Pub Date : 2025-12-01DOI: 10.1016/j.lanmic.2025.101200
Chao Yan MD , Shanwei Tong MS , Yarong Wu PhD , Yujie Chen MBBS , Xinyu Jia MBBS , Yan Guo PhD , Mengnan Cui MS , Guangqian Pei MS , Zuming Zhang BSc , Hao Zhou BAdmin , Kai Mu MS , Xue Ren MS , Bing Du MS , Hanqing Zhao MBBS , Yanling Feng MBBS , Jinghua Cui MD , Yuyan Xia MBBS , Zhen Wang MS , Yu Sun MS , Prof Linqing Zhao MD , Prof Yujun Cui PhD
Background
After a prolonged period of low detection rates, Mycoplasma pneumoniae resurged in China, during September to November, 2023, raising global concern. This study aims to gain a better understanding of the genetic mechanisms underlying the 2023 increase in cases and the evolutionary dynamics of the epidemic populations, which has been previously hampered due to limited genomic data of this pathogen.
Methods
We sequenced 685 M pneumoniae isolates, including 248 isolates from 11 Chinese provinces and municipalities in 2023 and 437 isolates from Beijing (2013–22). By analysing these isolates and 436 publicly global sequences, we reconstructed the pathogen’s evolutionary history using time-calibrated phylogenies and effective population size inference. We investigated potential genomic variations contributing to the 2023 resurgence through genome-wide association study and conducted phylogeographic analysis of the 2023 isolates across China.
Findings
Two macrolide-resistant epidemic clusters (T1-2-EC1 and T2-2-EC2) were responsible for the 2023 resurgence in China. Both clusters, having acquired the 23S ribosomal RNA A2063G mutation conferring macrolide resistance, emerged in approximately 1997 and 2014, respectively, and subsequently outcompeted their predecessor populations. This coincided with China’s large-scale adoption of azithromycin for paediatric community-acquired pneumonia around the early 2000s. Aside from macrolide resistance, T1-2-EC1 independently acquired 17 clade-specific mutations and T2-2-EC2 four clade-specific mutations, which could further explain their increased competitiveness. Whole-genome analysis revealed no resurgence-specific mutations in the 2023 isolates. Phylogeographic analysis showed rapid mixing of T1-2-EC1 isolates between different sampled regions within China.
Interpretation
Our study provides evidence that the 2023 resurgence in China is a continuation of the pre-COVID epidemic, rather than emergence of novel variants. The high prevalence of macrolide resistance and rapid intranational spread emphasise the urgent need for enhanced global surveillance of this pathogen.
Funding
National Key Research and Development Program of China, National Natural Science Foundation of China for Key Programs of China Grants, and Beijing High-Level Public Health Technical Talent Project.
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Pub Date : 2025-12-01DOI: 10.1016/j.lanmic.2025.101306
The Lancet Microbe
{"title":"Neglected tropical diseases: golden age of elimination?","authors":"The Lancet Microbe","doi":"10.1016/j.lanmic.2025.101306","DOIUrl":"10.1016/j.lanmic.2025.101306","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 12","pages":"Article 101306"},"PeriodicalIF":20.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145655843","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 : 2025-12-01DOI: 10.1016/j.lanmic.2025.101210
Ruan Spies MSc , Prof Derrick W Crook FRCPath , Prof Timothy E A Peto FRCP , Philip W Fowler PhD , Robert Turner PhD , Hieu Thai BE , James A Watson DPhil , Timothy M Walker DPhil
<div><h3>Background</h3><div>Reliance on complex, custom-built bioinformatics pipelines is a barrier to the implementation of whole-genome sequencing (WGS) of <em>Mycobacterium tuberculosis</em> in high-burden settings in some low-income and middle-income countries (LMICs). Automated analysis pipelines could address this inequity in access to WGS-based diagnostics and surveillance. This study aimed to systematically evaluate the performance and usability of publicly available WGS pipelines for <em>M tuberculosis</em>.</div></div><div><h3>Methods</h3><div>We identified automated <em>M tuberculosis</em> WGS analysis pipelines through searches of PubMed and GitHub from database inception up to Aug 31, 2024. Accuracy, cost, accessibility, and scalability were assessed for each pipeline. We evaluated the accuracy of genotypic drug susceptibility testing (gDST) using publicly available sequences with phenotypic susceptibility data for 12 antituberculosis drugs. We estimated pooled sensitivity and specificity for each pipeline, across all drugs, by conducting a bivariate meta-analysis, with random effects representing between-drug variability. Lineage classifications were compared, and a previously epidemiologically well-characterised dataset was used to compare measures of genomic relatedness.</div></div><div><h3>Findings</h3><div>Among 28 candidate pipelines, 16 were excluded as they were unmaintained and inexecutable. 12 pipelines (11 compatible with Illumina and four compatible with Nanopore), all free to use, were included for evaluation. Six pipelines processed and stored data remotely, but for five of these six, scalability was limited by the need to upload sequences through web portals. For local processing pipelines, scalability was dependent on substantial local computational resources, data storage capacity, and command-line interfaces that limited user-friendliness. Only one of six remote-processing pipelines removed human DNA sequences before server upload. gDST was similarly accurate across ten of 11 Illumina-compatible pipelines and three of four Nanopore-compatible pipelines. All pipelines classified the main lineages consistently, although there were differences at sublineage resolution. Outputs from three of four pipelines reporting genomic relatedness were compatible with commonly cited single nucleotide polymorphism difference thresholds.</div></div><div><h3>Interpretation</h3><div>Numerous automated analysis pipelines capable of enhancing equity in <em>M tuberculosis</em> WGS are available. Given the overall similarities between the pipelines evaluated in this study in terms of gDST performance, lineage classification, and genomic relatedness inference, non-functional attributes such as availability, accessibility, scalability, and privacy could represent the point of difference for prospective users in LMICs with a high burden of tuberculosis.</div></div><div><h3>Funding</h3><div>The Rhodes Trust, Wellcome, Ellison Institute of Tec
{"title":"Evaluating 12 automated, whole-genome sequencing analysis pipelines for Mycobacterium tuberculosis complex: a comparative study","authors":"Ruan Spies MSc , Prof Derrick W Crook FRCPath , Prof Timothy E A Peto FRCP , Philip W Fowler PhD , Robert Turner PhD , Hieu Thai BE , James A Watson DPhil , Timothy M Walker DPhil","doi":"10.1016/j.lanmic.2025.101210","DOIUrl":"10.1016/j.lanmic.2025.101210","url":null,"abstract":"<div><h3>Background</h3><div>Reliance on complex, custom-built bioinformatics pipelines is a barrier to the implementation of whole-genome sequencing (WGS) of <em>Mycobacterium tuberculosis</em> in high-burden settings in some low-income and middle-income countries (LMICs). Automated analysis pipelines could address this inequity in access to WGS-based diagnostics and surveillance. This study aimed to systematically evaluate the performance and usability of publicly available WGS pipelines for <em>M tuberculosis</em>.</div></div><div><h3>Methods</h3><div>We identified automated <em>M tuberculosis</em> WGS analysis pipelines through searches of PubMed and GitHub from database inception up to Aug 31, 2024. Accuracy, cost, accessibility, and scalability were assessed for each pipeline. We evaluated the accuracy of genotypic drug susceptibility testing (gDST) using publicly available sequences with phenotypic susceptibility data for 12 antituberculosis drugs. We estimated pooled sensitivity and specificity for each pipeline, across all drugs, by conducting a bivariate meta-analysis, with random effects representing between-drug variability. Lineage classifications were compared, and a previously epidemiologically well-characterised dataset was used to compare measures of genomic relatedness.</div></div><div><h3>Findings</h3><div>Among 28 candidate pipelines, 16 were excluded as they were unmaintained and inexecutable. 12 pipelines (11 compatible with Illumina and four compatible with Nanopore), all free to use, were included for evaluation. Six pipelines processed and stored data remotely, but for five of these six, scalability was limited by the need to upload sequences through web portals. For local processing pipelines, scalability was dependent on substantial local computational resources, data storage capacity, and command-line interfaces that limited user-friendliness. Only one of six remote-processing pipelines removed human DNA sequences before server upload. gDST was similarly accurate across ten of 11 Illumina-compatible pipelines and three of four Nanopore-compatible pipelines. All pipelines classified the main lineages consistently, although there were differences at sublineage resolution. Outputs from three of four pipelines reporting genomic relatedness were compatible with commonly cited single nucleotide polymorphism difference thresholds.</div></div><div><h3>Interpretation</h3><div>Numerous automated analysis pipelines capable of enhancing equity in <em>M tuberculosis</em> WGS are available. Given the overall similarities between the pipelines evaluated in this study in terms of gDST performance, lineage classification, and genomic relatedness inference, non-functional attributes such as availability, accessibility, scalability, and privacy could represent the point of difference for prospective users in LMICs with a high burden of tuberculosis.</div></div><div><h3>Funding</h3><div>The Rhodes Trust, Wellcome, Ellison Institute of Tec","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 12","pages":"Article 101210"},"PeriodicalIF":20.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356400","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 : 2025-12-01DOI: 10.1016/j.lanmic.2025.101211
Diane Gbesemete PhD , Maheshi N Ramasamy PhD , Muktar Ibrahim PhD , Alison R Hill PhD , Lucy Raud BSc , Daniela M Ferreira PhD , Jonathan Guy BSc , Adam P Dale PhD , Jay R Laver PhD , Tyween Coutinho MSc , Saul N Faust PhD , Thomas A N Reed MD , Gavin Babbage MPhil , Lisa Weissfeld PhD , Wei Lang PhD , Camille Locht PhD , Vivek Samal MD , Peter Goldstein MS , Ken Solovay MS , Keith Rubin MD , Robert C Read MD
<div><h3>Background</h3><div>Pertussis is a severe respiratory disease caused by <em>Bordetella pertussis</em>. Although vaccines prevent disease for a limited duration, they do not prevent infection and transmission. We aimed to assess the safety and efficacy of BPZE1 at preventing or substantially reducing colonisation by virulent <em>B pertussis</em> using a robust controlled human infection model.</div></div><div><h3>Methods</h3><div>This randomised, placebo-controlled, phase 2b trial was conducted at University Hospital Southampton and University of Oxford in the UK. Eligible participants were healthy adults aged 18–50 years, who complied with the protocol, refrained from smoking and nasal sprays, and were fully vaccinated against SARS-CoV-2. Exclusion criteria were pertussis vaccination or illness (<5 years), baseline anti-pertussis toxin serum IgG (>20 International Units [IU]/mL) or anti-pertactin serum IgG (>30 IU/mL) concentrations, and a positive SARS-CoV-2 test. Participants were randomly assigned (1:1), using permuted blocks with a block size of four, to receive an intranasal dose of 10<sup>9</sup> colony-forming units (CFU) of BPZE1 or placebo (lyophilised buffer) and were challenged 60–120 days later with 10<sup>5</sup> CFU virulent <em>B pertussis</em>. Masked staff administered the study vaccine. Nasal mucosal secretion and blood samples were collected. The primary outcome was negative <em>B pertussis</em> cultures of nasal washes at days 9, 11, and 14 after virulent challenge in the modified intention-to-treat (mITT; defined as all participants randomly assigned to treatment who were vaccinated, challenged, and had at least one culture result at day 9, 11, or 14 post-challenge) and per protocol adequate inoculum populations (defined as all participants in the mITT population who received a challenge inoculum equal to or higher than the target (≥0·5 × 10<sup>5</sup> CFU; sensitivity analysis). This trial is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT05461131</span><svg><path></path></svg></span>.</div></div><div><h3>Findings</h3><div>Between June 23, 2022, and Oct 26, 2023, 141 participants were assessed for eligibility, of whom 88 were ineligible and 53 were randomly assigned (26 to the BPZE1 group and 27 to the placebo group). 26 (49%) participants were male and 27 (51%) were female, with a mean age of 30·42 years (SD 8·49). Participants self-identified as White (42 [79%]), Black (six [11%]), or Asian (five [9%]). Five (9%) participants did not receive virulent challenge and two (4%) were lost to follow-up before virulent challenge. 46 (87%) participants received virulent challenge at 60–120 days (24 in the BPZE1 group <em>vs</em> 22 in the placebo group). One in the BPZE1 group withdrew consent and one in the placebo group was not evaluable due to COVID-19. 44 (83%) completed the challenge trial unit stay (23 [88%] <em>vs</em> 21 [78%]). 24 (92%) participants i
{"title":"Efficacy, immunogenicity, and safety of the live attenuated nasal pertussis vaccine, BPZE1, in the UK: a randomised, placebo-controlled, phase 2b trial using a controlled human infection model with virulent Bordetella pertussis","authors":"Diane Gbesemete PhD , Maheshi N Ramasamy PhD , Muktar Ibrahim PhD , Alison R Hill PhD , Lucy Raud BSc , Daniela M Ferreira PhD , Jonathan Guy BSc , Adam P Dale PhD , Jay R Laver PhD , Tyween Coutinho MSc , Saul N Faust PhD , Thomas A N Reed MD , Gavin Babbage MPhil , Lisa Weissfeld PhD , Wei Lang PhD , Camille Locht PhD , Vivek Samal MD , Peter Goldstein MS , Ken Solovay MS , Keith Rubin MD , Robert C Read MD","doi":"10.1016/j.lanmic.2025.101211","DOIUrl":"10.1016/j.lanmic.2025.101211","url":null,"abstract":"<div><h3>Background</h3><div>Pertussis is a severe respiratory disease caused by <em>Bordetella pertussis</em>. Although vaccines prevent disease for a limited duration, they do not prevent infection and transmission. We aimed to assess the safety and efficacy of BPZE1 at preventing or substantially reducing colonisation by virulent <em>B pertussis</em> using a robust controlled human infection model.</div></div><div><h3>Methods</h3><div>This randomised, placebo-controlled, phase 2b trial was conducted at University Hospital Southampton and University of Oxford in the UK. Eligible participants were healthy adults aged 18–50 years, who complied with the protocol, refrained from smoking and nasal sprays, and were fully vaccinated against SARS-CoV-2. Exclusion criteria were pertussis vaccination or illness (<5 years), baseline anti-pertussis toxin serum IgG (>20 International Units [IU]/mL) or anti-pertactin serum IgG (>30 IU/mL) concentrations, and a positive SARS-CoV-2 test. Participants were randomly assigned (1:1), using permuted blocks with a block size of four, to receive an intranasal dose of 10<sup>9</sup> colony-forming units (CFU) of BPZE1 or placebo (lyophilised buffer) and were challenged 60–120 days later with 10<sup>5</sup> CFU virulent <em>B pertussis</em>. Masked staff administered the study vaccine. Nasal mucosal secretion and blood samples were collected. The primary outcome was negative <em>B pertussis</em> cultures of nasal washes at days 9, 11, and 14 after virulent challenge in the modified intention-to-treat (mITT; defined as all participants randomly assigned to treatment who were vaccinated, challenged, and had at least one culture result at day 9, 11, or 14 post-challenge) and per protocol adequate inoculum populations (defined as all participants in the mITT population who received a challenge inoculum equal to or higher than the target (≥0·5 × 10<sup>5</sup> CFU; sensitivity analysis). This trial is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT05461131</span><svg><path></path></svg></span>.</div></div><div><h3>Findings</h3><div>Between June 23, 2022, and Oct 26, 2023, 141 participants were assessed for eligibility, of whom 88 were ineligible and 53 were randomly assigned (26 to the BPZE1 group and 27 to the placebo group). 26 (49%) participants were male and 27 (51%) were female, with a mean age of 30·42 years (SD 8·49). Participants self-identified as White (42 [79%]), Black (six [11%]), or Asian (five [9%]). Five (9%) participants did not receive virulent challenge and two (4%) were lost to follow-up before virulent challenge. 46 (87%) participants received virulent challenge at 60–120 days (24 in the BPZE1 group <em>vs</em> 22 in the placebo group). One in the BPZE1 group withdrew consent and one in the placebo group was not evaluable due to COVID-19. 44 (83%) completed the challenge trial unit stay (23 [88%] <em>vs</em> 21 [78%]). 24 (92%) participants i","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 12","pages":"Article 101211"},"PeriodicalIF":20.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679007","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 : 2025-11-24DOI: 10.1016/j.lanmic.2025.101290
T Jacob John, Dhanya Dharmapalan, Robert Steinglass, Norbert Hirschhorn
{"title":"Polio outbreaks due to vaccine-derived viruses demand a re-definition of vaccine safety.","authors":"T Jacob John, Dhanya Dharmapalan, Robert Steinglass, Norbert Hirschhorn","doi":"10.1016/j.lanmic.2025.101290","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101290","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101290"},"PeriodicalIF":20.4,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145641382","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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