Pub Date : 2026-01-01DOI: 10.1016/j.lanmic.2025.101224
Patrick Musicha PhD , Mathew A Beale PhD , Derek Cocker PhD , Fiona A Oruru MPH , Allan Zuza MSc , Chifundo Salifu MSc , George Katende MSc , Sylvia Nanono MSc , Fred Isaasi MSc , Kondwani Chidziwisano PhD , Lawrence Mugisha PhD , Henry Kajumbula MMed , David Musoke PhD , Prof Tracy Morse PhD , Shevin T Jacob MD , Prof Nicholas A Feasey PhD , Prof Nicholas R Thomson PhD
<div><h3>Background</h3><div>The One Health paradigm considers interdependence of human, animal, and environmental health. However, there is little evidence from high-income countries to support the importance of a One Health approach to addressing spread of antimicrobial resistance (AMR). Given AMR is a global threat, understanding how the close interactions of humans with animals and the environment in low-income settings affect the spread of AMR is important. We aimed to investigate diversity and transmission of extended spectrum β-lactamase (ESBL)-producing <em>Escherichia coli</em> across household-linked One Health compartments using genomic data.</div></div><div><h3>Methods</h3><div>We sequenced whole genomes of ESBL-producing <em>E coli</em> isolates from humans, animals, and the environment from a prospective, longitudinal cohort study conducted in Malawi (April 29, 2019, to Dec 3, 2020) and Uganda (July 16, 2020, to Aug 6, 2021). In the cohort study, 259 households were enrolled at baseline in Malawi and 92 in Uganda from a mix of urban, peri-urban, and rural areas. Households were followed up at months 1, 3, and 6 in Malawi and at months 1, 2, and 4 in Uganda. Samples collected at each visit included human and animal stool, environmental samples from hand-contact areas, food, and water, and broader environmental samples such as river water. Samples were cultured in buffered peptone water and then ESBL chromogenic agar to isolate ESBL-producing <em>E coli</em>. ESBL-producing <em>E coli</em> isolates underwent whole-genome sequencing. We performed phylogenetic analyses, and in-silico multi-locus sequence typing, characterised AMR determinants and linked genotypes with sample location, ecological source, and other covariates. We performed fine-scale single nucleotide polymorphism (SNP) and network analysis to infer strain and plasmid transmission across ecological compartments. The primary outcome was colonisation with ESBL-producing <em>E coli</em>. Secondary outcomes were genomic clusters and ESBL genomic determinants within and between One Health compartments.</div></div><div><h3>Findings</h3><div>We found high diversity of ESBL-producing <em>E coli</em>, with 170 sequence types and 166 genomic clusters identified from 2344 genomes, including 1814 genomes from Malawi (907 human, 221 animal, and 686 environmental) and 530 genomes from Uganda (380 human, 147 animal, and three environmental). Sequence type (ST)131 dominated in Malawi (209 [11·5%] of 1814 genomes), and ST10 dominated in Uganda (45 [8·5%] of 530 genomes). Common ESBL genes <em>bla</em><sub>CTX−M−15</sub> (1604 [68·4%] of 2344 genomes) and <em>bla</em><sub>CTX−M−27</sub> (336 [14·3%] of 2344 genomes) were carried on a complex network of 55 and 30 different plasmids. This diversity of plasmids presented multiple pathways for dissemination and revealed high force of selection. Phylogenetic analyses revealed common intermixing of isolates between humans, animals, and the envir
{"title":"Transmission of extended spectrum β-lactamase-producing Escherichia coli and antimicrobial resistance gene flow across One Health compartments in eastern Africa: a whole-genome sequence analysis from a prospective cohort study","authors":"Patrick Musicha PhD , Mathew A Beale PhD , Derek Cocker PhD , Fiona A Oruru MPH , Allan Zuza MSc , Chifundo Salifu MSc , George Katende MSc , Sylvia Nanono MSc , Fred Isaasi MSc , Kondwani Chidziwisano PhD , Lawrence Mugisha PhD , Henry Kajumbula MMed , David Musoke PhD , Prof Tracy Morse PhD , Shevin T Jacob MD , Prof Nicholas A Feasey PhD , Prof Nicholas R Thomson PhD","doi":"10.1016/j.lanmic.2025.101224","DOIUrl":"10.1016/j.lanmic.2025.101224","url":null,"abstract":"<div><h3>Background</h3><div>The One Health paradigm considers interdependence of human, animal, and environmental health. However, there is little evidence from high-income countries to support the importance of a One Health approach to addressing spread of antimicrobial resistance (AMR). Given AMR is a global threat, understanding how the close interactions of humans with animals and the environment in low-income settings affect the spread of AMR is important. We aimed to investigate diversity and transmission of extended spectrum β-lactamase (ESBL)-producing <em>Escherichia coli</em> across household-linked One Health compartments using genomic data.</div></div><div><h3>Methods</h3><div>We sequenced whole genomes of ESBL-producing <em>E coli</em> isolates from humans, animals, and the environment from a prospective, longitudinal cohort study conducted in Malawi (April 29, 2019, to Dec 3, 2020) and Uganda (July 16, 2020, to Aug 6, 2021). In the cohort study, 259 households were enrolled at baseline in Malawi and 92 in Uganda from a mix of urban, peri-urban, and rural areas. Households were followed up at months 1, 3, and 6 in Malawi and at months 1, 2, and 4 in Uganda. Samples collected at each visit included human and animal stool, environmental samples from hand-contact areas, food, and water, and broader environmental samples such as river water. Samples were cultured in buffered peptone water and then ESBL chromogenic agar to isolate ESBL-producing <em>E coli</em>. ESBL-producing <em>E coli</em> isolates underwent whole-genome sequencing. We performed phylogenetic analyses, and in-silico multi-locus sequence typing, characterised AMR determinants and linked genotypes with sample location, ecological source, and other covariates. We performed fine-scale single nucleotide polymorphism (SNP) and network analysis to infer strain and plasmid transmission across ecological compartments. The primary outcome was colonisation with ESBL-producing <em>E coli</em>. Secondary outcomes were genomic clusters and ESBL genomic determinants within and between One Health compartments.</div></div><div><h3>Findings</h3><div>We found high diversity of ESBL-producing <em>E coli</em>, with 170 sequence types and 166 genomic clusters identified from 2344 genomes, including 1814 genomes from Malawi (907 human, 221 animal, and 686 environmental) and 530 genomes from Uganda (380 human, 147 animal, and three environmental). Sequence type (ST)131 dominated in Malawi (209 [11·5%] of 1814 genomes), and ST10 dominated in Uganda (45 [8·5%] of 530 genomes). Common ESBL genes <em>bla</em><sub>CTX−M−15</sub> (1604 [68·4%] of 2344 genomes) and <em>bla</em><sub>CTX−M−27</sub> (336 [14·3%] of 2344 genomes) were carried on a complex network of 55 and 30 different plasmids. This diversity of plasmids presented multiple pathways for dissemination and revealed high force of selection. Phylogenetic analyses revealed common intermixing of isolates between humans, animals, and the envir","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101224"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145641355","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 : 2026-01-01DOI: 10.1016/j.lanmic.2025.101304
Paul Adepoju
{"title":"A new chapter for pathogen surveillance in Africa","authors":"Paul Adepoju","doi":"10.1016/j.lanmic.2025.101304","DOIUrl":"10.1016/j.lanmic.2025.101304","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101304"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696506","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 : 2026-01-01DOI: 10.1016/j.lanmic.2025.101266
Mitchell Leus MPH , Chukwunomso E Osakwe PhD , Danjuma Adda MPH , Manal El-Sayed PhD , Jessica Hicks BComm , Yasmin Ibrahim PhD , Philippa C Matthews PhD , Nicaise Ndembi PhD , Theobald Owusu-Ansah MS , Catherine Wendy Spearman PhD , Mark W Sonderup MMed , John Ward MD , Robin Schaefer PhD , Veronica Miller PhD
Africa bears a disproportionate burden of hepatitis B virus (HBV) infection, with 68 million chronically infected individuals and 65% of global new infections. However, only 18 (1%) of 1804 global HBV clinical trials have been conducted in Africa, limiting the generalisability of therapeutic findings. The HBV arm of the Forum for Collaborative Research convened a series of multistakeholder discussions between 2023 and 2024, to identify gaps in clinical research and identify solutions. This Personal View synthesises insights from these convenings, highlighting key barriers and potential solutions to the disparities in HBV clinical research. Barriers include inadequate funding, insufficient political will, low community awareness, and logistical challenges due to health-care infrastructure and regulatory systems. This Personal View emphasises the urgent need for African-led research, given region-specific factors such as diverse HBV genotypes and co-infections with HIV and hepatitis D virus. We propose solutions, including strengthening regulatory frameworks, leveraging existing research networks, establishing industry funding consortiums, and advocating for increased investment.
{"title":"Strengthening hepatitis B virus clinical research in Africa: the need for multistakeholder collaboration, funding, and political will","authors":"Mitchell Leus MPH , Chukwunomso E Osakwe PhD , Danjuma Adda MPH , Manal El-Sayed PhD , Jessica Hicks BComm , Yasmin Ibrahim PhD , Philippa C Matthews PhD , Nicaise Ndembi PhD , Theobald Owusu-Ansah MS , Catherine Wendy Spearman PhD , Mark W Sonderup MMed , John Ward MD , Robin Schaefer PhD , Veronica Miller PhD","doi":"10.1016/j.lanmic.2025.101266","DOIUrl":"10.1016/j.lanmic.2025.101266","url":null,"abstract":"<div><div>Africa bears a disproportionate burden of hepatitis B virus (HBV) infection, with 68 million chronically infected individuals and 65% of global new infections. However, only 18 (1%) of 1804 global HBV clinical trials have been conducted in Africa, limiting the generalisability of therapeutic findings. The HBV arm of the Forum for Collaborative Research convened a series of multistakeholder discussions between 2023 and 2024, to identify gaps in clinical research and identify solutions. This Personal View synthesises insights from these convenings, highlighting key barriers and potential solutions to the disparities in HBV clinical research. Barriers include inadequate funding, insufficient political will, low community awareness, and logistical challenges due to health-care infrastructure and regulatory systems. This Personal View emphasises the urgent need for African-led research, given region-specific factors such as diverse HBV genotypes and co-infections with HIV and hepatitis D virus. We propose solutions, including strengthening regulatory frameworks, leveraging existing research networks, establishing industry funding consortiums, and advocating for increased investment.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101266"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846858","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 : 2026-01-01DOI: 10.1016/j.lanmic.2025.101217
Francisco José Martínez-Martínez MSc , Álvaro Chiner-Oms PhD , Victoria Furió PhD
<div><h3>Background</h3><div>Rising antimicrobial resistance of <em>Helicobacter pylori</em> is a public health challenge. Genomic-based susceptibility testing allows for the identification of resistance-associated mutations, complementing conventional diagnostics and advancing towards pathogen-based personalised therapies. Our study aimed to identify genes and mutations involved in antimicrobial resistance in <em>H pylori</em> and evaluate the extent to which these markers can be used as predictors of phenotypic resistance against clarithromycin and levofloxacin.</div></div><div><h3>Methods</h3><div>In this retrospective phenotypic and genotypic observational study, we included 1011 <em>H pylori</em> whole-genome sequences and strains of known geographical origin from the <em>H pylori</em> Genome Project (<em>Hp</em>GP) collection. We performed phenotypic clarithromycin and levofloxacin susceptibility testing on a subset of 419 <em>Hp</em>GP strains using Etest at a centralised laboratory. A genomic analysis was conducted to identify <em>23S rRNA</em> and <em>gyrA</em> variants and build a curated catalogue of mutations associated with resistance to clarithromycin (ie, <em>23S rRNA</em> 2142A→G, 2142A→C, and 2143A→G) and levofloxacin (ie, <em>gyrA</em> A88V or A88P, N87K or N87I, and D91G, D91N, or D91Y). Genotype–phenotype concordance was assessed to estimate sensitivity and specificity, and the curated catalogue of resistance-associated mutations was applied to the complete <em>Hp</em>GP set. Region-specific prevalence of resistance-associated mutations was calculated for a combined dataset including the <em>Hp</em>GP genomes and 768 whole-genome sequences retrieved from the US National Center for Biotechnology Information Sequence Read Archive repository. Associations between resistance genotypes, <em>H pylori</em> subpopulations, and minimum inhibitory concentrations (MICs) were tested.</div></div><div><h3>Findings</h3><div>Clarithromycin-resistant and levofloxacin-resistant <em>Hp</em>GP strains were estimated with a sensitivity and specificity of 100%, with all confidence intervals ranging from 96% to 100%. The combined analysis (n=1779) found the highest prevalence of clarithromycin resistance in the western Pacific region (173 [51·2%] of 338 in southeast Asia and 75 [29·8%] of 252 in eastern Asia), north African region (seven [38·9%] of 18), and western Asian region (12 [31·6%] of 38), whereas the highest prevalence of levofloxacin resistance was found in south Asia (14 [51·85%] of 27), Central America (48 [38·7%] of 124), eastern Europe (four [36·4%] of 11), and southern Africa (three [33·3%] of nine). Similarly, <em>23S rRNA</em> and <em>gyrA</em> genotypes are variable across <em>H pylori</em> subpopulations. MIC values changed depending on the specific mutation in <em>23S rRNA</em> (mean clarithromycin MIC 24·61 mg/L [95% CI 12·27–36·96] for 2143A→G and 142·25 mg/L [95% CI 77·88–206·61] for 2142A→G) and <em>gyrA</em> (mean levofloxac
{"title":"Genomic determinants of antibiotic resistance for Helicobacter pylori treatment: a retrospective phenotypic and genotypic observational study","authors":"Francisco José Martínez-Martínez MSc , Álvaro Chiner-Oms PhD , Victoria Furió PhD","doi":"10.1016/j.lanmic.2025.101217","DOIUrl":"10.1016/j.lanmic.2025.101217","url":null,"abstract":"<div><h3>Background</h3><div>Rising antimicrobial resistance of <em>Helicobacter pylori</em> is a public health challenge. Genomic-based susceptibility testing allows for the identification of resistance-associated mutations, complementing conventional diagnostics and advancing towards pathogen-based personalised therapies. Our study aimed to identify genes and mutations involved in antimicrobial resistance in <em>H pylori</em> and evaluate the extent to which these markers can be used as predictors of phenotypic resistance against clarithromycin and levofloxacin.</div></div><div><h3>Methods</h3><div>In this retrospective phenotypic and genotypic observational study, we included 1011 <em>H pylori</em> whole-genome sequences and strains of known geographical origin from the <em>H pylori</em> Genome Project (<em>Hp</em>GP) collection. We performed phenotypic clarithromycin and levofloxacin susceptibility testing on a subset of 419 <em>Hp</em>GP strains using Etest at a centralised laboratory. A genomic analysis was conducted to identify <em>23S rRNA</em> and <em>gyrA</em> variants and build a curated catalogue of mutations associated with resistance to clarithromycin (ie, <em>23S rRNA</em> 2142A→G, 2142A→C, and 2143A→G) and levofloxacin (ie, <em>gyrA</em> A88V or A88P, N87K or N87I, and D91G, D91N, or D91Y). Genotype–phenotype concordance was assessed to estimate sensitivity and specificity, and the curated catalogue of resistance-associated mutations was applied to the complete <em>Hp</em>GP set. Region-specific prevalence of resistance-associated mutations was calculated for a combined dataset including the <em>Hp</em>GP genomes and 768 whole-genome sequences retrieved from the US National Center for Biotechnology Information Sequence Read Archive repository. Associations between resistance genotypes, <em>H pylori</em> subpopulations, and minimum inhibitory concentrations (MICs) were tested.</div></div><div><h3>Findings</h3><div>Clarithromycin-resistant and levofloxacin-resistant <em>Hp</em>GP strains were estimated with a sensitivity and specificity of 100%, with all confidence intervals ranging from 96% to 100%. The combined analysis (n=1779) found the highest prevalence of clarithromycin resistance in the western Pacific region (173 [51·2%] of 338 in southeast Asia and 75 [29·8%] of 252 in eastern Asia), north African region (seven [38·9%] of 18), and western Asian region (12 [31·6%] of 38), whereas the highest prevalence of levofloxacin resistance was found in south Asia (14 [51·85%] of 27), Central America (48 [38·7%] of 124), eastern Europe (four [36·4%] of 11), and southern Africa (three [33·3%] of nine). Similarly, <em>23S rRNA</em> and <em>gyrA</em> genotypes are variable across <em>H pylori</em> subpopulations. MIC values changed depending on the specific mutation in <em>23S rRNA</em> (mean clarithromycin MIC 24·61 mg/L [95% CI 12·27–36·96] for 2143A→G and 142·25 mg/L [95% CI 77·88–206·61] for 2142A→G) and <em>gyrA</em> (mean levofloxac","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101217"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844272","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 : 2026-01-01DOI: 10.1016/j.lanmic.2025.101229
Amber Barton DPhil , Petra Pospíšilová PhD , Camila G Beiras PhD , Lucy N John MD , Wendy Houinei MPH , Prof Lorenzo Giacani PhD , Prof David Šmajs PhD , Prof Michael Marks PhD , Prof Oriol Mitjà PhD , Mathew A Beale PhD , Prof Nicholas R Thomson PhD
<div><h3>Background</h3><div>Yaws, a neglected tropical disease caused by <em>Treponema pallidum</em> subspecies <em>pertenue</em> (<em>T p pertenue</em>), has evaded eradication, in part due to a high proportion of asymptomatic cases. Repeated mass drug administration (MDA), whereby an entire population is repeatedly treated irrespective of disease, could provide a solution. Here, we aimed to investigate the effect of MDA on the genomic epidemiology of <em>T p pertenue</em>.</div></div><div><h3>Methods</h3><div>We conducted a retrospective genomic epidemiology study on samples collected during a cluster-randomised trial of mass administration of azithromycin for yaws eradication in the Namatanai District of Papua New Guinea. Participants were in 38 wards (administrative units encompassing several villages) in three local-level government areas (LLGs). The experimental group received an initial round of MDA followed by two further rounds 6 months and 12 months after the first round. The control group received one round of MDA followed by two rounds of treatment targeting clinical cases and contacts only, on the same schedule as the MDA in the experimental group. A follow-up survey on both groups was done 18 months after the first MDA round. Swab samples were collected at each round from ulcerative and nodular skin lesions, and blood was collected by finger-prick for serological testing at 18 months. Metadata on ulcer size (cm) and duration (days) were recorded at each round, and treponemal and non-treponemal antibodies were recorded at 18 months. Samples from swabs positive for <em>T p pertenue</em> underwent library preparation and whole-genome sequencing. We examined the phylogenetic relationships between genomes, linking them with geospatial and patient metadata to understand the impact of MDA on <em>T p pertenue</em> diversity and transmission.</div></div><div><h3>Findings</h3><div>Swabs collected from 297 individuals with active yaws from April 30, 2018, to Nov 2, 2019, yielded 222 good-quality <em>T</em> <em>p pertenue</em> genomes. We identified 20 sublineages of <em>T p pertenue</em> in the control group and 21 in the experimental group at the beginning of the study. At the end of the study, there were 13 sublineages in the control group and three in the experimental group, of which two persisted in both groups. Three sublineages not detected at baseline were observed in the control group after commencing MDA. The two sublineages that persisted in both groups had non-synonymous mutations in penicillin-binding proteins. One of these sublineages evolved macrolide resistance in three individuals and was associated with lowered treponemal antibody (p=0·0036) and longer ulcer duration (p=0·015). Despite the study taking place within a small island, sublineages were geographically clustered, with pairs of samples from the same ward (odds ratio 7·1, 95% CI 5·7–8·8; p<0·0001) or neighbouring wards (4·3, 3·3–5·4; p<0·0001) more likely to sha
背景：雅司病是一种被忽视的热带病，由梅毒螺旋体亚种pertenue （T p pertenue）引起，一直未能根除，部分原因是无症状病例比例很高。重复大规模给药（MDA）可以提供一种解决方案，即不论疾病如何，整个人群都要反复接受治疗。本研究旨在探讨丙二醛对前列腺癌基因组流行病学的影响。方法：我们对在巴布亚新几内亚Namatanai地区大规模使用阿奇霉素根除雅司病的整群随机试验中收集的样本进行了回顾性基因组流行病学研究。参与者来自三个地方一级政府区域（llg）的38个区（包括几个村庄的行政单位）。实验组在第一轮治疗后6个月和12个月接受第一轮MDA治疗。对照组接受1轮丙二醛治疗，随后仅针对临床病例和接触者进行2轮治疗，疗程与实验组相同。在第一轮MDA后18个月对两组进行了随访调查。每轮从溃疡性和结节性皮肤病变处采集拭子样本，18个月时手指穿刺采血进行血清学检测。每轮记录溃疡大小（cm）和持续时间（天）的元数据，并在18个月时记录密螺旋体和非密螺旋体抗体。对tp阳性拭子样本进行文库制备和全基因组测序。我们研究了基因组之间的系统发育关系，将它们与地理空间和患者元数据联系起来，以了解MDA对tp浓度多样性和传播的影响。研究结果：2018年4月30日至2019年11月2日，从297名活动性雅司病患者身上收集的拭子，产生了222个高质量的Tp值基因组。在研究开始时，我们在对照组中发现了20个tp亚型，在实验组中发现了21个。研究结束时，对照组有13个亚谱系，实验组有3个亚谱系，两组都有2个亚谱系。在开始MDA治疗后，对照组观察到基线时未检测到的3个亚谱系。在两组中持续存在的两个亚谱系在青霉素结合蛋白中具有非同义突变。其中一个亚谱系在3个个体中进化为大环内酯类耐药，并与螺旋体抗体降低（p= 0.0036）和溃疡持续时间延长（p= 0.015）相关。尽管研究发生在一个小岛上，但亚谱系在地理上聚集，来自同一病区的成对样本（优势比为7.1,95% CI为5.7 - 8.8;）解释：重复的MDA成功地降低并维持了低水平的遗传多样性，但与大环内酯类药物耐药性的发展有关。雅司病在MDA后再次出现归因于多个亚系，其中大多数是在MDA之前的人群中发现的。同一病房内的参与者比那些地理位置分散的参与者更有可能共享子谱系，这表明再次出现是由当地传播驱动的。这些发现可以为未来消除雅司病的战略提供信息。资助：欧洲研究理事会，欧盟，巴塞罗那省代表团，barberoberSolidària基金会，Wellcome和Fundació“la Caixa”。
{"title":"Effect of repeated mass drug administration on the transmission of yaws: a retrospective genomic epidemiology study","authors":"Amber Barton DPhil , Petra Pospíšilová PhD , Camila G Beiras PhD , Lucy N John MD , Wendy Houinei MPH , Prof Lorenzo Giacani PhD , Prof David Šmajs PhD , Prof Michael Marks PhD , Prof Oriol Mitjà PhD , Mathew A Beale PhD , Prof Nicholas R Thomson PhD","doi":"10.1016/j.lanmic.2025.101229","DOIUrl":"10.1016/j.lanmic.2025.101229","url":null,"abstract":"<div><h3>Background</h3><div>Yaws, a neglected tropical disease caused by <em>Treponema pallidum</em> subspecies <em>pertenue</em> (<em>T p pertenue</em>), has evaded eradication, in part due to a high proportion of asymptomatic cases. Repeated mass drug administration (MDA), whereby an entire population is repeatedly treated irrespective of disease, could provide a solution. Here, we aimed to investigate the effect of MDA on the genomic epidemiology of <em>T p pertenue</em>.</div></div><div><h3>Methods</h3><div>We conducted a retrospective genomic epidemiology study on samples collected during a cluster-randomised trial of mass administration of azithromycin for yaws eradication in the Namatanai District of Papua New Guinea. Participants were in 38 wards (administrative units encompassing several villages) in three local-level government areas (LLGs). The experimental group received an initial round of MDA followed by two further rounds 6 months and 12 months after the first round. The control group received one round of MDA followed by two rounds of treatment targeting clinical cases and contacts only, on the same schedule as the MDA in the experimental group. A follow-up survey on both groups was done 18 months after the first MDA round. Swab samples were collected at each round from ulcerative and nodular skin lesions, and blood was collected by finger-prick for serological testing at 18 months. Metadata on ulcer size (cm) and duration (days) were recorded at each round, and treponemal and non-treponemal antibodies were recorded at 18 months. Samples from swabs positive for <em>T p pertenue</em> underwent library preparation and whole-genome sequencing. We examined the phylogenetic relationships between genomes, linking them with geospatial and patient metadata to understand the impact of MDA on <em>T p pertenue</em> diversity and transmission.</div></div><div><h3>Findings</h3><div>Swabs collected from 297 individuals with active yaws from April 30, 2018, to Nov 2, 2019, yielded 222 good-quality <em>T</em> <em>p pertenue</em> genomes. We identified 20 sublineages of <em>T p pertenue</em> in the control group and 21 in the experimental group at the beginning of the study. At the end of the study, there were 13 sublineages in the control group and three in the experimental group, of which two persisted in both groups. Three sublineages not detected at baseline were observed in the control group after commencing MDA. The two sublineages that persisted in both groups had non-synonymous mutations in penicillin-binding proteins. One of these sublineages evolved macrolide resistance in three individuals and was associated with lowered treponemal antibody (p=0·0036) and longer ulcer duration (p=0·015). Despite the study taking place within a small island, sublineages were geographically clustered, with pairs of samples from the same ward (odds ratio 7·1, 95% CI 5·7–8·8; p<0·0001) or neighbouring wards (4·3, 3·3–5·4; p<0·0001) more likely to sha","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101229"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145946552","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 : 2026-01-01DOI: 10.1016/j.lanmic.2025.101225
Xiaoqing Fan , Jingyuan Ning
{"title":"Drug-resistant fungi: the unintended consequence of modern immunosuppression","authors":"Xiaoqing Fan , Jingyuan Ning","doi":"10.1016/j.lanmic.2025.101225","DOIUrl":"10.1016/j.lanmic.2025.101225","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101225"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144973844","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 : 2026-01-01DOI: 10.1016/j.lanmic.2025.101259
Krishna Prasad Acharya , Sarita Phuyal , Richard Trevor Wilson , Narayan Acharya , Sher Bahadur Pun , Kishor Pandey
{"title":"Why did rabies control fail in low-income and middle-income countries?","authors":"Krishna Prasad Acharya , Sarita Phuyal , Richard Trevor Wilson , Narayan Acharya , Sher Bahadur Pun , Kishor Pandey","doi":"10.1016/j.lanmic.2025.101259","DOIUrl":"10.1016/j.lanmic.2025.101259","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101259"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337785","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 : 2026-01-01DOI: 10.1016/j.lanmic.2025.101219
Anja Saso MBBS , Janeri Fröberg PhD , Haddijatou Jobe MSc , Marc Eleveld BSc , Michael Okoye MSc , Ebrima Kanteh BSc , Annemijn Arns BSc , Fred van Opzeeland BSc , Michelle Kumado MSc , Amadou Faal MSc , Elishia Roberts MSc , Modou-Lamin Fofana BSc , Aru-Kumba Baldeh MPH , Karamo Conteh BSc , Bram van Cranenbroek BSc , Sophie Roetynck PhD , Prof Marien de Jonge PhD , Prof Thushan I de Silva PhD , Prof Martijn Huynen PhD , Prof Beate Kampmann MD PhD , Dimitri A Diavatopoulos PhD
<div><h3>Background</h3><div>Mucosal protection against pertussis depends on antibodies and the activation of mucosal-resident memory T cells, both of which are differentially induced by acellular pertussis and whole-cell pertussis vaccines. We aimed to investigate the effect of primary vaccination with these two vaccine types on pertussis-specific mucosal immunity in infants after their mothers received an acellular pertussis-containing vaccine (tetanus–diphtheria–acellular pertussis–inactivated poliovirus; Tdap–IPV) or a tetanus-toxoid (TT)-only vaccine during pregnancy.</div></div><div><h3>Methods</h3><div>This immunological substudy was embedded within the Gambian Pertussis Study (GaPs), a single-centre, randomised, controlled, double-blind, phase 4 trial conducted in The Gambia. In GaPs, healthy, pregnant participants aged 18–40 years were randomly assigned (1:1) to receive a pertussis-containing (Tdap–IPV) vaccine or a TT-only vaccine at 28–34 weeks’ gestation, and their infants were randomly assigned (1:1) to receive a primary immunisation series comprising either a diphtheria–tetanus–whole-cell pertussis (DTwP) vaccine or a diphtheria–tetanus–acellular pertussis (DTaP) vaccine at the ages of 8, 12, and 16 weeks. Nasosorption devices were used to collect nasal mucosal lining fluid (MLF) from infants at the ages of 8, 16, 17, and 20 weeks, and 9 months. The immunological substudy was conducted in a subset of infants in the GaPs trial for whom MLF and paired cord blood and serum samples were available; outcomes were the concentrations of nasal anti-<em>B pertussis</em> IgG and IgA and anti-pertussis toxin IgG, before and after the DTaP or DTwP primary immunisation series at the ages of 8 weeks, 20 weeks, and 9 months, and the concentrations of nasal T-cell-associated cytokines at age 17 weeks. This study is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT03606096</span><svg><path></path></svg></span>.</div></div><div><h3>Findings</h3><div>This substudy included 160 infants enrolled in the main GaPs trial between Feb 13, 2019, and May 17, 2021. At age 8 weeks, before primary vaccination, infants born to mothers who had received the Tdap–IPV vaccine in pregnancy had higher concentrations of maternally derived nasal anti-pertussis toxin IgG (geometric mean ratio 3·84 [95% CI 3·22–4·59]; p<0·0001) and anti-<em>B pertussis</em> IgG (6·45 [5·94–7·01]; p<0·0001), but not IgA, than infants whose mothers received the TT vaccine in pregnancy. After primary vaccination, both groups of infants who received the DTwP vaccine had significantly higher geometric mean concentrations (GMCs) of nasal anti-<em>B pertussis</em> IgG than infants who received the DTaP vaccine (5·42 arbitrary units [AU] per mL [95% CI 3·79–7·75], p=0·0036 for the TT–DTwP group and 4·40 AU/mL [2·99–6·45], p=0·024 for the Tdap–IPV–DTwP group <em>vs</em> 2·16 AU/mL [1·40–3·32] for the Tdap–IPV–DTaP group). Furthermore, DTaP-vac
背景：粘膜对百日咳的保护依赖于抗体和粘膜驻留记忆T细胞的激活，这两者在非细胞百日咳和全细胞百日咳疫苗诱导下是不同的。我们的目的是研究在母亲在怀孕期间接种了无细胞百日咳疫苗（破伤风-白喉-无细胞百日咳-灭活脊髓灰质炎病毒；Tdap-IPV）或破伤风-类毒素（TT）单一疫苗后，首次接种这两种疫苗对婴儿百日咳特异性粘膜免疫的影响。方法：冈比亚百日咳研究（GaPs）是一项在冈比亚进行的单中心、随机、对照、双盲、4期试验。在GaPs中，年龄在18-40岁的健康孕妇被随机分配（1:1）在妊娠28-34周接受含百日咳（Tdap-IPV）疫苗或tt -单纯疫苗，她们的婴儿被随机分配（1:1）接受初级免疫系列，包括白喉-破伤风-全细胞百日咳（DTwP）疫苗或白喉-破伤风-无细胞百日咳（DTaP）疫苗，年龄在8、12和16周。采用鼻吸装置收集8、16、17、20周和9个月婴儿的鼻黏膜衬里液（MLF）。免疫亚研究是在GaPs试验中的一组婴儿中进行的，这些婴儿可以获得MLF和配对脐带血和血清样本；结果是在8周龄、20周龄和9月龄DTaP或DTwP一次免疫系列前后，鼻腔抗b型百日咳IgG、IgA和抗百日咳毒素IgG的浓度，以及17周龄鼻腔t细胞相关细胞因子的浓度。本研究已在ClinicalTrials.gov注册，编号NCT03606096。研究结果：该亚研究包括160名在2019年2月13日至2021年5月17日期间参加主要GaPs试验的婴儿。妊娠期接种Tdap-IPV疫苗的母亲所生的婴儿，在初次接种疫苗前8周时，其母源性鼻腔抗百日咳毒素IgG浓度较高（几何平均比3.84 [95% CI 3.22 - 4.59]）；解释：妊娠期接种Tdap-IPV疫苗可诱导抗体通过胎盘转移至婴儿上呼吸道粘膜，有助于局部保护。尽管母源性抗体调节了婴儿对一次接种百日咳毒素特异性IgG的反应，但与接受DTaP疫苗的婴儿相比，接受DTwP疫苗的婴儿对全细胞B型百日咳始终产生更高的粘膜IgG，并表现出更强的局部细胞激活，证实了从动物研究中发现的DTwP特异性粘膜效应。综上所述，这些发现为怀孕期间免疫接种所赋予的早期生命保护提供了机制支持，并证明了DTwP疫苗接种引起的更广泛的粘膜免疫，为产前疫苗接种规划和婴儿百日咳疫苗接种时间表的政策讨论提供了信息。资助：创新药物倡议联合事业、地平线2020、欧洲制药工业和协会联合会、盖茨基金会、威康信托基金会和BactiVac。
{"title":"Mucosal immune responses to Bordetella pertussis in Gambian infants after maternal and primary vaccination: an immunological substudy of a single-centre, randomised, controlled, double-blind, phase 4 trial","authors":"Anja Saso MBBS , Janeri Fröberg PhD , Haddijatou Jobe MSc , Marc Eleveld BSc , Michael Okoye MSc , Ebrima Kanteh BSc , Annemijn Arns BSc , Fred van Opzeeland BSc , Michelle Kumado MSc , Amadou Faal MSc , Elishia Roberts MSc , Modou-Lamin Fofana BSc , Aru-Kumba Baldeh MPH , Karamo Conteh BSc , Bram van Cranenbroek BSc , Sophie Roetynck PhD , Prof Marien de Jonge PhD , Prof Thushan I de Silva PhD , Prof Martijn Huynen PhD , Prof Beate Kampmann MD PhD , Dimitri A Diavatopoulos PhD","doi":"10.1016/j.lanmic.2025.101219","DOIUrl":"10.1016/j.lanmic.2025.101219","url":null,"abstract":"<div><h3>Background</h3><div>Mucosal protection against pertussis depends on antibodies and the activation of mucosal-resident memory T cells, both of which are differentially induced by acellular pertussis and whole-cell pertussis vaccines. We aimed to investigate the effect of primary vaccination with these two vaccine types on pertussis-specific mucosal immunity in infants after their mothers received an acellular pertussis-containing vaccine (tetanus–diphtheria–acellular pertussis–inactivated poliovirus; Tdap–IPV) or a tetanus-toxoid (TT)-only vaccine during pregnancy.</div></div><div><h3>Methods</h3><div>This immunological substudy was embedded within the Gambian Pertussis Study (GaPs), a single-centre, randomised, controlled, double-blind, phase 4 trial conducted in The Gambia. In GaPs, healthy, pregnant participants aged 18–40 years were randomly assigned (1:1) to receive a pertussis-containing (Tdap–IPV) vaccine or a TT-only vaccine at 28–34 weeks’ gestation, and their infants were randomly assigned (1:1) to receive a primary immunisation series comprising either a diphtheria–tetanus–whole-cell pertussis (DTwP) vaccine or a diphtheria–tetanus–acellular pertussis (DTaP) vaccine at the ages of 8, 12, and 16 weeks. Nasosorption devices were used to collect nasal mucosal lining fluid (MLF) from infants at the ages of 8, 16, 17, and 20 weeks, and 9 months. The immunological substudy was conducted in a subset of infants in the GaPs trial for whom MLF and paired cord blood and serum samples were available; outcomes were the concentrations of nasal anti-<em>B pertussis</em> IgG and IgA and anti-pertussis toxin IgG, before and after the DTaP or DTwP primary immunisation series at the ages of 8 weeks, 20 weeks, and 9 months, and the concentrations of nasal T-cell-associated cytokines at age 17 weeks. This study is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT03606096</span><svg><path></path></svg></span>.</div></div><div><h3>Findings</h3><div>This substudy included 160 infants enrolled in the main GaPs trial between Feb 13, 2019, and May 17, 2021. At age 8 weeks, before primary vaccination, infants born to mothers who had received the Tdap–IPV vaccine in pregnancy had higher concentrations of maternally derived nasal anti-pertussis toxin IgG (geometric mean ratio 3·84 [95% CI 3·22–4·59]; p<0·0001) and anti-<em>B pertussis</em> IgG (6·45 [5·94–7·01]; p<0·0001), but not IgA, than infants whose mothers received the TT vaccine in pregnancy. After primary vaccination, both groups of infants who received the DTwP vaccine had significantly higher geometric mean concentrations (GMCs) of nasal anti-<em>B pertussis</em> IgG than infants who received the DTaP vaccine (5·42 arbitrary units [AU] per mL [95% CI 3·79–7·75], p=0·0036 for the TT–DTwP group and 4·40 AU/mL [2·99–6·45], p=0·024 for the Tdap–IPV–DTwP group <em>vs</em> 2·16 AU/mL [1·40–3·32] for the Tdap–IPV–DTaP group). Furthermore, DTaP-vac","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101219"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949404","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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