Jessica T Lin, Derrick K Mathias, Guozheng Yang, Mwajabu Loya, Meredith S Muller, Christopher Basham, Vincent Nyasembe, Kano Amagai, Isaack Rutha, Claudia Gaither, Mwanaidi Nyange, Hamza Said, Srijana B Chhetri, Brian Swinehart, Feng-Chang Lin, Rhoel R Dinglasan, Jonathan J Juliano, Brian Tarimo, Billy Ngasala
Background Asymptomatic malaria carriers often harbor low parasite densities missed by rapid diagnostic tests (RDTs), yet they contribute to transmission. Direct skin feeding assays (DSFs) can sensitively measure their infectiousness to mosquitoes. Methods To characterize human-to-mosquito transmission from the asymptomatic reservoir in Bagamoyo, Tanzania, DSFs were performed in persons >5 years of age positive for P. falciparum by RDT or real-time PCR. Fifty colony-reared Anopheles gambiae were fed on the posterior calves. Successful mosquito infection was defined as ≥1 oocyst-positive mosquito midgut among 25 dissected eight days post-skin feeding. Results Among 491 participants with median parasite density of 5.1 parasites/uL who underwent DSF, 22% were infectious to mosquitoes. RDT-positive participants infected roughly twice as many mosquitoes compared to RDT-negative/PCR-positive persons. However, up to 21% of infectious carriers were PCR-negative at the time of skin feeding, after screening PCR-positive a few days earlier. Overall, 9.1% (342/3,741) of mosquitoes fed on infectious carriers were parasite-positive at dissection. Half of infectious individuals infected a single mosquito, while the top 16 transmitters (3% of those undergoing DSF) cumulatively infected 57% of infected mosquitoes. RDT-positive school-age children (6-15yo), 27% of the DSF cohort, contributed to 58% of infected mosquitoes. Unexpectedly, mosquito midguts from 39 DSFs (44% of oocyst-positive feeds analyzed) tested positive for Plasmodium ovale. Conclusions Parasites circulating at the limit of PCR detection commonly infect mosquitoes. However, a small proportion of highly infectious carriers contribute disproportionately to transmission, offering potential for targeted interventions. Plasmodium ovale was frequently co-transmitted with P. falciparum to mosquitoes.
{"title":"Uneven Plasmodium falciparum transmission and cryptic ovale transmission from the asymptomatic reservoir in Bagamoyo, Tanzania","authors":"Jessica T Lin, Derrick K Mathias, Guozheng Yang, Mwajabu Loya, Meredith S Muller, Christopher Basham, Vincent Nyasembe, Kano Amagai, Isaack Rutha, Claudia Gaither, Mwanaidi Nyange, Hamza Said, Srijana B Chhetri, Brian Swinehart, Feng-Chang Lin, Rhoel R Dinglasan, Jonathan J Juliano, Brian Tarimo, Billy Ngasala","doi":"10.1093/infdis/jiaf634","DOIUrl":"https://doi.org/10.1093/infdis/jiaf634","url":null,"abstract":"Background Asymptomatic malaria carriers often harbor low parasite densities missed by rapid diagnostic tests (RDTs), yet they contribute to transmission. Direct skin feeding assays (DSFs) can sensitively measure their infectiousness to mosquitoes. Methods To characterize human-to-mosquito transmission from the asymptomatic reservoir in Bagamoyo, Tanzania, DSFs were performed in persons >5 years of age positive for P. falciparum by RDT or real-time PCR. Fifty colony-reared Anopheles gambiae were fed on the posterior calves. Successful mosquito infection was defined as ≥1 oocyst-positive mosquito midgut among 25 dissected eight days post-skin feeding. Results Among 491 participants with median parasite density of 5.1 parasites/uL who underwent DSF, 22% were infectious to mosquitoes. RDT-positive participants infected roughly twice as many mosquitoes compared to RDT-negative/PCR-positive persons. However, up to 21% of infectious carriers were PCR-negative at the time of skin feeding, after screening PCR-positive a few days earlier. Overall, 9.1% (342/3,741) of mosquitoes fed on infectious carriers were parasite-positive at dissection. Half of infectious individuals infected a single mosquito, while the top 16 transmitters (3% of those undergoing DSF) cumulatively infected 57% of infected mosquitoes. RDT-positive school-age children (6-15yo), 27% of the DSF cohort, contributed to 58% of infected mosquitoes. Unexpectedly, mosquito midguts from 39 DSFs (44% of oocyst-positive feeds analyzed) tested positive for Plasmodium ovale. Conclusions Parasites circulating at the limit of PCR detection commonly infect mosquitoes. However, a small proportion of highly infectious carriers contribute disproportionately to transmission, offering potential for targeted interventions. Plasmodium ovale was frequently co-transmitted with P. falciparum to mosquitoes.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730782","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}
Julien Tran,Kate Maddaford,Jason J Ong,Ei T Aung,Christopher K Fairley,Eric P F Chow
INTRODUCTIONPrimary anorectal syphilis may go unnoticed in men who have sex with men (MSM) engaging in receptive anal sex. This study examined whether weekly digital anorectal examination (DARE) could help men self-detect abnormalities indicative of primary anorectal syphilis.METHODSA cohort study of MSM aged ≥18 years who engage in receptive anal sex was conducted at the Melbourne Sexual Health Centre from 9 March 2022 to 4 August 2023. Participants received instructions on how to perform DARE, along with weekly text reminders for 48 weeks. Those who self-detected abnormalities were advised to seek clinical consultation. The primary outcome was the proportion of syphilis cases detected via DARE. Secondary outcomes included reports of DARE-related abnormalities, adherence, and experiences.RESULTSOf the 222 men recruited, 181 (81.5%) completed the study. Six men (2.7%; 95% CI: 0.9 to 5.8) were diagnosed with syphilis-one primary anorectal infection detected by DARE, two secondary infections and three early latent syphilis infections. There were 32 clinical consultations prompted by DARE. On average, men performed 78.2% (95% CI: 77.3 to 79.0) of their weekly DARE which showed no significant variation over time (ptrend=0.26). Most found DARE easy to perform (>95.0%) and would continue performing it if recommended for early syphilis detection (77.6%).CONCLUSIONSMen's high adherence to performing we DARE suggests that it may complement routine screening for primary anorectal syphilis. However, its sensitivity may be limited, as five out of six early syphilis cases did not have primary lesions that were self-detected by the five men.
{"title":"Digital anorectal examination to self-detect primary syphilis: a prospective cohort study.","authors":"Julien Tran,Kate Maddaford,Jason J Ong,Ei T Aung,Christopher K Fairley,Eric P F Chow","doi":"10.1093/infdis/jiaf628","DOIUrl":"https://doi.org/10.1093/infdis/jiaf628","url":null,"abstract":"INTRODUCTIONPrimary anorectal syphilis may go unnoticed in men who have sex with men (MSM) engaging in receptive anal sex. This study examined whether weekly digital anorectal examination (DARE) could help men self-detect abnormalities indicative of primary anorectal syphilis.METHODSA cohort study of MSM aged ≥18 years who engage in receptive anal sex was conducted at the Melbourne Sexual Health Centre from 9 March 2022 to 4 August 2023. Participants received instructions on how to perform DARE, along with weekly text reminders for 48 weeks. Those who self-detected abnormalities were advised to seek clinical consultation. The primary outcome was the proportion of syphilis cases detected via DARE. Secondary outcomes included reports of DARE-related abnormalities, adherence, and experiences.RESULTSOf the 222 men recruited, 181 (81.5%) completed the study. Six men (2.7%; 95% CI: 0.9 to 5.8) were diagnosed with syphilis-one primary anorectal infection detected by DARE, two secondary infections and three early latent syphilis infections. There were 32 clinical consultations prompted by DARE. On average, men performed 78.2% (95% CI: 77.3 to 79.0) of their weekly DARE which showed no significant variation over time (ptrend=0.26). Most found DARE easy to perform (>95.0%) and would continue performing it if recommended for early syphilis detection (77.6%).CONCLUSIONSMen's high adherence to performing we DARE suggests that it may complement routine screening for primary anorectal syphilis. However, its sensitivity may be limited, as five out of six early syphilis cases did not have primary lesions that were self-detected by the five men.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145728379","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":"Clinical Commentary on: Targeting Tryptophan Metabolism for Tuberculosis Biomarkers and Host Directed Therapy.","authors":"Joel D Ernst","doi":"10.1093/infdis/jiaf624","DOIUrl":"https://doi.org/10.1093/infdis/jiaf624","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145728380","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}
Maribeth R Nicholson, Siyuan Ma, Britton A Strickland, Mia Cecala, Lisa Zhang, Seth Reasoner, Emma R Guiberson, Matthew J Munneke, Meghan H Shilts, Eric P Skaar, Suman R Das
Background and Aims Symptomatic Clostridioides difficile infection (CDI) can cause significant morbidity and mortality. Conversely, patients can be colonized with toxigenic C. difficile in the absence of symptoms, termed asymptomatic colonization. We previously demonstrated that the presence and function of C. difficile toxins do not differentiate between asymptomatic colonization and CDI in children, suggesting the influence of other factors. This study aimed to interrogate the intestinal microbiome and butyrate in stool samples from children with CDI and asymptomatic colonization. Methods Design: Case-control study Setting: Tertiary care children’s hospital Participants and measures: Asymptomatic children had stool tested for C. difficile by nucleic-acid amplification-based testing (NAAT) and were considered colonized if positive (N=50). Residual stool was also obtained from symptomatic children who tested positive for C. difficile by NAAT (N=55). The microbiome was assessed via 16S rRNA sequencing and butyrate via liquid chromatography-mass spectrometry. Results Compared to clinical co-variates and comorbidities, C. difficile symptom status (i.e., asymptomatic colonization versus symptomatic CDI) demonstrated the strongest differential abundance association on gut microbes. Symptomatic CDI was associated with increased abundance of Escherichia/Shigella (Benjamini-Hochberg adjusted q=3.94x10-5), Haemophilus (q=0.022), and Gemella (q=0.085), and depleted abundance of gut commensals such as Faecalibacterium (q=0.041), Blautia (q=0.041), and Bifidobacterium (q=0.063). We also observed depletion in the abundance of microbial butyrate producers and fecal butyrate in participants with symptomatic CDI versus asymptomatic colonization. Conclusion The gut microbiota and butyrate differ between participants with asymptomatic C. difficile colonization and symptomatic CDI, suggesting their potential role in symptom development.
{"title":"The Gut Microbiome and Butyrate Differentiate Clostridioides difficile Colonization and Infection in Children","authors":"Maribeth R Nicholson, Siyuan Ma, Britton A Strickland, Mia Cecala, Lisa Zhang, Seth Reasoner, Emma R Guiberson, Matthew J Munneke, Meghan H Shilts, Eric P Skaar, Suman R Das","doi":"10.1093/infdis/jiaf631","DOIUrl":"https://doi.org/10.1093/infdis/jiaf631","url":null,"abstract":"Background and Aims Symptomatic Clostridioides difficile infection (CDI) can cause significant morbidity and mortality. Conversely, patients can be colonized with toxigenic C. difficile in the absence of symptoms, termed asymptomatic colonization. We previously demonstrated that the presence and function of C. difficile toxins do not differentiate between asymptomatic colonization and CDI in children, suggesting the influence of other factors. This study aimed to interrogate the intestinal microbiome and butyrate in stool samples from children with CDI and asymptomatic colonization. Methods Design: Case-control study Setting: Tertiary care children’s hospital Participants and measures: Asymptomatic children had stool tested for C. difficile by nucleic-acid amplification-based testing (NAAT) and were considered colonized if positive (N=50). Residual stool was also obtained from symptomatic children who tested positive for C. difficile by NAAT (N=55). The microbiome was assessed via 16S rRNA sequencing and butyrate via liquid chromatography-mass spectrometry. Results Compared to clinical co-variates and comorbidities, C. difficile symptom status (i.e., asymptomatic colonization versus symptomatic CDI) demonstrated the strongest differential abundance association on gut microbes. Symptomatic CDI was associated with increased abundance of Escherichia/Shigella (Benjamini-Hochberg adjusted q=3.94x10-5), Haemophilus (q=0.022), and Gemella (q=0.085), and depleted abundance of gut commensals such as Faecalibacterium (q=0.041), Blautia (q=0.041), and Bifidobacterium (q=0.063). We also observed depletion in the abundance of microbial butyrate producers and fecal butyrate in participants with symptomatic CDI versus asymptomatic colonization. Conclusion The gut microbiota and butyrate differ between participants with asymptomatic C. difficile colonization and symptomatic CDI, suggesting their potential role in symptom development.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145729061","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 L Reed,Matthew A Butzler,Claudia A Hawkins,Yukari C Manabe,Jeffrey Holden,David L Thomas,Andrea L Cox,Sally M McFall
BACKGROUNDHepatitis C virus (HCV) infection is a major public health problem despite the availability of highly effective and curative direct acting antiviral (DAA) treatments. Low diagnostic rates, driven in part by a two-step diagnostic process and the need for molecular confirmation, pose a significant barrier to timely treatment. Here we describe the development, analytical characterization, and a preliminary clinical validation study of a rapid, user-friendly, sensitive, qualitative molecular test for point-of-care HCV testing.METHODSThis study evaluated the analytical performance of a 15-minute time to result qualitative molecular test for HCV on the sample-to-answer point-of-care DASH® Rapid PCR System. The dynamic range, limit of detection, analytical specificity, and the equivalent detection of genotypes 1-6 were assessed. A small clinical validation study was independently conducted by Johns Hopkins investigators using retrospectively collected specimens.RESULTSThe Research Use Only (RUO) DASH® HCV assay has wide dynamic range, can detect HCV genotypes 1-6, and has a detection limit of 200 IU/mL with 100 μL specimen volume addition. In a preliminary study of 97 plasma specimens, the DASH® HCV assay demonstrated 100% positive percent agreement (PPA) and 100% negative percent agreement (NPA) when compared to commercial platforms.CONCLUSIONSThe DASH® HCV test holds potential to enable same-day diagnosis and treatment in support of HCV elimination efforts.
{"title":"Development of a Rapid Automated Point-of-Care Test for Hepatitis C Viral RNA on the DASH® Rapid PCR System.","authors":"Jennifer L Reed,Matthew A Butzler,Claudia A Hawkins,Yukari C Manabe,Jeffrey Holden,David L Thomas,Andrea L Cox,Sally M McFall","doi":"10.1093/infdis/jiaf608","DOIUrl":"https://doi.org/10.1093/infdis/jiaf608","url":null,"abstract":"BACKGROUNDHepatitis C virus (HCV) infection is a major public health problem despite the availability of highly effective and curative direct acting antiviral (DAA) treatments. Low diagnostic rates, driven in part by a two-step diagnostic process and the need for molecular confirmation, pose a significant barrier to timely treatment. Here we describe the development, analytical characterization, and a preliminary clinical validation study of a rapid, user-friendly, sensitive, qualitative molecular test for point-of-care HCV testing.METHODSThis study evaluated the analytical performance of a 15-minute time to result qualitative molecular test for HCV on the sample-to-answer point-of-care DASH® Rapid PCR System. The dynamic range, limit of detection, analytical specificity, and the equivalent detection of genotypes 1-6 were assessed. A small clinical validation study was independently conducted by Johns Hopkins investigators using retrospectively collected specimens.RESULTSThe Research Use Only (RUO) DASH® HCV assay has wide dynamic range, can detect HCV genotypes 1-6, and has a detection limit of 200 IU/mL with 100 μL specimen volume addition. In a preliminary study of 97 plasma specimens, the DASH® HCV assay demonstrated 100% positive percent agreement (PPA) and 100% negative percent agreement (NPA) when compared to commercial platforms.CONCLUSIONSThe DASH® HCV test holds potential to enable same-day diagnosis and treatment in support of HCV elimination efforts.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"162 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145711098","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}
Putu A I Shanti, King Alexander, Freis Candrawati, Benediktus Andries, Noy Norman Kambuaya, Hasrini Rini, Aisah R Amelia, Agatha M Puspitasari, Ristya Amalia, Desandra A Rahmayenti, Leo Leonardo, Pak Prayoga, Leily Trianty, Zuleima Pava, Enny Kenangalem, Sarah Auburn, Ric N Price, Ida Safitri Laksanawati, Pierre A Buffet, Rintis Noviyanti, Nicholas M Anstey, Jeanne R Poespoprodjo, Steven Kho
Splenic rupture is a recognised complication of acute Plasmodium falciparum and P. vivax malaria, but the risk of splenic rupture in chronic asymptomatic infections is unknown. In Timika, Papua, Indonesia, we determined the proportion of PCR-detectable asymptomatic peripheral parasitaemia in patients undergoing trauma-related splenectomy (2015-21), and found it was more than twice the proportion compared to a 2013 household survey of the general population (87.9% [29/33] vs 38.6% [697/1,807]; p<0.0001). Our findings suggest asymptomatic parasitaemia with either P. falciparum or P. vivax is associated with splenic rupture following trauma, pointing towards an additional consequence of chronic infection in malaria-endemic areas.
{"title":"Chronic malaria is associated with trauma-related splenic rupture requiring splenectomy","authors":"Putu A I Shanti, King Alexander, Freis Candrawati, Benediktus Andries, Noy Norman Kambuaya, Hasrini Rini, Aisah R Amelia, Agatha M Puspitasari, Ristya Amalia, Desandra A Rahmayenti, Leo Leonardo, Pak Prayoga, Leily Trianty, Zuleima Pava, Enny Kenangalem, Sarah Auburn, Ric N Price, Ida Safitri Laksanawati, Pierre A Buffet, Rintis Noviyanti, Nicholas M Anstey, Jeanne R Poespoprodjo, Steven Kho","doi":"10.1093/infdis/jiaf629","DOIUrl":"https://doi.org/10.1093/infdis/jiaf629","url":null,"abstract":"Splenic rupture is a recognised complication of acute Plasmodium falciparum and P. vivax malaria, but the risk of splenic rupture in chronic asymptomatic infections is unknown. In Timika, Papua, Indonesia, we determined the proportion of PCR-detectable asymptomatic peripheral parasitaemia in patients undergoing trauma-related splenectomy (2015-21), and found it was more than twice the proportion compared to a 2013 household survey of the general population (87.9% [29/33] vs 38.6% [697/1,807]; p&lt;0.0001). Our findings suggest asymptomatic parasitaemia with either P. falciparum or P. vivax is associated with splenic rupture following trauma, pointing towards an additional consequence of chronic infection in malaria-endemic areas.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717478","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}
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}
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