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Crucial role of biosensors in the detection of helminth biomarkers in public health programmes 生物传感器在公共卫生计划中检测蠕虫生物标志物的关键作用。
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2025-02-01 DOI: 10.1016/j.lanmic.2024.100964
Maria Cambra-Pellejà MS , Lisette van Lieshout PhD , Luis Baptista-Pires PhD , Miguel Vilaplana MD , José Muñoz MD PhD , Javier Gandasegui PhD , Claudio Parolo PhD
Helminthiases are highly prevalent but neglected infections that affect more than 1·5 billion people worldwide. Considering the worldwide prevalence of helminthiases, WHO has declared them a public health concern since 2001, necessitating rigorous control and elimination efforts. However, only a few reliable point-of-care diagnostic tests are available for assessing the effectiveness of public health interventions targeting helminthiases, thus increasing the risk of suboptimal outcomes, misallocation of resources, and emergence of drug-resistant helminths. This Review provides an introduction on helminthiases and strategies to achieve control, elimination, interruption in transmission, and eradication of these infections. The Review then comprehensively details the existent biosensors that can be used to detect these infections in human samples, focusing on their target biomarkers, the bioreceptors used, and the sensing readouts. The Review concludes with an in-depth discussion on the persistent challenges related to helminthiases, aiming to encourage the development of much-needed diagnostics specific to these neglected infections.
蠕虫病是一种发病率很高但却被忽视的传染病,影响着全球超过 15 亿人。考虑到蠕虫病在全球的流行情况,世卫组织自 2001 年起宣布蠕虫病为公共卫生问题,因此有必要开展严格的控制和消除工作。然而,目前只有少数可靠的护理点诊断检测可用于评估针对蠕虫病的公共卫生干预措施的效果,从而增加了结果不理想、资源分配不当和出现耐药性蠕虫病的风险。本综述介绍了蠕虫病以及实现控制、消除、阻断传播和根除这些感染的战略。然后,综述全面详述了可用于检测人体样本中这些感染的现有生物传感器,重点介绍了其目标生物标志物、所使用的生物受体和传感读数。综述》最后深入探讨了与蠕虫病有关的长期挑战,旨在鼓励开发急需的专门针对这些被忽视的感染的诊断方法。
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引用次数: 0
Molecular features of the serological IgG repertoire elicited by egg-based, cell-based, or recombinant haemagglutinin-based seasonal influenza vaccines: a comparative, prospective, observational cohort study 基于蛋的、基于细胞的或基于重组血凝素的季节性流感疫苗引发的血清IgG库的分子特征:一项比较、前瞻性、观察性队列研究
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2025-02-01 DOI: 10.1016/j.lanmic.2024.06.002
Juyeon Park PhD , Foteini Bartzoka PhD , Troy von Beck PhD , Zhu-Nan Li PhD , Margarita Mishina BSc , Luke S Hebert BSc , Jessica Kain MSc , Feng Liu PhD , Suresh Sharma PhD , Weiping Cao PhD , Devon J Eddins PhD , Amrita Kumar PhD , Jin Eyun Kim PhD , Justin S Lee PhD , Yuanyuan Wang PhD , Evan A Schwartz PhD , Axel F Brilot PhD , Ed Satterwhite PhD , Dalton M Towers BSc , Eric McKnight BSc , George Georgiou Prof
<div><h3>Background</h3><div>Egg-based inactivated quadrivalent seasonal influenza vaccine (eIIV4), cell culture-based inactivated quadrivalent seasonal influenza vaccine (ccIIV4), and recombinant haemagglutinin (HA)-based quadrivalent seasonal influenza vaccine (RIV4) have been licensed for use in the USA. In this study, we used antigen-specific serum proteomics analysis to assess how the molecular composition and qualities of the serological antibody repertoires differ after seasonal influenza immunisation by each of the three vaccines and how different vaccination platforms affect the HA binding affinity and breadth of the serum antibodies that comprise the polyclonal response.</div></div><div><h3>Methods</h3><div>In this comparative, prospective, observational cohort study, we included female US health-care personnel (mean age 47·6 years [SD 8]) who received a single dose of RIV4, eIIV4, or ccIIV4 during the 2018–19 influenza season at Baylor Scott & White Health (Temple, TX, USA). Eligible individuals were selected based on comparable day 28 serum microneutralisation titres and similar vaccination history. Laboratory investigators were blinded to assignment until testing was completed. The preplanned exploratory endpoints were assessed by deconvoluting the serological repertoire specific to A/Singapore/INFIMH-16–0019/2016 (H3N2) HA before (day 0) and after (day 28) immunisation using bottom-up liquid chromatography–mass spectrometry proteomics (referred to as Ig-Seq) and natively paired variable heavy chain–variable light chain high-throughput B-cell receptor sequencing (referred to as BCR-Seq). Features of the antigen-specific serological repertoire at day 0 and day 28 for the three vaccine groups were compared. Antibodies identified with high confidence in sera were recombinantly expressed and characterised in depth to determine the binding affinity and breadth to time-ordered H3 HA proteins.</div></div><div><h3>Findings</h3><div>During September and October of the 2018–19 influenza season, 15 individuals were recruited and assigned to receive RIV4 (n=5), eIIV4 (n=5), or ccIIV4 (n=5). For all three cohorts, the serum antibody repertoire was dominated by back-boosted antibody lineages (median 98% [95% CI 88–99]) that were present in the serum before vaccination. Although vaccine platform-dependent differences were not evident in the repertoire diversity, somatic hypermutation, or heavy chain complementarity determining region 3 biochemical features, antibodies boosted by RIV4 showed substantially higher binding affinity to the vaccine H3/HA (median half-maximal effective concentration [EC50] to A/Singapore/INFIMH-16–0019/2016 HA: 0·037 μg/mL [95% CI 0·012–0·12] for RIV4; 4·43 μg/mL [0·030–100·0] for eIIV4; and 18·50 μg/mL [0·99–100·0] μg/mL for ccIIV4) and also the HAs from contemporary H3N2 strains than did those elicited by eIIV4 or ccIIV4 (median EC50 to A/Texas/50/2012 HA: 0·037 μg/mL [0·017–0·32] for RIV4; 1·10 μg/mL [0·045–100] fo
背景:基于鸡蛋的四价季节性流感灭活疫苗(eIIV4)、基于细胞培养的四价季节性流感灭活疫苗(ccIIV4)和基于重组血凝素(HA)的四价季节性流感疫苗(RIV4)已获准在美国使用。在这项研究中,我们使用抗原特异性血清蛋白质组学分析来评估三种疫苗接种季节性流感疫苗后血清抗体谱的分子组成和质量的差异,以及不同的疫苗接种平台如何影响构成多克隆应答的HA结合亲和力和血清抗体的宽度。方法:在这项比较、前瞻性、观察性队列研究中,我们纳入了2018-19年流感季节期间在Baylor Scott & White Health (Temple, TX, USA)接受单剂量RIV4、eIIV4或ccIIV4的美国女性卫生保健人员(平均年龄47.6岁[SD 8])。根据可比的第28天血清微量中和滴度和相似的疫苗接种史选择符合条件的个体。在测试完成之前,实验室调查人员对任务不知情。预先计划的探索性终点是通过在免疫前(第0天)和免疫后(第28天)使用自下而上的液相色谱-质谱蛋白质组学(称为Ig-Seq)和天然配对的可变重链-可变轻链高通量b细胞受体测序(称为BCR-Seq)对A/Singapore/INFIMH-16-0019/2016 (H3N2) HA特异性血清学库进行解旋来评估的。比较三个疫苗组在第0天和第28天抗原特异性血清学库的特征。在血清中鉴定出高可信度的抗体进行重组表达和深度表征,以确定与时间顺序的H3 HA蛋白的结合亲和力和广度。结果:在2018- 2019年流感季节的9月和10月,招募了15名个体并分配接受RIV4 (n=5), eIIV4 (n=5)或ccIIV4 (n=5)。在所有三个队列中,血清抗体库以接种前血清中存在的反向增强抗体谱系(中位数为98% [95% CI 88-99])为主。尽管疫苗平台依赖性差异在库多样性、体细胞超突变或决定3区生化特征的重链互补性方面不明显,但RIV4增强的抗体与疫苗H3/HA的结合亲和力显著提高(对A/Singapore/INFIMH-16-0019/2016 HA的中位半最大有效浓度[EC50]: 0.037 μg/mL [95% CI 0.012 - 0.12];eIIV4为4.43 μg/mL[0·030 ~ 100·0];与eIIV4或ccIIV4诱导的H3N2株相比,H3N2株的HA值为18.50 μg/mL (0.99 ~ 100 μg/mL), RIV4株的中位EC50为0.037 μg/mL (0.017 ~ 0.32);eIIV4为1·10 μg/mL[0·045-100];ccIIV4为12.6 μg/mL[1·8 ~ 100])。第7天的B细胞受体测序谱比较显示,eIIV4增加了典型蛋聚糖靶向B细胞的中位数频率(0.20% [95% CI 0.067 - 0.37]);RIV4为0.058% [0.050 - 0.11];ccIIV4和0.035%[0- 0.062]),而RIV4疫苗降低了与膜近端锚定靶向抗体相关的典型特征的b细胞受体的中位数频率(0.062% [95% CI 0- 0.084]);eIIV4为0.12% [0.066 - 0.16];ccIIV4为0.18%[0.016 - 0.20]。在探索性分析中,我们描述了一种高度丰富的单克隆抗体的结构,该抗体与1组和2组HA结合,并识别HA三聚体界面,尽管其序列类似于膜近端锚定结合抗体中发现的典型序列基序。解释:尽管所有三种已获许可的季节性流感疫苗均可诱导血清学抗体库,其特征由重印迹形成,难以区分,但RIV4疫苗选择性地增强了针对当代菌株的高亲和力单克隆抗体,并引发了更大的血清结合效力和广度,这可能是由于该疫苗制剂中HA免疫原的多价结构特征所致。总的来说,我们的研究结果显示了RIV4疫苗的优势,更普遍地强调了多价HA免疫原在促进高亲和力血清抗体反应方面的益处。资助:疾病控制和预防中心,国家卫生研究院,比尔和梅林达·盖茨基金会。
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引用次数: 0
Effectiveness of the primary Bacillus Calmette-Guérin vaccine against the risk of Mycobacterium tuberculosis infection and tuberculosis disease: a meta-analysis of individual participant data 卡介苗-谷氨酰胺原代疫苗预防结核分枝杆菌感染和结核病风险的有效性:对个体参与者数据的荟萃分析
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2025-02-01 DOI: 10.1016/j.lanmic.2024.100961
Puck T Pelzer MSc , Logan Stuck PhD , Leonardo Martinez PhD , Alexandra S Richards PhD , Carlos Acuña-Villaorduña MD , Prof Naomi E Aronson MD , Maryline Bonnet PhD , Anna C Carvalho PhD , Prof Pei-Chun Chan PhD , Prof Li-Min Huang PhD , Chi-Tai Fang PhD , Prof Gavin Churchyard PhD , Helena del Corral-Londoño PhD , Manjula Datta MSc , Marcos A Espinal MD , Prof Katherine Fielding PhD , Andrew J Fiore-Gartland PhD , Alberto Garcia-Basteiro PhD , Prof Willem Hanekom PhD , Mark Hatherill MD , Prof Frank G J Cobelens PhD
<div><h3>Background</h3><div>Tuberculosis vaccine trials using disease as the primary endpoint are large, time consuming, and expensive. An earlier immunological measure of the protection against disease would accelerate tuberculosis vaccine development. We aimed to assess whether the effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine for prevention of <em>Mycobacterium tuberculosis</em> infection was consistent with that for prevention of tuberculosis disease.</div></div><div><h3>Methods</h3><div>We conducted an individual participant data (IPD) meta-analysis on experimental and observational longitudinal studies before April 6, 2018, identified through systematic reviews, known to us through expert knowledge in the field, reporting on BCG vaccination status, <em>M tuberculosis</em> infection test (QuantiFERON IFN-γ release assay [IGRA] and tuberculin skin test [TST]), and tuberculosis incidence. Cohort studies were included only for countries with a mandatory neonatal BCG vaccination policy. Exclusion criteria were previous or current tuberculosis disease, HIV infection, tuberculosis preventive treatment usage, and for household contacts, a positive baseline IGRA or TST test and young children aged 0–2 years; for randomised controlled trials, TST results within 2 years after random assignation were excluded. We contacted the investigators of the identified studies to provide IPD. We compared the protective efficacy of the BCG vaccine against <em>M tuberculosis</em> infection with that against tuberculosis disease using mixed-effects, multivariable proportional hazards modelling, by study type, <em>M tuberculosis</em> infection test (IGRA and TST), cutoff for defining test positivity, age, sex, and latitude.</div></div><div><h3>Findings</h3><div>We identified 79 studies eligible for full screening and of these, IPD datasets from 14 studies were included in our analysis: 11 household contact studies (29 147 participants), two adolescent cohort studies (11 368 participants), and one randomised controlled trial (2963 participants). Among 28 188 participants we found no protection by the BCG vaccine against TST conversion regardless of cutoff in any type of study. Among 1491 household contacts, but not among 5644 adolescents, the BCG vaccine protected against QuantiFERON conversion at the primary cutoff of 0·7 IU/mL or more with the adjusted hazard ratio (0·65, 95% CI 0·51–0·82) being consistent with that for protection against disease (0·68, 0·18–2·59). Protection against QuantiFERON conversion at cutoff of 0·35 IU/mL or more (0·64, 0·51–0·81) was similar.</div></div><div><h3>Interpretation</h3><div>Protection from the BCG vaccination against <em>M tuberculosis</em> infection, measured as QuantiFERON conversion, is inconsistent across different groups. Among groups with recent household exposure, QuantiFERON conversion is consistent with protection against disease and could be evaluated as a proxy for disease in tuberculosis vaccine trials
背景:以疾病为主要终点的结核病疫苗试验规模大、耗时且昂贵。早期预防疾病的免疫措施将加速结核病疫苗的开发。我们的目的是评估卡介苗预防结核分枝杆菌感染的有效性是否与预防结核病的有效性一致。方法:我们对2018年4月6日之前的实验和观察性纵向研究进行了个体参与者数据(IPD) meta分析,这些研究是通过系统评价确定的,我们通过该领域的专家知识了解,报告了卡介苗接种状况、结核分枝杆菌感染试验(QuantiFERON IFN-γ释放试验[IGRA]和结核菌素皮肤试验[TST])和结核病发病率。队列研究仅纳入了强制性新生儿卡介苗接种政策的国家。排除标准为既往或目前患有结核病、艾滋病毒感染、结核病预防性治疗使用情况,对于家庭接触者,IGRA或TST基线检测呈阳性,以及0-2岁的幼儿;对于随机对照试验,排除随机分配后2年内的TST结果。我们联系了已确定研究的研究者以提供IPD。我们采用混合效应、多变量比例风险模型,根据研究类型、结核分枝杆菌感染试验(IGRA和TST)、确定试验阳性的截止点、年龄、性别和纬度,比较卡介苗对结核分枝杆菌感染的保护效果与对结核病的保护效果。结果:我们确定了79项符合全面筛查条件的研究,其中14项研究的IPD数据集纳入了我们的分析:11项家庭接触研究(29147名参与者),2项青少年队列研究(11368名参与者)和1项随机对照试验(2963名参与者)。在28188名参与者中,我们发现卡介苗对TST转化没有保护作用,无论在任何类型的研究中是否有阻断。在1491名家庭接触者中,而不是在5644名青少年中,卡介苗对QuantiFERON转化的保护作用在0.7 IU/mL或更高,调整后的风险比(0.65,95% CI 0.51 - 0.82)与疾病保护(0.68,0.18 - 2.59)一致。在0.35 IU/mL或更高(0.64,0.51 - 0.81)的截止值下,对QuantiFERON转换的保护作用相似。解释:卡介苗接种对结核分枝杆菌感染的保护作用,以QuantiFERON转换来衡量,在不同的群体中是不一致的。在最近有家庭接触的人群中,QuantiFERON转化与预防疾病一致,可以在结核病疫苗试验中作为疾病的替代指标进行评估。我们发现TST在2b期概念验证试验中缺乏预防价值。资助:比尔及梅琳达·盖茨基金会。
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引用次数: 0
Brain microbiome: is it all in our heads?
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2025-02-01 DOI: 10.1016/j.lanmic.2025.101075
The Lancet Microbe
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引用次数: 0
Genomic epidemiology of Salmonella: the need to consider vaccination history and nutritional status in resistance transmission studies 沙门氏菌基因组流行病学:在耐药性传播研究中需要考虑疫苗接种史和营养状况。
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2025-02-01 DOI: 10.1016/j.lanmic.2024.101011
lianwei Zhou , Minye Wang , Wenbo Li
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引用次数: 0
Data for action: the crucial role of hospitals in controlling Clostridioides difficile infection in England 行动数据:英国医院在控制艰难梭状芽孢杆菌感染中的关键作用》(Data for Action: the crucial role of hospitals in controlling Clostridioides difficile infection in England)。
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2025-02-01 DOI: 10.1016/j.lanmic.2024.100991
Akaninyene Otu , Dimple Chudasama , Russell Hope , Dakshika Jeyaratnam
{"title":"Data for action: the crucial role of hospitals in controlling Clostridioides difficile infection in England","authors":"Akaninyene Otu ,&nbsp;Dimple Chudasama ,&nbsp;Russell Hope ,&nbsp;Dakshika Jeyaratnam","doi":"10.1016/j.lanmic.2024.100991","DOIUrl":"10.1016/j.lanmic.2024.100991","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 2","pages":"Article 100991"},"PeriodicalIF":20.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The spread of molecular markers of artemisinin partial resistance and diagnostic evasion in Eritrea: a retrospective molecular epidemiology study 青蒿素部分耐药和漏诊分子标记在厄立特里亚的传播:回顾性分子流行病学研究
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2025-02-01 DOI: 10.1016/S2666-5247(24)00172-1
Selam Mihreteab BSc , Karen Anderson CBLT , Irene Molina de la Fuente MD , Prof Colin J. Sutherland PhD , David Smith DLT , Jane Cunningham MD , Khalid B. Beshir PhD , Qin Cheng PhD
<div><h3>Background</h3><div>Eritrea was the first African country to discontinue the use of histidine rich protein 2 (HRP2)-detecting rapid diagnostic tests (RDTs) for malaria diagnosis following reports of a high prevalence of <em>pfhrp2</em>/<em>3-</em>deleted <em>Plasmodium falciparum</em> parasites causing false-negative results in the country. Eritrea was also the first African country to report partial artemisinin resistance due to the <em>P falciparum</em> kelch13 (<em>pfk13</em>) Arg622Ile mutation. We aimed to characterise the spatial distribution of <em>pfk13</em> mutants and their interactions with <em>pfhrp2/3</em> deletions in Eritrea and to assess the role of the use of HRP2-detecting RDTs and antimalarial (artesunate–amodiaquine) therapy in the spread of the two variants.</div></div><div><h3>Methods</h3><div>We conducted a retrospective molecular epidemiological analysis of <em>pfk13</em> mutations and <em>pfhrp2/3</em> deletions in existing <em>P falciparum</em>-infected blood samples collected as part of previous <em>pfhrp2/3</em> deletion and severe malaria studies. Samples were collected in March, 2016 and between September, 2018, and January, 2020, from symptomatic patients seeking care at 15 health centres in four administration zones (Semenawi Keyih Bahri, Gash Barka, Anseba, and Debub) in Eritrea. A fragment spanning the propeller region of <em>pfk13</em> was amplified from samples and sequenced using Sanger sequencing or targeted amplicon sequencing to identify genetic mutations. Deletions of <em>pfhrp2/3</em> genes in samples were determined using multiplex quantitative PCR. Parasite haplotypes and genetic relatedness of parasite haplotypes were determined previously using microsatellite marker typing. The primary objective was to determine the prevalence of <em>pfk13</em> mutations at health centres and administrative zones. The secondary objective was to investigate whether <em>pfk13</em> mutants and <em>pfhrp2/3</em> deleted parasites converge.</div></div><div><h3>Findings</h3><div>We sequenced 50 samples collected in March, 2016 from the Semenawi Keyih Bahri zone and identified no <em>pfk13</em> mutations. By contrast, in 587 samples included in this study that were collected from health centres in Gash Barka, Anseba, and Debub in 2018–20, we detected five different single non-synonymous mutations: Glu605Lys, Arg622Ile, Asn657Lys, Lys658Glu, and Ser679Leu. The most prevalent mutation was <em>pfk13</em> Arg622Ile, which was detected in samples collected from all nine health centres where more than five samples were available across all three administration zones, with an overall prevalence of 11·9% (70 of 587 samples; range 5·9–28·0%). We identified 22 unique <em>pfk13</em> Arg622Ile mutant haplotypes among 26 samples tested, of which 13 (59·1%) were genetically related, whereas the remaining nine (40·9%) were not. The prevalence of <em>pfk13</em> Arg622Ile was significantly higher in parasites with a single <em>pfhrp
背景:厄立特里亚是第一个停止使用富组氨酸蛋白2 (HRP2)检测快速诊断试验(RDTs)进行疟疾诊断的非洲国家,此前有报告称,该国高流行的富组氨酸蛋白2/3缺失的恶性疟原虫导致假阴性结果。厄立特里亚也是第一个报告因恶性疟原虫kelch13 (pfk13) Arg622Ile突变而产生部分青蒿素耐药性的非洲国家。我们的目的是表征厄立特里亚pfk13突变体的空间分布及其与pfhrp2/3缺失的相互作用,并评估使用hrp2检测rdt和抗疟疾(青蒿琥酯-阿莫地喹)治疗在两种变体传播中的作用。方法:我们对pfk13突变和pfhrp2/3缺失的现有恶性疟原虫感染血液样本进行了回顾性分子流行病学分析,这些样本是之前pfhrp2/3缺失和严重疟疾研究的一部分。2016年3月和2018年9月至2020年1月期间,从厄立特里亚四个行政区(Semenawi Keyih Bahri、Gash Barka、Anseba和Debub)的15个卫生中心就诊的有症状患者中采集了样本。从样本中扩增出跨越pfk13螺旋桨区域的片段,并使用Sanger测序或靶向扩增子测序进行测序,以确定基因突变。采用多重定量PCR检测样品中pfhrp2/3基因的缺失。寄生虫的单倍型和遗传亲缘关系以前是用微卫星标记分型确定的。主要目标是确定pfk13突变在保健中心和行政区域的流行情况。次要目的是研究pfk13突变体和pfhrp2/3缺失寄生虫是否会聚。研究结果:我们对2016年3月从Semenawi Keyih Bahri区收集的50份样本进行了测序,未发现pfk13突变。相比之下,在2018- 2020年从Gash Barka、Anseba和Debub的卫生中心收集的587份样本中,我们检测到5种不同的单一非同义突变:Glu605Lys、Arg622Ile、Asn657Lys、Lys658Glu和Ser679Leu。最普遍的突变是pfk13 Arg622Ile,在所有9个卫生中心收集的样本中检测到,所有3个行政区都有5个以上的样本,总体患病率为11.9%(587个样本中有70个;范围5·9-28·0%)。我们在26个样本中鉴定出22个独特的pfk13 Arg622Ile突变单倍型,其中13个(59.1%)与遗传相关,其余9个(40.9%)与遗传无关。单个pfhrp3缺失的疟原虫(255份样本中46份[18.0%])中pfk13 Arg622Ile的流行率显著高于非pfhrp3 /3缺失的疟原虫(161份样本中10份[6.2%]);优势比3.89 [95% CI 1.59 ~ 7.61];P = 0.0006)和双pfhrp2/3缺失疟原虫(145例中13例[9.0%];2·23(常规··68);p = 0·018)。解释:pfk13 Arg622Ile突变的地理传播最初可能是由于使用hrp2检测rdt的检测和治疗策略下pfhrp2/3缺失的克隆扩增和传播。随后,青蒿素联合治疗的选择性压力可能进一步促进了pfk13 Arg622Ile和pfhrp2/3缺失的传播。需要持续监测pfk13和pfhrp2/3变异的趋势,以便为厄立特里亚和其他非洲国家的有效疟疾控制和消除战略提供信息。资助:美国国防部武装部队健康监测处、全球新发感染监测处(AFHSD/GEIS)和威康信托基金。
{"title":"The spread of molecular markers of artemisinin partial resistance and diagnostic evasion in Eritrea: a retrospective molecular epidemiology study","authors":"Selam Mihreteab BSc ,&nbsp;Karen Anderson CBLT ,&nbsp;Irene Molina de la Fuente MD ,&nbsp;Prof Colin J. Sutherland PhD ,&nbsp;David Smith DLT ,&nbsp;Jane Cunningham MD ,&nbsp;Khalid B. Beshir PhD ,&nbsp;Qin Cheng PhD","doi":"10.1016/S2666-5247(24)00172-1","DOIUrl":"10.1016/S2666-5247(24)00172-1","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Eritrea was the first African country to discontinue the use of histidine rich protein 2 (HRP2)-detecting rapid diagnostic tests (RDTs) for malaria diagnosis following reports of a high prevalence of &lt;em&gt;pfhrp2&lt;/em&gt;/&lt;em&gt;3-&lt;/em&gt;deleted &lt;em&gt;Plasmodium falciparum&lt;/em&gt; parasites causing false-negative results in the country. Eritrea was also the first African country to report partial artemisinin resistance due to the &lt;em&gt;P falciparum&lt;/em&gt; kelch13 (&lt;em&gt;pfk13&lt;/em&gt;) Arg622Ile mutation. We aimed to characterise the spatial distribution of &lt;em&gt;pfk13&lt;/em&gt; mutants and their interactions with &lt;em&gt;pfhrp2/3&lt;/em&gt; deletions in Eritrea and to assess the role of the use of HRP2-detecting RDTs and antimalarial (artesunate–amodiaquine) therapy in the spread of the two variants.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We conducted a retrospective molecular epidemiological analysis of &lt;em&gt;pfk13&lt;/em&gt; mutations and &lt;em&gt;pfhrp2/3&lt;/em&gt; deletions in existing &lt;em&gt;P falciparum&lt;/em&gt;-infected blood samples collected as part of previous &lt;em&gt;pfhrp2/3&lt;/em&gt; deletion and severe malaria studies. Samples were collected in March, 2016 and between September, 2018, and January, 2020, from symptomatic patients seeking care at 15 health centres in four administration zones (Semenawi Keyih Bahri, Gash Barka, Anseba, and Debub) in Eritrea. A fragment spanning the propeller region of &lt;em&gt;pfk13&lt;/em&gt; was amplified from samples and sequenced using Sanger sequencing or targeted amplicon sequencing to identify genetic mutations. Deletions of &lt;em&gt;pfhrp2/3&lt;/em&gt; genes in samples were determined using multiplex quantitative PCR. Parasite haplotypes and genetic relatedness of parasite haplotypes were determined previously using microsatellite marker typing. The primary objective was to determine the prevalence of &lt;em&gt;pfk13&lt;/em&gt; mutations at health centres and administrative zones. The secondary objective was to investigate whether &lt;em&gt;pfk13&lt;/em&gt; mutants and &lt;em&gt;pfhrp2/3&lt;/em&gt; deleted parasites converge.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;We sequenced 50 samples collected in March, 2016 from the Semenawi Keyih Bahri zone and identified no &lt;em&gt;pfk13&lt;/em&gt; mutations. By contrast, in 587 samples included in this study that were collected from health centres in Gash Barka, Anseba, and Debub in 2018–20, we detected five different single non-synonymous mutations: Glu605Lys, Arg622Ile, Asn657Lys, Lys658Glu, and Ser679Leu. The most prevalent mutation was &lt;em&gt;pfk13&lt;/em&gt; Arg622Ile, which was detected in samples collected from all nine health centres where more than five samples were available across all three administration zones, with an overall prevalence of 11·9% (70 of 587 samples; range 5·9–28·0%). We identified 22 unique &lt;em&gt;pfk13&lt;/em&gt; Arg622Ile mutant haplotypes among 26 samples tested, of which 13 (59·1%) were genetically related, whereas the remaining nine (40·9%) were not. The prevalence of &lt;em&gt;pfk13&lt;/em&gt; Arg622Ile was significantly higher in parasites with a single &lt;em&gt;pfhrp","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 2","pages":"Article 100930"},"PeriodicalIF":20.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Global epidemiological trend of Klebsiella pneumoniae ST340: emergence of subclade KL15 co-producing K pneumoniae carbapenemase-2 and New Delhi metallo-β-lactamase-7 in the Americas 肺炎克雷伯菌 ST340 的全球流行趋势:美洲出现了同时产生肺炎克雷伯菌碳青霉烯酶-2 和新德里金属-β-内酰胺酶-7 的 KL15 亚支系。
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2025-02-01 DOI: 10.1016/j.lanmic.2024.100990
Felipe Vásquez-Ponce , Marco Vianello , Johana Becerra , Jesus G M Pariona , Karine Dantas , Gregory Melocco , Guilherme M Oliveira , Fernanda Esposito , Nilton Lincopan
{"title":"Global epidemiological trend of Klebsiella pneumoniae ST340: emergence of subclade KL15 co-producing K pneumoniae carbapenemase-2 and New Delhi metallo-β-lactamase-7 in the Americas","authors":"Felipe Vásquez-Ponce ,&nbsp;Marco Vianello ,&nbsp;Johana Becerra ,&nbsp;Jesus G M Pariona ,&nbsp;Karine Dantas ,&nbsp;Gregory Melocco ,&nbsp;Guilherme M Oliveira ,&nbsp;Fernanda Esposito ,&nbsp;Nilton Lincopan","doi":"10.1016/j.lanmic.2024.100990","DOIUrl":"10.1016/j.lanmic.2024.100990","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 2","pages":"Article 100990"},"PeriodicalIF":20.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rapidly evolving recombinant monkeypox virus strains compound the challenges of the 2024 mpox outbreak 快速进化的重组猴痘病毒株加剧了 2024 年猴痘爆发的挑战。
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2025-02-01 DOI: 10.1016/j.lanmic.2024.101017
Ting-Yu Yeh , Patrick J Feehley , Michael C Feehley , Chieh-Fan Chen , Tung-Yuan Tsai , Hsiang-Lan Cheng , Gregory P Contreras
{"title":"Rapidly evolving recombinant monkeypox virus strains compound the challenges of the 2024 mpox outbreak","authors":"Ting-Yu Yeh ,&nbsp;Patrick J Feehley ,&nbsp;Michael C Feehley ,&nbsp;Chieh-Fan Chen ,&nbsp;Tung-Yuan Tsai ,&nbsp;Hsiang-Lan Cheng ,&nbsp;Gregory P Contreras","doi":"10.1016/j.lanmic.2024.101017","DOIUrl":"10.1016/j.lanmic.2024.101017","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 2","pages":"Article 101017"},"PeriodicalIF":20.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Artemether–lumefantrine–amodiaquine or artesunate–amodiaquine combined with single low-dose primaquine to reduce Plasmodium falciparum malaria transmission in Ouélessébougou, Mali: a five-arm, phase 2, single-blind, randomised controlled trial 蒿甲醚-氨苯曲林-阿莫地喹或青蒿琥酯-阿莫地喹联合单次低剂量伯氨喹减少马里ousamlessacimadbougou地区恶性疟原虫疟疾传播:一项5组、2期、单盲、随机对照试验。
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2025-02-01 DOI: 10.1016/j.lanmic.2024.100966
Almahamoudou Mahamar PhD , Leen N Vanheer MD , Merel J Smit MD , Koualy Sanogo MD , Youssouf Sinaba MD , Sidi M Niambele PharmD , Makonon Diallo MD , Oumar M Dicko MD , Richard S Diarra MD , Seydina O Maguiraga MD , Ahamadou Youssouf PharmD , Adama Sacko MS , Sekouba Keita MS , Siaka Samake PharmD , Adama Dembele MS , Karina Teelen , Yahia Dicko MD , Sekou F Traore PhD , Prof Arjen Dondorp MD , Prof Chris Drakeley PhD , Prof Alassane Dicko MD
<div><h3>Background</h3><div>Triple artemisinin-based combination therapies (TACTs) can delay the spread of antimalarial drug resistance. Artesunate–amodiaquine is widely used for uncomplicated <em>Plasmodium falciparum</em> malaria. We therefore aimed to determine the safety and efficacy of artemether–lumefantrine–amodiaquine and artesunate–amodiaquine with and without single low-dose primaquine for reducing gametocyte carriage and transmission to mosquitoes.</div></div><div><h3>Methods</h3><div>We did a five-arm, single-blind, phase 2 randomised controlled trial at the Ouélessébougou Clinical Research Unit of the Malaria Research and Training Centre of the University of Sciences, Techniques and Technologies of Bamako in Mali. Eligible participants were aged 10–50 years, with asymptomatic <em>P falciparum</em> microscopy-detected gametocyte carriage. Eligible participants were randomly allocated (1:1:1:1:1) to receive either artemether–lumefantrine, artemether–lumefantrine–amodiaquine, artemether–lumefantrine–amodiaquine plus primaquine, artesunate–amodiaquine, or artesunate–amodiaquine plus primaquine. Treatment regimens were administered on days 0, 1, and 2; primaquine was given as a single dose on day 0. All staff except the trial pharmacist and participants were masked to the treatment allocation. The primary outcome was the median percentage change in mosquito infection rate between pretreatment and 2 days after treatment initiation, assessed by direct membrane feeding assay. Data were analysed using a per-protocol analysis. This study is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT05550909</span><svg><path></path></svg></span>.</div></div><div><h3>Findings</h3><div>Between Oct 16, 2022, and Dec 28, 2022, a total of 1249 individuals were screened; of whom, 100 were enrolled and randomly assigned to one of the five treatment groups (20 per group). Before treatment, 61 (61%) of 100 participants were infectious to mosquitoes, with a median of 7·3% (IQR 3·2 to 23·5) of mosquitoes becoming infected. Among infectious participants, the median percentage reduction in mosquito infection rate between pretreatment and 2 days after treatment was 100% (IQR 100 to 100) in the artemether–lumefantrine (p=0·0018), artemether–lumefantrine–amodiaquine (p=0·0018), and artemether–lumefantrine–amodiaquine plus primaquine (p=0·0009) treatment groups. In the artesunate–amodiaquine group the median percentage reduction in mosquito infection rate was only 32% (IQR –10·9 to 79·4; p=0·19), whereas a 100% median reduction was seen in the artesunate–amodiaquine plus primaquine group (IQR 100 to 100; p=0·0009). At day 2, two (10%) of 20 participants in the artemether–lumefantrine group, two (11%) of 19 in the artemether–lumefantrine–amodiaquine group, and 15 (75%) of 20 in the artesunate–amodiaquine group infected any number of mosquitoes whereas no infected mosquitoes were observed at this timepoint in the groups
背景:以青蒿素为基础的三联疗法(TACTs)可以延缓抗疟药耐药性的传播。青蒿琥酯-阿莫地喹广泛用于治疗无并发症的恶性疟原虫疟疾。因此,我们的目的是确定蒿甲醚-氨芳啶-阿莫地喹和青蒿琥酯-阿莫地喹加或不加单一低剂量伯氨喹对减少配子体携带和传播给蚊子的安全性和有效性。方法:我们在马里巴马科科学、技术和技术大学疟疾研究和培训中心的ousamlessbougou临床研究部进行了一项五臂、单盲、2期随机对照试验。符合条件的参与者年龄在10-50岁之间,显微镜下检测到配子细胞携带无症状的恶性疟原虫。符合条件的参与者被随机分配(1:1:1:1:1)接受蒿甲醚-甲苯胺、蒿甲醚-甲苯胺-阿莫地喹、蒿甲醚-甲苯胺-阿莫地喹加伯氨喹、青蒿琥酯-阿莫地喹或蒿甲酯-阿莫地喹加伯氨喹。治疗方案分别在第0、1、2天实施;伯氨喹在第0天单剂量给药。除试验药剂师和参与者外,所有工作人员都不知道治疗分配。主要观察指标为治疗前和治疗开始后2天蚊虫感染率变化的中位数百分比,采用直接膜饲养法评估。使用每个协议分析来分析数据。本研究已在ClinicalTrials.gov注册,编号NCT05550909。研究结果:在2022年10月16日至2022年12月28日期间,共筛查了1249人;其中100人被招募并随机分配到5个治疗组(每组20人)。治疗前,100名参与者中61人(61%)被蚊子感染,中位数为7.3% (IQR为3.2 ~ 23.5%)。在感染参与者中,蒿甲醚-甲苯胺-阿莫地喹(p= 0.0018)、蒿甲醚-甲苯胺-阿莫地喹(p= 0.0018)和蒿甲醚-甲苯胺-阿莫地喹加伯氨喹(p= 0.009)治疗组的蚊子感染率在治疗前和治疗后2天的中位数百分比降低为100% (IQR 100 ~ 100)。在青蒿琥酯-阿莫地喹组中,蚊子感染率下降的中位数百分比仅为32% (IQR -10·9 ~ 79·4;p= 0.19),而在青蒿琥酯-阿莫地喹+伯氨喹组中位值降低100% (IQR 100 ~ 100;p = 0·0009)。在第2天,20名受试者中有2人(10%)感染了任意数量的蚊子,19名受试者中有2人(11%)感染了青蒿琥酯-阿莫地喹组,20名受试者中有15人(75%)感染了任意数量的蚊子,而在这个时间点上,布氨喹组没有观察到受感染的蚊子。100名参与者中有85人(85%)在随访期间共发生262起不良事件;其中,181例(69%)为轻度,81例(31%)为中度。无严重不良事件报告。解释:我们的研究结果支持蒿甲醚-氨苯曲明单独或作为TACT的一部分在48小时内预防几乎所有人-蚊子疟疾寄生虫传播的有效性。相比之下,用青蒿琥酯-阿莫地喹治疗后观察到大量传播。添加单次低剂量的伯氨喹可迅速阻断蚊虫传播,无论是否使用裂裂剂。资助:比尔及梅琳达·盖茨基金会。
{"title":"Artemether–lumefantrine–amodiaquine or artesunate–amodiaquine combined with single low-dose primaquine to reduce Plasmodium falciparum malaria transmission in Ouélessébougou, Mali: a five-arm, phase 2, single-blind, randomised controlled trial","authors":"Almahamoudou Mahamar PhD ,&nbsp;Leen N Vanheer MD ,&nbsp;Merel J Smit MD ,&nbsp;Koualy Sanogo MD ,&nbsp;Youssouf Sinaba MD ,&nbsp;Sidi M Niambele PharmD ,&nbsp;Makonon Diallo MD ,&nbsp;Oumar M Dicko MD ,&nbsp;Richard S Diarra MD ,&nbsp;Seydina O Maguiraga MD ,&nbsp;Ahamadou Youssouf PharmD ,&nbsp;Adama Sacko MS ,&nbsp;Sekouba Keita MS ,&nbsp;Siaka Samake PharmD ,&nbsp;Adama Dembele MS ,&nbsp;Karina Teelen ,&nbsp;Yahia Dicko MD ,&nbsp;Sekou F Traore PhD ,&nbsp;Prof Arjen Dondorp MD ,&nbsp;Prof Chris Drakeley PhD ,&nbsp;Prof Alassane Dicko MD","doi":"10.1016/j.lanmic.2024.100966","DOIUrl":"10.1016/j.lanmic.2024.100966","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Triple artemisinin-based combination therapies (TACTs) can delay the spread of antimalarial drug resistance. Artesunate–amodiaquine is widely used for uncomplicated &lt;em&gt;Plasmodium falciparum&lt;/em&gt; malaria. We therefore aimed to determine the safety and efficacy of artemether–lumefantrine–amodiaquine and artesunate–amodiaquine with and without single low-dose primaquine for reducing gametocyte carriage and transmission to mosquitoes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We did a five-arm, single-blind, phase 2 randomised controlled trial at the Ouélessébougou Clinical Research Unit of the Malaria Research and Training Centre of the University of Sciences, Techniques and Technologies of Bamako in Mali. Eligible participants were aged 10–50 years, with asymptomatic &lt;em&gt;P falciparum&lt;/em&gt; microscopy-detected gametocyte carriage. Eligible participants were randomly allocated (1:1:1:1:1) to receive either artemether–lumefantrine, artemether–lumefantrine–amodiaquine, artemether–lumefantrine–amodiaquine plus primaquine, artesunate–amodiaquine, or artesunate–amodiaquine plus primaquine. Treatment regimens were administered on days 0, 1, and 2; primaquine was given as a single dose on day 0. All staff except the trial pharmacist and participants were masked to the treatment allocation. The primary outcome was the median percentage change in mosquito infection rate between pretreatment and 2 days after treatment initiation, assessed by direct membrane feeding assay. Data were analysed using a per-protocol analysis. 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;NCT05550909&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;Between Oct 16, 2022, and Dec 28, 2022, a total of 1249 individuals were screened; of whom, 100 were enrolled and randomly assigned to one of the five treatment groups (20 per group). Before treatment, 61 (61%) of 100 participants were infectious to mosquitoes, with a median of 7·3% (IQR 3·2 to 23·5) of mosquitoes becoming infected. Among infectious participants, the median percentage reduction in mosquito infection rate between pretreatment and 2 days after treatment was 100% (IQR 100 to 100) in the artemether–lumefantrine (p=0·0018), artemether–lumefantrine–amodiaquine (p=0·0018), and artemether–lumefantrine–amodiaquine plus primaquine (p=0·0009) treatment groups. In the artesunate–amodiaquine group the median percentage reduction in mosquito infection rate was only 32% (IQR –10·9 to 79·4; p=0·19), whereas a 100% median reduction was seen in the artesunate–amodiaquine plus primaquine group (IQR 100 to 100; p=0·0009). At day 2, two (10%) of 20 participants in the artemether–lumefantrine group, two (11%) of 19 in the artemether–lumefantrine–amodiaquine group, and 15 (75%) of 20 in the artesunate–amodiaquine group infected any number of mosquitoes whereas no infected mosquitoes were observed at this timepoint in the groups ","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 2","pages":"Article 100966"},"PeriodicalIF":20.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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