Journal of Infectious Diseases最新文献

{"title":"When PD-1 Meets Plaque: Making CD8 Senescence Signals Clinically Actionable in Treated HIV.","authors":"Xiaowei Zhang","doi":"10.1093/infdis/jiag081","DOIUrl":"10.1093/infdis/jiag081","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e1083-e1084"},"PeriodicalIF":4.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127447","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":"Response to Dr Belviranli Keskin's Comments.","authors":"James J Knox, Ingi Lee, Emily A Blumberg, Eline T Luning Prak","doi":"10.1093/infdis/jiag056","DOIUrl":"10.1093/infdis/jiag056","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e1078"},"PeriodicalIF":4.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114771","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":"Population Pharmacokinetic Modeling of Standard- and High-Dose Rifampicin for Tuberculosis Preventive Therapy in the 2R2 Randomized Controlled Trial.","authors":"Fajri Gafar, Elin M Svensson, Vycke Yunivita, Federica Fregonese, Dina Fisher, Greg J Fox, Thu Anh Nguyen, Binh Hoa Nguyen, James Johnston, Richard Long, Chantal Valiquette, Rob E Aarnoutse, Rovina Ruslami, Dick Menzies","doi":"10.1093/infdis/jiag052","DOIUrl":"10.1093/infdis/jiag052","url":null,"abstract":"<p><strong>Background: </strong>High-dose rifampicin could potentially shorten tuberculosis preventive therapy (TPT) and improve outcomes. We aimed to characterize population pharmacokinetics of standard- and high-dose rifampicin for TPT among individuals with tuberculosis infection.</p><p><strong>Methods: </strong>Intensive and sparse pharmacokinetic substudies were conducted in Indonesia, Canada, and Vietnam within the 2R2 randomized trial, which compared 2 months of high-dose rifampicin at 20 mg/kg/day (2R20) or 30 mg/kg/day (2R30) with 4 months of standard-dose rifampicin at 10 mg/kg/day (4R10) in adults and adolescents aged ≥ 10 years. Venous blood samples were collected after 4 weeks of treatment. Rifampicin pharmacokinetics were analyzed using nonlinear mixed-effects modeling in NONMEM.</p><p><strong>Results: </strong>Among 1368 trial participants, 440 were included in model development (51 intensive and 389 sparse sampling), with 191 (43%) assigned to 4R10, 159 (36%) to 2R20, and 90 (20%) to 2R30. A 1-compartment model with saturable hepatic extraction and transit-compartment absorption best described rifampicin pharmacokinetics. All disposition parameters were allometrically scaled using fat-free mass. Country-specific differences, particularly variation in drug formulation, were associated with lower bioavailability in Canada {-21.8% (95% confidence interval [CI] -27.9 to -18.0%)} and Vietnam (-12.3% [95% CI -17.7 to -7.9%]) compared with Indonesia. The 24-hour area under the concentration-time curve increased more than proportionally with dose and was higher across treatment arms in Indonesia, followed by Vietnam and Canada.</p><p><strong>Conclusions: </strong>High-dose rifampicin for TPT resulted in greater-than-proportional increases in exposure due to nonlinear clearance at higher doses. Substantial between-country variability in exposure was observed, which may have been due to multiple factors, including differences in country-specific formulations, fat-free mass, and unmeasured confounders.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e999-e1010"},"PeriodicalIF":4.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146054829","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":"Antibody-Dependent Neutrophil Phagocytosis of Plasmodium falciparum-Infected Erythrocytes Is Mediated by FcγRIIa.","authors":"Maria Saeed, Elizabeth H Aitken, Bruce D Wines, Stephen J Rogerson","doi":"10.1093/infdis/jiag071","DOIUrl":"10.1093/infdis/jiag071","url":null,"abstract":"<p><strong>Background: </strong>Fc gamma receptor III b (FcγRIIIb), a glycosylphosphatidylinositol-linked receptor, is the most abundant neutrophil FcγR on neutrophils, followed by FcγRIIa. FcγRs interact with IgG, and studies have reported the association of antibody-dependent neutrophil phagocytosis (ADNP) with protection against malaria; however, the role of specific FcγRs is not clear.</p><p><strong>Methods: </strong>To investigate the relative importance of FcγRIIIb and FcγRIIa as mediators of the ADNP of Plasmodium falciparum-infected erythrocytes, purified neutrophils from healthy donors were treated with tumor necrosis factor (TNF) to mobilize the intracellular stores of FcγRIIIb to the surface, followed by enzymatic cleavage of glycosylphosphatidylinositol-linked FcγRIIIb with phosphatidylinositol phospholipase C (PIPLC).</p><p><strong>Results: </strong>In TNF/PIPLC-treated neutrophils, detectable FcγRIII decreased by 79% (relative geometric mean fluorescence intensity, 21 ± 4.5 [mean ± SD]), while FcγRIIa detection increased by 82% (182 ± 2.3) as compared with untreated neutrophils (100%). When opsonized infected erythrocytes were incubated with TNF/PIPLC-treated neutrophils, ADNP by FcγRIIIb-depleted neutrophils increased significantly (relative phagocytosis, 585% ± 108%) as compared with untreated neutrophils (100%, P = .042). Using FcγR blocking, we show that when compared with no blocker (relative phagocytosis, 100%), ADNP was reduced >5-fold by FcγRIIa blocker alone (∼17% ± 1.5%, P < .05) and to a similar extent by combined FcγRIIa and FcγRIII blockers (∼24% ± 5.5%, P < .05).</p><p><strong>Conclusions: </strong>Our data suggest that FcγRIIa is the main phagocytic receptor that mediates the ADNP of infected erythrocytes and that FcγRIIIb acts as a decoy receptor.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e882-e890"},"PeriodicalIF":4.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127454","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":"Doxycycline Post-exposure Prophylaxis and Off-target Antimicrobial Resistance: Potential Amplification Within Sexual Networks.","authors":"Manon Roberts, Peter Davis","doi":"10.1093/infdis/jiaf439","DOIUrl":"10.1093/infdis/jiaf439","url":null,"abstract":"<p><p>Doxycycline post-exposure prophylaxis is now included in many clinical guidelines, yet concerns remain regarding antimicrobial resistance, particularly off-target effects on commensal bacteria in the oropharynx, with intimate behaviours potentially facilitating resistance transmission within sexual networks.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"625-627"},"PeriodicalIF":4.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884194","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":"Re: Estimating the Early Transmission Inhibition of New Treatment Regimens for Drug-Resistant Tuberculosis.","authors":"Tom A Yates, David A Barr","doi":"10.1093/infdis/jiaf655","DOIUrl":"10.1093/infdis/jiaf655","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e1069-e1070"},"PeriodicalIF":4.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145935792","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":"Beyond Antibodies: Influenza Vaccine Induced T-Cell Response in Hematological Malignancy- Commentary on Insights From Hall et al.","authors":"Katja M Sauer, Eloísa Felipe Fumero, Oliver A Cornely, Anna Nordlander, Sigrun Einarsdottir, Sibylle C Mellinghoff","doi":"10.1093/infdis/jiag079","DOIUrl":"10.1093/infdis/jiag079","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e1079-e1080"},"PeriodicalIF":4.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146159025","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":"National- and State-level SARS-CoV-2 Immunity Trends From January 2020 to December 2023: a Mathematical Modeling Analysis.","authors":"Fayette Klaassen, Nicole A Swartwood, Melanie H Chitwood, Rafael Lopes, Masahiko Haraguchi, Joshua A Salomon, Ted Cohen, Nicolas A Menzies","doi":"10.1093/infdis/jiaf532","DOIUrl":"10.1093/infdis/jiaf532","url":null,"abstract":"<p><strong>Background: </strong>Effective immune protection against SARS-CoV-2 infection and severe COVID-19 disease continues to change due to viral evolution and waning immunity. We estimated population-level immunity to SARS-CoV-2 for each of the 50 United States (U.S.) and the District of Columbia from January 2020 through December 2023.</p><p><strong>Methods: </strong>We updated a model of SARS-CoV-2 infections to align with the latest evidence on SARS-CoV-2 natural history and waning of immunity, and to integrate various data sources available throughout the pandemic. We used this model to produce population estimates of effective protection against SARS-CoV-2 infection and severe COVID-19 disease.</p><p><strong>Results: </strong>On 30 December 2023, 98.6% of the U.S. population had experienced immunological exposure to SARS-CoV-2 through infection and/or vaccination, with 88.3% (95% credible interval: 78.4%, 95.5%) having had at least one SARS-CoV-2 infection. Despite this high exposure, the average population-level protection against infection was 31.6% (25.1%, 41.2%). Population-level protection against severe disease was 66.1% (59.2%, 74.3%).</p><p><strong>Conclusion: </strong>A new wave of SARS-CoV-2 infections and COVID-19-associated hospitalizations began near the end of 2023, with the introduction of the JN.1 variant. This upturn suggests that the U.S. population remains at risk of SARS-CoV-2 infection and severe COVID-19 disease despite the high level of cumulative exposure in the United States. This decline in effective protection is likely due to both waning and continued viral evolution.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"714-724"},"PeriodicalIF":4.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356718","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":"Multiancestry Genome-Wide Association Study Identifies Variants in a Zinc Finger Gene Cluster as Novel Regulators of HIV Control.","authors":"Abraham Awada, Riley H Tough, Jacques Fellay, Paul J McLaren","doi":"10.1093/infdis/jiag072","DOIUrl":"10.1093/infdis/jiag072","url":null,"abstract":"<p><strong>Background: </strong>Human immunodeficiency virus 1 (HIV-1) remains a global health challenge, emphasizing the need to identify new host factors that influence pathogenesis to serve as drug targets. Identifying genetic determinants of HIV-1 control across diverse populations remains a top priority.</p><p><strong>Methods: </strong>We conducted a multiancestry genome-wide association study (GWAS) of HIV-1 set-point viral load (spVL) leveraging genotype and viral load data from 10 723 individuals with HIV-1. To prioritize candidate genes and mechanisms, we integrated GWAS findings with transcriptome-wide association study (TWAS) and expression quantitative trait loci (eQTL) data.</p><p><strong>Results: </strong>We implicate the potential role of zinc finger proteins in pathogenesis through identification of a novel signal in the zinc finger protein 586 (ZNF586) gene on chromosome 19, which is predicted to regulate RNA polymerase II transcription. The top variant, (rs35962362-G) is intronic to the ZNF586 gene, and is associated with an approximate 0.1 log increase in spVL per mutant allele. Our subsequent TWAS along with interrogation of eQTL data suggest that increased ZNF586 expression is associated with increased spVL in whole blood.</p><p><strong>Conclusions: </strong>Our findings suggest ZNF586 as a novel host factor for HIV-1 control and highlight the role of zinc finger proteins as potential contributors to viral persistence. Although ZNF586 has not previously been linked to HIV-1 pathogenesis, its potential role in maintaining retroviral latency and modulating genomic regulation warrants further investigation.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"664-673"},"PeriodicalIF":4.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120901","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":"Cerebrospinal Fluid Hypo-inflammation Drives Mortality in HIV-Associated Tuberculous Meningitis.","authors":"Anna L Wilt, David B Meya, Fiona V Cresswell, Abduljewad Wele, Mable Kabahubya, Enock Kagimu, Jane Gakuru, Timothy Mugabi, Sarah Kimuda, Suzan Namombwe, Asmus Tukundane, Elizabeth C Okafor, Samuel Okurut, James E Scriven, Biyue Dai, Nicole Engen, Nathan C Bahr, David R Boulware, Tyler D Bold","doi":"10.1093/infdis/jiag032","DOIUrl":"10.1093/infdis/jiag032","url":null,"abstract":"<p><strong>Background: </strong>Outcomes in tuberculous meningitis (TBM) are closely linked to host inflammation. Anti-inflammatory corticosteroid therapy improves survival in HIV-negative TBM, but not in people with HIV, among whom TBM is fatal in 40-50% of cases. Therefore, we investigated how mortality is associated with the local immune response in people with HIV-associated TBM.</p><p><strong>Methods: </strong>We measured baseline concentrations of immune signaling mediators in cerebrospinal fluid (CSF) of 149 adults with HIV in Uganda, who presented with definite or probable TBM. Participants received both antimycobacterial and corticosteroid therapy.</p><p><strong>Results: </strong>At baseline, non-survivors had more severe TBM disease and lower blood CD4 T cells than survivors. Mortality at 90 days was strongly associated with CSF hypo-inflammation. Cerebrospinal fluid interferon gamma (IFN-γ) was most differentially expressed by survivors (2.2 log2-fold change higher, P = .003), and 90-day mortality was lower with increasing concentrations (tertile-1 = 50%, tertile-2 = 41%, tertile-3 = 18%; P = .006). Even among people who successfully mounted a CSF cellular immune response (>5 white cells/µL CSF), those with low CSF IFN-γ had higher risk of death (hazard ratio = 3.10 [1.44-6.68]). Interleukin-13 had a more complex relationship, with lower mortality among people with intermediate CSF interleukin-13 concentrations but higher at the 2 extremes (tertile-1 = 45%, tertile-2 = 22%, tertile-3 = 40%; P = .017). Of all subgroups, those with both peripheral CD4 depletion and low CSF IFN-γ had the highest mortality (63%).</p><p><strong>Conclusions: </strong>In adults with HIV-associated TBM receiving dexamethasone, mortality was strongly associated with CSF hypo-inflammation. Although steroids may be appropriate in those with high inflammation, personalized approaches to immunotherapy are likely necessary to improve outcomes.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"787-798"},"PeriodicalIF":4.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12933416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145960762","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}