Lancet MicrobePub Date : 2025-05-24DOI: 10.1016/j.lanmic.2025.101158
Kenneth Iregbu, Rong Zhang, Yuqing Zhou, Timothy R Walsh
{"title":"Global health equity and diagnosis of sepsis in low-income and middle-income countries.","authors":"Kenneth Iregbu, Rong Zhang, Yuqing Zhou, Timothy R Walsh","doi":"10.1016/j.lanmic.2025.101158","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101158","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101158"},"PeriodicalIF":20.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162806","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 : 2025-05-24DOI: 10.1016/j.lanmic.2025.101102
Joshua C D'Aeth, Marta Bertran, Fariyo Abdullahi, Seyi Eletu, Erjola Hani, Norman K Fry, Shamez N Ladhani, David J Litt
{"title":"Whole-genome sequencing, strain composition, and predicted antimicrobial resistance of Streptococcus pneumoniae causing invasive disease in England in 2017-20: a prospective national surveillance study.","authors":"Joshua C D'Aeth, Marta Bertran, Fariyo Abdullahi, Seyi Eletu, Erjola Hani, Norman K Fry, Shamez N Ladhani, David J Litt","doi":"10.1016/j.lanmic.2025.101102","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101102","url":null,"abstract":"<p><strong>Background: </strong>Surveillance of the invasive disease burden caused by Streptococcus pneumoniae in England is performed by the UK Health Security Agency (UKHSA). In 2017, UKHSA switched from phenotypic methods to whole-genome sequencing (WGS) approaches for pneumococcal surveillance. Here, we present the first results of national WGS surveillance, up to the start of the COVID-19 pandemic, with the aim of describing the population genomics of this important pathogen.</p><p><strong>Methods: </strong>We examined prospective national surveillance data from England, using bacterial isolates from cases of invasive pneumococcal disease (IPD) submitted to the national reference laboratory at UKHSA. A bioinformatic pipeline was developed to quality control WGS data and routinely report species and serotype. We assembled isolate data, assigned global pneumococcal sequencing clusters (GPSCs), and predicted antimicrobial resistance (AMR) profiles for isolates that passed further quality control. We collected additional data on patient outcomes and characteristics using enhanced surveillance questionnaires completed by patients' general practitioners. We used logistic regression analysis to assess the effects of various genomic and patient characteristics on the outcomes of IPD.</p><p><strong>Findings: </strong>In England, between July 1, 2017, and Feb 29, 2020, there were 15 400 cases of IPD. From these cases, 13 749 (89·3%) isolates were sequenced, passed quality control, and were included in analyses. Serotype diversity was high during the study period, with 2751 (20%) isolates serotyped as 13-valent pneumococcal conjugate vaccine (PCV13) types, whereas serotype 8 was the most prevalent serotype (n=3074 [22·4%]) overall. There were 157 GPSCs within the collection, with GSPC3 the most common, encompassing 98·7% (3033 of 3074) of serotype 8 isolates. Most isolates (n=10 198 [74·2%]) did not contain AMR-associated genes. Resistance to co-trimoxazole was the most frequently predicted resistance (n=2331 [17%]), followed by resistance to tetracycline (n=1199 [8·7%]) and β-lactams (n=1149 [8·4%]). Logistic regression analysis found the presence of AMR-associated genes significantly increased the odds of patient death (odds ratio 1·18, 95% CI 1·01-1·38). Some GPSCs were also associated with a significant increase in the odds of patient death, such as GPSC12 (1·88, 1·48-2·38). Isolates from 2018 were associated with a significant increase in the odds of patient death (1·12, 1·00-1·25), whereas younger patient age was significantly associated with a reduction in the odds of patient death compared with being aged 85 years or older.</p><p><strong>Interpretation: </strong>WGS-based surveillance has allowed us to interrogate country-wide population dynamics driving changes in pneumococcal serotype frequency. Here, we observe a stable but diverse population before the COVID-19 pandemic restrictions were enforced in England, with low rates of AMR. These fin","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101102"},"PeriodicalIF":20.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162808","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 : 2025-05-21DOI: 10.1016/j.lanmic.2024.101065
Benjamin J Singer, Mireille Gomes, Jean T Coulibaly, Minoli Daigavane, Sophia T Tan, Isaac I Bogoch, Nathan C Lo
{"title":"Population-level impact of mass drug administration against schistosomiasis with anthelmintic drugs targeting juvenile schistosomes: a modelling study.","authors":"Benjamin J Singer, Mireille Gomes, Jean T Coulibaly, Minoli Daigavane, Sophia T Tan, Isaac I Bogoch, Nathan C Lo","doi":"10.1016/j.lanmic.2024.101065","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.101065","url":null,"abstract":"<p><strong>Background: </strong>Schistosomiasis is a neglected disease caused by parasitic flatworms of the genus Schistosoma and affects more than 150 million people worldwide. Praziquantel, the drug used in public health control programmes, has minimal activity against juvenile schistosomes (within 6 weeks of infection) and imperfect cure rates. We aimed to model the population-level impact of hypothetical novel drug candidates, targeting both juvenile and adult schistosomes with various efficacies, across a range of baseline epidemiological settings.</p><p><strong>Methods: </strong>In this modelling study, we used a stochastic, individual-based mechanistic model of Schistosoma mansoni infection and simulated mass drug administration control programmes in diverse epidemiological environments. These programmes involved the administration, over a 5-year period at 75% coverage, of praziquantel (single-dose or two-dose regimens) or hypothetical novel drugs with various assumed efficacies against adult and juvenile schistosome parasites: novel drug A, with equivalent efficacy to praziquantel against adult schistosomes plus perfect (100%) efficacy against juvenile schistosomes; novel drug B, with higher efficacy than praziquantel against adult schistosomes and no activity against juveniles; and novel drug C, with higher efficacy than praziquantel against adult schistosomes plus perfect efficacy against juveniles. The outcomes were median observed S mansoni infection prevalence and infection intensity over time in simulated populations.</p><p><strong>Findings: </strong>In a simulated high-endemicity setting (baseline prevalence of S mansoni infection of 53%), modelled prevalence after a single treatment was 20·8% (uncertainty interval 15·8-23·6) for single-dose praziquantel, 17·8% (15·2-19·8) for two-dose praziquantel, 18·4% (13·4-21·4) for novel drug A, 16·0% (15·0-16·8) for novel drug B, and 13·4% (12·6-14·0) for novel drug C; at year 5, modelled prevalence was 14·6% (12·2-16·4) for single-dose praziquantel, 13·6% (11·6-14·6) for two-dose praziquantel, 11·8% (9·4-13·4) for novel drug A, 12·6% (11·6-13·4) for novel drug B, and 9·6% (9·0-10·4) for novel drug C. In a simulated low-endemicity setting (baseline prevalence 15%), modelled prevalence after a single treatment was 4·8% (3·6-5·8) for single-dose praziquantel, 4·2% (3·6-5·0) for two-dose praziquantel, 4·6% (3·2-5·4) for novel drug A, 4·0% (3·4-4·6) for novel drug B, and 3·6% (3·2-4·2) for novel drug C; at year 5, modelled prevalence was 3·0% (2·2-3·6) for single-dose praziquantel, 2·8% (2·2-3·4) for two-dose praziquantel, 2·6% (1·8-3·2) for novel drug A, 2·7% (2·2-3·2) for novel drug B, and 2·2% (1·8-2·6) for novel drug C.</p><p><strong>Interpretation: </strong>This study provides policy-relevant data that could help to guide the development and selection of novel drugs for schistosomiasis. Novel anthelmintic drugs that can kill both adult and juvenile schistosomes with higher efficacy than pra","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101065"},"PeriodicalIF":20.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144055","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 : 2025-05-16DOI: 10.1016/j.lanmic.2024.101041
Chama Chanda, Freddie Kibengo, Michael Mutua, Fred Ogada, Vincent Muturi-Kioi, Belkis M Akis Yildirim, Mary Amondi, Andrea Baines, Vincent Basajja, Nicola Borthwick, Kefa Bosire, Elias Chambula, Paramesh Chetty, Kundai Chinyenze, Oscar Chirro, Alison Crook, Jan De Bont, Natalia Fernandez, Peter Ejou, Bashir Farah, Molly Glaze, Ben Gombe, Anne Gumbe, Peter Hayes, Sally Itwi, Sheba Juma, Anita Kabarambi, Chishiba Kabengele, Paddy Kafeero, Ayoub Kakande, Jennifer Kanungi, William Kidega, Deborah King, Rose Mahira, Roselyn Malogo, Mabela Matsoso, Clive Michelo, Annie Moyo, Susan Mugaba, Irene Mugenya, Patrick Muhumuza, Yama F Mujadidi, Moses Muriuki, Vernon Musale, Gaudensia Mutua, Meya Muwowo, Fatima Mwale, Irene Mwangi, Maria Nakimbugwe, Angella Namuyanja, Eunice Nduati, Leslie Nielsen, Jaquelyn Nyange, Geofrey Oino, Brenda Okech, Gloria Omosa-Manyonyi, Dan Otieno, Shaun Palmer, Hilda Phiri, Kelly Ramko, Rachel L Rutishauser, Eddy Sayeed, Rose Sajabi, Jennifer Serwanga, Edmund G-T Wee, Claire Wenden, Paola Cicconi, Patricia Fast, Jill Gilmour, Walter Jaoko, Pontiano Kaleebu, William Kilembe, Hester Kuipers, Eduard J Sanders, Tomáš Hanke
{"title":"Safety and broad immunogenicity of HIVconsvX conserved mosaic candidate T-cell vaccines vectored by ChAdOx1 and MVA in HIV-CORE 006: a double-blind, randomised, placebo-controlled phase 1 trial in healthy adults living without HIV-1 in eastern and southern Africa.","authors":"Chama Chanda, Freddie Kibengo, Michael Mutua, Fred Ogada, Vincent Muturi-Kioi, Belkis M Akis Yildirim, Mary Amondi, Andrea Baines, Vincent Basajja, Nicola Borthwick, Kefa Bosire, Elias Chambula, Paramesh Chetty, Kundai Chinyenze, Oscar Chirro, Alison Crook, Jan De Bont, Natalia Fernandez, Peter Ejou, Bashir Farah, Molly Glaze, Ben Gombe, Anne Gumbe, Peter Hayes, Sally Itwi, Sheba Juma, Anita Kabarambi, Chishiba Kabengele, Paddy Kafeero, Ayoub Kakande, Jennifer Kanungi, William Kidega, Deborah King, Rose Mahira, Roselyn Malogo, Mabela Matsoso, Clive Michelo, Annie Moyo, Susan Mugaba, Irene Mugenya, Patrick Muhumuza, Yama F Mujadidi, Moses Muriuki, Vernon Musale, Gaudensia Mutua, Meya Muwowo, Fatima Mwale, Irene Mwangi, Maria Nakimbugwe, Angella Namuyanja, Eunice Nduati, Leslie Nielsen, Jaquelyn Nyange, Geofrey Oino, Brenda Okech, Gloria Omosa-Manyonyi, Dan Otieno, Shaun Palmer, Hilda Phiri, Kelly Ramko, Rachel L Rutishauser, Eddy Sayeed, Rose Sajabi, Jennifer Serwanga, Edmund G-T Wee, Claire Wenden, Paola Cicconi, Patricia Fast, Jill Gilmour, Walter Jaoko, Pontiano Kaleebu, William Kilembe, Hester Kuipers, Eduard J Sanders, Tomáš Hanke","doi":"10.1016/j.lanmic.2024.101041","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.101041","url":null,"abstract":"<p><strong>Background: </strong>Even within the context of antiretroviral treatment and prevention, an HIV-1 vaccine remains the best strategy for ending the HIV/AIDS epidemic. A vaccine is particularly needed in sub-Saharan Africa, where HIV-1 greatly affects people's lives and economy. Here, we aimed to assess the safety and immunogenicity of candidate T-cell vaccines in African populations.</p><p><strong>Methods: </strong>HIV-CORE 006 was a double-blind, randomised, placebo-controlled phase 1 trial conducted across four clinical research centres in Uganda, Kenya, and Zambia. Eligible participants were not pregnant, were living without HIV-1 or HIV-2, had a low likelihood of acquiring HIV-1, were aged 18-50 years, fully comprehended the purpose and details of this study as outlined in the participant information sheet, and passed an assessment of understanding before providing written informed consent. Participants were randomly assigned (9:2) to receive either a vaccine regimen or a placebo. The vaccine was administered as ChAdOx1.tHIVconsv1 (C1) followed by MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) in regimen C1-M3M4. The first primary outcome was the vaccines' safety assessment, assessed in all participants who received at least one vaccine or placebo dose. The second primary outcome evaluated the C1-M3M4 regimen's induction of HIVconsvX-specific T-cell responses by assessing the proportion of vaccine recipients who responded to the vaccination, assessed in all participants who received all doses of vaccine or placebo as per protocol. This study is registered with ClinicalTrials.gov, NCT04553016, and the Pan-African Clinical Trials Registry PACTR202006495409011, and is now closed.</p><p><strong>Findings: </strong>Between July 15, 2021, and Nov 2, 2022, 89 healthy adults living without HIV-1 were randomly assigned, with 88 receiving either the vaccine (n=72) or placebo (n=16). Of these 88 participants, 57 (65%) were male and 31 (35%) were female. The C1, M3, and M4 vaccine components were well tolerated and induced HIVconsvX-specific responses in 70 (99%) of the 71 participants who completed all vaccine doses. Vaccine-elicited T cells peaked at a median of 2310 (IQR 1080-4480) IFN-γ spot-forming units per 10<sup>6</sup> peripheral blood mononuclear cells and recognised a median of eight (five to ten) of ten peptide pools spanning the HIVconsvX immunogen. The total frequencies of elicited T cells decreased 4·6 times over a 40-week follow-up period compared with the peak responses. Upon antigenic re-exposure, T cells proliferated, exhibited multiple effector functions, and inhibited HIV-1 representatives from clades A, B, C, and D.</p><p><strong>Interpretation: </strong>Results from key sub-Saharan African populations supported the safety of the vaccine regimen previously shown in the first-in-human trial in the UK. The induction of T cells and their characteristics encourage vaccine integration into HIV-1 cure strategies, which could inform ","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101041"},"PeriodicalIF":20.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102989","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 : 2025-05-03DOI: 10.1016/j.lanmic.2025.101123
Gabrielle de Crombrugghe, Lionel Schiavolin, Joshua Osowicki, Andrew C Steer, Anne Botteaux, Pierre R Smeesters
{"title":"M1 and done? Global assessment of the invasive potential of group A streptococcal strains.","authors":"Gabrielle de Crombrugghe, Lionel Schiavolin, Joshua Osowicki, Andrew C Steer, Anne Botteaux, Pierre R Smeesters","doi":"10.1016/j.lanmic.2025.101123","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101123","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101123"},"PeriodicalIF":20.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987879","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 : 2025-05-01DOI: 10.1016/j.lanmic.2024.101013
Caitlin Pley MB , Laura Jung MD , Nadra Nurdin MB , Tim Venkatesan MSc , Vasanth V Naidu MRCP , Rosemary James MB , Laura Kmentt MB , Isaac Florence MSc , Ellie Delight MSc , Christina Guo MD , Alex Paddy Abdel Salam DPhil
{"title":"Duration of viral persistence in human semen after acute viral infection: a systematic review","authors":"Caitlin Pley MB , Laura Jung MD , Nadra Nurdin MB , Tim Venkatesan MSc , Vasanth V Naidu MRCP , Rosemary James MB , Laura Kmentt MB , Isaac Florence MSc , Ellie Delight MSc , Christina Guo MD , Alex Paddy Abdel Salam DPhil","doi":"10.1016/j.lanmic.2024.101013","DOIUrl":"10.1016/j.lanmic.2024.101013","url":null,"abstract":"<div><div>The persistence of viruses in human semen following acute infection can contribute to the ongoing transmission of a disease or cause resurgence after an outbreak has been declared ended. Viral persistence in semen affects embryonic development and male fertility, and the development of drugs and vaccines. We conducted a systematic review of viral persistence in semen in accordance with PRISMA guidelines. 373 original studies were included in this Review after screening 29 739 articles from five databases. Evidence was found of detection of 22 viruses in human semen following acute infection, including pathogens with pandemic potential. In addition to collating the largest evidence base to date on viral detection in semen following acute infection, this Review reports the maximal and median viral persistence (in days) after the onset of illness and evidence for sexual transmission and viability of the viruses in semen. Finally, the Review presents research gaps that need to be prioritised to guide further study of the dynamics of viral persistence in semen.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 5","pages":"Article 101013"},"PeriodicalIF":20.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822741","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 : 2025-05-01DOI: 10.1016/j.lanmic.2024.101002
Xin Hui S Chan DPhil , Ilsa L Haeusler BMBCh , Bennett J K Choy MBChB , Md Zakiul Hassan MBBS , Junko Takata BMBCh , Tara P Hurst PhD , Luke M Jones PhD , Shanghavie Loganathan BMBCh , Elinor Harriss MSc , Jake Dunning PhD , Prof Joel Tarning PhD , Prof Miles W Carroll PhD , Prof Peter W Horby PhD , Prof Piero L Olliaro PhD
{"title":"Therapeutics for Nipah virus disease: a systematic review to support prioritisation of drug candidates for clinical trials","authors":"Xin Hui S Chan DPhil , Ilsa L Haeusler BMBCh , Bennett J K Choy MBChB , Md Zakiul Hassan MBBS , Junko Takata BMBCh , Tara P Hurst PhD , Luke M Jones PhD , Shanghavie Loganathan BMBCh , Elinor Harriss MSc , Jake Dunning PhD , Prof Joel Tarning PhD , Prof Miles W Carroll PhD , Prof Peter W Horby PhD , Prof Piero L Olliaro PhD","doi":"10.1016/j.lanmic.2024.101002","DOIUrl":"10.1016/j.lanmic.2024.101002","url":null,"abstract":"<div><div>Nipah virus disease is a bat-borne zoonosis with person-to-person transmission, a case-fatality rate of 38–75%, and well recognised potential to cause a pandemic. The first reported outbreak of Nipah virus disease occurred in Malaysia and Singapore in 1998, which has since been followed by multiple outbreaks in Bangladesh and India. To date, no therapeutics or vaccines have been approved to treat Nipah virus disease, and only few such candidates are in development. In this Review, we aim to assess the safety and efficacy of the therapeutic options (monoclonal antibodies and small molecules) for Nipah virus disease and other henipaviral diseases to support prioritisation of drug candidates for further evaluation in clinical trials. At present, sufficient evidence exists to suggest trialling 1F5, m102.4, and remdesivir (alone or in combination) for prophylaxis and early treatment of Nipah virus disease. In addition to well designed clinical efficacy trials, in-vivo pharmacokinetic–pharmacodynamic studies are needed to optimise the selection and dosing of therapeutic candidates in animal challenge and natural human infection.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 5","pages":"Article 101002"},"PeriodicalIF":20.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644707","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 : 2025-05-01DOI: 10.1016/j.lanmic.2024.101034
Anne Karmisholt Grosen PhD , Susan Mikkelsen PhD , Lotte Aas Hindhede MSc , Sara Ellegaard Paaske MD , Simon Mark Dahl Baunwall PhD , Mette Mejlby Hansen MSc , Jens Frederik Dahlerup DMSc , Martin Steen Mortensen PhD , Prof Tine Rask Licht PhD , Jens Kjærgaard Boldsen PhD , Lise Tornvig Erikstrup PhD , Prof Christian Lodberg Hvas PhD , Prof Christian Erikstrup PhD
{"title":"Effects of clinical donor characteristics on the success of faecal microbiota transplantation for patients in Denmark with Clostridioides difficile infection: a single-centre, prospective cohort study","authors":"Anne Karmisholt Grosen PhD , Susan Mikkelsen PhD , Lotte Aas Hindhede MSc , Sara Ellegaard Paaske MD , Simon Mark Dahl Baunwall PhD , Mette Mejlby Hansen MSc , Jens Frederik Dahlerup DMSc , Martin Steen Mortensen PhD , Prof Tine Rask Licht PhD , Jens Kjærgaard Boldsen PhD , Lise Tornvig Erikstrup PhD , Prof Christian Lodberg Hvas PhD , Prof Christian Erikstrup PhD","doi":"10.1016/j.lanmic.2024.101034","DOIUrl":"10.1016/j.lanmic.2024.101034","url":null,"abstract":"<div><h3>Background</h3><div>Faecal microbiota transplantation (FMT) is an effective treatment for patients with recurrent <em>Clostridioides difficile</em> infection, but donor selection can influence its clinical success. We aimed to investigate the effect of clinical donor characteristics on FMT outcomes in patients with <em>C difficile</em> infection.</div></div><div><h3>Methods</h3><div>In this single-centre, prospective cohort study, we included all donors who fulfilled the national criteria for faeces donation and delivered donations to the Centre for Faecal Microbiota Transplantation, Aarhus University Hospital, Denmark, between May 2, 2016, and Oct 31, 2023, and corresponding recipients treated with one-dose FMT for primary or recurrent <em>C difficile</em> infection. In mixed-effects models, we evaluated the effect of donor sex, age, BMI, smoking status, donation stool consistency, total donation weight, antibiotic use, <em>Helicobacter pylori</em> carriage, birth mode, donor−recipient sex concordance, and the alpha diversity of faeces donations on FMT outcomes in recipients. The primary outcome was the resolution of diarrhoea associated with <em>C difficile</em> infection in patients 8 weeks after FMT.</div></div><div><h3>Findings</h3><div>Among 145 blood donors who also donated faeces, 115 (79·3%) were men and 30 (20·7%) were women. 90 (62·1%) provided faeces for 1351 evaluable FMTs in 952 patients with <em>C difficile</em> infection. 1037 (76·8%) FMTs were administered through oral capsules, 151 (11·2%) via colonoscopy, and 163 FMTs (12·1%) via nasojejunal tube. Antibiotic use 3–12 months before donation decreased the effectiveness of FMT (odds ratio 0·55 [95% CI 0·33–0·91]; p=0·019). Compared with donations with a Bristol Stool Form Scale (BSFS) score of 3, donations with a score of 4 (odds ratio 1·38 [95% CI 1·04–1·83]; p=0·024) and 5 or above (2·89 [1·33–6·26]; p=0·0072) showed improved FMT effectiveness. Donor sex, BMI, smoking status, <em>H pylori</em> carriage, birth mode, total donation weight, and donor−recipient sex concordance did not affect FMT outcomes.</div></div><div><h3>Interpretation</h3><div>Expanding current donor selection criteria to avoid antibiotic use in the 12 months preceding donation and including donations with a BSFS score of 5 might improve FMT outcomes for patients with <em>C difficile</em> infection. Our findings call for the revision of current clinical donor screening practices, and future studies could further optimise the criteria for selecting optimal faeces donors.</div></div><div><h3>Funding</h3><div>Innovation Fund Denmark.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 5","pages":"Article 101034"},"PeriodicalIF":20.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537901","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}