Journal of Infectious Diseases最新文献

{"title":"Widespread variants of the highly polymorphic Plasmodium falciparum vaccine candidate antigen MSP2 across Sub-Saharan Africa.","authors":"Julia Zerebinski, Ioanna Broumou, Kelvin M Kimenyi, Eleni Aklillu, Carolina M Andrade, Hamza Babiker, Philip Bejon, Mariama K Cherif, Peter D Crompton, Cláudia Fançony, Fariba Foroogh, José Pedro Gil, Manijeh Vafa Homann, Maria de Jesus Trovoada, Melissa Kapulu, Steven M Kiwuwa, Margaret A Kweku, Anne Liljander, Dinora Lopes, Kevin Marsh, Doreen D Mutemi, Billy Ngasala, Johan Normark, Judy Orikiiriza, Kristina E M Persson, Silvia Portugal, Ulf Ribacke, Sodiomon B Sirima, Klara Sondén, Taís N de Sousa, Boubacar Traore, Muyideen K Tijani, Nils Eckerdal, Pär Villner, L Isabella Ochola-Oyier, David F Plaza, Anna Färnert","doi":"10.1093/infdis/jiag377","DOIUrl":"https://doi.org/10.1093/infdis/jiag377","url":null,"abstract":"<p><strong>Background: </strong>A multicomponent vaccine is increasingly recognized as a necessary tool to control and eliminate malaria globally. However, genetic diversity in Plasmodium falciparum poses a significant challenge, particularly for blood-stage antigens associated with protective immunity. Individuals in endemic regions acquire clinical immunity without exposure to all antigenic variants, suggesting that a deeper understanding of antigen diversity could inform more effective vaccine strategies.</p><p><strong>Methods: </strong>The genetic diversity of the polymorphic gene locus for merozoite surface protein 2 was assessed with nested PCR and capillary electrophoresis fragment sizing in P. falciparum isolates from 34 countries across Sub-Saharan Africa. High fidelity long-read sequencing was used to investigate sequence diversity within msp2 variants.</p><p><strong>Results: </strong>We successfully genotyped msp2 from 2761 P. falciparum-positive samples using capillary electrophoresis, identifying 412 distinct msp2 size variants. Several msp2 size variants were consistently overrepresented across geographical regions, transmission intensities, and time points. These variants comprised multiple unique sequences, of which several were geographically and temporally widespread. Nucleotide and amino acid sequences showed high diversity without geographical clustering.</p><p><strong>Conclusions: </strong>This study provides a comprehensive assessment of msp2 diversity across Sub-Saharan Africa. The widespread prevalence of certain variants of this highly polymorphic antigen suggests possible structural constraints or selective advantages for the parasite. Maintenance of specific gene lengths and sequences across diverse settings highlights their potential as targets for next-generation, multicomponent malaria vaccines.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551246","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}

{"title":"Monitoring HLA-A2-restricted T cell responses and BCLA-specific serostatus during human latent Toxoplasma gondii infection suggests the implication of CD8+ T cells in parasite containment.","authors":"Raphaëlle Romieu-Mourez, Pierre Emmanuel Paulet, Emilie Bassot, Arthur Palak, Thomas Carvaillo, Léa Dépéry, Marie Gladys Robert, Xavier Iriart, Judith Fillaux, Antoine Berry, Mohamed-Ali Hakimi, Nicolas Blanchard","doi":"10.1093/infdis/jiag333","DOIUrl":"https://doi.org/10.1093/infdis/jiag333","url":null,"abstract":"<p><strong>Background: </strong>T cells are critical to control Toxoplasma gondii (T. gondii) parasite infection. Yet, our understanding of T. gondii-specific CD8+ T cell responses in humans remains scarce. Here, we studied 56 HLA-A2+ healthy blood donors, including 40 latently infected subjects.</p><p><strong>Methods: </strong>In addition to routine T. gondii serodiagnosis, we quantified IgG specific for the bradyzoite-restricted Brain Cyst Load-associated Antigen (BCLA) and we enumerated blood-circulating parasite-specific CD8+ T cells by IFN-γ ELISPOT using a panel of 29 T. gondii peptides, previously reported to be HLA-A2 ligands.</p><p><strong>Results: </strong>We identified a set of 16 epitopes that stimulates detectable CD8+ T cell responses in 50% routine T. gondii seropositive subjects, yet none was a universal immunodominant T. gondii epitope. Among individuals with either positive BCLA-specific serology and/or detectable T. gondii-specific T cell response, T. gondii-specific ELISPOT responses were inversely correlated with BCLA-specific IgG titers, suggesting that stronger CD8+ T cell responses may contribute to reduce chronic parasite burden or that certain long-standing infections may result in waning of antibody levels but persistence of CD8+ T cell memory. Furthermore, 2 out of 56 subjects displayed null T. gondii-specific humoral responses across 4 serological assays, but had measurable CD8+ T cell responses to 2 T. gondii peptides.</p><p><strong>Conclusions: </strong>This study sheds light on the complexity of T. gondii-specific immune responses in humans and rationalizes the cellular and serological toolkits for immune monitoring of latent T. gondii infection in humans.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148363798","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}

{"title":"Optimizing the Use of Proviral DNA HIV Drug Resistance Testing: Clinical Applications and Cautions.","authors":"Lillian Seo, Roger Paredes, Rami Kantor","doi":"10.1093/infdis/jiag340","DOIUrl":"https://doi.org/10.1093/infdis/jiag340","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148363807","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}

{"title":"A comparative analysis of the immunotranscriptomic features of DENV-1, -3, and -4 human challenge models.","authors":"Céline S C Hardy, Lisa A Ware, Heather Friberg, Joel V Chua, Kirsten E Lyke, Stephen J Thomas, Adam T Waickman","doi":"10.1093/infdis/jiag338","DOIUrl":"10.1093/infdis/jiag338","url":null,"abstract":"<p><strong>Background: </strong>Dengue virus (DENV) infections cause a range of clinical symptoms, from a mild febrile illness to severe disease. Higher levels of DENV RNAemia are associated with severe dengue, although this relationship is incompletely understood. Dengue Human Infection Models (DHIMs), in which volunteers are experimentally infected with underattenuated DENV strains, provide an invaluable tool for studying early virologic, transcriptional, and immunologic features of infection. DHIM studies using DENV-1, DENV-3, and DENV-4 have demonstrated qualitatively distinct clinical features, however, the contribution of RNAemia and serotype to divergent transcriptional and clinical profiles in these challenge models remains unclear.</p><p><strong>Methods: </strong>In this work, we performed a comparative analysis of DHIM-1, DHIM-3, and DHIM-4 studies to determine shared and unique features of the transcriptional response to infection and their associations with RNAemia and clinical symptoms. We then exposed primary human PBMC in vitro to DENV-1 or DENV-3 at varying titers and performed bulk RNA sequencing.</p><p><strong>Results: </strong>Across DHIMs, we identified a set of conserved, upregulated genes at day of peak RNAemia, representing a core antiviral response independent of serotype. Further, a unique gene signature indicating downregulated cytoplasmic translation emerged in a subset of DHIM-3 participants with elevated RNAemia and symptomatology. In vitro PBMC exposure to DENV demonstrated that conserved and unique gene expression signatures varied as a function of viral dose rather than serotype.</p><p><strong>Conclusions: </strong>These data show that viral burden correlates with transcriptional responses and clinical symptomatology following experimental DENV infection, contributing to our understanding of dengue pathogenesis and immunity.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148341023","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}

{"title":"CMV IgG and EBV Cell-Associated DNA Independently Associate With Veterans Aging Cohort Study (VACS) Index 2.0 Scores in People With HIV on Antiretroviral Therapy.","authors":"Patricia K Riggs, Gordon Honerkamp-Smith, Milenka Meneses, Gemma Caballero, Antoine Chaillon, Donald Franklin, Ronald J Ellis, Scott L Letendre, Sara Gianella","doi":"10.1093/infdis/jiag310","DOIUrl":"https://doi.org/10.1093/infdis/jiag310","url":null,"abstract":"<p><strong>Background: </strong>People with HIV (PWH) are at increased risk for non-AIDS comorbidities despite suppressive antiretroviral therapy (ART). Chronic co-infections with Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) may contribute to systemic immune activation and comorbidities, but the relative contribution of viral activity versus host immune response is unclear.</p><p><strong>Methods: </strong>We evaluated associations between viral measures and the Veterans Aging Cohort Study (VACS) Index 2.0, a validated 5-year mortality risk score for PWH. Plasma CMV and EBV IgG were quantified by ELISA, and CMV, EBV, and HIV cell-associated DNA (CA-DNA) was measured in peripheral blood mononuclear cells by ddPCR. Total globulin levels were abstracted from clinical panels as a marker of generalized immune activation. Regression models were adjusted for sex, race, ethnicity, HIV duration, and history of AIDS.</p><p><strong>Results: </strong>Among 485 ART-suppressed PWH (mean age 54 years; 17% women; 59% White), 96.5% were CMV-seropositive, 100% EBV-seropositive, CMV CA-DNA was detected in 45.9%, EBV in 95.4%, and HIV in 99.0%. Higher VACS scores were associated with higher CMV IgG, EBV IgG, EBV CA-DNA, HIV CA-DNA, and total globulin in adjusted models. In multivariable models, CMV IgG, EBV CA-DNA, and total globulins remained independently associated with VACS 2.0. HIV CA-DNA and sex were retained in the best-fit model with trend level significance.</p><p><strong>Conclusion: </strong>These findings suggest distinct mechanisms by which CMV, EBV and HIV may contribute to morbidity in PWH on ART: CMV through immune activation, and EBV and HIV through viral persistence. Longitudinal studies are needed to clarify causal pathways and guide interventions.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148279686","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}

{"title":"Selective Immune Tolerance: A Unifying Mechanism Linking Heavy Malaria Exposure, Waning Vaccine Antibodies, and Burkitt Lymphoma.","authors":"Jacquelyn R Bedsaul-Fryer, Sam M Mbulaiteye","doi":"10.1093/infdis/jiag312","DOIUrl":"https://doi.org/10.1093/infdis/jiag312","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148279826","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}

{"title":"Cerebrospinal fluid transcriptional immune pathways linked to survival in HIV-associated tuberculous meningitis.","authors":"Martineau Louine, Ravi Dandekar, Sumanth P Reddy, Mary C Karalius, Greer Waldrop, Shiyin Wang, Jane Gakuru, Sarah Kimuda, Timothy Mugabi, Abdu K Musubire, Enock Kagimu, Mahsa Abassi, Mable Kabahubya, Darlisha A Williams, Hoang Van Phan, Biyue Dai, Maham Zia, Kelsey C Zorn, Camille Fouassier, Chloe Gerungan, Pedro S Marra, Caleb P Skipper, Nathan C Bahr, Charles R Langelier, Fiona V Creswell, David R Boulware, David B Meya, Michael R Wilson","doi":"10.1093/infdis/jiag313","DOIUrl":"10.1093/infdis/jiag313","url":null,"abstract":"<p><strong>Background: </strong>TB meningitis (TBM) has up to 50% mortality in people living with HIV. We investigated differences in cerebrospinal fluid (CSF) host immune responses associated with short-term mortality.</p><p><strong>Methods: </strong>We enrolled a prospective cohort of adults with definite, probable and possible HIV-related TBM in Kampala, Uganda. Metagenomic next-generation sequencing (mNGS) of bulk CSF RNA was used to detect co-infecting or alternate CNS pathogens and refine cohort diagnosis. Host transcriptomic profiles from the refined cohort were then compared between 14-day survivors and non-survivors.</p><p><strong>Results: </strong>CSF mNGS reclassified or excluded 14% of participants based on pathogen detection, yielding 110 participants for transcriptomic analysis, of whom 23% (n=25) died within 14 days. More than 2000 genes were differentially expressed in the CSF based on 14-day mortality (adjusted p-value <0.05). Survivors upregulated T-cell receptor signaling (LCK, FYN, LAT), T-cell survival and differentiation (IL7, CD27, IL12RB1), B-cell receptor signaling (CD81, PLCG2, TNFRSF13C), cytotoxic lymphocyte and NK cell genes (KLRD1, ULBP1), TNF signaling, and class I MHC antigen processing pathways, while downregulating neutrophil chemoattractant CXCL1 and classical complement genes C4A and C4B. Unsupervised clustering identified a hypoinflammatory subgroup with significantly elevated mortality.</p><p><strong>Conclusions: </strong>Short-term TBM survival was associated with upregulation of adaptive immunity - including T-cell, B-cell, NK cell, and cytotoxic lymphocyte signaling - alongside TNF signaling and IFN-γ-driven class I MHC antigen processing pathways, with concurrent restraint of complement and neutrophil pathways. This supports investigation of targeted immunomodulatory agents that preserve protective responses while selectively dampening injurious innate pathways, rather than broad immunosuppression with corticosteroids.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CMV and EBV: a dynamic, powerful, and dangerous duo in PLWH.","authors":"Miriam Lichtner, Serena Vita","doi":"10.1093/infdis/jiag311","DOIUrl":"https://doi.org/10.1093/infdis/jiag311","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148279648","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}

{"title":"When Does Clostridioides difficile \"Recur\"? Reconcile Epidemiologic & Bedside Recurrent CDI definitions.","authors":"Sahil Khanna, Paul Feuerstadt, Jessica R Allegretti, Darrell S Pardi","doi":"10.1093/infdis/jiag307","DOIUrl":"https://doi.org/10.1093/infdis/jiag307","url":null,"abstract":"<p><p>Recurrent Clostridioides difficile infection (CDI) is a clinical syndrome, a trial endpoint, and a surveillance construct. Epidemiologic and administrative datasets count repeat positive tests or coded episodes, but conflate colonization or test of cure with recurrence. Trials operationalize recurrent CDI with symptoms, testing, but have variable follow-up. Clinically, recurrent CDI requires response, and recurrent illness excluding post-infection bowel dysfunction and mimics. Relapse and reinfection remain difficult to distinguish without strain typing which is more relevant for research. We propose a pragmatic lens: explicitly name the definition used, match it to the decision, and adjudicate clinical recurrence before escalating therapy.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148266851","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}

{"title":"Molecular phenotypes of sex and age specific differences relating to outcome in patients with Ebola virus disease.","authors":"Xiaofeng Dong, Natasha Y Rickett, Piet Maes, Robert Orr, Tracy MacGill, Todd Myers, Tom Fletcher, Miles W Carroll, Julian A Hiscox","doi":"10.1093/infdis/jiag305","DOIUrl":"https://doi.org/10.1093/infdis/jiag305","url":null,"abstract":"<p><strong>Background: </strong>Ebola virus (EBOV) causes a severe, potentially fatal, disease, with outcome likely related to both viral and host factors. There is a clear correlation between viral load and outcome (survival/death) and inflammatory as well as other cellular pathways are differentially activated in the acute stage between patients who go on to survive versus those who go on to die. Age and sex may influence the course of Ebola virus disease (EVD) with potential differences at the molecular level.</p><p><strong>Methods: </strong>To investigate whether there were age and/or sex-specific differences in patients with EVD, previously published data from an RNAseq analysis of the blood transcriptome in patients from the 2013-2016 West African outbreak was stratified according to age/sex of the individual. This was correlated with the outcome of infection.</p><p><strong>Results: </strong>Similar to the previously published data, immune responses were downregulated during the acute phase in hospitalised survivors compared to hospitalized fatal cases, regardless of the sex of the patient. However, aspects of the blood transcriptome/host response differed between females and males and certain age groups at the transcriptomic level. Genes associated with the lymphocyte differentiation pathway decreased in expression level with age in hospitalised fatal cases. However, this was the opposite in hospitalised survivors.</p><p><strong>Conclusions: </strong>From a medical countermeasure perspective, the work indicated that selection of animal models should consider age and sex, depending on the research question, and cellular pathways were identified that could be chemotherapeutically enhanced to promote survival.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148266912","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}