Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106642
Jing-ying Zhan , Luo Ren , Cheng-kai Li , Ling Zhong , Qiao-ping Wu , Run Wang , Da-peng Chen , Xiao Chen , Kang-yi Ren , Zheng-rong Chen , Zhe-min Zhou , Enmei Liu , Hong Tang
Mycoplasma pneumoniae (MP) infection in children has recently re-emerged with a higher rate of hospitalization in the post-COVID-19 period. However, understanding of how the adaptive immunity plays a role in the bacterial pneumonia is often restrained by recurrent infection and complex co-infection with M. pneumoniae. Herein, we took advantage of the single-cell RNA sequencing (scRNA-seq) and high-dimensional flow cytometry to characterize the impairment of peripheral T and B lymphocytes in pediatric patients with mild Mycoplasma pneumonia (MMPP). These patients were M. pneumoniae mono-infected at hospitalization, and showed an expansion of both effector and memory CD8+ T cells, with exhausted KLRG1hi CD8+ T compartments prevailed. Moreover, they exhibited a hyperactivation of IgM+ plasma cells and unswitched memory B cells, which could partly explain the IgM seroconversion routinely diagnosed in MMPP. Therefore, the hypo-functional CD8+ T cells and polarization of IgM secreting cells might help explain the ill-controlled bacterial replication in MMPP. Furthermore, compared to the healthy controls, IL-17A producing Th17 cells were reduced in MMPP, but cytotoxic granzymes increased significantly. Reduced IL-17A would suggest elevated M. pneumoniae colonization and reduced bacterial clearance in the respiratory tract, whereas cytotoxic property of this pathogenic Th17 cells might play a role in the pulmonary hyper inflammation. Therefore, this work managed to characterize the landscape of dysfunctional T and B lymphocytes that associates with the immune evasion and immunopathogenesis of MMPP.
{"title":"Exhausted KLRG1hi CD8+ T and pathogenic GZMA+ Th17 cells are associated with the mild Mycoplasma pneumoniae pneumonia in children","authors":"Jing-ying Zhan , Luo Ren , Cheng-kai Li , Ling Zhong , Qiao-ping Wu , Run Wang , Da-peng Chen , Xiao Chen , Kang-yi Ren , Zheng-rong Chen , Zhe-min Zhou , Enmei Liu , Hong Tang","doi":"10.1016/j.jinf.2025.106642","DOIUrl":"10.1016/j.jinf.2025.106642","url":null,"abstract":"<div><div><em>Mycoplasma pneumoniae</em> (MP) infection in children has recently re-emerged with a higher rate of hospitalization in the post-COVID-19 period. However, understanding of how the adaptive immunity plays a role in the bacterial pneumonia is often restrained by recurrent infection and complex co-infection with <em>M. pneumoniae</em>. Herein, we took advantage of the single-cell RNA sequencing (scRNA-seq) and high-dimensional flow cytometry to characterize the impairment of peripheral T and B lymphocytes in pediatric patients with mild Mycoplasma pneumonia (MMPP). These patients were <em>M. pneumoniae</em> mono-infected at hospitalization, and showed an expansion of both effector and memory CD8<sup>+</sup> T cells, with exhausted KLRG1<sup>hi</sup> CD8<sup>+</sup> T compartments prevailed. Moreover, they exhibited a hyperactivation of IgM<sup>+</sup> plasma cells and unswitched memory B cells, which could partly explain the IgM seroconversion routinely diagnosed in MMPP. Therefore, the hypo-functional CD8<sup>+</sup> T cells and polarization of IgM secreting cells might help explain the ill-controlled bacterial replication in MMPP. Furthermore, compared to the healthy controls, IL-17A producing Th17 cells were reduced in MMPP, but cytotoxic granzymes increased significantly. Reduced IL-17A would suggest elevated <em>M. pneumoniae</em> colonization and reduced bacterial clearance in the respiratory tract, whereas cytotoxic property of this pathogenic Th17 cells might play a role in the pulmonary hyper inflammation. Therefore, this work managed to characterize the landscape of dysfunctional T and B lymphocytes that associates with the immune evasion and immunopathogenesis of MMPP.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106642"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106649
David Crawford-Jones, Maisy Charlett, Louise Downs, Katie Jeffery
{"title":"Real-world utility of antigen-based testing (LumiraDX) for SARS-CoV-2 and influenza A/B in an acute hospital emergency care setting: a useful triage tool","authors":"David Crawford-Jones, Maisy Charlett, Louise Downs, Katie Jeffery","doi":"10.1016/j.jinf.2025.106649","DOIUrl":"10.1016/j.jinf.2025.106649","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106649"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145472487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106639
Yanan Li , Wenya Feng , Yunhua Yao , Lingyun Guo , Yuchuan Li , Huan Liu , Chengsong Zhao , Gang Liu
Objective
We aimed to investigate the temporal trends in the clinical and molecular epidemiology of pediatric hand, foot, and mouth disease (HFMD) since its designation as a notifiable disease (2008).
Methods
We retrospectively analyzed the pediatric HFMD cases from a single-center database from 2008 to 2024 and performed a binary logistic regression model to identify risk factors for severe disease among laboratory-confirmed cases.
Results
114,420 HFMD cases were reported over 17 years, including 569 severe cases (0.50%, 569/114,420) and 27 deaths (4.75%, 27/569). Following a peak in 2010, annual case numbers stabilized at approximately 10,000 from 2016, declined markedly after vaccine introduction, and dropped further during the COVID-19 pandemic, with a rebound in 2023. Before 2016, Coxsackievirus A16 (CV-A16) (30.66%) and Enterovirus 71 (EV-A71) (23.15%) were the predominant serotypes; subsequently, Coxsackievirus A6 (CV-A6) gradually emerged as the dominant circulating strain. A gradual increase in the age of affected children was observed, with a notable rise in cases among those aged ≥5 years during the post-pandemic period. Multivariable analysis revealed younger age, EV-A71 infection, and rural residence as independent risk factors for severe HFMD.
Conclusions
The evolving epidemiology of pediatric HFMD and the rising age of susceptibility highlight the need for continuous surveillance and early warning to guide prevention and strengthen public health response.
{"title":"Temporal trends in clinical and molecular epidemiology of pediatric hand, foot, and mouth disease, 2008-2024: Insights from 17 years of surveillance","authors":"Yanan Li , Wenya Feng , Yunhua Yao , Lingyun Guo , Yuchuan Li , Huan Liu , Chengsong Zhao , Gang Liu","doi":"10.1016/j.jinf.2025.106639","DOIUrl":"10.1016/j.jinf.2025.106639","url":null,"abstract":"<div><h3>Objective</h3><div>We aimed to investigate the temporal trends in the clinical and molecular epidemiology of pediatric hand, foot, and mouth disease (HFMD) since its designation as a notifiable disease (2008).</div></div><div><h3>Methods</h3><div>We retrospectively analyzed the pediatric HFMD cases from a single-center database from 2008 to 2024 and performed a binary logistic regression model to identify risk factors for severe disease among laboratory-confirmed cases.</div></div><div><h3>Results</h3><div>114,420 HFMD cases were reported over 17 years, including 569 severe cases (0.50%, 569/114,420) and 27 deaths (4.75%, 27/569). Following a peak in 2010, annual case numbers stabilized at approximately 10,000 from 2016, declined markedly after vaccine introduction, and dropped further during the COVID-19 pandemic, with a rebound in 2023. Before 2016, Coxsackievirus A16 (CV-A16) (30.66%) and Enterovirus 71 (EV-A71) (23.15%) were the predominant serotypes; subsequently, Coxsackievirus A6 (CV-A6) gradually emerged as the dominant circulating strain. A gradual increase in the age of affected children was observed, with a notable rise in cases among those aged ≥5 years during the post-pandemic period. Multivariable analysis revealed younger age, EV-A71 infection, and rural residence as independent risk factors for severe HFMD.</div></div><div><h3>Conclusions</h3><div>The evolving epidemiology of pediatric HFMD and the rising age of susceptibility highlight the need for continuous surveillance and early warning to guide prevention and strengthen public health response.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106639"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145418040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106632
Gijs Teunis , Timothy J. Dallman , Magdalena Zając , Magdalena Skarżyńska , Liljana Petrovska , Angela Pista , Leonor Silveira , Lurdes Clemente , Amandine Thépault , Laetitia Bonifait , Annaëlle Kerouanton , Marianne Chemaly , Julio Alvarez , Robert Söderlund , Eva Møller Nielsen , Marie Chattaway , Kaye Burgess , William Byrne , Aldert L. Zomer , Maaike van den Beld , Lapo Mughini-Gras
Non-typhoidal Salmonella is the second most frequently reported zoonotic pathogen in the European Union and European Economic Area. Most human infections are caused by serovars Enteritidis and Typhimurium. Genomic characterisation of Salmonella isolates from humans and animals has become a routine public health surveillance tool in many countries. In this study, the relative contributions of several potential sources of human infection of the five frequently reported Salmonella serovars were estimated using machine-learning methods based on a large, cross-sectional collection of genomes from human cases, and animal and environmental sources, across ten European countries. To define the population structure, core-genome Multilocus Sequence Typing was performed. A supervised machine-learning approach was applied for source attribution in the form of a Random Forest classifier. The source and country attribution models achieved moderate accuracy (F1=0.6–0.9), which is lower than in previous studies using machine-learning on Whole Genome Sequencing data. However, attributions of human clinical isolates to different sources were generally in line with previous findings for these five serovars. While the lack of clonality in some sources hindered their prediction, it is also likely that certain sources (e.g., pets) do not serve as major contributors to human infection. Therefore, in most cases attributing these sources to the livestock species they are typically associated with, is likely appropriate. Country attributions showed that substantial human cases are attributable to countries other than their own, indicating geographical interrelatedness of sources. This highlights the value of internationally harmonised Salmonella-control policies in the food production chain.
{"title":"Attributable sources of the five most prevalent non-typhoidal Salmonella serovars across ten European countries","authors":"Gijs Teunis , Timothy J. Dallman , Magdalena Zając , Magdalena Skarżyńska , Liljana Petrovska , Angela Pista , Leonor Silveira , Lurdes Clemente , Amandine Thépault , Laetitia Bonifait , Annaëlle Kerouanton , Marianne Chemaly , Julio Alvarez , Robert Söderlund , Eva Møller Nielsen , Marie Chattaway , Kaye Burgess , William Byrne , Aldert L. Zomer , Maaike van den Beld , Lapo Mughini-Gras","doi":"10.1016/j.jinf.2025.106632","DOIUrl":"10.1016/j.jinf.2025.106632","url":null,"abstract":"<div><div>Non-typhoidal <em>Salmonella</em> is the second most frequently reported zoonotic pathogen in the European Union and European Economic Area. Most human infections are caused by serovars Enteritidis and Typhimurium. Genomic characterisation of <em>Salmonella</em> isolates from humans and animals has become a routine public health surveillance tool in many countries. In this study, the relative contributions of several potential sources of human infection of the five frequently reported <em>Salmonella</em> serovars were estimated using machine-learning methods based on a large, cross-sectional collection of genomes from human cases, and animal and environmental sources, across ten European countries. To define the population structure, core-genome Multilocus Sequence Typing was performed. A supervised machine-learning approach was applied for source attribution in the form of a Random Forest classifier. The source and country attribution models achieved moderate accuracy (F1=0.6–0.9), which is lower than in previous studies using machine-learning on Whole Genome Sequencing data. However, attributions of human clinical isolates to different sources were generally in line with previous findings for these five serovars. While the lack of clonality in some sources hindered their prediction, it is also likely that certain sources (e.g., pets) do not serve as major contributors to human infection. Therefore, in most cases attributing these sources to the livestock species they are typically associated with, is likely appropriate. Country attributions showed that substantial human cases are attributable to countries other than their own, indicating geographical interrelatedness of sources. This highlights the value of internationally harmonised <em>Salmonella</em>-control policies in the food production chain.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106632"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145304231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106650
Lifang Yu , Mengwei Niu , Zhuofan Dong , Xue Dong , Yao Han , Jing An , Tao Jiang , Yuehong Chen , Ye Feng , Yansong Sun , Hao Li
Objectives
Human adenovirus 55 (HAdV-55), a highly pathogenic double-stranded DNA virus, presents a serious global public health challenge due to its rapid transmission and complex pathogenesis. Current antiviral treatment options for HAdV-55 are limited, with no specific antiviral drugs available. The CRISPR-Cas system, capable of precisely targeting viral genomes, has emerged as a novel approach for antiviral therapy. This study aimed to leverage targeted DNA cleavage activity of the CRISPR-Cas12a system to develop a therapeutic strategy for effectively inhibiting HAdV-55 replication.
Methods
We developed a rapid and efficient screening platform for identifying antiviral targets by integrating CRISPR-Cas12a fluorescence detection technology with bioinformatics analysis. Using this platform, we systematically screened 194 candidate targets against HAdV-55.
Results
The E1B-crRNA6-Cas12a system was identified, demonstrating a highly potent antiviral activity with 99.17% inhibitory efficiency and a selectivity index (SI) of 2482.80. This target significantly outperformed the clinical broad-spectrum anti-adenovirus drug cidofovir in both inhibitory efficacy and duration.
Conclusions
This study not only holds promise for providing safe and highly effective antiviral candidate targets for HAdV-55 therapy but also, through the construction of an interdisciplinary technical platform, is expected to enhance the translational potential of CRISPR antiviral technology for preclinical applications.
{"title":"High-efficiency inhibition of human adenovirus type 55 replication by CRISPR-Cas12a","authors":"Lifang Yu , Mengwei Niu , Zhuofan Dong , Xue Dong , Yao Han , Jing An , Tao Jiang , Yuehong Chen , Ye Feng , Yansong Sun , Hao Li","doi":"10.1016/j.jinf.2025.106650","DOIUrl":"10.1016/j.jinf.2025.106650","url":null,"abstract":"<div><h3>Objectives</h3><div>Human adenovirus 55 (HAdV-55), a highly pathogenic double-stranded DNA virus, presents a serious global public health challenge due to its rapid transmission and complex pathogenesis. Current antiviral treatment options for HAdV-55 are limited, with no specific antiviral drugs available. The CRISPR-Cas system, capable of precisely targeting viral genomes, has emerged as a novel approach for antiviral therapy. This study aimed to leverage targeted DNA cleavage activity of the CRISPR-Cas12a system to develop a therapeutic strategy for effectively inhibiting HAdV-55 replication.</div></div><div><h3>Methods</h3><div>We developed a rapid and efficient screening platform for identifying antiviral targets by integrating CRISPR-Cas12a fluorescence detection technology with bioinformatics analysis. Using this platform, we systematically screened 194 candidate targets against HAdV-55.</div></div><div><h3>Results</h3><div>The E1B-crRNA6-Cas12a system was identified, demonstrating a highly potent antiviral activity with 99.17% inhibitory efficiency and a selectivity index (SI) of 2482.80. This target significantly outperformed the clinical broad-spectrum anti-adenovirus drug cidofovir in both inhibitory efficacy and duration.</div></div><div><h3>Conclusions</h3><div>This study not only holds promise for providing safe and highly effective antiviral candidate targets for HAdV-55 therapy but also, through the construction of an interdisciplinary technical platform, is expected to enhance the translational potential of CRISPR antiviral technology for preclinical applications.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106650"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106645
Shumeng Han , Yiwen Liu , Baodi Xing , Yucheng Yang , Zijun Liu , Yixuan Li , Xuechen Wang , Jie Yu , Fan Ping , Wei Li , Lingling Xu , Tao Qi , Yuelun Zhang , Yuxiu Li , Huabing Zhang
Objective
To assess whether GLP-1 RA treatment influences infection risk in randomized clinical trials (RCTs).
Methods
Systematic searches were conducted across PubMed, EMBASE, Cochrane Library, and Web of Science (inception to September 24, 2024), and reference lists of eligible articles. RCTs comparing GLP-1 RA treatment with placebo or non-GLP-1 RA treatments were included. Dual reviewer resolved disagreements by consensus. Two reviewers independently extracted data following PRISMA recommendations and assessed risk of bias via Cochrane tool.
Results
A total of 136 RCTs (n = 164,322) were included. GLP-1 RA treatment was associated with a significant reduction in serious infections (RR, 0.89; 95% CI, 0.86–0.93; absolute risk difference, −30 per 10,000 persons/year; I² = 0%), non-serious (RR, 0.90; 95% CI, 0.85–0.97; I² = 77%), and total infections (RR, 0.89; 95% CI, 0.84–0.94; I² = 77%). Reductions were observed for serious respiratory (RR, 0.84; 95% CI, 0.79–0.90), skin and subcutaneous (RR, 0.77; 95% CI, 0.68–0.87), musculoskeletal (RR, 0.79; 95% CI, 0.65–0.97), vascular (RR, 0.65; 95% CI, 0.47–0.90), and COVID-19 infections (RR, 0.82; 95% CI, 0.72–0.92), all with I² = 0%. Meta-regression showed greater weight loss (β = −0.011; P =.045), hemoglobin A1c reduction (β = –0.229; P =.026), and higher GLP-1 RA doses (RR, 0.87; 95% CI, 0.83–0.92) were associated with lower risk.
Conclusion
GLP-1 RA use was associated with reduced risk of serious infections, particularly in respiratory, skin, musculoskeletal, vascular systems and COVID-19, partially explained by weight loss and improved glycemic control.
{"title":"Association of glucagon-like peptide-1 receptor agonist use with risk of infections: A systematic review and meta-analysis","authors":"Shumeng Han , Yiwen Liu , Baodi Xing , Yucheng Yang , Zijun Liu , Yixuan Li , Xuechen Wang , Jie Yu , Fan Ping , Wei Li , Lingling Xu , Tao Qi , Yuelun Zhang , Yuxiu Li , Huabing Zhang","doi":"10.1016/j.jinf.2025.106645","DOIUrl":"10.1016/j.jinf.2025.106645","url":null,"abstract":"<div><h3>Objective</h3><div>To assess whether GLP-1 RA treatment influences infection risk in randomized clinical trials (RCTs).</div></div><div><h3>Methods</h3><div>Systematic searches were conducted across PubMed, EMBASE, Cochrane Library, and Web of Science (inception to September 24, 2024), and reference lists of eligible articles. RCTs comparing GLP-1 RA treatment with placebo or non-GLP-1 RA treatments were included. Dual reviewer resolved disagreements by consensus. Two reviewers independently extracted data following PRISMA recommendations and assessed risk of bias via Cochrane tool.</div></div><div><h3>Results</h3><div>A total of 136 RCTs (n = 164,322) were included. GLP-1 RA treatment was associated with a significant reduction in serious infections (RR, 0.89; 95% CI, 0.86–0.93; absolute risk difference, −30 per 10,000 persons/year; <em>I²</em> = 0%), non-serious (RR, 0.90; 95% CI, 0.85–0.97; <em>I²</em> = 77%), and total infections (RR, 0.89; 95% CI, 0.84–0.94; <em>I²</em> = 77%). Reductions were observed for serious respiratory (RR, 0.84; 95% CI, 0.79–0.90), skin and subcutaneous (RR, 0.77; 95% CI, 0.68–0.87), musculoskeletal (RR, 0.79; 95% CI, 0.65–0.97), vascular (RR, 0.65; 95% CI, 0.47–0.90), and COVID-19 infections (RR, 0.82; 95% CI, 0.72–0.92), all with <em>I²</em> = 0%. Meta-regression showed greater weight loss (β = −0.011; <em>P</em> =.045), hemoglobin A1c reduction (β = –0.229; <em>P</em> =.026), and higher GLP-1 RA doses (RR, 0.87; 95% CI, 0.83–0.92) were associated with lower risk.</div></div><div><h3>Conclusion</h3><div>GLP-1 RA use was associated with reduced risk of serious infections, particularly in respiratory, skin, musculoskeletal, vascular systems and COVID-19, partially explained by weight loss and improved glycemic control.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106645"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.jinf.2025.106647
Gábor Endre Tóth , Marike Petersen , Francois Chevenet , Marcy Sikora , Alexandru Tomazatos , Alexandra Bialonski , Heike Baum , Balázs Horváth , Padet Siriyasatien , Anna Heitmann , Stephanie Jansen , Ruth Offergeld , Raskit Lachmann , Michael Schmidt , Jonas Schmidt-Chanasit , Dániel Cadar
Background
West Nile virus (WNV) has emerged as a public health concern in Germany since its first detection in 2018, with evidence of expanding geographic spread. Genomic surveillance is critical for tracking viral evolution, identifying introductions, and monitoring local transmission. However, genome recovery from low-viremia samples such as those obtained through blood donor screening remains technically challenging.
Aim
To develop and validate a sensitive amplicon-based sequencing protocol optimized for WNV lineage 2 and apply it to low-titer samples to support genomic surveillance in Germany.
Methods
A novel primer scheme was designed for WNV lineage 2 and applied to 43 nucleic acid testing (NAT)-positive blood donor samples collected between 2020 and 2024. Amplicon-based sequencing performance was benchmarked against metagenomic next-generation sequencing (mNGS). Recovered genomes were subjected to phylogenomic analysis to assess viral diversity and transmission dynamics.
Results
The amplicon protocol enabled genome recovery (>70% coverage) from samples with viral loads as low as ∼10¹ RNA copies/µL, outperforming metagenomic NGS (mNGS). Of the 43 samples, 30 yielded complete or near-complete genomes. Six distinct WNV subclades (2A–2F), including German strains, were identified, indicating multiple introductions into Germany from Central Europe. Subclade 2F emerged as the dominant and widely distributed group. Berlin, Brandenburg, Saxony, and Saxony-Anhalt were identified as persistent transmission hubs.
Conclusion
This study highlights blood donors as valuable sentinels for WNV genomic surveillance. The validated amplicon-based sequencing approach enables sensitive, scalable genome recovery from low-viremia samples, and when integrated with routine blood donor screening, provides a robust framework for early detection, transmission dynamics, and public health preparedness.
{"title":"Blood donors as sentinels for genomic surveillance of West Nile virus in Germany using a sensitive amplicon-based sequencing approach","authors":"Gábor Endre Tóth , Marike Petersen , Francois Chevenet , Marcy Sikora , Alexandru Tomazatos , Alexandra Bialonski , Heike Baum , Balázs Horváth , Padet Siriyasatien , Anna Heitmann , Stephanie Jansen , Ruth Offergeld , Raskit Lachmann , Michael Schmidt , Jonas Schmidt-Chanasit , Dániel Cadar","doi":"10.1016/j.jinf.2025.106647","DOIUrl":"10.1016/j.jinf.2025.106647","url":null,"abstract":"<div><h3>Background</h3><div>West Nile virus (WNV) has emerged as a public health concern in Germany since its first detection in 2018, with evidence of expanding geographic spread. Genomic surveillance is critical for tracking viral evolution, identifying introductions, and monitoring local transmission. However, genome recovery from low-viremia samples such as those obtained through blood donor screening remains technically challenging.</div></div><div><h3>Aim</h3><div>To develop and validate a sensitive amplicon-based sequencing protocol optimized for WNV lineage 2 and apply it to low-titer samples to support genomic surveillance in Germany.</div></div><div><h3>Methods</h3><div>A novel primer scheme was designed for WNV lineage 2 and applied to 43 nucleic acid testing (NAT)-positive blood donor samples collected between 2020 and 2024. Amplicon-based sequencing performance was benchmarked against metagenomic next-generation sequencing (mNGS). Recovered genomes were subjected to phylogenomic analysis to assess viral diversity and transmission dynamics.</div></div><div><h3>Results</h3><div>The amplicon protocol enabled genome recovery (>70% coverage) from samples with viral loads as low as ∼10¹ RNA copies/µL, outperforming metagenomic NGS (mNGS). Of the 43 samples, 30 yielded complete or near-complete genomes. Six distinct WNV subclades (2A–2F), including German strains, were identified, indicating multiple introductions into Germany from Central Europe. Subclade 2F emerged as the dominant and widely distributed group. Berlin, Brandenburg, Saxony, and Saxony-Anhalt were identified as persistent transmission hubs.</div></div><div><h3>Conclusion</h3><div>This study highlights blood donors as valuable sentinels for WNV genomic surveillance. The validated amplicon-based sequencing approach enables sensitive, scalable genome recovery from low-viremia samples, and when integrated with routine blood donor screening, provides a robust framework for early detection, transmission dynamics, and public health preparedness.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106647"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号