Edwin J Asturias,Robert Schechter,H Keipp Talbot,Julie Boom,Oliver T Brooks,Lin H Chen,Helen Y Chu,Sybil Cineas,Dana J Hawkinson,Mini Kamboj,Jamie Loehr,Karyn L Lyons,Yvonne A Maldonado,Charlotte A Moser,Mysheika W Roberts,Albert C Shaw,Zanthia Wiley,Jane R Zucker,Noel T Brewer
Since June 2025, the restructuring of the U.S. Advisory Committee on Immunization Practices (ACIP)-including the abrupt replacement of all voting members and leadership-marked a significant departure from its longstanding norms of continuity and governance. Subsequent deviations from evidence-based policymaking raise concerns about the independence, transparency, and scientific rigor of vaccine policies under the new Department of Health and Human Services (DHHS) administration. The politicization of deliberations, selective use of questionable evidence, and disregard for established methodological standards threaten to undermine vaccine development, access, and public trust. Potential consequences include diminished credibility of federal vaccine recommendations, reduced advisory capacity for advancing key and new vaccines (e.g., cytomegalovirus, Lyme disease), and disruption of critical and leading research infrastructure. Safeguarding ACIP's integrity through legislative and structural reforms is essential to restoring its credibility, preserving U.S. leadership in global vaccine science, and maintaining population protection through robust, evidence-based immunization policy.
{"title":"The Erosion of a Pillar of Public Health: ACIP's Role and the Future of U.S. Vaccine Policy Post-June 2025.","authors":"Edwin J Asturias,Robert Schechter,H Keipp Talbot,Julie Boom,Oliver T Brooks,Lin H Chen,Helen Y Chu,Sybil Cineas,Dana J Hawkinson,Mini Kamboj,Jamie Loehr,Karyn L Lyons,Yvonne A Maldonado,Charlotte A Moser,Mysheika W Roberts,Albert C Shaw,Zanthia Wiley,Jane R Zucker,Noel T Brewer","doi":"10.1093/cid/ciag042","DOIUrl":"https://doi.org/10.1093/cid/ciag042","url":null,"abstract":"Since June 2025, the restructuring of the U.S. Advisory Committee on Immunization Practices (ACIP)-including the abrupt replacement of all voting members and leadership-marked a significant departure from its longstanding norms of continuity and governance. Subsequent deviations from evidence-based policymaking raise concerns about the independence, transparency, and scientific rigor of vaccine policies under the new Department of Health and Human Services (DHHS) administration. The politicization of deliberations, selective use of questionable evidence, and disregard for established methodological standards threaten to undermine vaccine development, access, and public trust. Potential consequences include diminished credibility of federal vaccine recommendations, reduced advisory capacity for advancing key and new vaccines (e.g., cytomegalovirus, Lyme disease), and disruption of critical and leading research infrastructure. Safeguarding ACIP's integrity through legislative and structural reforms is essential to restoring its credibility, preserving U.S. leadership in global vaccine science, and maintaining population protection through robust, evidence-based immunization policy.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"71 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146069987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Preventing Long COVID With Metformin.","authors":"Carolyn T Bramante, David R Boulware","doi":"10.1093/cid/ciaf700","DOIUrl":"https://doi.org/10.1093/cid/ciaf700","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Portia Mira, Ruben Dyrhovden, Marit Gjerde Tellevik, Tomas Mikal Eagan, Abigail Krause, Oscar Lopez-Martinez, Matthew Wolf, Kaiser G Lim, Ryan M Kern, Eva Carmona Porquera, Oyvind Kommedal, Robin Patel
Objective New insights into community acquired pleural infection microbiology may enable development of more rapid and accessible diagnostics that can streamline treatment. This study systematically compared molecular approaches for pathogen detection in pleural fluid from patients with such infections. Considering the need for rapid results with minimum hands-on time and test complexity, off-label use of the cassette-based, random-access BIOFIRE® Joint Infection (JI) Panel (bioMérieux) with and without supplementary in-house PCRs was evaluated. Methods Pleural fluids from 162 subjects from the Mayo Clinic (Rochester, Minnesota) and Haukeland University Hospital (Bergen, Norway), where molecular tests are routinely used for analyzing pleural fluid, were studied. The performance of the BIOFIRE JI Panel was compared to 16S ribosomal RNA gene PCR followed by Sanger and next-generation sequencing (16S rRNA gene PCR/sequencing), an in-house PCR panel specifically designed for pleural space infections, and culture. Main Results The BIOFIRE JI Panel supplemented with three in-house PCRs targeting Fusobacterium nucleatum group, Streptococcus intermedius/constellatus and Aggregatibacter aphrophilus detected 96.8% of pleural infections, providing complete microbial profiles in 70.8%. In comparison, the detection rate of 16S rRNA gene PCR/sequencing was 92.2%, providing complete microbial profiles in 87.0%. Culture detected bacteria in only 31.9% of pleural fluids, providing complete microbial profiles in 15.3%. Conclusions These results underscore the importance of molecular approaches in diagnosing pleural space infections and demonstrate the feasibility of panel-based PCR-based diagnostics for these sometimes-complex infections. The BIOFIRE JI Panel, designed for testing synovial fluid, could be modified to provide a useful diagnostic for testing pleural fluid.
目的对社区获得性胸膜感染的微生物学研究有新的认识，有助于开发更快速、更便捷的诊断方法，简化治疗。本研究系统地比较了分子方法在此类感染患者胸膜液中的病原体检测。考虑到需要以最少的操作时间和测试复杂性获得快速结果，我们评估了在标签外使用基于卡带的随机访问BIOFIRE®联合感染（JI）面板（biomrieux），并评估了是否使用补充的内部pcr。方法对来自梅奥诊所（明尼苏达州罗彻斯特）和豪克兰大学医院（挪威卑尔根）的162名受试者的胸膜液进行研究，分子测试是常规用于分析胸膜液的方法。将BIOFIRE JI面板的性能与16S核糖体RNA基因PCR进行比较，然后进行Sanger和下一代测序（16S rRNA基因PCR/测序），这是一种专门为胸膜腔感染设计的内部PCR面板，并进行培养。BIOFIRE JI Panel补充了3种针对核梭杆菌群、中间/星座链球菌和嗜aphrophilus聚集杆菌的内部pcr，检测出96.8%的胸膜感染，70.8%的胸膜感染提供了完整的微生物谱。相比之下，16S rRNA基因PCR/测序的检出率为92.2%，提供完整微生物图谱的比例为87.0%。培养仅在31.9%的胸膜液中检测到细菌，在15.3%的胸膜液中提供完整的微生物谱。结论这些结果强调了分子方法在诊断胸膜腔感染中的重要性，并证明了基于pcr的小组诊断这些有时复杂的感染的可行性。BIOFIRE JI面板，设计用于测试滑液，可以修改为提供一个有用的诊断测试胸膜液。
{"title":"Microbial Detection in Community Acquired Pleural Space Infection Using the BioFire Joint Infection Panel and Individual PCR Assays","authors":"Portia Mira, Ruben Dyrhovden, Marit Gjerde Tellevik, Tomas Mikal Eagan, Abigail Krause, Oscar Lopez-Martinez, Matthew Wolf, Kaiser G Lim, Ryan M Kern, Eva Carmona Porquera, Oyvind Kommedal, Robin Patel","doi":"10.1093/cid/ciag050","DOIUrl":"https://doi.org/10.1093/cid/ciag050","url":null,"abstract":"Objective New insights into community acquired pleural infection microbiology may enable development of more rapid and accessible diagnostics that can streamline treatment. This study systematically compared molecular approaches for pathogen detection in pleural fluid from patients with such infections. Considering the need for rapid results with minimum hands-on time and test complexity, off-label use of the cassette-based, random-access BIOFIRE® Joint Infection (JI) Panel (bioMérieux) with and without supplementary in-house PCRs was evaluated. Methods Pleural fluids from 162 subjects from the Mayo Clinic (Rochester, Minnesota) and Haukeland University Hospital (Bergen, Norway), where molecular tests are routinely used for analyzing pleural fluid, were studied. The performance of the BIOFIRE JI Panel was compared to 16S ribosomal RNA gene PCR followed by Sanger and next-generation sequencing (16S rRNA gene PCR/sequencing), an in-house PCR panel specifically designed for pleural space infections, and culture. Main Results The BIOFIRE JI Panel supplemented with three in-house PCRs targeting Fusobacterium nucleatum group, Streptococcus intermedius/constellatus and Aggregatibacter aphrophilus detected 96.8% of pleural infections, providing complete microbial profiles in 70.8%. In comparison, the detection rate of 16S rRNA gene PCR/sequencing was 92.2%, providing complete microbial profiles in 87.0%. Culture detected bacteria in only 31.9% of pleural fluids, providing complete microbial profiles in 15.3%. Conclusions These results underscore the importance of molecular approaches in diagnosing pleural space infections and demonstrate the feasibility of panel-based PCR-based diagnostics for these sometimes-complex infections. The BIOFIRE JI Panel, designed for testing synovial fluid, could be modified to provide a useful diagnostic for testing pleural fluid.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"29 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Changing Course.","authors":"Koray K Demir, Matthew P Cheng, Joanna Nelson","doi":"10.1093/cid/ciaf720","DOIUrl":"https://doi.org/10.1093/cid/ciaf720","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":7.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146060502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Methodology Misrepresented: Correcting the Record on the ATS Community-acquired Pneumonia Guideline Process.","authors":"Kevin C Wilson,Eyal Oren","doi":"10.1093/cid/ciag040","DOIUrl":"https://doi.org/10.1093/cid/ciag040","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"30 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Coccidioidomycosis continues to shape life across California's southern San Joaquin Valley, where thousands fall ill each year. Yet for many, diagnosis marks not the end of uncertainty but the start of another challenge, staying in care. In communities already strained by clinician shortages, distance, and limited insurance coverage, the year-long follow-up recommended after Valley Fever is rarely feasible. Lessons from other rural Latino populations show that continuity can be rebuilt through community-rooted approaches: trusted health workers, mobile clinics, peer education, and simple digital tools that meet patients where they are. Bringing these models into existing county and safety-net systems will require dedicated funding and shared commitment across institutions. Strengthening continuity of care, not only diagnostic capacity, offers the most realistic path to better outcomes for those living in the heart of California's Valley Fever region.
{"title":"Valley Fever in Central California: Diagnosis is Not the Finish Line, the Real Gap is Longitudinal Care.","authors":"Geetha Sivasubramanian","doi":"10.1093/cid/ciaf728","DOIUrl":"https://doi.org/10.1093/cid/ciaf728","url":null,"abstract":"Coccidioidomycosis continues to shape life across California's southern San Joaquin Valley, where thousands fall ill each year. Yet for many, diagnosis marks not the end of uncertainty but the start of another challenge, staying in care. In communities already strained by clinician shortages, distance, and limited insurance coverage, the year-long follow-up recommended after Valley Fever is rarely feasible. Lessons from other rural Latino populations show that continuity can be rebuilt through community-rooted approaches: trusted health workers, mobile clinics, peer education, and simple digital tools that meet patients where they are. Bringing these models into existing county and safety-net systems will require dedicated funding and shared commitment across institutions. Strengthening continuity of care, not only diagnostic capacity, offers the most realistic path to better outcomes for those living in the heart of California's Valley Fever region.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"95 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marian Loveday,Emma Clarence,Sindisiwe Hlangu,Nalini Singh,Sunitha Chotoo,James C M Brust,Catriona Waitt,Richard Court,Jennifer Furin
BACKGROUNDThere is limited experience of the all-oral 6-month regimens containing bedaquiline, delamanid, linezolid and levofloxacin/clofazimine (BDLLfx/BDLCfz) in pregnant women with MDR/RR-TB. We report maternal treatment, pregnancy, and infant outcomes to 12 months of age in a cohort of pregnant women treated with these regimens.METHODSWe included pregnant women treated for MDR/RR-TB from September 2023 to January 2025 in KwaZulu-Natal, South Africa in a prospective observational study. Outcomes were collected through ongoing record reviews. Infant clinical assessments were conducted at six weeks, six and 12 months.RESULTSOf 25 pregnant women with MDR/RR-TB, 21 received BDLLfx/BDLCfz; 12 (57%) were living with HIV. Although 10/21 (48%) of the women developed anaemia, 18 (86%) had favourable treatment outcomes. All 21 infants were born alive; median gestational age 39 weeks (interquartile range [IQR]:38-40) and median birth weight 3160g (IQR: 2818-3308). Three women had unfavourable pregnancy outcomes, with infants born prematurely, two with low birth weight, one of whom developed respiratory distress syndrome. Of the 18 infants evaluated at 12 months, ten (56%) had possible or confirmed unfavourable outcomes. Two infants had confirmed congenital anomalies and three possible congenital anomalies, but only one had first-trimester drug exposure. One infant died, another was diagnosed with MDR/RR-TB and started on treatment, and three infants had signs/symptoms of TB necessitating referral for care.CONCLUSIONSThese limited data suggests that in pregnant women, the BDLLfx/BDLCfz regimens have improved treatment and pregnancy outcomes compared to prior regimens. However, there is a high prevalence of unfavourable infant outcomes.
{"title":"Pregnant women with MDR/RR-TB and the all-oral 6-month regimen: experiences from a patient series in South Africa.","authors":"Marian Loveday,Emma Clarence,Sindisiwe Hlangu,Nalini Singh,Sunitha Chotoo,James C M Brust,Catriona Waitt,Richard Court,Jennifer Furin","doi":"10.1093/cid/ciag032","DOIUrl":"https://doi.org/10.1093/cid/ciag032","url":null,"abstract":"BACKGROUNDThere is limited experience of the all-oral 6-month regimens containing bedaquiline, delamanid, linezolid and levofloxacin/clofazimine (BDLLfx/BDLCfz) in pregnant women with MDR/RR-TB. We report maternal treatment, pregnancy, and infant outcomes to 12 months of age in a cohort of pregnant women treated with these regimens.METHODSWe included pregnant women treated for MDR/RR-TB from September 2023 to January 2025 in KwaZulu-Natal, South Africa in a prospective observational study. Outcomes were collected through ongoing record reviews. Infant clinical assessments were conducted at six weeks, six and 12 months.RESULTSOf 25 pregnant women with MDR/RR-TB, 21 received BDLLfx/BDLCfz; 12 (57%) were living with HIV. Although 10/21 (48%) of the women developed anaemia, 18 (86%) had favourable treatment outcomes. All 21 infants were born alive; median gestational age 39 weeks (interquartile range [IQR]:38-40) and median birth weight 3160g (IQR: 2818-3308). Three women had unfavourable pregnancy outcomes, with infants born prematurely, two with low birth weight, one of whom developed respiratory distress syndrome. Of the 18 infants evaluated at 12 months, ten (56%) had possible or confirmed unfavourable outcomes. Two infants had confirmed congenital anomalies and three possible congenital anomalies, but only one had first-trimester drug exposure. One infant died, another was diagnosed with MDR/RR-TB and started on treatment, and three infants had signs/symptoms of TB necessitating referral for care.CONCLUSIONSThese limited data suggests that in pregnant women, the BDLLfx/BDLCfz regimens have improved treatment and pregnancy outcomes compared to prior regimens. However, there is a high prevalence of unfavourable infant outcomes.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"4 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julia M Baker,Jennifer L Cannon,Claire P Mattison,Hannah Browne,Kenny Nguyen,Rachel M Burke,Eddie Bartlett,Shannon C Conrey,Allison R Burrell,Mary Allen Staat,Ardythe L Morrow,Umesh D Parashar,Jan Vinjé,Sara A Mirza,Daniel C Payne
INTRODUCTIONNorovirus is the leading cause of medically attended acute gastroenteritis in the United States. Efforts to reduce the disease burden are constrained by uncertainty around fundamental aspects of norovirus epidemiology. This study describes characteristics of norovirus infections and explores potential risk factors for symptomatic infections in early life.METHODSThe Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal birth cohort study followed 245 children from birth to 2 years of age with weekly stool sample collection and symptom surveys. Stool samples were tested by reverse transcriptase-realtime polymerase chain reaction to detect norovirus genogroup (G)I and GII; positive samples were genotyped. Infections accompanied by diarrhea and/or vomiting were considered symptomatic. Children were categorized as adherent if they participated for ≥18 months and submitted ≥70% of samples.RESULTSA total of 72 GI and 330 GII norovirus infections (among 156 children) were identified. One-fifth (20.8%) of adherent children experienced ≥1 norovirus infection by 6 months of age, increasing to 84.2% children by 2 years of age. About one-third of infections were symptomatic, including half of infections with cycle threshold values <25. Infection with norovirus genotype GII.4 Sydney was the strongest predictor of symptomatic infection in adjusted analyses, as was older age and higher viral load. Childcare attendance, breastfeeding, mother's secretor status, and prior infections were not predictive of symptom status.CONCLUSIONThis study highlights fundamental characteristics of norovirus epidemiology in early life with implications for understanding the full natural history of the disease, disease transmission and prevention approaches.
{"title":"Symptomatic and asymptomatic norovirus infections in early life; The PREVAIL Cohort, 2017-2020.","authors":"Julia M Baker,Jennifer L Cannon,Claire P Mattison,Hannah Browne,Kenny Nguyen,Rachel M Burke,Eddie Bartlett,Shannon C Conrey,Allison R Burrell,Mary Allen Staat,Ardythe L Morrow,Umesh D Parashar,Jan Vinjé,Sara A Mirza,Daniel C Payne","doi":"10.1093/cid/ciag033","DOIUrl":"https://doi.org/10.1093/cid/ciag033","url":null,"abstract":"INTRODUCTIONNorovirus is the leading cause of medically attended acute gastroenteritis in the United States. Efforts to reduce the disease burden are constrained by uncertainty around fundamental aspects of norovirus epidemiology. This study describes characteristics of norovirus infections and explores potential risk factors for symptomatic infections in early life.METHODSThe Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal birth cohort study followed 245 children from birth to 2 years of age with weekly stool sample collection and symptom surveys. Stool samples were tested by reverse transcriptase-realtime polymerase chain reaction to detect norovirus genogroup (G)I and GII; positive samples were genotyped. Infections accompanied by diarrhea and/or vomiting were considered symptomatic. Children were categorized as adherent if they participated for ≥18 months and submitted ≥70% of samples.RESULTSA total of 72 GI and 330 GII norovirus infections (among 156 children) were identified. One-fifth (20.8%) of adherent children experienced ≥1 norovirus infection by 6 months of age, increasing to 84.2% children by 2 years of age. About one-third of infections were symptomatic, including half of infections with cycle threshold values <25. Infection with norovirus genotype GII.4 Sydney was the strongest predictor of symptomatic infection in adjusted analyses, as was older age and higher viral load. Childcare attendance, breastfeeding, mother's secretor status, and prior infections were not predictive of symptom status.CONCLUSIONThis study highlights fundamental characteristics of norovirus epidemiology in early life with implications for understanding the full natural history of the disease, disease transmission and prevention approaches.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"30 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUNDAccurate non-sputum tests are essential for improving tuberculosis (TB) detection. We report the first evaluation of the Xpert TB/LTBI assay (research-use-only, Cepheid, USA), which detects nine Mycobacterium tuberculosis antigen-stimulated mRNA targets from blood.METHODSWe enrolled individuals ≥12 years with presumptive TB from clinics in Uganda and Vietnam. All participants underwent sputum- (liquid culture; Xpert MTB/RIF Ultra) and blood-based (Xpert TB/LTBI; QuantiFERON-TB Gold Plus [QFT-Plus]) testing. Participants were classified as having active TB (positive sputum results), latent TB infection (LTBI; positive QFT-Plus with negative sputum results), or no TB infection. Diagnostic accuracy for active TB (primary analysis) and of a two-step algorithm that first predicted TB infection (active TB or LTBI) and then distinguished active TB from LTBI was assessed using logistic regression and receiver operating characteristic analysis.RESULTSAmong 214 participants included, 56.5% were male, 9.3% were living with HIV, 29.0% had active TB, and 31.8% had LTBI. Xpert TB/LTBI area under the curve (AUC) was 0.92 (95% CI 0.88-0.96) for identifying active TB, and sensitivity was 93.5% (95% CI 84.6-97.5) and specificity 76.3% (95% CI 69.0-82.4) at a cut-point that achieved ≥90% sensitivity. In the two-step algorithm, Xpert TB/LTBI had high accuracy for identifying TB infection in the first step, but accuracy was lower for distinguishing active TB from LTBI in the second step.CONCLUSIONSXpert TB/LTBI exceeded World Health Organization (WHO)-recommended minimum accuracy targets for a TB screening test. However, further refinement is needed to improve its ability to distinguish active TB from LTBI.
背景：准确的非痰液检测对于提高结核病的检出率至关重要。我们报告了对Xpert TB/LTBI检测（仅供研究使用，造父变星，美国）的首次评估，该检测从血液中检测出9个结核分枝杆菌抗原刺激的mRNA靶点。方法：我们从乌干达和越南的诊所招募了年龄≥12岁的推定结核病患者。所有参与者都进行了痰液（液体培养；Xpert MTB/RIF Ultra）和血液（Xpert TB/LTBI; QuantiFERON-TB Gold Plus [QFT-Plus]）检测。参与者被分类为活动性结核（痰液结果阳性）、潜伏性结核感染（LTBI； QFT-Plus阳性，痰液结果阴性）或无结核感染。对活动性结核病的诊断准确性（初步分析）以及首先预测结核病感染（活动性结核病或LTBI），然后将活动性结核病与LTBI区分开来的两步算法，使用逻辑回归和患者工作特征分析进行了评估。结果在214名参与者中，56.5%为男性，9.3%为艾滋病毒携带者，29.0%为活动性结核病，31.8%为LTBI。Xpert TB/LTBI识别活动性TB的曲线下面积（AUC）为0.92 (95% CI 0.88-0.96)，在达到≥90%灵敏度的切点上，灵敏度为93.5% (95% CI 84.6-97.5)，特异性为76.3% （95% CI 69.0-82.4）。在两步算法中，Xpert TB/LTBI在第一步识别结核感染的准确率较高，但在第二步区分活动性结核和LTBI的准确率较低。结论专家结核病/LTBI超过了世界卫生组织（WHO）推荐的结核病筛查试验的最低准确性目标。然而，需要进一步改进以提高其区分活动性结核和LTBI的能力。
{"title":"Evaluating the Cepheid Xpert TB/LTBI research-use-only assay for detection of active and latent Mycobacterium tuberculosis infection.","authors":"Brittney Sweetser,Hoang Nguyen,Hai Dang,David Katumba,Tessa Mochizuki,Qiao Wang,Mangeni Wilson,Ha Phan,Patrick Phillips,Seda Yerlikaya,Payam Nahid,Claudia M Denkinger,Adithya Cattamanchi,William Worodria, ","doi":"10.1093/cid/ciag005","DOIUrl":"https://doi.org/10.1093/cid/ciag005","url":null,"abstract":"BACKGROUNDAccurate non-sputum tests are essential for improving tuberculosis (TB) detection. We report the first evaluation of the Xpert TB/LTBI assay (research-use-only, Cepheid, USA), which detects nine Mycobacterium tuberculosis antigen-stimulated mRNA targets from blood.METHODSWe enrolled individuals ≥12 years with presumptive TB from clinics in Uganda and Vietnam. All participants underwent sputum- (liquid culture; Xpert MTB/RIF Ultra) and blood-based (Xpert TB/LTBI; QuantiFERON-TB Gold Plus [QFT-Plus]) testing. Participants were classified as having active TB (positive sputum results), latent TB infection (LTBI; positive QFT-Plus with negative sputum results), or no TB infection. Diagnostic accuracy for active TB (primary analysis) and of a two-step algorithm that first predicted TB infection (active TB or LTBI) and then distinguished active TB from LTBI was assessed using logistic regression and receiver operating characteristic analysis.RESULTSAmong 214 participants included, 56.5% were male, 9.3% were living with HIV, 29.0% had active TB, and 31.8% had LTBI. Xpert TB/LTBI area under the curve (AUC) was 0.92 (95% CI 0.88-0.96) for identifying active TB, and sensitivity was 93.5% (95% CI 84.6-97.5) and specificity 76.3% (95% CI 69.0-82.4) at a cut-point that achieved ≥90% sensitivity. In the two-step algorithm, Xpert TB/LTBI had high accuracy for identifying TB infection in the first step, but accuracy was lower for distinguishing active TB from LTBI in the second step.CONCLUSIONSXpert TB/LTBI exceeded World Health Organization (WHO)-recommended minimum accuracy targets for a TB screening test. However, further refinement is needed to improve its ability to distinguish active TB from LTBI.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"39 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patricia Winokur,Oyeniyi Diya,David Fitz-Patrick,Michael Dever,Juleen Gayed,Stephen Lockhart,Xia Xu,Ying Zhang,Vishva Bangad,L Tyler Wadsworth,Kevin Cannon,Jose F Cardona,Lisa Usdan,John Ginis,Federico J Mensa,Jing Zou,Xuping Xie,Claire Lu,Sandra Buitrago,Ingrid L Scully,David Cooper,Kenneth Koury,Kathrin U Jansen,Ӧzlem Türeci,Uğur Şahin,Kena A Swanson,William C Gruber,Nicholas Kitchin
BACKGROUNDEmergence of SARS-CoV-2 sublineages warrants the use of sequence-adapted vaccines to provide protection against COVID-19.METHODSIn this phase 3 trial, adults 18‒55 years old who had previously received three 30-μg doses of BNT162b2 vaccine were randomized to receive a 60- or 30-μg dose of bivalent Omicron BA.1‒adapted BNT162b2 comprising equal amounts of ancestral and monovalent messenger RNA BA.1 (bivalent BA.1) or a 60-μg dose of monovalent Omicron BA.1‒adapted BNT162b2 (monovalent BA.1). Safety (local reactions, systemic events, adverse events [AEs], and serious AEs) was the primary objective. Exploratory analyses assessed immune responses against Omicron-BA.1, BA.4, and BA.5 subvariants and ancestral strain.RESULTSAmong the 1054 randomized participants who received monovalent BA.1 or bivalent BA.1, frequencies of local reactions, systemic events, and AEs were slightly higher with 60-µg monovalent BA.1 than either bivalent BA.1 dose level. One month after vaccination, bivalent BA.1 (30 μg and 60 μg) and monovalent BA.1 (60 μg) induced substantial neutralizing responses against Omicron BA.1 (50% neutralizing titer geometric mean fold rises [GMFRs]: 15.4 [95% CI 12.4-19.2], 17.1 [13.7-21.4], and 24.6 [19.3-31.4], respectively) and ancestral strain (GMFRs: 6.2 [5.1-7.6], 7.3 [6.0-8.9], and 7.0 [5.7-8.7], respectively). In a smaller (n=30/treatment arm) sentinel cohort, all study vaccines modestly neutralized Omicron BA.4 and BA.5.CONCLUSIONSBivalent and monovalent BA.1‒adapted vaccines had a safety profile similar to original BNT162b2 30 μg and induced substantial neutralizing responses against Omicron BA.1 and ancestral strains.NCT04955626.
{"title":"Safety and Immunogenicity of a Fourth Dose of Omicron-BA.1-Adapted BNT162b2 COVID-19 Vaccines in Adults 18‒55 Years Old.","authors":"Patricia Winokur,Oyeniyi Diya,David Fitz-Patrick,Michael Dever,Juleen Gayed,Stephen Lockhart,Xia Xu,Ying Zhang,Vishva Bangad,L Tyler Wadsworth,Kevin Cannon,Jose F Cardona,Lisa Usdan,John Ginis,Federico J Mensa,Jing Zou,Xuping Xie,Claire Lu,Sandra Buitrago,Ingrid L Scully,David Cooper,Kenneth Koury,Kathrin U Jansen,Ӧzlem Türeci,Uğur Şahin,Kena A Swanson,William C Gruber,Nicholas Kitchin","doi":"10.1093/cid/ciag026","DOIUrl":"https://doi.org/10.1093/cid/ciag026","url":null,"abstract":"BACKGROUNDEmergence of SARS-CoV-2 sublineages warrants the use of sequence-adapted vaccines to provide protection against COVID-19.METHODSIn this phase 3 trial, adults 18‒55 years old who had previously received three 30-μg doses of BNT162b2 vaccine were randomized to receive a 60- or 30-μg dose of bivalent Omicron BA.1‒adapted BNT162b2 comprising equal amounts of ancestral and monovalent messenger RNA BA.1 (bivalent BA.1) or a 60-μg dose of monovalent Omicron BA.1‒adapted BNT162b2 (monovalent BA.1). Safety (local reactions, systemic events, adverse events [AEs], and serious AEs) was the primary objective. Exploratory analyses assessed immune responses against Omicron-BA.1, BA.4, and BA.5 subvariants and ancestral strain.RESULTSAmong the 1054 randomized participants who received monovalent BA.1 or bivalent BA.1, frequencies of local reactions, systemic events, and AEs were slightly higher with 60-µg monovalent BA.1 than either bivalent BA.1 dose level. One month after vaccination, bivalent BA.1 (30 μg and 60 μg) and monovalent BA.1 (60 μg) induced substantial neutralizing responses against Omicron BA.1 (50% neutralizing titer geometric mean fold rises [GMFRs]: 15.4 [95% CI 12.4-19.2], 17.1 [13.7-21.4], and 24.6 [19.3-31.4], respectively) and ancestral strain (GMFRs: 6.2 [5.1-7.6], 7.3 [6.0-8.9], and 7.0 [5.7-8.7], respectively). In a smaller (n=30/treatment arm) sentinel cohort, all study vaccines modestly neutralized Omicron BA.4 and BA.5.CONCLUSIONSBivalent and monovalent BA.1‒adapted vaccines had a safety profile similar to original BNT162b2 30 μg and induced substantial neutralizing responses against Omicron BA.1 and ancestral strains.NCT04955626.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"49 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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