Lancet MicrobePub Date : 2025-04-01DOI: 10.1016/j.lanmic.2024.101010
Gabriel Heyman MD , Sofia Jonsson MSc , Nikos Fatsis-Kavalopoulos PhD , Karin Hjort PhD , Hervé Nicoloff PhD , Mia Furebring MD PhD , Dan I Andersson PhD
{"title":"Prevalence, misclassification, and clinical consequences of the heteroresistant phenotype in Escherichia coli bloodstream infections in patients in Uppsala, Sweden: a retrospective cohort study","authors":"Gabriel Heyman MD , Sofia Jonsson MSc , Nikos Fatsis-Kavalopoulos PhD , Karin Hjort PhD , Hervé Nicoloff PhD , Mia Furebring MD PhD , Dan I Andersson PhD","doi":"10.1016/j.lanmic.2024.101010","DOIUrl":"10.1016/j.lanmic.2024.101010","url":null,"abstract":"<div><h3>Background</h3><div>Antibiotic heteroresistance is a common bacterial phenotype characterised by the presence of small resistant subpopulations within a susceptible population. During antibiotic exposure, these resistant subpopulations can be enriched and potentially lead to treatment failure. In this study, we examined the prevalence, misclassification, and clinical effect of heteroresistance in <em>Escherichia coli</em> bloodstream infections for the clinically important antibiotics cefotaxime, gentamicin, and piperacillin–tazobactam.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort analysis of patients (n=255) admitted to in-patient care and treated for <em>E coli</em> bloodstream infections within the Uppsala region in Sweden between Jan 1, 2014, and Dec 31, 2015. Patient inclusion criteria were admission to hospital on suspicion of infection, starting systemic antibiotics at the time of admission, positive blood cultures for the growth of <em>E coli</em> upon admission, and residency in the Uppsala health-care region at the time of admission. Exclusion criteria were growth of an additional pathogen than <em>E coli</em> in blood cultures taken at admission or previous inclusion of the patients in the study for another bloodstream infection. Antibiotic susceptibility of preserved blood culture isolates of <em>E coli</em> was assessed for cefotaxime, gentamicin, and piperacillin–tazobactam by disk diffusion and breakpoint crossing heteroresistance (BCHR) was identified using population analysis profiling. The clinical outcome parameters were obtained from patient records. The primary outcome variable was length of hospital stay due to the <em>E coli</em> bloodstream infection, defined as the time between admission and discharge from inpatient care as noted on the physician’s notes. Secondary outcomes were time to fever resolution, admission to intermediary care unit or intensive care unit during time in hospital, switching or adding another intravenous antibiotic treatment, re-admission to hospital within 30 days of original admission, recurrent <em>E coli</em> infection within 30 days of admission to hospital, and all-cause mortality within 90 days of admission.</div></div><div><h3>Findings</h3><div>A total of 255 participants with a corresponding <em>E coli</em> isolate (out of 500 screened for eligibility) met the inclusion criteria, with 135 female patients and 120 male patients. One (<1%) of 255 strains was BCHR for cefotaxime, 109 (43%) of 255 strains were BCHR for gentamicin, and 22 (9%) of 255 strains were BCHR for piperacillin–tazobactam. Clinical susceptibility testing misclassified 120 (96%) of 125 heteroresistant bacterial strains as susceptible. The BCHR phenotypes had no correlation to length of hospital stay due to the <em>E coli</em> bloodstream infection. However, patients with piperacillin–tazobactam BCHR strains who received piperacillin–tazobactam had 3·1 times higher odds for admittance t","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 4","pages":"Article 101010"},"PeriodicalIF":20.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143013815","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}
Lancet MicrobePub Date : 2025-03-29DOI: 10.1016/j.lanmic.2025.101127
Nicole Kilian, Liza Ding
{"title":"Innovating the future of science: inspiring trainees on different career paths in infectious diseases.","authors":"Nicole Kilian, Liza Ding","doi":"10.1016/j.lanmic.2025.101127","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101127","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101127"},"PeriodicalIF":20.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765352","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 : 2025-03-26DOI: 10.1016/j.lanmic.2024.101038
Thel K Hla, Joshua Osowicki, Julie A Marsh, Sam Salman, Madhu Page-Sharp, Okhee Yoo, Kristy Azzopardi, Michael Morici, Kevin T Batty, Renae K Barr, Stephanie L Enkel, Joseph Kado, Lara Hatchuel, Alma Fulurija, James S McCarthy, Thomas L Snelling, Andrew C Steer, Jonathan Carapetis, Laurens Manning
{"title":"Establishing the lowest penicillin concentration to prevent pharyngitis due to Streptococcus pyogenes using a human challenge model (CHIPS): a randomised, double-blind, placebo-controlled trial.","authors":"Thel K Hla, Joshua Osowicki, Julie A Marsh, Sam Salman, Madhu Page-Sharp, Okhee Yoo, Kristy Azzopardi, Michael Morici, Kevin T Batty, Renae K Barr, Stephanie L Enkel, Joseph Kado, Lara Hatchuel, Alma Fulurija, James S McCarthy, Thomas L Snelling, Andrew C Steer, Jonathan Carapetis, Laurens Manning","doi":"10.1016/j.lanmic.2024.101038","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.101038","url":null,"abstract":"<p><strong>Background: </strong>The in-vivo plasma concentration of penicillin needed to prevent Streptococcus pyogenes pharyngitis, recurrent acute rheumatic fever, and progressive rheumatic heart disease is not known. We used a human challenge model to assess the minimum penicillin concentration required to prevent streptococcal pharyngitis.</p><p><strong>Methods: </strong>In CHIPS, a randomised, double-blind, placebo-controlled, human challenge trial, healthy adult volunteers were randomly assigned by a computer-generated random sequence to target steady-state penicillin plasma concentrations (placebo, 3, 6, 9, 12, or 20 ng/mL). The study was a single-centre trial held in Perth, WA, Australia. Participants had to be healthy adults, aged 18-40 years, at low risk of complicated S pyogenes disease, and without high type-specific IgG antibodies against the emm75 S pyogenes challenge strain. Participants and staff involved in clinical care remained masked to treatment allocation for the duration of the study. Individualised 5-day continuous intravenous infusions of penicillin were commenced 12 h before direct pharyngeal application of the emm75 challenge strain. The primary endpoint was clinical pharyngitis. This trial is registered on the Australian New Zealand Clinical Trials Registry, ACTRN12621000751875, and is completed.</p><p><strong>Findings: </strong>Between Aug 23, 2022, and July 31, 2023, 60 participants were randomly assigned (35 [58%] were female and 25 [42%] were male), with 57 included in the analysis. The clinical pharyngitis endpoint was met in eight (57%) of 14 in the placebo group, four (44%) of nine in the 3 ng/mL target steady-state penicillin plasma concentration group, four (44%) of nine in the 6 ng/mL group, none of eight in the 9 ng/mL group, none of eight in the 12 ng/mL group, and none of nine in the 20 ng/mL group. No severe or serious adverse events occurred. Using Bayesian concentration-response modelling, the minimum steady-state plasma concentration of penicillin for which 90% of participants would avoid clinical pharyngitis was 8·1 ng/mL (95% credible interval 6·1-10·9).</p><p><strong>Interpretation: </strong>When steady-state penicillin concentrations are greater than 9 ng/mL, few people will develop experimental emm75 S pyogenes pharyngitis. These data will inform efforts to improve long-acting penicillin preparations and dosage regimens to prevent recurrent rheumatic fever and rheumatic heart disease.</p><p><strong>Funding: </strong>The National Health and Medical Research Council of Australia.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101038"},"PeriodicalIF":20.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744213","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 : 2025-03-26DOI: 10.1016/j.lanmic.2025.101125
Peter Hyland, Jan Jacobs, Liselotte Hardy
{"title":"The cost of blood cultures: a barrier to diagnosis in low-income and middle-income countries.","authors":"Peter Hyland, Jan Jacobs, Liselotte Hardy","doi":"10.1016/j.lanmic.2025.101125","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101125","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101125"},"PeriodicalIF":20.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744214","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 : 2025-03-26DOI: 10.1016/j.lanmic.2024.101064
Elizabeth T Rogawski McQuade, Jie Liu, Mustafa Mahfuz, Alexandre Havt, Tintu Varghese, Jasmin Shrestha, Furqan Kabir, Pablo Peñataro Yori, Amidou Samie, Queen Saidi, Adil Kalam, Fatima Aziz, Sahrish Muneer, Rashidul Haque, Aldo A M Lima, Maheswari Kalaivanan, Sanjaya Shrestha, Najeeha Talat Iqbal, Zulfiqar Bhutta, Margaret N Kosek, Pascal Bessong, Estomih Mduma, James A Platts-Mills, Eric R Houpt
{"title":"Epidemiology of Shigella species and serotypes in children: a retrospective substudy of the MAL-ED observational birth cohort study.","authors":"Elizabeth T Rogawski McQuade, Jie Liu, Mustafa Mahfuz, Alexandre Havt, Tintu Varghese, Jasmin Shrestha, Furqan Kabir, Pablo Peñataro Yori, Amidou Samie, Queen Saidi, Adil Kalam, Fatima Aziz, Sahrish Muneer, Rashidul Haque, Aldo A M Lima, Maheswari Kalaivanan, Sanjaya Shrestha, Najeeha Talat Iqbal, Zulfiqar Bhutta, Margaret N Kosek, Pascal Bessong, Estomih Mduma, James A Platts-Mills, Eric R Houpt","doi":"10.1016/j.lanmic.2024.101064","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.101064","url":null,"abstract":"<p><strong>Background: </strong>Shigellosis is a leading cause of diarrhoea in children globally. We aimed to assess the burden of specific Shigella species and Shigella flexneri serotypes, characterise their clinical syndromes and natural immunity, and evaluate their relevance as causes of diarrhoea and linear growth faltering.</p><p><strong>Methods: </strong>In the MAL-ED birth cohort study, children younger than 17 days were enrolled from Nov 3, 2009, to Feb 29, 2012, in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, Tanzania, and South Africa and were followed up for 2 years. In this retrospective substudy, we retested Shigella quantitative PCR-positive diarrhoeal and non-diarrhoeal stool samples with molecular subtyping assays. We estimated the prevalence of specific Shigella species and serotypes, estimated their associations with diarrhoea and clinical characteristics using generalised linear mixed models, estimated their associations with linear growth using linear regression, and used longitudinal infection data to estimate protection due to previous infection using the Andersen and Gill extension of the Cox model.</p><p><strong>Findings: </strong>1715 children (874 [51·0%] male and 841 [49·0%] female) with complete follow-up to 2 years provided 45 835 stool samples collected between age 0 and 2 years. 1294 (75·5%) children had at least one Shigella detection in a non-diarrhoeal or asymptomatic stool and 507 (29·6%) had at least one Shigella-attributed diarrhoea episode. In this substudy, we were able to type 1202 samples. The most common species and serotypes were Shigella sonnei (366 [30·4%] of 1202), S flexneri 2a (250 [20·8%]), and S flexneri 6 (296 [24·6%]). The associations of S flexneri and S sonnei detection with diarrhoea versus asymptomatic control stools were similar. Compared with diarrhoea episodes attributable to S flexneri, those attributable to S sonnei were less likely to be bloody (prevalence ratio 0·36 [95% CI 0·23 to 0·56]) or severe (prevalence ratio 0·58 [0·35 to 0·96]). The associations between asymptomatic Shigella infections and impaired linear growth at age 2 years were stronger for S flexneri than S sonnei (S flexneri length-for-age Z score difference -0·18 [95% CI -0·29 to -0·07] and S sonnei length-for-age Z score difference -0·07 [-0·21 to 0·07]). Examination of longitudinal infections showed that previous S sonnei infection was associated with a lower hazard of subsequent S sonnei diarrhoea (calibrated hazard ratio 0·41 [95% CI 0·19 to 0·90]). Otherwise, evidence for homotypic or heterotypic natural immunity was not apparent.</p><p><strong>Interpretation: </strong>This study provides data on prevailing Shigella species and serotypes in settings with a high burden of disease, underscoring the importance of asymptomatic S flexneri infection on growth impairment and the severity of S flexneri diarrhoea. Upcoming Shigella vaccines might need to induce immune responses that improve upon those produced by natu","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101064"},"PeriodicalIF":20.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744211","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 : 2025-03-25DOI: 10.1016/j.lanmic.2025.101120
Lita M Proctor, Joel Dore, Emmanuelle Maguin, Kristin Wannerberger, Claude Vincent
{"title":"A global partnership to advance the microbiome in human, plant, animal, and planetary health.","authors":"Lita M Proctor, Joel Dore, Emmanuelle Maguin, Kristin Wannerberger, Claude Vincent","doi":"10.1016/j.lanmic.2025.101120","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101120","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101120"},"PeriodicalIF":20.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744161","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 : 2025-03-24DOI: 10.1016/j.lanmic.2024.101047
Teck-Phui Chua, Lenka A Vodstrcil, Gerald L Murray, Erica L Plummer, Jørgen S Jensen, Magnus Unemo, Eric P F Chow, Nicola Low, David M Whiley, Emma L Sweeney, Jane S Hocking, Jennifer A Danielewski, Suzanne M Garland, Christopher K Fairley, Lei Zhang, Catriona S Bradshaw, Dorothy A Machalek
{"title":"Evolving patterns of macrolide and fluoroquinolone resistance in Mycoplasma genitalium: an updated systematic review and meta-analysis.","authors":"Teck-Phui Chua, Lenka A Vodstrcil, Gerald L Murray, Erica L Plummer, Jørgen S Jensen, Magnus Unemo, Eric P F Chow, Nicola Low, David M Whiley, Emma L Sweeney, Jane S Hocking, Jennifer A Danielewski, Suzanne M Garland, Christopher K Fairley, Lei Zhang, Catriona S Bradshaw, Dorothy A Machalek","doi":"10.1016/j.lanmic.2024.101047","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.101047","url":null,"abstract":"<p><strong>Background: </strong>Over the past 5 years, since publication of the initial review, studies have provided additional data on macrolide and fluoroquinolone resistance in Mycoplasma genitalium, including data from regions previously lacking this information. We aimed to provide contemporary estimates of macrolide and fluoroquinolone resistance in M genitalium to inform national, regional, and global treatment guidelines.</p><p><strong>Methods: </strong>This is an update of a previous systematic review and meta-analysis, which was performed up to Jan 7, 2019. In this update, we searched PubMed, Embase, and MEDLINE from Jan 1, 2018, to April 18, 2023, for published studies reporting macrolide, fluoroquinolone, or dual-class (macrolide and fluoroquinolone) resistance in M genitalium. Data were combined with the previous meta-analysis to examine resistance prevalence in M genitalium samples collected up to and including 2021. Random-effects meta-analyses were used to calculate summary estimates of prevalence. Subgroup analyses by WHO region and four time periods (before 2012 to 2018-21) were performed. This study was registered with PROSPERO, number CRD42021273340.</p><p><strong>Findings: </strong>166 studies (59 from the previous search period reporting data from M genitalium samples collected between 2003 and 2017, and 107 from the updated search period reporting data from M genitalium samples collected between 2005 and 2021) were included: 157 reporting macrolide resistance (41 countries; 22 974 samples), 89 reporting fluoroquinolone resistance (35 countries; 14 165 samples), and 74 reporting dual-class resistance (34 countries; 11 070 samples). In 2018-21, the overall prevalence of macrolide, fluoroquinolone, and dual-class resistance were 33·3% (95% CI 27·2-39·7), 13·3% (10·0-17·0), and 6·5% (4·0-9·4), respectively. Over time, there was a slight, although not statistically significant, decline in macrolide resistance in the Western Pacific and the Americas, but there was an increase in macrolide resistance in the European region. Fluoroquinolone resistance was highest in the Western Pacific and increased in the European non-Nordic region. ParC S83I was the most common variant associated with fluoroquinolone resistance, increasing from 0% (95% CI <0·0001-0·30) before 2012 to 7·3% (4·7-10·3) in 2018-21; p<sub>trend</sub>=0·055.</p><p><strong>Interpretation: </strong>Macrolide and fluoroquinolone resistance in M genitalium requires ongoing international surveillance, use of resistance assays for optimal antibiotic stewardship, and novel treatment options.</p><p><strong>Funding: </strong>Australian Research Council.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101047"},"PeriodicalIF":20.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732322","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 : 2025-03-18DOI: 10.1016/j.lanmic.2025.101107
A A Saied, Boshra A El-Saeed
{"title":"Infectiousness of raw (unpasteurised) milk from influenza H5N1-infected cows beyond the USA.","authors":"A A Saied, Boshra A El-Saeed","doi":"10.1016/j.lanmic.2025.101107","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101107","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101107"},"PeriodicalIF":20.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674745","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 : 2025-03-17DOI: 10.1016/j.lanmic.2024.101027
Cecile P G Meier-Scherling, Oliver J Watson, Victor Asua, Isaac Ghinai, Thomas Katairo, Shreeya Garg, Melissa D Conrad, Philip J Rosenthal, Lucy C Okell, Jeffrey A Bailey
{"title":"Selection of Plasmodium falciparum kelch13 mutations in Uganda in comparison with southeast Asia: a modelling study.","authors":"Cecile P G Meier-Scherling, Oliver J Watson, Victor Asua, Isaac Ghinai, Thomas Katairo, Shreeya Garg, Melissa D Conrad, Philip J Rosenthal, Lucy C Okell, Jeffrey A Bailey","doi":"10.1016/j.lanmic.2024.101027","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.101027","url":null,"abstract":"<p><strong>Background: </strong>Artemisinin partial resistance, mediated by mutations in the Plasmodium falciparum kelch13 gene (k13), rapidly spread in southeast Asia, undermining the antimalarial effectiveness of artemisinin-based combination therapies. k13 mutations have also arisen in Africa, but their rates of increase are not well characterised. We aimed to quantify the selection of k13 mutations in Africa and compare the selection with that in southeast Asia.</p><p><strong>Methods: </strong>In this modelling study, we investigated k13 mutation allele frequency at 16 sites in Uganda (2016-22) and five sites in southeast Asia (in Cambodia, Thailand, and Viet Nam; 2003-14). The Ugandan data were obtained from annual clinical surveillance studies and the southeast Asian data were obtained from the MalariaGEN Pf7 dataset. We investigated five validated and candidate k13 mutations: Pro441Leu, Cys469Phe, Cys469Tyr, Arg561His, and Ala675Val. We calculated annual selection coefficients using Bayesian mixed-effect linear models. We then tested whether the k13 mutation allele frequency in southeast Asia could have been forecast accurately using up to the first 5 years of available data and forecast future k13 mutation allele frequency in Uganda.</p><p><strong>Findings: </strong>We used data from 7564 samples from Uganda and 6568 samples from southeast Asia. The annual selection coefficient of evaluable k13 mutations (Pro441Leu, Cys469Phe/Tyr, Arg561His, and Ala675Val) across all sites was estimated at 0·381 (95% credible interval 0·298 to 0·472) per year, a 38% increase in relative allele frequency. Selection coefficients across Uganda were 0·494 (-0·462 to 1·410) for Pro441Leu, 0·324 (-0·629 to 1·150) for Cys469Phe, 0·383 (0·207 to 0·591) for Cys469Tyr, and 0·237 (0·087 to 0·403) for Ala675Val. In southeast Asia, the selection coefficients were 0·627 (-0·088 to 1·312) for Cys580Tyr, 0·224 (-0·903 to 1·397) for Arg539Thr, and 0·330 (-0·075 to 0·683) for all validated k13 mutations. Compared with out-of-sample data, the forecasts for southeast Asia underestimated mutation allele frequency and were of variable accuracy. Overall, forecast allele frequencies for Uganda, assuming constant selection, neared fixation (>0·95 allele frequency) within a decade (between 2031 and 2033) for combined k13 mutations.</p><p><strong>Interpretation: </strong>k13 mutation selection in Uganda was similar to that observed in southeast Asia, suggesting that frequencies of k13 mutations will continue to increase quickly in Uganda. These commensurate levels of selection indicate a high potential for rapid transmission across other parts of Africa, underscoring the urgent need for treatments and policies to mitigate the spread and impact of k13 mutations.</p><p><strong>Funding: </strong>US National Institutes of Health.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101027"},"PeriodicalIF":20.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671583","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}