The Journal of Infectious Diseases最新文献_第9页

Emergence of ceftriaxone-resistant Neisseria gonorrhoeae through horizontal gene transfer among Neisseria spp 耐头孢曲松淋病奈瑟菌在奈瑟菌属间的水平基因转移

The Journal of Infectious Diseases Pub Date : 2025-01-08 DOI: 10.1093/infdis/jiaf008

Ken Shimuta, Yuki Ohama, Shin Ito, Shinji Hoshina, Hideyuki Takahashi, Gene Igawa, Misato Dorin Yamamoto, Yukihiro Akeda, Makoto Ohnishi

{"title":"Emergence of ceftriaxone-resistant Neisseria gonorrhoeae through horizontal gene transfer among Neisseria spp","authors":"Ken Shimuta, Yuki Ohama, Shin Ito, Shinji Hoshina, Hideyuki Takahashi, Gene Igawa, Misato Dorin Yamamoto, Yukihiro Akeda, Makoto Ohnishi","doi":"10.1093/infdis/jiaf008","DOIUrl":"https://doi.org/10.1093/infdis/jiaf008","url":null,"abstract":"Objectives It has been suggested that the emergence of ceftriaxone-resistant strains of Neisseria gonorrhoeae involves the incorporation of the penA gene from commensal Neisseria spp. that are resistant to ceftriaxone. However, the mechanism of this mosaic penA generation is unknown. Methods We obtained 10 strains of commensal Neisseria spp. showing ceftriaxone MIC &gt;0.5 mg/L. The similarity of the penA gene region of these commensal Neisseria spp. strains and some ceftriaxone-resistant N. gonorrhoeae strains was investigated. To obtain transformants, commensal Neisseria spp., Neisseria lactamica, gDNA was used as donor DNA and a N. gonorrhoeae strain as the recipient. Results The sequence similarity in certain regions of penA-murE between some of the commensal Neisseria spp. strains and the N. gonorrhoeae FC428 strain was very high. The sequence of these regions was very similar among some ceftriaxone-resistant strains of Neisseria spp. The PenA of the transformants matched the full PenA 60 of the original FC428 strain. Furthermore, our findings indicated that the source of resistance could have been a penA fragment derived from Neisseria spp. that originally carried the same sequence. Conclusions We suggest that FC428 developed ceftriaxone resistance by acquiring part of the penA–murE gene region from N. lactamica through horizontal gene transfer. The ceftriaxone-resistant N. lactamica shown here may also have emerged by acquiring part of penA from other Neisseria spp. From this work, our data provide insights into the understanding of the mechanism underlying the evolution of drug-resistant gonorrhea-causing strains.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936833","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}

引用次数: 0

High dose inactivated influenza vaccine inconsistently improves heterologous antibody responses in an elderly human cohort 高剂量灭活流感疫苗在老年人队列中不一致地改善异源抗体反应

The Journal of Infectious Diseases Pub Date : 2025-01-07 DOI: 10.1093/infdis/jiaf003

W Zane Billings, Yang Ge, Jessica H Knight, Hayley Hemme, Savannah M Hammerton, Amanda L Skarlupka, Wangnan Cao, Ye Shen, Justin Bahl, Paul G Thomas, Ted M Ross, Andreas Handel

{"title":"High dose inactivated influenza vaccine inconsistently improves heterologous antibody responses in an elderly human cohort","authors":"W Zane Billings, Yang Ge, Jessica H Knight, Hayley Hemme, Savannah M Hammerton, Amanda L Skarlupka, Wangnan Cao, Ye Shen, Justin Bahl, Paul G Thomas, Ted M Ross, Andreas Handel","doi":"10.1093/infdis/jiaf003","DOIUrl":"https://doi.org/10.1093/infdis/jiaf003","url":null,"abstract":"Background Older adults often mount a weak immune response to standard inactivated influenza vaccines. To induce a stronger response and better protection, a high-dose (HD) version of the inactivated Fluzone vaccine is recommended for individuals &gt;65 years of age. While better immunogenicity and protection against the vaccine strain has been shown, it is not known if the HD vaccine also induces a robust antibody response to heterologous strains. Methods We fit bayesian multilevel regression models to hemagglutination inhibition (HAI) antibody data from an influenza vaccine cohort spanning the 2013/14-2021/22 influenza seasons. We used this model to estimate the average causal effect (ACE) of obtaining the HD vaccine, relative to the SD vaccine. Results We show that while there is generally a benefit derived from the HD vaccine, the impact is small and inconsistent. For some strains, the HD vaccine might even result in less robust heterologous responses. Conclusions We suggest that further increases in dose might be worth investigating to help induce a stronger broad response.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935936","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}

引用次数: 0

Cobalt chloride-mimicked hepatocyte cell hypoxia induces TREX1 leading to Hepatitis B virus restriction 氯化钴模拟肝细胞细胞缺氧诱导TREX1导致乙型肝炎病毒限制

The Journal of Infectious Diseases Pub Date : 2025-01-07 DOI: 10.1093/infdis/jiaf002

Rodolphe Suspène, Vincent Caval, Pierre Khalfi, Emmanuelle Pitré, Agnès Marchio, Pascal Pineau, Jean-Pierre Vartanian

{"title":"Cobalt chloride-mimicked hepatocyte cell hypoxia induces TREX1 leading to Hepatitis B virus restriction","authors":"Rodolphe Suspène, Vincent Caval, Pierre Khalfi, Emmanuelle Pitré, Agnès Marchio, Pascal Pineau, Jean-Pierre Vartanian","doi":"10.1093/infdis/jiaf002","DOIUrl":"https://doi.org/10.1093/infdis/jiaf002","url":null,"abstract":"Background Restriction factors are host cell proteins that play a role in limiting virus replication. They form part of the intrinsic immune system and function as a first line of defense against viral infections. Hepatitis B virus (HBV) does not escape this rule and TREX1, a host restriction enzyme acts as an antiviral factor, leading to the inhibition of the virus. Methods TREX1-expressing constructs were generated and modified by site-directed mutagenesis. The location and activity of the different TREX1 constructs were analyzed by Immunofluorescence and FACS. HepaD38 cells were either transfected or transduced with the different TREX1 constructs in presence or absence of cobalt chloride-mimicked hypoxia and released HBV was quantified by qPCR. Results We identified TREX1 as a restriction factor that suppresses HBV replication. Furthermore, TREX1 expression was increased in the presence of cobalt chloride, a chemical agent mimicking hypoxia. Thus, by treating cells with cobalt chloride, TREX1 reduced HBV replication by a factor of 2, demonstrating that under hypoxic conditions, TREX1 restricts HBV replication. Finally, an analysis of 36 HBV-infected patients with hepatocellular carcinoma revealed that TREX1 expression was inversely correlated to the HBV viral and HBV cccDNA. Conclusion Current treatments are unable to eliminate HBV genomic reservoirs, which persist as covalently closed episomal circular DNA. TREX1 is a novel restriction factor that blocks HBV replication. It would be therapeutically relevant to study whether HBV nucleocapsid recycling containing TREX1 enzyme could be released into the nucleus and degrade the viral and nuclear DNA of infected cells.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935146","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}

引用次数: 0

Distinguishing Multisystem Inflammatory Syndrome in Children from Typhus Using Artificial Intelligence: MIS-C vs. Endemic Typhus (AI-MET) 应用人工智能鉴别儿童斑疹伤寒多系统炎症综合征：MIS-C与地方性斑疹伤寒（AI-MET）

The Journal of Infectious Diseases Pub Date : 2025-01-07 DOI: 10.1093/infdis/jiaf004

Angela Chun, Abraham Bautista-Castillo, Isabella Osuna, Kristiana Nasto, Flor M Munoz, Gordon E Schutze, Sridevi Devaraj, Eyal Muscal, Marietta M de Guzman, Kristen Sexson Tejtel, Tiphanie P Vogel, Ioannis A Kakadiaris

{"title":"Distinguishing Multisystem Inflammatory Syndrome in Children from Typhus Using Artificial Intelligence: MIS-C vs. Endemic Typhus (AI-MET)","authors":"Angela Chun, Abraham Bautista-Castillo, Isabella Osuna, Kristiana Nasto, Flor M Munoz, Gordon E Schutze, Sridevi Devaraj, Eyal Muscal, Marietta M de Guzman, Kristen Sexson Tejtel, Tiphanie P Vogel, Ioannis A Kakadiaris","doi":"10.1093/infdis/jiaf004","DOIUrl":"https://doi.org/10.1093/infdis/jiaf004","url":null,"abstract":"Background The pandemic emergent disease multisystem inflammatory syndrome in children (MIS-C) following coronavirus disease-19 infection can mimic endemic typhus. We aimed to use artificial intelligence (AI) to develop a clinical decision support system that accurately distinguishes MIS-C versus Endemic Typhus (MET). Methods Demographic, clinical, and laboratory features rapidly available following presentation were extracted for 133 patients with MIS-C and 87 patients hospitalized due to typhus. An attention module assigned importance to inputs used to create the two-phase AI-MET. Phase 1 uses 17 features to arrive at a classification manually (MET-17). If the confidence level is not surpassed, 13 additional features are added to calculate MET-30 using a recurrent neural network. Results While 24 of 30 features differed statistically, the values overlapped sufficiently that the features were clinically irrelevant distinguishers as individual parameters. However, AI-MET successfully classified typhus and MIS-C with 100% accuracy. A validation cohort of 111 additional patients with MIS-C was classified with 99% accuracy. Conclusions Artificial intelligence can successfully distinguish MIS-C from typhus using rapidly available features. This decision support system will be a valuable tool for front-line providers facing the difficulty of diagnosing a febrile child in endemic areas.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935149","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}

引用次数: 0

Helminth infection induces innate immune priming in plasmacytoid dendritic cells 蠕虫感染诱导浆细胞样树突状细胞的先天免疫启动

The Journal of Infectious Diseases Pub Date : 2025-01-07 DOI: 10.1093/infdis/jiaf009

Lamin B Cham, Bradley Whitehead, Marvin Werner, Frederikke Jensen, Mads Zippor, Trine H Mogensen, Mihai G Netea, Andrew R Williams, Peter Nejsum

引用次数: 0

Phage-Encoded Virulence Factor, Gp05, Alters Membrane Phospholipids and Reduces Antimicrobial Susceptibility in Methicillin-Resistant Staphylococcus aureus 噬菌体编码毒力因子Gp05改变膜磷脂并降低耐甲氧西林金黄色葡萄球菌的抗菌敏感性

The Journal of Infectious Diseases Pub Date : 2024-12-31 DOI: 10.1093/infdis/jiae640

Yi Li, Nagendra N Mishra, Liang Chen, Adhar C Manna, Ambrose L Cheung, Richard A Proctor, Yan Q Xiong

{"title":"Phage-Encoded Virulence Factor, Gp05, Alters Membrane Phospholipids and Reduces Antimicrobial Susceptibility in Methicillin-Resistant Staphylococcus aureus","authors":"Yi Li, Nagendra N Mishra, Liang Chen, Adhar C Manna, Ambrose L Cheung, Richard A Proctor, Yan Q Xiong","doi":"10.1093/infdis/jiae640","DOIUrl":"https://doi.org/10.1093/infdis/jiae640","url":null,"abstract":"Background Methicillin-resistant Staphylococcus aureus (MRSA) is a leading pathogen causing severe endovascular infections. The prophage-encoded protein Gp05 has been identified as a critical virulence factor that contributes to MRSA persistence during vancomycin (VAN) treatment in an experimental endocarditis model. However, the underlining mechanisms driving this persistence phenotype remain poorly understood. Methods The current study aimed to elucidate the genetic factors contributing to Gp05-associated MRSA persistence by utilizing RNA sequencing (RNA-seq) on an isogenic MRSA strain set, including a clinical persistent bacteremia isolate (PB 300-169), its isogenic chromosomal gp05 deletion mutant, and gp05-complemented strains. Results RNA-seq analysis revealed significantly downregulation of the graSR-vraFG regulatory system and its downstream genes, mprF and dltABCD, in the gp05 deletion mutant compared to the wild-type and gp05-complemented strains. Notably, this downregulation led to a substantial shift in cell membrane composition, with a marked increase in negatively charged phosphatidylglycerol (PG) and a concomitant decrease in positively charged lysyl-PG (LPG). These changes in membrane lipid composition resulted in increased susceptibility of the gp05 deletion mutant to human cationic antimicrobial peptide (CAMP) LL-37, polymorphonuclear neutrophil (PMN) and VAN. Similar findings were observed in an isogenic gp05 overexpression strain set with different genetic background (MRSA USA300 JE2). Conclusions These findings suggest that Gp05 plays a pivotal role in MRSA persistence by modulating cell surface components and surface charge. This study provides new insights into the molecular mechanisms underlying Gp05-mediated persistence in MRSA endovascular infections and highlights potential therapeutic targets to combat persistent MRSA infections.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908298","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}

引用次数: 0

A core glycolipid vaccine elicits cross-reactive antibodies against Salmonella spp. and protects against invasive nontyphoidal Salmonella disease in mice 一种核心糖脂疫苗可诱导抗沙门氏菌交叉反应抗体，并保护小鼠免受侵袭性非伤寒沙门氏菌病的侵袭

The Journal of Infectious Diseases Pub Date : 2024-12-31 DOI: 10.1093/infdis/jiae641

Scott M Baliban, Surekha Shridhar, Kun Luo, Jacqueline Kolasny, Sang Hyun, Zhiyong Zhao, Sharon M Tennant, Alan S Cross

{"title":"A core glycolipid vaccine elicits cross-reactive antibodies against Salmonella spp. and protects against invasive nontyphoidal Salmonella disease in mice","authors":"Scott M Baliban, Surekha Shridhar, Kun Luo, Jacqueline Kolasny, Sang Hyun, Zhiyong Zhao, Sharon M Tennant, Alan S Cross","doi":"10.1093/infdis/jiae641","DOIUrl":"https://doi.org/10.1093/infdis/jiae641","url":null,"abstract":"Background Enteric fever caused by Salmonella enterica serovars Typhi and Paratyphi A in addition to gastroenteritis and invasive disease, predominantly attributable to nontyphoidal Salmonella serovars Typhimurium and Enteritidis, are major causes of death and disability across the globe. A broad-spectrum vaccine that protects against disease caused by typhoidal and nontyphoidal serovars of Salmonella is not available for humans but would prevent a considerable burden of disease worldwide. Methods We previously developed a broad-spectrum vaccine for Gram-negative bacteria that is based on the inner core domain of detoxified Escherichia coli O111, Rc (J5) mutant lipooligosaccharide, a highly conserved antigen across Gram-negative bacteria, complexed with an outer membrane protein of group B Neisseria meningitidis. In this study, mice and rabbits were immunized with the J5 core/outer membrane protein subunit vaccine. We assessed the cross-reactivity of antisera with various Salmonella species lipopolysaccharides and the protective efficacy of passive and active immunization with J5 vaccine against experimental nontyphoidal Salmonella infection in mice. Results Vaccination with J5 induced IgG responses that strongly recognized lipopolysaccharide from both typhoidal and nontyphoidal Salmonella and imparted a survival benefit against lethal heterologous challenges with S. Typhimurium and S. Enteritidis. Additionally, passive transfer studies with rabbit hyperimmune sera raised against the J5 vaccine revealed that anti-core antibodies were protective against lipopolysaccharide challenge in D-galactosamine-sensitized mice. Conclusions Our findings support the development of core glycolipids as a novel Salmonella vaccine candidate. Further investigation is warranted to determine the efficacy of the J5 core/outer membrane protein vaccine against other Salmonella serovars of concern.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908407","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}

引用次数: 0

Combined Sequential Antiretroviral Therapy-Induced Immune Reconstitution Bone Loss and Estrogen Deficiency Bone Loss are Cumulative in Mice Models 联合序贯抗逆转录病毒治疗诱导的免疫重建骨质流失和雌激素缺乏骨质流失在小鼠模型中是累积性的

The Journal of Infectious Diseases Pub Date : 2024-12-27 DOI: 10.1093/infdis/jiae643

Sadaf Dabeer, Ashish Kumar Tripathi, Daiana Weiss, Tatyana Vikulina, Ighovwerha Ofotokun, M Neale Weitzmann

{"title":"Combined Sequential Antiretroviral Therapy-Induced Immune Reconstitution Bone Loss and Estrogen Deficiency Bone Loss are Cumulative in Mice Models","authors":"Sadaf Dabeer, Ashish Kumar Tripathi, Daiana Weiss, Tatyana Vikulina, Ighovwerha Ofotokun, M Neale Weitzmann","doi":"10.1093/infdis/jiae643","DOIUrl":"https://doi.org/10.1093/infdis/jiae643","url":null,"abstract":"Background Antiretroviral therapy (ART) causes osteoporosis and bone fractures, increasing morbidity and mortality in people living with HIV (PLH). ART induces immune reconstitution bone loss (IRBL), an inflammatory reaction associated with immune system reactivation. Women represent &gt;50% of PLH, and many are now undergoing menopause, a major cause of postmenopausal osteoporosis that also increases fracture risk. However, the interactions between IRBL and postmenopausal bone loss are poorly understood and were investigated in this study. Methods We used a mouse model of IRBL, applied simultaneously or sequentially with surgical ovariectomy (Ovx), a mouse model of postmenopausal osteoporosis. Cortical and trabecular bone in vertebrae and femurs was assessed using micro-computed tomography (µCT) and bone turnover quantified by serum markers of bone resorption and formation via ELISA. T cell production of osteoclastogenic cytokines was analyzed by flow cytometry. Results Although simultaneous Ovx and IRBL did not have additive effects, sequential Ovx and IRBL caused cumulative bone loss. Vertebral bone loss from combined Ovx and IRBL (Δ=-42.6 vs. Control: p&lt;0.01) was significantly reduced by the anti-inflammatory agent Abatacept (Δ=-13.9 vs. Control: p=not significant) and the probiotic Lactobacillus rhamnosus GG (LGG) (Δ=-8.6 vs. Control: p=not significant). Both treatments reduced bone resorption, stimulated formation, and suppressed CD4+ T cell production of the osteoclastogenic cytokines TNF-α and IL-17A. Conclusion Sequential IRBL and postmenopausal bone loss appear to be cumulative. If validated in humans, early screening and prophylaxis could reduce fracture risk in postmenopausal women living with HIV (WLH). Probiotic therapy may provide a beneficial alternative to pharmacotherapy.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887693","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}

引用次数: 0

Plasma Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Biomarkers of Cognitive Decline in People Living with HIV 血浆神经丝轻链和胶质纤维酸性蛋白作为HIV感染者认知能力下降的生物标志物

The Journal of Infectious Diseases Pub Date : 2024-12-26 DOI: 10.1093/infdis/jiae623

Shibani S Mukerji, Petra Bachanová, Hemi Park, Linzy V Rosen, Rommi Kashlan, Pia Kivisäkk, Albert M Anderson, Felicia C Chow, Kunling Wu, Raha M Dastgheyb, Leah H Rubin, Katherine Tassiopoulos, Robert A Parker, Emily P Hyle

{"title":"Plasma Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Biomarkers of Cognitive Decline in People Living with HIV","authors":"Shibani S Mukerji, Petra Bachanová, Hemi Park, Linzy V Rosen, Rommi Kashlan, Pia Kivisäkk, Albert M Anderson, Felicia C Chow, Kunling Wu, Raha M Dastgheyb, Leah H Rubin, Katherine Tassiopoulos, Robert A Parker, Emily P Hyle","doi":"10.1093/infdis/jiae623","DOIUrl":"https://doi.org/10.1093/infdis/jiae623","url":null,"abstract":"Background This study examined the relationship between neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) and cognition in people living with HIV (PLWH) at baseline and over time. Methods Plasma and clinical data were available from PLWH aged ≥45 years with HIV RNA &lt;200 copies/mL enrolled in the AIDS Clinical Trials Group HAILO cohort study. We measured plasma NfL and GFAP using a single molecule array platform. Four neuropsychological assessments, standardized to z-scores and averaged (NPZ-4), were used as a marker of cognitive function. Date of plasma collection marked study baseline; longitudinal changes in NPZ-4 were summarized by slope. Linear regressions between biomarkers and baseline NPZ-4 were adjusted for demographic factors. Regressions of longitudinal data were adjusted for baseline NPZ-4 and weighted by number of visits. Results The study included 503 participants with a median [IQR] age of 52 [48, 57] years, observation of 6 [5, 7] years, and 26% had baseline cognitive impairment defined by HAILO. Cross-sectionally, higher NfL (β=-0.76, p&lt;0.01) and GFAP (β=-0.44, p=0.02) were associated with worse baseline NPZ-4. Longitudinally, the median [IQR] NPZ-4 slope was 0.003 [-0.06, 0.06] units/year with 48% demonstrating cognitive decline (slope&lt;0). Higher NfL (β=-0.08, p&lt;0.01), but not GFAP (β=-0.03, p=0.08), was associated with cognitive decline. Conclusions NfL and GFAP were associated with worse cognition cross-sectionally; only NfL was associated with longitudinal cognitive decline. However, the clinical utility of NfL and GFAP is uncertain given small effect sizes and should be studied in populations with more rapid decline (e.g., aged ≥60).","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"114 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887690","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}

引用次数: 0

Pre-HIV α4β7hi CD4+ T cells and HIV risk among heterosexual individuals in Africa 非洲异性恋者HIV前α4β7hi CD4+ T细胞与HIV风险

The Journal of Infectious Diseases Pub Date : 2024-12-25 DOI: 10.1093/infdis/jiae638

Tosin E Omole, Huong Mai Nguyen, Agata Marcinow, Myo Minn Oo, Naima Jahan, Aloysious Ssemaganda, Giulia Severini, Katherine K Thomas, Connie Celum, Nelly Mugo, Andrew Mujugira, James Kublin, Lawrence Corey, Aida Sivro, Jairam R Lingappa, Glenda Gray, Lyle R McKinnon

{"title":"Pre-HIV α4β7hi CD4+ T cells and HIV risk among heterosexual individuals in Africa","authors":"Tosin E Omole, Huong Mai Nguyen, Agata Marcinow, Myo Minn Oo, Naima Jahan, Aloysious Ssemaganda, Giulia Severini, Katherine K Thomas, Connie Celum, Nelly Mugo, Andrew Mujugira, James Kublin, Lawrence Corey, Aida Sivro, Jairam R Lingappa, Glenda Gray, Lyle R McKinnon","doi":"10.1093/infdis/jiae638","DOIUrl":"https://doi.org/10.1093/infdis/jiae638","url":null,"abstract":"Background CD4+ T cells expressing α4β7 are optimal targets for HIV infections, with higher pre-HIV α4β7hi expression linked to increased HIV acquisition and progression in South African women. However, similar associations were not observed in men who have sex with men (MSM) or people who inject drugs (PWID) in the Americas, indicating need for further research. Methods This retrospective case-control study enrolled heterosexual men and women from South Africa (HIV Vaccine Trials Network; HVTN 503) and East Africa (Partners Pre-Exposure Prophylaxis/Couples’ Observational Study; PP/COS), quantifying α4β7 expression on CD4+ T cells as a predictor of subsequent HIV risk using flow cytometry analyses. Results Associations between α4β7hi expression and HIV acquisition varied across cohorts. In HVTN 503, women had a higher risk estimate compared to men, but this was not significant. In PP/COS, α4β7hi expression was generally protective, particularly in Ugandans. Additionally, α4β7hi expression inversely correlated with peak viral load in PP/COS but not in HVTN 503; in the latter cohort, α4β7hi expression was inversely correlated with the CD4/CD8 ratio and predicted rapid CD4+ T cell decline, similar to what was observed previously in South Africa. Conclusions These findings suggest that α4β7hi expression on CD4+ T cells may not predict HIV acquisition and progression in all contexts, which may be due to cohort effects, modes of transmission, viral clade, or other factors.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884137","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}

引用次数: 0