The Journal of Infectious Diseases最新文献

{"title":"Plasmodium falciparum Parasitemia Does Not Diminish Neutralizing Antibody Responses After mRNA COVID-19 Booster Vaccination in HIV-infected Adults","authors":"Taraz Samandari, Millicent Achola, Jack N Hutter, Grace Mboya, Walter Otieno, Jia Jin Kee, Yunda Huang, John J Aponte, Christian F Ockenhouse, Cynthia K Lee, Laura Polakowski, Margaret Yacovone, Asa Tapley, Sufia Dadabhai, Nonhlanhla N Mkhize, Haajira Kaldine, Sinethemba Bhebhe, Penny L Moore, John Hural, Nigel Garrett, James G Kublin","doi":"10.1093/infdis/jiaf398","DOIUrl":"https://doi.org/10.1093/infdis/jiaf398","url":null,"abstract":"mRNA vaccines have emerged as powerful tools for the prevention of infectious diseases, but subclinical malaria may reduce vaccine immunogenicity. We evaluated neutralizing antibody responses in asymptomatic HIV-infected adults with and without PCR-confirmed Plasmodium falciparum who received either monovalent mRNA-1273 or bivalent mRNA-1273.222 (WA-1 and BA.4/5) booster vaccines. In previous studies, a 50% pseudovirus inhibitory dose neutralizing antibody (ID50) titer of 1,000 correlated with 96% efficacy in preventing COVID-19. We observed ID50 geometric mean titers >22,000 in both parasitemic and non-parasitemic participants one month after boosting. We conclude that COVID-19 mRNA vaccine antibody responses are unimpaired by concurrent asymptomatic parasitemia.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763274","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":"Comparability of gastrointestinal microbiome and bile acid profiles in patients with first or multiply recurrent Clostridioides difficile infection","authors":"Jessica A Bryant, Timothy J Straub, Darrell S Pardi, Kevin D Litcofsky, Colleen R Kelly, Meghan E Chafee, Stuart H Cohen, Sahil Khanna, Charles S Berenson, Jennifer Wortman, Matthew Sims, Christopher B Ford, Mary-Jane Lombardo, Barbara H McGovern, Lisa von Moltke, Colleen S Kraft, Matthew R Henn, Brooke R Hasson","doi":"10.1093/infdis/jiaf408","DOIUrl":"https://doi.org/10.1093/infdis/jiaf408","url":null,"abstract":"Background Clostridioides difficile infection (CDI) treatment guidelines suggest varied approaches for patients with first (frCDI) or multiply recurrent CDI (mrCDI). Low microbial diversity, elevated primary bile acids (BA), and low secondary BA concentrations favor germination of C. difficile spores into toxin-producing bacteria and are believed to increase rCDI risk. Greater understanding of the gastrointestinal (GI) microbiome in rCDI may inform management of the disease. We describe a post hoc comparison of GI microbiome and bile acid profiles between patients with frCDI and mrCDI in a Phase 3 open-label trial, ECOSPOR IV, of fecal microbiota spores, live-brpk (VOWST®; VOS, formerly SER-109), an orally-administered live microbiome therapeutic. Methods Patients received VOS following symptom resolution after standard-of-care antibiotics. Pre-treatment baseline (within 3 days following antibiotic completion) and week 1 post-dosing stool samples were collected for whole metagenomic sequencing and metabolomics. Diversity was calculated from MetaPhlAn2 species profiles. Concentrations of primary and secondary BAs were measured via targeted LC-MS/MS. Results rCDI rates through week 8 were similarly low in both frCDI and mrCDI patients (6.5% vs. 9.7%, respectively). Baseline microbial diversity was similarly low between frCDI and mrCDI subgroups (p>0.05). Diversity and secondary BA concentrations increased in both subgroups, whereas primary BA concentrations declined following VOS dosing, leading to few differences between subgroups at Week 1. Conclusions These data suggest commonalities in microbiome disruption in patients with frCDI and mrCDI that contribute to recurrence and suggest that antibiotics followed by a live microbiome therapy may be an optimal treatment strategy for rCDI, regardless of number of prior CDI recurrences.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763275","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":"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":"Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Pneumonia Hospitalization Among Medicare Beneficiaries Aged ≥65 in Long-Term Care","authors":"Lindsay Zielinski, Kristin Andrejko, Nong Shang, Soyoun Park, Gordana Derado, Arnstein Lindaas, Yuanxin Zhang, Bradley Lufkin, Yoganand Chillarige, Miwako Kobayashi","doi":"10.1093/infdis/jiaf405","DOIUrl":"https://doi.org/10.1093/infdis/jiaf405","url":null,"abstract":"Background Pneumonia causes high rates of hospitalization among adults living in long-term care (LTC) facilities and is a major cause of mortality in this population. Since 2014, pneumococcal conjugate vaccines (PCVs) have been recommended for U.S. adults aged ≥65 years; however, effectiveness of PCVs against all-cause pneumonia hospitalization among adults living in LTC remains unclear. Methods We used Medicare Fee-for-Service claims data to construct an open cohort of beneficiaries aged ≥65 years between September 2014 and December 2019. We estimated 13-valent PCV (PCV13) vaccine effectiveness (VE) by comparing rates of pneumonia hospitalization among PCV13-exposed and PCV13-unexposed time during LTC stays. Discrete-time logistic regression models with generalized estimating equations were used to estimate VE, incorporating time-varying exposures and covariates. Results Among 3,485,071 beneficiaries meeting the eligibility criteria, the proportion vaccinated with PCV13 increased from 1.1% to 52.7% during the study period. The characteristics of beneficiaries with shorter LTC stays differed from those with longer LTC stays: a lower proportion of beneficiaries aged ≥85 years (LTC stay ≤100 days vs >100 days: 38.5% vs. 48.2%), but a higher proportion with chronic medical conditions (71.4% vs 66.4%), immunocompromising conditions (36.6% vs. 25.2%), and recent hospitalizations (84.1% vs. 74.7%). VE of PCV13-only against all-cause pneumonia hospitalization was 3.8% (95% confidence interval 2.4%-5.2%) overall; 5.6% (3.9%-7.2%) for LTC stays ≤100 days and 0.3% (-2.1%- 2.77%) for LTC stays >100 days. Conclusions PCV13 reduced the risk of pneumonia hospitalization among this population. Differences in beneficiary characteristics could explain differences in VE by length of LTC stay.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763276","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":"Brain imaging and whole blood targeted transcriptomic analyses to characterise cerebral infarctions in children with tuberculous meningitis","authors":"Julie Huynh, Pieter M Pretorius, Wajanat Jan, Carolina Kachramanoglou, Nhat Hoang Thanh Le, Van La Ngoc, Hai Thanh Hoang, Ny Thi Hong Tran, Tram Ngoc Pham, Thu Anh Dang Do, Dung Thi Mong Vu, Tram Bich Trinh, Vinh Dinh Do, Tung Huu Trinh, Nguyen Dinh Qui, Minh Ha Thi Dang, Elena Frangou, Sierra Santana, Caitlin Muller, Suzanne T Anderson, Diana M Gibb, Nhung Thi Hong Nguyen, Nguyen Thuong Thuy Thuong, Guy Thwaites","doi":"10.1093/infdis/jiaf399","DOIUrl":"https://doi.org/10.1093/infdis/jiaf399","url":null,"abstract":"We characterised cerebral infarctions in children with TBM and explored their relationship with systemic inflammatory mediators using targeted transcriptomic analysis. Children with TBM had baseline MRI scans and whole blood RNA sequencing for matrix metalloproteinases (MMP-8, MMP-9, TIMP-1), cytokines (IL-10, IL-1β, TNF-α, IFN-γ), and growth factors (VEGF). 22(73%) children had mild disease; 19 (63%) had cerebral infarctions, which were commonly acute (9; 47%), multiple (14; 74%) and bilateral (12; 63%), occurring in cerebral hemispheres (12; 59%), basal ganglia (10; 53%) and thalamus (5; 26%). Children with infarctions had significantly higher CSF protein, lower CSF glucose and higher systemic MMP-8 expression.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763428","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}