Journal of Infectious Diseases最新文献

{"title":"One Hundred Days, Incalculable Losses.","authors":"Emily J Erbelding","doi":"10.1093/infdis/jiaf317","DOIUrl":"https://doi.org/10.1093/infdis/jiaf317","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276494","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":"Cytolethal Distending Toxin-increased DNA damage and ploidy involve the YAP/TAZ-TEAD signaling pathway.","authors":"Ruxue Jia, Lamia Azzi-Martin, Mariana Saraiva, Elodie Sifré, Pierre Dubus, Christine Varon, Armelle Ménard","doi":"10.1093/infdis/jiaf312","DOIUrl":"https://doi.org/10.1093/infdis/jiaf312","url":null,"abstract":"<p><strong>Background: </strong>Bacterial genotoxins, CDT and colibactin, cause severe DNA damage in host cells and impair the DNA-damage response, leading to genomic instability. Some phenotypes induced by these genotoxins (actin cytoskeleton remodeling, stress fibers accumulation, disturbance of focal adhesion, cell-cell junctions' disassembly, increased ploidy and genome instability, endoreplication) are known to involve the Hippo signaling pathway, suggesting a link between some effects induced by these toxins and Hippo pathway.</p><p><strong>Methods: </strong>We investigated the Hippo signaling pathway in normal and cancer-derived epithelial intestinal and hepatic cell lines following intoxication with CDT/CdtB and colibactin.</p><p><strong>Results: </strong>We have shown that active CdtB subunit of CDT modulates the expression of transcripts and proteins of the Hippo downstream central transcriptional coactivators YAP/TAZ. CdtB exposure drove increased TEAD-mediated transcription confirmed by the upregulation of direct TEAD target genes. Inhibition of the YAP/TAZ binding to TEADs (verteporfin and K-975) dampened the effects of CdtB, particularly DNA damage and repair, and increased ploidy. These findings suggest that YAP/TAZ-TEAD signaling is involved in increased ploidy in cells surviving the DNA damage induced by CDT/CdtB. In addition, exposure to colibactin, a genotoxic metabolite produced by Escherichia coli, induced similar effects.</p><p><strong>Conclusions: </strong>Overall, these data show that infection with genotoxin-producing bacteria involves the YAP/TAZ-TEAD signaling pathway to control ploidy following DNA damage in epithelial cells.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276493","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":"Decrease in Incidence of Diarrhea Due to Cryptosporidium in Bangladeshi Children Is Associated With an Increase in Anti-Cryptosporidium Antibody Avidity.","authors":"Carol A Gilchrist, William A O Petri, Biplob Hossain, Mamun Kabir, Hannah H So, G Brett Moreau, Uma Nayak, Jennie Z Ma, Zannatun Noor, Abu S G Faruque, Masud Alam, Rashidul Haque, William A Petri","doi":"10.1093/infdis/jiaf253","DOIUrl":"https://doi.org/10.1093/infdis/jiaf253","url":null,"abstract":"<p><strong>Background: </strong>Cryptosporidium is a cause of diarrhea morbidity and mortality in infants in low- and middle-income countries.</p><p><strong>Methods: </strong>A cohort of children was followed longitudinally in a high-transmission-intensity community in Bangladesh.</p><p><strong>Results: </strong>Diarrhea attributed to Cryptosporidium (cryptosporidiosis) decreased from a peak of 0.19 episodes per child at 1-2 years to 0.05 episodes per child at 3-4 years of age (P = .0064). Notably, the decrease in cryptosporidiosis was not accompanied by a decline in subclinical infections. Using an episode-based analysis confirmed that the parasite burden declined with repeated infections (P < .0001 from the mixed-effects model included data from all infection frequencies; Cq value of the first and fourth infections (last reinfection with >10 cases): Cq 28.65 ± 5.533 versus 32.42 ± 4.046). There was also a decrease in the time required to clear a parasitic infection: longer infections (>1 month) occurred in 43% of the first infections compared to 24% in the fourth infections (P = .00017 from the mixed-effects model). The avidity of anti-Cp23 and anti-Cp17 plasma IgG increased in older children who had fewer diarrheal infections (ratio of the avidity index after the first infection versus that in the older repeatedly infected children: 1.81 ± 1.02 for anti-Cp23 IgG P > .0001 and 1.14 ± 0.35 anti-Cp17 IgG P = .0056).</p><p><strong>Conclusions: </strong>Our results are consistent with the development of an anti-Cryptosporidium adaptive immune response over repeated infections (average number of previous infections at 4 years, 2.42 ± 1.24) characterized by an increase in anti-Cryptosporidium antibody avidity that is associated with a decrease in cryptosporidiosis but not in subclinical Cryptosporidium infections. Clinical Trials Registration. NCT02764918.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250612","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":"Mitochondrial DNA Haplogroups, Biomarkers of Inflammation and Immune Activation, and Risk of Diabetes in Veterans with and without HIV.","authors":"Aiwei Yan, Suman Kundu, David C Samuels, Samuel Bailin, Ke Xu, Kaku So-Armah, Adeel A Butt, Mariana Gerschenson, Matthew Bidwell Goetz, Margaret Doyle, Russell Tracy, Vincent C Marconi, Amy Justice, Matthew Freiberg, John R Koethe, Todd Hulgan","doi":"10.1093/infdis/jiaf304","DOIUrl":"https://doi.org/10.1093/infdis/jiaf304","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (DM) is common among people with HIV (PWH). We previously reported that DM risk was greater in women of African ancestry with HIV who had mitochondrial DNA (mtDNA) haplogroup L3. We examined haplogroup associations with DM and selected soluble and cellular immune biomarkers among PWH and those without HIV in the Veterans Aging Cohort Study (VACS) Biomarker Cohort.</p><p><strong>Methods: </strong>VACS participants had mtDNA haplogroups determined from genome-wide genotyping and adjudicated DM outcomes. Serum IL-6, D-dimer, and soluble CD14 were quantified, and cellular phenotyping performed by flow cytometry, on blood collected 2005-2007. Analyses included logistic and Cox regression of prevalent and incident DM, stratified by self-reported ancestry and HIV status, and adjusted for selected covariates.</p><p><strong>Results: </strong>mtDNA haplogroups, soluble and/or cellular biomarkers, and DM outcomes were available for 2019 participants (65% with HIV; 68% non-Hispanic Black; 95% male). Among 781 Black PWH, mtDNA haplogroup L3 (40%) was associated with incident DM (HR 1.56; 95% CI 1.01-2.40) adjusting for covariates including senescent (CD28-negative) CD4+ T-cells, which were lower in Black PWH having haplogroup L3 vs. other African haplogroups (p=0.05). No other haplogroups were associated with DM. There were no significant associations observed in Veterans without HIV, although the effect size was similar.</p><p><strong>Conclusion: </strong>mtDNA haplogroup L3 was associated with incident DM in predominantly male non-Hispanic Black PWH, replicating an association reported previously. This haplogroup was associated with fewer senescent CD4+ T-cells, but the association with DM was independent of T-cell phenotype.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250613","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":"Immunotherapy for Infectious Diseases: Back to the Future.","authors":"Jatin M Vyas","doi":"10.1093/infdis/jiaf306","DOIUrl":"https://doi.org/10.1093/infdis/jiaf306","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227432","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":"The kinetics of bedaquiline diffusion in tuberculous cavities open a window for emergence of resistance.","authors":"Annamarie E Bustion, Jacqueline P Ernest, Firat Kaya, Connie Silva, Jansy Sarathy, Landry Blanc, Marjorie Imperial, Martin Gengenbacher, Min Xie, Matthew Zimmerman, Gregory T Robertson, Danielle Weiner, Laura E Via, Clifton E Barry, Radojka M Savic, Véronique Dartois","doi":"10.1093/infdis/jiaf303","DOIUrl":"https://doi.org/10.1093/infdis/jiaf303","url":null,"abstract":"<p><strong>Background: </strong>Cavitary tuberculosis is difficult to cure and constitutes a site of relapse. Bedaquiline has been a wonder drug in the treatment of multidrug resistanttuberculosis, but emergence of resistance threatens the sustainability of its success. We designed site-of-disease pharmacokinetic studies in preclinical species to spatially resolve the penetration of bedaquiline, and two next generation diarylquinolines TBAJ587 and TBAJ876, in the necrotic center (caseum) of cavities.</p><p><strong>Methods: </strong>Rabbits with cavitary tuberculosis received the study drugs at human equivalent doses. A laser-capture microdissections scheme was developed to measure drug concentrations as a function of distance from blood supply in caseum. To simulate drug coverage in patient cavities, the data were modeled, and pharmacokinetic parameter estimates were linked to clinical plasma pharmacokinetic models for bedaquiline and the new diarylquinolines.</p><p><strong>Results: </strong>Pharmacokinetic-pharmacodynamic simulations in caseum revealed that bedaquiline reaches steady state and efficacious concentrations in deep caseum after several weeks to months and lingers at subtherapeutic concentrations up to 3 years after therapy ends. TBAJ876 and TBAJ587, currently in clinical development, achieve bactericidal concentrations in caseum layers more rapidly (within 2 hours and 1.8 days respectively) and shorten the window of suboptimal concentrations post treatmentcompared to bedaquiline. Simulations of clinically plausible dosing schemes can inform strategies to mitigate resistance development and guide the design of clinical trials for cavitary TB.</p><p><strong>Conclusions: </strong>The slow kinetics of diffusion of bedaquiline into and out of caseum creates spatio-temporal windows of subtherapeutic concentrations. Site-of-disease simulations of TBAJ587 and TBAJ876 predict reduced opportunities for resistance development.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217425","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":"B-Cell Subset Representation Predicts SARS-CoV-2 Vaccine Response in Solid Organ Transplant Recipients.","authors":"James J Knox, Ingi Lee, Emily A Blumberg, Aaron M Rosenfeld, Wenzhao Meng, Fang Liu, Charlotte Kearns, Una O'Doherty, Abraham Shaked, Kim M Olthoff, Eline T Luning Prak","doi":"10.1093/infdis/jiaf250","DOIUrl":"https://doi.org/10.1093/infdis/jiaf250","url":null,"abstract":"<p><strong>Background: </strong>Solid organ transplant recipients (SOTRs) suffer increased morbidity and mortality due, in part, to chronic immunosuppression. The determination of an individual's immune competence is currently difficult but would improve risk assessment and inform medical decisions. We reasoned that correlating qualitative and quantitative measures of the B-cell compartment with serologic responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination would reveal novel B-cell-based predictors of immune competence.</p><p><strong>Methods: </strong>We performed an integrated analysis of B-cell phenotypes, serology, and antibody repertoires in heart, lung, liver, kidney, and multiorgan transplant recipients and healthcare worker (HCW) controls (62 individuals total). We utilized K-means clustering and correlation analyses to identify B-cell features that correlated with vaccine serology.</p><p><strong>Results: </strong>K-means clustering identified 3 distinct B-cell compartment-based groups in SOTRs, which correlated with serum responses to SARS-CoV-2 vaccination. Group 1 SOTRs had a naive-dominant circulating B-cell pool and serologic responses closest to HCWs. Group 2 SOTRs had reduced naive but hyperexpanded memory B cells (MBCs) and variable vaccine responses that segregated by immunosuppression. Group 3 SOTRs had lymphopenia across B-cell subsets and poor serologic responses. Antibody repertoire analysis showed reduced clonal diversity across SOTRs, regardless of MBC numbers. Even in SOTRs with the largest immune responses, vaccine-specific B cells showed evidence of reduced maturation and clonal diversity.</p><p><strong>Conclusions: </strong>These findings reveal a hierarchy of B-cell impairment in SOTRs that can be measured rapidly, with implications for immune monitoring and intervention in immunocompromised individuals.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210075","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":"Further Evidence for Plausible Transmission of Fishborne Trematodiases in the United States: Game Fish Carry Human-Infectious Trematodes and Are Eaten Raw.","authors":"Emma M Palmer, Daniel C G Metz, Ryan F Hechinger","doi":"10.1093/infdis/jiaf180","DOIUrl":"https://doi.org/10.1093/infdis/jiaf180","url":null,"abstract":"<p><p>Historically, locally transmitted fishborne trematodiasis has not been a public health concern in the United States (US). However, the widespread introduction of the first intermediate host snail Melanoides tuberculata and 2 of the fishborne trematodes it transmits (Haplorchis pumilio and Centrocestus formosanus), along with their discovery at freshwater fishing localities throughout southern California, reveals a need to further evaluate the risk of local transmission of fishborne trematodiasis in the US. Here, we confirm that the trematode stages infectious to people (metacercariae) commonly infect and can be abundant in 7 commonly caught and eaten fish species at California fishing localities. Further, via an online social media search, we provide evidence that people throughout the US eat those same fish species in ways conducive to trematode transmission (namely, eating fish unfrozen and raw). These findings further indicate the plausibility for locally transmitted fishborne trematodiasis in the US.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210076","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":"Evaluation of Cellular Immune Responses After mRNA-1273 Vaccination in Children 6 Months to 11 Years of Age.","authors":"Christina A Rostad, James D Campbell, Grant C Paulsen, Sabine Schnyder Ghamloush, Wenqin Xu, Lingyi Zheng, M Juliana McElrath, Stephen C De Rosa, Bethany Girard, Rituparna Das, Evan J Anderson, C Buddy Creech","doi":"10.1093/infdis/jiaf144","DOIUrl":"10.1093/infdis/jiaf144","url":null,"abstract":"<p><strong>Background: </strong>Cell-mediated immunity (CMI) may help protect against emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that are less susceptible to neutralizing antibodies. We present CMI data after the mRNA-1273 primary series in a subset of participants aged 6 months to 11 years from the phase 2/3 KidCOVE trial.</p><p><strong>Methods: </strong>T-cell responses were assessed after 2 doses of mRNA-1273 (6 months to 5 years, 25 μg; 6-11 years, 50 μg) or placebo administered 28 days apart. Magnitude, phenotype, and percentage of ancestral SARS-CoV-2 spike (S) protein T-cell responses to pooled peptides were assessed by intracellular cytokine staining and polyfunctionality analyses.</p><p><strong>Results: </strong>A total of 68 children aged 6 months to 11 years received either the 2-dose mRNA-1273 primary series or placebo (51 and 17, respectively) at 28-day interval. mRNA-1273 induced S-protein-specific CD4+ T-cell responses exhibiting a type 1 T helper (Th1)-biased profile at day 43 and day 209 compared with placebo. S-protein-specific CD8+ T-cell responses were less frequently detected in children <5 years and undetectable in those <2 years. Compared with placebo, mRNA-1273 induced higher frequencies of S-specific polyfunctional CD4+ T cells at day 43; frequencies declined but remained detectable at day 209. Correlation between Th1 CD4+ responses and neutralizing antibodies was observed across age groups following mRNA-1273 vaccination.</p><p><strong>Conclusions: </strong>The 2-dose mRNA-1273 primary series elicited robust and durable (≥ 6 months) Th1-biased CD4+ T-cell responses in children aged 6 months to 11 years. CD8+ T-cell responses varied by age. Clinical Trials Registration. NCT04796896.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e945-e955"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677373","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":"Influence of Cellular Aging on Liver Stiffness in Patients With Hepatitis C Virus Achieving Sustained Viral Response.","authors":"Alejandro Gonzalez-Serna, Anaïs Corma-Gomez, Mercedes Cano, Ricardo Rubio-Sánchez, Carmen Martín-Sierra, Pilar Rincón, Jesica Martín-Carmona, Margarita Pérez, Juan Antonio Pineda, Luis Miguel Real, Juan Macias","doi":"10.1093/infdis/jiaf087","DOIUrl":"10.1093/infdis/jiaf087","url":null,"abstract":"<p><strong>Background: </strong>Liver stiffness (LS) is not reduced in 10%-30% of patients who achieve sustained viral response (SVR) after hepatitis C virus (HCV) elimination with direct-acting antivirals (DAA). Our aim was to analyze whether the parameters associated with cellular aging measured at the DAA initiation date are related to LS reduction upon achieving SVR.</p><p><strong>Methods: </strong>In a prospective cohort study (GEHEP-011) we measured several parameters associated with cellular aging, such as telomere attrition, mitochondrial alterations, and soluble biomarkers associated with senescence-associated secretory phenotype at the DAA initiation date, and examined their associations with a significant (≥20%) LS decrease at the SVR time point.</p><p><strong>Results: </strong>In total, 175 individuals were included in this study. In 101 (57.7%) patients, the LS reduction was ≥20% at SVR. In the multivariate analysis adjusted for sex, age, CXCL10, hsPCR, and CCL11 levels, greater relative telomere length (RTL) emerged as the sole variable independently associated with a significant LS decrease in SVR (1.102; 95% confidence interval, 1.001-1.1214; P = .047). Furthermore, changes in LS, including significant decrease, decrease <20%, or increase, were congruently associated with RTL (P = .011).</p><p><strong>Conclusions: </strong>Greater RTL was independently associated with a significant LS reduction in SVR. Thus, increased cellular aging may be responsible for the absence of liver regeneration after HCV eradication. Further studies are required to assess the long-term effects of cellular aging after SVR.</p><p><strong>Clinical trials registration: </strong>NCT04460157.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e846-e852"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460420","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}