Lancet Microbe最新文献

{"title":"The concept of external quality assessment super challenges with special consideration of their importance during pandemics.","authors":"Christoph Buchta, Stephan W Aberle, Stéphanie Albarède, Xavier Albe, Tony Badrick, Andreas Bietenbeck, Vincent Delatour, Gro Gidske, Andrea Griesmacher, Jaap J van Hellemond, Gitte M Henriksen, Jim F Huggett, István Juhos, Martin Kammel, Piet Meijer, Ingo Schellenberg, Heinz Zeichhardt, Cas Weykamp","doi":"10.1016/j.lanmic.2025.101292","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101292","url":null,"abstract":"<p><p>In this Personal View, we introduce the concept of external quality assessment (EQA) super challenges, in which multiple EQA providers, at approximately the same time and in a coordinated manner, use test samples with identical characteristics in their programmes. The evaluation of test results from the resulting increase in the number of laboratories and test systems used (considering the resulting greater variety of influencing factors that apply to the analysis in the individual laboratories) enables the collection of data that reveals differences, advantages, and disadvantages of individual test systems, in addition to the extent of individual influencing factors. By comparing the analytical performance of test systems and highlighting their limitations, EQA super challenges and the examination results collected by them are valuable contributions for post-market surveillance of diagnostic tests, aid harmonisation in laboratory medicine, and help to identify areas for improvement for manufacturers, policy makers, and regulators. Especially during or in preparation for epidemics or pandemics, EQA super challenges are particularly valuable for public health institutions to quickly gain a clear picture of the testing performance.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101292"},"PeriodicalIF":20.4,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688472","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":"Protecting the future of vaccine development amidst US funding withdrawal for mRNA vaccine research","authors":"Eskild Petersen ,&nbsp;Giuseppe Ippolito ,&nbsp;Markus Maeurer ,&nbsp;Francine Ntoumi ,&nbsp;Jean B Nachega ,&nbsp;David S Hui ,&nbsp;Alimuddin Zumla","doi":"10.1016/j.lanmic.2025.101226","DOIUrl":"10.1016/j.lanmic.2025.101226","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 12","pages":"Article 101226"},"PeriodicalIF":20.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006684","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":"Tick-borne viruses: moving the dial on diagnostics with diverse technological advances","authors":"Xinyu Wang ,&nbsp;Xinyi Jiao ,&nbsp;Ruihua Dong ,&nbsp;Xiaoling Li ,&nbsp;Di Wang ,&nbsp;Zhiwen Jiang ,&nbsp;Mei Kang ,&nbsp;Andres Merits ,&nbsp;Hao Li ,&nbsp;Longxian Zhang ,&nbsp;Zhihang Peng ,&nbsp;Na He ,&nbsp;Shuo Su","doi":"10.1016/j.lanmic.2025.101234","DOIUrl":"10.1016/j.lanmic.2025.101234","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 12","pages":"Article 101234"},"PeriodicalIF":20.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066024","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":"Fast-acting single-dose vesicular stomatitis virus-Sudan virus vaccine: a challenge study in macaques","authors":"Paige Fletcher PhD ,&nbsp;Kyle L O’Donnell PhD ,&nbsp;Friederike Feldmann ASS ,&nbsp;Joseph F Rhoderick BSc ,&nbsp;Chad S Clancy DVM PhD ,&nbsp;Jil A Haase PhD ,&nbsp;Cecilia A Prator PhD ,&nbsp;Brian J Smith DVM ,&nbsp;Bronwyn M Gunn PhD ,&nbsp;Heinz Feldmann MD ,&nbsp;Andrea Marzi PhD","doi":"10.1016/j.lanmic.2025.101244","DOIUrl":"10.1016/j.lanmic.2025.101244","url":null,"abstract":"<div><h3>Background</h3><div>The Sudan virus (SUDV) outbreaks in recent years, including the most recent outbreak in Uganda, created a public health emergency in the eastern Africa region. There are no licensed vaccines or therapeutics approved against SUDV; however, we have previously developed a vesicular stomatitis virus (VSV)-based vaccine expressing the SUDV glycoprotein and showed its single-dose efficacy in non-human primates (NHPs) with pre-existing Ebola virus (EBOV) immunity. Here, we determined the fast-acting capacity of this vaccine in naive NHPs. In addition, we examined if the licensed VSV-EBOV vaccine would provide any prophylactic benefit against SUDV infection.</div></div><div><h3>Methods</h3><div>We used four groups of male cynomolgus macaques (n=6 per group) aged 2·5–4·5 years and weighing 2·9–5·2 kg. NHPs were vaccinated by intramuscular injection 28 days before challenge with either 1 × 10⁷ plaque-forming units (PFUs) VSV-SUDV, VSV-EBOV, or control vaccine (VSV-LASV). Another group was vaccinated with 1 × 10⁷ PFU VSV-SUDV 7 days before challenge. On day 0, all 24 NHPs were challenged with a lethal dose of SUDV (1 × 10⁴ 50% tissue culture infectious doses [TCID₅₀] SUDV-Gulu, backtitred as 1·1 × 10⁴ TCID₅₀). We assessed anaesthetised NHPs on days –28, –21, –14, and –7 before challenge; days 0, 3, 6, 9, 14, 21, 28, and 35 after challenge; and at euthanasia (day 42 for survivors).</div></div><div><h3>Findings</h3><div>All VSV-SUDV-vaccinated NHPs were protected from disease after the lethal SUDV challenge. In contrast, the VSV-EBOV-vaccinated and control NHPs succumbed to disease between days 5 and 7 after challenge presenting with classical signs of Sudan virus disease associated with high-titre viraemia (&gt;1 × 10⁸ TCID₅₀ per mL), high viral organ load (&gt;1 × 10⁸ TCID₅₀ per g), dysregulated cytokine profiles, and typical pathological changes. The humoral immune response in the NHPs vaccinated with VSV-SUDV 1 month before challenge resulted in a profound and sustained serum antibody response (20 000–30 000 U/mL) with a diverse functionality profile (antibody-dependent cellular phagocytosis and antibody-dependent complement), which was not observed to the same extent in NHPs vaccinated 1 week before challenge.</div></div><div><h3>Interpretation</h3><div>We showed that a single dose of VSV-SUDV protected NHPs from lethal SUDV infection within 1 week. The fast-acting nature highlights VSV-SUDV as an ideal countermeasure for ring vaccination during outbreaks of Sudan virus disease pending further preclinical and clinical assessment. In contrast, VSV-EBOV provided no relevant protection against SUDV infection in NHPs, highlighting the need for species-specific filovirus vaccines.</div></div><div><h3>Funding</h3><div>National Institutes of Health, US Department of Health and Human Services.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 12","pages":"Article 101244"},"PeriodicalIF":20.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757985","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":"Whom tuberculosis tests detect and why it matters: implications for diagnostic algorithms","authors":"Emily A Kendall MD ,&nbsp;Prof Claudia M Denkinger MD ,&nbsp;Prof Adithya Cattamanchi MD ,&nbsp;Prof David W Dowdy MD ,&nbsp;Prof Jason R Andrews MD","doi":"10.1016/j.lanmic.2025.101237","DOIUrl":"10.1016/j.lanmic.2025.101237","url":null,"abstract":"<div><div>Tuberculosis encompasses a spectrum of characteristics—including bacillary burden, clinical severity, and access to care—that are relevant to clinical and epidemiological outcomes and the performance of diagnostic assays. The value of diagnostic assays depends not only on their numerical accuracy, which can vary substantially between populations, but also on which individuals with and without tuberculosis the assays identify. Moreover, detectable features of tuberculosis, such as pathogen burden or host responses, are often correlated, making it difficult to predict the accuracy and impact of diagnostic algorithms from the accuracies of individual component tests. Therefore, when evaluating novel tuberculosis diagnostics, greater consideration should be given to characterising which segments of the disease spectrum are detected, how these segments overlap across tests, and how they are prioritised for detection. Understanding these relationships is particularly crucial for screening, given that screening seeks to detect a broad spectrum of disease and often uses multistep algorithms. We present a framework for understanding the sensitivity and specificity of assays and algorithms as the degree of alignment between different subsets of the disease spectrum. Based on this framework, we make recommendations for the measurement, reporting, target setting, and interpretation of diagnostic accuracy to guide both novel test development and the optimal use of existing diagnostics.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 12","pages":"Article 101237"},"PeriodicalIF":20.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337784","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":"Suriname: first malaria-free country in the Amazon region","authors":"Manjulika Das","doi":"10.1016/j.lanmic.2025.101246","DOIUrl":"10.1016/j.lanmic.2025.101246","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 12","pages":"Article 101246"},"PeriodicalIF":20.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179398","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":"Direct and indirect protection against scabies through ivermectin mass drug administration designed for malaria in Mozambique: a substudy nested within a cluster-randomised, controlled trial","authors":"Joanna Furnival-Adams PhD ,&nbsp;Amelia Houana MD ,&nbsp;Francisco Saute PhD ,&nbsp;Eldo Elobolobo MSc ,&nbsp;Matthew Rudd PhD ,&nbsp;Patricia Nicolas MSc ,&nbsp;Julia Montaña MSc ,&nbsp;Samuel Martinho MPH ,&nbsp;Hansel Mundaca MSc ,&nbsp;Jenisse Mbanze MSc ,&nbsp;Arlindo Soares BSc ,&nbsp;Saimado Imputiua BSc ,&nbsp;Paula Ruiz-Castillo PhD ,&nbsp;Marta Ribes PhD ,&nbsp;Almudena Sanz MSc ,&nbsp;Mussa Mamudo Salé PhD ,&nbsp;Antonio Macucha MD ,&nbsp;Aina Casellas MSc ,&nbsp;Valeria Lopez MD ,&nbsp;Vegovito Vegove BSc ,&nbsp;Carlos Chaccour PhD","doi":"10.1016/j.lanmic.2025.101189","DOIUrl":"10.1016/j.lanmic.2025.101189","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Ivermectin is an endectocide effective against scabies that is under evaluation as a malaria vector control tool. During the BOHEMIA malaria trial, we did a substudy with the aim of assessing the efficacy of ivermectin mass drug administration (MDA) against scabies.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The BOHEMIA trial was an open-label, assessor-masked, cluster-randomised trial done in a malaria and scabies co-endemic community in Mozambique. Clusters were randomised (1:1:1) to receive a single dose of either ivermectin 400 μg/kg to all eligible humans, 400 μg/kg to humans and 200 μg/kg to eligible livestock, or 400 mg albendazole in humans only (control) for 3 consecutive months. In this scabies substudy, 39 clusters were randomly selected from the main trial. The primary endpoint was scabies prevalence at 3 months. Secondary endpoints were scabies prevalence in directly exposed participants (those who took the study drug) at 1, 2, and 3 months, and indirectly exposed children younger than 5 years (who were living in clusters but did not take the study drug) at 3 and 6 months. An intention-to-treat analysis was done by use of a logistic regression model with a generalised estimating equation approach. 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;NCT04966702&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;, and on the Pan African Clinical Trial Registry, PACTR202106695877303, and is complete.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;Recruitment started on March 15, 2022 and was completed on July 6, 2022. Of 40 524 participants from 100 clusters accessed in the BOHEMIA trial, 1951 participants were enrolled from 39 clusters (13 per group) in the scabies substudy. Scabies prevalence in the ivermectin group was lower after 3 months (2·11%, 95% CI 1·21–3·41) than at baseline (8·10%, 6·36–9·85), whereas it did not change in the albendazole group (13·71%, 10·81–17·05, at 3 months &lt;em&gt;vs&lt;/em&gt; 12·30%, 9·43–15·17, at baseline). The odds of having scabies was lower in pooled ivermectin clusters than in albendazole clusters after 3 months (adjusted odds ratio [aOR] 0·18, 95% CI 0·07–0·45, p=0·0002). This effect was observed both in directly exposed participants who took ivermectin after 1 month (aOR 0·27, 95% CI 0·11–0·66, p=0·0023), 2 months (0·18, 0·07–0·47, p=0·0006), and 3 months (0·16, 0·06–0·45, p=0·0004), and in indirectly exposed children after 3 months (0·17, 0·05–0·58, p=0·0048) and 6 months (0·21, 0·06–0·72, p=0·013). There were two severe adverse events; both were deaths in the ivermectin group that were not considered related to the study drug. No safety signal was detected.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Interpretation&lt;/h3&gt;&lt;div&gt;Ivermectin MDA designed for malaria might have significant benefits against scabies. In addition to directly exposed participants, our results also suggested an effect in indirectly exposed participants, which might reflect a community benefit.&lt;/di","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 12","pages":"Article 101189"},"PeriodicalIF":20.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582558","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":"Beyond bacteria: a multikingdom ecological perspective on neonatal gut and severe viral lower respiratory tract infection risk","authors":"Jiaqi Wang ,&nbsp;Zengguo Cao ,&nbsp;Xuemin Jin","doi":"10.1016/j.lanmic.2025.101202","DOIUrl":"10.1016/j.lanmic.2025.101202","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 12","pages":"Article 101202"},"PeriodicalIF":20.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676095","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":"Effect of decreasing the frequency of screening for Neisseria gonorrhoeae and Chlamydia trachomatis on the incidence of these infections and antimicrobial use among men who have sex with men using HIV PrEP in Belgium: a retrospective cohort study","authors":"Thibaut Vanbaelen PhD ,&nbsp;Irith De Baetselier PhD ,&nbsp;Achilleas Tsoumanis MSc ,&nbsp;Bernadette Hensen PhD ,&nbsp;Prof Chris Kenyon PhD","doi":"10.1016/j.lanmic.2025.101214","DOIUrl":"10.1016/j.lanmic.2025.101214","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;There is growing evidence that the benefits of systematic screening for &lt;em&gt;Neisseria gonorrhoeae&lt;/em&gt; and &lt;em&gt;Chlamydia trachomatis&lt;/em&gt; among men who have sex with men (MSM) using HIV pre-exposure prophylaxis (PrEP) are scarce and that screening leads to high antimicrobial consumption. The PrEP clinic of the Institute of Tropical Medicine (ITM) in Antwerp, Belgium, discontinued systematic screening for these infections in MSM taking PrEP in 2023. In this study, we estimated the effect of reducing the frequency of screening on the incidence of these infections and antimicrobial use among MSM using PrEP.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We did a retrospective cohort analysis of medical records, laboratory results, and antimicrobial prescriptions (ceftriaxone, doxycycline, and azithromycin) of MSM attending the PrEP clinic of the ITM in Antwerp, Belgium, between Jan 1, 2019, and Dec 31, 2024. We estimated yearly testing rates for &lt;em&gt;N gonorrhoeae&lt;/em&gt; and &lt;em&gt;C trachomatis&lt;/em&gt;, incidence rates of overall and symptomatic infections, and antimicrobial prescription rates. Results were analysed using Poisson regression, with the number of events as the outcome, years as a continuous predictor and the log(person-time) as offset. Additionally, we did three sensitivity analyses: limiting our study population to individuals engaged in PrEP care in 2019; excluding participants of the Gonoscreen study; and using time as a categorical variable.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;Between Jan 1, 2019, and Dec 31, 2024, 3955 MSM attended the clinic. Over the study period, 11 720 tests were done during 9853·85 person-years. The testing rate decreased significantly from 2267·78 tests per 1000 person-years (95% CI 2176·49–2361·92) in 2019 to 552·81 tests per 1000 person-years (521·53–585·47) in 2024 (yearly rate ratio 0·78, 95% CI 0·77–0·78; p&lt;0·0001). The incidence of &lt;em&gt;N gonorrhoeae&lt;/em&gt; decreased from 170·84 cases per 1000 person-years (95% CI 146·47–198·11) in 2019 to 85·81 cases per 1000 person-years (73·77–99·27) in 2024 (yearly incidence rate ratio [IRR] 0·91, 95% CI 0·88–0·94; p&lt;0·0001). In the same period, the incidence of &lt;em&gt;C trachomatis&lt;/em&gt; decreased from 198·17 cases per 1000 person-years (95% CI 171·85–227·39) in 2019 to 60·69 cases per 1000 person-years (50·63–72·16) in 2024 (yearly IRR 0·84, 95% CI 0·81–0·87; p&lt;0·0001). There was no increase in the incidence of symptomatic &lt;em&gt;N gonorrhoeae&lt;/em&gt; (IRR 0·98, 95% CI 0·92–1·03)&lt;em&gt;, C trachomatis&lt;/em&gt; (0·95, 0·88–1·01), or lymphogranuloma venereum (0·95, 0·84–1·09). Ceftriaxone, doxycycline, and azithromycin prescriptions decreased (rate ratio 0·95, 95% CI 0·91–0·99; p=0·023, 0·47, 0·43–0·52; p&lt;0·0001, and 0·90, 0·87–0·94; p&lt;0·0001, respectively). Similar results were found in the first sensitivity analysis. In the sensitivity analysis excluding participants of the Gonoscreen study, rates of ceftriaxone and doxycycline prescriptions decreased bet","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 12","pages":"Article 101214"},"PeriodicalIF":20.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423140","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":"HIV drug resistance during antiretroviral therapy scale-up in Uganda, 2012–19: a population-based, longitudinal study","authors":"Michael A Martin PhD ,&nbsp;Steven James Reynolds MD ,&nbsp;Brian T Foley PhD ,&nbsp;Fred Nalugoda PhD ,&nbsp;Prof Thomas C Quinn MD ,&nbsp;Steven A Kemp PhD ,&nbsp;Margaret Nakalanzi MS ,&nbsp;Edward Nelson Kankaka MD ,&nbsp;Godfrey Kigozi PhD ,&nbsp;Robert Ssekubugu MSPH ,&nbsp;Prof Ravindra K Gupta MD ,&nbsp;Lucie Abeler-Dörner PhD ,&nbsp;Joseph Kagaayi PhD ,&nbsp;Oliver Ratmann PhD ,&nbsp;Prof Christophe Fraser PhD ,&nbsp;Ronald Moses Galiwango PhD ,&nbsp;David Bonsall PhD ,&nbsp;M Kate Grabowski PhD","doi":"10.1016/j.lanmic.2025.101218","DOIUrl":"10.1016/j.lanmic.2025.101218","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;With scale-up of antiretroviral therapy (ART) in sub-Saharan Africa, increasing pretreatment HIV drug resistance has been reported; however, the broader effect of ART expansion on population-level resistance patterns remains insufficiently quantified. We aimed to estimate the longitudinal prevalence of drug resistance and resistance-conferring mutations.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This study used data collected as part of the Rakai Community Cohort Study (RCCS), an open population-based census and cohort study conducted in southern Uganda. At each survey round, residents aged 15–49 years are invited to participate and receive a structured questionnaire that obtains sociodemographic, behavioural, and health information, including self-reported past and current ART use. Voluntary HIV testing is conducted using a rapid test algorithm and a venous blood sample. People with HIV provide samples for viral load quantification and deep sequencing. We analysed RCCS survey, HIV viral load, and deep sequencing (which was used to predict resistance) data from five survey rounds. The key outcomes were the population prevalence of viraemic people with HIV with non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), protease inhibitor, or multiclass resistance among all participants (regardless of HIV serostatus) in the 2015 and 2017 surveys. Prevalence of class-specific resistance and resistance-conferring substitutions were estimated using robust log-Poisson regression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;Between Aug 10, 2011, and Nov 4, 2020, there were 43 361 participants in the RCCS and 7923 (18·27%) people with HIV. Over five survey rounds, 93 622 participant visits occurred, among which 17 460 (18·65%) were from people with HIV. Over the analysis period, the median age of study participants remained similar (28 years [22–35] in 2012 and 29 years [21–38] in 2019). Sufficient data were available to reliably genotype 4072 (90·03%) of 4523 participant visits from 3407 people with HIV for at least one drug. Overall population prevalence of resistance contributed by viraemic pretreatment people with HIV decreased between 2012 and 2017 from 0·56% (95% CI 0·42–0·75) to 0·25% (0·18–0·33) for NNRTI and from 0·24% (0·15–0·37) to 0·05% (0·02–0·10) for NRTI (prevalence ratio 0·44 [0·29–0·68] for NNRTI and 0·21 [0·09–0·47] for NRTI). Between 2012 and 2017, NNRTI resistance among viraemic pretreatment people with HIV increased from 4·86% (3·69–6·42) to 9·61% (7·27–12·7; prevalence ratio 1·98 [1·34–2·91]). The prevalence of NNRTI and NRTI resistance was substantially higher among viraemic treatment-experienced people with HIV (51·49% [46·24–57·34] for NNRTI and 36·46% [30·06–44·22] for NRTI in 2017) than among pretreatment people with HIV. NNRTI and NRTI resistance was predominantly attributable to rtK103N and rtM184V. inT97A was observed at a similar prevalence among viraemic tre","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 12","pages":"Article 101218"},"PeriodicalIF":20.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649611","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}