The Journal of Infectious Diseases最新文献

{"title":"Genetic landscape of a cohort of children with varicella-zoster virus encephalitis, cerebellitis and stroke","authors":"Franziska Winzig, Kerstin De Keukeleere, Esther Bartholomeus, Nicolas Deconinck, Christophe Barrea, Inge Matthijs, Anna C Jansen, Helene Verhelst, Charlotte Dielman, Maria Kuznetsova, My Ha, Arvid Suls, Renee M van der Sluis, Benson Ogunjimi, Trine H Mogensen","doi":"10.1093/infdis/jiaf448","DOIUrl":"https://doi.org/10.1093/infdis/jiaf448","url":null,"abstract":"Varicella-zoster virus (VZV) is a neurotropic member of the Herpesviridae family which causes varicella in primary infection and zoster during reactivation but in rare cases can lead to severe neurological complications, such as encephalitis. To identify inborn errors of immunity (IEI) and unravel pathways involved in VZV CNS immune responses and pathogenesis, we performed whole exome sequencing on a cohort of 38 children with neurological manifestations, including VZV encephalitis, cerebellitis, or stroke. We identified a total of 46 rare potentially pathogenic variants predicted to be deleterious, including variants in innate antiviral immunity, inflammation, cell stress responses, and autophagy. Collectively these findings represent a knowledge base for further functional studies and provide new insights into the genetic landscape of VZV CNS infections and highlight potential genetic defects that may compromise host defense, enabling new avenues for diagnosis and personalized treatment strategies for VZV CNS infections.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"114 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899621","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":"Schistosome Infection is Associated with High-Risk Human Papillomavirus Persistence, Together with Altered Cervicovaginal Microbiota","authors":"Crispin Mukerebe, Alexandra A Cordeiro, Christine Aristide, Soledad Colombe, Brooke W Bullington, Samuel Kalluvya, Govert J van Dam, Claudia J de Dood, Paul L A M Corstjens, Jane K Maganga, John M Changalucha, Lucy A Namkinga, Victor Anacletus Makene, Myung Hee Lee, Jennifer A Downs","doi":"10.1093/infdis/jiaf447","DOIUrl":"https://doi.org/10.1093/infdis/jiaf447","url":null,"abstract":"Schistosoma haematobium infection may impair female genital mucosal antiviral defense. We sought to determine whether women with S. haematobium infection had higher odds of high-risk human papillomavirus (HR-HPV) persistence, a pre-requisite to cervical cancer. We also examined cervicovaginal dysbiosis, which has been linked to HR-HPV persistence and schistosome infection. In 96 Tanzanian women with baseline and 9-12-month follow-up samples, we performed HPV genotyping, schistosome antigen quantification, and 16S rRNA sequencing. Both S. haematobium (Odds ratio (OR): 4.7 [1.3-16.5], p=0.017) and Gardnerella-dominant microbiome (p=0.049) were associated with HR-HPV persistence, suggesting these factors may contribute to high cervical cancer rates in Africa.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899625","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":"Accurate measurement of viral clearance in early phase antiviral studies in COVID-19.","authors":"Phrutsamon Wongnak,James A Watson,Podjanee Jittamala,William H K Schilling,Timothy Seers,Stije J Leopold,Nicholas J White","doi":"10.1093/infdis/jiaf442","DOIUrl":"https://doi.org/10.1093/infdis/jiaf442","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930294","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":"Cerebrospinal Fluid Mononuclear Cell Phenotype and Activation Predictors of 2-week and 1-year survival among Persons with HIV-Associated Cryptococcal Meningitis","authors":"Morris K Rutakingirwa, Kenneth Ssebambulidde, Samuel Okurut, Richard Kwizera, Martin Nabwana, Jane Gakuru, Jane Francis Ndyetukira, Suzan Mulwana, Lydia Nankungu, Kizza K Tadeo, Abdu K Musubire, David R Boulware, David B Meya","doi":"10.1093/infdis/jiaf449","DOIUrl":"https://doi.org/10.1093/infdis/jiaf449","url":null,"abstract":"Background Despite efforts to optimize therapy for HIV-associated cryptococcal meningitis (CM), survival outcomes remain poor. It is unclear how the cerebrospinal fluid (CSF) cellular immune phenotype and activation contribute to 2-week and 1-year survival following CM. Methods We compared baseline CSF mononuclear cell phenotype and activation among adults with HIV-associated cryptococcal meningitis who died within 2-weeks of CM diagnosis to survivors who were alive at 1-year. The activated CSF T-lymphocytes, CD14+monocytes, and CD56+natural killer cells were determined from freshly collected CSF using Cytek Aurora Spectroflo cytometry. Quantitative CSF soluble cryptococcal antigen (CrAg) titer from frozen CSF at baseline and 1-year was determined using CrAg lateral flow assay. Data were analyzed using STATA v9. Results Compared to survivors, participants who died within 2 weeks had significantly low absolute CSF CD8+T cells at baseline. For every 10% increase in PD-1 expression at baseline, the relative risk of 2-week mortality increased by 20-60%. CSF CD14+ monocytes among those who died demonstrated low HLA-DR+ and high CD163+ expression compared to survivors. We noted a significant reduction in the median CSF CrAg titer from 1:2560 at baseline to 1:5 at 1-year (p <0.0001) with 8/21 (38%) participants testing negative for CSF CrAg. Conclusions Expression of CD163 on CD14+macrophages and immune exhaustion of CSF mononuclear cells at baseline are associated with an increased risk of early mortality in CM. After one year of treatment, approximately 4 in 10 patients with CM have a negative CSF CrAg.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901737","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":"Cervicovaginal Secretions in Young Women with Bacterial Vaginosis Enhance HIV Infection","authors":"Marla J Keller, Tao Wang, Kerry Murphy, Myrna G Serrano, William Kandalaft, Ian Michael, Glenn Decety, Jessica McWalters, Greg A Buck, Libusha Kelly, Betsy C Herold","doi":"10.1093/infdis/jiaf444","DOIUrl":"https://doi.org/10.1093/infdis/jiaf444","url":null,"abstract":"Background Bacterial vaginosis (BV) is a major health problem associated with increased HIV risk. To explore underlying mechanisms, we assessed the cervicovaginal mucosal immune environment before and after metronidazole treatment in women with BV and healthy controls. Methods Women with BV diagnosed clinically by Amsel criteria were treated with oral or intravaginal metronidazole. Vaginal swabs and cervicovaginal lavage (CVL) were obtained at enrollment and approximately two and four weeks later for assessment of immune mediators, antiviral activity, and 16s rRNA gene sequencing. Healthy controls had sampling at enrollment and four weeks. Results Vaginal pH, Nugent score, Shannon alpha diversity index, and vaginal community state types (CST) differed significantly at enrollment comparing women with clinical BV (n=19) and controls (n=13) (p<0.001). BV cases had significantly higher CVL IL-1α and TNF-α, but lower IgG at enrollment compared to controls, which improved following treatment. Similar results were observed if participants with discordant molecular results (n=3) were excluded. Most notably, CVL from BV cases enhanced whereas control CVL inhibited HIV infection of cells relative to buffer (138.4 ± 109.8% vs 30.9 ±37.9%, p=0.001). There was a transient reduction in HIV enhancement following treatment, which was not sustained. Enhancement correlated with CST and markers of dysbiosis. Specifically, decreases in lactobacilli and increases in Prevotella, Dialister micraerophilus, and Peptoniphilus lacrimalis were associated with enhancement. Conclusions These findings provide a potential mechanistic link that may contribute to the increased risk of HIV in association with BV and highlight the importance of early diagnosis and improved treatments.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"107 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899356","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":"Precision Vaccinology: Making Vaccines Work Better for Women and Men","authors":"Eileen P Scully, Rosemary Morgan, Sabra L Klein","doi":"10.1093/infdis/jiaf397","DOIUrl":"https://doi.org/10.1093/infdis/jiaf397","url":null,"abstract":"Sex and gender have impacts on the responses to vaccination. Incorporating consideration of differences by sex and gender may facilitate more accurate communication about vaccines, the development of tailored approaches, and may enhance public trust.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899379","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":"Virological and Immunological Outcomes of Combined Therapeutic Interventions and Dendritic Cell Therapy in People Living with HIV.","authors":"Lishomwa C Ndhlovu,Leila B Giron,Juliana Galinskas,Thomas A Premeaux,Alina P S Pang,Danilo Dias,Marcela Vassao de Almeida Baptista,Iart Luca Shytaj,Juliana T Maricato,Paulo R A Ferreira,Gisele Gosuen,Michael J Corley,Courtney M Friday,Scott A Bowler,Ermelindo Della Libera,Maria Cecilia Sucupira,James R Hunter,Luis Mário Janini,Mauro Schechter,Andrea Savarino,Ricardo Sobhie Diaz, ","doi":"10.1093/infdis/jiaf430","DOIUrl":"https://doi.org/10.1093/infdis/jiaf430","url":null,"abstract":"BACKGROUNDSeveral strategies have been devised to decrease the size of the HIV reservoir. Except for hematopoietic cell transplantation, therapeutic-driven HIV-1 curative approaches have had limited success. Here we describe a two-step randomized clinical trial designed to evaluate the safety and impact of individual and combinatorial therapeutic strategies on changes in peripheral and gut mucosal HIV reservoirs, immune activation and immune function in people living with HIV in the chronic disease stage of disease and presenting with high CD4 T cell nadirs.METHODSThirty participants were enrolled and randomized equally into six study arms based on treatments with either standard antiretroviral therapy (ART) alone or a combination of candidate anti-HIV reservoir strategies that included ART intensification, auranofin (an apoptotic-inducer antirheumatic drug), nicotinamide (vitamin B3), and a personalized dendritic cell therapy.RESULTSAfter an analytical treatment interruption (ATI) post intervention, all eligible participants rebounded within 14 weeks, except for one participant with rebound detected at 84 weeks, and two participants receiving all combined therapies who both maintained viral loads below 1000 copies/mL through the study period. These three post-treatment controllers incidentally were all on nicotinamide containing regimens and exhibited immune cellular epigenetic age reversal over the period of the interventions.CONCLUSIONSThis proof-of-concept clinical trial demonstrates the safety of multiple interventions with distinct anti-reservoir activities in people with HIV and argues for continued investigation and investment towards both single and combinatorial intervention towards post-therapy HIV control.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851048","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":"Prognostic Divergence in HIV/HBV vs. HBV- Associated HCC after Resection: Intrahepatic Pre-S Deletions Mutants and T-cell Depletion under Viral Suppression.","authors":"Quanyang Gao,Xianglong Lan,Fan Yang,Haisheng Yu,Baojin Li,Fengyu Hu","doi":"10.1093/infdis/jiaf433","DOIUrl":"https://doi.org/10.1093/infdis/jiaf433","url":null,"abstract":"BACKGROUNDDespite effective antiretroviral (ART) use, the incidence of hepatocellular carcinoma (HCC) has not decreased in human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection. Our study compared postoperative prognosis, HBV Pre-S deletion, and immune microenvironment in co-infected and HBV mono-infected individuals.METHODSThis retrospective study included 143 HBV-associated HCC patients who underwent curative resection. Virologically suppressed patients (HBV DNA <1000 IU/ml and HIV RNA <20 copies/ml) were matched by 1:3 propensity score matching (PSM). HBV Pre-S region was amplified by nested PCR and sequenced. Tumor infiltrating lymphocytes (CD3, CD4, CD8) were quantified by immunohistochemistry (IHC). Survival outcomes (recurrence-free survival [RFS] and overall survival [OS]) were analyzed using Kaplan-Meier curves.RESULTSBaseline analysis showed higher rates of microvascular invasion (76.9% vs. 40.0%, p=0.010) and capsular invasion (30.8% vs. 8.5%, p=0.043) in the HIV/HBV-HCC group. After PSM, compared with HBV-HCC, HIV/HBV-HCC had a higher rate of RFS (hazard ratio [HR]=4.03, 95%CI 0.96-16.81; p=0.0058) and OS (HR=12.04, 95%CI 2.24-64.65; p<0.0001) were significantly worse. HIV/HBV-HCC liver tissues showed an increased frequency of Pre-S quasispecies deletion (p=0.003) and decreased intrahepatic CD4+ infiltration (tumor: p=0.01; adjacent: p=0.007). CD8+expression was lower in co-infected tumors than in HBV mono-infected tumors (p=0.039).CONCLUSIONSVirus-suppressed HIV/HBV-HCC showed a worse prognosis, with more Pre-S deletion mutants and more severe T-cell depletion observed in the liver, requiring further investigation of the mechanism.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"179 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851085","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":"Manuscript title: Cytokines Associated With Moderate and Severe Adverse Events During a Sporozoite Malaria Vaccine Trial with Controlled Human Malaria Infection.","authors":"Lauren P Jatt,Kevin M Gillespie,Phuong Van,Stephen L Hoffman,Lisa A Jackson,Sean C Murphy,James R Heath,James G Kublin","doi":"10.1093/infdis/jiaf435","DOIUrl":"https://doi.org/10.1093/infdis/jiaf435","url":null,"abstract":"Ensuring the safety and efficacy of candidate vaccines is critical. Although mechanisms underpinning protective immune responses to malaria vaccines are frequently investigated, immune responses correlating with moderate and severe adverse events are rarely examined. Here, we leverage a malaria vaccine trial with a higher-than-expected adverse event rate and frequent sampling to investigate cytokine profiles associated with adverse events. We found that Interleukin-6 was elevated on days in which individuals experienced moderate and severe adverse events. More research on immune responses associated with adverse events is warranted in order to identify biomarkers associated with systemic reactogenicity and accelerate vaccine development.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851047","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":"Epitope conservation of AZD5148, a broadly neutralizing anti-Toxin B monoclonal antibody, among diverse and global contemporary Clostridioides difficile isolates.","authors":"Kelly Ann Mahool,Emily Nguyen,Victoria Godfrey,Ann Marie Stanley,Tyler Brady,Adam Gamson,Kim Rosenthal,Justin Green,Ondrej Podlaha,Bret Sellman,Christine Tkaczyk,Vancheswaran Gopalakrishnan","doi":"10.1093/infdis/jiaf423","DOIUrl":"https://doi.org/10.1093/infdis/jiaf423","url":null,"abstract":"BACKGROUNDC. difficile Toxin B is a virulence factor for C. difficile infections (CDI), and a clinically validated target for prevention of CDI recurrence. AZD5148 is a Toxin B neutralizing human monoclonal antibody that binds to an epitope on the Toxin B glucosyltransferase domain. Herein, we aim to evaluate the conservation of this binding epitope using a collection of 9,134 global C. difficile genomes obtained from a public repository to confirm that residues that are crucial for neutralization are conserved.METHODSUsing isolates collected between 2015-2023 from two independent sources, we performed variant calling, sequence typing and phylogenetic analysis. We tested in vitro neutralization of cytotoxicity by AZD5148 using two different cell-lines.RESULTSHerein, we showed that the AZD5148 epitope is highly conserved across all geographic regions and sequence types (STs) and has a higher average conservation frequency in its binding site (99.58%) when compared to bezlotoxumab (82.47%). AZD5148 also exhibited broad neutralization in vitro against 8 recently circulating ribotypes.CONCLUSIONSOur comprehensive analysis of global sequences found the AZD5148 epitope to be highly conserved, and thus unlikely to be impacted by most of the genotypic variations in recently circulating C. difficile ribotypes and STs.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851208","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}