In allogeneic hematopoietic cell transplant (HCT)-recipients, prophylactic management strategies are essential for preventing CMV-reactivation and associated disease. We report on a 63-year-old male patient with a D-/R+ CMV-serostatus, who showed ongoing low-level CMV-replication post-HCT despite receiving letermovir prophylaxis. Sanger-sequencing failed to detect drug resistance mutations (DRM) until CMV-pneumonitis developed, revealing a UL56-C325R-DRM linked to high-level letermovir resistance. Retrospective analysis with next-generation-sequencing (NGS) revealed the DRM at a low frequency of 6% two weeks prior to detection by Sanger-sequencing. This study highlights the importance of advanced NGS-methods for early detection of CMV-DRMs, allowing for faster adjustments in antiviral treatment strategies.
{"title":"Revealing the unseen: next generation sequencing for early detection of drug-resistant cytomegalovirus variants upon letermovir prophylaxis failure","authors":"Klaudia Nägele, Veronika Bättig, Rainer Gosert, Carla S Walti, Spasenija Savic Prince, Jörg Halter, Roby Mathews, Claudia Stühler, Nina Khanna, Karoline Leuzinger","doi":"10.1093/infdis/jiae414","DOIUrl":"https://doi.org/10.1093/infdis/jiae414","url":null,"abstract":"In allogeneic hematopoietic cell transplant (HCT)-recipients, prophylactic management strategies are essential for preventing CMV-reactivation and associated disease. We report on a 63-year-old male patient with a D-/R+ CMV-serostatus, who showed ongoing low-level CMV-replication post-HCT despite receiving letermovir prophylaxis. Sanger-sequencing failed to detect drug resistance mutations (DRM) until CMV-pneumonitis developed, revealing a UL56-C325R-DRM linked to high-level letermovir resistance. Retrospective analysis with next-generation-sequencing (NGS) revealed the DRM at a low frequency of 6% two weeks prior to detection by Sanger-sequencing. This study highlights the importance of advanced NGS-methods for early detection of CMV-DRMs, allowing for faster adjustments in antiviral treatment strategies.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100627","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}
Prisha Balgovind, Eithandee Aung, Hannah Shilling, Gerald L Murray, Monica Molano, Suzanne M Garland, Christopher K Fairley, Marcus Y Chen, Jane S Hocking, Catriona Ooi, Anna McNulty, Jenny McCloskey, Kathleen McNamee, Deborah Bateson, Louise Owen, Sepehr N Tabrizi, Dorothy A Machalek
Background Australia introduced a national HPV vaccination program for girls in 2007 and boys in 2013, achieving high coverage in both populations. We assessed HPV prevalence among men who have sex with women (MSW) and men who have sex with men (MSM) aged 18–35 years and examined program effects by vaccination status. Methods Men recruited between 2015–2018 self-collected a penile or intra-anal swab for HPV genotyping. HPV vaccination status was confirmed with the National Register. HPV prevalence was examined by age groups and vaccination status. Results Of 1,625 men included (median age 27 years; IQR [23–30]), 231 (14.2%) were vaccinated, and 1,370 (84.3%) were unvaccinated. Among 984 MSW, the prevalence of quadrivalent vaccine-targeted HPV types (6,11,16,18) was 10.6% (95%CI: 8.7–12.8) in unvaccinated and 10.7% (5.7–19.3%) in vaccinated men (p=0.96). Prevalence was lowest in the youngest age groups regardless of vaccination status. Among MSM, quadrivalent HPV type prevalence was 40.3% (36.0–44.8%) in unvaccinated and 29.9% (23.1–37.8%) in vaccinated men (p=0.02). In unvaccinated MSM, prevalence was high regardless of age, whereas among vaccinated MSM, prevalence was lowest in the youngest age-group (p=0.001). Among those with confirmed doses, quadrivalent HPV types were detected in 0% (0–7.7%; n=46) of men who had their first dose at 13–19 years and 37.2% (27.5–47.8%; n=94) of those who received their first dose at 20 years or older. Conclusion Our data demonstrates the importance of universal adolescent HPV vaccination to ensure MSM receive the same benefits as MSW.
{"title":"Human papillomavirus prevalence among Australian men aged 18–35 years in 2015–2018 according to vaccination status and sexual preference","authors":"Prisha Balgovind, Eithandee Aung, Hannah Shilling, Gerald L Murray, Monica Molano, Suzanne M Garland, Christopher K Fairley, Marcus Y Chen, Jane S Hocking, Catriona Ooi, Anna McNulty, Jenny McCloskey, Kathleen McNamee, Deborah Bateson, Louise Owen, Sepehr N Tabrizi, Dorothy A Machalek","doi":"10.1093/infdis/jiae412","DOIUrl":"https://doi.org/10.1093/infdis/jiae412","url":null,"abstract":"Background Australia introduced a national HPV vaccination program for girls in 2007 and boys in 2013, achieving high coverage in both populations. We assessed HPV prevalence among men who have sex with women (MSW) and men who have sex with men (MSM) aged 18–35 years and examined program effects by vaccination status. Methods Men recruited between 2015–2018 self-collected a penile or intra-anal swab for HPV genotyping. HPV vaccination status was confirmed with the National Register. HPV prevalence was examined by age groups and vaccination status. Results Of 1,625 men included (median age 27 years; IQR [23–30]), 231 (14.2%) were vaccinated, and 1,370 (84.3%) were unvaccinated. Among 984 MSW, the prevalence of quadrivalent vaccine-targeted HPV types (6,11,16,18) was 10.6% (95%CI: 8.7–12.8) in unvaccinated and 10.7% (5.7–19.3%) in vaccinated men (p=0.96). Prevalence was lowest in the youngest age groups regardless of vaccination status. Among MSM, quadrivalent HPV type prevalence was 40.3% (36.0–44.8%) in unvaccinated and 29.9% (23.1–37.8%) in vaccinated men (p=0.02). In unvaccinated MSM, prevalence was high regardless of age, whereas among vaccinated MSM, prevalence was lowest in the youngest age-group (p=0.001). Among those with confirmed doses, quadrivalent HPV types were detected in 0% (0–7.7%; n=46) of men who had their first dose at 13–19 years and 37.2% (27.5–47.8%; n=94) of those who received their first dose at 20 years or older. Conclusion Our data demonstrates the importance of universal adolescent HPV vaccination to ensure MSM receive the same benefits as MSW.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100631","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}
Sergio Serrano-Villar, Akshay Gala, Peter Bacchetti, Rebecca Hoh, Clara di Germanio, Lillian B Cohn, Timothy J Henrich, Peter W Hunt, Gregory M Laird, Satish K Pillai, Steven G Deeks, Michael J Peluso
Background During antiretroviral therapy (ART), the HIV reservoir exhibits variability as cells with intact genomes decay faster than those with defective genomes, especially in the first years of therapy. The host factors influencing this decay are yet to be characterized. Methods Observational study in 74 PWH on ART, of whom 70 (94.6%) were male. We used the intact proviral DNA assay to measure intact proviruses and Luminex immunoassay to measure 32 inflammatory cytokines in plasma. Linear spline models, with a knot at seven years, evaluated the impact of baseline cytokine levels and their trajectories on intact HIV kinetics over these years. Results Baseline Gal-9 was the most predictive marker for intact HIV kinetics, with lower Gal-9 predicting faster decay over the subsequent seven years. For each 10-fold decrease in Gal-9 at baseline, there was a mean 45% (95%CI 14%-84%) greater decay of intact HIV genomes per year. Conversely, higher baseline ITAC, IL-17, and MIP-1α predicted faster intact HIV decreases. Longitudinal changes in MIP-3α and IL-6 levels strongly associated with intact HIV kinetics, with a 10-fold increase in MIP-3α and a 10-fold decrease in IL-6 associated with a a 9.5% and 10% faster decay of intact HIV genomes per year, respectively. Conclusion The pronounced association between baseline Gal-9 levels and subsequent intact HIV decay suggests that strategies reducing Gal-9 levels could accelerate reservoir decay. Additionally, the correlations of MIP-3α and IL-6 with HIV kinetics indicate a broader cytokine-mediated regulatory network, hinting at multi-targeted interventions that could modulate HIV reservoir dynamics.
背景 在抗逆转录病毒疗法（ART）期间，HIV 病毒库表现出多变性，因为基因组完整的细胞比基因组有缺陷的细胞衰减得更快，尤其是在治疗的最初几年。影响这种衰减的宿主因素尚不明确。方法 对 74 名接受抗逆转录病毒疗法的感染者进行观察研究，其中 70 人（94.6%）为男性。我们使用完整病毒前体 DNA 检测法检测完整病毒前体，并使用 Luminex 免疫测定法检测血浆中的 32 种炎症细胞因子。线性样条模型以 7 年为节点，评估了基线细胞因子水平及其轨迹对这些年完整 HIV 动力学的影响。结果 基线 Gal-9 是最能预测完整 HIV 动力学的标志物，Gal-9 越低，预测其后七年的衰减速度越快。基线 Gal-9 每降低 10 倍，每年完整 HIV 基因组的平均衰减率就会增加 45%（95%CI 14%-84%）。相反，基线 ITAC、IL-17 和 MIP-1α 越高，则完整 HIV 基因组的衰减速度越快。MIP-3α和IL-6水平的纵向变化与完整HIV动力学密切相关，MIP-3α增加10倍和IL-6减少10倍分别与每年完整HIV基因组衰减速度加快9.5%和10%有关。结论 Gal-9 基线水平与随后的完整 HIV 基因组衰减之间的明显关联表明，降低 Gal-9 水平的策略可加速病毒库的衰减。此外，MIP-3α和IL-6与HIV动力学的相关性表明，细胞因子介导的调控网络更为广泛，暗示着多靶点干预措施可以调节HIV库的动态变化。
{"title":"Galectin-9 Levels as a Potential Predictor of Intact HIV Reservoir Decay","authors":"Sergio Serrano-Villar, Akshay Gala, Peter Bacchetti, Rebecca Hoh, Clara di Germanio, Lillian B Cohn, Timothy J Henrich, Peter W Hunt, Gregory M Laird, Satish K Pillai, Steven G Deeks, Michael J Peluso","doi":"10.1093/infdis/jiae426","DOIUrl":"https://doi.org/10.1093/infdis/jiae426","url":null,"abstract":"Background During antiretroviral therapy (ART), the HIV reservoir exhibits variability as cells with intact genomes decay faster than those with defective genomes, especially in the first years of therapy. The host factors influencing this decay are yet to be characterized. Methods Observational study in 74 PWH on ART, of whom 70 (94.6%) were male. We used the intact proviral DNA assay to measure intact proviruses and Luminex immunoassay to measure 32 inflammatory cytokines in plasma. Linear spline models, with a knot at seven years, evaluated the impact of baseline cytokine levels and their trajectories on intact HIV kinetics over these years. Results Baseline Gal-9 was the most predictive marker for intact HIV kinetics, with lower Gal-9 predicting faster decay over the subsequent seven years. For each 10-fold decrease in Gal-9 at baseline, there was a mean 45% (95%CI 14%-84%) greater decay of intact HIV genomes per year. Conversely, higher baseline ITAC, IL-17, and MIP-1α predicted faster intact HIV decreases. Longitudinal changes in MIP-3α and IL-6 levels strongly associated with intact HIV kinetics, with a 10-fold increase in MIP-3α and a 10-fold decrease in IL-6 associated with a a 9.5% and 10% faster decay of intact HIV genomes per year, respectively. Conclusion The pronounced association between baseline Gal-9 levels and subsequent intact HIV decay suggests that strategies reducing Gal-9 levels could accelerate reservoir decay. Additionally, the correlations of MIP-3α and IL-6 with HIV kinetics indicate a broader cytokine-mediated regulatory network, hinting at multi-targeted interventions that could modulate HIV reservoir dynamics.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100632","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}
Carmen Serrano-Rísquez, Mohamed Omar, Norma Rallón, José Miguel Benito, Amparo Gómez-Vidal, Francisco José Márquez, Martina Alján, Antonio Rivero-Juárez, Ignacio Pérez-Valero, Antonio Rivero, Faruk Sinangil, Irma Saulle, Mara Biasin, Mario Clerici, Donald Forthal, Maria Eugenia Saéz, Antonio Caruz
HLA-I/KIR genotypes influence HIV-1 disease progression and viral load, but their role in primary infection is uncertain. Inconsistent results from previous studies suggest that the inoculum size and transmission route—parenteral vs. sexual—may influence this association. We conducted a GWAS in a population of people living with HIV-1 and HIV-1-exposed seronegative individuals exposed to the virus through the sexual route. Our data do not support any role of the HLA/KIR system in susceptibility to sexually transmitted HIV-1 infection. The genetics basis of HIV-1 viral load and disease progression are distinct from the genetics of HIV resistance, a paradox worth exploring.
{"title":"Impact of HLA allele-KIR partners on sexually transmitted HIV-1 infection","authors":"Carmen Serrano-Rísquez, Mohamed Omar, Norma Rallón, José Miguel Benito, Amparo Gómez-Vidal, Francisco José Márquez, Martina Alján, Antonio Rivero-Juárez, Ignacio Pérez-Valero, Antonio Rivero, Faruk Sinangil, Irma Saulle, Mara Biasin, Mario Clerici, Donald Forthal, Maria Eugenia Saéz, Antonio Caruz","doi":"10.1093/infdis/jiae436","DOIUrl":"https://doi.org/10.1093/infdis/jiae436","url":null,"abstract":"HLA-I/KIR genotypes influence HIV-1 disease progression and viral load, but their role in primary infection is uncertain. Inconsistent results from previous studies suggest that the inoculum size and transmission route—parenteral vs. sexual—may influence this association. We conducted a GWAS in a population of people living with HIV-1 and HIV-1-exposed seronegative individuals exposed to the virus through the sexual route. Our data do not support any role of the HLA/KIR system in susceptibility to sexually transmitted HIV-1 infection. The genetics basis of HIV-1 viral load and disease progression are distinct from the genetics of HIV resistance, a paradox worth exploring.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100633","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}
Ruth Namazzi, Kagan A Mellencamp, Robert O Opoka, Dibyadyuti Datta, Giselle Lima-Cooper, Claire Liepmann, Julian Sherman, Ana Rodriguez, Caroline Kazinga, Russell E Ware, Michael G Goings, Marcus Lacerda, Marco Abreu, Tae-Hwi Schwantes-An, Chandy C John, Andrea L Conroy
Background Recently, there has been an unexplained increase in the incidence of blackwater fever (BWF) in Eastern Uganda. In this study, we evaluate the association between immune complexes, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and the occurrence and recurrence of BWF in children with severe malaria (SM). Methods Between 2014 and 2017, children aged six months to <4 years hospitalized with SM and community children (CC) were recruited at two hospitals in Central and Eastern Uganda. We measured serum circulating immune complexes (cIC) and their relationship to SM complications and post-discharge outcomes and evaluated effect mediation through G6PD deficiency. Results 557 children with SM and 101 CC were enrolled. The mean age of children was 2.1 years. Children with SM had higher cIC levels than CC, p<0.001. After controlling for age, sex, and site, cIC were associated with severe anemia, jaundice, and BWF (adjusted odds ratio, 95% confidence interval: 7.33 (3.45, 15.58), p<0.0001; 4.31 (1.68, 11.08), p=0.002; and 5.21 (2.06, 13.18), p<0.0001), respectively. cIC predicted readmissions for SM, severe anemia, and BWF (adjusted incidence rate ratios (95% confidence interval): 2.11 (1.33, 3.34), p=0.001; 8.62 (2.80, 26.59), p<0.0001; and 7.66 (2.62, 22.45), p<0.0001), respectively. The relationship was most evident in males where the frequency of the G6PD African allele (A-) was 16.8%. G6PD deficiency was associated with increases in cIC in males (p=0.01) and mediation analysis suggested G6PD deficiency contributes to recurrent severe anemia and BWF via increased cIC. Conclusions Immune complexes are associated with hemolytic complications and predict recurrences in SM survivors.
{"title":"Circulating immune complexes and G6PD deficiency predict readmissions for blackwater fever and severe anemia in children with severe malaria in Eastern Uganda","authors":"Ruth Namazzi, Kagan A Mellencamp, Robert O Opoka, Dibyadyuti Datta, Giselle Lima-Cooper, Claire Liepmann, Julian Sherman, Ana Rodriguez, Caroline Kazinga, Russell E Ware, Michael G Goings, Marcus Lacerda, Marco Abreu, Tae-Hwi Schwantes-An, Chandy C John, Andrea L Conroy","doi":"10.1093/infdis/jiae431","DOIUrl":"https://doi.org/10.1093/infdis/jiae431","url":null,"abstract":"Background Recently, there has been an unexplained increase in the incidence of blackwater fever (BWF) in Eastern Uganda. In this study, we evaluate the association between immune complexes, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and the occurrence and recurrence of BWF in children with severe malaria (SM). Methods Between 2014 and 2017, children aged six months to &lt;4 years hospitalized with SM and community children (CC) were recruited at two hospitals in Central and Eastern Uganda. We measured serum circulating immune complexes (cIC) and their relationship to SM complications and post-discharge outcomes and evaluated effect mediation through G6PD deficiency. Results 557 children with SM and 101 CC were enrolled. The mean age of children was 2.1 years. Children with SM had higher cIC levels than CC, p&lt;0.001. After controlling for age, sex, and site, cIC were associated with severe anemia, jaundice, and BWF (adjusted odds ratio, 95% confidence interval: 7.33 (3.45, 15.58), p&lt;0.0001; 4.31 (1.68, 11.08), p=0.002; and 5.21 (2.06, 13.18), p&lt;0.0001), respectively. cIC predicted readmissions for SM, severe anemia, and BWF (adjusted incidence rate ratios (95% confidence interval): 2.11 (1.33, 3.34), p=0.001; 8.62 (2.80, 26.59), p&lt;0.0001; and 7.66 (2.62, 22.45), p&lt;0.0001), respectively. The relationship was most evident in males where the frequency of the G6PD African allele (A-) was 16.8%. G6PD deficiency was associated with increases in cIC in males (p=0.01) and mediation analysis suggested G6PD deficiency contributes to recurrent severe anemia and BWF via increased cIC. Conclusions Immune complexes are associated with hemolytic complications and predict recurrences in SM survivors.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100716","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}
Stephan Brouwer, Swairindhree Das, Andrew J Hayes, Olivia M Bertolla, Mark R Davies, Mark J Walker, David M Whiley, Adam D Irwin, Jacob A Tickner
Background The gradual replacement of the Streptococcus pyogenes M1global genotype by a newly emergent M1UK variant is a global public health threat warranting increased surveillance. M1UK differs from progenitor M1global genotype by 27 single nucleotide polymorphisms (SNPs) and is characterised by increased speA superantigen expression in vitro. Methods An allele-specific real-time PCR assay was developed for the rapid detection of M1UK strains. The assay was used in combination with whole-genome sequencing to determine emm (sub)type distribution for 51 invasive (n = 9) and non-invasive (n = 42) S. pyogenes clinical isolates. Results Emm1 was the most prevalent S. pyogenes emm serotype (n = 11) in this set of clinical isolates, with M1UK being the dominant emm1 genotype (4/5 invasive, 3/6 non-invasive isolates). The assay accurately detected M1UK strains. Whole genome sequencing revealed continued presence of Australian M1UK sub-lineages associated with epidemic scarlet fever-causing S. pyogenes in Asia. Conclusions Our study establishes a suitable target for detection of the toxigenic M1UK, and confirms the maintenance of M1UK strains in Queensland, Australia. This assay can be deployed in laboratories and provides a valuable, cost-effective tool to enhance surveillance of the expanding M1UK clone.
{"title":"A rapid molecular detection tool for toxigenic M1UK Streptococcus pyogenes","authors":"Stephan Brouwer, Swairindhree Das, Andrew J Hayes, Olivia M Bertolla, Mark R Davies, Mark J Walker, David M Whiley, Adam D Irwin, Jacob A Tickner","doi":"10.1093/infdis/jiae437","DOIUrl":"https://doi.org/10.1093/infdis/jiae437","url":null,"abstract":"Background The gradual replacement of the Streptococcus pyogenes M1global genotype by a newly emergent M1UK variant is a global public health threat warranting increased surveillance. M1UK differs from progenitor M1global genotype by 27 single nucleotide polymorphisms (SNPs) and is characterised by increased speA superantigen expression in vitro. Methods An allele-specific real-time PCR assay was developed for the rapid detection of M1UK strains. The assay was used in combination with whole-genome sequencing to determine emm (sub)type distribution for 51 invasive (n = 9) and non-invasive (n = 42) S. pyogenes clinical isolates. Results Emm1 was the most prevalent S. pyogenes emm serotype (n = 11) in this set of clinical isolates, with M1UK being the dominant emm1 genotype (4/5 invasive, 3/6 non-invasive isolates). The assay accurately detected M1UK strains. Whole genome sequencing revealed continued presence of Australian M1UK sub-lineages associated with epidemic scarlet fever-causing S. pyogenes in Asia. Conclusions Our study establishes a suitable target for detection of the toxigenic M1UK, and confirms the maintenance of M1UK strains in Queensland, Australia. This assay can be deployed in laboratories and provides a valuable, cost-effective tool to enhance surveillance of the expanding M1UK clone.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100714","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}
Fang Fang Li, Alison Faber, Jessica M Caleta, David M Goldfarb, Inna Sekirov, Natalie A Prystajecky, Jocelyn A Srigley, Ram Mishaal, Agatha N Jassem
Gullain-Barré syndrome (GBS) is an acute peripheral neuropathy often preceded by respiratory or gastrointestinal infections, though molecular testing of cerebrospinal fluid (CSF) is often inconclusive. In a recent case of severe pediatric GBS in British Columbia, Canada, we detected CSF antibodies against enterovirus D (EV-D) to link GBS with prior EV-D68 respiratory infection.
{"title":"Clinical application of phage immunoprecipitation sequencing to diagnose enterovirus D68 as the underlying etiology in a case of Gullain-Barré syndrome","authors":"Fang Fang Li, Alison Faber, Jessica M Caleta, David M Goldfarb, Inna Sekirov, Natalie A Prystajecky, Jocelyn A Srigley, Ram Mishaal, Agatha N Jassem","doi":"10.1093/infdis/jiae411","DOIUrl":"https://doi.org/10.1093/infdis/jiae411","url":null,"abstract":"Gullain-Barré syndrome (GBS) is an acute peripheral neuropathy often preceded by respiratory or gastrointestinal infections, though molecular testing of cerebrospinal fluid (CSF) is often inconclusive. In a recent case of severe pediatric GBS in British Columbia, Canada, we detected CSF antibodies against enterovirus D (EV-D) to link GBS with prior EV-D68 respiratory infection.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100718","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}
Yasir Arshad, Nayab Mehmood, Muhammad Masroor Alam, Adnan Khurshid, Ribqa Akhtar, Ghulam Mujtaba, Lubna Rehman, Nighat Mushtaq, Bisma Sarfraz, Rabia Hakim, Massab Umair, Muhammad Suleman Rana, Muhammad Salman, Salmaan Sharif, Sadia Sattar, Sundus Javed, Muzzamil Ahmed, Zainul Abedin Khan, Mohammed Ahmed Soghaier, Nazish Bostan
Background Pakistan is one of the two countries endemic for wild poliovirus type 1 (WPV1). Active clinical and environmental wastewater surveillance along with laboratory investigation is an integral and primary component of the polio eradication strategies. The current study is mainly focused on the virological data to understand the current epidemiology of WPV1 in Pakistan during 2019-2022. Methods 141,037 stool specimens of patients reported with acute flaccid paralysis (AFP) and 3,171 wastewater samples were tested for poliovirus detection using cell culture and PCR. Phylogenetic analysis of WPV1 was performed using MEGA and Nextstrain. Results Poliovirus isolates were classified into 15 distinct genetic clusters with multiple transmission lineages. Spatio-temporal trends indicated a significant decline in the incidence of poliomyelitis reported in 58 districts in 2019 to just 3 in 2022. The historical reservoirs in Peshawar, Quetta, and Karachi successfully eliminated the indigenous transmission chains of wild poliovirus active there for years Conclusions Our findings reinforce the evolving epidemiology of poliovirus in Pakistan which is now confined to South KP. All historically known reservoirs in Peshawar, Karachi and Quetta blocs are now free of poliovirus. Intensified clinical and environmental surveillance should be maintained to eliminate the very few remaining transmission lineages and certify the poliovirus eradication by 2026.
{"title":"Molecular Epidemiology of Wild Poliovirus Type 1 and Shift in the Historically Reservoir Areas of Pakistan During 2019-2022","authors":"Yasir Arshad, Nayab Mehmood, Muhammad Masroor Alam, Adnan Khurshid, Ribqa Akhtar, Ghulam Mujtaba, Lubna Rehman, Nighat Mushtaq, Bisma Sarfraz, Rabia Hakim, Massab Umair, Muhammad Suleman Rana, Muhammad Salman, Salmaan Sharif, Sadia Sattar, Sundus Javed, Muzzamil Ahmed, Zainul Abedin Khan, Mohammed Ahmed Soghaier, Nazish Bostan","doi":"10.1093/infdis/jiae439","DOIUrl":"https://doi.org/10.1093/infdis/jiae439","url":null,"abstract":"Background Pakistan is one of the two countries endemic for wild poliovirus type 1 (WPV1). Active clinical and environmental wastewater surveillance along with laboratory investigation is an integral and primary component of the polio eradication strategies. The current study is mainly focused on the virological data to understand the current epidemiology of WPV1 in Pakistan during 2019-2022. Methods 141,037 stool specimens of patients reported with acute flaccid paralysis (AFP) and 3,171 wastewater samples were tested for poliovirus detection using cell culture and PCR. Phylogenetic analysis of WPV1 was performed using MEGA and Nextstrain. Results Poliovirus isolates were classified into 15 distinct genetic clusters with multiple transmission lineages. Spatio-temporal trends indicated a significant decline in the incidence of poliomyelitis reported in 58 districts in 2019 to just 3 in 2022. The historical reservoirs in Peshawar, Quetta, and Karachi successfully eliminated the indigenous transmission chains of wild poliovirus active there for years Conclusions Our findings reinforce the evolving epidemiology of poliovirus in Pakistan which is now confined to South KP. All historically known reservoirs in Peshawar, Karachi and Quetta blocs are now free of poliovirus. Intensified clinical and environmental surveillance should be maintained to eliminate the very few remaining transmission lineages and certify the poliovirus eradication by 2026.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100717","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}
The ongoing Mpox (Monkeypox) outbreak in Africa, now classified as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO), presents a severe challenge, particularly for vulnerable populations like sex workers. Despite the endemic presence of Mpox in Africa since the 1970s, recent developments, including the emergence of a new clade Ib strain with increased transmissibility, have exacerbated the situation. Sex workers are at heightened risk due to their occupational exposure, compounded by stigma, criminalization, and limited access to healthcare. These factors significantly impede efforts to control the spread of the virus, leading to underreporting and inadequate intervention. This article highlights the urgent need for an inclusive public health response that prioritizes the health and safety of sex workers. Such a response should involve tailored health services, legal protections, and community engagement to ensure that this marginalized group is not overlooked. The decriminalization of sex work is also proposed as a critical public health measure to improve access to care and reduce stigma, ultimately curbing the spread of Mpox in Africa.
{"title":"Sex Workers and the Mpox Response in Africa","authors":"Yusuff Adebayo Adebisi, Somtochukwu Marycynthia Ezema, Obasanjo Bolarinwa, Archibong Edem Bassey, Isaac Olushola Ogunkola","doi":"10.1093/infdis/jiae435","DOIUrl":"https://doi.org/10.1093/infdis/jiae435","url":null,"abstract":"The ongoing Mpox (Monkeypox) outbreak in Africa, now classified as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO), presents a severe challenge, particularly for vulnerable populations like sex workers. Despite the endemic presence of Mpox in Africa since the 1970s, recent developments, including the emergence of a new clade Ib strain with increased transmissibility, have exacerbated the situation. Sex workers are at heightened risk due to their occupational exposure, compounded by stigma, criminalization, and limited access to healthcare. These factors significantly impede efforts to control the spread of the virus, leading to underreporting and inadequate intervention. This article highlights the urgent need for an inclusive public health response that prioritizes the health and safety of sex workers. Such a response should involve tailored health services, legal protections, and community engagement to ensure that this marginalized group is not overlooked. The decriminalization of sex work is also proposed as a critical public health measure to improve access to care and reduce stigma, ultimately curbing the spread of Mpox in Africa.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100719","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}
Natthawan Chaimongkol, Daniel Y Kim, Yuki Matsushima, Jessica Durkee-Shock, Karenna Barton, Courtney N Ahorrio, Gary A Fahle, Karin Bok, Allison Behrle-Yardley, Jordan A Johnson, Dennise A de Jesús-Díaz, Gabriel I Parra, Eric A Levenson, Fernando Yukio Maeda, Stanislav V Sosnovtsev, Kim Y Green
Background Noroviruses are an important viral cause of chronic diarrhea in immunocompromised individuals. Method We collected norovirus-positive stool samples (n=448) from immunocompromised patients (n=88) at the National Institutes of Health Clinical Research Center, U.S. from 2010-2022. We assessed clinical characteristics of the cohort, norovirus molecular epidemiology, and infectivity of norovirus specimens in human intestinal enteroids (HIEs) monolayers. Results Thirty-nine of the 88 patients had sequential stool samples that allowed documentation of chronic norovirus infection with shedding levels ranging from 104 to 1011 genome copies/g of stool. The majority with confirmed chronic norovirus infection in this cohort (32/39, 82%) had clinical evidence of an inborn error of immunity (13 identified monogenic diseases), most with combined immunodeficiency (15 of 32) or common variable immunodeficiency (11 of 32). Noroviruses detected in the cohort were genetically diverse: both Genogroup I (GI.2, GI.3, GI.5, and GI.6) and Genogroup II (GII.1-GII.4, GII.6, GII.7, GII.12, GII.14, and GII.17) genotypes were detected, with GII.4 variants (Osaka, Apeldoorn, Den Haag, New Orleans, and Sydney) predominant (51 of 88, 57.9%). Viruses belonging to the GII.4 Sydney variant group that replicated in HIEs (n=9) showed a higher fold-increase in RNA genome copies during infection compared to others that replicated. Conclusions Genetically and biologically diverse noroviruses established chronic infection in individuals with both inborn and acquired immunologic defects enrolled in an NIH surveillance study spanning 12 years, demonstrating the unique nature of each virus and host interaction.
{"title":"A Decade of Chronic Norovirus Infection Surveillance at the NIH Clinical Research Center: Clinical Characteristics, Molecular Epidemiology, and Replication","authors":"Natthawan Chaimongkol, Daniel Y Kim, Yuki Matsushima, Jessica Durkee-Shock, Karenna Barton, Courtney N Ahorrio, Gary A Fahle, Karin Bok, Allison Behrle-Yardley, Jordan A Johnson, Dennise A de Jesús-Díaz, Gabriel I Parra, Eric A Levenson, Fernando Yukio Maeda, Stanislav V Sosnovtsev, Kim Y Green","doi":"10.1093/infdis/jiae440","DOIUrl":"https://doi.org/10.1093/infdis/jiae440","url":null,"abstract":"Background Noroviruses are an important viral cause of chronic diarrhea in immunocompromised individuals. Method We collected norovirus-positive stool samples (n=448) from immunocompromised patients (n=88) at the National Institutes of Health Clinical Research Center, U.S. from 2010-2022. We assessed clinical characteristics of the cohort, norovirus molecular epidemiology, and infectivity of norovirus specimens in human intestinal enteroids (HIEs) monolayers. Results Thirty-nine of the 88 patients had sequential stool samples that allowed documentation of chronic norovirus infection with shedding levels ranging from 104 to 1011 genome copies/g of stool. The majority with confirmed chronic norovirus infection in this cohort (32/39, 82%) had clinical evidence of an inborn error of immunity (13 identified monogenic diseases), most with combined immunodeficiency (15 of 32) or common variable immunodeficiency (11 of 32). Noroviruses detected in the cohort were genetically diverse: both Genogroup I (GI.2, GI.3, GI.5, and GI.6) and Genogroup II (GII.1-GII.4, GII.6, GII.7, GII.12, GII.14, and GII.17) genotypes were detected, with GII.4 variants (Osaka, Apeldoorn, Den Haag, New Orleans, and Sydney) predominant (51 of 88, 57.9%). Viruses belonging to the GII.4 Sydney variant group that replicated in HIEs (n=9) showed a higher fold-increase in RNA genome copies during infection compared to others that replicated. Conclusions Genetically and biologically diverse noroviruses established chronic infection in individuals with both inborn and acquired immunologic defects enrolled in an NIH surveillance study spanning 12 years, demonstrating the unique nature of each virus and host interaction.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100720","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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