Lancet MicrobePub Date : 2024-10-15DOI: 10.1016/j.lanmic.2024.101008
Mohamed A Imam, Atef Abdelrahman, Adam Zumla, Rizwan Ahmed, Giovanni Satta, Alimuddin Zumla
{"title":"Intersection of artificial intelligence, microbes, and bone and joint infections: a new frontier for improving management outcomes.","authors":"Mohamed A Imam, Atef Abdelrahman, Adam Zumla, Rizwan Ahmed, Giovanni Satta, Alimuddin Zumla","doi":"10.1016/j.lanmic.2024.101008","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.101008","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142477427","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}
Lancet MicrobePub Date : 2024-10-14DOI: 10.1016/j.lanmic.2024.100974
Liuying Li, Hao Zhou
{"title":"Development of an all-in-one pan-sarbecovirus ferritin nanoparticle vaccine in humans.","authors":"Liuying Li, Hao Zhou","doi":"10.1016/j.lanmic.2024.100974","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.100974","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142477423","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}
Lancet MicrobePub Date : 2024-10-14DOI: 10.1016/S2666-5247(24)00169-1
Yuan Li, Joy Rivers, Saundra Mathis, Zhongya Li, Sopio Chochua, Benjamin J Metcalf, Bernard Beall, Lesley McGee
{"title":"Genomic cluster formation among invasive group A streptococcal infections in the USA: a whole-genome sequencing and population-based surveillance study.","authors":"Yuan Li, Joy Rivers, Saundra Mathis, Zhongya Li, Sopio Chochua, Benjamin J Metcalf, Bernard Beall, Lesley McGee","doi":"10.1016/S2666-5247(24)00169-1","DOIUrl":"https://doi.org/10.1016/S2666-5247(24)00169-1","url":null,"abstract":"<p><strong>Background: </strong>Clusters of invasive group A streptococcal (iGAS) infection, linked to genomically closely related group A streptococcal (GAS) isolates (referred to as genomic clusters), pose public health threats, and are increasingly identified through whole-genome sequencing (WGS) analysis. In this study, we aimed to assess the risk of genomic cluster formation among iGAS cases not already part of existing genomic clusters.</p><p><strong>Methods: </strong>In this WGS and population-based surveillance study, we analysed iGAS case isolates from the Active Bacterial Core surveillance (ABCs), which is part of the US Centers for Disease Control and Prevention's Emerging Infections Program, in ten US states from Jan 1, 2015, to Dec 31, 2019. We included all residents in ABCs sites with iGAS infections meeting the case definition and excluded non-conforming GAS infections and cases with whole-genome assemblies of the isolate containing fewer than 1·5 million total bases or more than 150 contigs. For iGAS cases we collected basic demographics, underlying conditions, and risk factors for infection from medical records, and for isolates we included emm types, antimicrobial resistance, and presence of virulence-related genes. Two iGAS cases were defined as genomically clustered if their isolates differed by three or less single-nucleotide variants. An iGAS case not clustered with any previous cases at the time of detection, with a minimum trace-back time of 1 year, was defined as being at risk of cluster formation. We monitored each iGAS case at risk for a minimum of 1 year to identify any cluster formation event, defined as the detection of a subsequent iGAS case clustered with the case at risk. We used the Kaplan-Meier method to estimate the cumulative incidence of cluster formation events over time. We used Cox regression to assess associations between features of cases at risk upon detection and subsequent cluster formation. We developed a random survival forest machine-learning model based on a derivation cohort (random selection of 50% of cases at risk) to predict cluster formation risk. This model was validated using a validation cohort consisting of the remaining 50% of cases at risk.</p><p><strong>Findings: </strong>We identified 2764 iGAS cases at risk from 2016 to 2018, of which 656 (24%) formed genomic clusters by the end of 2019. Overall, the cumulative incidence of cluster formation was 0·057 (95% CI 0·048-0·066) at 30 days after detection, 0·12 (0·11-0·13) at 90 days after detection, and 0·16 (0·15-0·18) at 180 days after detection. A higher risk of cluster formation was associated with emm type (adjusted hazard ratio as compared with emm89 was 2·37 [95% CI 1·71-3·30] for emm1, 2·72 [1·82-4·06] for emm3, 2·28 [1·49-3·51] for emm6, 1·47 [1·05-2·06] for emm12, and 2·21 [1·38-3·56] for emm92), homelessness (1·42 [1·01-1·99]), injection drug use (2·08 [1·59-2·72]), residence in a long-term care facility (1·78 [1·29-2·45]), and ","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142477425","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}
Lancet MicrobePub Date : 2024-10-14DOI: 10.1016/j.lanmic.2024.07.007
Seun Anjorin, Betty Nabatte, Simon Mpooya, Benjamin Tinkitina, Christopher K Opio, Narcis B Kabatereine, Goylette F Chami
{"title":"Epidemiology of periportal fibrosis and relevance of current Schistosoma mansoni infection within the context of repeated mass drug administration in rural Uganda: a population-based, cross-sectional study.","authors":"Seun Anjorin, Betty Nabatte, Simon Mpooya, Benjamin Tinkitina, Christopher K Opio, Narcis B Kabatereine, Goylette F Chami","doi":"10.1016/j.lanmic.2024.07.007","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.07.007","url":null,"abstract":"<p><strong>Background: </strong>WHO guidelines for schistosomiasis-related morbidity control and elimination rely on current infection as a proxy indicator for morbidity. We evaluated these guidelines within the context of repeated mass drug administration and periportal fibrosis attributable to chronic intestinal schistosomiasis.</p><p><strong>Methods: </strong>We examined 1442 households randomly sampled from 38 villages in Buliisa, Pakwach, and Mayuge districts of Uganda within the SchistoTrack cohort. Periportal fibrosis was diagnosed in 2834 individuals aged 5-90 years using ultrasound and image patterns C-F from the Niamey protocol. Schistosoma mansoni status and intensity were diagnosed by Kato-Katz microscopy and point-of-care circulating cathodic antigen tests. Schistosome infection, co-infections, and comorbidities were examined as exposures for periportal fibrosis. Multivariable logistic regressions were run with SEs clustered by household.</p><p><strong>Findings: </strong>Between Jan 6 and Feb 3, 2022, 342 (12·1%) of 2834 participants were diagnosed with periportal fibrosis. By Kato-Katz microscopy, 1229 (43·4%) of 2834 participants were infected. 1863 (65·7%) of 2834 participants had trace positive point-of-care circulating cathodic antigen tests, which was higher than prevalence by Kato-Katz microscopy, and 1158 (40·9%) of 2834 participants had trace negative point-of-care circulating cathodic antigen tests. Individual schistosome status, intensity, and prevalence of heavy intensity infections of less than 1% and less than 5% were not correlated with periportal fibrosis likelihood or village prevalence. Periportal fibrosis likelihood linearly increased with age from age 5 years to age 25 years, non-linearly increased from age 26 years to age 45 years, attenuated or remained unchanged from age 46 years to age 60 years, and steadily decreased past 60 years of age. History of liver diseases, HIV, and ultrasound-detected chronic hepatitis or early cirrhosis-like disease were associated with more than two-times increased periportal fibrosis likelihood.</p><p><strong>Interpretation: </strong>WHO guidelines reliant on current schistosome status and intensity are uninformative for identifying probable cases or communities with periportal fibrosis. History of HIV and underlying chronic hepatitis or early cirrhosis-like disease are risk factors that could be investigated for periportal fibrosis surveillance and management.</p><p><strong>Funding: </strong>NDPH Pump Priming Fund, Wellcome Trust, John Fell Fund, Robertson Foundation, and UK Research and Innovation Engineering and Physical Sciences Research Council.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142477424","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}
Lancet MicrobePub Date : 2024-10-10DOI: 10.1016/j.lanmic.2024.100973
Reina Yamaji, Wenqing Zhang, Akiko Kamata, Cornelia Adlhoch, David E Swayne, Dmitriy Pereyaslov, Dayan Wang, Gabriele Neumann, Gounalan Pavade, Ian G Barr, Malik Peiris, Richard J Webby, Ron A M Fouchier, Sophie Von Dobschütz, Thomas Fabrizio, Yuelong Shu, Magdi Samaan
{"title":"Pandemic risk characterisation of zoonotic influenza A viruses using the Tool for Influenza Pandemic Risk Assessment (TIPRA).","authors":"Reina Yamaji, Wenqing Zhang, Akiko Kamata, Cornelia Adlhoch, David E Swayne, Dmitriy Pereyaslov, Dayan Wang, Gabriele Neumann, Gounalan Pavade, Ian G Barr, Malik Peiris, Richard J Webby, Ron A M Fouchier, Sophie Von Dobschütz, Thomas Fabrizio, Yuelong Shu, Magdi Samaan","doi":"10.1016/j.lanmic.2024.100973","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.100973","url":null,"abstract":"<p><p>A systematic risk assessment approach is essential for evaluating the relative risk of influenza A viruses (IAVs) with pandemic potential. To achieve this, the Tool for Influenza Pandemic Risk Assessment (TIPRA) was developed under the Global Influenza Programme of WHO. Since its release in 2016 and update in 2020, TIPRA has been used to assess the pandemic risk of 11 zoonotic IAVs across ten evaluation rounds. Notably, A(H7N9), A(H9N2), and A(H5) clade 2.3.4.4 viruses were re-evaluated owing to changes in epidemiological characteristics or virus properties. A(H7N9) viruses had the highest relative risk at the time of assessment, highlighting the importance of continuous monitoring and reassessment as changes in epidemiological trends within animal and human populations can alter risk profiles. The knowledge gaps identified throughout the ten risk assessments should help to guide the efficient use of resources for future research, including surveillance. The TIPRA tool reflects the One Health approach and has proven crucial for closely monitoring virus dynamics in both human and non-human populations to enhance preparedness for potential IAV pandemics.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142477429","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}
Lancet MicrobePub Date : 2024-10-09DOI: 10.1016/S2666-5247(24)00175-7
Andrew J Lee, Stephen Carson, Marina I Reyne, Andrew Marshall, Daniel Moody, Danielle M Allen, Pearce Allingham, Ashley Levickas, Arthur Fitzgerald, Stephen H Bell, Jonathan Lock, Jonathon D Coey, Cormac McSparron, Behnam F Nejad, Evan P Troendle, David A Simpson, David G Courtney, Gisli G Einarsson, James P McKenna, Derek J Fairley, Tanya Curran, Jennifer M McKinley, Deirdre F Gilpin, Ken Lemon, John W McGrath, Connor G G Bamford
{"title":"Wastewater monitoring of human and avian influenza A viruses in Northern Ireland: a genomic surveillance study.","authors":"Andrew J Lee, Stephen Carson, Marina I Reyne, Andrew Marshall, Daniel Moody, Danielle M Allen, Pearce Allingham, Ashley Levickas, Arthur Fitzgerald, Stephen H Bell, Jonathan Lock, Jonathon D Coey, Cormac McSparron, Behnam F Nejad, Evan P Troendle, David A Simpson, David G Courtney, Gisli G Einarsson, James P McKenna, Derek J Fairley, Tanya Curran, Jennifer M McKinley, Deirdre F Gilpin, Ken Lemon, John W McGrath, Connor G G Bamford","doi":"10.1016/S2666-5247(24)00175-7","DOIUrl":"https://doi.org/10.1016/S2666-5247(24)00175-7","url":null,"abstract":"<p><strong>Background: </strong>Influenza A viruses (IAVs) are significant pathogens of humans and other animals. Although endemic in humans and birds, novel IAV strains can emerge, jump species, and cause epidemics, like the latest variant of H5N1. Wastewater-based epidemiology (WBE) has been shown capable of detecting human IAVs. We aimed to assess whether whole-genome sequencing (WGS) of IAVs from wastewater is possible and can be used to discriminate between circulating strains of human and any non-human IAVs, such as those of avian origin.</p><p><strong>Methods: </strong>Using a pan-IAV RT-quantitative PCR assay, six wastewater treatment works (WWTWs) across Northern Ireland were screened from Aug 1 to Dec 5, 2022. A nanopore WGS approach was used to sequence RT-qPCR-positive samples. Phylogenetic analysis of sequences relative to currently circulating human and non-human IAVs was performed. For comparative purposes, clinical data (PCR test results) were supplied by The Regional Virus Laboratory, Belfast Health and Social Care Trust (Belfast, Northern Ireland, UK).</p><p><strong>Findings: </strong>We detected a dynamic IAV signal in wastewater from Sept 5, 2022, onwards across Northern Ireland, which did not show a clear positive relationship with the clinical data obtained for the region. Meta (mixed strain) whole-genome sequences were generated from wastewater samples displaying homology to only human and avian IAV strains. The relative proportion of IAV reads of human versus avian origin differed across time and sample site. A diversity in subtypes and lineages was detected (eg, H1N1, H3N2, and several avian). Avian segment 8 related to those found in recent H5N1 clade 2.3.4.4b was identified.</p><p><strong>Interpretation: </strong>WBE affords a means to monitor circulating human and avian IAV strains and provide crucial genetic information. As such, WBE can provide rapid, cost-effective, year-round One Health surveillance to help control IAV epidemic and pandemic-related threats. However, optimisation of WBE protocols are necessary to ensure observed wastewater signals not only correlate with clinical case data, but yield information on the wider environmental pan-influenz-ome.</p><p><strong>Funding: </strong>Department of Health for Northern Ireland.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142477433","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}
Lancet MicrobePub Date : 2024-10-09DOI: 10.1016/S2666-5247(24)00139-3
Olivier Lortholary, Dea Garcia-Hermoso, Aude Sturny-Leclère, Karine Sitbon, Céline Nourrisson, Valérie Letscher-Bru, Nicole Desbois-Nogard, Ferouze Bani-Sadr, Frédéric Bastides, Boris Bienvenu, Camille Cordier, Anne Coste, François Danion, Tristan Dégot, David Delarbre, Arnaud Fekkar, Christophe Garcie, Cyril Garrouste, Maud Gits-Muselli, Emilie Guemas, Antoine Huguenin, Frédéric Janvier, Nassim Kamar, Cyril Kervinio, Solène Le Gal, Olivier Lesens, Marie Machouart, Florence Persat, Sandrine Picot, Anahita Rouze, Stéphane Ranque, Yvon Ruch, Matthieu Saada, Sarah Stabler, Alexandre Alanio, Fanny Lanternier, Guillaume Desoubeaux
{"title":"Reappraising Cladophialophora bantiana phaeohyphomycosis in France: retrospective nation-based study.","authors":"Olivier Lortholary, Dea Garcia-Hermoso, Aude Sturny-Leclère, Karine Sitbon, Céline Nourrisson, Valérie Letscher-Bru, Nicole Desbois-Nogard, Ferouze Bani-Sadr, Frédéric Bastides, Boris Bienvenu, Camille Cordier, Anne Coste, François Danion, Tristan Dégot, David Delarbre, Arnaud Fekkar, Christophe Garcie, Cyril Garrouste, Maud Gits-Muselli, Emilie Guemas, Antoine Huguenin, Frédéric Janvier, Nassim Kamar, Cyril Kervinio, Solène Le Gal, Olivier Lesens, Marie Machouart, Florence Persat, Sandrine Picot, Anahita Rouze, Stéphane Ranque, Yvon Ruch, Matthieu Saada, Sarah Stabler, Alexandre Alanio, Fanny Lanternier, Guillaume Desoubeaux","doi":"10.1016/S2666-5247(24)00139-3","DOIUrl":"https://doi.org/10.1016/S2666-5247(24)00139-3","url":null,"abstract":"<p><strong>Background: </strong>Cladophialophora bantiana is one of the most virulent phaeohyphomycetes, typically causes non-angiogenic single (or sometimes multiple) cystic brain lesions, and has resulted in a mortality rate of up to 70%. Most C bantiana cases are described either in a series of isolated reports or in very small cohorts. The aim of this retrospective nation-based study was to share the data on C bantiana phaeohyphomycosis cases reported in France and French overseas territories over the past two decades to improve understanding of this disease.</p><p><strong>Methods: </strong>Patients with C bantiana infection were processed through the active surveillance programme of invasive fungal infections launched by the National Reference Center for Mycoses and Antifungals, Institut Pasteur (Paris, France), and the French Surveillance Network of Invasive Fungal Infections, which involved 29 hospitals from mainland France and overseas French territories. Only proven and probable cases of infection, according to the revised and updated consensus definitions from the European Organization for Research and Treatment of Cancer and Mycoses Study Group, were included in the study. Patients were diagnosed or confirmed, or both, using a polyphasic approach at the Institut Pasteur between 2002 and 2022. Patients were separated into two groups: those with CNS involvement and those with no CNS involvement. The primary outcome was the survival rate.</p><p><strong>Findings: </strong>A total of 23 patients with a C bantiana invasive infection were included during the study period (Jan 1, 2002, to Dec 31, 2022). The median age was 56 years in the CNS involvement group and 65 years in the non-CNS involvement group. Until 2021, the annual number of cases varied between zero and two, with six cases observed in 2022, the warmest year recorded in France since 1900. CNS involvement was observed in 15 (65%) patients, including three disseminated cases; skin and soft tissue involvement in seven (30%) patients and an isolated lung infection in one case. Diabetes was observed in five patients, and any immunodepression factor was observed in 14 (61%) of 23 patients. When considering only patients with CNS involvement, 9-month survival appeared higher in patients who underwent exeresis or large drainage (three [75%] of four patients vs three [27%] of 11 patients; p=0·24) and significantly higher in those treated for 2 or more weeks with triple antifungal therapy (liposomal amphotericin B plus posaconazole and flucytosine; seven [78%] of nine patients vs one [17%] of six patients; p=0·040). Two patients were treated with excision surgery alone (one patient with success, and the other patient lost to follow-up).</p><p><strong>Interpretation: </strong>This study shows that the clinical presentations and underlying medical conditions of C bantiana infections are more diverse than previously described. It also emphasises a significant difference in mortality rate betwe","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142477431","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}
Lancet MicrobePub Date : 2024-10-07DOI: 10.1016/j.lanmic.2024.100969
Jessica R Webb, Patiyan Andersson, Eby Sim, Alireza Zahedi, Angela Donald, Tuyet Hoang, Anne E Watt, Jessica E Agius, Celeste M Donato, Max L Cummins, Tehzeeb Zulfiqar, Son Nghiem, Chantel Lin, Dimitrios Menouhos, Lex E X Leong, Rob Baird, Karina Kennedy, Louise Cooley, David Speers, Chuan Kok Lim, Joep de Ligt, Angeline Ferdinand, Katie Glass, Martyn D Kirk, Steven P Djordjevic, Clare Sloggett, Kristy Horan, Torsten Seemann, Vitali Sintchenko, Amy V Jennison, Benjamin P Howden
{"title":"Implementing a national programme of pathogen genomics for public health: the Australian Pathogen Genomics Program (AusPathoGen).","authors":"Jessica R Webb, Patiyan Andersson, Eby Sim, Alireza Zahedi, Angela Donald, Tuyet Hoang, Anne E Watt, Jessica E Agius, Celeste M Donato, Max L Cummins, Tehzeeb Zulfiqar, Son Nghiem, Chantel Lin, Dimitrios Menouhos, Lex E X Leong, Rob Baird, Karina Kennedy, Louise Cooley, David Speers, Chuan Kok Lim, Joep de Ligt, Angeline Ferdinand, Katie Glass, Martyn D Kirk, Steven P Djordjevic, Clare Sloggett, Kristy Horan, Torsten Seemann, Vitali Sintchenko, Amy V Jennison, Benjamin P Howden","doi":"10.1016/j.lanmic.2024.100969","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.100969","url":null,"abstract":"<p><p>Delivering large-scale routine pathogen genomics surveillance for public health is of considerable interest, although translational research models that promote national-level implementation are not well defined. We describe the development and deployment of the Australian Pathogen Genomics Program (AusPathoGen), a comprehensive national partnership between academia, public health laboratories, and public health agencies that commenced in January, 2021. Successfully establishing and delivering a national programme requires inclusive and transparent collaboration between stakeholders, defined and clear focus on public health priorities, and support for strengthening national genomics capacity. Major enablers for delivering such a programme include technical solutions for data integration and analysis, such as the genomics surveillance platform AusTrakka, standard bioinformatic analysis methods, and national ethics and data sharing agreements that promote nationally integrated surveillance systems. Training of public health officials to interpret and act on genomic data is crucial, and evaluation and cost-effectiveness programmes will provide a benchmark and evidence for sustainable investment in genomics nationally and globally.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401599","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}
Lancet MicrobePub Date : 2024-10-05DOI: 10.1016/S2666-5247(24)00152-6
Samuel Lipworth, Derrick Crook, A Sarah Walker, Tim Peto, Nicole Stoesser
{"title":"Exploring uncatalogued genetic variation in antimicrobial resistance gene families in Escherichia coli: an observational analysis.","authors":"Samuel Lipworth, Derrick Crook, A Sarah Walker, Tim Peto, Nicole Stoesser","doi":"10.1016/S2666-5247(24)00152-6","DOIUrl":"https://doi.org/10.1016/S2666-5247(24)00152-6","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance (AMR) in Escherichia coli is a global problem associated with substantial morbidity and mortality. AMR-associated genes are typically annotated based on similarity to variants in a curated reference database, with the implicit assumption that uncatalogued genetic variation within these is phenotypically unimportant. In this study, we evaluated the performance of the AMRFinder tool and, subsequently, the potential for discovering new AMR-associated gene families and characterising variation within existing ones to improve genotype-to-susceptibility phenotype predictions in E coli.</p><p><strong>Methods: </strong>In this cross-sectional study of international genome sequence data, we assembled a global dataset of 9001 E coli sequences from five publicly available data collections predominantly deriving from human bloodstream infections from: Norway, Oxfordshire (UK), Thailand, the UK, and Sweden. 8555 of these sequences had linked antibiotic susceptibility data. Raw reads were assembled using Shovill and AMR genes (relevant to amoxicillin-clavulanic acid, ampicillin, ceftriaxone, ciprofloxacin, gentamicin, piperacillin-tazobactam, and trimethoprim) extracted using the National Center for Biotechnology Information AMRFinder tool (using both default and strict [100%] coverage and identity filters). We assessed the predictive value of the presence of these genes for predicting resistance or susceptibility against US Food and Drug Administration thresholds for major and very major errors. Mash was used to calculate the similarity between extracted genes using Jaccard distances. We empirically reclustered extracted gene sequences into AMR-associated gene families (≥70% match) and antibiotic-resistance genes (ARGs; 100% match) and categorised these according to their frequency in the dataset. Accumulation curves were simulated and correlations between gene frequency in the Oxfordshire and other datasets calculated using the Spearman coefficient. Firth regression was used to model the association between the presence of bla<sub>TEM-1</sub> variants and amoxicillin-clavulanic acid or piperacillin-tazobactam resistance, adjusted for the presence of other relevant ARGs.</p><p><strong>Findings: </strong>The performance of the AMRFinder database for genotype-to-phenotype predictions using strict 100% identity and coverage thresholds did not meet US Food and Drug Administration thresholds for any of the seven antibiotics evaluated. Relaxing filters to default settings improved sensitivity with a specificity cost. For all antibiotics, most explainable resistance was associated with the presence of a small number of genes. There was a proportion of resistance that could not be explained by known ARGs; this ranged from 75·1% for amoxicillin-clavulanic acid to 3·4% for ciprofloxacin. Only 18 199 (51·5%) of the 35 343 ARGs detected had a 100% identity and coverage match in the AMRFinder database. After empiric","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394172","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}