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Reactogenicity and immunogenicity following heterologous and homologous third dose COVID-19 vaccination in UK adolescents (Com-COV3): A randomised controlled non-inferiority trial 英国青少年异源和同源第三剂COVID-19疫苗(Com-COV3)的反应原性和免疫原性:一项随机对照非劣效性试验
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-01 DOI: 10.1016/j.jinf.2025.106663
E. Kelly , M. Greenland , P. de Whalley , G.C. Macaulay , P.K. Aley , E. Plested , S. Koleva , J. Cotton , J. Kinch , T. Madupuri , R.C. Read , M. Ramsay , C. Cameron , D.P.J. Turner , P. Heath , P. Connor , K. Cathie , S.N. Faust , I. Banerjee , K. Man , X. Liu

Background

The emergence of SARS-CoV2 variants combined with waning vaccine-induced immunity and breakthrough infections has highlighted the need for booster doses to maintain protection against SARS-CoV2 infection and disease.

Methods

Com-COV3 was a phase II, multicentre, randomised controlled trial, recruiting across 11 UK sites from June 2022 to June 2023, with follow-up visits to February 2024. Healthy 12–15-year-olds who had received a two-30 μg dose BNT162b2 primary regimen at least 90 days previously were randomised 1:1:1:1:1 to receive either BNT162b2 30 μg, BNT162b2 10 μg (adult vaccine formulation), BNT162b2 10 μg (paediatric formulation), NVXCoV2373, or Meningococcal B vaccine (control). The primary objective was to determine if SARS-CoV-2 anti-spike antibody following a 10 μg dose of the adult formulation of BNT162b2 was non-inferior to the paediatric formulation at 28 days post-third vaccination. The last five participants were randomised using a 1:3:3:1:1 ratio to prioritise recruitment to the study groups required for the co-primary endpoint. Although recruitment ceased early, the sample size required to fulfil the primary objective was met.

Findings

281 participants were recruited (mean age 14 years old, 57% female). Adverse reactions were mostly mild-to-moderate. Local reactogenicity was mildest following NVXCoV2373. Frequency of adverse events was similar for both full dose and fractional dose BNT162b2 groups. Four serious adverse events occurred: three in the paediatric and one in the adult 10 μg BNT162b2 group. Immunogenicity of 10 μg BNT162b2 (adult) was both non-inferior and superior to that of 10 μg BNT162b2 (paediatric); adjusted geometric mean ratio (aGMR) anti-spike IgG 1.50 (one-sided 95% CI 1.25 to ∞). Compared with 30 μg BNT162b2, anti-spike IgG at day 28 post-third dose were similar in the 10 μg BNT162b2 (adult) group [aGMR 0.93 (95% CI 0.75–1.14)] and significantly lower in the 10 μg BNT162b2 (paediatric) [aGMR 0.64 (95% CI 0.52–0.78)] and NVXCoV2373 [aGMR 0.77 (95% CI 0.63–0.95)] groups. Compared with 30 μg BNT162b2, levels of neutralising antibodies against Omicron BA.5 and XBB.15 were similar across vaccine groups.

Interpretation

All booster regimens evaluated elicited a robust immune response. 10 μg fractional adult BNT162b2 vaccine demonstrated similar immunogenicity compared with 30 μg BNT162b2 and superior immunogenicity compared with 10 μg paediatric BNT162b2 vaccine. Fractional doses of the adult BNT162b2 vaccine are an alternative to the paediatric formulation for booster campaigns in adolescents.
背景:SARS-CoV2变异的出现,加上疫苗诱导的免疫力下降和突破性感染,突出了加强剂量以维持对SARS-CoV2感染和疾病的保护的必要性。方法:Com-COV3是一项II期、多中心、随机对照试验,于2022年6月至2023年6月在英国11个地点招募,随访至2024年2月。至少90天前接受过2- 30μg剂量BNT162b2初级方案的12-15岁健康儿童按1:1:1:1:1随机分组,分别接受BNT162b2 30μg、BNT162b2 10μg(成人疫苗制剂)、BNT162b2 10μg(儿科疫苗制剂)、NVXCoV2373或脑膜炎球菌B疫苗(对照)。主要目的是确定在第三次接种后28天,接种10μg剂量的成人剂型BNT162b2后的SARS-CoV-2抗刺突抗体是否优于儿科剂型。最后5名参与者使用1:3:3:1:1的比例随机分组,优先招募到共同主要终点所需的研究组。虽然征聘工作提前停止,但达到了实现主要目标所需的样本量。结果:281名参与者被招募(平均年龄14岁,57%为女性)。不良反应大多为轻至中度。NVXCoV2373的局部反应性最轻。BNT162b2全剂量组和部分剂量组的不良事件发生率相似。发生了4例严重不良事件:3例发生在儿科,1例发生在10μg BNT162b2成人组。10μg BNT162b2(成人)的免疫原性优于10μg BNT162b2(儿童);校正几何平均比(aGMR)抗峰值IgG 1.50(单侧95%CI 1.25至∞)。与30μg BNT162b2相比,第3次给药后第28天,10μg BNT162b2(成人)组的抗刺突IgG水平相似[aGMR 0.93 (95%CI 0.75 ~ 1.14)],而10μg BNT162b2(儿童)组[aGMR 0.64 (95%CI 0.52 ~ 0.78)]和NVXCoV2373 [aGMR 0.77 (95%CI 0.63 ~ 0.95)]的抗刺突IgG水平则显著低于10μg BNT162b2(儿童)组[aGMR 0.64 (95%CI 0.52 ~ 0.78)]。与30μg BNT162b2相比,不同疫苗组抗Omicron BA.5和XBB.15的中和抗体水平相似。解释:所有评估的强化方案都引起了强大的免疫反应。10μg分级成人BNT162b2疫苗与30μg BNT162b2疫苗具有相似的免疫原性,与10μg儿科BNT162b2疫苗具有更强的免疫原性。部分剂量的成人BNT162b2疫苗是用于青少年加强运动的儿科配方的替代方案。资助:国家卫生研究所、疫苗工作组和流行病防范创新联盟。
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引用次数: 0
Interpretable machine learning based comorbidity specific mortality risk score for bloodstream infections 基于可解释机器学习的血液感染共病特定死亡风险评分。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-01 DOI: 10.1016/j.jinf.2025.106656
Chen Cui , Jinyi Zhao , Fei Mu , Dahua Wang , Yamei Li , Meng Tang , Kexin Sun , Rui Gong , Zhen Yan , Jingwen Wang

Objectives

Bloodstream infections (BSI) are a leading cause of sepsis, necessitating early risk stratification during the critical window for effective management. We aimed to develop a model that leverages early-phase clinical data to predict 28-day mortality by integrating longitudinal trends and addressing comorbidity-driven heterogeneity.

Methods

The BSI Heterogeneity Score (BHScore) was developed using machine learning on longitudinal clinical data (first 7 days post-culture) from 2524 BSI patients at Xijing Hospital. The model uses interpretable methods to establish comorbidity-stratified thresholds (global, renal disease, liver disease, metastatic malignancy) to enhance prediction accuracy.

Results

The BHScore demonstrated superior discriminatory performance (area under the receiver operating characteristic curve: 0.81–0.91) and temporal stability compared to established scores including the Sequential Organ Failure Assessment (SOFA), representing an improvement of 10% to 25%. Our analysis revealed that coagulation biomarkers have greater prognostic significance in the malignancy subgroup, inflammatory thresholds are more sensitive in the liver disease subgroup, and urea levels exhibit U-shaped mortality curves in the renal disease subgroup. To support clinical application, a freely accessible web tool has been developed.

Conclusions

The BHScore enables the early identification of high-risk BSI patients with diverse comorbidities using straightforward clinical indicators, facilitating timely and targeted interventions to reduce mortality.
目的:血流感染(BSI)是脓毒症的主要原因,需要在有效管理的关键窗口期进行早期风险分层。我们的目标是建立一个模型,通过整合纵向趋势和解决合并症驱动的异质性,利用早期临床数据预测28天死亡率。方法:利用机器学习对西京医院2524例BSI患者的纵向临床数据(培养后7天)进行BSI异质性评分(BHScore)。该模型使用可解释的方法来建立合并症分层阈值(全局、肾脏疾病、肝脏疾病、转移性恶性肿瘤),以提高预测准确性。结果:与包括顺序器官衰竭评估(SOFA)在内的现有评分相比,BHScore表现出更好的区分性能(受试者工作特征曲线下面积:0.81-0.91)和时间稳定性,提高了10%至25%。我们的分析显示,凝血生物标志物在恶性肿瘤亚组中具有更大的预后意义,炎症阈值在肝脏疾病亚组中更敏感,尿素水平在肾脏疾病亚组中呈现u型死亡率曲线。为了支持临床应用,我们开发了一个免费访问的网络工具。结论:BHScore可以通过简单明了的临床指标,早期发现具有多种合并症的高危BSI患者,及时、有针对性地进行干预,降低死亡率。
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引用次数: 0
The epidemic pattern of a chikungunya outbreak in China exhibits a three-stage migratory trend 基孔肯雅热疫情在中国的流行模式表现为三个阶段的迁移趋势。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-01 DOI: 10.1016/j.jinf.2025.106646
Jiajia Zhang , Juncheng Cai , Changhai Liu , Marco Túlio Dos Santos Costa , Tao Ren , Libin Chen
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引用次数: 0
Lipoarabinomannan (LAM) for the diagnosis of tuberculosis from sputum 脂阿拉伯甘露聚糖(LAM)对痰液结核的诊断价值。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-18 DOI: 10.1016/j.jinf.2025.106662
Steffen Pichlo, Patricia Sanchez Carballo, Maja Reimann, Nika Zielinski, Yassir Adam Shuaib, Niklas Köhler, Sönke Andres, Jan Heyckendorf , Barbara Kalsdorf, Ioana D. Olaru , Helmut J.F. Salzer , Christoph Lange
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引用次数: 0
Evolving pneumococcal epidemiology and vaccine impact in the Netherlands, 2004–2024: Carriage and invasive disease 2004-2024年荷兰肺炎球菌流行病学和疫苗影响的演变:传播和侵袭性疾病。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-13 DOI: 10.1016/j.jinf.2025.106658
Maurits T. Wulffraat , Nelleke G. van de Weijer , Alienke J. Wijmenga-Monsuur , Paul Badoux , Anneke Steens , Debbie Smit , Rob Mariman , Krzysztof P. Trzciński , Nina M. van Sorge , Nynke Y. Rots , Marianne A. van Houten

Objectives

Since pneumococcal conjugate vaccines (PCVs) were introduced into the Dutch childhood National Immunization Program in 2006, colonization and invasive disease of Streptococcus pneumoniae have declined, alongside shifts in serotype prevalence towards non-vaccine serotypes (NVTs). To monitor changes and estimate the added value of higher-valent PCVs, serotype-specific carriage, invasive pneumococcal disease (IPD) and invasive disease potential were analyzed.

Methods

During the winters of 2018/2019 and 2022/2023 pneumococcal carriage was determined among 24-month-old children and parents, and compared to carriage studies from 2005 to 2016. IPD data from Dutch surveillance (2004–2024) were included. Pneumococcal isolates were serotyped using agglutination and Quellung. Serotype-specific disease potential determined as odds ratios (OR) for IPD versus carriage.

Results

Pneumococcal carriage in children decreased from 66% in 2005 to 49% in 2018/2019 and 46% in 2022/2023. In 2022/2023, 29% of children carried NVTs, followed by PCV20- (11%), PCV13- (4%), PCV15- (2%) and PCV10- (0%) specific serotypes. Among parents, carriage declined from 17% in 2005 to 2% by 2022/2023. IPD incidence increased from 6·7 to 8·4 per 100,000 children under 5 years between 2018–2020 and 2022–2024, predominantly caused by an increase in serotype 19A. Serotypes 8 and 3 have the highest invasive disease potential.

Conclusions

This study shows stabilized pneumococcal carriage from 2018 to 2023 with low invasive disease potential for common serotypes, except for serotype 19A. However, rising IPD incidence from other non-vaccine serotypes highlights the need for higher-valency vaccines. The newly introduced PCV15 covers 58% of IPD cases, while PCV20 could cover 73%.
目的:自从2006年将肺炎球菌结合疫苗(PCVs)引入荷兰儿童国家免疫规划以来,肺炎链球菌的定植和侵袭性疾病有所下降,同时血清型患病率向非疫苗血清型(NVTs)转变。分析血清型特异性携带、侵袭性肺炎球菌病(IPD)和侵袭性疾病的可能性,以监测高价pcv的变化并估计其附加值。方法:在2018/2019年和2022/2023年冬季,对24月龄儿童和家长进行肺炎球菌携带测定,并与2005-2016年的携带研究进行比较。纳入了荷兰监测(2004-2024年)IPD数据。用凝集法和Quellung法对分离的肺炎球菌进行血清分型。血清型特异性疾病的可能性由IPD与携带的比值比(OR)决定。结果:儿童肺炎球菌携带率从2005年的66%下降到2018/2019年的49%和2022/2023年的46%。在2022/2023年,29%的儿童携带NVTs,其次是PCV20-(11%)、PCV13-(4%)、PCV15-(2%)和PCV10-(0%)特定血清型。在父母中,乘车比例从2005年的17%下降到2022/2023年的2%。2018-2020年和2022-2024年期间,IPD发病率从每10万名5岁以下儿童6.7例增加到8.4例,主要原因是血清型19A增加。血清型8和3具有最高的侵袭性疾病可能性。结论:本研究显示,2018-2023年肺炎球菌携带稳定,除19A血清型外,其他常见血清型的侵袭性疾病可能性较低。然而,其他非疫苗血清型引起的IPD发病率上升,突出表明需要更高效价的疫苗。新引入的PCV15可覆盖58%的IPD病例,而PCV20可覆盖73%。
{"title":"Evolving pneumococcal epidemiology and vaccine impact in the Netherlands, 2004–2024: Carriage and invasive disease","authors":"Maurits T. Wulffraat ,&nbsp;Nelleke G. van de Weijer ,&nbsp;Alienke J. Wijmenga-Monsuur ,&nbsp;Paul Badoux ,&nbsp;Anneke Steens ,&nbsp;Debbie Smit ,&nbsp;Rob Mariman ,&nbsp;Krzysztof P. Trzciński ,&nbsp;Nina M. van Sorge ,&nbsp;Nynke Y. Rots ,&nbsp;Marianne A. van Houten","doi":"10.1016/j.jinf.2025.106658","DOIUrl":"10.1016/j.jinf.2025.106658","url":null,"abstract":"<div><h3>Objectives</h3><div>Since pneumococcal conjugate vaccines (PCVs) were introduced into the Dutch childhood National Immunization Program in 2006, colonization and invasive disease of <em>Streptococcus pneumoniae</em> have declined, alongside shifts in serotype prevalence towards non-vaccine serotypes (NVTs). To monitor changes and estimate the added value of higher-valent PCVs, serotype-specific carriage, invasive pneumococcal disease (IPD) and invasive disease potential were analyzed.</div></div><div><h3>Methods</h3><div>During the winters of 2018/2019 and 2022/2023 pneumococcal carriage was determined among 24-month-old children and parents, and compared to carriage studies from 2005 to 2016. IPD data from Dutch surveillance (2004–2024) were included. Pneumococcal isolates were serotyped using agglutination and Quellung. Serotype-specific disease potential determined as odds ratios (OR) for IPD versus carriage.</div></div><div><h3>Results</h3><div>Pneumococcal carriage in children decreased from 66% in 2005 to 49% in 2018/2019 and 46% in 2022/2023. In 2022/2023, 29% of children carried NVTs, followed by PCV20- (11%), PCV13- (4%), PCV15- (2%) and PCV10- (0%) specific serotypes. Among parents, carriage declined from 17% in 2005 to 2% by 2022/2023. IPD incidence increased from 6·7 to 8·4 per 100,000 children under 5 years between 2018–2020 and 2022–2024, predominantly caused by an increase in serotype 19A. Serotypes 8 and 3 have the highest invasive disease potential.</div></div><div><h3>Conclusions</h3><div>This study shows stabilized pneumococcal carriage from 2018 to 2023 with low invasive disease potential for common serotypes, except for serotype 19A. However, rising IPD incidence from other non-vaccine serotypes highlights the need for higher-valency vaccines. The newly introduced PCV15 covers 58% of IPD cases, while PCV20 could cover 73%.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106658"},"PeriodicalIF":11.9,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530881","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}
引用次数: 0
Plasmodium falciparum gene expression signatures and antibody profiling implicate the fikk, phist, and surf multigene families in severe malaria syndromes 恶性疟原虫基因表达特征和抗体谱分析暗示fikk、phist和surf多基因家族在严重疟疾综合征中的作用。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-12 DOI: 10.1016/j.jinf.2025.106655
Bryan E. Cummings , Emily M. Stucke , Drissa Coulibaly , Jonathan G. Lawton , Rafal S. Sobota , Abdoulaye Kassoum Kone , Bourama Kane , Bouréima Guindo , Bourama Tangara , Mody Sissoko , Fayçal Maiga , Karim Traore , Aichatou Diawara , Amidou Traore , Ali Thera , Antoine Dara , Amadou Niangaly , Modibo Daou , Issa Diarra , Youssouf Tolo , Mark A. Travassos
Plasmodium falciparum is the most virulent Plasmodium species, responsible for the life-threatening severe malaria syndromes of cerebral malaria and severe malarial anemia. In a Mali case-control study, we determined parasite gene expression in cerebral malaria, severe malarial anemia, and concurrent disease featuring both syndromes by comparing RNA-seq data from severe malaria cases to matched uncomplicated malaria controls with or without a history of cerebral malaria. While severe malarial anemia comparisons produced comparatively low levels of differential expression, the comparisons of cerebral malaria and concurrent disease yielded significant differential expression of multigene families (fikk, phist, and surf) implicated in processes that escalate disease severity, such as cytoadherence and erythrocytic remodeling. We probed custom microarrays featuring these antigens with acute and convalescent sera. Children with severe malaria developed antibody responses to subsets of these proteins following severe malaria infection, suggesting exposure to these antigens during illness and their potential as targets in the development of natural protective immunity against severe malaria. Our findings address knowledge gaps surrounding parasite gene expression in severe malarial anemia. Further, these results broaden the scope of multigene families implicated in severe malaria pathogenesis and underscore the utility of transcriptome-wide approaches for a comprehensive understanding of severe disease, particularly when developing therapeutics or vaccines.
恶性疟原虫是毒性最强的疟原虫,可导致危及生命的脑型疟疾和严重疟疾性贫血等严重疟疾综合征。在马里的一项病例对照研究中,我们通过比较来自严重疟疾病例的RNA-seq数据与匹配的有或没有脑疟疾病史的简单疟疾对照者的RNA-seq数据,确定了脑疟疾、严重疟疾贫血和具有这两种综合征的并发疾病中的寄生虫基因表达。虽然严重疟疾性贫血的比较产生了相对较低水平的差异表达,但脑疟疾和并发疾病的比较产生了涉及疾病严重程度升级过程的多基因家族(fikk, phist和surf)的显著差异表达,如细胞粘附性和红细胞重塑。我们用急性和恢复期血清检测了具有这些抗原的定制微阵列。患有严重疟疾的儿童在严重疟疾感染后对这些蛋白质的亚群产生抗体反应,这表明在疾病期间暴露于这些抗原以及它们作为发展针对严重疟疾的自然保护性免疫的靶标的潜力。我们的研究结果解决了严重疟疾贫血中寄生虫基因表达的知识空白。此外,这些结果扩大了与严重疟疾发病机制有关的多基因家族的范围,并强调了全转录组方法在全面了解严重疾病方面的效用,特别是在开发治疗方法或疫苗时。
{"title":"Plasmodium falciparum gene expression signatures and antibody profiling implicate the fikk, phist, and surf multigene families in severe malaria syndromes","authors":"Bryan E. Cummings ,&nbsp;Emily M. Stucke ,&nbsp;Drissa Coulibaly ,&nbsp;Jonathan G. Lawton ,&nbsp;Rafal S. Sobota ,&nbsp;Abdoulaye Kassoum Kone ,&nbsp;Bourama Kane ,&nbsp;Bouréima Guindo ,&nbsp;Bourama Tangara ,&nbsp;Mody Sissoko ,&nbsp;Fayçal Maiga ,&nbsp;Karim Traore ,&nbsp;Aichatou Diawara ,&nbsp;Amidou Traore ,&nbsp;Ali Thera ,&nbsp;Antoine Dara ,&nbsp;Amadou Niangaly ,&nbsp;Modibo Daou ,&nbsp;Issa Diarra ,&nbsp;Youssouf Tolo ,&nbsp;Mark A. Travassos","doi":"10.1016/j.jinf.2025.106655","DOIUrl":"10.1016/j.jinf.2025.106655","url":null,"abstract":"<div><div><em>Plasmodium falciparum</em> is the most virulent <em>Plasmodium</em> species, responsible for the life-threatening severe malaria syndromes of cerebral malaria and severe malarial anemia. In a Mali case-control study, we determined parasite gene expression in cerebral malaria, severe malarial anemia, and concurrent disease featuring both syndromes by comparing RNA-seq data from severe malaria cases to matched uncomplicated malaria controls with or without a history of cerebral malaria. While severe malarial anemia comparisons produced comparatively low levels of differential expression, the comparisons of cerebral malaria and concurrent disease yielded significant differential expression of multigene families (<em>fikk</em>, <em>phist</em>, and <em>surf</em>) implicated in processes that escalate disease severity, such as cytoadherence and erythrocytic remodeling. We probed custom microarrays featuring these antigens with acute and convalescent sera. Children with severe malaria developed antibody responses to subsets of these proteins following severe malaria infection, suggesting exposure to these antigens during illness and their potential as targets in the development of natural protective immunity against severe malaria. Our findings address knowledge gaps surrounding parasite gene expression in severe malarial anemia. Further, these results broaden the scope of multigene families implicated in severe malaria pathogenesis and underscore the utility of transcriptome-wide approaches for a comprehensive understanding of severe disease, particularly when developing therapeutics or vaccines.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106655"},"PeriodicalIF":11.9,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524659","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}
引用次数: 0
Long-term impact of nirsevimab on prevention of respiratory syncytial virus infection using a real-world global database 使用真实世界的全球数据库研究尼塞维单抗对预防呼吸道合胞病毒感染的长期影响。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-07 DOI: 10.1016/j.jinf.2025.106652
Taito Kitano , Shinya Tsuzuki , Haruhisa Fukuda , Sayaka Yoshida

Objective

The preventive effect of nirsevimab, a long-acting monoclonal antibody, on infants with respiratory syncytial virus (RSV) infection beyond six months has rarely been evaluated. The objective of this study was to evaluate the preventive effects of nirsevimab beyond 6 months after RSV infection using a global database.

Methods

This was a multi-centre retrospective study using a global database (TriNetX). The participants were children under 24 months of age who required nucleic acid testing for RSV between July 2023 and June 2025. Children who received the last dose of nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months were compared with those who did not receive any nirsevimab dose by epidemic season after propensity score matching.

Results

A total of 4627, 861, and 532 children aged <24 months who received nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months before RSV testing, respectively, and 210,626 children who did not receive any nirsevimab were identified. Compared with those who did not receive nirsevimab, the odds ratios (OR) of a positive RSV test result among those who received nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months before testing were 0.49 [95% confidence interval (CI) 0.42, 0.57] (p<0.001), 0.67 [0.48, 0.94] (p<0.020), and 1.21 [0.89, 1.65] (p=0.234) in the last epidemic season, respectively.

Conclusion

This study indicated that the preventive effect of nirsevimab against RSV infection was maintained for up to 12 months following administration, whereas a preventive effect beyond 12 months was not observed. The results of this study need to be interpreted with caution owing to some important limitations.
目的:尼塞维单抗(nirseimab)是一种长效单克隆抗体,对6个月以上呼吸道合胞病毒(RSV)感染的婴儿的预防作用尚未得到评价。本研究的目的是利用全球数据库评估尼罗维单抗在RSV感染后6个月以上的预防效果。方法:这是一项使用全球数据库(TriNetX)的多中心回顾性研究。参与者是在2023年7月至2025年6月期间需要进行RSV微生物检测(PCR或抗原检测)的24个月以下儿童。倾向评分匹配后,将6个月内、6 - 11个月和12个月以上接受最后一剂尼西莫单抗的儿童与未接受任何尼西莫单抗剂量的儿童按流行季节进行比较。结果:共有4,627,861和532名年龄的儿童。结论:本研究表明,尼塞维单抗对RSV感染的预防作用在给药后维持了长达12个月,而未观察到超过12个月的预防作用。由于一些重要的局限性,本研究的结果需要谨慎解释。
{"title":"Long-term impact of nirsevimab on prevention of respiratory syncytial virus infection using a real-world global database","authors":"Taito Kitano ,&nbsp;Shinya Tsuzuki ,&nbsp;Haruhisa Fukuda ,&nbsp;Sayaka Yoshida","doi":"10.1016/j.jinf.2025.106652","DOIUrl":"10.1016/j.jinf.2025.106652","url":null,"abstract":"<div><h3>Objective</h3><div>The preventive effect of nirsevimab, a long-acting monoclonal antibody, on infants with respiratory syncytial virus (RSV) infection beyond six months has rarely been evaluated. The objective of this study was to evaluate the preventive effects of nirsevimab beyond 6 months after RSV infection using a global database.</div></div><div><h3>Methods</h3><div>This was a multi-centre retrospective study using a global database (TriNetX). The participants were children under 24 months of age who required nucleic acid testing for RSV between July 2023 and June 2025. Children who received the last dose of nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months were compared with those who did not receive any nirsevimab dose by epidemic season after propensity score matching.</div></div><div><h3>Results</h3><div>A total of 4627, 861, and 532 children aged &lt;24 months who received nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months before RSV testing, respectively, and 210,626 children who did not receive any nirsevimab were identified. Compared with those who did not receive nirsevimab, the odds ratios (OR) of a positive RSV test result among those who received nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months before testing were 0.49 [95% confidence interval (CI) 0.42, 0.57] (p&lt;0.001), 0.67 [0.48, 0.94] (p&lt;0.020), and 1.21 [0.89, 1.65] (p=0.234) in the last epidemic season, respectively.</div></div><div><h3>Conclusion</h3><div>This study indicated that the preventive effect of nirsevimab against RSV infection was maintained for up to 12 months following administration, whereas a preventive effect beyond 12 months was not observed. The results of this study need to be interpreted with caution owing to some important limitations.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106652"},"PeriodicalIF":11.9,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483615","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}
引用次数: 0
Antibodies to female Aedes albopictus salivary proteins promote dengue virus infection with salivary proteins 雌性白纹伊蚊唾液蛋白抗体促进登革热病毒与唾液蛋白的感染
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-01 DOI: 10.1016/j.jinf.2025.106638
Na Liu , Yanmei Li , Zhouyu Wu , Wenfei Qiao , Qianqian Zheng , Jing Zhuo , Yangzi Liu , Mengjie Lin , Ying Fu , Jiugang Zhao

Objective

Mosquito saliva can facilitate arboviral infection, yet whether host antibodies to salivary proteins modulate dengue virus (DENV) infection remains unclear. To test whether antibodies induced by Aedes albopictus salivary proteins (AaSP) enhance DENV infection when AaSP is present.

Methods

We used RAW264.7 cells and BALB/c mice; generated anti-AaSP antisera; co-incubated DENV with AaSP; quantified NS1 mRNA, envelope protein, and cytopathic effects (CPE); and assessed tissue pathology. We compared female- versus male-derived AaSP and antisera, performed proteomics, tested recombinant Obp1 and D7L, purified IgG, and evaluated papain digestion and Fcγ receptor (anti-CD16/32, clone 2.4G2) blockade.

Results

Antiserum with AaSP increased DENV infection in vitro and aggravated pathology in vivo. Repeated A. albopictus bites induced anti-AaSP antibodies and led to more severe disease after infection with AaSP-preincubated virus. Only female-AaSP antisera enhanced infection; proteomics showed sex-distinct salivary profiles. Obp1 and D7L enhanced infection with antiserum. Purified IgG reproduced the increase, which was lost after papain digestion or FcγR blockade.

Conclusion

Anti-AaSP IgG can increase DENV infection in the presence of AaSP. These findings add to understanding of DENV pathogenesis and may help inform future exploration of prevention targets.
目的蚊虫唾液可促进虫媒病毒感染,但宿主唾液蛋白抗体是否调节登革热病毒(DENV)感染尚不清楚。目的:检测唾液白纹伊蚊蛋白(AaSP)诱导的抗体是否增强DENV感染。方法采用RAW264.7细胞和BALB/c小鼠;生成抗aasp抗血清;DENV与AaSP共孵育;定量NS1 mRNA、包膜蛋白和细胞病变效应(CPE);并评估组织病理学。我们比较了女性和男性来源的AaSP和抗血清,进行了蛋白质组学,测试了重组Obp1和D7L,纯化了IgG,并评估了木瓜蛋白酶消化和Fcγ受体(抗cd16 /32,克隆2.4G2)的阻断。结果AaSP抗血清可增加DENV体外感染,加重体内病理。白纹伊蚊多次叮咬可诱导抗aasp抗体,感染aasp预孵育病毒后病情加重。仅女性- aasp抗血清增强感染;蛋白质组学显示不同性别的唾液谱。Obp1和D7L增强抗血清感染。纯化后的IgG在木瓜蛋白酶消化或FcγR阻断后消失。结论抗AaSP IgG可增加猪流行性出血热感染。这些发现增加了对DENV发病机制的理解,并可能有助于未来探索预防目标。
{"title":"Antibodies to female Aedes albopictus salivary proteins promote dengue virus infection with salivary proteins","authors":"Na Liu ,&nbsp;Yanmei Li ,&nbsp;Zhouyu Wu ,&nbsp;Wenfei Qiao ,&nbsp;Qianqian Zheng ,&nbsp;Jing Zhuo ,&nbsp;Yangzi Liu ,&nbsp;Mengjie Lin ,&nbsp;Ying Fu ,&nbsp;Jiugang Zhao","doi":"10.1016/j.jinf.2025.106638","DOIUrl":"10.1016/j.jinf.2025.106638","url":null,"abstract":"<div><h3>Objective</h3><div>Mosquito saliva can facilitate arboviral infection, yet whether host antibodies to salivary proteins modulate dengue virus (DENV) infection remains unclear. To test whether antibodies induced by <em>Aedes albopictus</em> salivary proteins (AaSP) enhance DENV infection when AaSP is present.</div></div><div><h3>Methods</h3><div>We used RAW264.7 cells and <em>BALB/c</em> mice; generated anti-AaSP antisera; co-incubated DENV with AaSP; quantified NS1 mRNA, envelope protein, and cytopathic effects (CPE); and assessed tissue pathology. We compared female- versus male-derived AaSP and antisera, performed proteomics, tested recombinant Obp1 and D7L, purified IgG, and evaluated papain digestion and Fcγ receptor (anti-CD16/32, clone 2.4G2) blockade.</div></div><div><h3>Results</h3><div>Antiserum with AaSP increased DENV infection in vitro and aggravated pathology in vivo. Repeated <em>A. albopictus</em> bites induced anti-AaSP antibodies and led to more severe disease after infection with AaSP-preincubated virus. Only female-AaSP antisera enhanced infection; proteomics showed sex-distinct salivary profiles. Obp1 and D7L enhanced infection with antiserum. Purified IgG reproduced the increase, which was lost after papain digestion or FcγR blockade.</div></div><div><h3>Conclusion</h3><div>Anti-AaSP IgG can increase DENV infection in the presence of AaSP. These findings add to understanding of DENV pathogenesis and may help inform future exploration of prevention targets.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106638"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145474436","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}
引用次数: 0
Association between pre-diagnostic fluoroquinolone exposure and possible acquired fluoroquinolone resistance in Mycobacterium tuberculosis in Shanghai: An EHR-based case-control study using whole-genome sequencing 上海结核分枝杆菌诊断前氟喹诺酮暴露与可能获得性氟喹诺酮耐药性之间的关系:基于ehr的全基因组测序病例对照研究
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-01 DOI: 10.1016/j.jinf.2025.106648
Yangyi Zhang , Danni Li , Jiazhen Liu , Yuan Jiang , Xin Shen , Biao Xu

Objectives

Fluoroquinolones (FQ) are one of the most prescribed broad-spectrum antibiotics and a cornerstone of tuberculosis (TB) treatment. TB patients may have had FQ resistance before treatment initiation. However, the association between pre-diagnostic FQ exposure and acquired FQ-resistant TB remains unclear.

Methods

A case-control study was conducted among all pulmonary TB patients in Shanghai during 2022–2023. Cases were TB patients who had possible acquired FQ resistance identified through whole-genome sequencing (WGS), while controls were FQ susceptible patients. Pre-diagnostic FQ prescriptions were extracted from the Shanghai Electronic Health Record (EHR) platform.

Results

Among 3496 patients, 7.4% had FQ-resistant TB, with 93.5% (243/260) phylogenetically inferred as possible acquired resistance. Multivariate analysis revealed FQ exposure was the strongest predictor of possible acquired FQ resistance with an aOR of 4.31 for a single prescription and 13.18 for multiple prescriptions. A nonlinear dose-response relationship between resistance probability and prescription number was found. Most prescriptions to cases were from non-TB-designated tertiary hospitals for non-TB respiratory diseases, with an exposure interval of ≥61 days prior to TB diagnosis.

Conclusion

Acquired resistance dominates FQ resistance in Shanghai TB patients. The dose-response relationship between pre-diagnostic FQ exposure and possible acquired resistance underscores the need for judicious FQ use.
目的:氟喹诺酮类药物(FQ)是最常用的广谱抗生素之一,也是结核病(TB)治疗的基石。结核病患者在开始治疗前可能已经有FQ耐药性。然而,诊断前FQ暴露与获得性FQ耐药结核病之间的关系尚不清楚。方法:对2022-2023年上海市所有肺结核患者进行病例对照研究。病例为通过全基因组测序(WGS)鉴定可能获得FQ耐药性的结核病患者,对照组为FQ易感患者。诊断前FQ处方提取自上海电子健康档案(EHR)平台。结果:在3,496例患者中,7.4%为fq耐药结核病,93.5%(243/260)的系统发育推断为可能的获得性耐药。多因素分析显示,FQ暴露是可能获得性FQ耐药性的最强预测因子,单处方的aOR为4.31,多处方的aOR为13.18。耐药概率与处方数呈非线性剂量-响应关系。大多数病例的处方来自非结核病定点三级医院,用于治疗非结核病呼吸道疾病,在结核病诊断前暴露间隔≥61天。结论:上海结核患者获得性耐药以FQ耐药为主。诊断前FQ暴露与可能获得性耐药性之间的剂量-反应关系强调了明智使用FQ的必要性。
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引用次数: 0
Global emergence and polycentric evolution of invasive Streptococcus pyogenes M1UK lineage 侵袭性化脓性链球菌M1UK谱系的全球出现和多中心进化
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-01 DOI: 10.1016/j.jinf.2025.106653
Hizbullah Khan , Haoyuan Lun , Guangxian Xu , Kaisong Huang
{"title":"Global emergence and polycentric evolution of invasive Streptococcus pyogenes M1UK lineage","authors":"Hizbullah Khan ,&nbsp;Haoyuan Lun ,&nbsp;Guangxian Xu ,&nbsp;Kaisong Huang","doi":"10.1016/j.jinf.2025.106653","DOIUrl":"10.1016/j.jinf.2025.106653","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 5","pages":"Article 106653"},"PeriodicalIF":11.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145472526","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}
引用次数: 0
期刊
Journal of Infection
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