Pub Date : 2025-02-01DOI: 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.
{"title":"Crucial role of biosensors in the detection of helminth biomarkers in public health programmes","authors":"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","doi":"10.1016/j.lanmic.2024.100964","DOIUrl":"10.1016/j.lanmic.2024.100964","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 2","pages":"Article 100964"},"PeriodicalIF":20.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606838","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}
Pub Date : 2025-02-01DOI: 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。
{"title":"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","authors":"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","doi":"10.1016/j.lanmic.2024.06.002","DOIUrl":"10.1016/j.lanmic.2024.06.002","url":null,"abstract":"<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","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 2","pages":"Article 100935"},"PeriodicalIF":20.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819554","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}
Pub Date : 2025-02-01DOI: 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
{"title":"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","authors":"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","doi":"10.1016/j.lanmic.2024.100961","DOIUrl":"10.1016/j.lanmic.2024.100961","url":null,"abstract":"<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","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 2","pages":"Article 100961"},"PeriodicalIF":20.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878320","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}
Pub Date : 2025-02-01DOI: 10.1016/j.lanmic.2025.101075
The Lancet Microbe
{"title":"Brain microbiome: is it all in our heads?","authors":"The Lancet Microbe","doi":"10.1016/j.lanmic.2025.101075","DOIUrl":"10.1016/j.lanmic.2025.101075","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 2","pages":"Article 101075"},"PeriodicalIF":20.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081414","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}
Pub Date : 2025-02-01DOI: 10.1016/j.lanmic.2024.101011
lianwei Zhou , Minye Wang , Wenbo Li
{"title":"Genomic epidemiology of Salmonella: the need to consider vaccination history and nutritional status in resistance transmission studies","authors":"lianwei Zhou , Minye Wang , Wenbo Li","doi":"10.1016/j.lanmic.2024.101011","DOIUrl":"10.1016/j.lanmic.2024.101011","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 2","pages":"Article 101011"},"PeriodicalIF":20.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510189","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}
Pub Date : 2025-02-01DOI: 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 , Dimple Chudasama , Russell Hope , 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}
Pub Date : 2025-02-01DOI: 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
{"title":"The spread of molecular markers of artemisinin partial resistance and diagnostic evasion in Eritrea: a retrospective molecular epidemiology study","authors":"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","doi":"10.1016/S2666-5247(24)00172-1","DOIUrl":"10.1016/S2666-5247(24)00172-1","url":null,"abstract":"<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","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}
Pub Date : 2025-02-01DOI: 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 , Marco Vianello , Johana Becerra , Jesus G M Pariona , Karine Dantas , Gregory Melocco , Guilherme M Oliveira , Fernanda Esposito , 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}
Pub Date : 2025-02-01DOI: 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
{"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 , 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","doi":"10.1016/j.lanmic.2024.100966","DOIUrl":"10.1016/j.lanmic.2024.100966","url":null,"abstract":"<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 ","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}