Journal of Infectious Diseases最新文献

{"title":"Transcriptome Analysis of Monocytes Treated with Dengue NS1 Revealed a Shift in Transcripts Involving in Self-Propagated Proinflammation and Antiviral Responses.","authors":"Khwankhao Saisingha, Tuksin Jearanaiwitayakul, Daniel Watterson, Naphak Modhiran, Marisa Ponpuak, Sukathida Ubol","doi":"10.1093/infdis/jiaf166","DOIUrl":"https://doi.org/10.1093/infdis/jiaf166","url":null,"abstract":"<p><p>Non-structural protein 1 (NS1) of dengue virus (DENV) can influence dengue severity. In this study, we used RNA sequencing analysis to assess blood monocyte response to different concentrations of NS1. Here we showed that NS1 at the level found in severe dengue may be involved in severe dengue development through two potential mechanisms which were induction of excessive inflammation and suppression of antiviral responses. At high levels, NS1 significantly up-regulated S100A8 and S100A9, ACOD1, and TREM-1, that might help amplifying the inflammatory loops. In terms of antiviral suppression, we found that high NS1 concentration significantly suppressed interferon signalling and MHCII transcripts. This potentially delayed the clearance of both DENV and NS1 protein. Our study highlighted the possible role of NS1-activated monocytes in dengue severity.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755594","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 viro-immunological model to characterize the antiviral effect of molnupiravir in SARS-CoV-2-infected outpatients: implication for treatment duration.","authors":"Bach Tran Nguyen, Julie Bertrand, Akosua A Agyeman, Shengyuan Zhang, Ly-Mee Yu, Victoria Harris, Paul Little, Christopher C Butler, Judith Breuer, David M Lowe, Joseph F Standing, Jérémie Guedj","doi":"10.1093/infdis/jiaf158","DOIUrl":"https://doi.org/10.1093/infdis/jiaf158","url":null,"abstract":"<p><strong>Background: </strong>The antiviral efficacy of molnupiravir against SARS-CoV-2 is controversial. Here, we develop a model integrating viral and immune dynamics to characterize the mechanism of action of molnupiravir in vivo and its impact on viral dynamics, during and after treatment.</p><p><strong>Methods: </strong>We analysed data from the PANORAMIC trial, where 577 outpatients were randomised shortly after symptom onset to receive usual care or molnupiravir for 5 days, and where viral and immunological data were collected for two weeks. We developed a mathematical model that characterized virus/host interaction and accounted for the impact of molnupiravir on viral replication and mutagenesis. The model was used to explore the impact of longer treatment duration.</p><p><strong>Results: </strong>Molnupiravir reduced RNA replication with an efficacy that reached 93% at the end of a five-day treatment. This effect was mediated through two different pathways, one that increased transition mutation frequency, and other that directly inhibited viral production. Accordingly five-day treatment shortened the median time to clearance of both RNA and infectious virus by approximately 2 days. Treatment duration of 10 days could reduce the time to RNA clearance by 5 days and reduce the occurrence of viral rebounds. Longer treatment durations might be needed in case of post-exposure prophylaxis.</p><p><strong>Conclusions: </strong>Our model suggests that molnupiravir acts primarily on viral replication, and does not act specifically on viral infectivity. Longer administration of molnupiravir may reduce rebound rate and shorten time to viral clearance.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755593","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 disorders after 12 months of HIV-1 preexposure prophylaxis based on tenofovir disoproxil fumarate plus emtricitabine in healthy adults.","authors":"Esperanza Muñoz-Muela, Marta Mejías-Trueba, Ana Serna-Gallego, Abraham Saborido-Alconchel, Susana Fernández-Pérez, Marta Herrero, Cesar Sotomayor, Alicia Gutiérrez-Valencia, María Trujillo-Rodríguez, Luis F López-Cortés","doi":"10.1093/infdis/jiaf156","DOIUrl":"https://doi.org/10.1093/infdis/jiaf156","url":null,"abstract":"<p><strong>Background: </strong>New nucleos(t)ide reverse transcriptase inhibitors are considerably less toxic than their predecessors, but they may not be entirely devoid of toxicity. However, their effect in healthy adults remains unknown. We aimed to analyze the impact of tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC)-based preexposure prophylaxis (PrEP) on mitochondria of subjects at high risk of HIV-1 infection.</p><p><strong>Methods: </strong>This is an observational, prospective study of 59 healthy adults enrolled in the PrEP program at Virgen del Rocio University Hospital. Mitochondrial DNA and common deletion 4977 were measured using digital droplet PCR. Mitochondrial density, membrane potential, oxidative stress, metabolic profile, and morphology were assessed by flow cytometry, real-time cellular bioenergetics measurements, and transmission electron microscope, respectively, at baseline and after 12 months. Values were compared by the Wilcoxon test, and correlations between variables were assessed using the Spearman rank correlation coefficient (ρ).</p><p><strong>Results: </strong>Our results showed that after 12 months, TDF/FTC induced a mitochondrial oxidative stress increase in myeloid and lymphoid populations. Mitochondrial density decreased in CD8+ T cells and NK cells, while mitochondrial membrane potential augmented in all lymphoid populations. Cell bioenergetic health was compromised, evidenced by reduced oxygen consumption rate, declined ATP production, and impaired response capacity to an energetic demand. Changes in mitochondrial shape, membrane integrity, cristae structure, size, and distribution throughout the cytoplasm were also observed. All participants experienced alterations in one or more measured parameters.</p><p><strong>Conclusions: </strong>TDF/FTC-based PrEP induces mitochondrial toxicity in healthy subjects after 12 months of treatment, negatively affecting mitochondrial function and morphology.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765636","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":"Influenza-associated hospitalization rates by underlying conditions, 2016-17 to 2019-20: A retrospective cohort study.","authors":"Aaron M Frutos, Mark W Tenforde, Devi Sundaresan, Allison L Naleway, Stephanie A Irving, Malini B DeSilva, Anupam B Kharbanda, Toan C Ong, Suchitra Rao, Kai Zheng, Shruti K Gohil, Sarah W Ball, Rebecca V Fink, Carrie Reed, Shikha Garg, Catherine H Bozio","doi":"10.1093/infdis/jiaf164","DOIUrl":"https://doi.org/10.1093/infdis/jiaf164","url":null,"abstract":"<p><strong>Background: </strong>Various underlying medical conditions (UMCs) elevate the risk of influenza-associated hospitalization. We evaluated how these rates changed by type and number of UMCs.</p><p><strong>Methods: </strong>Retrospective cohorts were constructed among adult members of two health systems aged ≥18 years with prior healthcare utilization. Across the 2016-17 to 2019-20 seasons, we estimated influenza-associated hospitalization rates by type and number of UMCs. Hospitalizations were defined using discharge diagnoses or laboratory confirmation. We calculated adjusted rate ratios (aRR) using Poisson regression controlling for site, season, and demographic characteristics. We used causal mediation to estimate the effect of UMCs on influenza-associated hospitalization accounting for influenza vaccination status.</p><p><strong>Results: </strong>Among 870,888 cohort members, 1,403 were hospitalized with influenza at least once within a season across four seasons. Compared to those without, the aRR for influenza-associated hospitalization was highest for individuals with congestive heart failure (4.2, 95% CI: 3.6-4.9). The aRRs also increased with each additional UMCs compared to those with no UMCs. The effect of UMCs on influenza-associated hospitalizations was higher when not mediated by vaccination status; for those with ≥4 UMCs compared to no UMCs, rates were about 60% higher.</p><p><strong>Conclusion: </strong>The burden of baseline medical conditions is associated with higher rates of influenza-associated hospitalization. Among those with varying types and number of UMCs, if vaccination prevalence had been lower than observed, influenza-associated hospitalization rates would have been higher. These findings highlight the importance of preventive medical care and annual influenza vaccination in reducing influenza-associated hospitalizations, particularly for individuals at high-risk.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744159","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":"Factors influencing virologic control during analytical treatment interruptions in HIV cure trials - a pooled analysis of individual level data.","authors":"Vibeke Klastrup, Jesper Damsgaard Gunst, Thomas Aagaard Rasmussen, Martin Tolstrup, Ole Schmeltz Søgaard","doi":"10.1093/infdis/jiaf163","DOIUrl":"https://doi.org/10.1093/infdis/jiaf163","url":null,"abstract":"<p><strong>Background: </strong>Achieving antiretroviral therapy (ART)-free virologic control remains a central goal in human immunodeficiency virus (HIV) cure research. To identify factors associated with time to detectable viremia and time to loss of virologic control, we conducted a pooled analysis of six interventional trials that included analytical ART interruption.</p><p><strong>Methods: </strong>We determined factors influencing time to detectable viremia (plasma HIV-RNA ≥50 copies/mL) and loss of virologic control (two consecutive measurements of plasma HIV-RNA ≥5,000 copies/mL or restart of ART) using cox proportional hazard regression.</p><p><strong>Results: </strong>Among the 91 included participants we found that high levels of total HIV-DNA (≥750 copies) and intact proviral DNA (≥80 copies/106 CD4+ T cells) were both associated with shorter time to detectable viremia (HR=1.98, 95% confidence interval [CI]: 1.22, 3.22; HR=1.67, 95% CI: 1.08, 2.58, respectively). Total HIV-DNA ≥750 copies/106 CD4+ T cells also predicted shorter time to loss of virologic control (HR=1.64, 95% CI: 1.01, 2.67); as did longer time ≥1 year from HIV diagnosis to ART start (HR=1.56, 95% CI: 1.02, 2.39). Having received histone deacetylase inhibitors predicted shorter time to loss of virologic control (HR=2.22, 95% CI: 1.12, 4.41), while broadly neutralizing anti-HIV-1 antibody (bNAb) treatment at ART initiation of individuals harboring 3BNC117-sensitive viruses trended towards delayed time to loss of virologic control (HR=0.32, 95% CI: 0.10, 1.01).</p><p><strong>Conclusions: </strong>Our findings highlight the positive impact of early ART and low HIV reservoirs on time to rebound among people undergoing ATI and provides new insight into therapeutic interventions aimed at achieving virologic control.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732995","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 Impact of COVID-19 Non-Pharmaceutical Interventions on Incidence of Acute Gastroenteritis and Acute Respiratory Infections Among US Military and Dependents.","authors":"Bevin Manuelpillai, Benjamin Lopman, Charlotte Doran, Chad Porter","doi":"10.1093/infdis/jiaf153","DOIUrl":"https://doi.org/10.1093/infdis/jiaf153","url":null,"abstract":"<p><p>Non-pharmaceutical interventions (NPIs) for COVID-19 resulted in the reduction of many viral diseases aside from SARS-CoV-2, but their impact on the US military or beneficiary population have not been assessed. Using TRICARE data (2016-2023), we modeled changes in acute gastroenteritis (AGE) and acute respiratory infection (ARI) encounters pre- and post-pandemic. In 2020, AGE and ARI encounters decreased substantially (RR = 0.50, 95% CI [0.31, 0.80]; RR = 0.60, [0.41, 0.88]). By 2022, AGE remained suppressed while ARI had rebounded. Since 2022, AGE encounters among military personnel remained reduced compared to beneficiaries. NPIs had a greater, lasting effect on AGE than ARI encounters.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711926","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":"Age-Dependent Assortativeness in Herpes Simplex Virus Type 1 Oral Transmission in the United States: A Mathematical Modeling Analysis.","authors":"Hassan Hachem, Houssein H Ayoub, Laith J Abu-Raddad","doi":"10.1093/infdis/jiaf157","DOIUrl":"https://doi.org/10.1093/infdis/jiaf157","url":null,"abstract":"<p><strong>Background: </strong>Herpes simplex virus type 1 (HSV-1) is a highly infectious, globally prevalent lifelong infection. Despite advancements in understanding its epidemiology, the assortativeness in the age-dependent transmission patterns remains unclear. This study aimed to estimate the degree of assortativeness in age group mixing for oral-to-oral HSV-1 transmission within the United States (U.S.) population.</p><p><strong>Methods: </strong>An age-structured mathematical model was employed to describe HSV-1 transmission dynamics in the population, incorporating its different modes of transmission. The model was fitted to nationally representative HSV-1 data from the National Health and Nutrition Examination Surveys (NHANES) spanning 1976-2016 using a Bayesian inference framework. The degree of assortativeness in age group mixing was calibrated on a scale from 0 (no age group bias in close-proximity interactions) to 1 (exclusive mixing within the same age group).</p><p><strong>Results: </strong>The model demonstrated robust fits to U.S. demographics, age-specific HSV-1 prevalence, and temporal trends in both HSV-1 prevalence and ever-symptomatic HSV-1 genital herpes prevalence. The degree of assortativeness was estimated as 0.87 (95% CI: 0.64-0.99) for children, indicating strong age-based assortativity, and as 0.04 (95% CI: 0.004-0.10) for adults, indicating weak age-based assortativity.</p><p><strong>Conclusion: </strong>Most HSV-1 infections among children are acquired from peers within their own age group, whereas adults acquire HSV-1 infections from a broad range of age groups.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711923","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":"Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections.","authors":"Claudia Fançony, Elsa Fortes-Gabriel, Félix Zage, Evangelia Alexiou, Ioanna Broumou, Leyre Pernaute-Lau, Jorge Panzo, Esperança J António, Mario S Cristovão, José M Domingos, Estevão Sassoma, Fernando Kuatoko, Edite V N Rosario, António Martins, Anna Färnert, Luis Bernardino, Tais N de Sousa, José Pedro Gil","doi":"10.1093/infdis/jiaf155","DOIUrl":"https://doi.org/10.1093/infdis/jiaf155","url":null,"abstract":"<p><strong>Background: </strong>Decreased efficacy of artemether-lumefantrine, the globally most used antimalarial, has recently emerged in Africa.</p><p><strong>Methods: </strong>An efficacy trial based on directly observed artemether-lumefantrine therapy at Bengo, Northern Angola. 100 Plasmodium falciparum uncomplicated malaria patients (2-10 year-old) were enrolled, hospitalized for the treatment period, and followed up for 42 days. PCR correction was performed with pfmsp1/2 + glurp, with analysis considering 2 or 3 coincident markers. Infections were tested by qPCR for pfmdr1 copy number (pfmdr1xN), a potential Plasmodium falciparum marker of lumefantrine resistance previously identified in the region. In-vitro clone mixtures were built and used to determine the relation between qPCR copy number scores and actual intra-infection quantitative fractions of pfmdr1xN.</p><p><strong>Results: </strong>We observed a significant post-treatment selection of gene amplification, suggesting a role in the parasite in vivo response to this drug. pfmdr1x2 qPCR scores of 1.3, 1.4 and 1.5 were determined to correspond to 15%, 25% and 35% intra-infection rates. Patients carrying infections with a score ≥1.4 at baseline were linked to decreased AL day 42 efficacy (79% vs 97% single-copy pfmdr1). All infections were pfmdr1 N86 carriers and no pfk13 mutations were found.</p><p><strong>Conclusions: </strong>Our study suggests pfmdr1xN as a marker of P. falciparum in vivo response to lumefantrine in Africa, while pointing for patients carrying infections with a pre-treatment pfmdr1xN score ≥1.4 before treatment as a group experiencing decreased artemether-lumefantrine performance.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732975","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":"Empowering Futures: Restoring T Cell Responses in Children Living with HIV.","authors":"John Patrick Toledo","doi":"10.1093/infdis/jiaf160","DOIUrl":"https://doi.org/10.1093/infdis/jiaf160","url":null,"abstract":"<p><p>This study examines how children with HIV recover mycobacteria-specific T cell responses after six months of antiretroviral therapy (ART). Persistent deficiencies raise concerns about tuberculosis susceptibility despite elevated Th1 CD4 T cells, emphasizing the necessity of focused treatments and continuous health empowerment in susceptible juvenile populations.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732992","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 Infection Control Practices and Democracy Collide: Reply to Paladino and Riva.","authors":"Olivia S Kates, Petros C Karakousis","doi":"10.1093/infdis/jiaf162","DOIUrl":"https://doi.org/10.1093/infdis/jiaf162","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732226","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}