Lancet Microbe最新文献

{"title":"Spatiotemporal patterns of Rift Valley fever virus in Africa: a retrospective genomic epidemiology and phylodynamic modelling study","authors":"John Juma PhD , Houriiyah Tegally PhD , Samson L Konongoi BVetMed , Kristina Roesel PhD , Prof Rosemary Sang PhD , Prof Tulio de Oliviera PhD , Prof M Kariuki Njenga PhD , Prof Alan Christoffels PhD , Bernard Bett PhD , Simon Dellicour PhD , Samuel O Oyola PhD","doi":"10.1016/j.lanmic.2025.101251","DOIUrl":"10.1016/j.lanmic.2025.101251","url":null,"abstract":"<div><h3>Background</h3><div>Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing outbreaks in humans and ruminants across Africa and the Arabian Peninsula. Originally restricted to the Great Rift Valley, RVFV has expanded geographically, prompting its classification by WHO as a pathogen of pandemic potential. We investigated the evolutionary and spatial dynamics of RVFV across Africa.</div></div><div><h3>Methods</h3><div>We used genomic data generated at the International Livestock Research Institute Nairobi genomic laboratory (BioProject PRJNA1106221) and combined with publicly available datasets retrieved from the National Center for Biotechnology (NCBI) GenBank nucleotide database. In retrieving RVFV genome sequences from the NCBI GenBank, we applied the search terms “Rift Valley fever virus segment L AND 6404[SLEN]”, “Rift Valley fever virus segment M AND 3885[SLEN]”, and “Rift Valley fever virus segment S AND 1520:1690[SLEN]” for L (Large), M (Medium), and S (Small) segments, respectively. For sequences without additional spatiotemporal information, we searched PubMed to extract the associated sequence metadata. We performed molecular clock analysis, phylogenetic inference, phylodynamic modelling (continuous phylogeographic reconstruction), and landscape phylogeography on the three RVFV genome segments (L, M, and S). We aimed to assess evolutionary rates, dispersal patterns, and environmental drivers. Focus was placed on lineage C, the most widely distributed variant.</div></div><div><h3>Findings</h3><div>The global dataset used in this study consisted of large (n=236), medium (n=237), and small (n=247), which were further filtered to exclude potential reassortants and vaccine strains. Genome sequences retrieved from NCBI GenBank database comprised large (n=180), medium (n=184), and small (n=202). The genome sequences from retrospective human and livestock isolates comprised large (n=56), medium (n=53), and small (n=45) collected in Burundi (2018), Kenya (2007, 2018, 2019, 2021, and 2022), and Rwanda (2018 and 2022). Our dataset revealed that RVFV exhibited low overall genetic diversity. Lineage C, however, showed evidence of active evolution, with substitution rates ranging from 3·58 × 10<sup>−4</sup> to 9·76 × 10<sup>−4</sup> substitutions per site per year. This lineage probably originated in Zimbabwe in the mid-1970s and has since expanded across eastern and southern Africa. Phylogeographic reconstructions revealed rapid spread, with diffusion coefficients exceeding 50 000 km<sup>2</sup> per year.</div></div><div><h3>Interpretation</h3><div>Lineage C appears capable of establishing endemic transmission in new regions, with ongoing diversification observed during interepidemic periods. These observations reinforce the value of continuous genomic surveillance, particularly during cryptic transmission phases when adaptive mutations might emerge. Although further evidence is needed, observed trends in climate variabi","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 3","pages":"Article 101251"},"PeriodicalIF":20.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776851","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}

{"title":"Bedaquiline resistance in patients with Xpert MTB/RIF Ultra-tested rifampicin-resistant tuberculosis in the Western Cape, South Africa: a prospective study","authors":"Janré Steyn MSc ,&nbsp;Jennifer Williams MSc ,&nbsp;Fahd Naufal MD ,&nbsp;Jason Limberis PhD ,&nbsp;Melanie Grobbelaar PhD ,&nbsp;Nabila Ismail PhD ,&nbsp;Yonas Ghebrekristos PhD ,&nbsp;Christoffel J Opperman MMed ,&nbsp;Alina Nalyvayko BS ,&nbsp;Sarishna Singh MMed ,&nbsp;Rebecca E Colman PhD ,&nbsp;Prof Timothy C Rodwell MD ,&nbsp;Prof Grant Theron PhD ,&nbsp;Prof Robin M Warren PhD ,&nbsp;Prof John Z Metcalfe","doi":"10.1016/j.lanmic.2025.101293","DOIUrl":"10.1016/j.lanmic.2025.101293","url":null,"abstract":"<div><h3>Background</h3><div>Bedaquiline-containing regimens have been widely used to treat patients with drug-resistant tuberculosis in South Africa since 2019. We aimed to estimate the prevalence of bedaquiline resistance among patients in the Western Cape with rifampicin-resistant tuberculosis tested by Xpert MTB/RIF Ultra (Xpert).</div></div><div><h3>Methods</h3><div>This prospective study analysed consecutive <em>Mycobacterium tuberculosis</em> diagnostic isolates collected from patients with Xpert-tested rifampicin-resistant tuberculosis in the Western Cape, South Africa, between March 30, 2023, and Jan 3, 2024. We used the Deeplex Myc-TB assay within routine clinical workflows to test genotypic resistance to bedaquiline and other antituberculosis drugs; <em>mmpR5</em> variants were classified according to Deeplex version 3.0.1 extended catalogue. Phenotypic drug susceptibility information was derived from the National Health Laboratory System and Stellenbosch University for isolates with a Deeplex-identified <em>mmpR5</em> variant. We estimated the prevalence of bedaquiline resistance and the diagnostic accuracy of Deeplex for bedaquiline susceptibility using a composite genotypic–phenotypic reference standard.</div></div><div><h3>Findings</h3><div>Of 701 sputum sediments, 131 (19%) were culture-negative. Of the 570 isolates accumulated during the study period, Deeplex was not performed for 139 during intervals trialling workflow optimisation procedures. Of 431 isolates, we successfully sequenced 401 (93%), of which 15 (4%) were found to be rifampicin-susceptible; 364 (91%) analysed isolates were baseline and 37 (9%) were longitudinal (median estimated time since previous diagnosis of 5·4 months [IQR 3·7–8·0]). Bedaquiline resistance was detected in 45 (12% [95% CI 9–16]) of 364 baseline and 15 (41% [25–58]) of 37 longitudinal isolates. Deeplex-tested resistance-associated and uncharacterised <em>mmpR5</em> variants had a similar likelihood of being phenotypic drug susceptibility testing-resistant (37 [97%] of 38 and 16 [94%] of 17, respectively; p=0·53). Combining both types of variants, Deeplex had a sensitivity of 93% (95% CI 83–98) and specificity of 99% (97–100).</div></div><div><h3>Interpretation</h3><div>In a prospective, representative sample of patients with Xpert-tested rifampicin-resistant tuberculosis, we found an elevated prevalence of bedaquiline resistance, particularly in patients with recent tuberculosis treatment. Efficient and accurate surveillance for bedaquiline resistance should be a high programmatic priority.</div></div><div><h3>Funding</h3><div>The National Institute of Allergy and Infectious Diseases (at the National Institutes of Health) and Unitaid.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 3","pages":"Article 101293"},"PeriodicalIF":20.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147272414","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}

{"title":"Therapeutic potential of targeting ORF6 in persistent SARS-CoV-2 infections","authors":"Yangguang Pan ,&nbsp;Quanren Pan ,&nbsp;Haiyan Xiao ,&nbsp;Qingjun Pan","doi":"10.1016/j.lanmic.2025.101253","DOIUrl":"10.1016/j.lanmic.2025.101253","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 3","pages":"Article 101253"},"PeriodicalIF":20.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179404","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}

{"title":"An overview of global public and philanthropic investments into antibacterial therapeutics (2017–23)","authors":"Lloyd Czaplewski PhD ,&nbsp;Usha Lamichhane MSc ,&nbsp;Ralf Sudbrak PhD ,&nbsp;Alan Hennessy PhD ,&nbsp;Lesley A Ogilvie PhD ,&nbsp;Prof Laura JV Piddock PhD","doi":"10.1016/j.lanmic.2025.101288","DOIUrl":"10.1016/j.lanmic.2025.101288","url":null,"abstract":"<div><div>Antibacterial research and development (R&amp;D) increasingly relies on public and philanthropic investments over private investments and on academia and small businesses over large pharmaceutical companies. To complement scientific reviews of the antibacterial pipeline, we examined global public and philanthropic funding for R&amp;D of antibacterial therapeutics from 2017 to 2023 using data obtained from the Global AMR R&amp;D Hub’s Dynamic Dashboard. Projects were analysed considering funders and recipients, geographical location, R&amp;D stage, mechanism of action, antibacterial class, clinical novelty, spectrum of activity, and alignment with the WHO bacterial priority pathogen list 2024. A total of US$2·51 billion was invested in antibacterial R&amp;D by 130 funders, with a marked concentration among a small number of major sources. Funding peaked at $445 million in 2020 but declined by 18% to $363 million in 2023. Universities received the most awards, yet more than half of the total funding volume went to industry recipients. Investment broadly followed the WHO bacterial priority pathogens list, with <em>Mycobacterium tuberculosis</em> accounting for a fifth of the total. While the funding for clinical development remained stable, that for discovery and preclinical research declined. In this environment, public–private partnerships, such as Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator and the Global Antibiotic Research and Development Partnership, are crucial for attracting, channelling, and targeting funding; however, these partnerships alone will be insufficient. Enhanced strategic alignment in funding priorities and continued public and private investment will be essential for ensuring the discovery and development of effective new antibacterials meeting priority public health needs.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 3","pages":"Article 101288"},"PeriodicalIF":20.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145960229","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}

{"title":"Efficacy and safety of lenacapavir, teropavimab, and zinlirvimab: week-26 primary outcome results from a multicentre, open-label, randomised, active-controlled, phase 2 study","authors":"Onyema Ogbuagu MD ,&nbsp;Aditya Gaur MD ,&nbsp;James H McMahon PhD ,&nbsp;Linda Gorgos MD ,&nbsp;Javier O Morales-Ramirez MD ,&nbsp;Kimberly Workowski MD ,&nbsp;Jason Brunetta MD ,&nbsp;Kwad Mponponsuo MD ,&nbsp;Sean E Collins MD ,&nbsp;Laurie A VanderVeen MD ,&nbsp;Nan Zhang PhD ,&nbsp;Hailin Huang PhD ,&nbsp;Jared M Baeten MD ,&nbsp;Joseph Eron MD","doi":"10.1016/j.lanmic.2025.101283","DOIUrl":"10.1016/j.lanmic.2025.101283","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;In a phase 1b study (&lt;span&gt;&lt;span&gt;NCT04811040&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;), lenacapavir combined with the broadly neutralising antibodies (bNAbs) teropavimab and zinlirvimab maintained virological suppression (HIV-1 RNA &lt;50 copies per mL) for 6 months in people with HIV-1 highly susceptible to both bNAbs. This phase 2 study evaluated the efficacy and safety of switching to twice-yearly lenacapavir, teropavimab, and zinlirvimab versus continuing an oral stable baseline regimen (SBR) of antiretroviral therapy (ART). Here, we report the week-26 primary efficacy endpoint results.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This randomised, open-label, phase 2 study was conducted at 34 clinical sites across Australia, Canada, and the USA. People with HIV-1 RNA who had less than 50 copies per mL on oral ART with HIV-1 highly susceptible to bNAbs teropavimab and zinlirvimab (90% inhibitory concentration ≤2 μg/mL) were randomly assigned (2:1) to receive subcutaneous lenacapavir 927 mg (plus oral loading) combined with intravenous teropavimab 2550 mg and zinlirvimab 2550 mg twice-yearly (combined treatment group), or to continue an oral SBR (SBR group). Efficacy and safety analyses included participants who received at least one complete dose of the lenacapavir, teropavimab, and zinlirvimab or SBR. The primary endpoint was the proportion of participants with HIV-1 RNA concentration of 50 copies per mL or higher at week 26. Secondary endpoints included week-26 change from baseline in CD4 cell count and safety. 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;NCT05729568&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;, and is ongoing.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;Between May 15, 2023, and Jan 2, 2024, of 241 participants screened, 80 were enrolled. At week 26, one (1·9%; 95% CI 0·0–10·1) of 53 participants receiving twice-yearly lenacapavir, teropavimab, and zinlirvimab and zero (95% CI 0·0–12·8) of 27 participants continuing SBR had HIV-1 RNA concentration of 50 copies per mL or higher; one participant per group had no virological data (US Food and Drug Administration Snapshot Algorithm). Excluding subcutaneous lenacapavir-related injection site reactions (n=33, predominantly grade 1), treatment-emergent adverse events occurred in 36 (68%) and 17 (63%) participants in the lenacapavir, teropavimab, and zinlirvimab group and SBR group, respectively. No infusion-related reactions to bNAbs, study drug-related grade 3 or worse adverse events, serious adverse events, deaths, or adverse events leading to discontinuation occurred in the lenacapavir, teropavimab, and zinlirvimab group.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Interpretation&lt;/h3&gt;&lt;div&gt;A single administration of lenacapavir, teropavimab, and zinlirvimab in the study population demonstrated similar efficacy to daily oral ART through to week 26. This regimen was well tolerated, with no serious adverse events, supporting its poten","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 3","pages":"Article 101283"},"PeriodicalIF":20.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259538","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}

{"title":"Amoebic CNS disease: when terminology obscures biology.","authors":"Tirlangi Praveen Kumar, Martin P Grobusch, Nitin Gupta","doi":"10.1016/j.lanmic.2026.101384","DOIUrl":"https://doi.org/10.1016/j.lanmic.2026.101384","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101384"},"PeriodicalIF":20.4,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345256","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}

{"title":"Pathogen access and benefit sharing in a pandemic: working towards fair exchange?","authors":"J Radeino Ambe, Anant Bhan, Blessing Silaigwana, Sofía P Salas, Sarah Edwards","doi":"10.1016/j.lanmic.2026.101376","DOIUrl":"https://doi.org/10.1016/j.lanmic.2026.101376","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101376"},"PeriodicalIF":20.4,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327772","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}

{"title":"Antimicrobial resistance in Helicobacter pylori: from mutation catalogues to clinical practice.","authors":"Anand Ramanathan, Nitya Krishnasamy, Eleni Georgakopoulou, Sameep Shetty","doi":"10.1016/j.lanmic.2026.101368","DOIUrl":"https://doi.org/10.1016/j.lanmic.2026.101368","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101368"},"PeriodicalIF":20.4,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327736","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}

{"title":"Drug-resistant fungi: the unintended consequence of modern immunosuppression.","authors":"Gilles Nevez, Yannick Le Meur, Claire V Hoffmann, Solène Le Gal","doi":"10.1016/j.lanmic.2026.101371","DOIUrl":"https://doi.org/10.1016/j.lanmic.2026.101371","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101371"},"PeriodicalIF":20.4,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327718","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}

{"title":"Spillover of pseudorabies virus variants to humans: an urgent call for pseudorabies eradication in domestic pigs.","authors":"Tong-Yun Wang, Chao Li, Xue-Hui Cai, Tongling Shan, Yan-Dong Tang","doi":"10.1016/j.lanmic.2026.101351","DOIUrl":"https://doi.org/10.1016/j.lanmic.2026.101351","url":null,"abstract":"<p><p>Pseudorabies virus, an α-herpesvirus historically considered a veterinary pathogen restricted to pigs, has now emerged as a zoonotic agent capable of causing severe and often fatal infections in humans. Since 2017, novel pseudorabies virus variants in China have been shown to be able to breach species barriers, leading to 31 laboratory-confirmed human cases of encephalitis and endophthalmitis with high mortality and disability rates by 2023. In this Personal View, we synthesise current evidence on the virological evolution, cross-species transmission dynamics, and clinical consequences of pseudorabies virus, highlighting the urgent need for a coordinated One Health response. We argue that eradication of pseudorabies virus from domestic pigs through enhanced vaccination, biosecurity, and policy support is both feasible and essential to mitigate this emerging public health threat.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101351"},"PeriodicalIF":20.4,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147318449","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}