The Journal of Infectious Diseases最新文献

{"title":"Mechanistic insights into increased vulnerability to respiratory infections in HIV-Exposed Uninfected Infants.","authors":"Cheryl Cohen,Penny Moore","doi":"10.1093/infdis/jiaf494","DOIUrl":"https://doi.org/10.1093/infdis/jiaf494","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood cultures contain populations of genetically diverse Candida albicans strains that may differ in echinocandin tolerance and fitness","authors":"Giuseppe Fleres, Shaoji Cheng, Hassan Badrane, Christopher L Dupont, Josh L Espinoza, Darren Abbey, Eileen Driscoll, Anthony Newbrough, Binghua Hao, Akila Mansour, M Hong Nguyen, Cornelius J Clancy","doi":"10.1093/infdis/jiaf495","DOIUrl":"https://doi.org/10.1093/infdis/jiaf495","url":null,"abstract":"Background It is unknown whether within-patient Candida albicans diversity is common during bloodstream infections (BSIs). Methods We determined whole genome sequences of 10 C. albicans strains from blood cultures (BCs) in each of 4 patients. We performed detailed phenotypic studies on strains from 1 patient. Results BCs in 3 patients contained mixed populations of strains that differed by large-scale genetic variants, including chromosome (Chr) 5 or 7 aneuploidy and Chr1 loss of heterozygosity (n=1 each). In patient M, Chr7 trisomy (Tri7) strains were attenuated for hyphal and biofilm formation in vitro, due at least in part to NRG1 over-expression. Nevertheless, representative Tri7 strain M1 underwent filamentation during disseminated candidiasis (DC) in mice. M1 was more fit than euploid strain M2 during DC and mouse gastrointestinal colonization, and in blood ex vivo. M1 and M2 exhibited identical echinocandin minimum inhibitory concentrations, but M2 was more tolerant to micafungin in vitro. Furthermore, M2 was more competitive with M1 in mouse kidneys following micafungin treatment than it was in absence of micafungin. Tri7 strains represented 74% of patient M’s baseline BC population, but euploid strains were 98% of the population after 3d of echinocandin treatment. Findings suggest that echinocandin tolerant, euploid strains were a subpopulation to more fit Tri7 strains at baseline and then were selected upon echinocandin exposure. Conclusions BCs in some patients are comprised of diverse C. albicans populations not recognized by the clinical lab, rather than single strains. Clinical relevance of C. albicans diversity and echinocandin tolerance merits further investigation.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral Infection and the Blood-Brain Barrier: Molecular Research Insights and Therapies.","authors":"Sarah A Boardman,Claire Hetherington,Thomas Hughes,Callum Cook,Ian Galea,Orla Hilton,Tom Solomon,Andrew D Luster,Stuart Allan,Evelyn Kurt-Jones,Joe Forth,Adjanie Patabendige,Franklyn N Egbe,Cordelia Dunai,Benedict D Michael","doi":"10.1093/infdis/jiaf455","DOIUrl":"https://doi.org/10.1093/infdis/jiaf455","url":null,"abstract":"The blood-brain barrier (BBB) protects the brain from pathogenic microorganisms. Neurologic complications from viral infections, including herpes simplex virus, varicella zoster virus, HIV, Japanese encephalitis virus, and SARS-CoV-2, are linked to BBB dysfunction and loss of barrier integrity. Increased BBB permeability associated with viral infections can occur through several mechanisms, such as direct neurotropism, Trojan horse mechanisms, or systemic infection and inflammation. Viruses cause direct and indirect immune-mediated damage. Understanding these neuroimmune mechanisms is critical to establish therapeutic strategies to protect BBB function. This review describes the effect of viral infection on the BBB, clinical methods to assess BBB integrity, and clinical management approaches to address viral-induced BBB damage.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Potential for Person-to-Person Transmission of Henipaviruses: A Systematic Review of the Literature.","authors":"","doi":"10.1093/infdis/jiaf487","DOIUrl":"https://doi.org/10.1093/infdis/jiaf487","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world prevalence of non-integrase INSTI resistance-associated mutations and virological outcomes in people who have recently acquired HIV-1 in the UK.","authors":"Christine Kelly,James S Lester,Daniel Bradshaw,David F Bibby,Hodan Mohamed,Gary Murphy,Alison Brown,Caroline Sabin,Anna-Maria Geretti,Jean L Mbisa","doi":"10.1093/infdis/jiaf500","DOIUrl":"https://doi.org/10.1093/infdis/jiaf500","url":null,"abstract":"INTRODUCTIONIntegrase strand transfer inhibitors(INSTIs) are the mainstay of antiretroviral therapy(ART) globally. Virological breakthrough is uncommon but often manifests as low level viraemia and only 50% of cases have identified drug resistance mutations in the integrase gene. Non-integrase mutations in the Gag-nucleocapsid protein (NC), envelope glycoprotein (Env) and 3'polypurine tract (3'PPT) have been identified in vitro.METHODSBetween 2015 and 2021, HIV-1 whole genome sequencing was performed on samples from people with recently acquired HIV-1 in the UK. Sequences were linked to demographic and clinical data within the UK Health Security Agency's HIV and AIDS Reporting System. The relationship between non-integrase enzyme mutations and virological outcomes was assessed.375 (34%) of 1106 participants started an INSTI-based regimen. Of these, 337 (90%) were men and 196 (52%) were living with subtype B. The median age was 33 years and number of viral loads within 24 months of starting ART was 4.RESULTSOverall, Env Y61H (33, 10%) and A539V (16, 5.0%), 3'PPT c9053t (17, 5.0%), and NC N8S (16, 4.8%) were the most prevalent non-integrase enzyme mutations. Univariable and multivariable Cox regression did not identify significant associations between the presence of these mutations individually and time to viral suppression, or to viral blip. Interestingly, accessory INSTI mutations were found significantly more frequently in people whose virus also harboured the Env mutation A539V (p=0.002).CONCLUSIONSeveral non-integrase mutations were prevalent, but we found no evidence of an impact upon virological outcomes within treatment-naïve individuals on INSTI-based regimens who had recently acquired HIV.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fostemsavir Decreases the Levels of Anti-gp120 CD4-Induced Antibodies in Heavily Treatment-Experienced People With HIV.","authors":"Mehdi Benlarbi,Jonathan Richard,Tommaso Clemente,Catherine Bourassa,William D Tolbert,Manyu Prakash,Monika Chandravanshi,Andrew Clark,Marzena Pazgier,Madeleine Durand,Antonella Castagna,Andrés Finzi","doi":"10.1093/infdis/jiaf461","DOIUrl":"https://doi.org/10.1093/infdis/jiaf461","url":null,"abstract":"BACKGROUNDHeavily treatment-experienced (HTE) people with HIV (PWH) have limited antiretroviral therapy (ART) treatment options, putting them at greater risk of unfavorable human immunodeficiency virus 1 (HIV-1) disease progression. Fostemsavir (BMS-663068) efficiently suppressed viremia and increased CD4 count when combined with other antiretrovirals in HTE PWH. Its active metabolite, temsavir (BMS-626529, GSK2616713), binds a conserved pocket within the envelope glycoprotein (Env) CD4 binding site and prevents CD4-induced conformational changes. Temsavir effect on Env conformation profoundly alters its glycosylation and cleavage, thereby modifying its antigenicity and reducing gp120 shedding. Here we evaluated if fostemsavir treatment in PWH modulated the levels of nonneutralizing gp120 CD4-induced (CD4i) antibodies (Abs) associated with CD4 depletion in vitro and in PWH.METHODSWe measured the levels of anti-gp120 CD4i Abs in plasma samples taken before and after fostemsavir treatment in HTE participants from the BRIGHTE trial and the PRESTIGIO registry and compared them to those of a control ART-treated group from the SAILING trial.RESULTSWe observed a significant decline of anti-gp120 CD4i Abs in the 2 fostemsavir-treated HTE groups, but not in the control group. Moreover, this effect was unique to anti-gp120 CD4i Abs, as no significant changes were observed in the levels of antibodies targeting Gag. Functionally, this decline in CD4i Abs was associated with a reduced capacity of plasma to recognize and eliminate uninfected primary CD4+ T cells coated with soluble gp120.CONCLUSIONSAltogether, fostemsavir may provide additional immune benefits to PWH, beyond blocking viral entry, by reducing anti-gp120 CD4i Abs levels.CLINICAL TRIALS REGISTRATIONNCT04098315, NCT01231516, and NCT02362503.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishing a Practical Approach to Sewer Monitoring for Antimicrobial Resistance Genes and Organisms at Healthcare Facilities.","authors":"Rachel S Poretsky,Dolores Sanchez Gonzalez,Adam Horton,Michael Schoeny,Chi-Yu Lin,Modou Lamin Jarju,Michael Secreto,Cecilia Chau,Ellen Gough,Erin Newcomer,Adit Chaudhary,Lisa Duffner,Nidhi Undevia,Angela Coulliette-Salmond,Amanda K Lyons,Florence Whitehill,Mary K Hayden,Stefan J Green,Michael Y Lin","doi":"10.1093/infdis/jiaf434","DOIUrl":"https://doi.org/10.1093/infdis/jiaf434","url":null,"abstract":"BACKGROUNDSurveillance of wastewater from healthcare facilities has the potential to identify the emergence of multidrug-resistance (MDR) genes of public health importance. Specifically, wastewater surveillance (WWS) can provide sentinel surveillance of novel MDR genes or organisms in healthcare facilities, helping to direct targeted prevention efforts and monitor longitudinal effects. Several knowledge gaps need to be addressed before WWS can be used routinely for MDR surveillance, including determining optimal approaches to sampling, processing, and testing wastewater.METHODSTo this end, we evaluated multiple methods for wastewater collection (passive, composite, and grab), concentration (nanoparticles, filtration, and centrifugation), and PCR quantification (real-time quantitative PCR vs. digital PCR) for Candida auris and 5 carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48-like) twice weekly for 6 months at a long-term acute care hospital in Chicago, IL. We also tested the effects of different transport and sample storage conditions on PCR quantification.RESULTSAll genes were detected in facility wastewater, with blaKPC being the most consistently abundant. Experiments were done in triplicate with gene copy, variance, and number of detections between triplicates used to determine method efficacy. We found that passive samples processed immediately by centrifugation followed by bead-beating and dPCR provided the most reliable results for detecting MDR genes and C. auris. We also present the tradeoffs of different approaches and use culture and metagenomics to elucidate clinical relevance.CONCLUSIONSThis study establishes a practical approach for WWS as a potential tool for public health monitoring of MDR burden in healthcare facilities.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pain is in the Brain with the Sugar-Coated Killer","authors":"Julia A Messina, John R Perfect","doi":"10.1093/infdis/jiaf496","DOIUrl":"https://doi.org/10.1093/infdis/jiaf496","url":null,"abstract":"Cryptococcus neoformans and C. gattii represent encapsulated yeasts which have become increasingly common central nervous system (CNS) pathogens during the enlarging age of the immunocompromised host. CNS disease represents a major interaction between the host and the yeast. In this regard, we have examined the myriads of tools that this group of yeasts possess that allow them to become very efficient pathogens in the human CNS, causing fatal meningoencephalitis if untreated. In the age of molecular pathogenesis for fungi, cryptococcosis has been studied extensively at the genetic level, and there is an impressive array of virulence factors that this basidiomycetous pathogen has developed to cause disease. This review details a series of virulence factors and their pathways. There is also some appreciation for the complexity of the host responses which are so essential to the outcome of these infections.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adrenal corticosteroids and increased intracranial pressure in nonimmunocompromised patients with cryptococcal meningitis.","authors":"John E Bennett,Seher Anjum,Peter R Williamson","doi":"10.1093/infdis/jiaf490","DOIUrl":"https://doi.org/10.1093/infdis/jiaf490","url":null,"abstract":"Elevated opening pressures on lumbar puncture were followed in seven nonimmunocompromised patients being treated for a post-inflammatory response syndrome that had begun following antifungal treatment of cryptococcal meningitis. During the initial period of high dose corticosteroid therapy, opening pressures on lumbar puncture fell an average of 14 cm. Despite this, five of seven later required a ventriculoperitonal shunt for pressure control.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Changing Paradigm in Infectious Diseases - Host-Directed Medicine: Implications for the Next Generation of ID Physicians.","authors":"Jatin M Vyas,Simon Feys,Michael K Mansour,Joost Wauters,Frank L van de Veerdonk","doi":"10.1093/infdis/jiaf497","DOIUrl":"https://doi.org/10.1093/infdis/jiaf497","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}