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Strengthening hepatitis B virus clinical research in Africa: the need for multistakeholder collaboration, funding, and political will 加强非洲乙型肝炎病毒临床研究:多方利益攸关方合作、供资和政治意愿的必要性
IF 20.4 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2026-01-01 DOI: 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.
非洲承受着不成比例的乙型肝炎病毒(HBV)感染负担,有6800万慢性感染者,占全球新感染病例的65%。然而,在全球1804项HBV临床试验中,只有18项(1%)是在非洲进行的,这限制了治疗结果的普遍性。合作研究论坛的HBV部门在2023年至2024年期间召集了一系列多利益攸关方讨论,以确定临床研究中的差距并确定解决方案。本个人观点综合了这些会议的见解,突出了HBV临床研究差异的主要障碍和潜在解决方案。障碍包括资金不足、政治意愿不足、社区意识低下以及卫生保健基础设施和监管系统带来的后勤挑战。这一个人观点强调,考虑到不同的HBV基因型以及与艾滋病毒和丁型肝炎病毒合并感染等区域特定因素,迫切需要由非洲主导的研究。我们提出了解决方案,包括加强监管框架,利用现有的研究网络,建立行业资助联盟,并倡导增加投资。
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引用次数: 0
Genomic determinants of antibiotic resistance for Helicobacter pylori treatment: a retrospective phenotypic and genotypic observational study 幽门螺杆菌治疗抗生素耐药性的基因组决定因素:一项回顾性表型和基因型观察研究。
IF 20.4 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2026-01-01 DOI: 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
背景:幽门螺杆菌耐药性的上升是一个公共卫生挑战。基于基因组的易感性检测允许鉴定耐药性相关突变,补充传统诊断并向基于病原体的个性化治疗迈进。我们的研究旨在鉴定与幽门螺杆菌耐药相关的基因和突变,并评估这些标记物在多大程度上可以作为对克拉霉素和左氧氟沙星表型耐药的预测因子。方法:在这项回顾性表型和基因型观察研究中,我们纳入了来自幽门螺杆菌基因组计划(HpGP)收集的1011个幽门螺杆菌全基因组序列和已知地理来源的菌株。我们在一个集中实验室使用Etest对419株HpGP菌株进行了表型克拉霉素和左氧氟沙星药敏试验。通过基因组分析鉴定23S rRNA和gyrA变异,并建立与克拉霉素耐药(即23S rRNA 2142A→G、2142A→C和2143A→G)和左氧氟沙星耐药(即gyrA A88V或A88P、N87K或N87I、D91G、D91N或D91Y)相关的突变目录。评估基因型-表型一致性以估计敏感性和特异性,并将抗性相关突变的策划目录应用于完整的HpGP集。利用从美国国家生物技术信息中心序列读取档案库检索到的HpGP基因组和768个全基因组序列,计算了耐药相关突变的区域特异性流行率。检测了耐药基因型、幽门螺杆菌亚群和最低抑菌浓度(mic)之间的关系。结果:克拉霉素耐药和左氧氟沙星耐药HpGP菌株的敏感性和特异性均为100%,所有置信区间为96% ~ 100%。联合分析(n=1779)发现,西太平洋地区克拉霉素耐药率最高(东南亚338例中有173例[51.2%],东亚252例中有75例[29.8%]),北非地区(18例中有7例[38.9%]),西亚地区(38例中有12例[31.6%]),而左氧氟沙星耐药率最高的地区是南亚(27例中有14例[51.85%])、中美洲(124例中有48例[38.7%])、东欧(11例中有4例[36.4%])。和南部非洲(9个中的3个[33.3%])。同样,23S rRNA和gyrA基因型在幽门螺杆菌亚群中是可变的。MIC值根据23S rRNA (2143A→G的克拉霉素平均MIC为24.61 mg/L [95% CI为12.27 ~ 36.96],2142A→G的克拉霉素平均MIC为142·25 mg/L [95% CI为77·88 ~ 206·61])和gyrA(密码子91突变的左氧氟沙星平均MIC为9.66 mg/L [95% CI为6.75 ~ 12.56],密码子87突变的左氧氟沙星平均MIC为27.97 mg/L [95% CI为25.82 ~ 30·11])的特定突变而变化。解释:特定基因的突变是幽门螺杆菌耐克拉霉素和左氧氟沙星的可靠指标,是开发诊断方法和分子监测的有用标记。我们的结果表明,经验性地使用克拉霉素和左氧氟沙星,没有先前的药敏试验,不适合在本研究覆盖的所有地理区域。资助:美国国家癌症研究所、欧洲研究委员会和西班牙科学与创新部的校内研究项目。
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引用次数: 0
Effect of repeated mass drug administration on the transmission of yaws: a retrospective genomic epidemiology study 反复大量给药对雅司病传播的影响:一项回顾性基因组流行病学研究。
IF 20.4 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2026-01-01 DOI: 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 ,&nbsp;Petra Pospíšilová PhD ,&nbsp;Camila G Beiras PhD ,&nbsp;Lucy N John MD ,&nbsp;Wendy Houinei MPH ,&nbsp;Prof Lorenzo Giacani PhD ,&nbsp;Prof David Šmajs PhD ,&nbsp;Prof Michael Marks PhD ,&nbsp;Prof Oriol Mitjà PhD ,&nbsp;Mathew A Beale PhD ,&nbsp;Prof Nicholas R Thomson PhD","doi":"10.1016/j.lanmic.2025.101229","DOIUrl":"10.1016/j.lanmic.2025.101229","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Yaws, a neglected tropical disease caused by &lt;em&gt;Treponema pallidum&lt;/em&gt; subspecies &lt;em&gt;pertenue&lt;/em&gt; (&lt;em&gt;T p pertenue&lt;/em&gt;), 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 &lt;em&gt;T p pertenue&lt;/em&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;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 &lt;em&gt;T p pertenue&lt;/em&gt; 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 &lt;em&gt;T p pertenue&lt;/em&gt; diversity and transmission.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;Swabs collected from 297 individuals with active yaws from April 30, 2018, to Nov 2, 2019, yielded 222 good-quality &lt;em&gt;T&lt;/em&gt; &lt;em&gt;p pertenue&lt;/em&gt; genomes. We identified 20 sublineages of &lt;em&gt;T p pertenue&lt;/em&gt; 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&lt;0·0001) or neighbouring wards (4·3, 3·3–5·4; p&lt;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}
引用次数: 0
Drug-resistant fungi: the unintended consequence of modern immunosuppression 耐药真菌:现代免疫抑制的意外后果。
IF 20.4 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2026-01-01 DOI: 10.1016/j.lanmic.2025.101225
Xiaoqing Fan , Jingyuan Ning
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引用次数: 0
Why did rabies control fail in low-income and middle-income countries? 为什么狂犬病控制在低收入和中等收入国家失败?
IF 20.4 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2026-01-01 DOI: 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 ,&nbsp;Sarita Phuyal ,&nbsp;Richard Trevor Wilson ,&nbsp;Narayan Acharya ,&nbsp;Sher Bahadur Pun ,&nbsp;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}
引用次数: 0
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 冈比亚婴儿在母体和初级疫苗接种后对百日咳杆菌的粘膜免疫反应:一项单中心、随机、对照、双盲、4期试验的免疫学亚研究
IF 20.4 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2026-01-01 DOI: 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 ,&nbsp;Janeri Fröberg PhD ,&nbsp;Haddijatou Jobe MSc ,&nbsp;Marc Eleveld BSc ,&nbsp;Michael Okoye MSc ,&nbsp;Ebrima Kanteh BSc ,&nbsp;Annemijn Arns BSc ,&nbsp;Fred van Opzeeland BSc ,&nbsp;Michelle Kumado MSc ,&nbsp;Amadou Faal MSc ,&nbsp;Elishia Roberts MSc ,&nbsp;Modou-Lamin Fofana BSc ,&nbsp;Aru-Kumba Baldeh MPH ,&nbsp;Karamo Conteh BSc ,&nbsp;Bram van Cranenbroek BSc ,&nbsp;Sophie Roetynck PhD ,&nbsp;Prof Marien de Jonge PhD ,&nbsp;Prof Thushan I de Silva PhD ,&nbsp;Prof Martijn Huynen PhD ,&nbsp;Prof Beate Kampmann MD PhD ,&nbsp;Dimitri A Diavatopoulos PhD","doi":"10.1016/j.lanmic.2025.101219","DOIUrl":"10.1016/j.lanmic.2025.101219","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;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-&lt;em&gt;B pertussis&lt;/em&gt; 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 &lt;span&gt;&lt;span&gt;ClinicalTrials.gov&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;NCT03606096&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;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&lt;0·0001) and anti-&lt;em&gt;B pertussis&lt;/em&gt; IgG (6·45 [5·94–7·01]; p&lt;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-&lt;em&gt;B pertussis&lt;/em&gt; 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 &lt;em&gt;vs&lt;/em&gt; 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}
引用次数: 0
Carbapenemase-producing Citrobacter species in Chinese children, 2015–24: emerging cefiderocol-resistant hypervirulent clones 中国儿童产碳青霉烯酶柠檬酸杆菌种类,2015-24:新出现的头孢地酚耐药高毒克隆。
IF 20.4 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2026-01-01 DOI: 10.1016/j.lanmic.2025.101221
Chen Xu , Lili Huang , Xiangkun Zeng , Ruichao Li , Ning Dong
{"title":"Carbapenemase-producing Citrobacter species in Chinese children, 2015–24: emerging cefiderocol-resistant hypervirulent clones","authors":"Chen Xu ,&nbsp;Lili Huang ,&nbsp;Xiangkun Zeng ,&nbsp;Ruichao Li ,&nbsp;Ning Dong","doi":"10.1016/j.lanmic.2025.101221","DOIUrl":"10.1016/j.lanmic.2025.101221","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101221"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144973787","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}
引用次数: 0
A pandemic toolbox for clade 2.3.4.4b A(H5N1) influenza virus risk assessment 2.3.4.4b A(H5N1)进化支流感病毒风险评估大流行工具箱。
IF 20.4 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2026-01-01 DOI: 10.1016/j.lanmic.2025.101240
Jessica A Belser
{"title":"A pandemic toolbox for clade 2.3.4.4b A(H5N1) influenza virus risk assessment","authors":"Jessica A Belser","doi":"10.1016/j.lanmic.2025.101240","DOIUrl":"10.1016/j.lanmic.2025.101240","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101240"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783193","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}
引用次数: 0
SARS-CoV-2 infectious shedding and rebound among adults with and without oral antiviral use: two case-ascertained prospective household studies 在使用和未使用口服抗病毒药物的成年人中,SARS-CoV-2传染性脱落和反弹:两项病例确定的前瞻性家庭研究
IF 20.4 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2026-01-01 DOI: 10.1016/j.lanmic.2025.101227
Melisa M Shah MD , Glen R Abedi MPH , Scott Lu MBBS , Miguel Garcia-Knight PhD , Jesus Pineda-Ramirez BA , Sarah A Goldberg MAS , Prof Carlos G Grijalva MD , Prof H Keipp Talbot MD MPH , Jonathan Schmitz MD PhD , Karen Lutrick PhD , Katherine D Ellingson PhD , Prof Melissa S Stockwell MD MPH , Ellen Sano DO , Huong Q Nguyen PhD , Suchitra Rao MBBS , Prof Edwin J Asturias MD , Mehul S Suthar PhD , Alexandra M Mellis PhD , Prof Steven G Deeks MD , Prof Jeffrey N Martin MD , Amethyst Zhang
<div><h3>Background</h3><div>The effect of COVID-19 oral antivirals on the duration of SARS-CoV-2 infectious viral shedding and viral rebound remains uncertain. This study aimed to examine the association of oral antivirals with viral dynamics, shedding of infectious virus, and SARS-CoV-2 rebound.</div></div><div><h3>Methods</h3><div>A prospective case-ascertained household study design was used. Participants were non-hospitalised adults older than 18 years with symptomatic SARS-CoV-2 enrolled in one of two prospective household transmission studies (University of California, San Francisco, FindCOVID and Respiratory Virus Transmission Network–Sentinel [RVTN–S]) conducted in the USA across six states at academic institutions from Jan 1, 2022 to June 10, 2023. We excluded those reporting receipt of multiple COVID-19 outpatient medications, treatment with remdesivir, a treatment duration of more than 6 days, and those from whom fewer than five daily anterior nasal swabs were collected during their illness. Participants were considered to be at high risk of severe COVID-19 (and, therefore, eligible for SARS-CoV-2 oral antiviral treatment) if they were aged 50 years or older or were aged 18 years or older and reporting at least one underlying condition. Study procedures included frequent self-collected nasal swabs (daily for 14 days after symptom onset and then every 3 days until day 28 after symptom onset in FindCOVID and two nasal swabs daily for 10 days from enrolment in RVTN-S) and viral testing by quantitative reverse transcriptase PCR (qRT-PCR), at-home antigen testing, and viral culture. Treatment was defined as self-reported receipt of an oral antiviral (nirmatrelvir–ritonavir or molnupiravir). The primary analysis compared viral detection by qRT-PCR, antigen test positivity, and culture positivity and assessed SARS-CoV-2 viral rebound (viral RNA, antigen, culture, and symptom rebound) in untreated and treated participants at high risk of severe outcomes. We used multivariable Poisson regression to assess associations between treatment, duration of test positivity, and the presence of viral culture rebound, adjusting for age, underlying conditions, and recent immunological events.</div></div><div><h3>Findings</h3><div>Between Jan 1, 2022, and June 10, 2023, 160 individuals with symptomatic COVID-19 and at high risk of severe outcomes were included in FindCOVID and RVTN–S. There was no significant difference in the duration of viral detection between treated and untreated participants at high risk of severe COVID-19 by antigen test positivity (6 days [IQR 5–11] <em>vs</em> 8 days [5–10]; adjusted relative risk [RR] 1·07, 95% CI 0·24–4·81) or viral culture (7 days [4–11] <em>vs</em> 6 days [5–9]; 2·21, 0·45–10·79). Among 122 participants without viral RNA rebound, the last day of antigen test positivity and detection of culturable virus post-symptom onset was earlier in treated participants than in untreated participants (5 days [4–8] <em>vs</em
背景:COVID-19口服抗病毒药物对SARS-CoV-2传染性病毒脱落和病毒反弹持续时间的影响尚不确定。本研究旨在探讨口服抗病毒药物与病毒动力学、传染性病毒脱落和SARS-CoV-2反弹的关系。方法:采用前瞻性病例确定的家庭研究设计。参与者是非住院的18岁以上有SARS-CoV-2症状的成年人,他们参加了两项前瞻性家庭传播研究中的一项(加州大学旧金山分校、FindCOVID和呼吸道病毒传播网络哨兵[RVTN-S]),该研究于2022年1月1日至2023年6月10日在美国六个州的学术机构进行。我们排除了那些报告接受过多种COVID-19门诊药物治疗、使用瑞德西韦治疗、治疗持续时间超过6天的患者,以及那些在患病期间每天收集的前鼻拭子少于5次的患者。如果参与者年龄在50岁或以上,或年龄在18岁或以上,并且报告至少有一种潜在疾病,则认为他们患有严重COVID-19的高风险(因此有资格接受SARS-CoV-2口服抗病毒治疗)。研究程序包括频繁地自行收集鼻拭子(在症状出现后的14天内每天一次,然后每3天一次,直到FindCOVID症状出现后的28天,以及从RVTN-S入组后的10天内每天两次鼻拭子),并通过定量逆转录酶PCR (qRT-PCR)、家庭抗原检测和病毒培养进行病毒检测。治疗定义为自我报告接受口服抗病毒药物(nirmatrelvir-ritonavir或molnupiravir)。初步分析比较了qRT-PCR病毒检测、抗原检测阳性和培养阳性,并评估了未治疗和治疗的高风险严重结局参与者的SARS-CoV-2病毒反弹(病毒RNA、抗原、培养和症状反弹)。我们使用多变量泊松回归来评估治疗、检测阳性持续时间和病毒培养反弹的存在之间的关系,并根据年龄、潜在条件和最近的免疫事件进行调整。研究结果:在2022年1月1日至2023年6月10日期间,FindCOVID和RVTN-S纳入了160例有症状的COVID-19和高危严重结局的个体。经抗原检测阳性的严重COVID-19高危患者中,治疗组和未治疗组的病毒检测持续时间无显著差异(6天[IQR 5-11] vs 8天[5-10];校正相对危险度[RR] 1.07, 95% CI 0.24 - 4.81)或病毒培养(7天[4-11]vs 6天[5-9];2.21,0.45 - 10.79)。在122名无病毒RNA反弹的受试者中,治疗组抗原检测阳性和可培养病毒症状后发病的最后一天比未治疗组早(抗原检测阳性的最后一天为5天[4-8]vs 8天[5-10];0.19,0.04 - 0.79;4天[3-6]vs 6天[4-9];0.18,0.004 - 0.85)。在160名符合抗病毒治疗条件的参与者中,157名参与者中有42名(27%)出现病毒学反弹(54名接受治疗的参与者中有17名[32%],104名未接受治疗的参与者中有25名[24%]),其中156名参与者中有34名(22%),131名中有10名(8%)出现抗原反弹,155名中有21名(14%)出现培养物反弹。在调整分析中,在严重COVID-19高风险的参与者中,接受治疗的参与者比未接受治疗的参与者更容易发生培养反弹(调整后的RR为3.18,95% CI为1.28 - 7.88)。解释:在没有病毒RNA反弹的情况下,COVID-19口服抗病毒治疗与感染性病毒脱落的早期停止有关。然而,抗病毒药物治疗也与SARS-CoV-2的短暂反弹有关。宣传这些传播风险和益处可以帮助符合条件的COVID-19严重风险高风险患者和临床医生就口服抗病毒药物的使用做出知情决定。资助:美国疾病控制和预防中心。
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引用次数: 0
Rethinking the role of animals in antimicrobial resistance 重新思考动物在抗菌素耐药性中的作用。
IF 20.4 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2026-01-01 DOI: 10.1016/j.lanmic.2025.101248
Elissa Khamisse , Xavier Bertrand , Damien Bouchard , Lucie Collineau , Olivier Fortineau , Marisa Haenni , Jean-Yves Madec , Claude Saegerman , Etienne Giraud , Eric Oswald
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引用次数: 0
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Lancet Microbe
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