Background: Invasive aspergillosis is a rare but severe complication of liver transplantation. Incidence varies from 1·2% to 5·6% and mortality is greater than 50%. Few studies have investigated this complication. We aimed to describe cases of, and identify the factors associated with, invasive aspergillosis occurrence and mortality.
Methods: This nationwide, retrospective, matched case-control study included cases of invasive aspergillosis occurring after liver transplantation between Jan 1, 2007, and Dec 31, 2021, matched 1:1 on centre and transplantation period to control individuals without invasive aspergillosis across 15 liver transplantation centres in France. Cases were patients aged 18 years or older who presented with proven or probable invasive aspergillosis. The matched control was the next patient who received a transplant at the same transplantation centre after the case. Cases were retrospectively identified in each centre using the mycology laboratory database and the French Medicalised Information System Programme. Data were retrieved from hospital charts. The primary outcome was the identification of risk factors associated with the development of invasive aspergillosis following liver transplantation. Multivariable analysis using conditional logistic regression with a random effect for study centres was done to establish risk factors.
Findings: Among 14 332 liver transplantations, 196 recipients with invasive aspergillosis (62 [32%] female and 134 [68%] male) were identified and matched with 196 control individuals (54 [28%] female and 142 [73%] male). Invasive aspergillosis occurred at a median of 29 days (IQR 7-173) after liver transplantation. Risk factors for developing invasive aspergillosis were history of chronic kidney disease (adjusted odds ratio 4·13 [95% CI 2·35-7·24]), liver transplantation for acute liver disease (3·41 [1·44-8·06]), post-liver transplantation renal replacement therapy (3·82 [1·96-7·42]), and post-liver transplantation vasopressor support for longer than 24 h (2·82 [1·70-4·68]).
Interpretation: This study identifies three patient populations at risk of invasive aspergillosis after liver transplantation: patients with history of chronic kidney disease, those who have received a transplant for acute liver disease, and those who had a post-operative period marked by organ failure. This identification could lead to new invasive aspergillosis prophylactic strategies.
{"title":"Invasive aspergillosis in liver transplant recipients in France (2007-21): a nationwide, retrospective, matched case-control study.","authors":"Coralie Le Hyaric, Cléa Melenotte, François Lefebvre, Faouzi Saliba, Françoise Botterel, Nada El-Domiaty, Jérome Dumortier, Florence Persat, Raphael Do, Grégoire Pasquier, Christophe Camus, Jean-Pierre Gangneux, Nassim Kamar, Xavier Iriart, Antoine Monsel, Arnaud Fekkar, Filomena Conti, Fanny Vuotto, Séverine Loridant, François Durand, Christine Bonnal, Mathilde Barbaz, Adélaïde Chesnay, Carole Vignals, Maxime Lefranc, Renaud Guerin, Maxime Moniot, Delphine Weil, Anne-Pauline Bellanger, Thomas Decaens, Daniele Maubon, Fanny Lebossé, Thierry Artzner, Guillaume Morel, Valérie Letscher-Bru, Raoul Herbrecht, Florence Ader, Olivier Lortholary, Agnès Lefort, Céline Guichon, François Danion","doi":"10.1016/j.lanmic.2025.101272","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101272","url":null,"abstract":"<p><strong>Background: </strong>Invasive aspergillosis is a rare but severe complication of liver transplantation. Incidence varies from 1·2% to 5·6% and mortality is greater than 50%. Few studies have investigated this complication. We aimed to describe cases of, and identify the factors associated with, invasive aspergillosis occurrence and mortality.</p><p><strong>Methods: </strong>This nationwide, retrospective, matched case-control study included cases of invasive aspergillosis occurring after liver transplantation between Jan 1, 2007, and Dec 31, 2021, matched 1:1 on centre and transplantation period to control individuals without invasive aspergillosis across 15 liver transplantation centres in France. Cases were patients aged 18 years or older who presented with proven or probable invasive aspergillosis. The matched control was the next patient who received a transplant at the same transplantation centre after the case. Cases were retrospectively identified in each centre using the mycology laboratory database and the French Medicalised Information System Programme. Data were retrieved from hospital charts. The primary outcome was the identification of risk factors associated with the development of invasive aspergillosis following liver transplantation. Multivariable analysis using conditional logistic regression with a random effect for study centres was done to establish risk factors.</p><p><strong>Findings: </strong>Among 14 332 liver transplantations, 196 recipients with invasive aspergillosis (62 [32%] female and 134 [68%] male) were identified and matched with 196 control individuals (54 [28%] female and 142 [73%] male). Invasive aspergillosis occurred at a median of 29 days (IQR 7-173) after liver transplantation. Risk factors for developing invasive aspergillosis were history of chronic kidney disease (adjusted odds ratio 4·13 [95% CI 2·35-7·24]), liver transplantation for acute liver disease (3·41 [1·44-8·06]), post-liver transplantation renal replacement therapy (3·82 [1·96-7·42]), and post-liver transplantation vasopressor support for longer than 24 h (2·82 [1·70-4·68]).</p><p><strong>Interpretation: </strong>This study identifies three patient populations at risk of invasive aspergillosis after liver transplantation: patients with history of chronic kidney disease, those who have received a transplant for acute liver disease, and those who had a post-operative period marked by organ failure. This identification could lead to new invasive aspergillosis prophylactic strategies.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101272"},"PeriodicalIF":20.4,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147366848","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}
Pub Date : 2026-03-01Epub Date: 2026-02-13DOI: 10.1016/j.lanmic.2025.101267
Konstantinos Liatsikos MBBS , Angela Hyder-Wright MRes , Kelly Davies BSc , Dima El Safadi PhD , Madlen Farrar BSc , Andre Goncalves PhD , Patricia Gonzalez-Dias PhD , Prof Stephen B Gordon PhD , Ashleigh Howard BSc , Prof Maia Lesosky PhD , Xinxue Liu PhD , Elena Mitsi PhD , Christopher Myerscough PhD , Tinashe K Nyazika PhD , Prof Andrew J Pollard PhD , Jesús Reiné PhD , Ryan E Robinson PhD , Carla Solórzano PhD , Britta C Urban PhD , Yiyuan Zhang PhD , Prof Daniela M Ferreira PhD
<div><h3>Background</h3><div>Although evidence suggests some direct protection from the 13-valent pneumococcal conjugate vaccine (PCV13) against <em>Streptococcus pneumoniae</em> serotype 3 (Spn3), Spn3 remains a frequent cause of pneumococcal disease in the UK, potentially due to lower vaccine effect on colonisation, shorter duration of protection, or the emergence of more successful Spn3 clades. To test these hypotheses, we compared PCV13 and 23-valent pneumococcal polysaccharide vaccine (PPV23) protection against prevalent Spn3 clades. Additionally, we assessed the long-term protection offered by pneumococcal vaccines against colonisation using <em>S pneumoniae</em> serotype 6B (Spn6B), a serotype PCV13 protects against in the short term.</div></div><div><h3>Methods</h3><div>This double-masked, randomised, controlled, phase 4 trial recruited healthy participants aged 18–50 years in Liverpool, UK, and assigned them (2:1:2) to PCV13, PPV23, or placebo (0·9% NaCl). Participants assigned to the PPV23 group were challenged with clade Iα, and participants in PCV13 and placebo groups were subsequently randomly assigned to receive clade Iα or II Spn3. Nasal challenge with Spn3 was at 1 month and with Spn6B in a subgroup at 6 months after vaccination. Selection for this subgroup was conducted on a first-come-first-served basis, with participants who enrolled earliest being offered participation in both challenges. Recruitment for the second challenge was discontinued once the target number of participants was reached. The primary outcome was the acquisition risk of the challenge strain as detected by nasal wash culture at 2 days, 7 days, 14 days, or 23 days in the vaccine versus the placebo groups. The analysis was performed in a modified intention-to-treat population, defined as all participants who received vaccination, underwent challenge, and had at least one nasal wash sample collected after the challenge. Randomisation used a computer-generated schedule that only the unmasked team could access. The unmasked team performed vaccinations and did not perform the nasal challenges or nasal washes. The laboratory staff and participants were masked to the vaccination status. This study was prospectively registered with the EU Drug Regulating Authorities Clinical Trials Database, 2019-004742-15, the International Standard Randomised Controlled Trial Number registry, ISRCTN15728847, and <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT04974294</span><svg><path></path></svg></span>, and is complete.</div></div><div><h3>Findings</h3><div>This trial was conducted between July 28, 2021, and Oct 3, 2023. The analysis included 407 participants challenged with Spn3 and 243 challenged with Spn6B. 1 month after vaccination, PCV13 was associated with a non-significant reduction (16%) in Spn3 colonisation acquisition when considering both clades combined(84 [56%] of 153 participants in the PCV13 group <em>vs</em> 101 [65%] of 155 i
{"title":"The effect of pneumococcal conjugate vaccine and pneumococcal polysaccharide vaccine on nasopharyngeal colonisation following human infection challenge with serotype 3 and serotype 6B (PREVENTING PNEUMO 2): a double-masked, randomised, controlled, phase 4 trial","authors":"Konstantinos Liatsikos MBBS , Angela Hyder-Wright MRes , Kelly Davies BSc , Dima El Safadi PhD , Madlen Farrar BSc , Andre Goncalves PhD , Patricia Gonzalez-Dias PhD , Prof Stephen B Gordon PhD , Ashleigh Howard BSc , Prof Maia Lesosky PhD , Xinxue Liu PhD , Elena Mitsi PhD , Christopher Myerscough PhD , Tinashe K Nyazika PhD , Prof Andrew J Pollard PhD , Jesús Reiné PhD , Ryan E Robinson PhD , Carla Solórzano PhD , Britta C Urban PhD , Yiyuan Zhang PhD , Prof Daniela M Ferreira PhD","doi":"10.1016/j.lanmic.2025.101267","DOIUrl":"10.1016/j.lanmic.2025.101267","url":null,"abstract":"<div><h3>Background</h3><div>Although evidence suggests some direct protection from the 13-valent pneumococcal conjugate vaccine (PCV13) against <em>Streptococcus pneumoniae</em> serotype 3 (Spn3), Spn3 remains a frequent cause of pneumococcal disease in the UK, potentially due to lower vaccine effect on colonisation, shorter duration of protection, or the emergence of more successful Spn3 clades. To test these hypotheses, we compared PCV13 and 23-valent pneumococcal polysaccharide vaccine (PPV23) protection against prevalent Spn3 clades. Additionally, we assessed the long-term protection offered by pneumococcal vaccines against colonisation using <em>S pneumoniae</em> serotype 6B (Spn6B), a serotype PCV13 protects against in the short term.</div></div><div><h3>Methods</h3><div>This double-masked, randomised, controlled, phase 4 trial recruited healthy participants aged 18–50 years in Liverpool, UK, and assigned them (2:1:2) to PCV13, PPV23, or placebo (0·9% NaCl). Participants assigned to the PPV23 group were challenged with clade Iα, and participants in PCV13 and placebo groups were subsequently randomly assigned to receive clade Iα or II Spn3. Nasal challenge with Spn3 was at 1 month and with Spn6B in a subgroup at 6 months after vaccination. Selection for this subgroup was conducted on a first-come-first-served basis, with participants who enrolled earliest being offered participation in both challenges. Recruitment for the second challenge was discontinued once the target number of participants was reached. The primary outcome was the acquisition risk of the challenge strain as detected by nasal wash culture at 2 days, 7 days, 14 days, or 23 days in the vaccine versus the placebo groups. The analysis was performed in a modified intention-to-treat population, defined as all participants who received vaccination, underwent challenge, and had at least one nasal wash sample collected after the challenge. Randomisation used a computer-generated schedule that only the unmasked team could access. The unmasked team performed vaccinations and did not perform the nasal challenges or nasal washes. The laboratory staff and participants were masked to the vaccination status. This study was prospectively registered with the EU Drug Regulating Authorities Clinical Trials Database, 2019-004742-15, the International Standard Randomised Controlled Trial Number registry, ISRCTN15728847, and <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT04974294</span><svg><path></path></svg></span>, and is complete.</div></div><div><h3>Findings</h3><div>This trial was conducted between July 28, 2021, and Oct 3, 2023. The analysis included 407 participants challenged with Spn3 and 243 challenged with Spn6B. 1 month after vaccination, PCV13 was associated with a non-significant reduction (16%) in Spn3 colonisation acquisition when considering both clades combined(84 [56%] of 153 participants in the PCV13 group <em>vs</em> 101 [65%] of 155 i","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 3","pages":"Article 101267"},"PeriodicalIF":20.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207975","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}
Pub Date : 2026-03-01Epub Date: 2026-03-02DOI: 10.1016/j.lanmic.2026.101392
The Lancet Microbe
{"title":"Action on infection needs grounding in the social sciences","authors":"The Lancet Microbe","doi":"10.1016/j.lanmic.2026.101392","DOIUrl":"10.1016/j.lanmic.2026.101392","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 3","pages":"Article 101392"},"PeriodicalIF":20.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147366663","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}
Pub Date : 2026-03-01Epub Date: 2026-01-13DOI: 10.1016/j.lanmic.2025.101317
Sanjeet Bagcchi
{"title":"Agreements to provide affordable lenacapavir","authors":"Sanjeet Bagcchi","doi":"10.1016/j.lanmic.2025.101317","DOIUrl":"10.1016/j.lanmic.2025.101317","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 3","pages":"Article 101317"},"PeriodicalIF":20.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991271","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}
Pub Date : 2026-03-01Epub Date: 2026-02-06DOI: 10.1016/j.lanmic.2025.101256
Kieran Tebben PhD , Virak Eng MD , Dynang Seng MSc , Baura Tat MSc , Lionel Brice Feufack-Donfack PhD , Agnes Orban PhD , Rominea Yeat MSc , Jeremy Salvador PhD , Sitha Sin BSc , Katie Ko , Nimol Khim PhD , Claude Flamand PhD , Cecile Sommen PhD , Dysoley Lek MD PhD , Prof David Serre PhD , Jean Popovici PhD
Background
Artemisinin-based combination therapies are the frontline drugs for the treatment of malaria infections, but, for Plasmodium falciparum, the efficacy of artemisinin is threatened by the spread of resistance. Plasmodium vivax is the second most common cause of human malaria, but there is little information on its susceptibility to artemisinin due to the lack of an in-vitro culture system. This study aims to characterise the response of P vivax to artesunate using clinical, genomic, and transcriptomic data from infected individuals in Cambodia.
Methods
We analysed 161 P vivax infections from 87 patients (six female and 81 male; median age 20 years [IQR 17–26]) enrolled between Nov 10, 2021, and Nov 18, 2022, in a drug efficacy study in Cambodia and treated with 2 mg/kg/day of artesunate for 7 days. To determine clearance rates, we measured parasitaemia before, and 1 h, 2 h, 4 h, 8 h, and 16 h after the first dose of artesunate, and then at 24-h intervals during the 7 days of artesunate therapy. We also examined the parasites’ genome sequences and used RNA sequencing of 31 infections to analyse changes in parasite gene expression upon treatment.
Findings
All infections were successfully cleared by day 3. However, 49 of the infections displayed a slow clearance after treatment, including nine (6%) infections with a parasite clearance slope half-life greater than 5 h. We observed no significant association between slow clearance and either patient or infection characteristics (including the infection’s stage composition). Analyses of gene expression showed that, while fast-clearing parasites displayed significant changes in gene expression immediately upon treatment, slow-clearing parasites had a delayed gene expression response characterised notably by a downregulation of genes associated with haemoglobin endocytosis and digestion.
Interpretation
Some Cambodian P vivax parasites clear slowly after artesunate treatment, possibly due to a downregulation of haemoglobin metabolism that might reduce the efficiency of the artesunate. The slow clearance could allow parasites to outlast artesunate treatment and facilitate emergence of resistance to the artemisinin-combination therapy partner drug, threatening malaria elimination effort.
{"title":"Parasite clearance in patients with Plasmodium vivax monoinfection treated with artesunate in Cambodia: an observational secondary analysis of trial data","authors":"Kieran Tebben PhD , Virak Eng MD , Dynang Seng MSc , Baura Tat MSc , Lionel Brice Feufack-Donfack PhD , Agnes Orban PhD , Rominea Yeat MSc , Jeremy Salvador PhD , Sitha Sin BSc , Katie Ko , Nimol Khim PhD , Claude Flamand PhD , Cecile Sommen PhD , Dysoley Lek MD PhD , Prof David Serre PhD , Jean Popovici PhD","doi":"10.1016/j.lanmic.2025.101256","DOIUrl":"10.1016/j.lanmic.2025.101256","url":null,"abstract":"<div><h3>Background</h3><div>Artemisinin-based combination therapies are the frontline drugs for the treatment of malaria infections, but, for <em>Plasmodium falciparum,</em> the efficacy of artemisinin is threatened by the spread of resistance. <em>Plasmodium vivax</em> is the second most common cause of human malaria, but there is little information on its susceptibility to artemisinin due to the lack of an in-vitro culture system. This study aims to characterise the response of <em>P vivax</em> to artesunate using clinical, genomic, and transcriptomic data from infected individuals in Cambodia.</div></div><div><h3>Methods</h3><div>We analysed 161 <em>P vivax</em> infections from 87 patients (six female and 81 male; median age 20 years [IQR 17–26]) enrolled between Nov 10, 2021, and Nov 18, 2022, in a drug efficacy study in Cambodia and treated with 2 mg/kg/day of artesunate for 7 days. To determine clearance rates, we measured parasitaemia before, and 1 h, 2 h, 4 h, 8 h, and 16 h after the first dose of artesunate, and then at 24-h intervals during the 7 days of artesunate therapy. We also examined the parasites’ genome sequences and used RNA sequencing of 31 infections to analyse changes in parasite gene expression upon treatment.</div></div><div><h3>Findings</h3><div>All infections were successfully cleared by day 3. However, 49 of the infections displayed a slow clearance after treatment, including nine (6%) infections with a parasite clearance slope half-life greater than 5 h. We observed no significant association between slow clearance and either patient or infection characteristics (including the infection’s stage composition). Analyses of gene expression showed that, while fast-clearing parasites displayed significant changes in gene expression immediately upon treatment, slow-clearing parasites had a delayed gene expression response characterised notably by a downregulation of genes associated with haemoglobin endocytosis and digestion.</div></div><div><h3>Interpretation</h3><div>Some Cambodian <em>P vivax</em> parasites clear slowly after artesunate treatment, possibly due to a downregulation of haemoglobin metabolism that might reduce the efficiency of the artesunate. The slow clearance could allow parasites to outlast artesunate treatment and facilitate emergence of resistance to the artemisinin-combination therapy partner drug, threatening malaria elimination effort.</div></div><div><h3>Funding</h3><div>US National Institutes of Health.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 3","pages":"Article 101256"},"PeriodicalIF":20.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150965","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}
Pub Date : 2026-03-01Epub Date: 2025-11-24DOI: 10.1016/j.lanmic.2025.101290
T Jacob John , Dhanya Dharmapalan , Robert Steinglass , Norbert Hirschhorn
{"title":"Polio outbreaks due to vaccine-derived viruses demand a re-definition of vaccine safety","authors":"T Jacob John , Dhanya Dharmapalan , Robert Steinglass , Norbert Hirschhorn","doi":"10.1016/j.lanmic.2025.101290","DOIUrl":"10.1016/j.lanmic.2025.101290","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 3","pages":"Article 101290"},"PeriodicalIF":20.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145641382","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}
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