Pub Date : 2026-03-04DOI: 10.1080/22221751.2026.2640699
Richard Olumide Daodu,Jennifer Chang,Joseph Prescott,Knut Reinert,Denise Kühnert
Lassa virus (LASV), a zoonotic, bi-segmented arenavirus endemic to West Africa, causes seasonal epidemics with substantial morbidity and mortality. Increasing frequency of exported cases emphasises the need for near real-time genomic surveillance to support outbreak response and clinical decision-making. We developed a suite of open-access resources on the Nextstrain and Nextclade platforms tailored to LASV. These include live phylogenetic and phylogeographic visualization, as well as Nextclade builds for rapid mutation detection and lineage assignment based on the L and S segments and the glycoprotein complex (GPC). A dedicated GPC phylogeny enables tracking of clinically relevant mutations, including immunologically relevant variants such as alanine at position 76 (A76), which is prevalent in lineage II and is implicated in reduced binding of monoclonal antibody 25.10C. The Nextclade tools distinguish LASV from other mammarenaviruses and assign lineages with Matthews correlation coefficients (all >85%). These tools are available at https://nextstrain.org/lassa for immediate use in surveillance, data annotation, outbreak response, and potentially support clinical decision-making in both endemic regions and exported-case scenarios. A key limitation is dependence on genomic data quality and recency. Although sampling-to-submission delays have decreased over the past 40 years, the average delay in the past five years remains ∼2 years. In many endemic LASV regions, challenges, such as limited resources, infrastructure, and previous experiences of stigmatization and political repercussions linked to outbreak reporting, restrict data sharing. The resulting disparities and delays may hinder comprehensive surveillance and timely response, with implications for global public health.
{"title":"Lassa Virus Live Tracking and Lineage Assignment: How Nextstrain Can Enhance Surveillance and Public Health in Africa and Beyond.","authors":"Richard Olumide Daodu,Jennifer Chang,Joseph Prescott,Knut Reinert,Denise Kühnert","doi":"10.1080/22221751.2026.2640699","DOIUrl":"https://doi.org/10.1080/22221751.2026.2640699","url":null,"abstract":"Lassa virus (LASV), a zoonotic, bi-segmented arenavirus endemic to West Africa, causes seasonal epidemics with substantial morbidity and mortality. Increasing frequency of exported cases emphasises the need for near real-time genomic surveillance to support outbreak response and clinical decision-making. We developed a suite of open-access resources on the Nextstrain and Nextclade platforms tailored to LASV. These include live phylogenetic and phylogeographic visualization, as well as Nextclade builds for rapid mutation detection and lineage assignment based on the L and S segments and the glycoprotein complex (GPC). A dedicated GPC phylogeny enables tracking of clinically relevant mutations, including immunologically relevant variants such as alanine at position 76 (A76), which is prevalent in lineage II and is implicated in reduced binding of monoclonal antibody 25.10C. The Nextclade tools distinguish LASV from other mammarenaviruses and assign lineages with Matthews correlation coefficients (all >85%). These tools are available at https://nextstrain.org/lassa for immediate use in surveillance, data annotation, outbreak response, and potentially support clinical decision-making in both endemic regions and exported-case scenarios. A key limitation is dependence on genomic data quality and recency. Although sampling-to-submission delays have decreased over the past 40 years, the average delay in the past five years remains ∼2 years. In many endemic LASV regions, challenges, such as limited resources, infrastructure, and previous experiences of stigmatization and political repercussions linked to outbreak reporting, restrict data sharing. The resulting disparities and delays may hinder comprehensive surveillance and timely response, with implications for global public health.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"43 1","pages":"2640699"},"PeriodicalIF":13.2,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-03DOI: 10.1080/22221751.2026.2640707
Joana Isidro,Filipa Dionísio,Frederico Alves,Soraia Almeida,Cláudia Santos,Manuel Mota Santos,Ernestina Reis,Júlio R Oliveira,João Paulo Gomes,Mónica Oleastro
Following an extended period of declining prevalence of the epidemic Clostridioides difficile ribotype 027 (RT027) in Portugal, a genetically distinct, multidrug-resistant (MDR) RT027 strain with reduced susceptibility to vancomycin has emerged, causing a 15-month outbreak. This investigation provides epidemiological and genomic evidence for renewed circulation and evolutionary adaptation of this high-risk lineage. A comprehensive outbreak investigation was conducted in a tertiary-care hospital in northern Portugal between 2023 and 2025. Epidemiological and clinical data, antimicrobial exposures, and infection-control measures were analysed. Whole-genome sequencing (WGS) was performed to characterize the outbreak clone. Sixty-six RT027 C. difficile infection (CDI) cases were confirmed, with incidence peaking at 5.46 cases per 10,000 patient-bed days in April 2024. WGS revealed an unusual accumulation of AMR determinants conferring a broad MDR phenotype. Notably, all isolates harboured the VanR T115A substitution, a rare mutation previously linked to reduced vancomycin susceptibility, raising concerns regarding evolving antimicrobial tolerance within RT027. The close relatedness to 2016-2018 USA isolates suggests a recent emergence of this clone. Transmission was facilitated by structural constraints, limited isolation capacity and shared sanitary facilities. This prolonged outbreak documents the re-emergence and genomic evolution of a hypervirulent RT027 lineage, characterised by a concerning expansion of antimicrobial resistance and decreased vancomycin susceptibility and a high recurrence rate (25%). These findings highlight the ongoing adaptive potential of C. difficile under antimicrobial pressure and underscore the need for strengthened surveillance, genomic monitoring, and infection-prevention strategies to mitigate re-establishment of epidemic RT027 strains in Europe and beyond.
{"title":"Genomic evolution and re-emergence of a multidrug-resistant Clostridioides difficile RT027 clone with reduced vancomycin susceptibility driving a prolonged hospital outbreak.","authors":"Joana Isidro,Filipa Dionísio,Frederico Alves,Soraia Almeida,Cláudia Santos,Manuel Mota Santos,Ernestina Reis,Júlio R Oliveira,João Paulo Gomes,Mónica Oleastro","doi":"10.1080/22221751.2026.2640707","DOIUrl":"https://doi.org/10.1080/22221751.2026.2640707","url":null,"abstract":"Following an extended period of declining prevalence of the epidemic Clostridioides difficile ribotype 027 (RT027) in Portugal, a genetically distinct, multidrug-resistant (MDR) RT027 strain with reduced susceptibility to vancomycin has emerged, causing a 15-month outbreak. This investigation provides epidemiological and genomic evidence for renewed circulation and evolutionary adaptation of this high-risk lineage. A comprehensive outbreak investigation was conducted in a tertiary-care hospital in northern Portugal between 2023 and 2025. Epidemiological and clinical data, antimicrobial exposures, and infection-control measures were analysed. Whole-genome sequencing (WGS) was performed to characterize the outbreak clone. Sixty-six RT027 C. difficile infection (CDI) cases were confirmed, with incidence peaking at 5.46 cases per 10,000 patient-bed days in April 2024. WGS revealed an unusual accumulation of AMR determinants conferring a broad MDR phenotype. Notably, all isolates harboured the VanR T115A substitution, a rare mutation previously linked to reduced vancomycin susceptibility, raising concerns regarding evolving antimicrobial tolerance within RT027. The close relatedness to 2016-2018 USA isolates suggests a recent emergence of this clone. Transmission was facilitated by structural constraints, limited isolation capacity and shared sanitary facilities. This prolonged outbreak documents the re-emergence and genomic evolution of a hypervirulent RT027 lineage, characterised by a concerning expansion of antimicrobial resistance and decreased vancomycin susceptibility and a high recurrence rate (25%). These findings highlight the ongoing adaptive potential of C. difficile under antimicrobial pressure and underscore the need for strengthened surveillance, genomic monitoring, and infection-prevention strategies to mitigate re-establishment of epidemic RT027 strains in Europe and beyond.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"40 1","pages":"2640707"},"PeriodicalIF":13.2,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Respiratory syncytial virus (RSV), a leading cause of severe lower respiratory tract infections in pediatric and elderly populations, presents an urgent need for improved therapeutic interventions. Although ribavirin (RBV) is an FDA-approved antiviral for treating RSV, its clinical application is constrained by dose-dependent toxicity and limited therapeutic efficacy. Here, we developed a high-throughput system to screen FDA-approved drugs that enhance RBV's antiviral efficacy. Unlike conventional combination therapies, this approach does not require both components to demonstrate direct antiviral activity; rather, it enhances antiviral efficacy by targeting cellular pathways, even when the synergistic agents exhibit minimal antiviral effects as monotherapies. We identified mycophenolate mofetil (MMF) and its active metabolite, mycophenolic acid (MPA), clinically approved inhibitors of inosine monophosphate dehydrogenase (IMPDH), which significantly enhance the antiviral efficacy of RBV against RSV. Mechanistically, through IMPDH knockdown and exogenous GTP supplementation, we propose that MMF and MPA reduce intracellular GTP levels by inhibiting IMPDH activity, thereby enhancing RBV incorporation and improving its antiviral efficacy. Our studies show that IMPDH inhibitors and RBV work synergistically to combat both RSV A/B genotypes and human metapneumovirus (hMPV) in vitro. Importantly, we further validated the therapeutic potential of this combination in a mouse model, showing enhanced viral clearance and reduced pathogenesis. These findings suggest that the combination of IMPDH inhibitors with RBV represents a promising therapeutic strategy for RSV and hMPV infection in clinical settings.
{"title":"FDA-approved IMPDH inhibitors synergize with ribavirin to inhibit respiratory syncytial virus by interfering with purine de novo synthesis.","authors":"Huina Hu,Qingxing Wang,Qiangyun Ai,Peiwen Zhou,Yang He,Zoudong Ye,Kaixiong Ma,Minmin Zhou,Shanzhi Huang,Lei Wang,Nan Qi,Gengfu Xiao,Shaobo Wang","doi":"10.1080/22221751.2026.2640289","DOIUrl":"https://doi.org/10.1080/22221751.2026.2640289","url":null,"abstract":"Respiratory syncytial virus (RSV), a leading cause of severe lower respiratory tract infections in pediatric and elderly populations, presents an urgent need for improved therapeutic interventions. Although ribavirin (RBV) is an FDA-approved antiviral for treating RSV, its clinical application is constrained by dose-dependent toxicity and limited therapeutic efficacy. Here, we developed a high-throughput system to screen FDA-approved drugs that enhance RBV's antiviral efficacy. Unlike conventional combination therapies, this approach does not require both components to demonstrate direct antiviral activity; rather, it enhances antiviral efficacy by targeting cellular pathways, even when the synergistic agents exhibit minimal antiviral effects as monotherapies. We identified mycophenolate mofetil (MMF) and its active metabolite, mycophenolic acid (MPA), clinically approved inhibitors of inosine monophosphate dehydrogenase (IMPDH), which significantly enhance the antiviral efficacy of RBV against RSV. Mechanistically, through IMPDH knockdown and exogenous GTP supplementation, we propose that MMF and MPA reduce intracellular GTP levels by inhibiting IMPDH activity, thereby enhancing RBV incorporation and improving its antiviral efficacy. Our studies show that IMPDH inhibitors and RBV work synergistically to combat both RSV A/B genotypes and human metapneumovirus (hMPV) in vitro. Importantly, we further validated the therapeutic potential of this combination in a mouse model, showing enhanced viral clearance and reduced pathogenesis. These findings suggest that the combination of IMPDH inhibitors with RBV represents a promising therapeutic strategy for RSV and hMPV infection in clinical settings.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"12 1","pages":"2640289"},"PeriodicalIF":13.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147329305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pertussis remains a leading cause of infant mortality globally, with rising cases in China post-COVID-19. Despite vaccination, waning immunity from acellular pertussis vaccines has driven resurgence. We evaluated a novel diphtheria, tetanus and pertussis (acellular, three components) combined vaccine, adsorbed (DTcP), China's first genetically engineered three-component pertussis vaccine, administered under two primary schedules (2/3/4 vs. 2/4/6 months) compared to licensed DTaP-IPV-Hib (Pentaxim). In this randomized, blinded, phase III clinical trial, 1380 healthy 2-month-old infants from Henan, China, received DTcP-1 (2/3/4 months) or DTcP-2 (2/4/6 months) or DTaP-IPV-Hib (2/3/4 months). The primary safety endpoints were the incidence of adverse reactions within 0∼30 days after primary vaccination. The primary immunogenicity endpoints were to evaluate the non-inferiority and superiority of seroconversion rates and geometric mean concentrations (GMCs) of anti-pertussis toxoid (PT), filamentous hemagglutinin (FHA), pertactin (PRN), diphtheria toxoid (DT), tetanus toxoid (TT), antibodies 30 days after primary vaccination. Immunogenicity was assessed via Luminex-based multiplex immunoassay. Both DTcP-1 and DTcP-2 schedules demonstrated non-inferior safety to DTaP-IPV-Hib (total adverse reactions: 14.52/16.59% vs. 16.91%, P = 0.183), with DTcP-2 (2/4/6 months) showing lower swelling (2.59% vs. 4.83%, P = 0.008) and irritability (0.07% vs. 1.02/1.40%, P < 0.001). DTcP-2 elicited higher GMCs against pertussis antigens (PT: 84.23 vs. 65.35; FHA: 132.16 vs. 102.13, both P < 0.001) and comparable DT/TT responses. DTcP exhibited favorable safety and superior pertussis immunogenicity, particularly with the 2/4/6-month schedule. Its genetically engineered three-component design offers a promising strategy to combat pertussis amid global resurgence.
百日咳仍然是全球婴儿死亡的主要原因，在2019冠状病毒病后，中国的百日咳病例有所上升。尽管接种了疫苗，但无细胞百日咳疫苗的免疫力下降导致了死灰复燃。我们评估了一种新型白喉、破伤风和百日咳（无细胞、三组分）吸附联合疫苗（DTcP），这是中国首个基因工程百日咳三组分疫苗，与许可的dtap - ipvv - hib （Pentaxim）相比，分两个主要时间表（2/3/4和2/4/6个月）施用。在这项随机、盲法的III期临床试验中，来自中国河南的1380名2个月大的健康婴儿接受了DTcP-1（2/3/4个月）或DTcP-2（2/4/6个月）或dtap - ipvv - hib（2/3/4个月）。主要安全终点是初次接种后0 ~ 30天内不良反应的发生率。主要免疫原性终点是评价初次接种后30天抗百日咳类毒素（PT）、丝状血凝素（FHA）、perpern、白喉类毒素（DT）、破伤风类毒素（TT）抗体的血清转化率和几何平均浓度（GMCs）的非劣效性和优越性。通过基于luminex的多重免疫分析法评估免疫原性。DTcP-1和DTcP-2方案的安全性均优于dtap - ipvv - hib方案（总不良反应：14.52/16.59% vs. 16.91%, P = 0.183）， DTcP-2方案（2/4/6个月）肿胀（2.59% vs. 4.83%, P = 0.008）和易怒（0.07% vs. 1.02/1.40%, P < 0.001）较低。DTcP-2对百日咳抗原诱导较高的gmc （PT: 84.23 vs. 65.35; FHA: 132.16 vs. 102.13， P均< 0.001）和可比较的DT/TT反应。DTcP表现出良好的安全性和优越的百日咳免疫原性，特别是在2/4/6个月的时间表上。它的基因工程三组分设计提供了一个有希望的策略，以对抗百日咳在全球复苏。
{"title":"Safety and Immunogenicity of Diphtheria, Tetanus and Pertussis (Acellular, Three Components) Combined Vaccine, Adsorbed after three-dose priming in 2 Months Age Infants: A Randomized, Blinded, Controlled Phase III Clinical Trial in China.","authors":"Wei Zhang,Chen Wei,Peng Wan,Guangwei Feng,Feiyu Wang,Lichan Wang,Jiebing Tan,Xuewen Wang,Xue Wang,Xiuwen Sui,Wangyang You,Jinbo Gou,Liyong Yuan,Tao Zhu,Haitao Huang,Xiao Ma,Yanxia Wang","doi":"10.1080/22221751.2026.2625556","DOIUrl":"https://doi.org/10.1080/22221751.2026.2625556","url":null,"abstract":"Pertussis remains a leading cause of infant mortality globally, with rising cases in China post-COVID-19. Despite vaccination, waning immunity from acellular pertussis vaccines has driven resurgence. We evaluated a novel diphtheria, tetanus and pertussis (acellular, three components) combined vaccine, adsorbed (DTcP), China's first genetically engineered three-component pertussis vaccine, administered under two primary schedules (2/3/4 vs. 2/4/6 months) compared to licensed DTaP-IPV-Hib (Pentaxim). In this randomized, blinded, phase III clinical trial, 1380 healthy 2-month-old infants from Henan, China, received DTcP-1 (2/3/4 months) or DTcP-2 (2/4/6 months) or DTaP-IPV-Hib (2/3/4 months). The primary safety endpoints were the incidence of adverse reactions within 0∼30 days after primary vaccination. The primary immunogenicity endpoints were to evaluate the non-inferiority and superiority of seroconversion rates and geometric mean concentrations (GMCs) of anti-pertussis toxoid (PT), filamentous hemagglutinin (FHA), pertactin (PRN), diphtheria toxoid (DT), tetanus toxoid (TT), antibodies 30 days after primary vaccination. Immunogenicity was assessed via Luminex-based multiplex immunoassay. Both DTcP-1 and DTcP-2 schedules demonstrated non-inferior safety to DTaP-IPV-Hib (total adverse reactions: 14.52/16.59% vs. 16.91%, P = 0.183), with DTcP-2 (2/4/6 months) showing lower swelling (2.59% vs. 4.83%, P = 0.008) and irritability (0.07% vs. 1.02/1.40%, P < 0.001). DTcP-2 elicited higher GMCs against pertussis antigens (PT: 84.23 vs. 65.35; FHA: 132.16 vs. 102.13, both P < 0.001) and comparable DT/TT responses. DTcP exhibited favorable safety and superior pertussis immunogenicity, particularly with the 2/4/6-month schedule. Its genetically engineered three-component design offers a promising strategy to combat pertussis amid global resurgence.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"1 1","pages":"2625556"},"PeriodicalIF":13.2,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-30DOI: 10.1080/22221751.2026.2616944
Lianne Presley,Jimena Pérez-Vargas,Anaïs Saintigny,Iván Villanueva,Michelle Ho,Jessica Fone,Lara Brinsden,Nidhi Kaushik,Syan Olver,Connor A H Thompson,Diana Bautista-Sánchez,Siobhan Ennis,Mike Chen,Matthew McCallum,Jack T Brown,Sára Ferková,Brian Hetrick,David Veesler,Richard Leduc,Masahiro Niikura,Pierre-Luc Boudreault,Bryce Warner,François Jean
Human TMPRSS2 is a type II transmembrane serine protease and an essential host factor for SARS-CoV-2 and influenza A virus (IAV H1N1) infections. It facilitates the cleavage of viral surface glycoproteins, which are required for membrane fusion. This importance makes it an attractive target for host-directed antiviral therapies. We previously identified N-0385 and N-0920 as nanomolar TMPRSS2 inhibitors and demonstrated their antiviral potency against several SARS-CoV-2 variants. Here, we screened another twelve N-0385/N-0920 analogs with improved pharmacokinetics. Compounds 9 and 10 showed strong inhibition of TMPRSS2 activity and viral entry: they blocked pseudoviruses and authentic SARS-CoV-2 JN.1 and IAV H1N1 in Calu-3 cells. Compound 9 displayed a synergistic effect with baloxavir during IAV H1N1 infection. Both compounds highly reduced H1N1 infection in air-liquid interface cultures and mouse models, thus highlighting their broad antiviral potential. The discovery of broad-spectrum, host-directed antivirals against current and emerging human viruses is critical in preparing for future pandemics.
{"title":"TMPRSS2 inhibitors with broad-spectrum efficacy against SARS-CoV-2 (JN.1) and influenza A (H1N1) viruses protect mice from influenza A infection.","authors":"Lianne Presley,Jimena Pérez-Vargas,Anaïs Saintigny,Iván Villanueva,Michelle Ho,Jessica Fone,Lara Brinsden,Nidhi Kaushik,Syan Olver,Connor A H Thompson,Diana Bautista-Sánchez,Siobhan Ennis,Mike Chen,Matthew McCallum,Jack T Brown,Sára Ferková,Brian Hetrick,David Veesler,Richard Leduc,Masahiro Niikura,Pierre-Luc Boudreault,Bryce Warner,François Jean","doi":"10.1080/22221751.2026.2616944","DOIUrl":"https://doi.org/10.1080/22221751.2026.2616944","url":null,"abstract":"Human TMPRSS2 is a type II transmembrane serine protease and an essential host factor for SARS-CoV-2 and influenza A virus (IAV H1N1) infections. It facilitates the cleavage of viral surface glycoproteins, which are required for membrane fusion. This importance makes it an attractive target for host-directed antiviral therapies. We previously identified N-0385 and N-0920 as nanomolar TMPRSS2 inhibitors and demonstrated their antiviral potency against several SARS-CoV-2 variants. Here, we screened another twelve N-0385/N-0920 analogs with improved pharmacokinetics. Compounds 9 and 10 showed strong inhibition of TMPRSS2 activity and viral entry: they blocked pseudoviruses and authentic SARS-CoV-2 JN.1 and IAV H1N1 in Calu-3 cells. Compound 9 displayed a synergistic effect with baloxavir during IAV H1N1 infection. Both compounds highly reduced H1N1 infection in air-liquid interface cultures and mouse models, thus highlighting their broad antiviral potential. The discovery of broad-spectrum, host-directed antivirals against current and emerging human viruses is critical in preparing for future pandemics.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"30 1","pages":"2616944"},"PeriodicalIF":13.2,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In humans, Borealpox virus (BRPV) is commonly associated with mild, self-limiting infections. However, in immunosuppressed individuals, infection can be severe and fatal. Due to a limited number of laboratory-confirmed cases and a lack of described animal models, little data on antiviral effectiveness against BRPV are available. Here we developed both immunocompetent and immunodeficient mouse models for the study of BRPV. In immunocompetent mice, BRPV infection resulted in high viral titers with organ-specific gross pathological abnormalities and route-dependant lethality. In immunodeficient mice, BRPV was uniformly lethal with varying times to lethal disease which appeared to coincide with viral replication. Notably, extensive fluid retention was also observed in these mice. Further assessment of cidofovir, brincidofovir, and tecovirimat therapy against BRPV infection demonstrated that all three compounds resulted in improved clinical condition and significant reductions in BRPV titers.
{"title":"Assessment of three antiviral compounds against Borealpox virus infection in a mouse model.","authors":"Jérémie Prévost,Nikesh Tailor,Angela Sloan,Kathleen Fulton,Sarah J Medina,Jonathan Audet,Geoff Soule,David Safronetz","doi":"10.1080/22221751.2026.2623694","DOIUrl":"https://doi.org/10.1080/22221751.2026.2623694","url":null,"abstract":"In humans, Borealpox virus (BRPV) is commonly associated with mild, self-limiting infections. However, in immunosuppressed individuals, infection can be severe and fatal. Due to a limited number of laboratory-confirmed cases and a lack of described animal models, little data on antiviral effectiveness against BRPV are available. Here we developed both immunocompetent and immunodeficient mouse models for the study of BRPV. In immunocompetent mice, BRPV infection resulted in high viral titers with organ-specific gross pathological abnormalities and route-dependant lethality. In immunodeficient mice, BRPV was uniformly lethal with varying times to lethal disease which appeared to coincide with viral replication. Notably, extensive fluid retention was also observed in these mice. Further assessment of cidofovir, brincidofovir, and tecovirimat therapy against BRPV infection demonstrated that all three compounds resulted in improved clinical condition and significant reductions in BRPV titers.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"43 1","pages":"2623694"},"PeriodicalIF":13.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-27DOI: 10.1080/22221751.2026.2623695
Cesar Cantero,Cynthia Vazquez,Sandra Gonzalez,Analia Rojas,Fatima Fleitas,Julio Barrios,Andrea Gomez de la Fuente,Shirley Villalba,Martha Torales,Andrea Ijeda,Vagner Fonseca,Luiz Carlos Junior Alcantara,Marta Giovanetti
We report the re-emergence of dengue virus serotype 3 (DENV-3) in Paraguay after 15 years of absence. Twelve laboratory-confirmed cases were detected in early 2025 in the Asunción metropolitan region. Genomic sequencing identified DENV-3 genotype III, lineage B.3.2, indicating a new introduction of an emerging lineage rather than renewed local transmission. Phylogenetic analyses support recent introduction events, underscoring the importance of strengthened genomic surveillance to enable early detection, track viral introductions, and inform public health responses in settings with intense dengue transmission.
{"title":"Re-emergence of DENV-3 in Paraguay After Two Decades: A Genomic and Epidemiological Investigation.","authors":"Cesar Cantero,Cynthia Vazquez,Sandra Gonzalez,Analia Rojas,Fatima Fleitas,Julio Barrios,Andrea Gomez de la Fuente,Shirley Villalba,Martha Torales,Andrea Ijeda,Vagner Fonseca,Luiz Carlos Junior Alcantara,Marta Giovanetti","doi":"10.1080/22221751.2026.2623695","DOIUrl":"https://doi.org/10.1080/22221751.2026.2623695","url":null,"abstract":"We report the re-emergence of dengue virus serotype 3 (DENV-3) in Paraguay after 15 years of absence. Twelve laboratory-confirmed cases were detected in early 2025 in the Asunción metropolitan region. Genomic sequencing identified DENV-3 genotype III, lineage B.3.2, indicating a new introduction of an emerging lineage rather than renewed local transmission. Phylogenetic analyses support recent introduction events, underscoring the importance of strengthened genomic surveillance to enable early detection, track viral introductions, and inform public health responses in settings with intense dengue transmission.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"64 1","pages":"2623695"},"PeriodicalIF":13.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVEThis study evaluated the economic and health benefits of hepatitis E (HEV) screening and vaccination in both outbreak and sporadic settings in China.METHODSDecision-analytic Markov models were used to evaluate the population impact and cost-effectiveness of HEV screening and vaccination for people with chronic hepatitis B (CHB), older adults, pregnant women, and women of childbearing age. Simulations projected outcomes over six months for outbreak settings and lifetime horizons for sporadic settings. Incremental cost-effectiveness ratios (ICERs) were derived from a health system perspective with costs in 2023 US$. Robustness was examined through sensitivity analyses.RESULTSPreventive universal screening combined with standard 3-dose HEV 239 vaccine was cost-effective only for people with CHB (Incremental cost-effectiveness ratio [ICER]: $25.38 thousand per Quality-Adjusted Life Year [QALY] gained), reducing symptomatic infections by 58.16% and HEV-related deaths by 57.51% in sporadic settings. This strategy may be economically viable for other vulnerable populations if the vaccine price is below $21 per dose. In outbreak settings, reactive universal screening combined with emergency 2-dose vaccination yielded cost-effective for older adults, pregnant women, and people with CHB (ICERs of $8.80, $26.26, and $31.81 thousand per QALY gained), reducing symptomatic infections and HEV-related deaths by over 70% within six months.CONCLUSIONSIn China, where sporadic settings are more common, preventive universal HEV screening combined with standard 3-dose vaccination is cost-effective only for people with CHB. High vaccine costs render this strategy economically unfeasible for older adults, pregnant women, and women of childbearing age.
{"title":"Cost-effectiveness Analysis of Hepatitis E Screening and Vaccination: Targeting Vulnerable Populations in Outbreak and Sporadic Settings in China.","authors":"Hanting Liu,Gang Chen,Yusheng Jie,Yong Jiang,Yao Huang,Xu Wang,Chun Hao,Jing Gu,Lei Zhang,Jinghua Li","doi":"10.1080/22221751.2026.2623707","DOIUrl":"https://doi.org/10.1080/22221751.2026.2623707","url":null,"abstract":"OBJECTIVEThis study evaluated the economic and health benefits of hepatitis E (HEV) screening and vaccination in both outbreak and sporadic settings in China.METHODSDecision-analytic Markov models were used to evaluate the population impact and cost-effectiveness of HEV screening and vaccination for people with chronic hepatitis B (CHB), older adults, pregnant women, and women of childbearing age. Simulations projected outcomes over six months for outbreak settings and lifetime horizons for sporadic settings. Incremental cost-effectiveness ratios (ICERs) were derived from a health system perspective with costs in 2023 US$. Robustness was examined through sensitivity analyses.RESULTSPreventive universal screening combined with standard 3-dose HEV 239 vaccine was cost-effective only for people with CHB (Incremental cost-effectiveness ratio [ICER]: $25.38 thousand per Quality-Adjusted Life Year [QALY] gained), reducing symptomatic infections by 58.16% and HEV-related deaths by 57.51% in sporadic settings. This strategy may be economically viable for other vulnerable populations if the vaccine price is below $21 per dose. In outbreak settings, reactive universal screening combined with emergency 2-dose vaccination yielded cost-effective for older adults, pregnant women, and people with CHB (ICERs of $8.80, $26.26, and $31.81 thousand per QALY gained), reducing symptomatic infections and HEV-related deaths by over 70% within six months.CONCLUSIONSIn China, where sporadic settings are more common, preventive universal HEV screening combined with standard 3-dose vaccination is cost-effective only for people with CHB. High vaccine costs render this strategy economically unfeasible for older adults, pregnant women, and women of childbearing age.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"164 1","pages":"2623707"},"PeriodicalIF":13.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dengue infection is a global health issue with significantly increased incidence and overall burden, especially since 2024. Specifically, epidemiological trends show a rising median age of affected individuals over 65 years/old. Older individuals face increased risks of severe disease, extended hospital stays, healthcare-associated infections, and higher mortality rates, mainly due to a decline in immune function, and multimorbidity. Antibody-dependent enhancement, cytokine dysregulation, and endothelial dysfunction exacerbate disease severity. Moreover, in older patients, dengue diagnosis can be difficult, due to atypical symptoms. To date, there are no specific prognostic markers and no specific antiviral drugs. Management requires age-specific considerations. Evidence on immunomodulatory and antiviral therapies is emerging, and vaccine efficacy and safety data in older adults remain limited, despite growing interest. With an aging global population, dengue represents an urgent clinical challenge: there is an unmet and increasing need for comprehensive, practical guidelines to help clinicians in the diagnosis, treatment, prevention, and control of dengue infection in older patients.Trial registration: ClinicalTrials.gov identifier: NCT05611710..Trial registration: ClinicalTrials.gov identifier: NCT06579755..
{"title":"Dengue and Aging: Challenges and Opportunities in Prevention and Care. A narrative review.","authors":"Alessia Beccacece,Laura Ponzetta,Maria Princiotto,Maria Elsa Gambuzza,Alessandra D'Abramo,Luca Soraci,Fabiola Olivieri,Fabrizia Lattanzio,Enrico Girardi,Leonardo Biscetti,Emanuele Nicastri","doi":"10.1080/22221751.2026.2622217","DOIUrl":"https://doi.org/10.1080/22221751.2026.2622217","url":null,"abstract":"Dengue infection is a global health issue with significantly increased incidence and overall burden, especially since 2024. Specifically, epidemiological trends show a rising median age of affected individuals over 65 years/old. Older individuals face increased risks of severe disease, extended hospital stays, healthcare-associated infections, and higher mortality rates, mainly due to a decline in immune function, and multimorbidity. Antibody-dependent enhancement, cytokine dysregulation, and endothelial dysfunction exacerbate disease severity. Moreover, in older patients, dengue diagnosis can be difficult, due to atypical symptoms. To date, there are no specific prognostic markers and no specific antiviral drugs. Management requires age-specific considerations. Evidence on immunomodulatory and antiviral therapies is emerging, and vaccine efficacy and safety data in older adults remain limited, despite growing interest. With an aging global population, dengue represents an urgent clinical challenge: there is an unmet and increasing need for comprehensive, practical guidelines to help clinicians in the diagnosis, treatment, prevention, and control of dengue infection in older patients.Trial registration: ClinicalTrials.gov identifier: NCT05611710..Trial registration: ClinicalTrials.gov identifier: NCT06579755..","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"17 1","pages":"2622217"},"PeriodicalIF":13.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1080/22221751.2026.2622215
Janin Nouhin,Daan Jansen,Touch Nay,Savuth Chin,Pedro H L F Dantas,Leakhena Pum,Limmey Khun,Chhayyuth Mov,Sothea Pho,Seangmai Keo,Lomor Kruy,Reaksa Lim,Kimtuo Chel,Kimlay Chea,Jurre Y Siegers,Sophoannadedh Rath,Jolein Gyonne Elise Laumen,Giorgio Gonnella,Darapheak Chau,Sidon Krang,Sovann Ly,Koen Vercauteren,Erik A Karlsson
Mpox is an infectious disease caused by the Monkeypox virus, which is divided into two main genetic clades: Clade I and Clade II. A large-scale outbreak linked to Clade IIb emerged in 2022 and rapidly spread to more than 100 countries worldwide. Here, we describe the first and only documented Mpox outbreak in Cambodia (2023-2024), the public health outbreak response efforts and analysis, and integrating epidemiological and genomic approaches.To investigate the outbreak, samples from suspect cases were confirmed using qPCR before virus whole genome sequences were obtained for phylogenomic analyses.Epidemiological investigation revealed transmission primarily through intimate contact within socially connected networks, exclusively among men who have sex with men. None of the confirmed cases reported recent international travel or zoonotic exposure. Phylogenomic analysis showed that all Cambodian Mpox genomes belonged to lineage C.1, nested within Clade IIb. Bayesian analysis of publicly available C.1 genomes indicated that the most closely related sequence was from Thailand. Monophyletic clustering of Cambodian sequences, alongside a high proportion of APOBEC3 mutations, indicates localized human-to-human transmission after introduction.Altogether, these results illustrate the risk of regional lineages like C.1 introducing Mpox into previously unaffected countries, where socially connected human networks can sustain outbreaks despite control efforts.
{"title":"Epidemiology and Phylogenomic Characterization of the Clade IIb C.1 Mpox Outbreak in Phnom Penh, Cambodia (2023-2024).","authors":"Janin Nouhin,Daan Jansen,Touch Nay,Savuth Chin,Pedro H L F Dantas,Leakhena Pum,Limmey Khun,Chhayyuth Mov,Sothea Pho,Seangmai Keo,Lomor Kruy,Reaksa Lim,Kimtuo Chel,Kimlay Chea,Jurre Y Siegers,Sophoannadedh Rath,Jolein Gyonne Elise Laumen,Giorgio Gonnella,Darapheak Chau,Sidon Krang,Sovann Ly,Koen Vercauteren,Erik A Karlsson","doi":"10.1080/22221751.2026.2622215","DOIUrl":"https://doi.org/10.1080/22221751.2026.2622215","url":null,"abstract":"Mpox is an infectious disease caused by the Monkeypox virus, which is divided into two main genetic clades: Clade I and Clade II. A large-scale outbreak linked to Clade IIb emerged in 2022 and rapidly spread to more than 100 countries worldwide. Here, we describe the first and only documented Mpox outbreak in Cambodia (2023-2024), the public health outbreak response efforts and analysis, and integrating epidemiological and genomic approaches.To investigate the outbreak, samples from suspect cases were confirmed using qPCR before virus whole genome sequences were obtained for phylogenomic analyses.Epidemiological investigation revealed transmission primarily through intimate contact within socially connected networks, exclusively among men who have sex with men. None of the confirmed cases reported recent international travel or zoonotic exposure. Phylogenomic analysis showed that all Cambodian Mpox genomes belonged to lineage C.1, nested within Clade IIb. Bayesian analysis of publicly available C.1 genomes indicated that the most closely related sequence was from Thailand. Monophyletic clustering of Cambodian sequences, alongside a high proportion of APOBEC3 mutations, indicates localized human-to-human transmission after introduction.Altogether, these results illustrate the risk of regional lineages like C.1 introducing Mpox into previously unaffected countries, where socially connected human networks can sustain outbreaks despite control efforts.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"35 1","pages":"2622215"},"PeriodicalIF":13.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：