{"title":"Effect of 5FU on paracoccidioidomycosis.","authors":"David A Stevens","doi":"10.1093/infdis/jiaf508","DOIUrl":"https://doi.org/10.1093/infdis/jiaf508","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201989","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}
Daniel Evans, Bree Friedman, Kelly Pung, Bonnie Weber, Matthew Plumb, Jacob Garfin, Christine Lees, Stacy Holzbauer, Ruth Lynfield, Xiong Wang
{"title":"Insights on recurrent and sequential Clostridioides difficile infections from genomic surveillance in Minnesota, USA, 2019-2021.","authors":"Daniel Evans, Bree Friedman, Kelly Pung, Bonnie Weber, Matthew Plumb, Jacob Garfin, Christine Lees, Stacy Holzbauer, Ruth Lynfield, Xiong Wang","doi":"10.1093/infdis/jiaf505","DOIUrl":"https://doi.org/10.1093/infdis/jiaf505","url":null,"abstract":"<p><strong>Background: </strong>The frequent temporal recurrence of Clostridioides difficile infection (CDI) may be the result of relapse with the same strain or reinfection with a different strain. We used whole-genome sequencing (WGS) to assess the genetic diversity and molecular evolution of strains that caused recurrent or sequential CDI.</p><p><strong>Methods: </strong>We analyzed data from active population- and laboratory-based surveillance of CDI in Minnesota, USA. We performed WGS on isolates collected from 306 patients with multiple CDI events during 2019-2021. We identified multi-locus sequence types (MLSTs), nucleotide variants, and putative mobile genetic elements (MGEs) from WGS data to study the genetic similarity and evolution of those C. difficile genomes.</p><p><strong>Results: </strong>Among patients with multiple CDI events in the surveillance period, 198 (64.7%) had multiple infections of the same MLST, including 49.6% of patients with subsequent infections beyond the 8-week limit of the case definition for recurrent CDI Among 232 temporally defined events of recurrent CDI, 155 (66.8%) involved isolates of the same MLST. There were no statistically significant correlations between accumulated mutations and elapsed time between same-MLST CDI events. Analysis of sequential same-MLST C. difficile genomes showed evidence of gain or loss of putative mobile genetic elements (MGEs) in 45.6% of genome pairs.</p><p><strong>Conclusions: </strong>Leveraging the largest CDI genomic dataset to date, our results confirm prior findings that recurrent CDI is a combination of reinfection and/or change in the ascendant strain in mixed infection, and relapse, while expanding knowledge on the evolution of pathogenic C. difficile strains in the human gastrointestinal tract.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202016","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}
Kelly Carey-Ewend, Aidan Marten, Julia Muller, Editruda Ernest Peter, Melic Odas, Msolo Credo Dominick, Meredith Muller, Srijana Chhetri, Kano Amagai, Isaack Rutha, Fatuma Kisandu, Lusekelo Beka, Oksana Kharabora, Zachary R Popkin-Hall, Jeffrey Bailey, Jessie K Edwards, Emily W Gower, Jonathan J Juliano, Billy E Ngasala, Jessica T Lin
{"title":"Seasonal variation and interspecies dynamics among Plasmodium falciparum and ovale species in Bagamoyo, Tanzania.","authors":"Kelly Carey-Ewend, Aidan Marten, Julia Muller, Editruda Ernest Peter, Melic Odas, Msolo Credo Dominick, Meredith Muller, Srijana Chhetri, Kano Amagai, Isaack Rutha, Fatuma Kisandu, Lusekelo Beka, Oksana Kharabora, Zachary R Popkin-Hall, Jeffrey Bailey, Jessie K Edwards, Emily W Gower, Jonathan J Juliano, Billy E Ngasala, Jessica T Lin","doi":"10.1093/infdis/jiaf498","DOIUrl":"https://doi.org/10.1093/infdis/jiaf498","url":null,"abstract":"<p><strong>Background: </strong>Malaria control in sub-Saharan Africa is typically focused on Plasmodium falciparum (Pf), but non-falciparum species like P. ovale curtisi (Poc) and P. ovale wallikeri (Pow) appear to be rising in prevalence, especially in parts of East Africa.</p><p><strong>Methods: </strong>We conducted polymerase chain reaction (PCR)-based screening of 7,173 asymptomatic individuals over 5 years of age in coastal Tanzania from 2018-2022, employing real-time 18S rRNA PCR assays for P. falciparum and P. ovale, followed by Poc/Pow detection. Plasmodium positivity was compared across seasons and demographic groups, and interactions between species were analyzed via binomial regression.</p><p><strong>Results: </strong>Pf infection (prevalence 27.4%) was associated with younger age, male sex, and higher recent cumulative rainfall, whereas these associations were not apparent for P. ovale (Po, prevalence 11.5%). Po infections appeared to peak during months with lower Pf prevalence, especially during the long wet season, when Po mono-infections predominated and fewer Pf-Po co-infections were detected than expected by independent assortment. This apparent antagonism was reversed during the short wet season: Pf-Po co-infections were comparatively enriched despite low overall Po prevalence. In contrast, excess mixed Poc/Pow infections were detected across all seasons, composing 23% of the Po-positive isolates in which a specific Po species could be detected.</p><p><strong>Conclusions: </strong>The epidemiology of P. ovale species in coastal Tanzania suggests they are frequently present when P. falciparum recedes, but also co-infect the same hosts during the short wet season. Meanwhile, the individual Poc and Pow species often co-exist within individuals, perhaps due to co-transmission or concurrent relapse.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193743","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}
Sushmita Sridhar, Colin J Worby, Ryan A Bronson, Sarah E Turbett, Elizabeth Oliver, Terrance Shea, Sowmya R Rao, Vanessa Sanchez, Margaret V Becker, Lucyna Kogut Holliday, Damien Slater, Jason B Harris, Maroya Spalding Walters, Allison Taylor Walker, Mark C Knouse, Daniel T Leung, Paul Kelly, Edward T Ryan, Regina C LaRocque, Ashlee M Earl
{"title":"Insights Into Global Antimicrobial Resistance Dynamics Through the Sequencing of Enteric Bacteria From US International Travelers.","authors":"Sushmita Sridhar, Colin J Worby, Ryan A Bronson, Sarah E Turbett, Elizabeth Oliver, Terrance Shea, Sowmya R Rao, Vanessa Sanchez, Margaret V Becker, Lucyna Kogut Holliday, Damien Slater, Jason B Harris, Maroya Spalding Walters, Allison Taylor Walker, Mark C Knouse, Daniel T Leung, Paul Kelly, Edward T Ryan, Regina C LaRocque, Ashlee M Earl","doi":"10.1093/infdis/jiaf469","DOIUrl":"10.1093/infdis/jiaf469","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance (AMR) is an urgent threat to public health, but gaps in surveillance limit the detection of emergent novel threats and knowledge about the global distribution of AMR genes. International travelers frequently acquire AMR organisms (AMROs) and thus may provide a window into AMR dynamics in otherwise poorly monitored regions and environments.</p><p><strong>Methods: </strong>To assess the utility of travelers as global AMR sentinels, we collected pre- and post-travel stool samples from 608 travelers between 2017 and 2019, which were screened for the presence of extended-spectrum beta-lactamase producing Enterobacterales, carbapenem-resistant Enterobacterales, and mcr-mediated colistin-resistant Enterobacterales. A total of 307 distinct AMROs were sequenced and analyzed in order to determine genotypic patterns and their association with geography and traveler behavior.</p><p><strong>Results: </strong>Travel-associated AMROs were overwhelmingly Escherichia coli, which exhibited considerable phylogenetic diversity regardless of travel region. However, the prevalence of resistance genes varied by region, with blaCTX-M-55 and blaCTX-M-27 significantly more common in isolates associated with South America and South-Eastern Asia, respectively. Plasmid reconstruction revealed the genomic neighborhood of blaCTX-M-55 frequently matched a motif previously linked to animal populations. The ColV plasmid, a driver of avian pathogenic E. coli, was found to be elevated in frequency in isolates acquired by travelers reporting animal contact. We identified novel variants of the mcr-1 gene in strains acquired from Western Africa.</p><p><strong>Conclusions: </strong>Traveler pathogen genomic surveillance can provide insight on global AMR dynamics and emerging clinical threats. Ongoing efforts to track travel-acquired organisms could complement existing global AMR surveillance frameworks.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132574","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":"Activin A mediated KAT8 expression induces ferroptosis during Mycobacterium tuberculosis infection.","authors":"Bijewar Ashish Satish, Smriti Sundar, Raju S Rajmani, Kithiganahalli Narayanaswamy Balaji","doi":"10.1093/infdis/jiaf482","DOIUrl":"https://doi.org/10.1093/infdis/jiaf482","url":null,"abstract":"<p><p>Activin A, a secretory glycoprotein, is upregulated in tuberculosis (TB) patients, and its levels are correlated with disease severity. During infection, Mycobacterium tuberculosis (Mtb) induces ferroptosis, an iron-induced mode of cell death, that aids in dissemination and survival. Here, we identify a functional role for activin A and the downstream SMAD2/3 signalling in Mtb-induced ferroptosis and disease progression. Molecular assays, including ChIP and loss-of-function analysis, demonstrated that Activin A regulates the expression of KAT8, which in-turn regulates levels of HO-1. Mechanistically, we identify that KAT8-mediated acetylation of NRF2 during Mtb infection enhances its nuclear availability leading to increased HO-1 expression. Finally, utilizing an in vivo mouse model of TB, we show that the pharmacological inhibition of activin A receptor and KAT8 restricts Mtb burden, limits dissemination and ameliorates TB pathology. Thus, we report a novel role for activin A in regulating NRF2 localisation and outline its potential consequences during TB.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114665","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}
Othmane Daoui, Pieter Monsieurs, Hasnaa Talimi, Gerald F Späth, Jean-Claude Dujardin, Senne Heeren, Meryem Lemrani, Malgorzata Anna Domagalska
{"title":"Direct genome sequencing of Leishmania tropica in tissues of Moroccan patients with cutaneous leishmaniasis reveals micro-focal transmission underlain by (pseudo-)clonal and sexual reproduction modes.","authors":"Othmane Daoui, Pieter Monsieurs, Hasnaa Talimi, Gerald F Späth, Jean-Claude Dujardin, Senne Heeren, Meryem Lemrani, Malgorzata Anna Domagalska","doi":"10.1093/infdis/jiaf485","DOIUrl":"https://doi.org/10.1093/infdis/jiaf485","url":null,"abstract":"<p><p>Leishmania tropica is causing cutaneous leishmaniasis (CL) from North Africa to India and in Ethiopia and is reported to be transmitted from humans to humans through sand fly bites. While this species is characterized by a high genomic diversity all over the area of endemicity, there is very little information on diversity at micro-epidemiological scale. Here, we zoomed on an epidemic Moroccan focus of CL and studied transmission patterns by comparative genomics of parasites in human patients. We used a culture-independent method of genome sequencing, applied directly on dermal scrapings. We identified 7 groups of nearly identical genotypes, as well as parasites with mixed ancestry. Our results reveal a micro-focal transmission among humans, underlain by (pseudo) clonal and sexual reproductive modes. This study demonstrates the power of direct genome sequencing for evolutionary genetics at a micro-epidemiological scale.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092761","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}
Annamarie E Bustion, Jacqueline P Ernest, Firat Kaya, Connie Silva, Jansy Sarathy, Landry Blanc, Marjorie Imperial, Martin Gengenbacher, Min Xie, Matthew D Zimmerman, Gregory T Robertson, Danielle Weiner, Laura E Via, Clifton E Barry, Radojka M Savic, Véronique Dartois
{"title":"The Kinetics of Bedaquiline Diffusion in Tuberculous Cavities Open a Window for the 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 D Zimmerman, Gregory T Robertson, Danielle Weiner, Laura E Via, Clifton E Barry, Radojka M Savic, Véronique Dartois","doi":"10.1093/infdis/jiaf303","DOIUrl":"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-resistant tuberculosis, but emergence of resistance threatens the sustainability of its success. We designed site-of-disease pharmacokinetic studies to spatially resolve the penetration of bedaquiline, and 2 next-generation diarylquinolines, TBAJ876 and TBAJ587, in cavities.</p><p><strong>Methods: </strong>Rabbits with established cavitary tuberculosis received the study drugs. 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 parameter estimates were linked to clinical plasma pharmacokinetic models.</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, achieve bactericidal concentrations in caseum layers more rapidly and shorten the window of suboptimal concentrations post treatment compared to bedaquiline.</p><p><strong>Conclusions: </strong>The slow kinetics of diffusion of bedaquiline into and out of caseum creates spatiotemporal 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":"e431-e441"},"PeriodicalIF":4.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455318/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
{"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":"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":"e362-e371"},"PeriodicalIF":4.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455312/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Betânia M F Nogueira, Francys Rangel, Alice M S Andrade, Evangeline Ann Daniel, Marina C Figueiredo, Cody Staats, Valeria C Rolla, Afrânio L Kritski, Marcelo Cordeiro-Santos, Amita Gupta, Luke Elizabeth Hanna, Timothy R Sterling, Mariana Araújo-Pereira, Bruno B Andrade
{"title":"Predictive Markers of Incident Tuberculosis in Close Contacts in Brazil and India.","authors":"Betânia M F Nogueira, Francys Rangel, Alice M S Andrade, Evangeline Ann Daniel, Marina C Figueiredo, Cody Staats, Valeria C Rolla, Afrânio L Kritski, Marcelo Cordeiro-Santos, Amita Gupta, Luke Elizabeth Hanna, Timothy R Sterling, Mariana Araújo-Pereira, Bruno B Andrade","doi":"10.1093/infdis/jiae642","DOIUrl":"10.1093/infdis/jiae642","url":null,"abstract":"<p><p>There are insufficient predictors of progression to tuberculosis among contacts. A case-control study within RePORT-Brazil matched 20 QuantiFERON-positive progressors and 40 nonprogressors by sex, age, and exposure duration. Twentynine cytokines were measured using a Luminex assay with QuantiFERON-TB Gold Plus supernatants collected at baseline and evaluated using machine learning for tuberculosis prediction. The same markers were evaluated in 8 QuantiFERON-positive progressors and 12 nonprogressors from India. Interleukin 8, interleukin 10, and CCL3 levels predicted incident tuberculosis (area under the receiver operating characteristic curve, 0.75) in 2 years with sensitivity and specificity >80%, in both cohorts. This signature predicted tuberculosis progression in close contacts meeting World Health Organization goals.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":"232 3","pages":"567-572"},"PeriodicalIF":4.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126382","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}