Pub Date : 2025-03-03DOI: 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。
{"title":"An artificial intelligence tool that may assist with interpretation of rapid plasma reagin test for syphilis: Development and on-site evaluation","authors":"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","doi":"10.1016/j.jinf.2025.106454","DOIUrl":"10.1016/j.jinf.2025.106454","url":null,"abstract":"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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%).</div></div><div><h3>Conclusions</h3><div>The tool assists in RPR interpretation standardization, enabling data traceability, and quality control for remote and underdeveloped areas.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106454"},"PeriodicalIF":14.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568779","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}
Pub Date : 2025-03-03DOI: 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.
{"title":"The spread of CTX-M-type extended-spectrum beta-lactamases in China: Epidemiology and evolutionary analyses","authors":"Keyi Yu , Zhenzhou Huang , Xiao Liu , He Gao , Xuemei Bai , Zhiwen Sun , Duochun Wang","doi":"10.1016/j.jinf.2025.106457","DOIUrl":"10.1016/j.jinf.2025.106457","url":null,"abstract":"<div><div>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%) <em>bla</em><sub>CTX-Ms</sub>-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 <em>bla</em><sub>CTX-Ms</sub>-positive isolates sourced from 19 provinces (1986–2022) including 300 (53.2%) clinical and 228 (40.4%) environmental <em>bla</em><sub>CTX-Ms</sub>. 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 (<em>P</em><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 <em>bla</em><sub>CTX-Ms</sub> in China, supporting health risk assessment for early warning systems.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106457"},"PeriodicalIF":14.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549642","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}
Pub Date : 2025-03-03DOI: 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.
{"title":"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","authors":"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","doi":"10.1016/j.jinf.2025.106458","DOIUrl":"10.1016/j.jinf.2025.106458","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 <em>Escherichia coli</em>, Enterobacterales, and <em>Staphylococcus aureus</em> 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"90 4","pages":"Article 106458"},"PeriodicalIF":14.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562595","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}
Pub Date : 2025-03-01DOI: 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.
{"title":"Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response","authors":"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","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}
Pub Date : 2025-03-01DOI: 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.
{"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 , 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","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><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 <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}
Pub Date : 2025-03-01DOI: 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 , 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","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<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.</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}
Pub Date : 2025-02-26DOI: 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 , Yang Xu , Yafei Li , Hui-Qi Qu, Hakon Hakonarson, Jin Li, 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}
Pub Date : 2025-02-26DOI: 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.
{"title":"Global epidemiology, seasonality and climatic drivers of the four human parainfluenza virus types","authors":"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","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}
Pub Date : 2025-02-24DOI: 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 , Jinjin Wang , Xinyu Wang , Jiao Tian , Linlin Zhang , Dilara Dilmurat , Mengjia Liu , Junhong Ai , Guoshuang Feng , Yueping Zeng , Ran Wang , 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}
Pub Date : 2025-02-24DOI: 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.
{"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 , Kaishan Jiang , Wenjin Xing , Qiudan Xin , Qiongjie Hu , Shiji Wu , Ziyong Sun , Hongyan Hou , Yi Ren , 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}