Journal of Infectious Diseases最新文献

{"title":"A Biomarker Profile Reflective of Preserved Thymic Function Is Associated With Reduced Comorbidities in Aging People With HIV: An AGEhIV Cohort Analysis.","authors":"Manon C Vanbellinghen, Anders Boyd, Neeltje A Kootstra, Maarten F Schim van der Loeff, Marc van der Valk, Peter Reiss","doi":"10.1093/infdis/jiae603","DOIUrl":"10.1093/infdis/jiae603","url":null,"abstract":"<p><strong>Background: </strong>People with HIV (PWH) experience a higher burden of aging-associated comorbidities, the underlying mechanisms of which remain to be fully elucidated. We aimed to identify profiles based on immune, inflammatory, and aging biomarkers in blood from PWH and controls, and explore their association with total comorbidities over time.</p><p><strong>Methods: </strong>Latent profile analysis was used to construct biomarker profiles in AGEhIV cohort participants (94 with well-controlled HIV on antiretroviral therapy [ART] and 95 controls without HIV) using baseline measurements of selected biomarkers. Factors associated with profile membership were assessed by multivariable logistic regression. The association between profiles and mean total comorbidities during follow-up was assessed by Poisson regression, stratified by HIV status. Comorbidities included type 2 diabetes, non-AIDS malignancies, cardiovascular disease, osteoporosis, chronic kidney disease. and frailty.</p><p><strong>Results: </strong>Three biomarker profiles were identified: \"high thymic output/low inflammation\" (HT/LI) profile (n = 27 PWH, n = 9 controls), \"low thymic output/high inflammation\" (LT/HI) profile (n = 29 PWH, n = 26 controls), and an \"intermediate\" profile (n = 38 PWH, n = 60 controls). Only HIV status was significantly associated with profile membership. PWH, relative to controls, more often exhibited the HT/LI profile compared to other profiles. In PWH, but not in controls, the HT/LI profile was associated with significantly lower mean comorbidities during a median 8.0 years (interquartile range, 7.1-8.1) of follow-up.</p><p><strong>Conclusions: </strong>People aging with well-controlled HIV on ART were more likely to exhibit a biomarker profile indicative of preserved thymic function and less chronic inflammation compared to controls. PWH with such a profile seemed relatively protected from developing aging-associated comorbidities.</p><p><strong>Clinical trials registration: </strong>NCT01466582.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"622-632"},"PeriodicalIF":5.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When Surviving Neglected Tropical Diseases Is Not Enough.","authors":"Fernando Almeida-Val, Cássia da Luz Goulart, Wuelton Marcelo Monteiro, Guilherme Peixoto Tinoco Areas","doi":"10.1093/infdis/jiae579","DOIUrl":"10.1093/infdis/jiae579","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"822-823"},"PeriodicalIF":5.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reconstitution of Norovirus-Specific T-Cell Responses Following Hematopoietic Stem Cell Transplantation in Patients With Inborn Errors of Immunity and Chronic Norovirus Infection.","authors":"Jessica Durkee-Shock, Ariella Cohen, Naseem Maghzian, Gloria Pezzella, Mariah Jensen-Wachspress, Anna Hostal, Karenna Barton, Krista Gangler, Blachy J Dávila Saldaña, Natthawan Chaimongkol, Catherine M Bollard, Stanislav V Sosnovtsev, Jeffrey Cohen, Bianca M Nagata, Derron A Alves, Rajarshi Ghosh, Bryce A Seifert, Alexandra Freeman, Corina Gonzalez, Luigi D Notarangelo, Kim Y Green, Michael D Keller","doi":"10.1093/infdis/jiae398","DOIUrl":"10.1093/infdis/jiae398","url":null,"abstract":"<p><strong>Background: </strong>Chronic norovirus infection (CNI) causes significant morbidity in immunocompromised patients. No effective prevention or treatment currently exists.</p><p><strong>Methods: </strong>Two patients with inborn errors of immunity, X-linked severe combined immunodeficiency (X-SCID) and DOCK8 deficiency, were followed longitudinally for clinical course, immune reconstitution, norovirus-specific T-cell (NST) response, B-cell reconstitution, and norovirus-specific antibody production. Samples were obtained in the peri-hematopoietic stem cell transplant (HSCT) setting before and after CNI clearance. The norovirus strain causing CNI was followed longitudinally for norovirus stool viral loads and sequencing.</p><p><strong>Results: </strong>The noroviruses were identified as GII.4 Sydney[P4 New Orleans] in 1 patient and GII.17[P17] in the other. An exacerbation of diarrhea post-HSCT in the patient with X-SCID was consistent with norovirus infection but not with graft-versus-host disease on pathologic samples. Both patients recovered polyfunctional NSTs in the CD4 and CD8 T-cell compartments that recognized multiple norovirus structural and nonstructural viral antigens. T-cell responses were minimal during active CNI but detectable after resolution. Mapping of NST responses between the patient with DOCK8 deficiency and his matched sibling donor were nearly identical. B-cell reconstitution or new endogenous antibody production for immunoglobulin A or immunoglobulin G was not observed.</p><p><strong>Conclusions: </strong>This report is the first to demonstrate reconstitution of NST immunity after HSCT closely temporally aligned with clearance of CNI, suggesting that cellular immunity is sufficient for norovirus clearance.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"773-783"},"PeriodicalIF":5.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional OmpA of Salmonella Typhimurium Provides Protection From Lysosomal Degradation and Inhibits Autophagic Processes in Macrophages.","authors":"Atish Roy Chowdhury, Dipasree Hajra, Debapriya Mukherjee, Abhilash Vijay Nair, Dipshikha Chakravortty","doi":"10.1093/infdis/jiae376","DOIUrl":"10.1093/infdis/jiae376","url":null,"abstract":"<p><p>Our previous study showed that OmpA-deficient Salmonella Typhimurium failed to retain LAMP-1 around the Salmonella-containing vacuoles (SCV), and escaped in to the host cell cytosol. Here we show that the cytosolic population of S. Typhimurium ΔompA sequestered autophagic markers, syntaxin17 and LC3B, in a sseL-dependent manner and initiated lysosomal fusion. Moreover, inhibition of autophagy using bafilomycinA1 restored its intracellular proliferation. Ectopic overexpression of OmpA in S. Typhimurium ΔsifA restored its vacuolar niche and increased its interaction with LAMP-1, suggesting a sifA-independent role of OmpA in maintaining an intact SCV. Mutations in the OmpA extracellular loops impaired the LAMP-1 recruitment to SCV and caused bacterial release into the cytosol of macrophages, but unlike S. Typhimurium ΔompA, they retained their outer membrane stability and did not activate the lysosomal degradation pathway, aiding in their intramacrophage survival. Finally, OmpA extracellular loop mutations protected cytosolic S. Typhimurium ΔsifA from lysosomal surveillance, revealing a unique OmpA-dependent strategy of S. Typhimurium for its intracellular survival.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"716-728"},"PeriodicalIF":5.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Immune Biomarkers Predictive of Progression to Active Tuberculosis in Household Contacts of Patients With Tuberculosis.","authors":"Anuradha Rajamanickam, Evangeline Ann Daniel, Bindu Dasan, Kannan Thiruvengadam, Padmapriyadarsini Chandrasekaran, Sanjay Gaikwad, Sathyamurthi Pattabiraman, Brindha Bhanu, Amsaveni Sivaprakasam, Vandana Kulkarni, Rajesh Karyakarte, Mandar Paradkar, Shri Vijay Bala Yogendra Shivakumar, Vidya Mave, Amita Gupta, Luke Elizabeth Hanna, Subash Babu","doi":"10.1093/infdis/jiae365","DOIUrl":"10.1093/infdis/jiae365","url":null,"abstract":"<p><strong>Background: </strong>The progression from Mycobacterium tuberculosis infection to active tuberculosis disease varies among individuals, and identifying biomarkers to predict progression is crucial for guiding interventions. In this study, we aimed to determine plasma immune biomarker profiles in healthy household contacts of index patients with pulmonary tuberculosis, who either progressed to tuberculosis or remained as nonprogressors.</p><p><strong>Methods: </strong>A cohort of household contacts of adults with pulmonary tuberculosis was enrolled, consisting of 15 contacts who progressed to tuberculosis disease and 15 nonprogressors. Plasma samples were collected at baseline, 4 months, and 12 months to identify predictive tuberculosis progression markers.</p><p><strong>Results: </strong>Our findings revealed that individuals in the progressor group exhibited significantly decreased levels of interferon (IFN) γ, tumor necrosis factor α, interleukin 2, IL-1α, IL-1β, and 17A, and interleukin 1 receptor antagonist (IL-1Ra) at baseline, month 4, and month 12. In contrast, the progressor group displayed significantly elevated levels of IFN-α, IFN-β, interleukin 6 and 12, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 10 (IL-10) and 33 (IL-33), CCL2, CCL11, CXCL8, CXCL10, CX3CL1, vascular endothelial growth factor, granzyme B, and programmed death ligand -1 compared to the nonprogressor group at baseline, months 4 and 12. Receiver operating characteristic analysis (ROC) identified IFN-γ, GM-CSF, IL-1Ra, CCL2, and CXCL10 as the most promising predictive markers, with an area under the receiver operating characteristic curve of ≥90. Furthermore, combinatorial analysis demonstrated that GM-CSF, CXCL10, and IL-1Ra, when used in combination, exhibited high accuracy in predicting progression to active tuberculosis disease.</p><p><strong>Conclusions: </strong>Our study suggests that a specific set of plasma biomarkers, GM-CSF, CXCL10, and IL-1Ra, can effectively identify household contacts at significant risk of developing tuberculosis disease. These findings have important implications for early intervention and preventive strategies in tuberculosis-endemic regions.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"696-705"},"PeriodicalIF":5.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 1b/2a Trial of a Half-life Extended Respiratory Syncytial Virus Neutralizing Antibody, Clesrovimab, in Healthy Preterm and Full-term Infants.","authors":"Shabir A Madhi, Eric A F Simões, Armando Acevedo, Jose M Novoa Pizarro, Julie S Shepard, Radha A Railkar, Xin Cao, Brian M Maas, Xiaowei Zang, Andrea Krick, Brad Roadcap, Kalpit A Vora, Antonios O Aliprantis, Andrew W Lee, Anushua Sinha","doi":"10.1093/infdis/jiae581","DOIUrl":"10.1093/infdis/jiae581","url":null,"abstract":"<p><strong>Background: </strong>Clesrovimab is an investigational monoclonal antibody with an extended half-life targeting site IV of the respiratory syncytial virus (RSV) fusion protein for the prevention of RSV disease in infants.</p><p><strong>Methods: </strong>In this phase 1b/2a, double-blind study, 183 healthy preterm and full-term infants 2 weeks to 8 months of age were randomized 4:1 within 5 panels (preterm 20, 50, 75, or 100 mg; full-term 100 mg) to receive 1 dose of clesrovimab or placebo. The objectives were to evaluate safety, pharmacokinetics, serum neutralizing antibodies (SNA), and antidrug antibodies (ADA). The incidence of RSV-associated end points (medically attended lower respiratory tract infection, hospitalization, and acute respiratory infection) were also evaluated through 150 days postdose.</p><p><strong>Results: </strong>The most common adverse event through day 14 was irritability; no treatment-related serious AEs were reported. Clesrovimab serum concentrations displayed a geometric mean apparent half-life of 44.9 days. Of participants receiving clesrovimab, 51 (36.7%) developed ADA with no apparent impact in pharmacokinetics. SNA titers increased in a dose-dependent manner at day 150. The incidences of RSV-associated end points were lower in infants treated with clesrovimab compared with placebo.</p><p><strong>Conclusions: </strong>Clesrovimab was generally well tolerated and exhibited an extended half-life compared to typical IgG1 antibodies, supporting its ongoing development in late-stage trials. Clinical Trial Registration. NCT03524118.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e478-e487"},"PeriodicalIF":5.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ascertainment of Community Exposure Sites to Ross River Virus During the 2020 Outbreak in Brisbane, Australia.","authors":"Tatiana Proboste, Damber Bista, Nicholas J Clark, Sahil Arora, Gregor Devine, Jonathan M Darbro, Deena S Malloy, Daniel Francis, Ricardo J Soares Magalhães","doi":"10.1093/infdis/jiae578","DOIUrl":"10.1093/infdis/jiae578","url":null,"abstract":"<p><p>This study investigated potential Ross River virus (RRV) exposure sites in Greater Brisbane during the Queensland coronavirus disease 2019 lockdown (January-July 2020). Using RRV notifications, cluster identification techniques, and mobile phone data for movement network analysis, the study examined 993 RRV cases and 9 million movement trajectories from residential RRV cluster areas (hot spots). The findings revealed that population movement was a key risk factor to RRV incidence within hot spots, whereby highly interconnected areas had more RRV cases during lockdown. While environmental conditions within RRV hot spots were less significant compared with their connectivity, areas with higher vegetation density had fewer RRV cases. The study also noted that individuals from RRV hot spots spent less time in green areas before lockdown than during and after lockdown. The results suggest that population movement significantly influenced the 2020 RRV outbreak. These insights can help adapt current vector control and surveillance protocols to target areas identified in this study.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e501-e510"},"PeriodicalIF":5.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Review: Current Laboratory and Point-of-Care Pharyngitis Diagnostic Testing and Knowledge Gaps.","authors":"","doi":"10.1093/infdis/jiaf024","DOIUrl":"10.1093/infdis/jiaf024","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e595"},"PeriodicalIF":5.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory Immune Checkpoints Predict 7-Day, In-Hospital, and 1-Year Mortality of Internal Medicine Patients Admitted With Bacterial Sepsis.","authors":"Filippo Mearelli, Alessio Nunnari, Annalisa Rombini, Federica Chitti, Francesca Spagnol, Chiara Casarsa, Giulia Bolzan, Ilaria Martini, Anna Marinelli, Stefania Rizzo, Cristiana Teso, Alessandra Macor, Nicola Fiotti, Giulia Barbati, Carlo Tascini, Venera Costantino, Stefano Di Bella, Filippo Giorgio Di Girolamo, Tiziana Bove, Daniele Orso, Giorgio Berlot, Michael Klompas, Gianni Biolo","doi":"10.1093/infdis/jiae370","DOIUrl":"10.1093/infdis/jiae370","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a life-threatening syndrome with complex pathophysiology and great clinical heterogeneity, which complicates the delivery of personalized therapies. Our goal was to demonstrate that some biomarkers identified as regulatory immune checkpoints in preclinical studies could guide the stratification of patients with sepsis into subgroups with shared characteristics of immune response or survival outcomes.</p><p><strong>Methods: </strong>We assayed the soluble counterparts of 12 biomarkers of immune response in 113 internal medicine patients with bacterial sepsis.</p><p><strong>Results: </strong>IL-1 receptor-associated kinase M (IRAK-M) exhibited the highest hazard ratios (HRs) for increased 7-day (1.94; 95% confidence interval [CI], 1.17-3.20) and 30-day mortality (1.61; 95% CI, 1.14-2.28). HRs of IRAK-M and galectin-1 for predicting 1-year mortality were 1.52 (95% CI, 1.20-1.92) and 1.64 (95% CI, 1.13-2.36), respectively. Patients with elevated serum levels of IRAK-M and galectin-1 had clinical traits of immune suppression and low survival rates.</p><p><strong>Conclusions: </strong>Two inhibitory immune checkpoint biomarkers (IRAK-M and galectin-1) helped identify 3 distinct sepsis phenotypes with distinct prognoses. These biomarkers shed light on the interplay between immune dysfunction and prognosis in patients with bacterial sepsis and may prove to be useful prognostic markers, therapeutic targets, and biochemical markers for targeted enrollment in therapeutic trials.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"706-715"},"PeriodicalIF":5.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Benefits of Medically Tailored Meals for People With Human Immunodeficiency Virus.","authors":"Seth A Berkowitz","doi":"10.1093/infdis/jiae196","DOIUrl":"10.1093/infdis/jiae196","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"549-551"},"PeriodicalIF":5.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}