存在广泛的种族异质性。我们成功地将10.07 %（51/506）重新纳入护理。具有潜在进行性hbv相关肝病的患者正在脱离护理途径，随之而来的是未能控制其感染可能产生的长期问题。

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引用次数: 0

More aggressive initiation of antiviral treatment contributes to blocking mother-to-child transmission of HBV DNA & RNA in neonatal umbilical cord blood 更积极的抗病毒治疗有助于阻断新生儿脐带血中HBV DNA和RNA的母婴传播

IF 3.4 3区医学 Q2 VIROLOGY

Journal of Clinical Virology

Pub Date : 2025-12-01 Epub Date: 2025-10-01 DOI: 10.1016/j.jcv.2025.105875

Huimin Liu , Wenting Chen , Yongjie Liang , Jing Wang , Lijian Ran , Shilian Li , Yi Wu , Zixuan He , Xuemei Kuang , Jie Xia , Li Jiang , Xuqing Zhang , Qing Mao

Background and aims

This study aimed to evaluate the efficacy of expanding antiviral indications in preventing mother-to-child transmission (MTCT) by analyzing hepatitis B virus (HBV) markers in neonatal umbilical-cord-blood (UCB) samples.

Methods

We conducted a real-world study of pregnant women aged >30 years with chronic hepatitis B (CHB) who received antenatal care between January 2022 and June 2024. Maternal HBV markers at 24–28 weeks of gestation and serum biochemical parameters at delivery were obtained. For infants, HBV markers were measured in UCB at birth and in venous blood at 7–12 months of age. Logistic regression analysis was used to identify the maternal factors associated with UCB outcomes.

Results

A total of 171 pregnant women with CHB were included. Antiviral therapy had been started before conception in 31.0 % (53/171). At 24–28 weeks of gestation, 87.8 % (150/171) had HBV DNA <5.3 Log₁₀ IU/mL, 56.1 % (96/171) had hepatitis B surface antigen (HBsAg) >3000 IU/mL and 32.7 % (56/171) were hepatitis B e antigen (HBeAg)-positive. At delivery, HBeAg-negative mothers had a median age of 33.4 ± 3.1 years, compared with 32.5 ± 2.9 years for those who were HBeAg-positive, respectively (t = 1.667, P = 0.970). 36 of 171 (21.1 %) infants were positive for HBsAg, including 12 of 115 born to HBeAg-negative mothers and 24 of 56 born to HBeAg-positive mothers (χ² = 23.82, P < 0.001). 41 of 171 (24.0 %) infants were positive for HBeAg, and all were born to HBeAg-positive mothers. HBV DNA and RNA were undetectable in all UCB samples, whereas hepatitis B core antibody (HBcAb) was present in every specimen. Receiver operating characteristic curve (ROC) analysis identified maternal HBeAg levels (AUC=0.683, cut-off value=0.494 COI) and maternal HBV DNA load (AUC=0.645, cut-off value=0.311 Log₁₀ IU/mL) as predictive of UCB HBsAg-positivity. No infants were infected with HBV, as confirmed by post-vaccination serologic testing (PVST).

Conclusions

Following the expansion of antiviral therapy indications, administering therapy to pregnant women aged >30 years with detectable HBV DNA effectively reduced HBsAg, HBV DNA and even HBV RNA level in infants’ UCB. Maternal HBeAg status was significantly associated with both HBsAg and HBeAg positivity in UCB.

背景与目的本研究旨在通过分析新生儿脐带血（UCB）样本中的乙型肝炎病毒（HBV）标志物，评价扩大抗病毒适应症在预防母婴传播（MTCT）中的疗效。方法：我们对2022年1月至2024年6月期间接受产前护理的30岁慢性乙型肝炎（CHB）孕妇进行了一项现实世界研究。测定产妇妊娠24 ~ 28周时HBV标志物及分娩时血清生化指标。对于婴儿，出生时在UCB和7-12个月时在静脉血中测量HBV标志物。采用Logistic回归分析确定与UCB结局相关的母体因素。结果共纳入171例CHB孕妇。怀孕前开始抗病毒治疗的占31.0% %（53/171）。妊娠24-28周，87.8 % (150/171)HBV DNA检出5.3 Log10 IU/mL, 56.1% %（96/171）乙肝表面抗原（HBsAg）检出3000 IU/mL， 32.7% %（56/171）乙肝e抗原（HBeAg）检出阳性。分娩时，hbeag阴性母亲的中位年龄为33.4 ± 3.1岁，而hbeag阳性母亲的中位年龄为32.5 ± 2.9岁（t = 1.667,P = 0.970）。171例婴儿中有36例（21.1% %）HBsAg阳性，其中hbeag阴性母亲115例中有12例，hbeag阳性母亲56例中有24例（χ2 = 23.82,P <； 0.001）。171例婴儿中有41例（24.0 %）HBeAg阳性，所有婴儿的母亲均为HBeAg阳性。在所有UCB样本中均检测不到HBV DNA和RNA，而在每个样本中均存在乙型肝炎核心抗体（HBcAb）。受试者工作特征曲线（ROC）分析发现，母体HBeAg水平（AUC=0.683，临界值=0.494 COI）和母体HBV DNA负荷（AUC=0.645，临界值=0.311 Log10 IU/mL）可作为UCB hbsag阳性的预测指标。通过疫苗接种后血清学检测（PVST）证实，没有婴儿感染HBV。结论随着抗病毒治疗适应症的扩大，对30岁且HBV DNA可检测的孕妇进行抗病毒治疗可有效降低婴儿UCB中HBsAg、HBV DNA甚至HBV RNA水平。母亲HBeAg水平与UCB中HBsAg和HBeAg阳性均显著相关。

{"title":"More aggressive initiation of antiviral treatment contributes to blocking mother-to-child transmission of HBV DNA & RNA in neonatal umbilical cord blood","authors":"Huimin Liu , Wenting Chen , Yongjie Liang , Jing Wang , Lijian Ran , Shilian Li , Yi Wu , Zixuan He , Xuemei Kuang , Jie Xia , Li Jiang , Xuqing Zhang , Qing Mao","doi":"10.1016/j.jcv.2025.105875","DOIUrl":"10.1016/j.jcv.2025.105875","url":null,"abstract":"<div><h3>Background and aims</h3><div>This study aimed to evaluate the efficacy of expanding antiviral indications in preventing mother-to-child transmission (MTCT) by analyzing hepatitis B virus (HBV) markers in neonatal umbilical-cord-blood (UCB) samples.</div></div><div><h3>Methods</h3><div>We conducted a real-world study of pregnant women aged >30 years with chronic hepatitis B (CHB) who received antenatal care between January 2022 and June 2024. Maternal HBV markers at 24–28 weeks of gestation and serum biochemical parameters at delivery were obtained. For infants, HBV markers were measured in UCB at birth and in venous blood at 7–12 months of age. Logistic regression analysis was used to identify the maternal factors associated with UCB outcomes.</div></div><div><h3>Results</h3><div>A total of 171 pregnant women with CHB were included. Antiviral therapy had been started before conception in 31.0 % (53/171). At 24–28 weeks of gestation, 87.8 % (150/171) had HBV DNA <5.3 Log<sub>10</sub> IU/mL, 56.1 % (96/171) had hepatitis B surface antigen (HBsAg) >3000 IU/mL and 32.7 % (56/171) were hepatitis B e antigen (HBeAg)-positive. At delivery, HBeAg-negative mothers had a median age of 33.4 ± 3.1 years, compared with 32.5 ± 2.9 years for those who were HBeAg-positive, respectively (t = 1.667, <em>P</em> = 0.970). 36 of 171 (21.1 %) infants were positive for HBsAg, including 12 of 115 born to HBeAg-negative mothers and 24 of 56 born to HBeAg-positive mothers (χ<sup>2</sup> = 23.82, <em>P</em> < 0.001). 41 of 171 (24.0 %) infants were positive for HBeAg, and all were born to HBeAg-positive mothers. HBV DNA and RNA were undetectable in all UCB samples, whereas hepatitis B core antibody (HBcAb) was present in every specimen. Receiver operating characteristic curve (ROC) analysis identified maternal HBeAg levels (AUC=0.683, cut-off value=0.494 COI) and maternal HBV DNA load (AUC=0.645, cut-off value=0.311 Log<sub>10</sub> IU/mL) as predictive of UCB HBsAg-positivity. No infants were infected with HBV, as confirmed by post-vaccination serologic testing (PVST).</div></div><div><h3>Conclusions</h3><div>Following the expansion of antiviral therapy indications, administering therapy to pregnant women aged >30 years with detectable HBV DNA effectively reduced HBsAg, HBV DNA and even HBV RNA level in infants’ UCB. Maternal HBeAg status was significantly associated with both HBsAg and HBeAg positivity in UCB.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"181 ","pages":"Article 105875"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anti-cluster A and anti-p24 antibodies in people with multidrug-resistant HIV: Preliminary observations from the PRESTIGIO registry 抗簇A抗体和抗p24抗体在多药耐药HIV患者中的作用：来自prestige注册中心的初步观察

IF 3.4 3区医学 Q2 VIROLOGY

Journal of Clinical Virology

Pub Date : 2025-12-01 Epub Date: 2025-11-03 DOI: 10.1016/j.jcv.2025.105886

Tommaso Clemente , Mehdi Benlarbi , Rebecka Papaioannu Borjesson , Elisa Garlassi , Maria Cristina Moioli , Elisa Fronti , Pierluigi Reali , Leonardo Calza , Maria Mazzitelli , Andrea Giacomelli , Maurizio Zazzi , Maria Mercedes Santoro , Andrés Finzi , Antonella Castagna , on behalf of the PRESTIGIO Study Group

Introduction

Data on soluble gp120 (sgp120) and anti-HIV antibodies are lacking in people with HIV (PWH) and multidrug resistance, characterized by high inflammation and disease burden. We aimed to investigate the relationship between immuno-virological features and sgp120, anti-cluster A, anti-p24, and anti-CD4 binding site (anti-CD4bs) antibodies in 4-class drug-resistant (4DR) individuals.

Methods

Cross-sectional study on PWH with resistance to nucleoside and non-nucleoside reverse transcriptase, protease, and integrase inhibitors. Sgp120, anti-cluster A, anti-p24, and anti-CD4bs antibodies were measured using enzyme-linked immunosorbent assays. K-means clustering based on normalized anti-cluster A and anti-p24 levels identified antibody profiles. Associations with clinical variables were assessed using descriptive statistics and multinomial logistic regression.

Results

Overall, 80 4DR-PWH evaluated. Sgp120 and anti-CD4bs antibodies were detected in 12.5 % and 8.8 %, respectively, and not significantly associated with immuno-virological characteristics.

Based on anti-cluster A and anti-p24 levels, four PWH clusters were identified. Participants with low anti-p24 and high anti-cluster A antibodies showed more frequent detectable viremia (p = 0.018), lower CD4⁺/CD8⁺ (p = 0.044), and shorter ART duration (p = 0.025). CD4⁺ nadir (p = 0.036) followed a similar trend, except with high anti-p24 levels. Recent 4DR onset (p = 0.029) was linked to increasing anti-cluster A antibodies. At multivariable analysis, detectable viremia (p = 0.035) and ART duration (p = 0.022) remained significantly associated with cluster assignment.

Conclusions

Among 4DR-PWH, a specific antibody signature characterized by high anti-cluster A and low anti-p24 levels was associated with unsuppressed viremia and, potentially, immunological impairment. These findings provide preliminary insights into the interplay between anti-HIV humoral responses and immuno-virological features in this fragile population.

在以高炎症和疾病负担为特征的多药耐药HIV （PWH）患者中，缺乏可溶性gp120 （sgp120）和抗HIV抗体的数据。我们旨在研究4级耐药（4DR）个体的免疫病毒学特征与sgp120、抗簇A、抗p24和抗cd4结合位点（抗cd4bs）抗体之间的关系。方法：对核苷类和非核苷类逆转录酶、蛋白酶和整合酶抑制剂耐药的PWH进行横断面研究。采用酶联免疫吸附法检测Sgp120、抗簇A、抗p24和抗cd4bs抗体。K-means聚类基于归一化抗聚类A和抗p24水平识别抗体谱。使用描述性统计和多项逻辑回归评估与临床变量的关联。结果：总体而言，评估了80例4DR-PWH。Sgp120和抗cd4bs抗体的检出率分别为12. %和8.8 %，与免疫病毒学特征无显著相关性。根据抗集群A和抗p24水平，鉴定出4个PWH集群。低抗p24抗体和高抗A簇抗体的参与者表现出更频繁的可检测病毒血症（p = 0.018），更低的CD4+/CD8+ (p = 0.044)，更短的ART持续时间（p = 0.025）。CD4+最低点（p = 0.036）也有类似的趋势，但抗p24水平较高。近期4DR发病（p = 0.029）与抗A簇抗体增加有关。在多变量分析中，可检测的病毒血症（p = 0.035）和抗逆转录病毒治疗持续时间（p = 0.022）仍然与聚类分配显著相关。结论：在4DR-PWH中，以高抗a簇和低抗p24水平为特征的特异性抗体特征与未抑制的病毒血症和潜在的免疫损伤相关。这些发现为这一脆弱人群的抗hiv体液反应和免疫病毒学特征之间的相互作用提供了初步的见解。

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引用次数: 0

Detection and molecular characterisation of tick-borne encephalitis virus in CSF and serum in relation to disease severity 脑脊液和血清中蜱传脑炎病毒的检测和分子特征与疾病严重程度的关系

IF 3.4 3区医学 Q2 VIROLOGY

Journal of Clinical Virology

Pub Date : 2025-12-01 Epub Date: 2025-11-05 DOI: 10.1016/j.jcv.2025.105885

Magnus Klinteskog , Anita Koskela von Sydow , Naveed Asghar , Magnus Johansson , Anna J. Henningsson , Martin Sundqvist , Per-Eric Lindgren , Lukas Frans Ocias

Objectives

We aimed to 1) detect tick-borne encephalitis virus (TBEV) RNA in clinical samples from patients with TBE, 2) characterise the detected RNA using Sanger sequencing, and 3) examine whether RNA detection was associated with disease severity.

Methods

We studied 137 patients infected and diagnosed with TBE between 2016 and 2021 in Region Örebro County and Region Värmland. Biobanked serum (n = 129) and cerebrospinal fluid (CSF; n = 110) samples were analysed. Serum was tested for TBEV-specific antibodies, and both serum and CSF for TBEV RNA using PCR. Following nested PCR, the 5′ non-coding region (5′NCR) of five samples underwent Sanger sequencing. Disease severity was assessed based on intensive care unit (ICU) admission, duration of ICU stay and need for mechanical ventilation.

Results

TBEV RNA was detected in 5 serum samples (3.9 %) and 7 CSF samples (6.4 %), representing 10 patients (7.3 %). Patients with detectable RNA were older, more frequently admitted to an ICU (p = 0.04), and more often required mechanical ventilation (p = 0.01) compared to those without detectable TBEV RNA. Sequencing of the 5′NCR in four patients revealed differences from the 5 ´NCR of the Swedish reference strain Torö-2003. The Örebro sequences were identical but differed from the Värmland sequences at two nucleotide positions.

Conclusions

TBEV RNA was detectable in both serum and CSF of TBE patients, and its presence was associated with more frequent ICU admission and need for mechanical ventilation. Sequencing of the 5′NCR revealed genetic variation between TBEV sequences from patients in Örebro and Värmland.

目的：1)在TBE患者的临床样本中检测蜱传脑炎病毒（TBEV） RNA, 2)利用Sanger测序对检测到的RNA进行表征，3)研究RNA检测是否与疾病严重程度相关。方法对2016 - 2021年在Örebro县和Värmland区感染并诊断为TBE的137例患者进行研究。分析生物银行血清（n = 129）和脑脊液（CSF; n = 110）样本。用PCR检测血清中是否有TBEV特异性抗体，血清和CSF中是否有TBEV RNA。采用巢式PCR方法，对5个样品的5 ‘非编码区（5 ’ ncr）进行Sanger测序。疾病严重程度根据重症监护病房（ICU）入院情况、ICU住院时间和机械通气需求进行评估。结果5份血清（3.9 %）和7份脑脊液（6.4 %）检出stbev RNA，共10例（7.3 %）。与未检测到TBEV RNA的患者相比，检测到RNA的患者年龄更大，更频繁地入住ICU (p = 0.04)，更频繁地需要机械通气（p = 0.01）。4例患者的5 ‘ NCR测序显示与瑞典参考菌株Torö-2003的5 ’ NCR存在差异。Örebro序列相同，但在两个核苷酸位置与Värmland序列不同。结论TBE患者血清和脑脊液中均可检测到stbev RNA，其存在与TBE患者入住ICU次数和机械通气需求增加有关。5'NCR测序揭示了Örebro和Värmland患者的TBEV序列之间的遗传差异。

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引用次数: 0