{"title":"Doxycycline post-exposure prophylaxis and off-target antimicrobial resistance: potential amplification within sexual networks.","authors":"Manon Roberts, Peter Davis","doi":"10.1093/infdis/jiaf439","DOIUrl":"10.1093/infdis/jiaf439","url":null,"abstract":"<p><p>Doxycycline post-exposure prophylaxis (doxyPEP) is now included in many clinical guidelines, yet concerns remain regarding antimicrobial resistance (AMR), particularly off-target effects on commensal bacteria in the oropharynx, with intimate behaviours potentially facilitating resistance transmission within sexual networks.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884194","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}
Maria Carolina Silva de Barros Puça, Isabela Marques Naziazeno, Viviane Cristina Fernandes Dos Santos, Priscila Rodrigues, Priscila Rodrigues Calil, Winni Alves Ladeia, José Pedro Gil, Marcelo Urbano Ferreira, Tais Nobrega de Sousa
{"title":"How CYP2D6 polymorphism modulates the community-wide risk of Plasmodium vivax infection: a panel study in Amazonian Brazil.","authors":"Maria Carolina Silva de Barros Puça, Isabela Marques Naziazeno, Viviane Cristina Fernandes Dos Santos, Priscila Rodrigues, Priscila Rodrigues Calil, Winni Alves Ladeia, José Pedro Gil, Marcelo Urbano Ferreira, Tais Nobrega de Sousa","doi":"10.1093/infdis/jiaf412","DOIUrl":"10.1093/infdis/jiaf412","url":null,"abstract":"<p><strong>Background: </strong>The CYP2D6 enzyme plays a critical role in the metabolism of primaquine, the most widely used drug for the radical cure of Plasmodium vivax malaria. Impaired CYP2D6 activity has been associated with an increased risk of relapse. However, the overall impact of CYP2D6 on infection dynamics is still not fully understood. We hypothesized that individuals with impaired CYP2D6 activity develop partial immunity more rapidly due to the ineffective clearance of hypnozoites.</p><p><strong>Methods: </strong>To test this hypothesis, we conducted a community-based study involving approximately 1,300 individuals genotyped for CYP2D6 and assessed repeatedly for P. vivax using molecular diagnosis. This approach allowed us to detect and monitor submicroscopic and asymptomatic infections over a 4-year follow-up period.</p><p><strong>Results: </strong>In our cohort, children with impaired CYP2D6 activity exhibited a higher frequency of P. vivax infections compared to those with normal enzyme activity. This pattern changed during the second decade of life, as the prevalence of P. vivax infection increased in adolescents with normal enzyme activity (P = 0.0008, Generalized additive mixed model). Consistent with this, parasite densities were lower in adults with impaired CYP2D6 activity compared with younger individuals with normal enzyme activity (P = 0.0383, Linear mixed model).</p><p><strong>Conclusions: </strong>These findings underscore the potential role of CYP2D6 in shaping infection dynamics and malaria immunity in endemic areas.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876542","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}
DeAnna J Friedman-Klabanoff, Travis L Jensen, Casey E Gelber, Richard S Pinapati, John C Tan, Gregory A Deye, Jason A Regules, Elke S Bergmann-Leitner, Matthew B Laurens, Mark A Travassos, Johannes B Goll, Shannon Takala-Harrison, Andrea A Berry
{"title":"Vaccine-induced antibodies to a C-terminal Plasmodium falciparum circumsporozoite protein epitope are associated with protection.","authors":"DeAnna J Friedman-Klabanoff, Travis L Jensen, Casey E Gelber, Richard S Pinapati, John C Tan, Gregory A Deye, Jason A Regules, Elke S Bergmann-Leitner, Matthew B Laurens, Mark A Travassos, Johannes B Goll, Shannon Takala-Harrison, Andrea A Berry","doi":"10.1093/infdis/jiaf391","DOIUrl":"10.1093/infdis/jiaf391","url":null,"abstract":"<p><strong>Background: </strong>Plasmodium falciparum circumsporozoite protein (CSP) is the target of multiple malaria vaccines that include only a part of the protein, such as RTS,S and R21. The monoclonal antibodies L9 and CIS43 are directed against key CSP junctional region epitopes not included in RTS,S and R21, and next generation vaccine candidates attempt to elicit similar antibodies. Understanding the effectiveness of multiple antibody responses against CSP peptides will inform next-generation vaccines.</p><p><strong>Methods: </strong>Using sera collected during controlled human malaria infection (CHMI) experiments that evaluated vaccine efficacy, we used a peptide array inclusive of CSP genetic variants to quantify anti-CSP antibody responses in unprotected adults who received a full-length CSP vaccine (rCSP), protected adults who received RTS,S, and unprotected adults who received RTS,S. We compared breadth and intensity of responses to CSP variants between groups.</p><p><strong>Results: </strong>Overall, rCSP recipients had lower CSP antibody responses compared with the protected RTS,S group. Compared to the unprotected groups, protected RTS,S vaccinees had higher breadth of responses to peptides in the junctional region, central repeat region, and C-terminal region. The protected RTS,S group also had higher intensity of responses to two C-terminal peptides, including part of Th3R. Additionally, protected RTS,S recipients had higher breadth of IgA responses to variants of the C-terminal epitope PNDPNRNV, identified as a dominant motif by motif-recognition software, and to similar sequences in the junctional region.</p><p><strong>Conclusions: </strong>Protection-associated antibody responses to the junctional region not contained in RTS,S suggest a cross-reactive, vaccine-induced response that provides additional benefit beyond antibodies targeting vaccine peptides.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876548","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}
Adam S Komorowski, Michael G Surette, Laura Rossi, Dominique Tertigas, Mark Gaskin, Shahrokh Shekarriz, Andrew G McArthur, Marek Smieja, Dominik Mertz
{"title":"Molecular Epidemiology of Clinical Infections Caused by Serratia marcescens Complex in a Tertiary Care Hospital System: Insights From Whole-Genome Sequencing.","authors":"Adam S Komorowski, Michael G Surette, Laura Rossi, Dominique Tertigas, Mark Gaskin, Shahrokh Shekarriz, Andrew G McArthur, Marek Smieja, Dominik Mertz","doi":"10.1093/infdis/jiaf392","DOIUrl":"10.1093/infdis/jiaf392","url":null,"abstract":"<p><strong>Background: </strong>Serratia marcescens is an opportunistic AmpC β-lactamase-producing Enterobacterales associated with intensive care unit outbreaks, causing high morbidity and mortality. The spatiotemporal dynamics of Serratia species and their implications for hospital infection prevention and control remain understudied.</p><p><strong>Methods: </strong>We prospectively identified patient culture specimens in a multihospital academic healthcare system from 2022 to 2024. We included first-time isolates of S. marcescens identified via culture and confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Isolates underwent whole-genome sequencing on the Illumina NextSeq 2000 platform. We queried assembled genomes using the Comprehensive Antibiotic Resistance Database to identify resistance genes and predict resistomes. We constructed a maximum-likelihood phylogenetic tree using GTDB-Tk-assigned taxonomies. We identified possible links between patients if there was a spatiotemporal overlap and the average nucleotide identity (ANI) of a sequence pair was > 99.0%. We collected relevant patient characteristics via retrospective chart review and analyzed data using descriptive statistics.</p><p><strong>Results: </strong>Of 147 identified isolates, we included 125. Phenotypic testing suggested either inducible or derepressed AmpC expression in all isolates. Whole-genome sequencing found species-level discordance with MALDI-TOF MS in 64 (51.2%) isolates, suggesting the presence of multiple members of the recently described S. marcescens complex causing hospital- or community-associated infections. Only 1 isolate pair had a spatiotemporal link and ANI > 99.0%.</p><p><strong>Conclusions: </strong>Between-patient transmission of S. marcescens complex outside of outbreaks is likely rare. Current MALDI-TOF MS-based identification methods are insufficient to identify S. marcescens complex and laboratory reporting should be modified to report only to the level of the complex.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876546","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}
Deng B Madut, Matthew P Rubach, Flemming Scheutz, Douglas R Call, Firdoos A Gogry, Manuela Carugati, Nathaniel Kalengo, Annette Marandu, Michael J Maze, Anne B Morrissey, Bingileki F Lwezaula, Blandina T Mmbaga, Kajiru G Kilonzo, Venance P Maro, John A Crump
{"title":"Population structure of Escherichia coli isolated from the human bloodstream, human and animal feces, and the environment in northern Tanzania.","authors":"Deng B Madut, Matthew P Rubach, Flemming Scheutz, Douglas R Call, Firdoos A Gogry, Manuela Carugati, Nathaniel Kalengo, Annette Marandu, Michael J Maze, Anne B Morrissey, Bingileki F Lwezaula, Blandina T Mmbaga, Kajiru G Kilonzo, Venance P Maro, John A Crump","doi":"10.1093/infdis/jiaf437","DOIUrl":"10.1093/infdis/jiaf437","url":null,"abstract":"<p><strong>Background: </strong>Extraintestinal pathogenic Escherichia coli (ExPEC) are a leading cause of human bloodstream infections (BSI) in sub-Saharan Africa, yet few studies have characterized African strains implicated in BSI or explored their potential reservoirs.</p><p><strong>Methods: </strong>We enrolled febrile patients at two hospitals in Moshi, Tanzania, 2007-2019, and performed blood cultures. Whole genome sequencing was conducted on E. coli originating from the bloodstream to characterize sequence types (STs), serotypes, and theoretical coverage of a 9-valent ExPEC polysaccharide conjugate vaccine (ExPEC9V). Separately, we evaluated 601 E. coli whole genome sequences from humans, animals, and environmental sources in nearby communities. We assessed genetic relatedness between bloodstream and community isolates based on single-nucleotide polymorphisms and allele differences.</p><p><strong>Findings: </strong>Of 3,046 participants receiving blood culture, 48 (0.2%) had BSI yielding 48 E. coli isolates. The median (range) age of participants with E. coli BSI was 40.7 (0.3-89.0) years, and 32 (68.1%) were female. We identified 16 STs including ST131 (n=16, 33.3%), ST73 (n=10, 20.8%), and ST69 (n=6, 12.5%), and 19 O groups including O25 (n=13, 27.1%), O6 (n=10, 20.3%), O17 (n=4, 8.3%), and O18 (n=4, 8.3%). Theoretical coverage for an ExPEC9V was 72.9%. None of the bloodstream and community E. coli pairs were closely related.</p><p><strong>Conclusions: </strong>We found a high diversity of sequence types among E. coli human bloodstream isolates in Tanzania. Despite this diversity, we observed that an EXPEC9V in development would provide good coverage. Reservoir attribution studies at finer spatial and temporal scales may better identify transmission networks and reservoirs of ExPECs.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876547","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":"Correction to: CircEXOC5 Aggravates Sepsis-Induced Acute Lung Injury by Promoting Ferroptosis Through the IGF2BP2/ATF3 Axis.","authors":"","doi":"10.1093/infdis/jiaf409","DOIUrl":"10.1093/infdis/jiaf409","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876541","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}
Aybüke Koyuncu, Robin Nesbitt, Catia Alvarez, Kinya Vincent Asilaza, Joseph Wamala, Melat Haile, Etienne Gignoux, Manuel Albela, Emily S Gurley, Frederick Beden Loro, Duol Biem, Monica Rull, John Rumunu, Iza Ciglenecki, Isabella Eckerle, Andrew S Azman
{"title":"Diagnostic performance and kinetics of hepatitis E viral RNA and IgM antibody test positivity in a genotype 1 outbreak in South Sudan.","authors":"Aybüke Koyuncu, Robin Nesbitt, Catia Alvarez, Kinya Vincent Asilaza, Joseph Wamala, Melat Haile, Etienne Gignoux, Manuel Albela, Emily S Gurley, Frederick Beden Loro, Duol Biem, Monica Rull, John Rumunu, Iza Ciglenecki, Isabella Eckerle, Andrew S Azman","doi":"10.1093/infdis/jiaf436","DOIUrl":"https://doi.org/10.1093/infdis/jiaf436","url":null,"abstract":"<p><strong>Background: </strong>Diagnostics are essential for understanding hepatitis E epidemiology, but the field performance of available tests remains unclear. We evaluated the performance of PCR, IgM ELISA, and the Assure HEV IgM rapid diagnostic test (RDT) during a HEV genotype 1 outbreak and assessed the duration of viremia and antibodies responses.</p><p><strong>Methods: </strong>We used data from enhanced surveillance at a health facility in Bentiu internally displaced persons camp, South Sudan (March-December 2022). As part of a vaccine effectiveness study suspected hepatitis E cases underwent testing with all three diagnostics at enrolment with a follow-up sample. We used a latent class model to estimate test performance and accelerated failure time models to estimate time from jaundice onset to a negative test for PCR and ELISA.</p><p><strong>Findings: </strong>Among 893 suspected cases, test sensitivity declined with time from jaundice onset. Within 30 days of jaundice onset, PCR sensitivity was 73% (95% Credible Interval (CrI) 27, 90), compared to 86% for RDT (95% CrI: 74, 93), and 95% for ELISA (95% CrI: 91, 98). Specificity was high across tests: PCR at 98% (95% CrI: 98, 99), RDT at 95% (95% CrI: 93, 96), and ELISA at 95% (95% CrI: 93, 96). Median time from jaundice onset to negative test was 19 days (95% CI: 17, 21) for PCR and 113 days (95% CI: 87, 163) for ELISA.</p><p><strong>Interpretation: </strong>The Assure IgM RDT showed higher sensitivity for identifying hepatitis E than PCR and similar specificity to IgM ELISA, supporting its use in surveillance. Care seeking delays can greatly influence the interpretation of diagnostic tests.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856847","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":"Unraveling the Epigenetic Landscape of Neurosyphilis: Implications for Diagnosis, Treatment, and Long-term Management.","authors":"Jia-Hao Cao, Wei Li","doi":"10.1093/infdis/jiaf025","DOIUrl":"10.1093/infdis/jiaf025","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e350-e351"},"PeriodicalIF":4.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967185","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":"Immune Complexes in Blackwater Fever and Severe Malarial Anemia: New Insights From Old Forgotten Friends.","authors":"David Torres-Fernandez, Quique Bassat","doi":"10.1093/infdis/jiae432","DOIUrl":"10.1093/infdis/jiae432","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"267-269"},"PeriodicalIF":4.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082429","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}
Wenhao Cao, Weihua Su, Xinyu Song, Lingling Ma, Yongzhong Li, Haiying Yan, Jie Li, Jun Yang, Jianqing Zhao, Kuan Liu, Rong Qiu, Gang He, Fei Shi, Jinxiang Wang, Lijun Suo, Xiao Liu, Yu Zhang, Liyu Li, Hong Zhao, Tianhao Li, Gao Yi, Zhiang Huang, Shuchun Gao, Yeming Wang, Bin Cao
{"title":"Efficacy and Safety of WXSH0208 Tablets in Treatment of Acute Uncomplicated Influenza Infection in Adults: A Multicenter Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.","authors":"Wenhao Cao, Weihua Su, Xinyu Song, Lingling Ma, Yongzhong Li, Haiying Yan, Jie Li, Jun Yang, Jianqing Zhao, Kuan Liu, Rong Qiu, Gang He, Fei Shi, Jinxiang Wang, Lijun Suo, Xiao Liu, Yu Zhang, Liyu Li, Hong Zhao, Tianhao Li, Gao Yi, Zhiang Huang, Shuchun Gao, Yeming Wang, Bin Cao","doi":"10.1093/infdis/jiaf075","DOIUrl":"10.1093/infdis/jiaf075","url":null,"abstract":"<p><strong>Background: </strong>WXSH0208 is a selective inhibitor of influenza RNA polymerase subunit, demonstrating antiviral activity in preclinical studies against influenza A and B virus infections. The purpose of this study was to investigate the efficacy and safety of WXSH0208 in adult outpatients with uncomplicated influenza.</p><p><strong>Methods: </strong>We conducted a multicenter phase 2 trial based on a randomized, double-blind, placebo-controlled design at 23 research centers in China from November 2023 to March 2024. Participants were randomized 1:1:1:1 to receive one of the following treatments within 48 hours of symptom onset: WXSH0208 10 mg once daily for 5 days, 20 mg once daily for 5 days, 30 mg once daily for 3 days, or placebo. The primary outcome was the time to negative detection of viral load by reverse transcriptase quantitative polymerase chain reaction in the intention-to-treat infected population.</p><p><strong>Results: </strong>Of 240 randomized patients, 209 were included in the intention-to-treat infected analysis. The median time to negative detection of viral load was 49.3 hours in the WXSH0208 10 mg group, 48.0 hours in the 20 mg group, and 48.2 hours in the 30 mg group, as compared with 95.6 hours in the placebo group (P < .001). Time to alleviation of influenza symptoms was comparable among all groups. Treatment-emergent adverse events were reported in 48.3% to 51.7% of WXSH0208 recipients and 58.3% of placebo recipients, with most being mild or moderate in severity.</p><p><strong>Conclusions: </strong>WXSH0208 showed no evident safety concerns and was superior to placebo in reducing viral load in adult outpatients with uncomplicated influenza. Clinical Trials Registration. CTR20233250 (www.chinadrugtrials.org.cn).</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"441-449"},"PeriodicalIF":4.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702073","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}