Pub Date : 2026-03-01Epub Date: 2025-10-24DOI: 10.1016/j.lanmic.2025.101269
Jingyuan Ning , Keran Sun
{"title":"Implementation of cholera RDTs: bridging laboratory precision and field reality","authors":"Jingyuan Ning , Keran Sun","doi":"10.1016/j.lanmic.2025.101269","DOIUrl":"10.1016/j.lanmic.2025.101269","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 3","pages":"Article 101269"},"PeriodicalIF":20.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147420424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-14DOI: 10.1016/j.lanmic.2025.101315
Claas Kirchhelle PhD , Mirza Y Alas Portillo PhD , Mark D M Davis PhD , Prof Assa Doron PhD , Anahí Dreser PhD , Nicolas Fortané PhD , Christian Haddad PhD , Prof Stephen Hinchliffe PhD , Prof Samuel Kariuki PhD , Sonia Lewycka PhD , Prof Sassy Molyneux PhD , Cristina Moreno Lozano PhD , Edna Mutua PhD , Prof Iruka N Okeke PhD , Mingyuan Zhang Betancourt PhD , Prof Clare I R Chandler PhD
Antimicrobial resistance (AMR) remains a major global health threat. Despite increasing international attention, AMR governance has often neglected social and equity dimensions, and there is a crucial need to synthesise evidence from social sciences and humanities scholarship to devise more people-centred approaches. In this Personal View, we report a qualitative stocktake of the intended and unintended consequences of the most recent phase of global AMR governance that started around the year 2000 and reached a high point with the 2015 Global Action Plan (GAP) on AMR. Our interdisciplinary analysis was guided by the five key objectives of current AMR governance, as organised in the 2015 GAP, to reduce AMR through awareness, surveillance, infection reduction, antimicrobial use optimisation, and research and innovation. The resulting assessment indicated mixed outcomes. Although the past decade witnessed unprecedented AMR-related action and investment, empirical studies highlight negative consequences of the decontextualised export of high-income governance frameworks and the neglect of upstream antibiotic-sensitive reforms of production, care, and innovation systems. Not embedding AMR within more general developmental and environmental challenges has also undermined local buy-in and contributed to the siloed status of AMR policies. For the next GAP, we recommend foregrounding equitable interventions; adopting a bottom-up, integrated perspective to incorporate local realities and solutions; and creating robust social sciences and humanities feedback loops for global AMR frameworks.
{"title":"(Un)intended consequences: a social sciences stocktake of a decade of Global Action Plan-inspired antimicrobial governance","authors":"Claas Kirchhelle PhD , Mirza Y Alas Portillo PhD , Mark D M Davis PhD , Prof Assa Doron PhD , Anahí Dreser PhD , Nicolas Fortané PhD , Christian Haddad PhD , Prof Stephen Hinchliffe PhD , Prof Samuel Kariuki PhD , Sonia Lewycka PhD , Prof Sassy Molyneux PhD , Cristina Moreno Lozano PhD , Edna Mutua PhD , Prof Iruka N Okeke PhD , Mingyuan Zhang Betancourt PhD , Prof Clare I R Chandler PhD","doi":"10.1016/j.lanmic.2025.101315","DOIUrl":"10.1016/j.lanmic.2025.101315","url":null,"abstract":"<div><div>Antimicrobial resistance (AMR) remains a major global health threat. Despite increasing international attention, AMR governance has often neglected social and equity dimensions, and there is a crucial need to synthesise evidence from social sciences and humanities scholarship to devise more people-centred approaches. In this Personal View, we report a qualitative stocktake of the intended and unintended consequences of the most recent phase of global AMR governance that started around the year 2000 and reached a high point with the 2015 Global Action Plan (GAP) on AMR. Our interdisciplinary analysis was guided by the five key objectives of current AMR governance, as organised in the 2015 GAP, to reduce AMR through awareness, surveillance, infection reduction, antimicrobial use optimisation, and research and innovation. The resulting assessment indicated mixed outcomes. Although the past decade witnessed unprecedented AMR-related action and investment, empirical studies highlight negative consequences of the decontextualised export of high-income governance frameworks and the neglect of upstream antibiotic-sensitive reforms of production, care, and innovation systems. Not embedding AMR within more general developmental and environmental challenges has also undermined local buy-in and contributed to the siloed status of AMR policies. For the next GAP, we recommend foregrounding equitable interventions; adopting a bottom-up, integrated perspective to incorporate local realities and solutions; and creating robust social sciences and humanities feedback loops for global AMR frameworks.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 3","pages":"Article 101315"},"PeriodicalIF":20.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994572","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}
<div><h3>Background</h3><div>The emergence of <em>Plasmodium falciparum</em> strains with reduced susceptibility to the artemisinin component of artemisinin combination therapies poses a serious threat to the treatment and control of malaria in sub-Saharan Africa. Regimens consisting of combinations of three or more conventional antimalarials have been proposed as a new treatment paradigm to overcome the impending problem of drug-resistant malaria. It was the aim of the MultiMal study to assess the safety, tolerability, and efficacy of the two novel multidrug antimalarial combination therapies, artesunate–pyronaridine–atovaquone–proguanil (APAP) and artesunate–fosmidomycin–clindamycin (AFC), in comparison with standard artesunate–pyronaridine (AP).</div></div><div><h3>Methods</h3><div>This open-label, randomised, controlled, clinical, phase 2 trial was done in Lambaréné, Gabon, and Kumasi, Ghana. Patients with uncomplicated malaria who had fever or a history of fever in the preceding 24 h and a parasitaemia in the range of 1000–100 000 per μL of blood were enrolled. Random permuted blocks of variable block sizes stratified by country were computed to generate a treatment allocation sequence. Recruitment was done across three age groups: children aged 6 months to 10 years, adolescents aged 11–17 years, and adults aged 18–65 years. Weight-adjusted oral, once-daily therapy was administered for 3 consecutive days for AP and APAP regimens dosed according to the recommendations of the manufacturer and twice daily for AFC (dose: artesunate 2 mg/kg, fosmidomycin 30 mg/kg, and clindamycin 10 mg/kg). Participants were followed up over a 42-day period. The primary endpoints of the trial, related to pharmacokinetic analyses, are being reported elsewhere; this Article reports the secondary endpoints—safety, tolerability, and efficacy of the treatment regimens (defined as adequate clinical and parasitological response [ACPR]) at days 28 and 42 after treatment initiation. ACPRs were calculated in the intention-to-treat and PCR-corrected per-protocol populations at these timepoints, whereas safety and tolerability outcomes were assessed continuously over the 42-day follow-up period in the safety population. This trial is registered with pactr.samrc.ac.za, PACTR202008909968293 and is complete.</div></div><div><h3>Findings</h3><div>Recruitment and follow-up took place between Jan 5 and Nov 5, 2021. Of 309 screened individuals, 100 patients with uncomplicated malaria were recruited into this clinical trial: 20 semi-immune patients aged 18–65 years, 40 adolescents aged between 11 and 17 years, and finally 40 patients aged 6 months to 10 years. PCR-corrected ACPR in the per-protocol set was 100% (95% CI 80–100) for AP, 100% (90–100) for APAP, and 97% (86–100) for AFC for day 28, and 87·5% (62–98) for AP, 85·3% (69–95) for APAP, and 94·4% (81–99) for AFC on day 42. Uncorrected ACPR in the intention-to-treat set was 85% (95% CI 62–97%) for AP, 87·5% (73–96) for APAP, a
{"title":"Artesunate–pyronaridine–atovaquone–proguanil and artesunate–fosmidomycin–clindamycin compared with standard artesunate–pyronaridine for the treatment of uncomplicated malaria (MultiMal): a randomised, controlled, clinical, phase 2 trial in Gabon and Ghana","authors":"Jean Claude Dejon Agobé MD PhD , Oumou Maïga-Ascofaré MSc PhD , Prof Ayôla Akim Adegnika MD PhD , Christoph Pfaffendorf , Joseph Marfo Boaheng MPhil PhD , Jean Ronald Edoa MD , Isaac Darko Agyiri , Romeo Bayode Adegbite MD PhD , Esi Yacoba Bart-Plange MD MPH , Ebenezer Ahenkan , Dorothea Ekoka Mbassi MD , Francisca Naana Sarpong MPhil , Esther Placca MPhil , Dominic Kwabena Kanin , Portia Bakari BSc , Wibke Loag , Jenny Kettenbeil BA , Prof Sanjeev Krishna PhD , Prof Bertrand Lell PhD , Prof Selidji Todagbe Agnandji PhD , Johannes Mischlinger MD PhD","doi":"10.1016/j.lanmic.2025.101245","DOIUrl":"10.1016/j.lanmic.2025.101245","url":null,"abstract":"<div><h3>Background</h3><div>The emergence of <em>Plasmodium falciparum</em> strains with reduced susceptibility to the artemisinin component of artemisinin combination therapies poses a serious threat to the treatment and control of malaria in sub-Saharan Africa. Regimens consisting of combinations of three or more conventional antimalarials have been proposed as a new treatment paradigm to overcome the impending problem of drug-resistant malaria. It was the aim of the MultiMal study to assess the safety, tolerability, and efficacy of the two novel multidrug antimalarial combination therapies, artesunate–pyronaridine–atovaquone–proguanil (APAP) and artesunate–fosmidomycin–clindamycin (AFC), in comparison with standard artesunate–pyronaridine (AP).</div></div><div><h3>Methods</h3><div>This open-label, randomised, controlled, clinical, phase 2 trial was done in Lambaréné, Gabon, and Kumasi, Ghana. Patients with uncomplicated malaria who had fever or a history of fever in the preceding 24 h and a parasitaemia in the range of 1000–100 000 per μL of blood were enrolled. Random permuted blocks of variable block sizes stratified by country were computed to generate a treatment allocation sequence. Recruitment was done across three age groups: children aged 6 months to 10 years, adolescents aged 11–17 years, and adults aged 18–65 years. Weight-adjusted oral, once-daily therapy was administered for 3 consecutive days for AP and APAP regimens dosed according to the recommendations of the manufacturer and twice daily for AFC (dose: artesunate 2 mg/kg, fosmidomycin 30 mg/kg, and clindamycin 10 mg/kg). Participants were followed up over a 42-day period. The primary endpoints of the trial, related to pharmacokinetic analyses, are being reported elsewhere; this Article reports the secondary endpoints—safety, tolerability, and efficacy of the treatment regimens (defined as adequate clinical and parasitological response [ACPR]) at days 28 and 42 after treatment initiation. ACPRs were calculated in the intention-to-treat and PCR-corrected per-protocol populations at these timepoints, whereas safety and tolerability outcomes were assessed continuously over the 42-day follow-up period in the safety population. This trial is registered with pactr.samrc.ac.za, PACTR202008909968293 and is complete.</div></div><div><h3>Findings</h3><div>Recruitment and follow-up took place between Jan 5 and Nov 5, 2021. Of 309 screened individuals, 100 patients with uncomplicated malaria were recruited into this clinical trial: 20 semi-immune patients aged 18–65 years, 40 adolescents aged between 11 and 17 years, and finally 40 patients aged 6 months to 10 years. PCR-corrected ACPR in the per-protocol set was 100% (95% CI 80–100) for AP, 100% (90–100) for APAP, and 97% (86–100) for AFC for day 28, and 87·5% (62–98) for AP, 85·3% (69–95) for APAP, and 94·4% (81–99) for AFC on day 42. Uncorrected ACPR in the intention-to-treat set was 85% (95% CI 62–97%) for AP, 87·5% (73–96) for APAP, a","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 3","pages":"Article 101245"},"PeriodicalIF":20.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146094720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-23DOI: 10.1016/j.lanmic.2025.101301
Katherine E Gallagher PhD , Fredrick Odiwour BSc , Prof Christian Bottomley PhD , John Ojal PhD , Aisha Adamu PhD , Esther Muthumbi PhD , Eunice W Kagucia PhD , Prof Laura L Hammitt MD , Sergio Massora PhD , Betuel Sigaúque PhD , Alberto Chaúque MSc , Leocadia Vilanculos MD , Jennifer R Verani MD , Maria da Gloria Carvalho PhD , Prof Anne von Gottberg PhD , Jackie Kleynhans PhD , Prof Shabir A Madhi PhD , Courtney P Olwagen PhD , Prof Grant Mackenzie PhD , Rasheed Salaudeen MSc , Prof J Anthony G Scott FRCP
Background
Serotype-specific estimates of pneumococcal invasiveness used in pneumococcal carriage transmission models to predict changes in disease incidence post-vaccination are largely derived from high-income settings. We conducted a systematic review of carriage prevalence and invasive pneumococcal disease (IPD) incidence to calculate case–carrier ratios (CCRs) in different income settings.
Methods
We conducted a systematic search of MEDLINE, Embase, and Global Health databases on March 14, 2022, to identify publications on pneumococcal carriage prevalence or IPD incidence; we requested individual-level data from authors of relevant texts. Serotype-specific CCRs, calculated as IPD incidence divided by carriage prevalence, were pooled across settings using random effects meta-analyses, stratified by before versus after pneumococcal conjugate vaccine (PCV) introduction, country income group, age group, sex, and HIV status.
Findings
We identified 80 publications from 18 countries (13 upper-middle-income countries [UMICS] or high-income countries [HICs], five low-income countries [LICs] or lower-middle-income countries [LMICs]) reporting carriage prevalence or IPD incidence in overlapping geographical areas, time periods, and age groups. We calculated CCRs for more than 70 serotypes, stratified by age group, income setting, and pre-PCV versus post-PCV introduction. In children younger than 5 years, pre-PCV CCRs for non-vaccine serotypes not included in the 13-valent PCV were higher in LICs and LMICs than in UMICs and HICs (177 [95% CI 124–251] vs 103 [60–176], respectively). Post-PCV CCRs for non-PCV13 serotypes dropped in UMICs and HICs (26 [22–30]) but not in LICs and LMICs (173 [139–216]). Pre-PCV versus post-PCV changes varied by serotype and age group. CCRs were lowest in 5–14-year-olds and were higher in HIV-positive than HIV-negative individuals. There were no differences in CCRs by sex.
Interpretation
Pneumococcal invasiveness varies by serotype, age group, country income group, HIV status, and over time; however, substantial variation remains unexplained. Our CCRs represent the most representative estimates of invasiveness currently available for use in statistical or mathematical prediction models of disease incidence, where only carriage prevalence data are available.
Funding
Wellcome Trust.
背景：肺炎球菌携带传播模型中用于预测疫苗接种后疾病发病率变化的肺炎球菌侵袭性血清型特异性估计主要来自高收入环境。我们对携带患病率和侵袭性肺炎球菌病（IPD）发病率进行了系统回顾，以计算不同收入环境下的病例携带比（CCRs）。方法：我们于2022年3月14日对MEDLINE、Embase和Global Health数据库进行了系统搜索，以确定关于肺炎球菌携带患病率或IPD发病率的出版物；我们要求相关文献作者提供个人层面的数据。用IPD发病率除以携带患病率计算的血清型特异性ccr，采用随机效应荟萃分析，按引入肺炎球菌结合疫苗（PCV）前后、国家收入群体、年龄组、性别和艾滋病毒状况进行分层。研究结果：我们确定了来自18个国家（13个中高收入国家[UMICS]或高收入国家[HICs]， 5个低收入国家[lic]或中低收入国家[LMICs]）的80篇出版物，报告了重叠地理区域、时间段和年龄组的携带患病率或IPD发病率。我们计算了超过70种血清型的ccr，并按年龄组、收入环境和感染前与感染后进行了分层。在5岁以下儿童中，未包括在13价PCV中的非疫苗血清型的PCV前ccr在低收入国家和低收入国家高于低收入国家和高收入国家（分别为177 [95% CI 124-251]和103[60-176]）。非pcv13血清型的pcv后ccr在低收入国家和高收入国家中下降（26[22-30]），但在低收入国家和低收入国家中没有下降（173[139-216]）。pcv前与pcv后的变化因血清型和年龄组而异。5-14岁儿童的ccr最低，hiv阳性个体的ccr高于hiv阴性个体。ccr无性别差异。解释：肺炎球菌侵袭性因血清型、年龄组、国家收入群体、艾滋病毒感染状况和时间而异；然而，实质性的变化仍然无法解释。我们的ccr代表了目前最具代表性的侵袭性估计，可用于疾病发病率的统计或数学预测模型，其中只有携带患病率数据可用。资助：惠康信托基金。
{"title":"Serotype-specific pneumococcal invasiveness: a global meta-analysis of paired estimates of disease incidence and carriage prevalence","authors":"Katherine E Gallagher PhD , Fredrick Odiwour BSc , Prof Christian Bottomley PhD , John Ojal PhD , Aisha Adamu PhD , Esther Muthumbi PhD , Eunice W Kagucia PhD , Prof Laura L Hammitt MD , Sergio Massora PhD , Betuel Sigaúque PhD , Alberto Chaúque MSc , Leocadia Vilanculos MD , Jennifer R Verani MD , Maria da Gloria Carvalho PhD , Prof Anne von Gottberg PhD , Jackie Kleynhans PhD , Prof Shabir A Madhi PhD , Courtney P Olwagen PhD , Prof Grant Mackenzie PhD , Rasheed Salaudeen MSc , Prof J Anthony G Scott FRCP","doi":"10.1016/j.lanmic.2025.101301","DOIUrl":"10.1016/j.lanmic.2025.101301","url":null,"abstract":"<div><h3>Background</h3><div>Serotype-specific estimates of pneumococcal invasiveness used in pneumococcal carriage transmission models to predict changes in disease incidence post-vaccination are largely derived from high-income settings. We conducted a systematic review of carriage prevalence and invasive pneumococcal disease (IPD) incidence to calculate case–carrier ratios (CCRs) in different income settings.</div></div><div><h3>Methods</h3><div>We conducted a systematic search of MEDLINE, Embase, and Global Health databases on March 14, 2022, to identify publications on pneumococcal carriage prevalence or IPD incidence; we requested individual-level data from authors of relevant texts. Serotype-specific CCRs, calculated as IPD incidence divided by carriage prevalence, were pooled across settings using random effects meta-analyses, stratified by before versus after pneumococcal conjugate vaccine (PCV) introduction, country income group, age group, sex, and HIV status.</div></div><div><h3>Findings</h3><div>We identified 80 publications from 18 countries (13 upper-middle-income countries [UMICS] or high-income countries [HICs], five low-income countries [LICs] or lower-middle-income countries [LMICs]) reporting carriage prevalence or IPD incidence in overlapping geographical areas, time periods, and age groups. We calculated CCRs for more than 70 serotypes, stratified by age group, income setting, and pre-PCV versus post-PCV introduction. In children younger than 5 years, pre-PCV CCRs for non-vaccine serotypes not included in the 13-valent PCV were higher in LICs and LMICs than in UMICs and HICs (177 [95% CI 124–251] <em>vs</em> 103 [60–176], respectively). Post-PCV CCRs for non-PCV13 serotypes dropped in UMICs and HICs (26 [22–30]) but not in LICs and LMICs (173 [139–216]). Pre-PCV versus post-PCV changes varied by serotype and age group. CCRs were lowest in 5–14-year-olds and were higher in HIV-positive than HIV-negative individuals. There were no differences in CCRs by sex.</div></div><div><h3>Interpretation</h3><div>Pneumococcal invasiveness varies by serotype, age group, country income group, HIV status, and over time; however, substantial variation remains unexplained. Our CCRs represent the most representative estimates of invasiveness currently available for use in statistical or mathematical prediction models of disease incidence, where only carriage prevalence data are available.</div></div><div><h3>Funding</h3><div>Wellcome Trust.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 3","pages":"Article 101301"},"PeriodicalIF":20.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147311096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-25DOI: 10.1016/j.lanmic.2025.101286
Winkie Fong PhD , Rebecca J Rockett PhD , Kingsley King-Gee Tam PhD , Trang Nguyen BSc , Eby M Sim PhD , Enoch Tay PhD , Carl J E Suster PhD , Jessica E Agius PhD , Shona Chandra PhD , Anne E Watt PhD , David Speers MBBS , Maryza Graham MBBS , Thomas Tran BAppSc , Chuan Kok Lim PhD , Michael C Wehrhahn MBBS , Andrew N Ginn PhD , Darcy Gray MD , Jennifer Robson MBBS , Indya Gardner BBiomedSc , Rodney McDougall MClSc , Prof Vitali Sintchenko PhD
Background
Bordetella pertussis continues to circulate globally despite widespread vaccination, with a notable epidemic in 2024. Its resurgence is confounded by the emergence of pertactin-deficient, macrolide-resistant B pertussis strains in Asia and Europe, which are under-recognised by conventional diagnostics. We aimed to apply targeted culture-independent next-generation sequencing (tNGS) of respiratory specimens to improve global B pertussis diagnostic capability and genomic surveillance.
Methods
We did a nationwide genomic epidemiology study of B pertussis RT-PCR-positive respiratory specimens that were retrospectively and prospectively collected by diagnostic and public health laboratories in six of seven states and territories of Australia. Specimens underwent tNGS and macrolide-resistant B pertussis-specific PCR, and an opportunistic subset from New South Wales and Queensland were cultured for confirmatory susceptibility testing and whole-genome sequencing. Sequencing data were analysed for genome recovery, virulence profiles, and macrolide resistance mutations, and were compared with international macrolide-resistant B pertussis genomes and ancestral Australian genomes. The performance of the tNGS approach was assessed with logistic regression relative to RT-PCR cycle threshold values, and sensitivity and specificity values were calculated.
Findings
255 respiratory specimens positive for B pertussis were included in the study. 64 (25%) were retrospectively collected between Jan 12, 2012, and Dec 31, 2023, and 191 (75%) were prospectively collected between Jan 1 and Oct 28, 2024. Of these 255 specimens, 148 (58%) yielded near-complete B pertussis genomes through tNGS. Seven co-circulating lineages of B pertussis were documented, including two associated with macrolide-resistance. Eight epidemiologically unrelated and geographically dispersed cases of macrolide-resistant B pertussis with a 23S rRNA 2037A→G mutation were identified by tNGS and confirmed by whole-genome sequencing. Three of these were further validated by phenotypic testing. The estimated prevalence of macrolide resistance among Australian cases positive for B pertussis was 4% (eight of 188).
Interpretation
tNGS can recover near-complete B pertussis genomes directly from clinical specimens, enabling identification of macrolide resistance mutations and high-resolution phylogenetic analysis. These findings show that tNGS complements PCR-based surveillance by providing genome-wide assessment of resistance, virulence, and genomic diversity in a single workflow.
{"title":"Characterisation of Bordetella pertussis virulence and macrolide resistance in Australia by targeted culture-independent sequencing: a genomic epidemiology study","authors":"Winkie Fong PhD , Rebecca J Rockett PhD , Kingsley King-Gee Tam PhD , Trang Nguyen BSc , Eby M Sim PhD , Enoch Tay PhD , Carl J E Suster PhD , Jessica E Agius PhD , Shona Chandra PhD , Anne E Watt PhD , David Speers MBBS , Maryza Graham MBBS , Thomas Tran BAppSc , Chuan Kok Lim PhD , Michael C Wehrhahn MBBS , Andrew N Ginn PhD , Darcy Gray MD , Jennifer Robson MBBS , Indya Gardner BBiomedSc , Rodney McDougall MClSc , Prof Vitali Sintchenko PhD","doi":"10.1016/j.lanmic.2025.101286","DOIUrl":"10.1016/j.lanmic.2025.101286","url":null,"abstract":"<div><h3>Background</h3><div><em>Bordetella pertussis</em> continues to circulate globally despite widespread vaccination, with a notable epidemic in 2024. Its resurgence is confounded by the emergence of pertactin-deficient, macrolide-resistant <em>B pertussis</em> strains in Asia and Europe, which are under-recognised by conventional diagnostics. We aimed to apply targeted culture-independent next-generation sequencing (tNGS) of respiratory specimens to improve global <em>B pertussis</em> diagnostic capability and genomic surveillance.</div></div><div><h3>Methods</h3><div>We did a nationwide genomic epidemiology study of <em>B pertussis</em> RT-PCR-positive respiratory specimens that were retrospectively and prospectively collected by diagnostic and public health laboratories in six of seven states and territories of Australia. Specimens underwent tNGS and macrolide-resistant <em>B pertussis-</em>specific PCR, and an opportunistic subset from New South Wales and Queensland were cultured for confirmatory susceptibility testing and whole-genome sequencing. Sequencing data were analysed for genome recovery, virulence profiles, and macrolide resistance mutations, and were compared with international macrolide-resistant <em>B pertussis</em> genomes and ancestral Australian genomes. The performance of the tNGS approach was assessed with logistic regression relative to RT-PCR cycle threshold values, and sensitivity and specificity values were calculated.</div></div><div><h3>Findings</h3><div>255 respiratory specimens positive for <em>B pertussis</em> were included in the study. 64 (25%) were retrospectively collected between Jan 12, 2012, and Dec 31, 2023, and 191 (75%) were prospectively collected between Jan 1 and Oct 28, 2024. Of these 255 specimens, 148 (58%) yielded near-complete <em>B pertussis</em> genomes through tNGS. Seven co-circulating lineages of <em>B pertussis</em> were documented, including two associated with macrolide-resistance. Eight epidemiologically unrelated and geographically dispersed cases of macrolide-resistant <em>B pertussis</em> with a 23S rRNA 2037A→G mutation were identified by tNGS and confirmed by whole-genome sequencing. Three of these were further validated by phenotypic testing. The estimated prevalence of macrolide resistance among Australian cases positive for <em>B pertussis</em> was 4% (eight of 188).</div></div><div><h3>Interpretation</h3><div>tNGS can recover near-complete <em>B pertussis</em> genomes directly from clinical specimens, enabling identification of macrolide resistance mutations and high-resolution phylogenetic analysis. These findings show that tNGS complements PCR-based surveillance by providing genome-wide assessment of resistance, virulence, and genomic diversity in a single workflow.</div></div><div><h3>Funding</h3><div>NSW Health Prevention Research Support Program.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 3","pages":"Article 101286"},"PeriodicalIF":20.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147322372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-23DOI: 10.1016/j.lanmic.2025.101278
Prof Chetan Seshadri MD , Prof JoAnne L Flynn PhD , Pauline Maiello MA , Prof Dirk Schnappinger PhD , Prof Robert J Wilkinson FMedSci , Prof Stephen B Gordon MD , Prof Henry C Mwandumba PhD , Prof Kondwani C Jambo PhD , Prof Daniel F Hoft MD PhD , Prof Eric J Rubin MD , Euzebiusz Jamrozik PhD , Prof Sarah M Fortune MD , Prof James G Kublin MD
Controlled human infection models (CHIMs) can accelerate vaccine development for infectious diseases. Mycobacterium tuberculosis is a human-adapted pathogen that is the leading infectious cause of death worldwide. M tuberculosis infection results in a spectrum of clinical outcomes that are incompletely modelled in animals. To date, the risks of infection, prolonged treatment, and sequelae related to CHIMs with M tuberculosis have been considered ethically unacceptable. However, recent advances in bacterial engineering have resulted in safe strains that could permit M tuberculosis CHIM studies with reduced risks. In this Personal View, we address the practical considerations for conducting a pulmonary M tuberculosis CHIM study. We summarise the ethical issues of M tuberculosis CHIM studies in tuberculosis-endemic and non-endemic settings; describe safety considerations, such as optimising the challenge dose and minimising risks to third parties; and outline and prioritise clinical, microbiological, immunological, and radiological endpoints that would render such a model useful for vaccine development.
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