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An artificial intelligence tool that may assist with interpretation of rapid plasma reagin test for syphilis: Development and on-site evaluation 一种可协助解释梅毒快速血浆反应素试验的人工智能工具:开发和现场评估。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-03-03 DOI: 10.1016/j.jinf.2025.106454
Jiaxuan Jin , Yan Han , Yueping Yin , Bangyong Zhu , Guanqun Wang , Wenjie Lu , Hongchun Wang , Kai Chen , Xiaoyu Zhu , Wenqi Xu , Hedan Yang , Xiangsheng Chen , Yin Yang , Tong Lin

Objectives

The rapid plasma reagin (RPR) test, a traditional method for diagnosing syphilis and evaluating treatment efficacy, relies on subjective interpretation and requires high technical proficiency. This study aimed to develop and validate a user-friendly RPR-artificial intelligence (AI) interpretative tool.

Methods

A dataset comprising 600 images of photographed RPR cards from 276 negative and 223 positive RPR samples was used for model development. The reference result was based on consistent interpretations by at least two out of three experienced laboratory personnel. Then an interpretative model was developed using deep learning algorithms and loaded into smartphones for on-site interpretation at two clinical centers from October 2023 to April 2024.

Results

The model demonstrated an accuracy of 82·67% (95% CI 71·82%–90·09%) for reactive circles and 84·44% (95% CI 69·94%–93·01%) for non-reactive circles. In the field study, 669 specimens showed a sensitivity of 94·85% (95% CI 89·29%–97·73%), specificity of 91·56% (95% CI 88·78%–93·71%), and concordance of 92·23% (95% CI 89·87%–94·09%). The positive predictive value was 74·14% (95% CI 66·86%–80·33%) and negative predictive value was 98.59% (95% CI 96·98%–99·38%).

Conclusions

The tool assists in RPR interpretation standardization, enabling data traceability, and quality control for remote and underdeveloped areas.
目的:快速血浆反应素(RPR)试验是诊断梅毒和评价治疗效果的传统方法,依赖于主观解释,技术熟练程度较高。本研究旨在开发和验证一个用户友好的人工智能(AI)解释工具。方法:利用276张RPR阴性样本和223张RPR阳性样本的600张RPR卡照片数据集进行模型开发。参考结果基于至少三分之二经验丰富的实验室人员的一致解释。然后利用深度学习算法开发了一个解释模型,并将其加载到智能手机中,在2023年10月至2024年4月期间在两个临床中心进行现场解释。结果:该模型对反应性圈的准确率为82.67% (95% CI为71.82% ~ 90.09%),对非反应性圈的准确率为84.44% (95% CI为69.94% ~ 93.01%)。在野外研究中,669份标本的敏感性为94.85% (95% CI 89.29% ~ 97.73%),特异性为91.56% (95% CI 88.78% ~ 93.71%),一致性为92.23% (95% CI 89.87% ~ 94.09%)。阳性预测值为71.4% (95% CI 66.86% ~ 8033%),阴性预测值为98.59% (95% CI 96.98% ~ 99.38%)。结论:该工具有助于RPR解释标准化,实现数据可追溯性,并对偏远和欠发达地区进行质量控制。
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引用次数: 0
The spread of CTX-M-type extended-spectrum beta-lactamases in China: Epidemiology and evolutionary analyses ctx - m型广谱β -内酰胺酶在中国的传播:流行病学和进化分析
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-03-03 DOI: 10.1016/j.jinf.2025.106457
Keyi Yu , Zhenzhou Huang , Xiao Liu , He Gao , Xuemei Bai , Zhiwen Sun , Duochun Wang
CTX-M-type extended-spectrum beta-lactamases (ESBLs) have shown a high level of global transmission, with limited systematic understanding of their epidemic patterns in China. A comprehensive analysis covering 1974–2023 identified 133 (3.2%) blaCTX-Ms-producing strains among 4146 strains from 25 Chinese cities across 82 genera were performed. Integrating with public database strains (n=431), the study comprised 564 blaCTX-Ms-positive isolates sourced from 19 provinces (1986–2022) including 300 (53.2%) clinical and 228 (40.4%) environmental blaCTX-Ms. The most frequent sources of infection were diarrhea (44%), upper respiratory tract infection (22.2%) and urinary tract infection (14%). Phylogenetic studies indicated CTX-M-1 and CTX-M-9 emerged as the predominant subgroups. Lineages exhibited diverse mutation sites without being restricted by geographical conditions. Ka/Ks ratio distribution varied significantly among lineages (P<0.05). Lineages 1 (L1) and L2 were characterized by neutral or purifying selection, whereas L3 was mainly under purifying selection. Adaptive evolution was noted at different loci within each lineage. The influence of geographic distance on phylogeny varied distinctly across different lineages. Notably, for Lineage L3, there was a remarkably strong correlation observed, which implies that human activities exerted a more substantial influence on genetic distances compared to geography. This research provides valuable insights into the epidemiology, genotypic diversity, and evolutionary traits of blaCTX-Ms in China, supporting health risk assessment for early warning systems.
ctx - m型广谱β -内酰胺酶(ESBLs)已显示出高水平的全球传播,但对其在中国的流行模式系统了解有限。对1974-2023年中国25个城市4146株82属产blactx - ms菌株进行综合分析,鉴定出产blactx - ms菌株133株(3.2%)。结合公共数据库菌株(n=431),该研究包括来自19个省份(1986-2022年)的564株blaCTX-Ms阳性分离株,其中临床blaCTX-Ms 300株(53.2%),环境blaCTX-Ms 228株(40.4%)。最常见的感染源为腹泻(44%)、上呼吸道感染(22.2%)和尿路感染(14%)。系统发育研究表明CTX-M-1和CTX-M-9是主要亚群。谱系表现出不同的突变位点,不受地理条件的限制。Ka/Ks比值在不同世系间分布差异显著(p < 0.05)。谱系1 (L1)和L2以中性选择和纯化选择为主,而L3以纯化选择为主。适应性进化在每个谱系的不同位点被注意到。地理距离对系统发育的影响在不同世系间差异明显。值得注意的是,对于谱系L3,观察到非常强的相关性,这意味着与地理位置相比,人类活动对遗传距离的影响更大。该研究为了解中国blaCTX-Ms的流行病学、基因型多样性和进化特征提供了有价值的见解,为早期预警系统的健康风险评估提供了支持。
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引用次数: 0
Host-derived Delta-like Canonical Notch ligand-1 in sepsis and septic shock: Infection site, pathogens and disease severity matter – Secondary analysis of data from a randomized controlled trial 宿主衍生的δ样规范Notch配体-1在败血症和脓毒性休克中的作用:感染部位、病原体和疾病严重程度的关系——一项随机对照试验数据的二次分析
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-03-03 DOI: 10.1016/j.jinf.2025.106458
Vivienne Theobald , Frank Bloos , Michael Bauer , Thorsten Brenner , Maik von der Forst , Patrick Meybohm , Judith Schenz , Felix C.F. Schmitt , Benedikt Siegler , Markus A. Weigand , Maximilian Dietrich , for the SepNet Critical Care Trials Group

Background

Sepsis is a life-threatening condition and many biomarkers for diagnosing and treatment guidance have been investigated in recent years. However, new ones are emerging almost daily, only few markers with diagnostic value have passed to entered clinical routine application. Delta-like canonical Notch ligand-1 (DLL-1) seems to be a potential contributor in the differentiation between sepsis and non-septic infection. Its role for clinical application and potential septic outcome prediction is yet unclear.

Methods

This study is a secondary analysis of data and DLL-1 measurements from plasma samples obtained in the SISPCT trial. Primary objective of this explorative study was to investigate the difference of DLL-1 values between patients with sepsis and septic shock. Secondary objectives were the differences in DLL-1 levels in patients with different blood culture results, with infections caused by different pathogens, by origin of infection and disease severity. Furthermore, the study investigated the use of DLL-1 for in-hospital and intensive care unit (ICU) mortality prediction. Therefore, data from 1.027 patients were analyzed.

Results

DLL-1 values were significantly higher in patients with septic shock than in septic patients (13,003 ± 7695 pg/mL and 9257 ± 4188 pg/mL, p<0.001). Patients with abdominal infections, primary bacteremia or surgical wound infections exhibited the highest DLL-1 values. In addition, patients with gram-negative pathogens had significantly higher DLL-1 levels than those with specific gram-positive pathogens or negative blood cultures (p<0.001). Infections caused by Escherichia coli, Enterobacterales, and Staphylococcus aureus were associated with the highest DLL-1 levels (18,341 pg/mL, (12,968; 23,250), 21,556 pg/mL (14,386; 30,939) and 16,352 pg/mL (11,905; 25,853), respectively). DLL-1 levels correlated with increasing SOFA scores and demonstrated predictive value for in-hospital and ICU mortality, with an AUC of 0.7, outperforming lactate and procalcitonin.

Conclusion

Delta-like canonical Notch ligand-1 (DLL-1) is increased in septic shock compared to sepsis. Its elevation appears to be dependent on the infection focus, the triggering pathogen and the disease severity. Furthermore, it has a predictive value for mortality.
脓毒症是一种危及生命的疾病,近年来研究了许多用于诊断和治疗指导的生物标志物。然而,几乎每天都有新的标志物出现,只有少数具有诊断价值的标志物通过进入临床常规应用。δ样典型Notch配体-1 (DLL-1)似乎是脓毒症和非脓毒症感染区分的潜在因素。其在临床应用和潜在脓毒性结局预测中的作用尚不清楚。方法本研究是对SISPCT试验中获得的血浆样本的数据和DLL-1测量的二次分析。本探索性研究的主要目的是探讨脓毒症和脓毒性休克患者dl1值的差异。次要目的是不同血培养结果、不同病原体感染、感染来源和疾病严重程度的患者中dl1水平的差异。此外,本研究还调查了dl1在院内和重症监护病房(ICU)死亡率预测中的应用。因此,我们分析了1.027例患者的数据。结果脓毒性休克患者的dll -1值明显高于脓毒性休克患者(13,003±7695 pg/mL和9257±4188 pg/mL, p < 0.001)。腹部感染、原发性菌血症或手术伤口感染患者的DLL-1值最高。此外,革兰氏阴性病原体患者的DLL-1水平显著高于特定革兰氏阳性病原体或血培养阴性患者(p<0.001)。大肠杆菌、肠杆菌和金黄色葡萄球菌引起的感染与最高的DLL-1水平相关(18,341 pg/mL, 12,968;23,250), 21,556 pg/mL (14,386;30,939)和16,352 pg/mL (11,905;25853),分别)。DLL-1水平与SOFA评分升高相关,并显示出对住院和ICU死亡率的预测价值,AUC为0.7,优于乳酸和降钙素原。结论与脓毒症相比,脓毒症患者δ样Notch配体-1 (dl -1)水平升高。它的升高似乎取决于感染病灶、触发病原体和疾病严重程度。此外,它对死亡率有预测价值。
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引用次数: 0
Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response 表征SARS-CoV-2核衣壳蛋白抗体反应。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-03-01 DOI: 10.1016/j.jinf.2025.106436
C.C.A. Noble , E. McDonald , S. Nicholson , S. Biering-Sørensen , L.F. Pittet , A.L. Byrne , J. Croda , M. Dalcolmo , M.V.G. Lacerda , M. Lucas , D.J. Lynn , C. Prat Aymerich , P.C. Richmond , A. Warris , N. Curtis , N.L. Messina , the BRACE Trial Consortium Group

Objectives

SARS-CoV-2 nucleocapsid (N) protein antibodies can be used to identify the serological response to natural infection in those who have previously received a COVID-19 spike-based vaccine. Anti-N antibody responses can also be induced by inactivated whole SARS-CoV-2 virus vaccines, such as CoronaVac. We aimed to characterise antibody responses to the N protein following COVID-19 and following vaccination with CoronaVac.

Methods

Using participants from an international randomised controlled trial, we investigated the evolution of anti-N antibody responses over time in two separate groups: adults following COVID-19, and in adults following vaccination with CoronaVac.

Results

In 212 participants who had COVID-19, the anti-N seroconversion rate was 96.9% in those infected following an incomplete course of COVID-19 (spike-based) vaccinations and 88.2% in those infected following a complete course. Anti-N antibody indices were highly variable between participants, and higher in participants who had more severe COVID-19 symptoms, were aged ≥60 years, were unvaccinated, had comorbidities and those resident in Brazil. Most participants remained seropositive after 12 months. In 317 separate participants, the anti-N seroconversion rate was 63.5% following CoronaVac vaccination, with variable antibody indices.

Conclusions

Anti-N responses to COVID-19 and CoronaVac are highly variable but persistent. A prior complete course of COVID-19 spike-based vaccination reduced both anti-N seroconversion and antibody indices following COVID-19.
目的:SARS-CoV-2核衣壳蛋白抗体可用于检测先前接种过COVID-19刺突疫苗的人对自然感染的血清学反应。在接受灭活的SARS-CoV-2全病毒疫苗(如CoronaVac)的患者中也可以检测到抗n抗体反应。我们的目的是表征COVID-19和冠状病毒疫苗接种后对N蛋白的抗体反应。方法:研究人员使用一项国际随机对照试验的参与者,研究了两组患者抗n抗体反应随时间的演变:感染COVID-19后,或接种冠状病毒疫苗后。结果:在212名患有COVID-19的参与者中,在未完成COVID-19疫苗接种过程(基于峰值)的感染者中,抗n血清转化率为96.9%,在完全接种疫苗的感染者中为88.2%。抗n抗体指数在参与者之间存在很大差异,在COVID-19症状更严重、年龄≥60岁、未接种疫苗、有合并症和巴西居民的参与者中,抗n抗体指数更高。大多数参与者在12个月后仍呈血清阳性。在317名单独的参与者中,冠状病毒疫苗接种后抗n血清转换率为63.5%,抗体指标可变。结论:对COVID-19和CoronaVac的抗n反应是高度可变的,但是持久的。先前完整的基于COVID-19尖峰的疫苗接种过程降低了COVID-19后的抗n血清转化和抗体指数。
{"title":"Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response","authors":"C.C.A. Noble ,&nbsp;E. McDonald ,&nbsp;S. Nicholson ,&nbsp;S. Biering-Sørensen ,&nbsp;L.F. Pittet ,&nbsp;A.L. Byrne ,&nbsp;J. Croda ,&nbsp;M. Dalcolmo ,&nbsp;M.V.G. Lacerda ,&nbsp;M. Lucas ,&nbsp;D.J. Lynn ,&nbsp;C. Prat Aymerich ,&nbsp;P.C. Richmond ,&nbsp;A. Warris ,&nbsp;N. Curtis ,&nbsp;N.L. Messina ,&nbsp;the BRACE Trial Consortium Group","doi":"10.1016/j.jinf.2025.106436","DOIUrl":"10.1016/j.jinf.2025.106436","url":null,"abstract":"<div><h3>Objectives</h3><div>SARS-CoV-2 nucleocapsid (N) protein antibodies can be used to identify the serological response to natural infection in those who have previously received a COVID-19 spike-based vaccine. Anti-N antibody responses can also be induced by inactivated whole SARS-CoV-2 virus vaccines, such as <em>CoronaVac</em>. We aimed to characterise antibody responses to the N protein following COVID-19 and following vaccination with <em>CoronaVac</em>.</div></div><div><h3>Methods</h3><div>Using participants from an international randomised controlled trial, we investigated the evolution of anti-N antibody responses over time in two separate groups: adults following COVID-19, and in adults following vaccination with <em>CoronaVac</em>.</div></div><div><h3>Results</h3><div>In 212 participants who had COVID-19, the anti-N seroconversion rate was 96.9% in those infected following an incomplete course of COVID-19 (spike-based) vaccinations and 88.2% in those infected following a complete course. Anti-N antibody indices were highly variable between participants, and higher in participants who had more severe COVID-19 symptoms, were aged ≥60 years, were unvaccinated, had comorbidities and those resident in Brazil. Most participants remained seropositive after 12 months. In 317 separate participants, the anti-N seroconversion rate was 63.5% following <em>CoronaVac</em> vaccination, with variable antibody indices.</div></div><div><h3>Conclusions</h3><div>Anti-N responses to COVID-19 and <em>CoronaVac</em> are highly variable but persistent. A prior complete course of COVID-19 spike-based vaccination reduced both anti-N seroconversion and antibody indices following COVID-19.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 3","pages":"Article 106436"},"PeriodicalIF":14.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Extensive dissemination of ESBL-producing Clonal Complex 14 Escherichia coli is likely spread through sexual transmission among men who have sex with men at risk of sexually transmitted infections 产生esbl的克隆复合体14大肠杆菌的广泛传播可能是通过性传播在与有性传播感染风险的男性发生性关系的男性中传播。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-03-01 DOI: 10.1016/j.jinf.2025.106453
Maxime Danjean , Laure Surgers , Guilhem Royer , Vanessa Demontant , Hadrien Kimseng , Amandine Caillault , Bryan Jimenez-Araya , Sarah Seng , Elisabeth Trawinski , Hayette Rougier , Jean-Winoc Decousser , Hervé Jacquier , Anders Boyd , Paul-Louis Woerther

Objectives

We characterized the genetic proximity of Sequence Type (ST) 131, 1193 and 14 Extended-Spectrum Beta-Lactamase-producing E. coli (ESBL-Ec) to assess human determinants of carriage in community settings.

Methods

In this cross-sectional study, we included individuals seeking care at a sexually transmitted infection (STI) or HIV outpatient clinic. ESBL-Ec were compared using phylogeny, core-genome Multi-Locus Sequence Typing and Single-Nucleotide Polymorphism (SNP) determination. Determinants were compared between STs and correlated to genetic distances.

Results

103 individuals carried 112 strains of ST131 (n=63), ST14 (n=26) and ST1193 (n=23). Compared to ST131, ST14 isolates were more commonly found in individuals with any STI (p=0.031), men who have sex with men (p<0.001) and recent antibiotic use (p=0.021); whereas ST1193 isolates were more commonly found in individuals who engaged in insertive anal sex in <6 months (p=0.017). ST131 isolates showed high genomic diversity, while other STs evidenced a high level of proximity. SNPs data indicated the likely spread of a single ST14 (range=1;32) and some ST1193 clusters (range=2;111), which were linked to ST-specific sexual behaviors.

Conclusions

In populations of those at risk of acquiring STI, ST14 and ST1193 ESBL-Ec are emerging. Specific sexual transmissions routes are likely to play a role in their spread.
目的:我们鉴定了序列型(ST) 131、1193和14产广谱β -内酰胺酶大肠杆菌(ESBL-Ec)的遗传接近性,以评估社区环境中人类携带的决定因素。方法:在这项横断面研究中,我们纳入了在性传播感染(STI)或艾滋病毒门诊寻求治疗的个体。采用系统发育、核心基因组多位点序列分型和单核苷酸多态性(SNP)测定对ESBL-Ec进行比较。决定因素在STs之间进行比较,并与遗传距离相关。结果:103人携带ST131 (n=63)、ST14 (n=26)和ST1193 (n=23)菌株112株。与ST131相比,ST14分离株更常见于任何STI患者(p=0.031)和男男性行为者(p结论:在感染STI的高危人群中,ST14和ST1193 ESBL-Ec正在出现。特定的性传播途径可能在其传播中起作用。
{"title":"Extensive dissemination of ESBL-producing Clonal Complex 14 Escherichia coli is likely spread through sexual transmission among men who have sex with men at risk of sexually transmitted infections","authors":"Maxime Danjean ,&nbsp;Laure Surgers ,&nbsp;Guilhem Royer ,&nbsp;Vanessa Demontant ,&nbsp;Hadrien Kimseng ,&nbsp;Amandine Caillault ,&nbsp;Bryan Jimenez-Araya ,&nbsp;Sarah Seng ,&nbsp;Elisabeth Trawinski ,&nbsp;Hayette Rougier ,&nbsp;Jean-Winoc Decousser ,&nbsp;Hervé Jacquier ,&nbsp;Anders Boyd ,&nbsp;Paul-Louis Woerther","doi":"10.1016/j.jinf.2025.106453","DOIUrl":"10.1016/j.jinf.2025.106453","url":null,"abstract":"<div><h3>Objectives</h3><div>We characterized the genetic proximity of Sequence Type (ST) 131, 1193 and 14 Extended-Spectrum Beta-Lactamase-producing <em>E. coli</em> (ESBL-Ec) to assess human determinants of carriage in community settings.</div></div><div><h3>Methods</h3><div>In this cross-sectional study, we included individuals seeking care at a sexually transmitted infection (STI) or HIV outpatient clinic. ESBL-Ec were compared using phylogeny, core-genome Multi-Locus Sequence Typing and Single-Nucleotide Polymorphism (SNP) determination. Determinants were compared between STs and correlated to genetic distances.</div></div><div><h3>Results</h3><div>103 individuals carried 112 strains of ST131 (<em>n</em>=63), ST14 (<em>n</em>=26) and ST1193 (<em>n</em>=23). Compared to ST131, ST14 isolates were more commonly found in individuals with any STI (<em>p</em>=0.031), men who have sex with men (<em>p</em>&lt;0.001) and recent antibiotic use (<em>p</em>=0.021); whereas ST1193 isolates were more commonly found in individuals who engaged in insertive anal sex in &lt;6 months (<em>p</em>=0.017). ST131 isolates showed high genomic diversity, while other STs evidenced a high level of proximity. SNPs data indicated the likely spread of a single ST14 (range=1;32) and some ST1193 clusters (range=2;111), which were linked to ST-specific sexual behaviors.</div></div><div><h3>Conclusions</h3><div>In populations of those at risk of acquiring STI, ST14 and ST1193 ESBL-Ec are emerging. Specific sexual transmissions routes are likely to play a role in their spread.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106453"},"PeriodicalIF":14.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy and safety of GLS4 with entecavir vs entecavir alone in chronic hepatitis B patients: A multicenter clinical trial GLS4联合恩替卡韦与单独恩替卡韦治疗慢性乙型肝炎患者的疗效和安全性:一项多中心临床试验
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-03-01 DOI: 10.1016/j.jinf.2025.106446
Mingyuan Zhang , Yanhang Gao , Fei Kong , Haibing Gao , Yongxiang Yi , Chao Wu , Yongning Xin , Sujun Zheng , Jiajie Lu , Tao Han , Yingren Zhao , Peng Hu , Xiaorong Mao , Qing Xie , Jie Zhang , Jinlin Hou , Zhiliang Gao , Jianqi Lian , Liang Chen , Jia Shang , Junqi Niu

Objectives

GLS4 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator that inhibits HBV replication by interfering with assembly and disassembly of the virus nucleocapsid, this prospective, open-label, comparative, phase 2b trial evaluated the antiviral activity and safety of GLS4/ritonavir (RTV) combined with entecavir in hepatitis B e antigen-positive patients.

Methods

250 CHB patients were enrolled, including treatment-naïve patients and those interrupted anti-HBV drugs for ≥ 6 months (Part A, n=125), and patients who had taken ETV for ≥1 year and had achieved viral suppression (Part B, n=125). Patients were randomly allocated to receive 120 mg GLS4/100 mg RTV plus 0.5 mg ETV or 0.5 mg ETV monotherapy for 96 weeks.

Results

In the mid-term, in Part A (n=122), greater least-squares mean (LSM) changes from baseline were observed in the GLS4/RTV plus ETV cohort than in ETV monotherapy cohort in HBV DNA (−6.28 vs −5.72 log10 IU/ml, p=0.0005), HBsAg (−0.87 vs −0.65 log10 IU/ml, p=0.0653), HBV pgRNA (−3.83 vs −1.91 log10 copies/ml, p<0.0001); The proportions of both HBV DNA and pgRNA negative patients were 17.3% (13/75, GLS4/RTV plus ETV) and 0% (0/30, ETV monotherapy). In Part B (n=123), greater mean LSM reductions in HBsAg (−0.17 vs −0.06 log10 IU/ml, p=0.0013), HBV pgRNA (−1.61 vs −0.28 log10 copies/ml, p<0.0001) were also observed in the GLS4/RTV+ETV cohort. the proportions of both HBV DNA and pgRNA-negative patients were 71.6% (48/67, GLS4/RTV plus ETV) and 18.9% (7/37, ETV monotherapy), respectively. No patients achieved HBsAg loss at week 48.
GLS4/RTV + ETV were well tolerated, the most common adverse events were elevated alanine aminotransferase levels and hypertriglyceridemia, which were reversed by temporary GLS4/RTV discontinuation.

Conclusions

The primary analysis at week 48 showed that the antiviral efficacy of GLS4/RTV with ETV was clearly superior to that of ETV monotherapy. GLS4/RTV with ETV was well tolerated; further studies evaluating its safety and efficacy are ongoing. (clinical trial identifier: NCT04147208).
目的:GLS4是一种首屈一指的乙型肝炎病毒(HBV)衣壳组装调节剂,通过干扰病毒核衣壳的组装和拆卸来抑制HBV复制,这项前瞻性、开放标签、比较的2b期试验评估了GLS4/利托那韦(RTV)联合恩替卡韦在乙型肝炎e抗原阳性患者中的抗病毒活性和安全性。方法:纳入250例CHB患者,包括treatment-naïve患者和抗hbv药物中断≥6个月的患者(A部分,n=125),以及服用ETV≥1年并实现病毒抑制的患者(B部分,n=125)。患者被随机分配接受120mg GLS4/100mg RTV + 0.5mg ETV或0.5mg ETV单药治疗,疗程96周。结果:中期,在A部分(n=122)中,GLS4/RTV + ETV组的HBV DNA (-6.28 vs -5.72 log10 IU/ml, p=0.0005)、HBsAg (-0.87 vs -0.65 log10 IU/ml, p=0.0653)、HBV pgRNA (-3.83 vs -1.91 log10 copies/ml, p)与基线相比的最小二乘平均值(LSM)变化大于ETV单药组。结论:第48周的初步分析显示GLS4/RTV联合ETV的抗病毒效果明显优于ETV单药组。GLS4/RTV联合ETV耐受良好;评估其安全性和有效性的进一步研究正在进行中。(临床试验编号:NCT04147208)。
{"title":"Efficacy and safety of GLS4 with entecavir vs entecavir alone in chronic hepatitis B patients: A multicenter clinical trial","authors":"Mingyuan Zhang ,&nbsp;Yanhang Gao ,&nbsp;Fei Kong ,&nbsp;Haibing Gao ,&nbsp;Yongxiang Yi ,&nbsp;Chao Wu ,&nbsp;Yongning Xin ,&nbsp;Sujun Zheng ,&nbsp;Jiajie Lu ,&nbsp;Tao Han ,&nbsp;Yingren Zhao ,&nbsp;Peng Hu ,&nbsp;Xiaorong Mao ,&nbsp;Qing Xie ,&nbsp;Jie Zhang ,&nbsp;Jinlin Hou ,&nbsp;Zhiliang Gao ,&nbsp;Jianqi Lian ,&nbsp;Liang Chen ,&nbsp;Jia Shang ,&nbsp;Junqi Niu","doi":"10.1016/j.jinf.2025.106446","DOIUrl":"10.1016/j.jinf.2025.106446","url":null,"abstract":"<div><h3>Objectives</h3><div>GLS4 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator that inhibits HBV replication by interfering with assembly and disassembly of the virus nucleocapsid, this prospective, open-label, comparative, phase 2b trial evaluated the antiviral activity and safety of GLS4/ritonavir (RTV) combined with entecavir in hepatitis B e antigen-positive patients.</div></div><div><h3>Methods</h3><div>250 CHB patients were enrolled, including treatment-naïve patients and those interrupted anti-HBV drugs for ≥ 6 months (Part A, n=125), and patients who had taken ETV for ≥1 year and had achieved viral suppression (Part B, n=125). Patients were randomly allocated to receive 120 mg GLS4/100 mg RTV plus 0.5 mg ETV or 0.5 mg ETV monotherapy for 96 weeks.</div></div><div><h3>Results</h3><div>In the mid-term, in Part A (n=122), greater least-squares mean (LSM) changes from baseline were observed in the GLS4/RTV plus ETV cohort than in ETV monotherapy cohort in HBV DNA (−6.28 vs −5.72 log10 IU/ml, p=0.0005), HBsAg (−0.87 vs −0.65 log10 IU/ml, p=0.0653), HBV pgRNA (−3.83 vs −1.91 log10 copies/ml, p&lt;0.0001); The proportions of both HBV DNA and pgRNA negative patients were 17.3% (13/75, GLS4/RTV plus ETV) and 0% (0/30, ETV monotherapy). In Part B (n=123), greater mean LSM reductions in HBsAg (−0.17 vs −0.06 log10 IU/ml, p=0.0013), HBV pgRNA (−1.61 vs −0.28 log10 copies/ml, p&lt;0.0001) were also observed in the GLS4/RTV+ETV cohort. the proportions of both HBV DNA and pgRNA-negative patients were 71.6% (48/67, GLS4/RTV plus ETV) and 18.9% (7/37, ETV monotherapy), respectively. No patients achieved HBsAg loss at week 48.</div><div>GLS4/RTV + ETV were well tolerated, the most common adverse events were elevated alanine aminotransferase levels and hypertriglyceridemia, which were reversed by temporary GLS4/RTV discontinuation.</div></div><div><h3>Conclusions</h3><div>The primary analysis at week 48 showed that the antiviral efficacy of GLS4/RTV with ETV was clearly superior to that of ETV monotherapy. GLS4/RTV with ETV was well tolerated; further studies evaluating its safety and efficacy are ongoing. (clinical trial identifier: NCT04147208).</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 3","pages":"Article 106446"},"PeriodicalIF":14.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genomic variation and impact on the proteins of Mpox virus m痘病毒基因组变异及其对蛋白质的影响
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-02-26 DOI: 10.1016/j.jinf.2025.106452
Hao Chen , Yang Xu , Yafei Li , Hui-Qi Qu, Hakon Hakonarson, Jin Li, Qianghua Xia
{"title":"Genomic variation and impact on the proteins of Mpox virus","authors":"Hao Chen ,&nbsp;Yang Xu ,&nbsp;Yafei Li ,&nbsp;Hui-Qi Qu,&nbsp;Hakon Hakonarson,&nbsp;Jin Li,&nbsp;Qianghua Xia","doi":"10.1016/j.jinf.2025.106452","DOIUrl":"10.1016/j.jinf.2025.106452","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106452"},"PeriodicalIF":14.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Global epidemiology, seasonality and climatic drivers of the four human parainfluenza virus types 四种人类副流感病毒类型的全球流行病学、季节性和气候驱动因素。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-02-26 DOI: 10.1016/j.jinf.2025.106451
Yi Song , Yu-Nong Gong , Kuan-Fu Chen , David K. Smith , Hassan Zaraket , Seweryn Bialasiewicz , Sarah Tozer , Paul KS Chan , Evelyn SC Koay , Hong Kai Lee , Kok Keng Tee , Pieter LA Fraaij , Lance Jennings , Matti Waris , Hidekazu Nishimura , Aripuana Watanabe , Theo Sloots , Jen Kok , Dominic E. Dwyer , Marion PG Koopmans , Tommy TY Lam

Objectives

Human parainfluenza viruses (hPIV) are a common cause of acute respiratory infections, especially in children under five years and the elderly. hPIV can be subclassified as types 1–4: these showed various seasonality patterns worldwide, and it is unclear how climatic factors might consistently explain their global epidemiology.

Methods

This study collected time-series incidence data from the literature and hPIV surveillance programs worldwide (47 locations). Wavelet analysis and circular statistics were used to detect the seasonality and the months of peak incidence for each hPIV type. Relationships between climatic drivers and incidence peaks were assessed using a generalized estimating equation.

Results

The average positive rate of hPIV among patients with respiratory symptoms was 5.6% and ranged between 0.69–3.48% for different types. In the northern temperate region, the median peak incidence months for hPIV1, hPIV2, and hPIV4 were from September to October, while for hPIV3, it was in late May. Seasonal peaks of hPIV3 were associated with higher monthly temperatures and lower diurnal temperatures range throughout the year; hPIV4 peaks appeared to correlate with lower monthly temperatures and higher precipitation throughout the year. Different hPIV types exhibit different patterns of global epidemiology and transmission.

Conclusions

Climate drivers may play a role in hPIV transmission. More comprehensive and coherent surveillance of hPIV types would enable more in-depth analyses and inform the timing of preventive measures.
目的:人类副流感病毒(hPIV)是急性呼吸道感染的常见原因,特别是在五岁以下儿童和老年人中。hPIV可细分为1-4型:它们在世界范围内表现出不同的季节性模式,气候因素如何一致地解释其全球流行病学尚不清楚。方法:本研究从文献和全球47个地点的hPIV监测项目中收集了时间序列发病率数据。采用小波分析和循环统计方法检测各类型hPIV的季节性和发病高峰月份。利用广义估计方程评估了气候驱动因素与发病率峰值之间的关系。结果:呼吸道症状患者hPIV平均阳性率为5.6%,不同类型hPIV阳性率在0.69 ~ 3.48%之间。在北温带地区,hPIV1、hPIV2和hPIV4的中位发病高峰期为9 - 10月,而hPIV3的中位发病高峰期为5月下旬。hPIV3的季节高峰与全年较高的月气温和较低的日温差有关;hPIV4峰值似乎与全年较低的月气温和较高的降水有关。不同类型的hPIV表现出不同的全球流行病学和传播模式。结论:气候因素可能在hPIV传播中发挥作用。对hPIV类型进行更全面和连贯的监测将能够进行更深入的分析,并为采取预防措施的时机提供信息。
{"title":"Global epidemiology, seasonality and climatic drivers of the four human parainfluenza virus types","authors":"Yi Song ,&nbsp;Yu-Nong Gong ,&nbsp;Kuan-Fu Chen ,&nbsp;David K. Smith ,&nbsp;Hassan Zaraket ,&nbsp;Seweryn Bialasiewicz ,&nbsp;Sarah Tozer ,&nbsp;Paul KS Chan ,&nbsp;Evelyn SC Koay ,&nbsp;Hong Kai Lee ,&nbsp;Kok Keng Tee ,&nbsp;Pieter LA Fraaij ,&nbsp;Lance Jennings ,&nbsp;Matti Waris ,&nbsp;Hidekazu Nishimura ,&nbsp;Aripuana Watanabe ,&nbsp;Theo Sloots ,&nbsp;Jen Kok ,&nbsp;Dominic E. Dwyer ,&nbsp;Marion PG Koopmans ,&nbsp;Tommy TY Lam","doi":"10.1016/j.jinf.2025.106451","DOIUrl":"10.1016/j.jinf.2025.106451","url":null,"abstract":"<div><h3>Objectives</h3><div>Human parainfluenza viruses (hPIV) are a common cause of acute respiratory infections, especially in children under five years and the elderly. hPIV can be subclassified as types 1–4: these showed various seasonality patterns worldwide, and it is unclear how climatic factors might consistently explain their global epidemiology.</div></div><div><h3>Methods</h3><div>This study collected time-series incidence data from the literature and hPIV surveillance programs worldwide (47 locations). Wavelet analysis and circular statistics were used to detect the seasonality and the months of peak incidence for each hPIV type. Relationships between climatic drivers and incidence peaks were assessed using a generalized estimating equation.</div></div><div><h3>Results</h3><div>The average positive rate of hPIV among patients with respiratory symptoms was 5.6% and ranged between 0.69–3.48% for different types. In the northern temperate region, the median peak incidence months for hPIV1, hPIV2, and hPIV4 were from September to October, while for hPIV3, it was in late May. Seasonal peaks of hPIV3 were associated with higher monthly temperatures and lower diurnal temperatures range throughout the year; hPIV4 peaks appeared to correlate with lower monthly temperatures and higher precipitation throughout the year. Different hPIV types exhibit different patterns of global epidemiology and transmission.</div></div><div><h3>Conclusions</h3><div>Climate drivers may play a role in hPIV transmission. More comprehensive and coherent surveillance of hPIV types would enable more in-depth analyses and inform the timing of preventive measures.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106451"},"PeriodicalIF":14.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical epidemiological characteristics of hospitalized pediatric viral community-acquired pneumonia in China 中国住院儿童病毒性社区获得性肺炎临床流行病学特征
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-02-24 DOI: 10.1016/j.jinf.2025.106450
Qianyu Feng , Jinjin Wang , Xinyu Wang , Jiao Tian , Linlin Zhang , Dilara Dilmurat , Mengjia Liu , Junhong Ai , Guoshuang Feng , Yueping Zeng , Ran Wang , Zhengde Xie

Background

Community acquired pneumonia (CAP) is a major global public health concern among children, with viral pathogens playing a significant role. Despite this, national multicenter studies on viral community acquired pneumonia (VCAP) in hospitalized children remain scarce. The study employed a multicenter approach to investigate the clinical epidemiology and burden of VCAP in hospitalized children across China.

Method

Data were extracted from the face sheets of discharge medical records (FSMRs) within the FuTang Update Medical Records (FUTURE) database, spanning 2016 to 2022. VCAP cases from 33 tertiary children's hospitals were identified and analyzed. Epidemiological characteristics, length of stay (LOS), and hospitalization costs were compared using appropriate statistical methods.

Results

Between January 2016 to December 2022, 72,905 hospitalized cases of CAP with confirmed diagnoses of viral pathogens were documented, accounting 4.07% of all CAP cases (72,905/1791,343). Respiratory syncytial virus (RSV) was the leading cause, responsible for 57.21% of cases, followed by adenovirus, parainfluenza virus, human rhinovirus and influenza virus. The male-to-female ratio was 1.69:1, and infants under 1 year of age represented 59.84% of hospitalizations. Temporal trends showed an increase in VCAP hospitalizations from 2016 to 2019, a decline in 2020, followed by a resurgence in 2021 and 2022. Seasonally, the majority of cases occurred during winter (December to February, 41.67%), while summer (June to August) had the lowest proportion (16.80%). A total of 40 deaths were reported, representing a mortality rate of 0.05%. The median LOS was 7 days, with a median hospitalization cost of 907.38 USD.

Conclusions

Although the proportion of CAP cases in children with confirmed viral pathogen in China is relatively low, VCAP remains a significant health burden for children. RSV is the most prevalent viral cause of VCAP, particularly affecting infants under 1 year of age, while adenovirus is associated with the highest mortality, longest LOS, and highest hospitalization costs. VCAP cases peak during the winter months. While the prognosis is generally favorable, the disease continues to pose a considerable public health challenge.
社区获得性肺炎(CAP)是全球主要的儿童公共卫生问题,病毒性病原体在其中起着重要作用。尽管如此,关于住院儿童病毒性社区获得性肺炎(VCAP)的全国性多中心研究仍然很少。本研究采用多中心方法调查中国住院儿童VCAP的临床流行病学和负担。方法数据提取自2016年至2022年FuTang Update medical records (FUTURE)数据库中出院病历(fsmr)的人脸表。对33家三级儿童医院的VCAP病例进行分析。采用适当的统计方法比较流行病学特征、住院时间(LOS)和住院费用。结果2016年1月至2022年12月,确诊为病毒性病原体的CAP住院病例72905例,占CAP总病例的4.07%(72905 /1791,343)。呼吸道合胞病毒(RSV)占57.21%,其次是腺病毒、副流感病毒、人鼻病毒和流感病毒。男女比例为1.69:1,1岁以下婴儿占住院人数的59.84%。时间趋势显示,从2016年到2019年,VCAP住院人数增加,2020年下降,随后在2021年和2022年回升。季节上,冬季(12 ~ 2月)发病最多,占41.67%,夏季(6 ~ 8月)发病比例最低,占16.80%。总共报告了40例死亡,死亡率为0.05%。平均生存期为7天,平均住院费用为907.38美元。结论虽然中国确诊的病毒性病原体儿童中CAP病例的比例相对较低,但VCAP仍然是儿童的重大健康负担。RSV是引起VCAP最常见的病毒,尤其影响1岁以下的婴儿,而腺病毒与最高死亡率、最长的LOS和最高的住院费用相关。VCAP病例在冬季达到高峰。虽然预后普遍良好,但该疾病继续构成相当大的公共卫生挑战。
{"title":"Clinical epidemiological characteristics of hospitalized pediatric viral community-acquired pneumonia in China","authors":"Qianyu Feng ,&nbsp;Jinjin Wang ,&nbsp;Xinyu Wang ,&nbsp;Jiao Tian ,&nbsp;Linlin Zhang ,&nbsp;Dilara Dilmurat ,&nbsp;Mengjia Liu ,&nbsp;Junhong Ai ,&nbsp;Guoshuang Feng ,&nbsp;Yueping Zeng ,&nbsp;Ran Wang ,&nbsp;Zhengde Xie","doi":"10.1016/j.jinf.2025.106450","DOIUrl":"10.1016/j.jinf.2025.106450","url":null,"abstract":"<div><h3>Background</h3><div>Community acquired pneumonia (CAP) is a major global public health concern among children, with viral pathogens playing a significant role. Despite this, national multicenter studies on viral community acquired pneumonia (VCAP) in hospitalized children remain scarce. The study employed a multicenter approach to investigate the clinical epidemiology and burden of VCAP in hospitalized children across China.</div></div><div><h3>Method</h3><div>Data were extracted from the face sheets of discharge medical records (FSMRs) within the FuTang Update Medical Records (FUTURE) database, spanning 2016 to 2022. VCAP cases from 33 tertiary children's hospitals were identified and analyzed. Epidemiological characteristics, length of stay (LOS), and hospitalization costs were compared using appropriate statistical methods.</div></div><div><h3>Results</h3><div>Between January 2016 to December 2022, 72,905 hospitalized cases of CAP with confirmed diagnoses of viral pathogens were documented, accounting 4.07% of all CAP cases (72,905/1791,343). Respiratory syncytial virus (RSV) was the leading cause, responsible for 57.21% of cases, followed by adenovirus, parainfluenza virus, human rhinovirus and influenza virus. The male-to-female ratio was 1.69:1, and infants under 1 year of age represented 59.84% of hospitalizations. Temporal trends showed an increase in VCAP hospitalizations from 2016 to 2019, a decline in 2020, followed by a resurgence in 2021 and 2022. Seasonally, the majority of cases occurred during winter (December to February, 41.67%), while summer (June to August) had the lowest proportion (16.80%). A total of 40 deaths were reported, representing a mortality rate of 0.05%. The median LOS was 7 days, with a median hospitalization cost of 907.38 USD.</div></div><div><h3>Conclusions</h3><div>Although the proportion of CAP cases in children with confirmed viral pathogen in China is relatively low, VCAP remains a significant health burden for children. RSV is the most prevalent viral cause of VCAP, particularly affecting infants under 1 year of age, while adenovirus is associated with the highest mortality, longest LOS, and highest hospitalization costs. VCAP cases peak during the winter months. While the prognosis is generally favorable, the disease continues to pose a considerable public health challenge.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 3","pages":"Article 106450"},"PeriodicalIF":14.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clustering Mycobacterium tuberculosis-specific CD154+CD4+ T cells for distinguishing tuberculosis disease from infection based on single-cell RNA-seq analysis 基于单细胞RNA-seq分析聚类结核分枝杆菌特异性CD154+CD4+ T细胞以区分结核病和感染
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-02-24 DOI: 10.1016/j.jinf.2025.106449
Xiaochen Wang , Kaishan Jiang , Wenjin Xing , Qiudan Xin , Qiongjie Hu , Shiji Wu , Ziyong Sun , Hongyan Hou , Yi Ren , Feng Wang

Background

Distinguishing between active tuberculosis disease (TBD) and latent tuberculosis infection (TBI) is crucial for TB control but remains challenging.

Methods

Single-cell RNA sequencing was conducted on purified Mycobacterium tuberculosis (MTB)-specific CD154+CD4+ T cells.

Results

We observe a superior role of CD154 in detecting MTB infection, whereas its ability in distinguishing TBD from TBI is still limited due to patient heterogeneity. Single-cell RNA sequencing of MTB-specific CD154+CD4+ T cells identifies 10 distinct clusters, including Treg, T_act, Th1_pex, Th1_eff, Tfh, T_na, Th17_ex, Th2, NKT, and Th1_cyt. Notably, effector and apoptotic Th1 cells are predominant in CD154+CD4+ T cells of TBD. However, Tfh cells are the primary component in TBI. Most Th1_pex cells are positioned at the end of the developmental trajectory and are regulated by key genes associated with apoptosis and early exhaustion, such as GADD45B, FOS, and EZH2. Oxidative stress-induced metabolic disorder, marked by increased metabolism of nitrogen, cysteine, and glutathione, also contributes to the apoptosis of Th1_pex cells. Using seven features including NA, CM, EM, EMRA, CXCR3+ Th1, IFN-γ+ Th1, and Tfh of CD154+CD4+ T cells, both TBD and TBI can be classified into different subtypes, and a further established random forest model can accurately differentiate TBD from TBI. Additionally, the key checkpoints of exhausted MTB-specific Th1 cells are identified and blocking ADORA2A efficiently restores their function.

Conclusions

We depict the cellular compositions, transcriptional characteristics, and developmental trajectories of MTB-specific CD154+CD4+ T cells from TBI to TBD, putting forward a new direction in the diagnosis and prognosis of disease.
背景区分活动性结核病(TBD)和潜伏性结核感染(TBI)对结核病控制至关重要,但仍然具有挑战性。方法对纯化的结核分枝杆菌(MTB)特异性CD154+CD4+ T细胞进行单细胞RNA测序。结果我们观察到CD154在检测MTB感染中的优越作用,然而由于患者异质性,其区分TBD和TBI的能力仍然有限。mtb特异性CD154+CD4+ T细胞的单细胞RNA测序鉴定出10个不同的簇,包括Treg, T_act, Th1_pex, Th1_eff, Tfh, T_na, Th17_ex, Th2, NKT和Th1_cyt。值得注意的是,TBD的CD154+CD4+ T细胞中以效应细胞和凋亡细胞为主。然而,Tfh细胞是TBI的主要组成部分。大多数Th1_pex细胞位于发育轨迹的末端,受与凋亡和早期衰竭相关的关键基因调控,如GADD45B、FOS和EZH2。氧化应激诱导的代谢紊乱,以氮、半胱氨酸和谷胱甘肽代谢增加为特征,也有助于Th1_pex细胞的凋亡。利用CD154+CD4+ T细胞NA、CM、EM、EMRA、CXCR3+ Th1、IFN-γ+ Th1、Tfh等7个特征将TBD和TBI分类为不同亚型,进一步建立随机森林模型可准确区分TBD和TBI。此外,耗尽mtb特异性Th1细胞的关键检查点被确定,阻断ADORA2A有效地恢复其功能。结论揭示了TBI到TBD过程中mtb特异性CD154+CD4+ T细胞的细胞组成、转录特征和发育轨迹,为疾病的诊断和预后提供了新的方向。
{"title":"Clustering Mycobacterium tuberculosis-specific CD154+CD4+ T cells for distinguishing tuberculosis disease from infection based on single-cell RNA-seq analysis","authors":"Xiaochen Wang ,&nbsp;Kaishan Jiang ,&nbsp;Wenjin Xing ,&nbsp;Qiudan Xin ,&nbsp;Qiongjie Hu ,&nbsp;Shiji Wu ,&nbsp;Ziyong Sun ,&nbsp;Hongyan Hou ,&nbsp;Yi Ren ,&nbsp;Feng Wang","doi":"10.1016/j.jinf.2025.106449","DOIUrl":"10.1016/j.jinf.2025.106449","url":null,"abstract":"<div><h3>Background</h3><div>Distinguishing between active tuberculosis disease (TBD) and latent tuberculosis infection (TBI) is crucial for TB control but remains challenging.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing was conducted on purified <em>Mycobacterium tuberculosis</em> (MTB)-specific CD154<sup>+</sup>CD4<sup>+</sup> T cells.</div></div><div><h3>Results</h3><div>We observe a superior role of CD154 in detecting MTB infection, whereas its ability in distinguishing TBD from TBI is still limited due to patient heterogeneity. Single-cell RNA sequencing of MTB-specific CD154<sup>+</sup>CD4<sup>+</sup> T cells identifies 10 distinct clusters, including Treg, T_act, Th1_pex, Th1_eff, Tfh, T_na, Th17_ex, Th2, NKT, and Th1_cyt. Notably, effector and apoptotic Th1 cells are predominant in CD154<sup>+</sup>CD4<sup>+</sup> T cells of TBD. However, Tfh cells are the primary component in TBI. Most Th1_pex cells are positioned at the end of the developmental trajectory and are regulated by key genes associated with apoptosis and early exhaustion, such as GADD45B, FOS, and EZH2. Oxidative stress-induced metabolic disorder, marked by increased metabolism of nitrogen, cysteine, and glutathione, also contributes to the apoptosis of Th1_pex cells. Using seven features including NA, CM, EM, EMRA, CXCR3<sup>+</sup> Th1, IFN-γ<sup>+</sup> Th1, and Tfh of CD154<sup>+</sup>CD4<sup>+</sup> T cells, both TBD and TBI can be classified into different subtypes, and a further established random forest model can accurately differentiate TBD from TBI. Additionally, the key checkpoints of exhausted MTB-specific Th1 cells are identified and blocking ADORA2A efficiently restores their function.</div></div><div><h3>Conclusions</h3><div>We depict the cellular compositions, transcriptional characteristics, and developmental trajectories of MTB-specific CD154<sup>+</sup>CD4<sup>+</sup> T cells from TBI to TBD, putting forward a new direction in the diagnosis and prognosis of disease.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106449"},"PeriodicalIF":14.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Journal of Infection
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