Journal of Infectious Diseases最新文献

{"title":"Plasma From Older Children in Malawi Inhibits Plasmodium falciparum Binding in 3-Dimensional Brain Microvessels.","authors":"Fatou Joof, Ruoqian Hu, Alex Saidi, Karl B Seydel, Lauren M Cohee, Ying Zheng, Joseph D Smith","doi":"10.1093/infdis/jiae315","DOIUrl":"10.1093/infdis/jiae315","url":null,"abstract":"<p><p>A hallmark of cerebral malaria is sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the brain microcirculation. Antibodies contribute to malaria immunity, but it remains unclear whether functional antibodies targeting parasite-expressed ligand can block cytoadhesion in the brain. Here, we screened the plasma of older children and young adults in Malawi to characterize the antibody response against the P. falciparum-IE surface and used a bioengineered 3-dimensional (3D) human brain microvessel model incorporating variable flow dynamics to measure adhesion-blocking responses. We found a strong correlation between surface antibody reactivity by flow cytometry and reduced P. falciparum-IE binding in 3D microvessels. Moreover, there was a threshold of surface antibody reactivity necessary to achieve robust inhibitory activity. Our findings provide evidence of the acquisition of adhesion-blocking antibodies against cerebral binding variants in people exposed to stable P. falciparum transmission and suggest the quality of the inhibitory response can be influenced by flow dynamics.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e1402-e1411"},"PeriodicalIF":5.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321876","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":"Disease-Specific Differences in Pharmacokinetics of Paromomycin and Miltefosine Between Post-Kala-Azar Dermal Leishmaniasis and Visceral Leishmaniasis Patients in Eastern Africa.","authors":"Wan-Yu Chu, Luka Verrest, Brima M Younis, Ahmed M Musa, Jane Mbui, Rezika Mohammed, Joseph Olobo, Koert Ritmeijer, Séverine Monnerat, Monique Wasunna, Ignace C Roseboom, Alexandra Solomos, Alwin D R Huitema, Fabiana Alves, Thomas P C Dorlo","doi":"10.1093/infdis/jiae413","DOIUrl":"10.1093/infdis/jiae413","url":null,"abstract":"<p><p>Treatment regimens for post-kala-azar dermal leishmaniasis (PKDL) are usually extrapolated from those for visceral leishmaniasis (VL), but drug pharmacokinetics (PK) can differ due to disease-specific variations in absorption, distribution, and elimination. This study characterized PK differences in paromomycin and miltefosine between 109 PKDL and 264 VL patients from Eastern Africa. VL patients showed 0.55-fold (95% confidence interval [CI], .41-.74) lower capacity for paromomycin saturable reabsorption in renal tubules, and required a 1.44-fold (95% CI, 1.23-1.71) adjustment when relating renal clearance to creatinine-based estimated glomerular filtration rate. Miltefosine bioavailability in VL patients was lowered by 69% (95% CI, 62%-76%) at treatment start. Comparing PKDL to VL patients on the same regimen, paromomycin plasma exposures were 0.74- to 0.87-fold, while miltefosine exposure until the end of treatment day was 1.4-fold. These pronounced PK differences between PKDL and VL patients in Eastern Africa highlight the challenges of directly extrapolating dosing regimens from one leishmaniasis presentation to another.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e1375-e1384"},"PeriodicalIF":5.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009855","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":"Long-Lived Plasma Cells can't forget the Original Antigenic Sin.","authors":"Chika Edward Uzoigwe","doi":"10.1093/infdis/jiae621","DOIUrl":"https://doi.org/10.1093/infdis/jiae621","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840193","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":"Efficacy and Safety of a Tetravalent Dengue Vaccine (TAK-003) in Children With Prior Japanese Encephalitis or Yellow Fever Vaccination.","authors":"Chukiat Sirivichayakul, Shibadas Biswal, Xavier Saez-Llorens, Eduardo López-Medina, Charissa Borja-Tabora, Lulu Bravo, Pope Kosalaraksa, Maria Theresa Alera, Humberto Reynales, Luis Rivera, Veerachai Watanaveeradej, Delia Yu, Felix Espinoza, Reynaldo Dietze, LakKumar Fernando, V Pujitha Wickramasinghe, Edson Duarte Moreira, Asvini D Fernando, Dulanie Gunasekera, Kleber Luz, Rivaldo Venâncio da Cunha, Ana Lucia Oliveira, Martina Rauscher, Huihao Fan, Astrid Borkowski, Ian Escudero, Suely Tuboi, Eric Lloyd, Vianney Tricou, Nicolas Folschweiller, Inge LeFevre, Luis Martinez Vargas, Derek Wallace","doi":"10.1093/infdis/jiae222","DOIUrl":"10.1093/infdis/jiae222","url":null,"abstract":"<p><strong>Background: </strong>We explored the impact of prior yellow fever (YF) or Japanese encephalitis (JE) vaccination on the efficacy of Takeda's dengue vaccine candidate, TAK-003.</p><p><strong>Methods: </strong>Children 4-16 years of age were randomized 2:1 to receive TAK-003 or placebo and were under active febrile surveillance. Symptomatic dengue was confirmed by serotype-specific reverse-transcription polymerase chain reaction. YF and JE vaccination history was recorded.</p><p><strong>Results: </strong>Of the 20 071 children who received TAK-003 or placebo, 21.1% had a YF and 23.9% had a JE vaccination history at randomization. Fifty-seven months after vaccination, vaccine efficacy (95% confidence interval) was 55.7% (39.7%-67.5%) in those with YF vaccination, 77.8% (70.8%-83.1%) for JE vaccination, and 53.5% (45.4%-60.4%) for no prior YF/JE vaccination. Regional differences in serotype distribution confound these results. The apparent higher vaccine efficacy in the JE vaccination subgroup could be largely explained by serotype-specific efficacy of TAK-003. Within 28 days of any vaccination, the proportions of participants with serious adverse events in the YF/JE prior vaccination population were comparable between the TAK-003 and placebo groups.</p><p><strong>Conclusions: </strong>The available data do not suggest a clinically relevant impact of prior JE or YF vaccination on TAK-003 performance. Overall, TAK-003 was well-tolerated and efficacious in different epidemiological settings. Clinical Trials Registration.  NCT02747927.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e1214-e1225"},"PeriodicalIF":5.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871101","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":"Contrasting Phenotypes of Neutrophils During Asymptomatic Versus Symptomatic Leishmania braziliensis Infection.","authors":"Jacilara A Conceição, Pedro P Carneiro, Andreza S Dórea, Walker N Oliveira, Aline C Muniz, Edgar M Carvalho, Mary E Wilson, Olívia Bacellar","doi":"10.1093/infdis/jiae317","DOIUrl":"10.1093/infdis/jiae317","url":null,"abstract":"<p><strong>Background: </strong>The mechanisms that mediate immune protection in individuals with subclinical (SC) or asymptomatic infection with Leishmania braziliensis are largely unknown. Neutrophils (polymorphonuclear leukocytes [PMNs]) have been implicated in progressive symptomatic cutaneous leishmaniasis (CL), but their potential participation in maintenance of subclinical infection is unexplored. The aim of this study was to compare the phenotypic and functional profiles of PMNs in individuals with SC infection versus patients with symptomatic CL due to L braziliensis.</p><p><strong>Methods: </strong>Subjects were recruited in the endemic region of Corte de Pedra, Bahia, Brazil. Surface markers to define activation status were characterized by flow cytometry. Functional responses of PMNs including phagocytic capacity, production of oxidative species, and oxidative killing of intracellular parasites were studied in vitro.</p><p><strong>Results: </strong>PMNs from individuals with SC infection displayed a more activated phenotype and greater ability to control the infection than PMNs from patients with CL. In contrast, PMNs from patients with CL exhibited higher expression of HLA-DR and higher production of oxidative species than PMNs from subjects with SC infection.</p><p><strong>Conclusions: </strong>PMNs from individuals with SC infection can control the infection more efficiently than PMNs from patients with CL, despite the lower production of oxidants. Our observations suggest that L braziliensis may evade microbicidal mechanisms of PMNs from patients with CL, contributing to parasite dissemination and the establishment of disease.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e1385-e1393"},"PeriodicalIF":5.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443646","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":"Efficacy of a Novel Affitoxin Targeting Major Outer Membrane Protein Against Chlamydia trachomatis In Vitro and In Vivo.","authors":"Mingyang Li, Jia Yang, Luqi Zhou, Jing Zhang, Yang Li, Jun Chen, Haiyan Dong, Lifang Zhang, Shanli Zhu","doi":"10.1093/infdis/jiae257","DOIUrl":"10.1093/infdis/jiae257","url":null,"abstract":"<p><p>Targeted therapy is an attractive approach for treating infectious diseases. Affibody molecules have similar capability to antibodies that facilitate molecular recognition in both diagnostic and therapeutic applications. Targeting major outer membrane protein (MOMP) for treating infection of Chlamydia trachomatis, one of the most common sexually transmitted pathogens, is a promising therapeutic approach. Previously, we have reported a MOMP-specific affibody (ZMOMP:461) from phage display library. Here, we first fused it with modified Pseudomonas exotoxin (PE38KDEL) and a cell-penetrating peptide (CPP) to develop an affitoxin, Z461X-CPP. We then verified the addition of both toxin and CPPs that did not affect the affinitive capability of ZMOMP:461 to MOMP. Upon uptake by C trachomatis-infected cells, Z461X-CPP induced cell apoptosis in vitro. In an animal model, Z461X significantly shortened the duration of C trachomatis infection and prevented pathological damage in the mouse reproductive system. These findings provide compelling evidence that the MOMP-specific affitoxin has great potential for targeting therapy of C trachomatis infection.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1476-1487"},"PeriodicalIF":5.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900137","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":"At the Mercy of the Artificial Intelligence Algorithm: Discrepant Polymerase Chain Reaction Results.","authors":"Mark Zuckerman, Temi Lampejo, Melvyn Smith","doi":"10.1093/infdis/jiae538","DOIUrl":"10.1093/infdis/jiae538","url":null,"abstract":"<p><p>As pathogen molecular diagnostics technology develops, the software analysis of polymerase chain reaction sigmoidal curves, cycle threshold (Ct) values, and the limit of nucleic acid detection for that assay is not always available when reporting test results. These are critical components in interpreting results and can affect the management of patients. Our view is that all commercial assay providers must ensure that users, as they can with laboratory-developed tests, are able to see the curve and Ct value for all samples. Some examples demonstrating this principle are included. Regulatory bodies have a key role to play.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1299-1301"},"PeriodicalIF":5.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591749","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":"Correlation of Genogroup I, Genotype 1 (GI.1) Norovirus Neutralizing Antibody Levels With GI.1 Histo-Blood Group Antigen-Blocking Antibody Levels.","authors":"Robert L Atmar, Khalil Ettayebi, Frederick H Neill, Ralph P Braun, James Sherwood, Sasirekha Ramani, Mary K Estes","doi":"10.1093/infdis/jiae311","DOIUrl":"10.1093/infdis/jiae311","url":null,"abstract":"<p><strong>Background: </strong>The in vitro cultivation of human noroviruses allows a comparison of antibody levels measured in neutralization and histo-blood group antigen (HBGA)-blocking assays.</p><p><strong>Methods: </strong>Serum samples collected during the evaluation of an investigational norovirus vaccine (HIL-214 [formerly TAK-214]) were assayed for neutralizing antibody levels against the vaccine's prototype Norwalk virus/genogroup I, genotype 1 (GI.1) (P1) virus strain. Results were compared with those previously determined using HBGA-blocking assays.</p><p><strong>Results: </strong>Neutralizing antibody seroresponses were observed in 83% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.81; P < .001) with those measured by HBGA blocking.</p><p><strong>Conclusions: </strong>Genogroup I, genotype 1 (GI.1)-specific HBGA-blocking antibodies are a surrogate for neutralization of GI.1 norovirus. Clinical Trials Registration.  Clinicaltrials.gov NCT02475278.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1376-1379"},"PeriodicalIF":5.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307316","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":"Viral Genomic Variation and the Severity of Genital Herpes Simplex Virus-2 Infection as Quantified by Shedding Rate: A Viral Genome-Wide Association Study.","authors":"Amanda M Casto, Hoseung Song, Hong Xie, Stacy Selke, Pavitra Roychoudhury, Michael C Wu, Anna Wald, Alexander L Greninger, Christine Johnston","doi":"10.1093/infdis/jiae283","DOIUrl":"10.1093/infdis/jiae283","url":null,"abstract":"<p><strong>Background: </strong>The clinical severity of genital herpes simplex virus-2 (HSV-2) infection varies widely among infected persons with some experiencing frequent genital lesions while others are asymptomatic. The viral genital shedding rate is closely associated with, and has been established as, a surrogate marker of clinical severity.</p><p><strong>Methods: </strong>To assess the relationship between viral genetics and shedding, we assembled a set of 145 persons who had the severity of their genital herpes quantified through determination of their HSV genital shedding rate. An HSV-2 sample from each person was sequenced and biallelic variants among these genomes were identified.</p><p><strong>Results: </strong>We found no association between metrics of genome-wide variation in HSV-2 and shedding rate. A viral genome-wide association study identified the minor alleles of 3 individual unlinked variants as significantly associated with higher shedding rate (P < 8.4 × 10-5): C44973T (A512T), a nonsynonymous variant in UL22 (glycoprotein H); A74534G, a synonymous variant in UL36 (large tegument protein); and T119283C, an intergenic variant. We also found an association between the total number of minor alleles for the significant variants and shedding rate (P = 6.6 × 10-7).</p><p><strong>Conclusions: </strong>These results add to a growing body of literature for HSV suggesting a connection between viral genetic variation and clinically important phenotypes of infection.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1357-1366"},"PeriodicalIF":5.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159071","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":"Acquired Human Immunodeficiency Virus Type 1 Drug Resistance in Rhode Island, USA, 2004-2021.","authors":"Su Aung, Vlad Novitsky, Jon Steingrimsson, Fizza S Gillani, Mark Howison, Katherine Nagel, Matthew Solomon, Thomas Bertrand, Lila Bhattarai, John Fulton, Utpala Bandy, Rami Kantor","doi":"10.1093/infdis/jiae344","DOIUrl":"10.1093/infdis/jiae344","url":null,"abstract":"<p><strong>Background: </strong>Human immunodeficiency virus type 1 (HIV-1) acquired drug resistance (ADR) compromises antiretroviral therapy (ART).</p><p><strong>Methods: </strong>We aggregated all HIV-1 protease-reverse transcriptase-integrase sequences over 2004-2021 at the largest HIV center in Rhode Island and evaluated ADR extent, trends, and impact using Stanford Database tools. Trends were measured with Mann-Kendall statistic, and multivariable regressions evaluated resistance predictors.</p><p><strong>Results: </strong>Sequences were available for 914 ART-experienced persons. Overall ADR to any drug decreased from 77% to 49% (-0.66 Mann-Kendall statistic); nucleoside reverse transcriptase inhibitors 65% to 32%, nonnucleoside reverse transcriptase inhibitors 53% to 43%, and protease inhibitors 28% to 7% (2004-2021), and integrase strand transfer inhibitors 16% to 13% (2017-2021). Multiclass resistance decreased from 44% to 12% (2-class) and 12% to 6% (3-class). In 2021, 94% had at least one 3-drug or 2-drug one-pill-once-daily (OPOD) option. Males and those exposed to more ART regimens were more likely to have ≥2-class resistance, and higher regimen exposure was also associated with fewer OPOD options.</p><p><strong>Conclusions: </strong>Comprehensive analyses within a densely-sampled HIV epidemic over 2004-2021 demonstrated decreasing ADR. Continued ADR monitoring is important to maintain ART success, particularly with rising INSTI use in all lines of therapy and 2-drug and long-acting formulations.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1422-1433"},"PeriodicalIF":5.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749475","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}