The Journal of Infectious Diseases最新文献_第4页

Effectiveness, safety, and pharmacokinetics of linezolid in pediatric bacterial central nervous system infections

The Journal of Infectious Diseases Pub Date : 2025-04-01 DOI: 10.1093/infdis/jiaf169

Lvchang Zhu, Xinxin Zeng, Yi Shi, Yuhang Wu, Xiaoshan Zhang, Shanshan Xu, Xuben Yu, Lisu Huang

{"title":"Effectiveness, safety, and pharmacokinetics of linezolid in pediatric bacterial central nervous system infections","authors":"Lvchang Zhu, Xinxin Zeng, Yi Shi, Yuhang Wu, Xiaoshan Zhang, Shanshan Xu, Xuben Yu, Lisu Huang","doi":"10.1093/infdis/jiaf169","DOIUrl":"https://doi.org/10.1093/infdis/jiaf169","url":null,"abstract":"Background Linezolid shows therapeutic potential for pediatric gram-positive bacterial central nervous system infections (CNSIs). However, its efficacy, safety profile, and cerebrospinal fluid (CSF) pharmacokinetics require detailed evaluation. Methods This prospective two-center observational study enrolled children with confirmed or suspected gram-positive CNSIs. Clinical outcomes and adverse events were compared between linezolid-treated patients and a matched vancomycin cohort. Population pharmacokinetic (PopPK) modeling with nonlinear mixed-effects analysis quantified linezolid exposure in plasma and CSF. Results Among 45 matched pediatric CNSIs patients per group, linezolid demonstrated a 91.1% clinical response rate and 68.9% cure rate (vancomycin cure rate: 68.9%). ‌However, non-inferiority to vancomycin was not established‌ for the primary endpoint, possibly influenced by intergroup baseline variability and extended treatment duration. Adverse events occurred more frequently with linezolid, including gastrointestinal (48.9% vs. 24.4%, p = 0.02) and hematologic effects (73.3% vs. 53.3%, p = 0.05). Plasma trough concentrations &gt; 7 µg/mL were correlated with elevated risk of leukopenia and neutropenia (odds ratio [OR] 9.38, 95% confidence interval [CI] 1.21–72.6; and OR 40.2, 95% CI 2.15–748.50). However, no treatment discontinuations occurred due to adverse events. The PopPK model analyzed 135 linezolid concentrations (90 plasma/45 CSF), identifying body weight as the primary covariate influencing distribution. Plasma and CSF trough concentrations showed a strong correlation (r = 0.87, 95% CI 0.75–0.98). Conclusions Linezolid demonstrated favorable clinical efficacy and tolerability in pediatric CNSIs, with CSF concentrations ‌that correlated with plasma levels‌ and ‌exhibited predictable pharmacokinetics‌.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775335","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}

引用次数: 0

Salmonella effector SseL induces PD-L1 up-regulation and T cell inactivation via β-catenin signalling axis

The Journal of Infectious Diseases Pub Date : 2025-03-19 DOI: 10.1093/infdis/jiaf131

Umesh Chopra, Maria Kondooparambil Sabu, Raju S Rajmani, Ayushi Devendrasingh Chaudhary, Shashi Kumar Gupta, Dipshikha Chakravortty

{"title":"Salmonella effector SseL induces PD-L1 up-regulation and T cell inactivation via β-catenin signalling axis","authors":"Umesh Chopra, Maria Kondooparambil Sabu, Raju S Rajmani, Ayushi Devendrasingh Chaudhary, Shashi Kumar Gupta, Dipshikha Chakravortty","doi":"10.1093/infdis/jiaf131","DOIUrl":"https://doi.org/10.1093/infdis/jiaf131","url":null,"abstract":"The upregulation of PD-L1 by various pathogens is a recognized strategy to evade the adaptive immune response. Salmonella infection also upregulates PD-L1 levels; however, the underlying mechanism remains unclear. Our study reveals that this upregulation is mediated by Salmonella pathogenicity island 2 (SPI-2) effectors, as PFA-fixed and STMΔssaV fail to alter PD-L1 levels. We have further investigated the role of the SPI-2 effector SseL (a deubiquitinase) in PD-L1 upregulation, and our study reveals SseL to be crucial for upregulating PD-L1 in vitro as well as in vivo murine models. STMΔsseL exhibits colonization defects in secondary infection sites such as the liver and spleen. Notably, STMΔsseL-infected mice show earlier mortality associated with heightened inflammation. Mechanistically, SseL stabilizes β-catenin, which translocates to the nucleus and leads to PD-L1 transcription, which is abrogated by the β-catenin/TCF inhibitor FH535. Collectively, our study elucidates the mechanism by which Salmonella mediates immune suppression through PD-L1 upregulation.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653431","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}

引用次数: 0

Assessing the impact of influenza epidemics in Hong Kong

The Journal of Infectious Diseases Pub Date : 2025-03-19 DOI: 10.1093/infdis/jiaf140

Jessica Y Wong, Justin K Cheung, Anne M Presanis, Daniela De Angelis, A Danielle Iuliano, Peng Wu, Benjamin J Cowling

{"title":"Assessing the impact of influenza epidemics in Hong Kong","authors":"Jessica Y Wong, Justin K Cheung, Anne M Presanis, Daniela De Angelis, A Danielle Iuliano, Peng Wu, Benjamin J Cowling","doi":"10.1093/infdis/jiaf140","DOIUrl":"https://doi.org/10.1093/infdis/jiaf140","url":null,"abstract":"Background Assessing the impact of influenza epidemics provides useful information to assess both population and healthcare system burden and can inform prevention and control measures for seasonal epidemics, such as vaccination and antivirals. Furthermore, it is an important component of pandemic preparedness. Methods We assessed and compared three influenza impact parameters: influenza-associated excess respiratory mortality, hospitalizations and ICU admissions, under the World Health Organization Pandemic Influenza Severity Assessment framework. We used a generalized additive model to estimate these parameters from 1998 through 2019 in Hong Kong based on historical mortality, hospitalization, ICU admission and influenza surveillance data. Intensity thresholds by influenza type were estimated using quantiles from the distribution of peak values of the parameters from 1998 through 2017 and were compared to the real-time estimates of excess parameters in 2018-2019. Influenza death and hospitalization data were used for validation. Findings There was good agreement between the different impact parameters after comparing the 2018-2019 data to the thresholds. The 2019 influenza A epidemic was characterized as having moderate impact overall and in all age groups, except 0-64 years for whom the excess ICU impact was high; whereas the 2018 influenza B epidemic was characterized as having very high impact overall and in all age groups. Interpretation The impact of influenza epidemics can vary from year to year. The PISA framework facilitates the impact assessment of seasonal influenza epidemics using different data sources and can be implemented in both real-time or at the end of seasons as policy makers and public health officials prepare for the next seasonal epidemic.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661192","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}

引用次数: 0

Recovery of Antibody Immunity After a Resurgence of Respiratory Syncytial Virus Infections

The Journal of Infectious Diseases Pub Date : 2025-03-18 DOI: 10.1093/infdis/jiaf101

Frederic Reicherz, Marina Viñeta Paramo, Jeffrey N Bone, Alexanne Lavoie, Sirui Li, Liam Golding, Agatha Jassem, Allison Watts, Bahaa Abu-Raya, Pascal M Lavoie

引用次数: 0

Estimated Efficacy of TAK-003 Against Asymptomatic Dengue Infection in Children/Adolescents Participating in the DEN-301 Trial in Asia Pacific and Latin America

The Journal of Infectious Diseases Pub Date : 2025-03-18 DOI: 10.1093/infdis/jiaf145

Tarek El Hindi, Maria Theresa Alera, Lulu Bravo, Edson Duarte Moreira, Reynaldo Dietze, Ana Lucia Oliveira, Veerachai Watanaveeradej, Yuan Zhao, Ivo Sonderegger, Vianney Tricou, Nicolas Folschweiller, Shibadas Biswal

{"title":"Estimated Efficacy of TAK-003 Against Asymptomatic Dengue Infection in Children/Adolescents Participating in the DEN-301 Trial in Asia Pacific and Latin America","authors":"Tarek El Hindi, Maria Theresa Alera, Lulu Bravo, Edson Duarte Moreira, Reynaldo Dietze, Ana Lucia Oliveira, Veerachai Watanaveeradej, Yuan Zhao, Ivo Sonderegger, Vianney Tricou, Nicolas Folschweiller, Shibadas Biswal","doi":"10.1093/infdis/jiaf145","DOIUrl":"https://doi.org/10.1093/infdis/jiaf145","url":null,"abstract":"Background TAK-003 has been shown to be well tolerated and effective against symptomatic dengue disease and hospitalization, irrespective of baseline serostatus. Most infections are asymptomatic/subclinical. This study assessed whether TAK-003 could protect against asymptomatic/subclinical infections by evaluating increased neutrlizing antibody titers (NAb) after natural infection. Methods DEN-301(NCT02747927) is a phase 3 trial among 4- to 16-year-old participants who received 2 doses of TAK-003/placebo 3 months apart. These exploratory analyses used NAb measured during the trial. As no well-accepted definition for asymptomatic infection exists, 3 algorithms were evaluated: (1) 4-fold increase in NAb, (2) 4-fold increase in NAb and a minimum titer of 40, and (3) 4-fold increase in NAb and a minimum titer of 4-fold lower-limit-of-quantification. Months 4-9, 9-15, and 15-27 after first vaccination were analyzed. Results NAb from 3765 participants were analyzed. From months 4-9, vaccine efficacy (VE) against asymptomatic infection was 51.1%(30.4 to 65.6), 36.1%(6.7–56.3), and 27.3%(−8.2 to 51.2) for algorithms 1, 2, and 3, respectively. VE in baseline seropositive participants per algorithms 1, 2, and 3 was 54.8%(28.8 to 71.3), 47.9%(16.8 to 67.4), and 44.3%(9.9 to 65.6), respectively, and in baseline seronegative participants was 44.4%(2.1 to 68.4), 4.6%(–85.1 to 50.8), and −29.3%(−172.1 to 38.6), respectively. VE against asymptomatic infection gradually decreased from months 4-9 to 9-15 and months 9-15 to 15-27. Conclusions The variability in VE algorithms indicates challenges in accurately assessing VE against asymptomatic infections. TAK-003 had a modest impact on asymptomatic dengue infections in the first months post-vaccination, mainly in baseline seropositive participants.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653434","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}

引用次数: 0

Circulating cell-free Nucleic Acid Detection for W. bancrofti infections

The Journal of Infectious Diseases Pub Date : 2025-03-17 DOI: 10.1093/infdis/jiaf147

Marisa Salazar, Paul Schaughency, Thomas B Nutman, Sasisekhar Bennuru

引用次数: 0

Identification of Coccidioidomycosis immunoreactive peptides that recall T-cell responses indicating past exposure

The Journal of Infectious Diseases Pub Date : 2025-03-17 DOI: 10.1093/infdis/jiaf118

Mrinalini Kala, Mame Diarra Bousso Ndiaye, Erin Kelley, Maxx Harvey, Farhan Babur, Garrett Grischo, Jessica S Marshall, Jinhee Yi, Anna L Engelbrektson, John A Altin, Bridget M Barker, Paul Keim, Kenneth S Knox, Erik W Settles

{"title":"Identification of Coccidioidomycosis immunoreactive peptides that recall T-cell responses indicating past exposure","authors":"Mrinalini Kala, Mame Diarra Bousso Ndiaye, Erin Kelley, Maxx Harvey, Farhan Babur, Garrett Grischo, Jessica S Marshall, Jinhee Yi, Anna L Engelbrektson, John A Altin, Bridget M Barker, Paul Keim, Kenneth S Knox, Erik W Settles","doi":"10.1093/infdis/jiaf118","DOIUrl":"https://doi.org/10.1093/infdis/jiaf118","url":null,"abstract":"Background Valley fever (VF) is a common cause of community acquired pneumonia in the American Southwest. Diagnosis is challenging due to VF’s similarities to other pulmonary diseases. The VF T-cell response is important to control the disease and measuring this response holds promise as an improved diagnostic. Objective Identification of VF T-cell epitopes and development of disease diagnostics and efficacy monitoring for vaccine trials. Methods We identified VF specific T-cell epitopes by using their ability to bind the Major Histocompatibility Complex Class II (MHC II) molecules and T-cell stimulation. We performed MHC binding prediction on known and unknown Coccidioides antigens and then empirically tested the predictions on unknown antigens with an in vitro multiplex MHC binding analysis. Peripheral blood mononuclear cells from clinical Coccidioides infections, and endemic or nonendemic healthy controls were stimulated with the identified peptides and evaluated for immunologic memory responses. Results A total of 108 Coccidioides peptides were identified by MHC class II binding. The 108 peptides (NAU108) were synthesized, pooled, and jointly evaluated for immunogenicity in VF positive individuals. The peptides re-activated memory CD4+ T-cells in VF confirmed and endemic VF specimens when compared to non-endemic control samples as determined by activation marker and cytokine secretion. Conclusion This study identified peptides that when pooled had immunogenic properties in humans infected with Coccidioides that can be used to distinguish infected individuals from endemic area healthy controls or non-exposed individuals outside the endemic area. This approach holds relevance for the development of diagnostic assays for VF.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635549","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}

引用次数: 0

Neutrophil elastase limits spread of Staphylococcus aureus during skin infection

The Journal of Infectious Diseases Pub Date : 2025-03-17 DOI: 10.1093/infdis/jiaf128

Michał Kanoza, Justyna Folkert, Izabela Ciastoń, Amir Aliramezani, Jan Potempa, Joanna Koziel, Jakub M Kwiecinski

引用次数: 0

Non-invasive monitoring of humoral immune responses in men with acute Chlamydia trachomatis urethral infection using first-catch urine

The Journal of Infectious Diseases Pub Date : 2025-03-17 DOI: 10.1093/infdis/jiaf139

John D Ryan, Caleb M Ardizzone, Stephen J Jordan, James A Williams, Aaron C Ermel, Waleed M Alrebdi, Teresa A Batteiger, Evelyn Toh, David E Nelson

引用次数: 0

A diagnostic approach to separate acute human bocavirus 1 respiratory tract infection from long-lasting virus shedding

The Journal of Infectious Diseases Pub Date : 2025-03-13 DOI: 10.1093/infdis/jiaf130

Rajita Rayamajhi Thapa, Cristiana Nascimento-Carvalho, Tobias Allander, Tuomas Jartti, Maria Söderlund-Venermo

引用次数: 0