Pub Date : 2026-01-07DOI: 10.1016/S1473-3099(25)00682-6
Deborah R Leitner, Stephen R Walsh, Masataka Suzuki, Michaël Desjardins, Alisse Hannaford, Amy C Sherman, Hannah Levine, Lena Carr, Elliot Hammerness, Akina Osaki, Emily Sullivan, Bryan Wang, George I Balazs, Jun Bai Park Chang, Damien M Slater, Nirajan Puri, Carole J Kuehl, Wilbur H Chen, Jason B Harris, Steven Piantadosi, Lindsey R Baden, Matthew K Waldor
<p><strong>Background: </strong>Killed whole-cell oral cholera vaccines can be used to prevent cholera but require multiple doses and have limited efficacy in young children. PanChol is a single-dose, live-attenuated, oral cholera vaccine derived from a current seventh pandemic Vibrio cholerae O1 strain. It co-expresses Inaba and Ogawa antigens, over-expresses the non-toxic cholera toxin B subunit, and is designed to minimise reactogenicity and be incapable of toxigenic reversion. We aimed to assess safety and immunogenicity of PanChol in a first-in-human trial.</p><p><strong>Methods: </strong>This phase 1a trial was conducted at the Brigham and Women's Hospital (Boston, MA, USA) and involved an open-label fixed dose-escalation module, followed by a randomised, double-blind, placebo-controlled dose-expansion module. Eligible participants were healthy adults aged 18-55 years without a previous V cholerae infection or cholera vaccination or a history of gastrointestinal disorders. In the open-label dose-escalation phase, eligible participants were enrolled into one of five cohorts receiving one dose of oral 10<sup>6</sup>-10<sup>10</sup> colony-forming units (CFU) of PanChol. A dose de-escalation (10<sup>4</sup> CFU and 10<sup>5</sup> CFU) module was added after protocol amendment. In the subsequent randomised, double-blind module, participants were randomly assigned (7:7:4) to one of two dosing groups of one oral dose of PanChol (2 × 10<sup>7</sup> CFU or 2 × 10<sup>8</sup> CFU) or one oral dose of placebo (matching diluent). The list of assignments was generated from a custom program written by the statistician using blocked random assignments with a hidden block size (two blocks of 18). The co-primary outcomes were safety, including solicited, unsolicited, and serious adverse events following a single-dose of PanChol, and seroconversion (four-fold rise in titre over baseline) of vibriocidal titres to both Inaba and Ogawa V cholerae at 14 days post-vaccination (day 15). Safety was assessed in all participants who received the study product, and immunogenicity was assessed in all vaccine recipients who had samples available past day 7. Stool shedding of PanChol organisms was assessed as a secondary outcome in all participants. This trial is registered with ClinicalTrials.gov, NCT05657782, and is ongoing.</p><p><strong>Findings: </strong>Between Dec 13, 2022, and Feb 7, 2025, 57 healthy adults were enrolled, including 15 in the dose-escalation module (three in each group), six in the dose de-escalation module (three in each group), and 36 in the dose-expansion module (14 assigned to 10<sup>7</sup> CFU PanChol, 14 to 10<sup>8</sup> CFU PanChol, and eight to placebo); all participants received the allocated intervention. 27 (47%) of 57 participants were male, 30 (53%) were female, and the median age was 30·6 years (IQR 25·1-45·1); the majority were White (35 [61%]) and not Hispanic or Latino (51 [89%]). 34 (69%) of 49 PanChol recipients reported at l
{"title":"Safety and immunogenicity of PanChol, a single-dose live-attenuated oral cholera vaccine: results from a phase 1a, double-blind, randomised, placebo-controlled trial.","authors":"Deborah R Leitner, Stephen R Walsh, Masataka Suzuki, Michaël Desjardins, Alisse Hannaford, Amy C Sherman, Hannah Levine, Lena Carr, Elliot Hammerness, Akina Osaki, Emily Sullivan, Bryan Wang, George I Balazs, Jun Bai Park Chang, Damien M Slater, Nirajan Puri, Carole J Kuehl, Wilbur H Chen, Jason B Harris, Steven Piantadosi, Lindsey R Baden, Matthew K Waldor","doi":"10.1016/S1473-3099(25)00682-6","DOIUrl":"https://doi.org/10.1016/S1473-3099(25)00682-6","url":null,"abstract":"<p><strong>Background: </strong>Killed whole-cell oral cholera vaccines can be used to prevent cholera but require multiple doses and have limited efficacy in young children. PanChol is a single-dose, live-attenuated, oral cholera vaccine derived from a current seventh pandemic Vibrio cholerae O1 strain. It co-expresses Inaba and Ogawa antigens, over-expresses the non-toxic cholera toxin B subunit, and is designed to minimise reactogenicity and be incapable of toxigenic reversion. We aimed to assess safety and immunogenicity of PanChol in a first-in-human trial.</p><p><strong>Methods: </strong>This phase 1a trial was conducted at the Brigham and Women's Hospital (Boston, MA, USA) and involved an open-label fixed dose-escalation module, followed by a randomised, double-blind, placebo-controlled dose-expansion module. Eligible participants were healthy adults aged 18-55 years without a previous V cholerae infection or cholera vaccination or a history of gastrointestinal disorders. In the open-label dose-escalation phase, eligible participants were enrolled into one of five cohorts receiving one dose of oral 10<sup>6</sup>-10<sup>10</sup> colony-forming units (CFU) of PanChol. A dose de-escalation (10<sup>4</sup> CFU and 10<sup>5</sup> CFU) module was added after protocol amendment. In the subsequent randomised, double-blind module, participants were randomly assigned (7:7:4) to one of two dosing groups of one oral dose of PanChol (2 × 10<sup>7</sup> CFU or 2 × 10<sup>8</sup> CFU) or one oral dose of placebo (matching diluent). The list of assignments was generated from a custom program written by the statistician using blocked random assignments with a hidden block size (two blocks of 18). The co-primary outcomes were safety, including solicited, unsolicited, and serious adverse events following a single-dose of PanChol, and seroconversion (four-fold rise in titre over baseline) of vibriocidal titres to both Inaba and Ogawa V cholerae at 14 days post-vaccination (day 15). Safety was assessed in all participants who received the study product, and immunogenicity was assessed in all vaccine recipients who had samples available past day 7. Stool shedding of PanChol organisms was assessed as a secondary outcome in all participants. This trial is registered with ClinicalTrials.gov, NCT05657782, and is ongoing.</p><p><strong>Findings: </strong>Between Dec 13, 2022, and Feb 7, 2025, 57 healthy adults were enrolled, including 15 in the dose-escalation module (three in each group), six in the dose de-escalation module (three in each group), and 36 in the dose-expansion module (14 assigned to 10<sup>7</sup> CFU PanChol, 14 to 10<sup>8</sup> CFU PanChol, and eight to placebo); all participants received the allocated intervention. 27 (47%) of 57 participants were male, 30 (53%) were female, and the median age was 30·6 years (IQR 25·1-45·1); the majority were White (35 [61%]) and not Hispanic or Latino (51 [89%]). 34 (69%) of 49 PanChol recipients reported at l","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":31.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-07DOI: 10.1016/S1473-3099(25)00725-X
David A Wohl, Carwolo Pewu, Chanhwa Lee, Emmanuel Kerkula, Martha Gayflowu, Nukal Doetein, Katie R Mollan, Taylor J Krajewski, Becky Straub, Alfred Flomo, Amara Fofana, Stanley Kerkula, Thomas Sumo, Alexander Sampson, Samuel Vouh, Fred Flomo, McKenzie A Colt, Thomas Remont, Eleanor Rose Watts, Marta Zizek, Catherine Nimely, Minnie Ricks, Jefferson Sibley, William A Fischer
<p><strong>Background: </strong>Lassa virus (LASV) is a persistent threat to public health in west Africa and beyond. LASV is endemic in west Africa and each year it is responsible for an estimated 2·7 million infections, 23 700 hospitalisations, and 5000 deaths. With over 32 reported cases of Lassa fever imported into non-endemic countries-one-third of which were fatal-the importance of enhanced detection and management of Lassa fever extends beyond west Africa.</p><p><strong>Methods: </strong>The prevalence, pathogenesis, and persistence (PREPARE) study was a prospective cohort study among patients admitted to two hospitals in a hyperendemic area of Liberia. Any patients aged 5 years or older with a febrile illness were eligible to enrol and be tested for Lassa fever. The study aimed to measure the prevalence of LASV infection and assess the signs and symptoms, LASV viral replication kinetics, and LASV-specific IgM and IgG responses longitudinally among adults and children with laboratory-confirmed Lassa fever.</p><p><strong>Findings: </strong>From July 10, 2018, to Aug 12, 2024, a total of 435 participants were enrolled, including 362 admitted with a febrile illness and 73 who were directly admitted with clinical suspicion for Lassa fever. Lassa fever was diagnosed by plasma LASV RT-PCR in 41 (11%) of 362 febrile participants and 47 (64%) of 73 participants directly admitted with suspected Lassa fever, resulting in a total of 88 cases of confirmed Lassa fever. At entry, anorexia (71 [81%] of 88 vs 178 [51%] of 347), severe fatigue or weakness (63 [72%] vs 178 [51%]), and nausea or vomiting (39 [44%] vs 95 [27%]) were more likely to be reported by participants with Lassa fever than by participants who tested LASV RNA negative. Among the participants with Lassa fever, 11 (13%) of 88 died after admission. Mental status changes, seizures, acute kidney failure, hyperkalaemia, and metabolic acidosis were more frequent in patients with Lassa fever who died than in patients who survived. Median cycle threshold values at study entry for glycoprotein complex gene (GPC) or polymerase gene (L) were lower in those who died (GPC cycle threshold 22·4 [IQR 20·0-27·9]; L cycle threshold 21·7 [19·0-27·7]) than in those who survived (GPC cycle threshold 31·5 [28·0-33·9]; L cycle threshold 32·3 [28·0-33·9]). Among the 70 participants with Lassa fever who consented to longitudinal follow-up through their hospitalisation, seven died and these participants tended to have lower cycle threshold values and lower IgM and IgG LASV responses compared with survivors.</p><p><strong>Interpretation: </strong>In a region of Liberia where it is endemic, Lassa fever is a prevalent cause of morbidity and mortality. Several symptoms were more likely in those with Lassa fever but overlap with those caused by other common infectious diseases. Compared with survivors, those who died during hospitalisation for Lassa fever tended to have evidence of organ dysfunction along with higher
{"title":"Lassa fever symptomatology, viral dynamics, and host immune response (PREPARE): a prospective, observational cohort study in Liberia.","authors":"David A Wohl, Carwolo Pewu, Chanhwa Lee, Emmanuel Kerkula, Martha Gayflowu, Nukal Doetein, Katie R Mollan, Taylor J Krajewski, Becky Straub, Alfred Flomo, Amara Fofana, Stanley Kerkula, Thomas Sumo, Alexander Sampson, Samuel Vouh, Fred Flomo, McKenzie A Colt, Thomas Remont, Eleanor Rose Watts, Marta Zizek, Catherine Nimely, Minnie Ricks, Jefferson Sibley, William A Fischer","doi":"10.1016/S1473-3099(25)00725-X","DOIUrl":"https://doi.org/10.1016/S1473-3099(25)00725-X","url":null,"abstract":"<p><strong>Background: </strong>Lassa virus (LASV) is a persistent threat to public health in west Africa and beyond. LASV is endemic in west Africa and each year it is responsible for an estimated 2·7 million infections, 23 700 hospitalisations, and 5000 deaths. With over 32 reported cases of Lassa fever imported into non-endemic countries-one-third of which were fatal-the importance of enhanced detection and management of Lassa fever extends beyond west Africa.</p><p><strong>Methods: </strong>The prevalence, pathogenesis, and persistence (PREPARE) study was a prospective cohort study among patients admitted to two hospitals in a hyperendemic area of Liberia. Any patients aged 5 years or older with a febrile illness were eligible to enrol and be tested for Lassa fever. The study aimed to measure the prevalence of LASV infection and assess the signs and symptoms, LASV viral replication kinetics, and LASV-specific IgM and IgG responses longitudinally among adults and children with laboratory-confirmed Lassa fever.</p><p><strong>Findings: </strong>From July 10, 2018, to Aug 12, 2024, a total of 435 participants were enrolled, including 362 admitted with a febrile illness and 73 who were directly admitted with clinical suspicion for Lassa fever. Lassa fever was diagnosed by plasma LASV RT-PCR in 41 (11%) of 362 febrile participants and 47 (64%) of 73 participants directly admitted with suspected Lassa fever, resulting in a total of 88 cases of confirmed Lassa fever. At entry, anorexia (71 [81%] of 88 vs 178 [51%] of 347), severe fatigue or weakness (63 [72%] vs 178 [51%]), and nausea or vomiting (39 [44%] vs 95 [27%]) were more likely to be reported by participants with Lassa fever than by participants who tested LASV RNA negative. Among the participants with Lassa fever, 11 (13%) of 88 died after admission. Mental status changes, seizures, acute kidney failure, hyperkalaemia, and metabolic acidosis were more frequent in patients with Lassa fever who died than in patients who survived. Median cycle threshold values at study entry for glycoprotein complex gene (GPC) or polymerase gene (L) were lower in those who died (GPC cycle threshold 22·4 [IQR 20·0-27·9]; L cycle threshold 21·7 [19·0-27·7]) than in those who survived (GPC cycle threshold 31·5 [28·0-33·9]; L cycle threshold 32·3 [28·0-33·9]). Among the 70 participants with Lassa fever who consented to longitudinal follow-up through their hospitalisation, seven died and these participants tended to have lower cycle threshold values and lower IgM and IgG LASV responses compared with survivors.</p><p><strong>Interpretation: </strong>In a region of Liberia where it is endemic, Lassa fever is a prevalent cause of morbidity and mortality. Several symptoms were more likely in those with Lassa fever but overlap with those caused by other common infectious diseases. Compared with survivors, those who died during hospitalisation for Lassa fever tended to have evidence of organ dysfunction along with higher ","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":31.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-20DOI: 10.1016/s1473-3099(25)00720-0
Alejandro Arbona-Lampaya, Ricardo A Pérez-Ojeda, Melanie Santos-Marrero, Adrián Pérez-Aybar
{"title":"Below-knee amputation following osteomyelitis from multidrug-resistant Stenotrophomonas maltophilia in a diabetic foot ulcer","authors":"Alejandro Arbona-Lampaya, Ricardo A Pérez-Ojeda, Melanie Santos-Marrero, Adrián Pérez-Aybar","doi":"10.1016/s1473-3099(25)00720-0","DOIUrl":"https://doi.org/10.1016/s1473-3099(25)00720-0","url":null,"abstract":"","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"16 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-20DOI: 10.1016/s1473-3099(25)00780-7
Ed Holt
{"title":"Promising early data for sorfequiline","authors":"Ed Holt","doi":"10.1016/s1473-3099(25)00780-7","DOIUrl":"https://doi.org/10.1016/s1473-3099(25)00780-7","url":null,"abstract":"","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"18 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/s1473-3099(25)00733-9
Marco De Ambrogi
{"title":"Introducing our cover artist for 2026: Daria Lada","authors":"Marco De Ambrogi","doi":"10.1016/s1473-3099(25)00733-9","DOIUrl":"https://doi.org/10.1016/s1473-3099(25)00733-9","url":null,"abstract":"","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"7 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/s1473-3099(25)00778-9
{"title":"Correction to Lancet Infect Dis 2025; published online Oct 10. https://doi.org/10.1016/S1473-3099(25)00482-7","authors":"","doi":"10.1016/s1473-3099(25)00778-9","DOIUrl":"https://doi.org/10.1016/s1473-3099(25)00778-9","url":null,"abstract":"","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"80 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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