Lancet Microbe最新文献

{"title":"Ocular infectivity and replication of a clade 2.3.4.4b A(H5N1) influenza virus associated with human conjunctivitis in a dairy farm worker in the USA: an in-vitro and ferret study.","authors":"Jessica A Belser, Joanna A Pulit-Penaloza, Nicole Brock, Xiangjie Sun, Troy J Kieran, Claudia Pappas, Hui Zeng, Michelle N Vu, Seema S Lakdawala, Terrence M Tumpey, Taronna R Maines","doi":"10.1016/j.lanmic.2024.101070","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.101070","url":null,"abstract":"<p><strong>Background: </strong>The human eye represents a potential site of influenza A virus (IAV) replication, and an entry point for the virus to reach the respiratory tract. The frequent detection of conjunctivitis among farm workers with confirmed infection with clade 2.3.4.4b A(H5N1) IAV from this ongoing outbreak represents an atypical disease presentation for this virus subtype. We aimed to investigate whether the occurrence of ocular complications reported following clade 2.3.4.4b A(H5N1) virus infection was associated with an enhanced capacity of this virus to replicate in mammalian ocular tissue and cause infection following ocular exposure.</p><p><strong>Methods: </strong>Primary human nasal and corneal tissue constructs were infected with A(H5N1) A/Texas/37/2024 (Texas/37), A(H1N1)pdm09 A/Nebraska/14/2019 (Neb/14), and A(H7N7) A/Netherlands/219/2003 (NL/219) viruses (multiplicity of infection [MOI] of 0·01-0·02, 33°C). Corneal tissue constructs were also infected with an expanded panel of IAVs (Texas/37, A[H5N1] A/Michigan/90/2024 [MI/90], A[H5N1] A/Chile/25945/2023 [Chile/25945], NL/219, A/Netherlands/230/2003 [NL/230], and Neb/14; MOI of 0·01, 37°C). In-vitro infections of tissue constructs were used to assess replication kinetics by infectious virus titration. Induction of innate host antiviral responses in infected corneal tissue constructs was assessed by PCR array (MOI of 2·00, 37°C). Ferrets (serologically naive or pre-immune to A[H1N1]pdm09 virus) were inoculated by the ocular route with Texas/37 A(H5N1) virus-using a liquid inoculum (10⁶ plaque forming units [PFU]), aerosol inhalation (15-16 PFU), or ocular-only aerosol exposure (18-132 PFU)-to assess pathogenicity and tropism of the virus following different exposure routes. Transmissibility was assessed by placing serologically naive or pre-immune ferrets inoculated by ocular-only aerosol exposure in direct contact with serologically naive ferrets, monitoring pathogenicity in contact animals, and measuring viral titres in nasal washes of both inoculated and contact ferrets.</p><p><strong>Findings: </strong>Nasal and corneal tissue constructs supported replication of all IAVs tested. In corneal tissue constructs, A(H7N7) and A(H1N1)pdm09 viruses reached 10-fold higher overall titres than A(H5N1) isolates. Relatively few genes (n=13) related to antiviral responses were significantly differentially expressed in corneal tissue constructs infected with IAV, with no consistent differential expression among clade 2.3.4.4b A(H5N1) viruses associated with either conjunctivitis or severe respiratory disease, although strain-specific differences were observed. Serologically naive ferrets inoculated by liquid ocular, aerosol inhalation, or aerosol-only ocular routes with Texas/37 virus exhibited a systemic and fatal infection in all animals, transmitting the virus to naive cagemates. By contrast, reduced disease severity following ocular-only aerosol inoculation was observed in anima","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101070"},"PeriodicalIF":20.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary efficacy endpoints in phase 3 non-inferiority trials to establish new tuberculosis treatment regimens should only include microbiological outcomes.","authors":"Tom A Yates, Daniel J Grint","doi":"10.1016/j.lanmic.2025.101117","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101117","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101117"},"PeriodicalIF":20.9,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A rapid, reliable, and revolutionary dual-path platform assay: a paradigm in typhoid diagnosis.","authors":"Rajesh Kanna Gopal, Pitchaipillai Sankar Ganesh, Naji Naseef Pathoor, Akshaya Viswanathan","doi":"10.1016/j.lanmic.2025.101108","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101108","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101108"},"PeriodicalIF":20.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eradication efficacy and the effect of vonoprazan-amoxicillin dual therapy on gut microbiota and antibiotic resistome.","authors":"Kai Zhou, Zhiqiang Song","doi":"10.1016/j.lanmic.2025.101116","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101116","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101116"},"PeriodicalIF":20.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between HIV-1 Nef-mediated MHC-I downregulation and the maintenance of the replication-competent latent viral reservoir in individuals with virally suppressed HIV-1 in Uganda: an exploratory cohort study.","authors":"Mitchell J Mumby, Jessica L Prodger, Jada Hackman, Sharada Saraf, Xianming Zhu, Roux-Cil Ferreira, Stephen Tomusange, Samiri Jamiru, Aggrey Anok, Taddeo Kityamuweesi, Paul Buule, Corby Fink, Cassandra R Edgar, Steven M Trothen, Gregory A Dekaban, Erin E Brown, Adam A Capoferri, Owen R Baker, Ethan Klock, Jernelle C Miller, Charles Kirby, Briana Lynch, Aaron A R Tobian, Art F Y Poon, Thomas C Quinn, Ronald M Galiwango, Steven J Reynolds, Andrew D Redd, Jimmy D Dikeakos","doi":"10.1016/j.lanmic.2024.101018","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.101018","url":null,"abstract":"<p><strong>Background: </strong>The persistence of a replication-competent latent viral reservoir (RC-LVR) during antiretroviral therapy (ART) is a barrier to the development of a cure for HIV-1, but the role of viral genes in influencing RC-LVR size is unclear. We aimed to assess whether the magnitude by which the HIV-1 accessory protein Nef evades the adaptive immune response by downregulating MHC-I or CD4, or both, from the surface of infected cells is associated with the rate at which the RC-LVR in people with HIV-1 changes during long-term ART (>1 year).</p><p><strong>Methods: </strong>We conducted an exploratory cohort study in which nef genes were sequenced from outgrowth viruses derived from the quantitative viral outgrowth assay (QVOA) for a group of people with ART-suppressed HIV-1 in Uganda between 2015 and 2020. Study participants were selected from the Rakai Health Sciences Program (RHSP) LVR cohort, a cohort of 90 adults (aged ≥18 years) who were HIV-1 positive, receiving ART, and had maintained viral suppression for at least 1 year at the time of study enrolment. For this study, participants were required to have available p24<sup>+</sup> QVOA wells that contained a single viral outgrowth isolate, as assessed by next-generation sequencing. In cases where further sequencing identified wells containing multiple viral clones, all sequenced nef variants were included for functional analysis. The unique isolated nef variants were used to generate pseudoviruses, which were employed to measure cell surface CD4 and MHC-I downregulation in infected CD4<sup>+</sup> Sup-T1 cells via flow cytometry. The size and rate of change of the RC-LVR in participants was estimated using previous QVOA results and a Bayesian model. We then assessed whether a correlation existed between the extent to which the Nef proteins downregulated cell surface MHC-I and CD4 and the calculated RC-LVR rate of change during the study period.</p><p><strong>Findings: </strong>14 (15%) of 90 participants from the RHSP cohort met the inclusion criteria and were enrolled in this study. 49 nef sequences were isolated from these participants. We observed variability in participant-derived Nef-mediated cell surface MHC-I downregulation (median 114·88% [IQR 104·93-121·51] of the downregulation capacity of NL4-3 Nef) and CD4 downregulation (94·50% [84·05-100·16] of NL4-3 Nef). The estimated rate of change of the RC-LVR was positive for four participants. For one donor, the rate of change was significantly positive (7·4 × 10<sup>-4</sup> logit infectious units per million [IUPM] per day [95% credibility interval 3·2 × 10<sup>-4</sup> to 1·2 × 10<sup>-3</sup>]) over the course of the study period (2015-20). The estimated rate of change of the RC-LVR for the remaining ten participants was negative, and significantly negative in four donors (-1·1 × 10<sup>-3</sup> logit IUPM per day [95% credibility interval -1·8 × 10<sup>-3</sup> to -3·7 × 10<sup>-4</sup>]; -1·4 × 10<sup>-3</sup> [-2","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101018"},"PeriodicalIF":20.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does anticancer therapy directly contribute to antimicrobial resistance?","authors":"Ishir Sharma, Richard C Wilson, Nina Zhu, Timothy Miles Rawson","doi":"10.1016/j.lanmic.2025.101115","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101115","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101115"},"PeriodicalIF":20.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccine shortage affects airline and public health efforts to prevent meningitis during Umrah.","authors":"Ziad A Memish, Majid M Alshamrani, Ali M Albarrak, Shahul Ebrahim","doi":"10.1016/j.lanmic.2025.101113","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101113","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101113"},"PeriodicalIF":20.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of inflammatory markers with post-acute clinical findings among survivors of Ebola virus disease with and without viral RNA shedding in the semen in Liberia: a nested case-control study.","authors":"Mosoka P Fallah, Collin Van Ryn, J Soka Moses, Moses Badio, Tamba Fayiah, Kumblytee Johnson, Dehkontee Gayedyu-Dennis, Allen O Eghrari, Sheri D Weiser, Travis C Porco, Jeffrey N Martin, Michael J Peluso, David R McIlwain, Bonnie Dighero-Kemp, Elizabeth Higgs, Lisa E Hensley, George W Rutherford, Cavan Reilly, J Daniel Kelly","doi":"10.1016/j.lanmic.2024.101033","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.101033","url":null,"abstract":"<p><strong>Background: </strong>A high proportion of survivors of Ebola virus disease (EVD) have post-acute sequelae of EVD (PASE), but the relationship between inflammation and PASE pathogenesis is poorly understood. This study tests the hypothesis that inflammation is associated with PASE among survivors with and without viral RNA shedding in the semen.</p><p><strong>Methods: </strong>This was a case-control study nested in a longitudinal cohort that recruited confirmed survivors of EVD and their uninfected contacts from the 2013-16 EVD epidemic in Liberia, starting on June 1, 2015. We included participants aged at least 18 years with clinical data and plasma available at cohort baseline for analysis. A semen donation substudy tested male survivors for Ebola virus RNA shedding in the semen. A sex-stratified and survivor-stratified random sample of cases (survivors) and controls (contacts) was obtained to select stored baseline plasma samples for cytokine testing of markers of inflammation, immune regulation, and antiviral responses. Serostatus of cases and controls was confirmed by Filovirus Animal Nonclinical Group assay. We identified inflammatory markers (adjusted p≤0·05) elevated in cases compared with controls and then used these biomarkers in analyses comparing survivors with and without pre-specified PASE-associated clinical findings (self-reported symptoms and abnormal examination findings). Survivors with viral RNA shedding in the semen formed subgroup analyses.</p><p><strong>Findings: </strong>Our analysis cohort consisted of 1044 participants (594 survivors of EVD and 450 uninfected contacts); 515 (49·3%) were female and 529 (50·7%) were male. The subcohort of 243 male survivors with data on viral shedding included 81 (33%) participants with viral shedding in semen. Median time from acute EVD to baseline was 317 days (IQR 271-366). Survivors of EVD showed a pattern of elevated inflammatory markers indicative of macrophage (MCP-1, IL-1β, and M-CSF) and angiogenic factor activation (VEGF-A) compared with controls (adjusted p<0·05). In survivors with viral shedding in the semen compared with controls, VEGF-A was the only inflammatory marker that was significantly higher (adjusted p<0·001). After restricting the analysis to survivors, each inflammatory marker had a specific pattern of clinical findings. Higher levels of IL-1β were associated with higher odds of urinary frequency (p=0·002), musculoskeletal abnormalities (p=0·003), and abdominal abnormalities (p=0·03). By contrast, higher levels of MCP-1 were associated with lower odds of the same clinical findings. M-CSF was the only inflammatory marker associated with lower odds of joint pain (p=0·04). Higher levels of VEGF-A were associated with higher odds of abnormal chest findings in the overall survivor group (p=0·02) and in the subgroup with viral shedding in the semen (p=0·02).</p><p><strong>Interpretation: </strong>We found evidence of distinct biological pathways for PASE. Altho","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101033"},"PeriodicalIF":20.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marburg virus outbreak in Tanzania.","authors":"Priya Venkatesan","doi":"10.1016/j.lanmic.2025.101121","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101121","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101121"},"PeriodicalIF":20.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virology Africa 2024: a short report.","authors":"Edward P Rybicki, Anna-Lise Williamson, Marietjie Venter","doi":"10.1016/j.lanmic.2025.101093","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101093","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101093"},"PeriodicalIF":20.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587836","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}