Pub Date : 2026-01-14DOI: 10.1016/j.lanmic.2025.101315
Claas Kirchhelle, Mirza Y Alas Portillo, Mark D M Davis, Assa Doron, Anahí Dreser, Nicolas Fortané, Christian Haddad, Stephen Hinchliffe, Samuel Kariuki, Sonia Lewycka, Sassy Molyneux, Cristina Moreno Lozano, Edna Mutua, Iruka N Okeke, Mingyuan Zhang Betancourt, Clare I R Chandler
Antimicrobial resistance (AMR) remains a major global health threat. Despite increasing international attention, AMR governance has often neglected social and equity dimensions, and there is a crucial need to synthesise evidence from social sciences and humanities scholarship to devise more people-centred approaches. In this Personal View, we report a qualitative stocktake of the intended and unintended consequences of the most recent phase of global AMR governance that started around the year 2000 and reached a high point with the 2015 Global Action Plan (GAP) on AMR. Our interdisciplinary analysis was guided by the five key objectives of current AMR governance, as organised in the 2015 GAP, to reduce AMR through awareness, surveillance, infection reduction, antimicrobial use optimisation, and research and innovation. The resulting assessment indicated mixed outcomes. Although the past decade witnessed unprecedented AMR-related action and investment, empirical studies highlight negative consequences of the decontextualised export of high-income governance frameworks and the neglect of upstream antibiotic-sensitive reforms of production, care, and innovation systems. Not embedding AMR within more general developmental and environmental challenges has also undermined local buy-in and contributed to the siloed status of AMR policies. For the next GAP, we recommend foregrounding equitable interventions; adopting a bottom-up, integrated perspective to incorporate local realities and solutions; and creating robust social sciences and humanities feedback loops for global AMR frameworks.
{"title":"(Un)intended consequences: a social sciences stocktake of a decade of Global Action Plan-inspired antimicrobial governance.","authors":"Claas Kirchhelle, Mirza Y Alas Portillo, Mark D M Davis, Assa Doron, Anahí Dreser, Nicolas Fortané, Christian Haddad, Stephen Hinchliffe, Samuel Kariuki, Sonia Lewycka, Sassy Molyneux, Cristina Moreno Lozano, Edna Mutua, Iruka N Okeke, Mingyuan Zhang Betancourt, Clare I R Chandler","doi":"10.1016/j.lanmic.2025.101315","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101315","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) remains a major global health threat. Despite increasing international attention, AMR governance has often neglected social and equity dimensions, and there is a crucial need to synthesise evidence from social sciences and humanities scholarship to devise more people-centred approaches. In this Personal View, we report a qualitative stocktake of the intended and unintended consequences of the most recent phase of global AMR governance that started around the year 2000 and reached a high point with the 2015 Global Action Plan (GAP) on AMR. Our interdisciplinary analysis was guided by the five key objectives of current AMR governance, as organised in the 2015 GAP, to reduce AMR through awareness, surveillance, infection reduction, antimicrobial use optimisation, and research and innovation. The resulting assessment indicated mixed outcomes. Although the past decade witnessed unprecedented AMR-related action and investment, empirical studies highlight negative consequences of the decontextualised export of high-income governance frameworks and the neglect of upstream antibiotic-sensitive reforms of production, care, and innovation systems. Not embedding AMR within more general developmental and environmental challenges has also undermined local buy-in and contributed to the siloed status of AMR policies. For the next GAP, we recommend foregrounding equitable interventions; adopting a bottom-up, integrated perspective to incorporate local realities and solutions; and creating robust social sciences and humanities feedback loops for global AMR frameworks.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101315"},"PeriodicalIF":20.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1016/j.lanmic.2025.101265
Caroline J Duncombe, Dianna E B Hergott, Weston Staubus, Mirte Balke-Buijs, James G Kublin, Patrick E Duffy, Sara A Healy, Angela Talley, Lisa Jackson, B Kim Lee Sim, Stephen L Hoffman, Robert W Sauerwein, Meta Roestenberg, Sean C Murphy
<p><strong>Background: </strong>Before infecting red blood cells and causing the clinical manifestations of malaria, the hepatotropic parasite Plasmodium falciparum completes a complex liver stage. Sex-based differences in pathogenesis by hepatotropic micro-organisms are well documented but unstudied for P falciparum in humans. We aimed to evaluate the effect of sex on the time to blood-stage positivity and initial blood-stage parasite densities as indicators of liver-stage dynamics and parasite replication.</p><p><strong>Methods: </strong>We conducted a pooled analysis of data from malaria-naive participants in control groups from controlled human malaria infection (CHMI) studies conducted between Jan 1, 2010, and Dec 31, 2024, in which samples were tested using Plasmodium 18S ribosomal RNA nucleic acid amplification tests (18S NAATs) at laboratories in Seattle (WA, USA) and Leiden (Netherlands). Participants aged 18-48 years were eligible for inclusion if they were in placebo or infectivity control groups in any CHMI study at the two laboratories and developed parasitaemia following CHMI. Patient demographics and 18S NAAT data were obtained from study leads at each centre and collated, standardised, and reviewed. Information on P falciparum strain, challenge route, and sampling schedule were extracted from study protocols or publications. The main outcome, time to positivity (TTP), was calculated as the study day of the first positive 18S NAAT of any density, measured during a 28-day monitoring period following CHMI. Using an interval-censored generalised gamma accelerated failure time model, we compared time to blood-stage positivity by sex, adjusting for challenge route, P falciparum strain, and study site. Odds of developing detectable infection after 7 days post-challenge was compared between male and female participants using a linear mixed-effects model adjusted for the same terms.</p><p><strong>Findings: </strong>Evaluable data were available from 102 control participants (48 [47%] female and 54 [53%] male) across 13 CHMI studies. There was moderate heterogeneity between studies (I<sup>2</sup>=31% [95% CI 0-57]). There were no notable demographic differences between male and female participants regarding age, challenge route, or strain. The mean time to first detectable parasitaemia was slightly longer in male participants (7·59 days [SD 1·15]) than in female participants (7·17 days [0·91]). Adjusted accelerated failure time analysis suggested that TTP occurred 8% later in male participants than female participants (time ratio 1·08 [1·03-1·16]). Male participants were significantly more likely than female participants to have a detectable infection after day 7 (19 [35%] of 54 male participants vs six [13%] of 48 female participants), with adjusted odds of delayed infection 5·20 times (95% CI 1·52-17·70) higher in male than female participants.</p><p><strong>Interpretation: </strong>Our findings suggest that male individuals are more like
背景：嗜肝性寄生虫恶性疟原虫（Plasmodium falciparum）在感染红细胞并引起疟疾临床表现之前，完成了复杂的肝期。嗜肝微生物在人类恶性疟原虫发病机制上的性别差异已得到充分记录，但尚未研究。我们的目的是评估性别对血期阳性时间和初始血期寄生虫密度的影响，作为肝期动态和寄生虫复制的指标。方法：我们对2010年1月1日至2024年12月31日在美国西雅图（WA， USA）和荷兰莱顿（Leiden）的实验室进行的控制性人疟疾感染（CHMI）研究中未患疟疾的对照组参与者的数据进行了汇总分析，其中样本使用疟原虫18S核糖体RNA核酸扩增试验（18S NAATs）进行了检测。年龄在18-48岁的参与者，如果他们在两个实验室的任何CHMI研究中处于安慰剂组或感染性对照组，并且在CHMI后出现寄生虫病，则有资格纳入。患者人口统计数据和18S NAAT数据从每个中心的研究线索中获得，并进行整理、标准化和审查。关于恶性疟原虫毒株、攻毒途径和采样计划的信息从研究方案或出版物中提取。在CHMI后的28天监测期间，以首次出现任何密度的18S NAAT阳性的研究天数为主要结果，即到达阳性时间（TTP）。使用间隔剔除广义伽玛加速失效时间模型，我们按性别比较时间与血期阳性，调整攻毒途径、恶性疟原虫品系和研究地点。使用线性混合效应模型对相同条件进行调整，比较了男性和女性参与者在攻击后7天发生可检测感染的几率。研究结果：在13项CHMI研究中，102名对照受试者（48名[47%]女性，54名[53%]男性）获得了可评估的数据。研究间存在中等异质性（I2=31% [95% CI 0-57]）。男性和女性参与者在年龄、挑战路线或压力方面没有显著的人口统计学差异。男性受试者首次检测到寄生虫病的平均时间（7.59 d [SD 1.15]）略长于女性受试者（7.17 d[0.91]）。校正加速失效时间分析表明，男性受试者TTP发生时间比女性受试者晚8%（时间比为1.08[1.03 -1·16]）。在第7天之后，男性参与者比女性参与者更有可能出现可检测到的感染（54名男性参与者中有19人[35%]对48名女性参与者中有6人[13%]），男性延迟感染的调整几率比女性参与者高5.20倍（95% CI 1.52 - 17.70）。解释：我们的研究结果表明，与女性个体相比，男性个体更有可能在CHMI合并恶性疟原虫后延迟检测到血期寄生虫。虽然不能直接测量肝期负荷是一个限制，但CHMI提供了一个受控的系统来推断肝期动力学。因此，恶性疟原虫感染可能涉及肝脏中性别特异性宿主-病原体相互作用，强调了在肝脏靶向临床干预中将性别作为生物学变量考虑的重要性。资助：盖茨基金会和华盛顿大学。
{"title":"Sex-based differences in Plasmodium infection in the control groups of controlled human malaria infection trials in malaria-naive populations in the USA and the Netherlands: a pooled analysis.","authors":"Caroline J Duncombe, Dianna E B Hergott, Weston Staubus, Mirte Balke-Buijs, James G Kublin, Patrick E Duffy, Sara A Healy, Angela Talley, Lisa Jackson, B Kim Lee Sim, Stephen L Hoffman, Robert W Sauerwein, Meta Roestenberg, Sean C Murphy","doi":"10.1016/j.lanmic.2025.101265","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101265","url":null,"abstract":"<p><strong>Background: </strong>Before infecting red blood cells and causing the clinical manifestations of malaria, the hepatotropic parasite Plasmodium falciparum completes a complex liver stage. Sex-based differences in pathogenesis by hepatotropic micro-organisms are well documented but unstudied for P falciparum in humans. We aimed to evaluate the effect of sex on the time to blood-stage positivity and initial blood-stage parasite densities as indicators of liver-stage dynamics and parasite replication.</p><p><strong>Methods: </strong>We conducted a pooled analysis of data from malaria-naive participants in control groups from controlled human malaria infection (CHMI) studies conducted between Jan 1, 2010, and Dec 31, 2024, in which samples were tested using Plasmodium 18S ribosomal RNA nucleic acid amplification tests (18S NAATs) at laboratories in Seattle (WA, USA) and Leiden (Netherlands). Participants aged 18-48 years were eligible for inclusion if they were in placebo or infectivity control groups in any CHMI study at the two laboratories and developed parasitaemia following CHMI. Patient demographics and 18S NAAT data were obtained from study leads at each centre and collated, standardised, and reviewed. Information on P falciparum strain, challenge route, and sampling schedule were extracted from study protocols or publications. The main outcome, time to positivity (TTP), was calculated as the study day of the first positive 18S NAAT of any density, measured during a 28-day monitoring period following CHMI. Using an interval-censored generalised gamma accelerated failure time model, we compared time to blood-stage positivity by sex, adjusting for challenge route, P falciparum strain, and study site. Odds of developing detectable infection after 7 days post-challenge was compared between male and female participants using a linear mixed-effects model adjusted for the same terms.</p><p><strong>Findings: </strong>Evaluable data were available from 102 control participants (48 [47%] female and 54 [53%] male) across 13 CHMI studies. There was moderate heterogeneity between studies (I<sup>2</sup>=31% [95% CI 0-57]). There were no notable demographic differences between male and female participants regarding age, challenge route, or strain. The mean time to first detectable parasitaemia was slightly longer in male participants (7·59 days [SD 1·15]) than in female participants (7·17 days [0·91]). Adjusted accelerated failure time analysis suggested that TTP occurred 8% later in male participants than female participants (time ratio 1·08 [1·03-1·16]). Male participants were significantly more likely than female participants to have a detectable infection after day 7 (19 [35%] of 54 male participants vs six [13%] of 48 female participants), with adjusted odds of delayed infection 5·20 times (95% CI 1·52-17·70) higher in male than female participants.</p><p><strong>Interpretation: </strong>Our findings suggest that male individuals are more like","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101265"},"PeriodicalIF":20.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1016/j.lanmic.2025.101317
Sanjeet Bagcchi
{"title":"Agreements to provide affordable lenacapavir.","authors":"Sanjeet Bagcchi","doi":"10.1016/j.lanmic.2025.101317","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101317","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101317"},"PeriodicalIF":20.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1016/j.lanmic.2026.101350
The Lancet Microbe
{"title":"Thank you to The Lancet Microbe statistical and peer reviewers in 2025.","authors":"The Lancet Microbe","doi":"10.1016/j.lanmic.2026.101350","DOIUrl":"https://doi.org/10.1016/j.lanmic.2026.101350","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101350"},"PeriodicalIF":20.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-09DOI: 10.1016/j.lanmic.2025.101319
Lita M Proctor
{"title":"Integrating microbiomes into One Health: insights from the 2025 One Health World Microbiome Partnership Summit.","authors":"Lita M Proctor","doi":"10.1016/j.lanmic.2025.101319","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101319","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101319"},"PeriodicalIF":20.4,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145960214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-09DOI: 10.1016/j.lanmic.2025.101288
Lloyd Czaplewski, Usha Lamichhane, Ralf Sudbrak, Alan Hennessy, Lesley A Ogilvie, Laura Jv Piddock
Antibacterial research and development (R&D) increasingly relies on public and philanthropic investments over private investments and on academia and small businesses over large pharmaceutical companies. To complement scientific reviews of the antibacterial pipeline, we examined global public and philanthropic funding for R&D of antibacterial therapeutics from 2017 to 2023 using data obtained from the Global AMR R&D Hub's Dynamic Dashboard. Projects were analysed considering funders and recipients, geographical location, R&D stage, mechanism of action, antibacterial class, clinical novelty, spectrum of activity, and alignment with the WHO bacterial priority pathogen list 2024. A total of US$2·51 billion was invested in antibacterial R&D by 130 funders, with a marked concentration among a small number of major sources. Funding peaked at $445 million in 2020 but declined by 18% to $363 million in 2023. Universities received the most awards, yet more than half of the total funding volume went to industry recipients. Investment broadly followed the WHO bacterial priority pathogens list, with Mycobacterium tuberculosis accounting for a fifth of the total. While the funding for clinical development remained stable, that for discovery and preclinical research declined. In this environment, public-private partnerships, such as Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator and the Global Antibiotic Research and Development Partnership, are crucial for attracting, channelling, and targeting funding; however, these partnerships alone will be insufficient. Enhanced strategic alignment in funding priorities and continued public and private investment will be essential for ensuring the discovery and development of effective new antibacterials meeting priority public health needs.
{"title":"An overview of global public and philanthropic investments into antibacterial therapeutics (2017-23).","authors":"Lloyd Czaplewski, Usha Lamichhane, Ralf Sudbrak, Alan Hennessy, Lesley A Ogilvie, Laura Jv Piddock","doi":"10.1016/j.lanmic.2025.101288","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101288","url":null,"abstract":"<p><p>Antibacterial research and development (R&D) increasingly relies on public and philanthropic investments over private investments and on academia and small businesses over large pharmaceutical companies. To complement scientific reviews of the antibacterial pipeline, we examined global public and philanthropic funding for R&D of antibacterial therapeutics from 2017 to 2023 using data obtained from the Global AMR R&D Hub's Dynamic Dashboard. Projects were analysed considering funders and recipients, geographical location, R&D stage, mechanism of action, antibacterial class, clinical novelty, spectrum of activity, and alignment with the WHO bacterial priority pathogen list 2024. A total of US$2·51 billion was invested in antibacterial R&D by 130 funders, with a marked concentration among a small number of major sources. Funding peaked at $445 million in 2020 but declined by 18% to $363 million in 2023. Universities received the most awards, yet more than half of the total funding volume went to industry recipients. Investment broadly followed the WHO bacterial priority pathogens list, with Mycobacterium tuberculosis accounting for a fifth of the total. While the funding for clinical development remained stable, that for discovery and preclinical research declined. In this environment, public-private partnerships, such as Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator and the Global Antibiotic Research and Development Partnership, are crucial for attracting, channelling, and targeting funding; however, these partnerships alone will be insufficient. Enhanced strategic alignment in funding priorities and continued public and private investment will be essential for ensuring the discovery and development of effective new antibacterials meeting priority public health needs.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101288"},"PeriodicalIF":20.4,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145960229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-07DOI: 10.1016/j.lanmic.2025.101334
Christoph Buchta, Jaap J van Hellemond, Karina Hellbert, Michael Neumaier, Christa M Cobbaert
{"title":"The disparaging requirements of Article 5.5 of the IVDR for laboratories.","authors":"Christoph Buchta, Jaap J van Hellemond, Karina Hellbert, Michael Neumaier, Christa M Cobbaert","doi":"10.1016/j.lanmic.2025.101334","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101334","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101334"},"PeriodicalIF":20.4,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1016/j.lanmic.2025.101332
Sema Mandal, Philippa C Matthews, Monica Desai, Matthew Hickman
{"title":"Towards the endgame: achieving elimination of viral hepatitis in England.","authors":"Sema Mandal, Philippa C Matthews, Monica Desai, Matthew Hickman","doi":"10.1016/j.lanmic.2025.101332","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101332","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101332"},"PeriodicalIF":20.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145946551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1016/j.lanmic.2025.101236
Marjorie J Gibbon, Natacha Couto, Keira Cozens, Samia Habib, Lauren Cowley, David M Aanensen, Jukka Corander, Harry A Thorpe, Marit A K Hetland, Davide Sassera, Cristina Merla, Marta Corbella, Carolina Ferrari, Katy M E Turner, Kwanrawee Sirikanchana, Punyawee Dulyayangkul, Nisanart Charoenlap, Visanu Thamlikitkul, Matthew B Avison, Edward J Feil
<p><strong>Background: </strong>Klebsiella pneumoniae is an important pathogen of humans and animals. In the past five years, increasing reports of convergent strains that carry both virulence factors and antimicrobial resistance genes (ARGs) have raised serious public health concerns. The aim of this study is to describe the global diversity of plasmids carrying iuc3 (a key virulence factor in K pneumoniae associated with pigs and clinical isolates) from diverse settings, and their role in the emergence of convergent strains through hybridisation with plasmids carrying ARGs.</p><p><strong>Methods: </strong>This population genomic analysis study was designed to describe both the global and local diversity of iuc3-carrying plasmids from diverse sources, and the co-occurrence of iuc3 with ARGs. We used all 4148 Klebsiella spp isolates from two large One-Health studies (SpARK, Italy, and OH-DART, Thailand), including 191 Klebsiella isolates from pigs, 635 from clinical isolates, 1040 from hospital and community carriage, and 2282 from other sources. Short-read sequencing of Klebsiella isolates was performed as part of the SpARK study. We sequenced Klebsiella isolates from the OH-DART (MicrobesNG, Birmingham, UK; HiSeq and NovaSeq, Illumina San Diego, CA, USA; GridION, Oxford Nanopore Technologies, Oxford, UK) and SpARK (MinION or GridION, Oxford Nanopore Technologies, Oxford, UK) studies. We also retrieved plasmid sequences carrying iuc3 from the National Centre for Biotechnology Information (NCBI). To ascertain the degree of diversity, evolutionary dynamics, and structuring across ecological and geographical axes, we detected ARGs and virulence loci, analysed clustering patterns and generated approximate maximum-likelihood phylogenetic trees.</p><p><strong>Findings: </strong>We identified 48 K pneumoniae isolates with iuc3 in the SpARK data and 79 in the OH-DART data. Three (2·4%) of these 127 isolates were from clinical sources, 73 (57·5%) were from pig or pork meat. iuc3 isolates corresponded to multiple (n=47) host sequence types (STs), with ST35, ST45, ST881, ST25, and ST967 harbouring iuc3 in both datasets. We generated hybrid assemblies for 44 (SpARK) and 36 (OH-DART) isolates, plus a single iuc3 isolate from Germany. 53 (65·4%) of these isolates were from pigs, three (3·7%) from clinical sources, and 25 (30·9%) from other sources. There were an additional 48 iuc3 positive isolates from our collections for which only short read data was available. A single iuc3-positive Klebsiella oxytoca isolate from a pig farm was detected in the SpARK data, which was also sequenced. We identified 330 iuc3-positive isolates and 58 iuc3-carrying plasmid assemblies from NCBI, of which 83 (21·4%) were from clinical sources, 120 from pigs (30·9%), and 185 (47·7%) from other sources or of unknown provenance. These isolates were from K pneumoniae except two isolates of Klebsiella quasipneumoniae subsp similipneumoniae and one of Enterobacter hormaechei. The combi
{"title":"Convergence and global molecular epidemiology of Klebsiella pneumoniae plasmids harbouring the iuc3 virulence locus: a population genomic analysis.","authors":"Marjorie J Gibbon, Natacha Couto, Keira Cozens, Samia Habib, Lauren Cowley, David M Aanensen, Jukka Corander, Harry A Thorpe, Marit A K Hetland, Davide Sassera, Cristina Merla, Marta Corbella, Carolina Ferrari, Katy M E Turner, Kwanrawee Sirikanchana, Punyawee Dulyayangkul, Nisanart Charoenlap, Visanu Thamlikitkul, Matthew B Avison, Edward J Feil","doi":"10.1016/j.lanmic.2025.101236","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101236","url":null,"abstract":"<p><strong>Background: </strong>Klebsiella pneumoniae is an important pathogen of humans and animals. In the past five years, increasing reports of convergent strains that carry both virulence factors and antimicrobial resistance genes (ARGs) have raised serious public health concerns. The aim of this study is to describe the global diversity of plasmids carrying iuc3 (a key virulence factor in K pneumoniae associated with pigs and clinical isolates) from diverse settings, and their role in the emergence of convergent strains through hybridisation with plasmids carrying ARGs.</p><p><strong>Methods: </strong>This population genomic analysis study was designed to describe both the global and local diversity of iuc3-carrying plasmids from diverse sources, and the co-occurrence of iuc3 with ARGs. We used all 4148 Klebsiella spp isolates from two large One-Health studies (SpARK, Italy, and OH-DART, Thailand), including 191 Klebsiella isolates from pigs, 635 from clinical isolates, 1040 from hospital and community carriage, and 2282 from other sources. Short-read sequencing of Klebsiella isolates was performed as part of the SpARK study. We sequenced Klebsiella isolates from the OH-DART (MicrobesNG, Birmingham, UK; HiSeq and NovaSeq, Illumina San Diego, CA, USA; GridION, Oxford Nanopore Technologies, Oxford, UK) and SpARK (MinION or GridION, Oxford Nanopore Technologies, Oxford, UK) studies. We also retrieved plasmid sequences carrying iuc3 from the National Centre for Biotechnology Information (NCBI). To ascertain the degree of diversity, evolutionary dynamics, and structuring across ecological and geographical axes, we detected ARGs and virulence loci, analysed clustering patterns and generated approximate maximum-likelihood phylogenetic trees.</p><p><strong>Findings: </strong>We identified 48 K pneumoniae isolates with iuc3 in the SpARK data and 79 in the OH-DART data. Three (2·4%) of these 127 isolates were from clinical sources, 73 (57·5%) were from pig or pork meat. iuc3 isolates corresponded to multiple (n=47) host sequence types (STs), with ST35, ST45, ST881, ST25, and ST967 harbouring iuc3 in both datasets. We generated hybrid assemblies for 44 (SpARK) and 36 (OH-DART) isolates, plus a single iuc3 isolate from Germany. 53 (65·4%) of these isolates were from pigs, three (3·7%) from clinical sources, and 25 (30·9%) from other sources. There were an additional 48 iuc3 positive isolates from our collections for which only short read data was available. A single iuc3-positive Klebsiella oxytoca isolate from a pig farm was detected in the SpARK data, which was also sequenced. We identified 330 iuc3-positive isolates and 58 iuc3-carrying plasmid assemblies from NCBI, of which 83 (21·4%) were from clinical sources, 120 from pigs (30·9%), and 185 (47·7%) from other sources or of unknown provenance. These isolates were from K pneumoniae except two isolates of Klebsiella quasipneumoniae subsp similipneumoniae and one of Enterobacter hormaechei. The combi","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101236"},"PeriodicalIF":20.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145946562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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