The Journal of Infectious Diseases最新文献

{"title":"Elevated Spleen Tyrosine Kinase in Low-Density Neutrophils During Bacterial Sepsis in a Nonhuman Primate Model","authors":"Heather L Teague, Seth Warner, Andrew P Platt, Sydney Stein, Marcos J Ramos-Benitez, Sabrina Ramelli, Shelly Curran, Izabella Lach, Kiana Allen, Heritage Adetola, Trevor Stantliff, Raquel Santana da Cruz, Mahnaz Minai, Heather Kendall, Kevin M Vannella, Derron A Alves, Richard Herbert, Daniel S Chertow, Jeffrey R Strich","doi":"10.1093/infdis/jiaf403","DOIUrl":"https://doi.org/10.1093/infdis/jiaf403","url":null,"abstract":"Background Sepsis is a leading cause of death world-wide. Identifying novel host-directed therapeutic targets may improve sepsis outcomes. Methods Six nonhuman primates were infected with Klebsiella pneumoniae to induce septic shock and provided supportive care for up to 72 hours. Flow cytometry was used to characterize whole blood neutrophils (WBNs) and low-density neutrophils (LDNs) at time (T0), T6, T24, and T48-hours post-infection; and postmortem examination (i.e. necropsy). Dimensional reduction with clustering via FlowSOM and traditional gating strategies were used to compare WBNs to LDNs and delineate spleen tyrosine kinase (SYK) expression across neutrophils subsets. We measured soluble biomarkers of end-organ dysfunction and neutrophil activation and quantified SYK and myeloperoxidase in tissue. Results At T6, we identified populations of active immature WBNs and a population of LDNs not detected at baseline. At T24, neutrophil heterogeneity increased across WBNs and LDNs with differential expression of myeloperoxidase (MPO). Compared to WBNs, LDNs were more activated with increased MPO expression. At T6, SYK expression surged in WBNs and LDNs and SYK+WBNs and LDNs expressed higher levels of MPO and lactoferrin compared to SYK- neutrophils. Circulating levels of SYK+LDNs significantly correlated with serum creatinine levels, indicative of acute kidney injury; prolonged prothrombin time and decreased fibrinogen, indicative of consumptive coagulopathy; and SYK expression in tissues. Conclusions Bacterial sepsis leads to heterogenous populations of circulating neutrophils, including LDNs. Elevated SYK expression in WBNs and LDNs correlates with end-organ dysfunction, highlighting SYK as a potential therapeutic target in bacterial sepsis.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic and phenotypic insights into antibiotic resistance and virulence of Klebsiella pneumoniae from the environment in Southern Taiwan","authors":"Chun-Hsing Liao, Ya-Ling Huang, Thomas Ioerger, Ke San Lim, Yu-Chieh Huang, Chen-Hsiu Huang, Chun-Ru Hsu","doi":"10.1093/infdis/jiaf396","DOIUrl":"https://doi.org/10.1093/infdis/jiaf396","url":null,"abstract":"Background Klebsiella pneumoniae is a major human pathogen responsible for healthcare- and community-associated infections and a critical contributor to the global antimicrobial resistance (AMR) crisis. Although widely present in the environment, its role in harboring multidrug-resistant (MDR) and hypervirulent strains (hvKp) remains insufficiently characterized. Methods This study assessed the prevalence, genomic diversity, and pathogenic potential of K. pneumoniae isolated from surface waters in southern Taiwan. A total of 62 sites were sampled, yielding 68 environmental isolates. Whole-genome sequencing (WGS), virulence phenotyping, in vivo infection models, and conjugation assays were used to evaluate resistance, virulence, and gene transfer potential. Results K. pneumoniae was detected at 91.9% of sampled sites. Among 68 isolates, 7.35% were MDR, and virulence-associated phenotypes were common: 26.47% exhibited serum resistance, 13.24% anti-phagocytic activity, 11.76% hypermucoviscosity, 22.06% strong biofilm formation, and 48.53% intestinal cell adhesion. WGS revealed 59 sequence types and 48 capsular types, indicating a high level of genetic diversity among environmental isolates. Hypervirulent clones KL1-ST23 and KL2-ST373 were identified and confirmed to be pathogenic in mice. Based on genomic and in vivo data, hvKp was detected in 5.88% of isolates. Phylogenetic analysis showed close relatedness to clinical reference strains NTUH-K2044 and MGH78578. Conjugation experiments demonstrated successful ciprofloxacin resistance transfer. Conclusions These findings provide evidence that environmental surface waters can serve as reservoirs for antimicrobial resistance and hypervirulence in K. pneumoniae. They highlight the need for integrated environmental surveillance and One Health strategies to address this emerging public health threat.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of Respiratory Syncytial Virus-Associated Hospitalization Among Adults in Ontario, Canada, 2017-2019.","authors":"Sarah A Buchan,Jenna Alessandrini,Samantha S M Drover,Melissa K Andrew,Susan E Bronskill,Kevin A Brown,Nick Daneman,Shelley L Deeks,Jonathan B Gubbay,Jennie Johnstone,Timothy M Karnauchow,Samantha Lee,Allison J McGeer,J Dayre McNally,Shelly A McNeil,Samira Mubareka,Michelle Murti,Marek Smieja,Sarah E Wilson,Jeffrey C Kwong","doi":"10.1093/infdis/jiaf343","DOIUrl":"https://doi.org/10.1093/infdis/jiaf343","url":null,"abstract":"BACKGROUNDRespiratory syncytial virus (RSV) causes substantial morbidity and mortality among adults. Given recent RSV vaccine authorizations, data on groups at highest risk are needed to support vaccine program decision making.METHODSWe identified adults aged ≥ 18 years hospitalized with laboratory-confirmed RSV and hospitalizations with RSV-related diagnostic codes in Ontario, Canada (2017-2019). We calculated incidence of hospitalization with 95% confidence intervals (CIs) using Poisson regression stratified by demographic and clinical risk factors, and substratified by age. We reported secondary outcomes including the proportion of individuals with fatal outcomes.RESULTSOver 2 respiratory virus seasons, we identified 3928 RSV-associated hospitalizations. Incidence increased steadily with age from 2.0 (95% CI, 1.8-2.3) per 100 000 for those aged 18-49 years to 43.7 (95% CI, 41.0-46.6) per 100 000 for those aged 70-79 years, with a sharp increase to 134.7 (95% CI, 128.6-141.1) per 100 000 for those aged ≥ 80 years. Incidence was higher for those with comorbidities, including chronic kidney disease (receiving dialysis) (494.7; 95% CI, 410.7-595.8) and transplant recipients (370.9; 95% CI, 318.0-432.6), as well as for those living in lower (22.4; 95% CI, 21.1-23.7) versus higher-income neighborhoods (11.8; 95% CI, 10.8-12.8). Among those hospitalized, 10.3% (n = 403) died within 30 days of admission, and 93.1% of deaths occurred in those aged ≥ 60 years. Of survivors, 44.6% of community-dwelling adults aged ≥ 60 years had functional decline requiring formal supports at discharge.DISCUSSIONWe found a substantial burden of RSV among older adults, particularly among those with preexisting medical conditions and those of lower socioeconomic status. These results will inform equitable vaccine recommendations for adults.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo evolution of Candida auris multi-drug resistance in a patient receiving antifungal treatment","authors":"Tristan W Wang, Nicole Putnam, J Kristie Johnson, Mary Ann Jabra-Rizk","doi":"10.1093/infdis/jiaf394","DOIUrl":"https://doi.org/10.1093/infdis/jiaf394","url":null,"abstract":"Candida auris is associated with life-threatening invasive disease due to high level of drug resistance. We present a clinical case of C. auris multi-drug resistance development in a patient acquired during antifungal treatment. Five isolates were prospectively recovered from a lung transplant patient receiving antifungal therapy over a one-year period. While isolates were initially only resistant to fluconazole, the terminal isolate became resistant to caspofungin and amphotericin B with significant increase in micafungin MIC. Sequencing of ERG11 and FKS1 genes identified mutations associated with fluconazole and echinocandin resistance in the multi-drug-resistant isolate, underscoring the threat of therapy-induced development of resistance.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistence is Resistance: The fight to End the HIV Epidemic Hangs in the Balance","authors":"Colleen F Kelley, Andrea Weddle, Allison Agwu, Philip J Bolduc, Anna K Person","doi":"10.1093/infdis/jiaf389","DOIUrl":"https://doi.org/10.1093/infdis/jiaf389","url":null,"abstract":"In this perspective piece, representatives from the HIV Medicine Association urge persistent advocacy to resist harmful federal policies to the field of HIV medicine, research, public health, and the communities we serve.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robust COVID-19 Mortality Risk Assessment: Validation of a Two-Step Algorithm from the National COVID Cohort Collaborative","authors":"Bingnan Li, Yuan Ke, Xianyan Chen, Leonardo Martinez, Ye Shen","doi":"10.1093/infdis/jiaf393","DOIUrl":"https://doi.org/10.1093/infdis/jiaf393","url":null,"abstract":"This study introduces and validates a Two-Step algorithm for assessing COVID-19 mortality risk, leveraging data from over 7 million COVID-19 cases in the National COVID Cohort Collaborative (N3C). The original algorithm stratifies patients into risk categories based on routine clinical metrics and was initially tested across diverse cohorts from multiple institutions, demonstrating strong predictive performance. Further validation of this algorithm on 2.4 million valid N3C COVID-19 records, including a subset of 768,957 with complete data, yielded a C-statistic exceeding 0.85. The algorithm adapts effectively to evolving mortality trends, particularly during the Omicron variant surge. Comparative analyses of full and imputed datasets underscore the algorithm’s robustness across varied clinical settings. Our work offers a scalable tool for pandemic management, highlighting the critical role of data-informed approaches in public health.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"144 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144712326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and environmental surveillance of poliovirus type 2 outbreak using a novel specific real-time quantitative PCR assay, Israel, 2022-2023","authors":"Itay Bar-Or, Merav Weil, Hadar Assraf, Areej Kabat, Roberto Azar, Batya Mannasse, Virginia Levy, Leah Weiss, Rinat Vasserman, Elias Dawood, Irina Aguvaev, Roaa Matar, Alex Aydenzon, Amit Holdhaim, Zvi Cohen, Nofar Levi, Ilana S Fratty, Neta S Zuckerman, Lester M Shulman, Ella Mendelson, Danit Sofer, Oran Erster","doi":"10.1093/infdis/jiaf387","DOIUrl":"https://doi.org/10.1093/infdis/jiaf387","url":null,"abstract":"Background An increase in the number of circulating vaccine derived poliovirus (VDPV) outbreaks is reported worldwide in recent years, necessitating improved surveillance and diagnostic tools. The current standard protocol for polio detection is lengthy, labor-intensive, and inefficient for direct wastewater testing. Methods Here we describe a multiplex poliovirus-2 (PV2) specific assay that directly detects PV2 RNA derived from Sabin-2 vaccine in wastewater and stool samples. The new PV2-specific assay was used for direct detection of PV2 in environmental and clinical samples. Results In-silico analysis suggested that the assay is specific for PV2 originated from Sabin-2 vaccine and identifies 98.3% of available sequences, including some with <95% similarity to the vaccine reference sequence. We show that the assay is specific for PV2 and does not identify 19 other enterovirus strains, including sabin-1 and Sabin-3 RNA. The new assay enabled fast detection of PV2 in suspected clinical samples, which was subsequently confirmed by isolation and sequencing. By analyzing 183 concentrated wastewater samples, we further show that the new assay specifically and directly identifies PV2 RNA, in the presence of PV1, PV3, and other enteroviruses RNA. Conclusions The assay provides quantitative results, allowing continuous monitoring of viral load dynamics. Comparison of the standard isolation protocol and the new assay showed excellent agreement in terms of specificity and sensitivity. This specific and rapid assay may therefore be a valuable tool for monitoring cVDPV2 outbreaks in real time, and promote the global efforts for eradication and containment poliovirus circulation","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144712348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methicillin-Resistant Staphylococcus aureus Bacteremia Relapses Show Diverse Genomic Profiles but Convergence in Bacteremia-Associated Genes.","authors":"Brooke M Talbot,Natasia F Jacko,Katrina S Hofstetter,Tara Alahakoon,Kevin Bouiller,Timothy D Read,Michael Z David","doi":"10.1093/infdis/jiaf352","DOIUrl":"https://doi.org/10.1093/infdis/jiaf352","url":null,"abstract":"BACKGROUNDRecurrence of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a high risk complication for patients. Distinguishing persistent lineages from new infections is not standardized across clinical studies.METHODSWe investigated factors contributing to recurrence of MRSA bacteremia among subjects in Philadelphia, Pennsylvania. Subject demographics and clinical history were collected and paired with whole-genome sequences of infection isolates. Recurrent bacteremia episodes were recorded and defined as relapse infections (same lineage) or new infections by genomic criteria, where a relapse contained isolates ≤ 25 single nucleotide polymorphisms (SNP) different, and by clinical criteria. All isolates were assessed for pairwise SNP distances, common mutations, and signatures of within-host adaptation using the McDonald-Kreitman test. Clusters of transmission between relapse-associated isolates and other subject lineages were identified.RESULTSAmong 411 sequential subjects with MRSA bacteremia, 32 experienced recurrent bacteremia episodes, with 24 subjects having exclusively relapse infections, 6 with infections exclusively from a new strain, and 2 patients with both relapse and new infections. No concordance between a genomic and a clinical definition of relapse was evident (Cohen κ = 0.18; confidence interval, -0.41). Recurrence-associated lineages exhibited signatures of positive selection (G test, < 0.01). Genes with SNPs occurring in multiple relapse lineages have roles in antibiotic resistance and virulence, including 5 lineages with mutations in mprF and 3 lineages with mutations in rpoB, which corresponded with evolved phenotypic changes in daptomycin and rifampin resistance.CONCLUSIONSRecurrent infections have a diverse strain background. Relapses can be readily distinguished from newly acquired infections using genomic sequencing but not clinical criteria.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of a novel IgG3 allele with malaria in children from the Sepik region of Papua New Guinea.","authors":"Maria Saeed,Elizabeth H Aitken,Myo T Naung,Caitlin Bourke,Kenneth W Wu,Rhea J Longley,Amy W Chung,Timon Damelang,Benson Kiniboro,Ivo Mueller,Stephen J Rogerson","doi":"10.1093/infdis/jiaf390","DOIUrl":"https://doi.org/10.1093/infdis/jiaf390","url":null,"abstract":"BACKGROUNDSusceptibility to malaria can be influenced by host genetic factors, including immune response genes. Antibodies against Plasmodium antigens are known to play an important role in protection from clinical disease. Polymorphisms in these antibodies may result in different functional properties that could provide protection from malaria.METHODSImmunoglobulin G1 (IgG1) and IgG3 alleles and IgG3 hinge region were investigated by polymerase chain reaction (PCR) and Sanger sequencing in a longitudinal cohort of children aged 1-3 years (N=203) from East Sepik region of Papua New Guinea (PNG). Linear regression was used to investigate associations between immunoglobulin alleles and Plasmodium infections.RESULTSSeventy-eight percent of the children were either heterozygous (n=82, 40%) or homozygous (n=77, 38%) for IGHG3*30 (G3m29), a novel IgG3 allele. G3m29 has a long hinge region of 4 exons. Significantly fewer Plasmodium spp. infections were observed in children with the IGHG3*30 allele compared to children without the allele (β= -1.736, 95% CI [-3.39, -0.079], p=0.038). This effect was most noticeable for Plasmodium vivax asymptomatic infections as IGHG3*30 carriers had on average one fewer infection in the 18-month follow-up period as compared to non-IGHG3*30 allele carriers (β= -1.06; 95% CI [-2.01, -0.12], p=0.028). Additionally, IGHG3*30 allele carriers had significantly lower levels of IgG to P. vivax vaccine candidate proteins compared to non-IGHG3*30 allele carriers.CONCLUSIONSThe IGHG3*30 allele is highly prevalent in the East Sepik region and is associated with fewer Plasmodium spp. infections.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144720195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Syphilis Pathogenesis: Host Immune Response versus Pathogen Immune Evasion.","authors":"Andy Liu,Lorenzo Giacani,Iskra Tuero,Jeffrey D Klausner","doi":"10.1093/infdis/jiaf388","DOIUrl":"https://doi.org/10.1093/infdis/jiaf388","url":null,"abstract":"Syphilis, caused by Treponema pallidum subspecies pallidum (T. pallidum), remains a significant global health problem despite being preventable and curable. The pathogen's ability to evade the immune system using virulence factor-based strategies and by invading immune-privileged sites enables persistent infection in the untreated host. This translational update describes the host innate and adaptive immune responses in syphilis and the sophisticated mechanisms employed by T. pallidum to avoid immune clearance. Recent advances in immune profiling have enhanced our understanding of the host immune response and identified potential biomarkers for disease staging and treatment monitoring. However, knowledge gaps remain regarding T. pallidum's immune evasion mechanisms, the dynamics of cellular and humoral immunity, and the characteristics of long-term protective immune responses against T. pallidum. Bridging these gaps by integrating microbiology, immunology, and multiomics approaches is crucial for advancing diagnostic tools, therapeutic strategies, and vaccine development to ultimately reduce the global burden of syphilis.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"96 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}