Journal of Infectious Diseases最新文献

{"title":"Resistance Analyses in Heavily Treatment-Experienced People With HIV Treated With the Novel HIV Capsid Inhibitor Lenacapavir After 2 Years.","authors":"Nicolas A Margot, Vamshi Jogiraju, Nina Pennetzdorfer, Vidula Naik, Laurie A VanderVeen, John Ling, Renu Singh, Hadas Dvory-Sobol, Onyema Ogbuagu, Sorana Segal-Maurer, Jean-Michel Molina, Martin S Rhee, Christian Callebaut","doi":"10.1093/infdis/jiaf050","DOIUrl":"10.1093/infdis/jiaf050","url":null,"abstract":"<p><strong>Background: </strong>Lenacapavir is a highly potent first-in-class inhibitor of HIV-1 capsid that was approved for the treatment of heavily treatment-experienced people with HIV-1 harboring multidrug-resistant virus, and it is used in combination with an optimized background regimen (OBR). Resistance analyses conducted after 2 years of lenacapavir treatment in the phase 2/3 CAPELLA study are described.</p><p><strong>Methods: </strong>CAPELLA enrollment consisted of viremic cases of heavily treatment-experienced people with HIV-1 and resistance to ≥2 drugs per class in at least 3 of the 4 main drug classes. Postbaseline resistance in participants experiencing virologic failure was evaluated by resistance assays (HIV-1 capsid, protease, reverse transcriptase, and integrase genotypic/phenotypic tests). Adherence to OBR was assessed by plasma drug measurement via liquid chromatography-tandem mass spectrometry.</p><p><strong>Results: </strong>After 2 years, lenacapavir + OBR treatment led to HIV-1 RNA suppression in 82% of participants (missing = excluded). Treatment-emergent capsid resistance occurred in 19% (14/72) of participants, including capsid mutations M66I, Q67H/K/N, K70H/N/R/S, and/or N74D/H/K, which were all associated with functional lenacapavir monotherapy. Seven participants with lenacapavir resistance reattained HIV-1 RNA <50 copies/mL upon OBR resumption or change while maintaining lenacapavir treatment.</p><p><strong>Conclusions: </strong>Emergence of lenacapavir resistance after 2 years in CAPELLA was a consequence of functional lenacapavir monotherapy. In half of participants with lenacapavir resistance, continued treatment with lenacapavir + active OBR led to HIV-1 RNA resuppression.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1239-1245"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054075","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":"Translational Modeling of BTZ-043 to Predict Phase 2A Efficacy and Evaluate Drug-Drug Interactions With Bedaquiline, Pretomanid, and Linezolid in Murine Models.","authors":"Bernard Ngara, Lorenzo Flori, Rob Christiaan van Wijk, Jacqueline P Ernest, Sandeep Tyagi, Heena Soni, Christoph Hölscher, Kerstin Walter, Julia Dreisbach, Michael Hoelscher, Eric L Nuermberger, Radojka M Savic","doi":"10.1093/infdis/jiaf088","DOIUrl":"10.1093/infdis/jiaf088","url":null,"abstract":"<p><strong>Background: </strong>BTZ-043 is a promising novel drug candidate for antituberculosis treatment. This study aimed to apply a previously developed mouse-to-human translational modeling platform for antituberculosis drugs to predict phase 2A outcomes for BTZ-043 in humans and evaluate the impact of observed drug-drug interactions on the contribution of BTZ-043 to combotherapy in a mouse model.</p><p><strong>Methods: </strong>The study utilized data from mouse experiments for BTZ-043 monotherapy and combotherapy with bedaquiline, pretomanid, and linezolid, and clinical information for BTZ-043 monotherapy. The translational models were applied to predict the colony-forming units as a measure of efficacy in humans treated with BTZ-043 monotherapy and evaluate the effect of BTZ-043 on the pharmacokinetics-pharmacodynamics of combotherapy bedaquiline, pretomanid, and linezolid.</p><p><strong>Results: </strong>The mouse-pharmacokinetic and mouse-pharmacodynamic data for BTZ-043 monotherapy were best described by 2-compartmental and direct Emax models, respectively. The model-based prediction of efficacy in humans was comparable to the observed phase 2A efficacy. Single-compartmental models, developed separately, best described the mouse-pharmacokinetic data for bedaquiline, pretomanid, and linezolid in combotherapy. Coadministration with BTZ-043 was associated with at least a 2-fold reduction in bedaquiline, pretomanid, and linezolid exposures in mice, and model-based simulations suggested that the observed decreases in exposure to these drugs would have resulted in even lower efficacy than what was observed when bedaquiline, pretomanid, and linezolid are coadministered with BTZ-043.</p><p><strong>Conclusions: </strong>The translational modeling platform adequately predicted the efficacy of BTZ-043 monotherapy. In the absence of drug-drug interactions, coadministration of BTZ-043 with bedaquiline, pretomanid, and linezolid in combotherapy is predicted to improve treatment efficacy. Clinical Trials Registration. NCT0404400.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e901-e911"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434302","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":"Tuberculous Meningitis Across the Lifespan.","authors":"Rentia Lourens, Gabriela Singh, Tracy Arendse, Guy Thwaites, Ursula Rohlwink","doi":"10.1093/infdis/jiaf181","DOIUrl":"10.1093/infdis/jiaf181","url":null,"abstract":"<p><p>Tuberculous meningitis remains the most lethal form of tuberculosis. Despite significant physiological differences adults and children with tuberculous meningitis receive similar treatment and are often grouped together in research. Consequently, differences in tuberculous meningitis characteristics across the lifespan are poorly understood but may be relevant to developing more effective and age-appropriate interventions. In this review we discuss potential age-specific considerations in pathogenesis and pathophysiology, and review literature over the last 5 years to describe clinical characteristics, management, and outcomes across age groups. Children aged <5 years are vulnerable to tuberculosis disease and dissemination due to an immature immune system and the developing brain is highly susceptible to injury associated with neuroinflammation, leading to a greater likelihood of disability that has lifelong impact. Amongst adults, those with human immunodeficiency virus and older people are at greatest risk of death, but more research into the frequency of neurocognitive disability is needed.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1101-1111"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804556","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":"Ten-Year Surveillance of Respiratory Syncytial Virus Hospitalizations in Adults: Incidence Rates and Case Definition Implications.","authors":"Arantxa Urchueguía-Fornes, Cintia Muñoz-Quiles, Ainara Mira-Iglesias, Mónica López-Lacort, Beatriz Mengual-Chuliá, F Xavier López-Labrador, Javier Díez-Domingo, Alejandro Orrico-Sánchez","doi":"10.1093/infdis/jiaf056","DOIUrl":"10.1093/infdis/jiaf056","url":null,"abstract":"<p><strong>Background: </strong>The impact of respiratory syncytial virus (RSV) in older adults is underrecognized, and the limited existing studies on the incidence of hospitalizations show great variability. This study aims to estimate the seasonal incidence rates (IRs) of RSV hospitalizations among adults aged ≥60 years and evaluate how different case definitions influence these estimates.</p><p><strong>Methods: </strong>A prospective, multicenter observational study with active monitoring was conducted over 10 seasons (2010-2011 to 2019-2020) in 4-10 hospitals (depending on the season) and covered 21%-46% of the region's total population (about 5 million people). RSV hospitalization IRs per 100 000 person-years and 95% confidence intervals were calculated with the exact Poisson method and were stratified by age group (≥60, ≥70, or ≥80 years), RSV season, sex, and the entire study period. Two case definitions were compared: influenzalike illness (ILI) and the combined use of ILI and extended severe acute respiratory infection (ILI/SARI).</p><p><strong>Results: </strong>A total of 40 600 hospitalizations of individuals aged ≥60 years were included. The RSV hospitalization IRs ranged from 21 to 402 per 100 000 person-years, varying by season, age group, and case definition. The highest IRs were observed in those aged ≥80 years. The ILI case definition underestimated RSV hospitalizations by 13%-40% when compared with the ILI/SARI case definition.</p><p><strong>Conclusions: </strong>On average, approximately 1 in every 1000 adults aged ≥60 years is hospitalized due to RSV. The risk of a severe RSV infection increases with age and varies significantly between seasons. These are key results for the estimation of the potential impact of the new available RSV vaccines.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e830-e839"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191357","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":"Mycobacterium tuberculosis Antigen Rv1471 Induces Innate Immune Memory and Adaptive Immunity Against Infection.","authors":"Xuejiao Huang, Juan Wu, Jinchuan Xu, Huiling Wang, Zhenyan Chen, Xiao-Yong Fan, Zhidong Hu","doi":"10.1093/infdis/jiae572","DOIUrl":"10.1093/infdis/jiae572","url":null,"abstract":"<p><p>Mycobacterium tuberculosis (Mtb) contains approximately 4000 individual proteins. However, only about 100 have been evaluated as antigens in tuberculosis (TB) subunit vaccine development. In addition, no trained immunity-targeting subunit TB vaccine has been reported yet. This study tested Rv1471, a thioredoxin secreted by Mtb, as a candidate TB vaccine antigen due to its capacity to stimulate functional maturation of macrophages. Transcription analysis of Rv1471-trained macrophages indicated that innate immune memory was activated through pathways of Akt-mTOR-HIF-1α and aerobic glycolysis. Rv1471 also enhanced innate immune memory responses and protection against intracellular infections of different mycobacteria. In a murine model of TB, immunization with Rv1471 produced robust antigen-specific multifunctional T-cell immune responses and had substantial protective efficacy against Mtb challenge. Analysis of recall immunity showed that the Rv1471 triggered robust T-cell immunity after Mtb infection. These findings support the development of an innate immune memory-targeting subunit TB vaccine to increase vaccine efficacy.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1127-1140"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631753","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":"Genotype III-Based Japanese Encephalitis Vaccines Exhibit Diminished Neutralizing Response to Reemerging Genotype V.","authors":"Ah-Ra Lee, Woo-Jin Kim, Haeyoun Choi, Sang-Hyun Kim, Su-Yeon Hong, Sang-Mu Shim, Hee Il Lee, Jae Min Song, Seong-Jun Kim, Tomohiro Ishikawa, Ji-Man Kang, Hyeon-Seok Eom, Sang-Uk Seo","doi":"10.1093/infdis/jiae589","DOIUrl":"10.1093/infdis/jiae589","url":null,"abstract":"<p><strong>Background: </strong>Japanese encephalitis (JE) has been predominantly controlled through vaccination. However, the isolation of JE virus (JEV) genotype V (GV) in China in 2009, and the subsequent alarming increase in JE cases in the Republic of Korea since 2010, present a new challenge.</p><p><strong>Methods: </strong>Serum samples from individuals vaccinated with genotype III (GIII)-based JE vaccines were analyzed for neutralizing seroresponse to GV isolates.</p><p><strong>Results: </strong>Serum from immunocompromised pediatric patients vaccinated with an inactivated JE vaccine showed higher 50% plaque reduction neutralization test geometric mean titer (GMT) against GIII Nakayama (11 358; 95% confidence interval [CI], 1790-29 658), but lower GMTs against GV isolates: GV Muar (499; 95% CI, 0-2437), GV 43279 (308; 95% CI, 159-582), and GV 43413 (231; 95% CI, 108-738). Similarly, 32 healthy volunteers receiving a live attenuated JE vaccine achieved 100% seroprotection against GIII Nakayama with GMT of 338 (95% CI, 304-651) at 1 month postvaccination. However, GMTs against GV isolates were 123 (95% CI, 102-446) for GV Muar, 81 (95% CI, 63-168) for GV 43279, and 107 (95% CI, 100-322) for GV 43413, not achieving 100% seroprotection against these isolates. At 6 months postvaccination, GMT against Nakayama increased to 696 (95% CI, 409-2353), while remaining similar for GV isolates.</p><p><strong>Conclusions: </strong>Our study underscores that current GIII-based vaccines do not provide comparable protection against GV JEVs, impacting individuals in both current and potential endemic regions, as well as travelers to these regions.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1281-1289"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689556","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":"Correction to: Relative Effectiveness and Waning of a Third Dose of mRNA COVID-19 Vaccine in Medicare Beneficiaries Aged 65 Years and Older during the BA.1/BA.2 Omicron Period.","authors":"","doi":"10.1093/infdis/jiaf137","DOIUrl":"10.1093/infdis/jiaf137","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e997-e1009"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062978","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":"Clinical Characteristics and In-hospital Outcomes Associated With Respiratory Syncytial Virus vs Other Viral Acute Lower Respiratory Infections in Hospitalized Children Younger Than 2 Years.","authors":"Acacia Ozturk, Mei Chan, Jahid Rahman Khan, Nan Hu, Brendan McMullan, Philip N Britton, Adam Bartlett, Rama Kandasamy, Gemma L Saravanos, Bernadette Prentice, Ting Shi, Adam Jaffe, Louisa Owens, Nusrat Homaira","doi":"10.1093/infdis/jiae543","DOIUrl":"10.1093/infdis/jiae543","url":null,"abstract":"<p><strong>Background: </strong>Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection (ALRI)-associated hospitalizations in children. It is unclear if hospitalized RSV-positive ALRI is clinically different from other viral ALRIs. We aimed to compare the disease impact of hospitalized RSV with other viral ALRI in children aged <2 years.</p><p><strong>Methods: </strong>We conducted a retrospective study using the electronic medical records of children aged <2 years who were hospitalized with ALRIs at Sydney Children's Hospital Network from 2020 to 2022. We compared demographics and clinical features between RSV-positive cases and RSV-negative ones (ie, positive for other viruses). Poisson quasi-likelihood regression was used to estimate adjusted prevalence ratios for 3 in-hospital outcomes: length of stay, need for respiratory support, and intensive care.</p><p><strong>Results: </strong>We examined 330 children aged <2 years hospitalized with RSV-positive ALRIs and 330 with RSV-negative ALRIs (positive for other viruses). RSV-positive cases were older (12 vs 8 months, P < .001) and more often presented with cough (99% vs 92%), fever (80% vs 58%), crackles (89% vs 76%), hypoxia (50% vs 36%), and lethargy (36% vs 20%). They were also more likely to undergo chest radiographs (74% vs 49%) and receive antibiotics (65% vs 35%). Adjusted analysis showed that children who were RSV positive had a higher likelihood of an extended length of stay (>2 days; adjusted prevalence ratio, 1.95; 95% CI, 1.14-3.36). However, there were no differences in the need for intensive care or respiratory support.</p><p><strong>Conclusions: </strong>Children with RSV-positive ALRI exhibited more severe symptoms, received more antibiotics, and had longer hospital stays as compared with those with other viral ALRIs, underscoring the need for effective prevention and treatment strategies for RSV.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1309-1317"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559269","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":"Fecal and Sputum Microbiota and Treatment Response in Patients With Mycobacterium abscessus Pulmonary Disease.","authors":"Joong-Yub Kim, Sujin An, So Yeon Kim, Eunhye Bae, Yong-Joon Cho, Nakwon Kwak, Donghyun Kim, Jae-Joon Yim","doi":"10.1093/infdis/jiae542","DOIUrl":"10.1093/infdis/jiae542","url":null,"abstract":"<p><strong>Background: </strong>The microbiota may provide biomarkers for clinical outcomes in chronic respiratory conditions, though its role in Mycobacterium abscessus pulmonary disease (PD) remains largely unknown. We aimed to identify microbial signatures in fecal and sputum microbiotas associated with treatment response in M abscessus PD.</p><p><strong>Methods: </strong>We prospectively enrolled patients undergoing antibiotic therapy, collecting fecal and sputum samples at baseline, 2 weeks, and 6 months. Using 16S rRNA amplicon sequencing, we analyzed microbiota diversity and composition in early treatment responders and nonresponders, classified by sputum culture results at 2 weeks.</p><p><strong>Results: </strong>Among 32 participants, 27 patients (median age, 66 years; 85.2% women; 48.1% with subspecies abscessus) were included for analysis. Fifteen patients (55.6%) achieved negative conversion at 2 weeks, sustained in 93.3% at 6 months. Responders showed signifcantly decreased fecal microbiota diversity at 2 weeks, unlike nonresponders (P = .029). Increased abundance of Eubacterium hallii in baseline fecal microbiota was indicative of unresponsiveness, whereas increased Enterococcus in feces at 2 weeks was linked with favorable response. In sputum, high baseline levels of Burkholderia-Caballeronia-Paraburkholderia and Porphyromonas, along with decreased Rothia at 2 weeks, were associated with good treatment response.</p><p><strong>Conclusions: </strong>In M abscessus PD, changes in microbial diversity and compositional signatures reflect treatment response.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1117-1126"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584731","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":"Neurovirulent Pathogens Across the Human Lifespan: A Balancing Act.","authors":"Lisa N Akhtar, Anita McElroy","doi":"10.1093/infdis/jiaf015","DOIUrl":"10.1093/infdis/jiaf015","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1098-1100"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383949","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}