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Shotgun metagenomics for the diagnosis of infections: A prospective study 霰弹枪宏基因组学用于感染诊断:一项前瞻性研究。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-01 DOI: 10.1016/j.jinf.2025.106619
Laure Surgers , Charlotte Lafont , Claudie Lamoureux , Vanessa Demontant , Melissa N’Debi , Justine Cheval , Laure Boizeau , Elisabeth Trawinski , Jean-Michel Pawlotsky , Paul-Louis Woerther , Christophe Rodriguez , Clinical Metagenomics Study Group

Background

Shotgun metagenomics (SMg) promises to significantly improve the microbiological diagnosis of infectious diseases. However, the prospective evaluation of its clinical utility in different infectious syndromes remains poorly documented.

Methods

We conducted a prospective study including all patients who underwent SMg as part of their care at the French Henri Mondor Hospital National Reference Laboratory for accredited SMg between February 2018 and January 2020. Patients were categorized as having either a "high likelihood" or "low likelihood" of infection based on their clinical presentation. The contribution of the SMg to the final diagnosis was assessed by a multidisciplinary team of infectious disease specialists.

Findings

202 patients were enrolled in the study. Of the 123 patients considered to have a high likelihood of infection, SMg confirmed the cause of infection in 38 cases (30.9%), including 12 cases (9.8%) diagnosed exclusively by this method. In the 79 patients classified as having a "low likelihood" of infection, SMg did not detect any microorganisms compatible with an infectious cause. In particular, patients undergoing immunosuppressive treatment within the latter group showed no deterioration after 6 months.

Interpretation

SMg facilitated microbiological diagnosis in over 30% of complex cases, regardless of sample type or site of infection. Compared with conventional techniques, SMg provided diagnoses in 10% more cases, highlighting its broad utility across different infectious diseases. Our results suggest that SMg is a promising tool for documenting complex infectious diseases alongside traditional microbiology tools. Furthermore, negative SMg results are useful for the management of patients with a low likelihood of infection.
背景:霰弹枪宏基因组学(SMg)有望显著改善传染病的微生物学诊断。然而,其在不同感染综合征的临床应用的前瞻性评价仍然缺乏文献记录。方法:我们进行了一项前瞻性研究,包括2018年2月至2020年1月期间在法国亨利蒙多医院国家参考实验室接受SMg治疗的所有患者。根据患者的临床表现,将其分为“高可能性”或“低可能性”感染。由传染病专家组成的多学科小组评估了SMg对最终诊断的贡献。结果:202例患者入组研究。在123例被认为有高感染可能性的患者中,有38例(30.9%)被SMg确诊为感染原因,其中12例(9.8%)是完全通过这种方法诊断的。在79名被归类为“低可能性”感染的患者中,SMg未检测到任何与感染原因相容的微生物。特别是后一组接受免疫抑制治疗的患者在6个月后没有出现恶化。解释:无论样本类型或感染部位如何,SMg有助于超过30%的复杂病例的微生物学诊断。与传统技术相比,SMg提供的诊断病例多10%,突出了其在不同传染病中的广泛应用。我们的研究结果表明,SMg是一种很有前途的工具,可以与传统的微生物学工具一起记录复杂的传染病。此外,阴性SMg结果对低感染可能性患者的管理是有用的。资助:本研究作为患者护理的一部分进行。
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引用次数: 0
Evaluation of Vitek2 and Etest for determining penicillin and ceftriaxone susceptibilities in penicillin-resistant Streptococcus pneumoniae 耐青霉素肺炎链球菌对青霉素和头孢曲松的敏感性测定及Vitek2的评价。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-01 DOI: 10.1016/j.jinf.2025.106625
Lin Liu , Tingting Hong , Yanfei Wang , Zengzeng Zhang, Shouyuan Chen, Ying Fu, Yunsong Yu, Xiaoxing Du , Xueqing Wu
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引用次数: 0
Bacteriophage combined with mNGS enhances the specificity of bacterial infection diagnosis 噬菌体联合mNGS可提高细菌感染诊断的特异性。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-01 DOI: 10.1016/j.jinf.2025.106618
Ying Liu , Yafeng Zheng , Lu Wang , Yuxin Guo , Guangyun Huang , Zhiyong Yuan , Fuhua Wang , Wei Gai , Jinyan Xing

Introduction

Metagenomic next-generation sequencing (mNGS) is an important tool for enhancing pathogen detection in infected patients. However, distinguishing between specimens that are infected or colonized is still a major challenge.

Objectives

To explore the composition of bacteriophages in the blood and respiratory tract of the human body, the association between bacteriophage detection and bacterial infections, and whether bacteriophages can assist in differentiating infectious pathogens according to mNGS results.

Methods

Clinical samples from hospitalized patients were collected between January 2023 and February 2024. DNA and cell-free DNA were extracted from BALF and plasma retrospectively to identify the pathogens present, and bacteriophage annotations were conducted.

Results

A total of 299 samples, comprising 136 blood samples and 163 BALF samples, were obtained from 218 patients. Compared with the samples negative for bacteria, both blood and bronchoalveolar lavage fluid (BALF) samples infected with Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and S. aureus showed a corresponding increase in the proportions of phages related to these pathogens. In BALF samples with Acinetobacter baumannii infection, the proportions of Autographiviridae, Siphoviridae, and Myoviridae were significantly greater than those in the Acinetobacter baumannii colonization group. The sensitivity of Myoviridae for differentiating between infection and colonization was 86.36%, and the specificity was 52.94%.

Conclusion

In sepsis, compared with conventional mNGS methods alone, the use of bacteriophages combined with mNGS was more effective in identifying causative pathogens and had higher specificity. These findings may provide new ideas and tools for improving clinical infection diagnosis.
新一代宏基因组测序(mNGS)是加强感染患者病原体检测的重要工具。然而,区分感染或定植的标本仍然是一项重大挑战。目的:探讨人体血液和呼吸道中噬菌体的组成,噬菌体检测与细菌感染的关系,以及根据mNGS结果,噬菌体是否能协助鉴别感染性病原体。方法:收集2023年1月至2024年2月住院患者的临床样本。从BALF和血浆中回顾性提取DNA和游离DNA,鉴定存在的病原体,并进行噬菌体注释。结果:218例患者共获得299份样本,其中血液样本136份,BALF样本163份。与细菌阴性的样本相比,感染鲍曼不动杆菌、肺炎克雷伯菌、铜绿假单胞菌和金黄色葡萄球菌的血液和支气管肺泡灌洗液(BALF)样本显示,与这些病原体相关的噬菌体比例相应增加。在鲍曼不动杆菌感染的BALF样本中,自噬病毒科、虹膜病毒科和肌病毒科的比例显著高于鲍曼不动杆菌定殖组。肌病毒科区分感染与定植的敏感性为86.36%,特异性为52.94%。结论:在脓毒症中,与单独使用常规mNGS方法相比,噬菌体联合mNGS方法对病原菌的识别更有效,特异性更高。这些发现可能为提高临床感染诊断水平提供新的思路和工具。
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引用次数: 0
Prevalence and impact of SARS-CoV-2, influenza, respiratory syncytial virus (RSV) infection and respiratory illness on UK healthcare workers during winter 2023/24 (September 2023 to March 2024): SIREN cohort study 2023/24冬季(2023年9月至2024年3月)英国医护人员SARS-CoV-2、流感、呼吸道合胞病毒(RSV)感染和呼吸道疾病的流行及其影响:SIREN队列研究
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-01 DOI: 10.1016/j.jinf.2025.106620
Sarah Foulkes , Katie Munro , Dominic Sparkes , Jameel Khawam , Sophie Russell , Angela Dunne , Jean Timeyin , Nipunadi Hettiarachchi , Michelle Cairns , Declan T. Bradley , Elen De Lacy , Kevin Wilson , Nick Andrews , Andre Charlett , Respiratory Virus and Microbiome Initiative (RVI) team , Katie Bellis , Ya-Lin Huang , Matthew Forbes , Andrea Frick-Kretschmer , Marissa Knoll , Victoria Hall

Background

During the winter, healthcare systems experience additional pressures due to increases in respiratory infections and staff absence. We aimed to determine the prevalence of respiratory viruses and impact on sickness absence in the SIREN healthcare worker (HCW) cohort during winter 2023/24.

Methods

SIREN is a cohort study with linked testing, vaccination, demographic, symptoms and sick leave data. Participants undergo fortnightly multiplex PCR testing for SARS-CoV-2, influenza and RSV, regardless of symptoms. The proportion of participants who took sick leave, the total number and median of sick leave days taken was calculated, overall and stratified by viral infection and vaccination status. Logistic regression was used to estimate the association between sick leave and vaccination status.

Results

A total of 5287 participants were included, 78·3% female, median age 54 years. There were 1828 infections (1161 SARS-CoV-2; 387 RSV; 280 influenza infections) among 1659 participants. Influenza and RSV peaked in December (1·2%; 1·9%), SARS-CoV-2 peaked in September and December 2023 (4·0%; 4·3%).
Regardless of a known infection, 35.8% (1892/5287) took sick leave, resulting in 10,168 days (median 5 days per person; range 1–98 days).

Discussion

Respiratory illness caused a substantial burden on the SIREN healthcare workforce over winter, with all three viruses contributing. Reduced number of staff at work and pressures to work through illness have implications for healthcare resilience.
背景:在冬季,由于呼吸道感染和工作人员缺勤的增加,卫生保健系统面临额外的压力。我们的目的是确定2023/24年冬季SIREN医护人员(HCW)队列中呼吸道病毒的流行率及其对缺勤的影响。方法:SIREN是一项队列研究,包括相关的检测、疫苗接种、人口统计学、症状和病假数据。无论症状如何,参与者每两周接受一次SARS-CoV-2、流感和RSV多重PCR检测。根据病毒感染和疫苗接种状况,计算了请病假的参与者的比例、病假天数的总数和中位数。使用Logistic回归来估计病假与疫苗接种状况之间的关联。结果:纳入5287例受试者,女性78.3%,中位年龄54岁。在1,659名参与者中,有1,828例感染(1,161例SARS-CoV-2; 387例RSV; 280例流感感染)。流感和RSV高峰在12月(1.2%;1.9%),SARS-CoV-2高峰在9月和12月(4.0%;4.3%)。无论是否有已知感染,35.8%(1892 / 5287)的人请了病假,总共请了10168天病假(平均每人5天,范围1-98天)。讨论:呼吸系统疾病在冬季给SIREN医护人员造成了沉重的负担,这三种病毒都起到了作用。工作人员数量的减少和带病工作的压力对医疗弹性有影响。资助:英国卫生安全局、英国卫生和社会保障部,北爱尔兰、威尔士和苏格兰政府提供资助,并提供惠康基金参考。
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引用次数: 0
Level III public health emergency response to a chikungunya outbreak in Jiangmen, China 中国江门基孔肯雅热暴发III级突发公共卫生事件应对措施
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-01 DOI: 10.1016/j.jinf.2025.106622
Liyan Zhou, Chenyuan Qin, Jue Liu
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引用次数: 0
Detection of pulmonary tuberculosis and drug resistance in sputum samples using targeted next-generation sequencing 利用靶向下一代测序技术检测痰样本中的肺结核和耐药性。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-01 DOI: 10.1016/j.jinf.2025.106621
Chang Song , Chun-Yan Zhao , Hang-Biao Qiang , Xue-Wen Huang, Ai-Chun Huang, Chun-Mei Zeng, Chun-Ming Gong, Qiu-Qing Tan, Zhen-Tao Huang, Xiao-Shi Lin, Qing-Dong Zhu, Zhou-Hua Xie
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引用次数: 0
Corrigendum to “Humoral and T-cell responses following MVA-BN booster vaccination against mpox virus clades Ib and IIb” [J Infect 91 (2025) 106602] “MVA-BN加强疫苗接种后对m痘病毒分支Ib和IIb的体液和t细胞反应”的更正[J] .传染病杂志91(2025)106602。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-10-01 DOI: 10.1016/j.jinf.2025.106631
Valentina Mazzotta , Giulia Matusali , Eleonora Cimini , Alessandro Caioli , Rozenn Esvan , Francesca Colavita , Eleonora Tartaglia , Jessica Paulicelli , Giulia Micheli , Aurora Bettini , Stefania Notari , Alessandro Giacinta , Licia Bordi , Simona Gili , Andrea Siddu , Enrico Girardi , Fabrizio Maggi , Andrea Antinori
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引用次数: 0
A systematic review of asymptomatic colonisation with Group A Streptococcus in lower- and middle-income countries 中低收入国家A群链球菌无症状定植的系统综述
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-09-18 DOI: 10.1016/j.jinf.2025.106615
Hermaleigh Townsley, Thomas E. Locke, Nicholas Laundy, Christopher Keil, Alexander J. Keeley, Jean Hamilton, Abdullah Pandor, Thomas C. Darton, Thushan I. de Silva
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引用次数: 0
Single cell sequencing analysis of respiratory syncytial virus–infected pediatric and adult human nose organoids reveals age differences, proliferative diversity and identifies novel cellular tropism 呼吸道合胞病毒感染儿童和成人鼻类器官的单细胞测序分析揭示了年龄差异、增殖多样性并确定了新的细胞趋向性。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-09-18 DOI: 10.1016/j.jinf.2025.106617
Anubama Rajan , Divya Nagaraj , Carolyn Bomidi , Gina M. Aloisio , Ashley M. Murray , Emily M. Schultz , Amal Kambal , Mary K. Estes , Erin Nicholson , Vasanthi Avadhanula , Sarah E. Blutt , Pedro A. Piedra
Respiratory syncytial virus (RSV) is a leading cause of infant death across the globe. Age is a significant factor that contributes to the severity of infection in young children. RSV primarily infects the ciliated cells of the airway epithelium, induces mucus hypersecretion, and impaired mucociliary clearance. Better understanding of RSV infection at the cellular level is needed for the development of effective therapeutic interventions. To investigate the age difference and comprehensively understand gene signatures associated with RSV infection, we performed single-cell transcriptomic analysis of adult and pediatric human nose organoids (HNOs) infected with RSV. Our analysis revealed a significant difference in transcriptomic signature associated with cellular differentiation and proliferative pathways between the adult and pediatric HNOs. Moreover, we found a distinct innate immune response to RSV infection, with pediatric HNO revealing a lower and dysregulated response. Through sub-clustering analysis of the ciliated cell population, we identified the primary ciliary cell as a novel and prominent susceptible ciliary cell type to RSV infection. Intriguingly and unexpectedly, we found that in the pediatric more than in the adult, HNO RSV infects other novel airway cells, including basal cells, and ionocytes/tuft cells, as demonstrated by increased RSV-gene counts and induction of interferon-related pathways. Together, our study provides the first HNO cell atlas dissecting the heterogeneity of RSV infection in airway epithelium between adult versus pediatric HNOs and identifies novel cell types that are susceptible to RSV infection, which altogether provides a key resource for research on RSV pathogenesis, therapeutics and vaccines.
呼吸道合胞病毒(RSV)是全球婴儿死亡的主要原因。年龄是影响幼儿感染严重程度的一个重要因素。RSV主要感染气道上皮纤毛细胞,诱导粘液分泌过多,损害纤毛黏液清除。为了开发有效的治疗干预措施,需要在细胞水平上更好地了解RSV感染。为了研究年龄差异并全面了解与RSV感染相关的基因特征,我们对感染RSV的成人和儿童人鼻类器官(HNOs)进行了单细胞转录组学分析。我们的分析揭示了成人和儿童HNOs在细胞分化和增殖途径相关的转录组特征上的显著差异。此外,我们发现对RSV感染有明显的先天免疫反应,儿童HNO反应较低且失调。通过对纤毛细胞群的亚聚类分析,我们确定了原代纤毛细胞是一种新的、突出的易感染RSV的纤毛细胞类型。有趣且出乎意料的是,我们发现在儿童中,与成人相比,HNO RSV感染其他新型气道细胞,包括基底细胞和离子细胞/簇状细胞,这可以通过RSV基因计数增加和干扰素相关途径的诱导来证明。总之,我们的研究提供了第一个HNO细胞图谱,揭示了成人和儿童HNO在呼吸道上皮中RSV感染的异质性,并鉴定了对RSV感染易感的新细胞类型,这为RSV发病机制、治疗方法和疫苗的研究提供了关键资源。
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引用次数: 0
Small-RNA sequencing identifies serum microRNAs associated with abnormal electrocardiography findings in patients with Chagas disease 小rna测序确定了与恰加斯病患者异常心电图结果相关的血清微小rna。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-09-12 DOI: 10.1016/j.jinf.2025.106613
Michael Mueller , Alice Blandino , Dominique Scherer , Inés Zulantay , Werner Apt , Nelson M. Varela , Marcelo Llancaqueo , Lineth Garcia , Lourdes Ortiz , Emanuele Nicastri , Maria Letizia Giancola , Andrea Angheben , Simona Gabrielli , Trine B. Rounge , Hilde Langseth , Melanie Waldenberger , Pamela Salinas-Alvarez , Justo Lorenzo Bermejo

Background

Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), affects around 6–7 million people in Latin America and hundreds of thousands in the United States and Europe. A main complication of chronic Chagas disease is cardiomyopathy, possibly manifesting as arrhythmias, heart failure, or sudden cardiac death. Understanding the link between T. cruzi infection and cardiomyopathy is essential for early diagnosis and adequate treatment.

Methods

We sequenced small RNAs in serum samples from 228 Chagas patients recruited in Chile, Bolivia and Italy. After bioinformatic processing of sequencing data to quantify serum miRNA expression, robust logistic regression was applied to identify miRNAs differentially expressed in Chagas patients with abnormalities in electrocardiography (ECG), bundle-branch block on ECG, and high Kuschnir scores. We also investigated the association between genotype-based miRNA expression and the risk of abnormal ECG findings.

Findings

As reported, the risk of abnormal ECG findings was higher in male patients and increased with age. Three miRNAs showed lower serum expression levels in patients with abnormal ECG: miRNA-101-3p, miRNA-576-3p and miRNA-629-5p (p < 0.0002), especially in patients with high Kuschnir scores. The expression of miRNA-629-5p was negatively correlated with the CCL5 expression (p = 3.7×10-8), a chemokine frequently reported in Chagas disease. Gene enrichment analyses indicated involvement of cytokine signalling in Chagas cardiomyopathy.

Interpretation

The findings demonstrate the potential of circulating miRNAs as diagnostic biomarkers for Chagas cardiomyopathy. The associations found with disease severity and immune response may help to improve our knowledge of complications’ development in Chagas disease.
背景:由克氏锥虫(T. cruzi)寄生虫引起的恰加斯病影响了拉丁美洲约600 - 700万人以及美国和欧洲数十万人。慢性恰加斯病的主要并发症是心肌病,可能表现为心律失常、心力衰竭或心源性猝死。了解克氏锥虫感染与心肌病之间的联系对于早期诊断和适当治疗至关重要。方法:我们对来自智利、玻利维亚和意大利的228名恰加斯病患者的血清样本中的小rna进行了测序。在对测序数据进行生物信息学处理以量化血清miRNA表达后,应用稳健逻辑回归识别心电图异常、心电图束支阻滞和高Kuschnir评分的Chagas患者的miRNA差异表达。我们还研究了基于基因型的miRNA表达与ECG异常风险之间的关系。结果:据报道,男性患者出现异常心电图的风险更高,并且随着年龄的增长而增加。在ECG异常患者中,miRNA-101-3p、miRNA-576-3p和miRNA-629-5p的血清表达水平较低(p < 0.0002),尤其是在Kuschnir评分高的患者中。miRNA-629-5p的表达与CCL5的表达呈负相关(p = 3.7×10-8), CCL5是恰加斯病中经常报道的一种趋化因子,基因富集分析表明细胞因子信号通路参与恰加斯心肌病。解释:这些发现证明了循环mirna作为恰加斯心肌病诊断生物标志物的潜力。发现与疾病严重程度和免疫反应的关联可能有助于提高我们对恰加斯病并发症发展的认识。
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引用次数: 0
期刊
Journal of Infection
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