The Journal of Infectious Diseases最新文献

{"title":"Activity of a three-phage combination against Mycobacterium tuberculosis in disease-relevant conditions","authors":"S Janssen, S E Larsen, M Pozuelo Torres, M Beldjenna, C A Guerrero Bustamante, I Florian, T Smytheman, T Guo, R C van Wijk, G F Hatfull, A H Diacon, R N Coler, J van Ingen","doi":"10.1093/infdis/jiag516","DOIUrl":"https://doi.org/10.1093/infdis/jiag516","url":null,"abstract":"Background Phage therapy offers promise to combat antimicrobial resistance, including drug-resistant tuberculosis. Understanding phage activity against Mycobacterium tuberculosis (Mtb) in granuloma-like microenvironments that induce non-replicating states, characterized by hypoxia and acidity, is essential. Objectives To evaluate a phage combination against Mtb under hypoxic, acidic (pH 5.5), and stationary-phase conditions in vitro. Methods Mtb H37Rv cultures were grown to exponential phase for time-kill studies (106 colony forming units (CFU)/mL) under normal, hypoxic, and acidic conditions. Hypoxia was generated using sealed containers with gas sachets. Stationary-phase cultures were grown for 14–21 days and used undiluted. Treatments included control media, single phages (Fred313cpm-1Δ33, FionnbharthΔ45Δ47and Muddy HRM N0157-2), phage combination (multiplicity of infection 10:1), and rifampicin or isoniazid (0.1 µg/mL each). Phage titers (measured using M. smegmatis overlays) and bacterial counts (CFU on Middlebrook 7H11) were assessed at repeated time-points. Longitudinal phage-bacteria dynamics mixed-effects modelling and simulation was performed. Results In actively growing cultures, phage levels rose by day 7, followed by sustained reductions in Mtb counts over 31 days. Phages prevented regrowth seen with antibiotics alone. Acidic conditions variably affected individual phage stability and activity. Under hypoxic and stationary conditions, phage titers remained stable, but no reduction in Mtb was observed. Model-based predictions adequately captured phage-mycobacterial interactions with and without rifampicin. Conclusions Productive lytic activity was not observed in assays with non-replicating mycobacteria. Established models can support future experimental designs. This study provides mechanistic insights driving progress in the field of phage therapy development.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187908","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":"Reply to the comment “Galleria mellonella Models and Fluconazole for Candida auris: Caution on Extrapolating Preclinical Data to Clinical Practice”","authors":"Vasiliki Kroustali,Spyros Pournaras,Joseph Meletiadis","doi":"10.1093/infdis/jiag509","DOIUrl":"https://doi.org/10.1093/infdis/jiag509","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149150393","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":"Soluble Indicators of Endothelial Injury and Activation Emerge During Acute HIV Infection and Persist Despite Rapid Antiretroviral Therapy Initiation","authors":"Phillip Chan, Kirati Tayutivutikul, Bonnie M Slike, Suteeraporn Pinyakorn, Kathryn B Holroyd, Carlo Sacdalan, Lily Metzger, Pathariya Promsena, Eugène Kroon, Donn Colby, Somchai Sriplienchan, Nittaya Phanuphak, Robert Paul, Victor Valcour, Lishomwa Ndhlovu, Lydie Trautmann, Shelly J Krebs, Serena Spudich","doi":"10.1093/infdis/jiag495","DOIUrl":"https://doi.org/10.1093/infdis/jiag495","url":null,"abstract":"Background Vascular activation occurs during human immunodeficiency virus (HIV) infection and is a risk factor for cardiovascular disease (CVD). This study investigates whether vascular endothelial and hemostatic perturbations emerge during acute HIV infection (AHI) and persist despite immediate antiretroviral therapy (ART) initiation. Methods Thirteen plasma biomarkers indicative of endothelial and hemostatic perturbations were measured in 83 RV254 AHI cohort participants during pre-ART AHI and at week 288 post-ART, compared with cross-sectional measures from 32 people without HIV (PWoH). Hierarchical clustering was applied to week 288 biomarker profiles of RV254 participants and PWoH to identify distinct biomarker phenotypes. Results During pre-ART AHI, RV254 participants exhibited higher intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tissue factor, neopterin, and myeloperoxidase than PWoH (P < .05), independent of age, sex, and body mass index (BMI). These markers correlated with plasma HIV RNA or the CD4/CD8 ratio (P < .05). At week 288, significant reductions in ICAM-1, VCAM-1, vascular endothelial growth factor (VEGF)–C, VEGF-D, neopterin, and myeloperoxidase and a significant increase in tissue plasminogen activator were observed in RV254 (P < .05). However, VCAM-1 and thrombomodulin remained higher, and VEGF-A remained lower in RV254 participants compared to PWoH (P < .05). Hierarchical clustering identified 2 distinct clusters. Despite comparable 10-year CVD risk, 1 cluster exhibited concomitant elevation of ICAM-1, ICAM-2, VCAM-1, and E-selectin. Notably, 45% of RV254 participants vs 13% of PWoH were classified into this phenotype. Conclusions Endothelial and hemostatic perturbations emerge during AHI and correlate with HIV-related parameters. Despite suppressive ART, RV254 participants remained approximately 3.5 times more likely than PWoH to exhibit an endothelial activation biomarker phenotype.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149152576","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":"Long-term Outcomes in Previously Healthy non-HIV Individuals with Cryptococcal Meningitis Treated with Pulse-taper Corticosteroids for Post-infectious Inflammatory Syndrome","authors":"Bickey H Chang, Jessica C Hargarten, Kenneth Ssebambulidde, Terri Scott, M Teresa Magone, H Jeff Kim, Jennifer A Chisholm, Chris Zalewski, Gayla L Poling, Joseph Snow, Bridgette Jeanne Billioux, Chantal Cousineau-Krieger, John E Bennett, Dima A Hammoud, Seher H Anjum, Peter R Williamson","doi":"10.1093/infdis/jiag511","DOIUrl":"https://doi.org/10.1093/infdis/jiag511","url":null,"abstract":"Background Post-infectious inflammatory response syndrome (PIIRS) is an increasingly recognized complication of cryptococcal meningoencephalitis (CM) in non-HIV infected hosts with significant morbidity and mortality. Data describing long-term outcomes following immunomodulatory therapy are limited. Methods We conducted a prospective observational study of 15 immunocompetent adults with CM-PIIRS treated with a pulse corticosteroid taper (PCT) regimen. Performance status, neurocognitive, ophthalmologic, audiologic, and radiologic assessments were performed at greater than one year following CM diagnosis. Results After one year, performance status continued to improve from both baseline and the post-pulse periods. Neurocognitive testing revealed mild residual deficits, within the limits of normal, most prominently in information processing and psychomotor speed. Ocular abnormalities were frequent at baseline but showed substantial and sustained reductions following PCT, particularly in retinal nerve fiber layer thickness. Visual field deficits improved by 40% and remained stable thereafter. Evidence for changes in hearing sensitivity at post 1-year follow-up was mixed with 44.5% of ears meeting criteria for improvement, 11% for worsening, and 44.5% being stable. Radiologic abnormalities improved in 79% of patients, although intermittent inflammatory flares occurred during PCT but responded to dose escalation. A prolonged corticosteroid taper may be helpful, and MRI imaging can be used to evaluate response to taper. Conclusions In immunocompetent patients with CM-PIIRS, adjunctive corticosteroid therapy was associated with sustained improvement in neurologic, visual, and radiologic outcomes with mixed improvement in hearing after a year of therapy, with mild residual deficits.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149152563","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 HPV16 E7-specific T cell responses in cervical lymphocytes and peripheral blood with regression of high-grade cervical intraepithelial neoplasia lesions","authors":"Kaori Nakayama-Hosoya,Kei Kawana,Saki Kamata,Naoko Tomita,Risa Yoshida,Mitsuru Toeda,Rina Kawatake,Yuki Okuma,Osamu Kobayashi,Keisuke Saito,Shizunobu Igimi,Ayumi Taguchi,Hiroyuki Yamamoto,Ai Kawana-Tachikawa","doi":"10.1093/infdis/jiag505","DOIUrl":"https://doi.org/10.1093/infdis/jiag505","url":null,"abstract":"Abstract Background While human papillomavirus (HPV)-specific T cell responses are believed to contribute to regression of HPV-associated cervical neoplasia, their role has not been fully elucidated. We investigated HPV16 E7-specific T cell responses in the cervix and peripheral blood and their association with pathological outcomes in cervical intraepithelial neoplasia grade 2 (CIN2). Methods HPV16 E7-specific T cell responses in cervical lymphocytes (CxLs) and peripheral blood mononuclear cells (PBMCs) were quantified using overlapping peptide (OLP) pools of E7 in 38 subjects with HPV16-positive CIN2 with defined pathological outcomes. Breadth and HLA restriction of these responses were assessed using single OLPs on in vitro-expanded PBMCs. Results HPV16 E7-specific T cell responses were detected in over 30% of CxL samples but rarely detected in PBMCs unless expanded in vitro. Higher magnitudes of E7-stimulated responses in CxLs, along with elevated non-specific background responses, were associated with pathological regression of CIN2 lesions. The E7-specific T cell responses in expanded PBMCs varied in breadth among subjects and were mediated by both CD4+ and CD8+ T cells with diverse HLA restrictions. Importantly, response breadth was significantly greater in subjects with lesion regression. Conclusions HPV-specific T cell responses are preferentially localized at the site of infection and maintained at low frequencies in peripheral blood. The magnitude of local E7-stimulated response in CxLs and the breadth of E7-specific responses in expanded PBMCs were associated with pathological regression of CIN2. These associations support a potential role for E7-specific T cell responses in the regression of HPV-related cervical neoplasia.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089484","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":"Plasma Proteome Signature of Immune Inhibition is Associated with Cytomegalovirus in People with HIV-1","authors":"Michael L Freeman,Gordon Honerkamp-Smith,Alan Wells,Brian M Clagett,Jean Huang-Gao,Patricia K Riggs,Scott L Letendre,Celestine N Wanjalla,Peter W Hunt,Sara Gianella","doi":"10.1093/infdis/jiag498","DOIUrl":"https://doi.org/10.1093/infdis/jiag498","url":null,"abstract":"Abstract Background Cytomegalovirus (CMV) is highly prevalent and associated with comorbidities in people with HIV-1 (PWH). CMV contributes to systemic inflammation, but comprehensive analyses of the plasma proteome in PWH with or without CMV are lacking. Methods Plasma proteomes from 59 age- and CD4 count-matched PWH on suppressive antiretroviral therapy (ART) with (CMV+) or without (CMV-) CMV were characterized by inflammation- and cardiometabolic-focused proteomics proximity extension assays. Normalized protein expression values were analyzed using linear mixed effects models, partial least squares-discriminant analysis, and gene set enrichment analysis. T cell phenotypes were assessed by flow cytometry. Results In covariate-unadjusted linear mixed effects models, 118/350 (33.7%) inflammatory and 27/363 (7.4%) cardiometabolic proteins were differentially expressed (FDR-adjusted p<0.05). Proteins most significantly upregulated in CMV+ participants were associated with immune inhibition (e.g., FcRL6, LY9, HLA-DRA), cytotoxic differentiation (e.g., KLRD1, CD70, SLAMF7), and interferon-associated chemotaxis (e.g., CXCL9, CXCL10). Several of the most significantly downregulated proteins in CMV+ PWH were associated with apoptosis (e.g., CASP2, TRIM21, TRAF2). Surface FcRL6 expression was significantly elevated on CD57+CD28- CD8 T cells of CMV+ PWH. Conclusions These data identify a CMV-associated plasma proteomic signature in treated HIV, characterized by immunoinhibitory/cytotoxic programs, supporting targeting CMV to reduce immune dysregulation and related comorbidities in PWH.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089529","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":"Bronchoalveolar Lavage Fluid Cellularity Reflects Peripheral Cytopenias and Fungal Burden but Not Short-Term Outcomes in Invasive Pulmonary Aspergillosis","authors":"Sung-Yeon Cho,Sebastian Wurster,Ying Jiang,Takahiro Matsuo,Scott E Evans,Ajay Sheshadri,Dimitrios P Kontoyiannis","doi":"10.1093/infdis/jiag475","DOIUrl":"https://doi.org/10.1093/infdis/jiag475","url":null,"abstract":"Abstract We characterized leukocyte profiles in bronchoalveolar lavage fluid (BALF) of 63 patients with hematologic malignancy and culture-documented invasive pulmonary aspergillosis and evaluated associations with peripheral blood leukocyte counts, Aspergillus burden, respiratory coinfections, and clinical outcomes. BALF cellularity mirrored peripheral cytopenias yet increased with higher Aspergillus burden and respiratory coinfections, consistent with both systemic immune availability and local inflammatory stimuli. However, BALF cellularity was not independently associated with 42-day mortality, which was driven by persistent neutropenia and critical illness. These findings suggest BALF cellularity may not be an independent determinant of short-term outcomes but rather reflects underlying host and disease context.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"156 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089539","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":"Isavuconazole and Micafungin Elicit Synergistic Antifungal and Immunomodulatory Activity Against Azole-Resistant\u0000 Aspergillus fumigatus","authors":"Sebastian Wurster,Nathaniel D Albert,Lauren Matula,Sung-Yeon Cho,Dimitrios P Kontoyiannis","doi":"10.1093/infdis/jiag461","DOIUrl":"https://doi.org/10.1093/infdis/jiag461","url":null,"abstract":"Abstract Azole/echinocandin combinations are often considered in invasive aspergillosis caused by azole-resistant Aspergillus fumigatus (ARAF). Therefore, we studied both direct and immune-mediated activity of isavuconazole and micafungin against 3 ARAF isolates. We observed synergistic activity against all isolates (checkerboard assay). In addition, pre-exposure of all ARAF isolates to subinhibitory concentrations of either drug enhanced hyphal inactivation by human mononuclear cells. While only micafungin-pretreated ARAF hyphae triggered increased NF-κB signaling in reporter macrophages, direct exposure of macrophages to low isavuconazole concentrations (≤1 μg/mL) enhanced Toll-like receptor signaling and stimulated effector pathways. Inversely, high isavuconazole concentrations (≥5 μg/mL) attenuated Toll-like receptor signaling, suggesting immunotoxicity.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089538","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":"Response to “Revisiting HPV Latency and Detectability: Considerations on the IPVS Consensus Statement”","authors":"Patti E Gravitt,Marc D Ryser,Anne Hammer","doi":"10.1093/infdis/jiag447","DOIUrl":"https://doi.org/10.1093/infdis/jiag447","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089175","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":"Host Immune Biosignatures Predict Septic Shock and Mortality in Solid Organ Transplant Recipients With Gram-Negative Bacteremia","authors":"Emily M Eichenberger,Felicia Ruffin,Geeta M Karadkhele,Christian P Larsen,Vance G Fowler","doi":"10.1093/infdis/jiag466","DOIUrl":"https://doi.org/10.1093/infdis/jiag466","url":null,"abstract":"Abstract Background The aim of this study was to determine whether the addition of immunologic biosignatures to a predictive model based solely on clinical data could improve the model's ability to predict patient outcome among solid organ transplant (SOT) recipients with gram-negative bacteremia (GNB). Methods Plasma was prospectively collected from SOT recipients with GNB. Twenty-seven cytokines, chemokines, and immunoglobulin levels were quantified. Two logistic regression models were specified: a clinical model including age, transplanted organ, and time since transplant and a clinical-immunologic model that additionally incorporated the first two principal components. Model performance was evaluated using area under the curve (AUC). Internal validation was performed by repeated 10-fold cross-validation. AUCs were compared with a paired t test. Results Of 169 SOT recipients with GNB, 45 (26.6%) experienced an adverse outcome (septic shock or death). When compared with the clinical model alone, the clinical-immunologic model demonstrated superior discrimination (AUC, 0.70 vs 0.84; P < .001). Principal component 1, characterized by broad immune dysregulation, was associated with increased risk for adverse outcome (odds ratio, 1.43; 95% CI, 1.24–1.69) and was characterized by strong contributions from innate proinflammatory mediators (TNF-α, IL-1β, IL-6, IL-8, MCP-1, MIP-1β, IL12p70, MIP-1α, and GMCSF), anti-inflammatory mediators (IL-10, IL-4, and IL-13), and IL-2. In contrast, principal component 2 was associated with a favorable outcome (odds ratio, 0.61; 95% CI, .43–.84) and reflected coordinated adaptive immunity, with dominant contributions from Th1, Th17, and humoral pathways (TNFβ, IFNg, IP-10, IL-17A, IgG, IgM). Conclusions Immune biosignatures significantly improved prediction of adverse outcomes beyond clinical factors in SOT recipients with GNB.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"404 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089540","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}