BACKGROUNDThe Neisseria gonorrhoeae pilE gene encodes the PilE protein, the major subunit of the Type IV pilus and a primary colonization and virulence factor. The pilE gene undergoes high-frequency diversification mainly through gene conversion from one of many pilS copies. These unique molecular processes contribute to gonococcal population diversity, facilitating immune evasion. While the process of pilin variation is understood, the diversity of pilE and pilS genes from clinical isolates is understudied.METHODSWe analyzed 15 186 N. gonorrhoeae genomes, including finished (n = 65) and draft (n = 15 121) genomes, in the PubMLST database to characterize pilE and pilS gene diversity.RESULTSThe finished genomes had one to nine pilS loci at conserved chromosomal locations. Only 52.13% of sequences contained a pilE gene, despite all genomes having other Type IV pilus genes. When the pilE was present, most defined conserved sequences were preserved. However, most predicted PilE protein sequences contained premature stop codons, which were found in several silent copies.CONCLUSIONSAll N. gonorrhoeae strains possess the genes necessary for pilin AV; however, most genomic sequences were derived from nonpiliated variants that emerged during in vitro culture through reversible pilus phase variation and irreversible deletion of the pilE gene.
{"title":"Publicly Available Neisseria Gonorrhoeae Genomes Predominantly Represent In Vitro-Derived Nonpiliated Variants.","authors":"Iryna Boiko,Selma Metaane,H Steven Seifert","doi":"10.1093/infdis/jiaf557","DOIUrl":"https://doi.org/10.1093/infdis/jiaf557","url":null,"abstract":"BACKGROUNDThe Neisseria gonorrhoeae pilE gene encodes the PilE protein, the major subunit of the Type IV pilus and a primary colonization and virulence factor. The pilE gene undergoes high-frequency diversification mainly through gene conversion from one of many pilS copies. These unique molecular processes contribute to gonococcal population diversity, facilitating immune evasion. While the process of pilin variation is understood, the diversity of pilE and pilS genes from clinical isolates is understudied.METHODSWe analyzed 15 186 N. gonorrhoeae genomes, including finished (n = 65) and draft (n = 15 121) genomes, in the PubMLST database to characterize pilE and pilS gene diversity.RESULTSThe finished genomes had one to nine pilS loci at conserved chromosomal locations. Only 52.13% of sequences contained a pilE gene, despite all genomes having other Type IV pilus genes. When the pilE was present, most defined conserved sequences were preserved. However, most predicted PilE protein sequences contained premature stop codons, which were found in several silent copies.CONCLUSIONSAll N. gonorrhoeae strains possess the genes necessary for pilin AV; however, most genomic sequences were derived from nonpiliated variants that emerged during in vitro culture through reversible pilus phase variation and irreversible deletion of the pilE gene.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer Momkus, Kathleen Mullan Harris, Jessie K Edwards, Y Claire Yang, Chantel L Martin, Allison E Aiello
Background Persistent infections, including cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1), Epstein-Barr Virus (EBV), and Helicobacter pylori (H. pylori), illicit chronic immune stimulation and may contribute to biological aging. While CMV has been associated with markers of biological aging in older adults, including immunosenescence, less is known about these associations earlier in adulthood or the role of other persistent infections. Methods Using data from a nationally representative U.S. cohort, we examined associations between CMV, HSV-1, EBV, and H. pylori infections (assessed at a median age of 28 years) and markers of biological aging, including epigenetic age acceleration (EAA) and cellular immunosenescence (measured ∼10 years later). EAA was assessed via GrimAge, PhenoAge, and DunedinPACE clocks while immunosenescence was estimated using DNA methylation-based immune cell ratios. Results CMV infection and antibody concentrations were consistently associated with accelerated epigenetic aging and increased cellular immunosenescence measures. For example, CMV seropositivity was associated with 0.36 higher CD4+ memory: naïve ratio (95% CI: 0.11, 0.62). H. pylori, HSV-1, and EBV demonstrated more limited but notable associations, particularly with EAA measures. For instance, increased EBV IgG was associated with higher GrimAge acceleration (GrimAgeAA) (β=0.006 years, 95% CI: 0.002, 0.01). Higher H. pylori IgG antibodies were unexpectedly associated with a higher CD4+/CD8+ cell ratio (β=0.002, 95% CI: 0.0002, 0.004). Conclusions Persistent infections, particularly CMV, shape biological aging via DNA methylation aging and immunosenescence before midlife. Future research is needed to clarify how the timing and burden of these infections influence biological aging and immune function across the life course.
{"title":"A Pathogen Penalty? Associations between Persistent Infections and Biological Aging in the US","authors":"Jennifer Momkus, Kathleen Mullan Harris, Jessie K Edwards, Y Claire Yang, Chantel L Martin, Allison E Aiello","doi":"10.1093/infdis/jiaf606","DOIUrl":"https://doi.org/10.1093/infdis/jiaf606","url":null,"abstract":"Background Persistent infections, including cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1), Epstein-Barr Virus (EBV), and Helicobacter pylori (H. pylori), illicit chronic immune stimulation and may contribute to biological aging. While CMV has been associated with markers of biological aging in older adults, including immunosenescence, less is known about these associations earlier in adulthood or the role of other persistent infections. Methods Using data from a nationally representative U.S. cohort, we examined associations between CMV, HSV-1, EBV, and H. pylori infections (assessed at a median age of 28 years) and markers of biological aging, including epigenetic age acceleration (EAA) and cellular immunosenescence (measured ∼10 years later). EAA was assessed via GrimAge, PhenoAge, and DunedinPACE clocks while immunosenescence was estimated using DNA methylation-based immune cell ratios. Results CMV infection and antibody concentrations were consistently associated with accelerated epigenetic aging and increased cellular immunosenescence measures. For example, CMV seropositivity was associated with 0.36 higher CD4+ memory: naïve ratio (95% CI: 0.11, 0.62). H. pylori, HSV-1, and EBV demonstrated more limited but notable associations, particularly with EAA measures. For instance, increased EBV IgG was associated with higher GrimAge acceleration (GrimAgeAA) (β=0.006 years, 95% CI: 0.002, 0.01). Higher H. pylori IgG antibodies were unexpectedly associated with a higher CD4+/CD8+ cell ratio (β=0.002, 95% CI: 0.0002, 0.004). Conclusions Persistent infections, particularly CMV, shape biological aging via DNA methylation aging and immunosenescence before midlife. Future research is needed to clarify how the timing and burden of these infections influence biological aging and immune function across the life course.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Balancing Pharmacokinetic Targets and Lymphocyte Declines With Once-Monthly Oral Islatravir for PrEP.","authors":"Anxin Wen","doi":"10.1093/infdis/jiaf618","DOIUrl":"https://doi.org/10.1093/infdis/jiaf618","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145711121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"On-Demand Dosing of HIV Preexposure Prophylaxis for Women: Has Their Time Finally Come?","authors":"Susan P Buchbinder,Peter L Anderson","doi":"10.1093/infdis/jiaf507","DOIUrl":"https://doi.org/10.1093/infdis/jiaf507","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annefleur D O Hensen,Céline Harmanus,Christine Voorvelt,Anoecim R Geelen,Maryam El Hamdioui,Ed J Kuijper,Laura Pattacini,Pim Schipper,Inge M van Amerongen-Westra,Pauline Meij,M Y Eileen C Van der Stoep-Yap,Meta Roestenberg,Wiep Klaas Smits
BACKGROUNDInfections with C. difficile remain a significant global healthcare problem for which novel (preventive) treatment strategies are urgently needed. Controlled human infection models (CHIMs) can contribute to a better understanding of the disease and accelerate (novel) medicinal product development.METHODSA robust production process for C. difficile spores for experimental human administration, was implemented. Direct-release capsules containing viable C. difficile spores were formulated. The manufacturing process aligns with good manufacturing practices (GMP) guidelines, including quality controls and release by a qualified person (QP).RESULTSSelected non-toxigenic and toxigenic C. difficile strains were used to create a master cell bank and working cell bank from which multiple batches of purified active substance were produced. Substance was then used to manufacture the final active product. The active product and its intermediate products passed all quality controls for identity, potency, purity and safety, and were individually released by the QP. Stability of active substance and product is confirmed up to 12 months.CONCLUSIONAlthough there are no clear standardized international guidelines for challenge material production, we demonstrate that it is feasible to produce C. difficile human challenge material for small scale application in CHIM trials. This application of GMP principles to an unconventional production process of a bacterial spore-forming anaerobic challenge agent is an example for the production of challenge material as described in the auxiliary medicinal product guidelines of EMA and FDA.
{"title":"Manufacture of Clostridioides difficile spores for experimental infection of human volunteers.","authors":"Annefleur D O Hensen,Céline Harmanus,Christine Voorvelt,Anoecim R Geelen,Maryam El Hamdioui,Ed J Kuijper,Laura Pattacini,Pim Schipper,Inge M van Amerongen-Westra,Pauline Meij,M Y Eileen C Van der Stoep-Yap,Meta Roestenberg,Wiep Klaas Smits","doi":"10.1093/infdis/jiaf612","DOIUrl":"https://doi.org/10.1093/infdis/jiaf612","url":null,"abstract":"BACKGROUNDInfections with C. difficile remain a significant global healthcare problem for which novel (preventive) treatment strategies are urgently needed. Controlled human infection models (CHIMs) can contribute to a better understanding of the disease and accelerate (novel) medicinal product development.METHODSA robust production process for C. difficile spores for experimental human administration, was implemented. Direct-release capsules containing viable C. difficile spores were formulated. The manufacturing process aligns with good manufacturing practices (GMP) guidelines, including quality controls and release by a qualified person (QP).RESULTSSelected non-toxigenic and toxigenic C. difficile strains were used to create a master cell bank and working cell bank from which multiple batches of purified active substance were produced. Substance was then used to manufacture the final active product. The active product and its intermediate products passed all quality controls for identity, potency, purity and safety, and were individually released by the QP. Stability of active substance and product is confirmed up to 12 months.CONCLUSIONAlthough there are no clear standardized international guidelines for challenge material production, we demonstrate that it is feasible to produce C. difficile human challenge material for small scale application in CHIM trials. This application of GMP principles to an unconventional production process of a bacterial spore-forming anaerobic challenge agent is an example for the production of challenge material as described in the auxiliary medicinal product guidelines of EMA and FDA.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dissecting the Impact of the Gut Microbiome on HIV Reservoir Dynamics.","authors":"Christopher M Basting,Nichole R Klatt","doi":"10.1093/infdis/jiaf560","DOIUrl":"https://doi.org/10.1093/infdis/jiaf560","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"140 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sun B Sowers,Huong Q Nguyen,Nina B Masters,Sara Mercader,Heather Colley,David L McClure,Carole J Hickman,Mona Marin,Stephen N Crooke
BACKGROUNDA third dose of measles, mumps, and rubella vaccine (MMR3) may be administered in outbreak and nonoutbreak settings. However, data on long-term immunogenicity to the mumps component of MMR are limited. We examined durability of mumps antibody response among adults up to 11 years after receipt of MMR3.METHODSPersons who received MMR3 at ages 18-28 years had sera collected before (baseline), 1 month, 1, 5, and 9-11 years after vaccination. Mumps antibodies were assessed by plaque reduction neutralization, immunoassay (EIA), and immunoglobulin G (IgG) avidity. Neutralizing antibodies were assessed against the vaccine strain (Genotype A) and a wild-type virus from Genotype G. Participants with neutralizing antibody titers <31 for Genotype A and <8 for Genotype G, and with EIA index values <1.10 were considered potentially susceptible.RESULTSAmong participants with data for all visits after MMR3 (40%, n = 262/655), susceptibility based on Genotype A titers increased from 15.7% (41/262) at baseline to 30.5% (80/262) 9-11 years after vaccination while susceptibility based on Genotype G titers remained relatively stable (30.2%-24.2%). The proportion of participants seronegative for mumps IgG by EIA increased from 0% (0/255) at baseline to 7.5% (19/255) 9-11 years after vaccination. The avidity index increased from 52% to 67% through Year 5 (P < .0001).CONCLUSIONSBy 9-11 years after receipt of MMR3, many participants had mumps antibody levels that predicted susceptibility to infection, comparable to those observed before receipt of MMR3. The antibody titers to Genotype G remained consistently lower than the titers to the vaccine strain.
{"title":"Durability of the Mumps Antibody Response After the Third Dose of MMR Vaccine.","authors":"Sun B Sowers,Huong Q Nguyen,Nina B Masters,Sara Mercader,Heather Colley,David L McClure,Carole J Hickman,Mona Marin,Stephen N Crooke","doi":"10.1093/infdis/jiaf520","DOIUrl":"https://doi.org/10.1093/infdis/jiaf520","url":null,"abstract":"BACKGROUNDA third dose of measles, mumps, and rubella vaccine (MMR3) may be administered in outbreak and nonoutbreak settings. However, data on long-term immunogenicity to the mumps component of MMR are limited. We examined durability of mumps antibody response among adults up to 11 years after receipt of MMR3.METHODSPersons who received MMR3 at ages 18-28 years had sera collected before (baseline), 1 month, 1, 5, and 9-11 years after vaccination. Mumps antibodies were assessed by plaque reduction neutralization, immunoassay (EIA), and immunoglobulin G (IgG) avidity. Neutralizing antibodies were assessed against the vaccine strain (Genotype A) and a wild-type virus from Genotype G. Participants with neutralizing antibody titers <31 for Genotype A and <8 for Genotype G, and with EIA index values <1.10 were considered potentially susceptible.RESULTSAmong participants with data for all visits after MMR3 (40%, n = 262/655), susceptibility based on Genotype A titers increased from 15.7% (41/262) at baseline to 30.5% (80/262) 9-11 years after vaccination while susceptibility based on Genotype G titers remained relatively stable (30.2%-24.2%). The proportion of participants seronegative for mumps IgG by EIA increased from 0% (0/255) at baseline to 7.5% (19/255) 9-11 years after vaccination. The avidity index increased from 52% to 67% through Year 5 (P < .0001).CONCLUSIONSBy 9-11 years after receipt of MMR3, many participants had mumps antibody levels that predicted susceptibility to infection, comparable to those observed before receipt of MMR3. The antibody titers to Genotype G remained consistently lower than the titers to the vaccine strain.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"372 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pavithra Daulagala, Yonna W Y Leung, Leo L H Luk, Faith Ho, Sofia H N Chu, Jing Lin, Samuel M S Cheng, Nancy H L Leung, Maryna C Eichelberger, Malik Peiris, A Danielle Iuliano, Mark G Thompson, Benjamin J Cowling, Hui-Ling Yen
Background Anti-neuraminidase antibodies have been identified as a correlate of protection for influenza virus infection. We evaluated the immunogenicity of enhanced influenza vaccines versus standard-dose vaccine in inducing neuraminidase inhibition (NAI) antibodies in older adults in a 2-year randomized trial. Methods In 2017/2018, older adults aged 65-82 years in Hong Kong were randomly allocated to receive standard-dose quadrivalent (SD-IIV4), high-dose trivalent (HD-IIV3), MF59-adjuvanted trivalent (aIIV3), or recombinant quadrivalent (RIV4) influenza vaccines of 2017/2018 northern hemisphere formations; HD-IIV3, aIIV3 and RIV4 are enhanced vaccines. NAI antibodies to the 2017/2018 A(H1N1)pdm09 and A(H3N2) vaccine strains were determined from 400 recipients (100 per vaccine group). In 2018/2019, participants were re-randomized to receive the same or a different type of vaccine of northern hemisphere formations. NAI antibodies to the 2018/2019 A(H1N1)pdm09 and A(H3N2) vaccine strains were determined from SD-IIV4 (n=45), HD-IIV3 (n=64), aIIV3 (n=75), or RIV4 (n=29) recipients. NAI antibody titers on the day of vaccination and 30 days post-vaccination were used to compare the geometric mean titer-fold-rise (GMFR) and seroconversion rates of enhanced influenza vaccines versus SD-IIV4. Results SD-IIV4, HD-IIV3, and aIIV3 induced detectable NAI antibodies to both N1 and N2 antigens with GMFR significantly greater than 1. In both years, aIIV3 induced significantly higher GMFR and seroconversion rates to N1 and N2 antigens than SD-IIV4. Notably, individual baseline NAI antibody titers were inversely associated with the post-vaccination antibody titer-fold-rises in all vaccine groups. Conclusions MF-59 adjuvanted aIIV3 induced superior NAI antibody response in older adults than SD-IIV4 in a 2-year randomized trial.
{"title":"Anti-neuraminidase antibody responses in older adults after consecutive vaccinations with enhanced influenza vaccines: a randomized controlled trial","authors":"Pavithra Daulagala, Yonna W Y Leung, Leo L H Luk, Faith Ho, Sofia H N Chu, Jing Lin, Samuel M S Cheng, Nancy H L Leung, Maryna C Eichelberger, Malik Peiris, A Danielle Iuliano, Mark G Thompson, Benjamin J Cowling, Hui-Ling Yen","doi":"10.1093/infdis/jiaf616","DOIUrl":"https://doi.org/10.1093/infdis/jiaf616","url":null,"abstract":"Background Anti-neuraminidase antibodies have been identified as a correlate of protection for influenza virus infection. We evaluated the immunogenicity of enhanced influenza vaccines versus standard-dose vaccine in inducing neuraminidase inhibition (NAI) antibodies in older adults in a 2-year randomized trial. Methods In 2017/2018, older adults aged 65-82 years in Hong Kong were randomly allocated to receive standard-dose quadrivalent (SD-IIV4), high-dose trivalent (HD-IIV3), MF59-adjuvanted trivalent (aIIV3), or recombinant quadrivalent (RIV4) influenza vaccines of 2017/2018 northern hemisphere formations; HD-IIV3, aIIV3 and RIV4 are enhanced vaccines. NAI antibodies to the 2017/2018 A(H1N1)pdm09 and A(H3N2) vaccine strains were determined from 400 recipients (100 per vaccine group). In 2018/2019, participants were re-randomized to receive the same or a different type of vaccine of northern hemisphere formations. NAI antibodies to the 2018/2019 A(H1N1)pdm09 and A(H3N2) vaccine strains were determined from SD-IIV4 (n=45), HD-IIV3 (n=64), aIIV3 (n=75), or RIV4 (n=29) recipients. NAI antibody titers on the day of vaccination and 30 days post-vaccination were used to compare the geometric mean titer-fold-rise (GMFR) and seroconversion rates of enhanced influenza vaccines versus SD-IIV4. Results SD-IIV4, HD-IIV3, and aIIV3 induced detectable NAI antibodies to both N1 and N2 antigens with GMFR significantly greater than 1. In both years, aIIV3 induced significantly higher GMFR and seroconversion rates to N1 and N2 antigens than SD-IIV4. Notably, individual baseline NAI antibody titers were inversely associated with the post-vaccination antibody titer-fold-rises in all vaccine groups. Conclusions MF-59 adjuvanted aIIV3 induced superior NAI antibody response in older adults than SD-IIV4 in a 2-year randomized trial.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUNDWest Nile virus (WNV) infection may result in a serious, neuroinvasive, life-threatening disease. Since there is no known therapy against the virus, treatment is based on supportive care. Little is known about the effect of corticosteroids in West Nile-infected patients, and their use remains controversial.AIMTo evaluate the effect of corticosteroid treatment in West Nile virus-infected patients.METHODSA retrospective cohort study was conducted at Rabin Medical Center, including West Nile virus-infected patients. Data was extracted from patients' electronic medical records. Inverse probability of treatment weighting was used to adjust patient characteristics. Our exposure of interest was corticosteroid prescription during the first 48 hours. IPTW-adjusted Cox proportional hazard models were used to compare the risk of hospital mortality. Secondary outcomes included the need for mechanical ventilation or intensive care unit transfer, and the need for rehabilitation or a long-term care facility at discharge.RESULTSData from 150 confirmed cases were extracted. 41 (27%) patients received corticosteroids. After adjusting for potential confounders, corticosteroid treatment was found to significantly increase hospital mortality (adjusted hazard ratio [aHR] 3.93, 95% confidence interval [CI] 1.14-13.51). A sensitivity analysis including patients with West Nile neuroinvasive disease (WNND) and patients hospitalized for more than 48 hours showed consistent results.CONCLUSIONSOur study suggests that corticosteroid use in WNV patients may be associated with an increased risk of hospital mortality, highlighting the need for caution in their use and further prospective investigation.
{"title":"The Impact of Corticosteroid Therapy on West Nile Virus-Infected Patients: A Retrospective Cohort Study.","authors":"Itamar Poran,Bar Basharim,Yaara Leibovici-Weisman,Michal Michaelis,Nassem Ghantous,Noa Eliakim-Raz","doi":"10.1093/infdis/jiaf601","DOIUrl":"https://doi.org/10.1093/infdis/jiaf601","url":null,"abstract":"BACKGROUNDWest Nile virus (WNV) infection may result in a serious, neuroinvasive, life-threatening disease. Since there is no known therapy against the virus, treatment is based on supportive care. Little is known about the effect of corticosteroids in West Nile-infected patients, and their use remains controversial.AIMTo evaluate the effect of corticosteroid treatment in West Nile virus-infected patients.METHODSA retrospective cohort study was conducted at Rabin Medical Center, including West Nile virus-infected patients. Data was extracted from patients' electronic medical records. Inverse probability of treatment weighting was used to adjust patient characteristics. Our exposure of interest was corticosteroid prescription during the first 48 hours. IPTW-adjusted Cox proportional hazard models were used to compare the risk of hospital mortality. Secondary outcomes included the need for mechanical ventilation or intensive care unit transfer, and the need for rehabilitation or a long-term care facility at discharge.RESULTSData from 150 confirmed cases were extracted. 41 (27%) patients received corticosteroids. After adjusting for potential confounders, corticosteroid treatment was found to significantly increase hospital mortality (adjusted hazard ratio [aHR] 3.93, 95% confidence interval [CI] 1.14-13.51). A sensitivity analysis including patients with West Nile neuroinvasive disease (WNND) and patients hospitalized for more than 48 hours showed consistent results.CONCLUSIONSOur study suggests that corticosteroid use in WNV patients may be associated with an increased risk of hospital mortality, highlighting the need for caution in their use and further prospective investigation.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
After being told that my work was “not independent enough” and that I was “not doing real science,” I began to question how academic medicine defines success. Through teamwork in translational HIV research and community-engaged programs like The Last Gift, I’ve come to see that independence is an illusion, and that collaboration, empathy, and connection are the true engines of discovery and impactful research. This reflection challenges the traditional, hegemonic, metrics of scientific achievement and calls for a broader definition that values mentorship, equity, and collective progress as essential to meaningful science.
{"title":"The Day I Was Told I Wasn’t Doing Science—And Why I’m Grateful for It","authors":"Sara Gianella","doi":"10.1093/infdis/jiaf614","DOIUrl":"https://doi.org/10.1093/infdis/jiaf614","url":null,"abstract":"After being told that my work was “not independent enough” and that I was “not doing real science,” I began to question how academic medicine defines success. Through teamwork in translational HIV research and community-engaged programs like The Last Gift, I’ve come to see that independence is an illusion, and that collaboration, empathy, and connection are the true engines of discovery and impactful research. This reflection challenges the traditional, hegemonic, metrics of scientific achievement and calls for a broader definition that values mentorship, equity, and collective progress as essential to meaningful science.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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