Matthew M Munch, Susan M Strenk, Sujatha Srinivasan, Tina L Fiedler, Sean Proll, David N Fredricks
Background: Bacterial vaginosis (BV) is a condition marked by high vaginal bacterial diversity. Gardnerella vaginalis has been implicated in BV but is also detected in healthy women. The Gardnerella genus has been expanded to encompass 6 validly named species and several genomospecies. We hypothesized that particular Gardnerella species may be more associated with BV.
Methods: Quantitative polymerase chain reaction (PCR) assays were developed targeting the cpn60 gene of species groups including G. vaginalis, G. piotii/pickettii, G. swidsinskii/greenwoodii, and G. leopoldii. These assays were applied to vaginal swabs from individuals with (n = 101) and without BV (n = 150) attending a sexual health clinic in Seattle, Washington. Weekly swabs were collected from 42 participants for up to 12 weeks.
Results: Concentrations and prevalence of each Gardnerella species group were significantly higher in participants with BV; 91.1% of BV-positive participants had 3 or more Gardnerella species groups detected compared to 32.0% of BV-negative participants (P < .0001). BV-negative participants with 3 or more species groups detected were more likely to develop BV within 100 days versus those with fewer (60.5% vs 3.7%, P < .0001).
Conclusions: These results suggest that BV reflects a state of high Gardnerella species diversity. No Gardnerella species group was a specific marker for BV.
{"title":"Gardnerella Species and Their Association With Bacterial Vaginosis.","authors":"Matthew M Munch, Susan M Strenk, Sujatha Srinivasan, Tina L Fiedler, Sean Proll, David N Fredricks","doi":"10.1093/infdis/jiae026","DOIUrl":"10.1093/infdis/jiae026","url":null,"abstract":"<p><strong>Background: </strong>Bacterial vaginosis (BV) is a condition marked by high vaginal bacterial diversity. Gardnerella vaginalis has been implicated in BV but is also detected in healthy women. The Gardnerella genus has been expanded to encompass 6 validly named species and several genomospecies. We hypothesized that particular Gardnerella species may be more associated with BV.</p><p><strong>Methods: </strong>Quantitative polymerase chain reaction (PCR) assays were developed targeting the cpn60 gene of species groups including G. vaginalis, G. piotii/pickettii, G. swidsinskii/greenwoodii, and G. leopoldii. These assays were applied to vaginal swabs from individuals with (n = 101) and without BV (n = 150) attending a sexual health clinic in Seattle, Washington. Weekly swabs were collected from 42 participants for up to 12 weeks.</p><p><strong>Results: </strong>Concentrations and prevalence of each Gardnerella species group were significantly higher in participants with BV; 91.1% of BV-positive participants had 3 or more Gardnerella species groups detected compared to 32.0% of BV-negative participants (P < .0001). BV-negative participants with 3 or more species groups detected were more likely to develop BV within 100 days versus those with fewer (60.5% vs 3.7%, P < .0001).</p><p><strong>Conclusions: </strong>These results suggest that BV reflects a state of high Gardnerella species diversity. No Gardnerella species group was a specific marker for BV.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anne Eudes Jean Baptiste, John Wagai, Susan Hahné, Adeyemi Adeniran, Richard Ipuragboma Koko, Stijn de Vos, Messeret Shibeshi, E A M Sanders, Balcha Masresha, Eelko Hak
Background: "Zero-dose" children are those who are without any routine vaccination or are lacking the first dose of the diphtheria, tetanus, and pertussis-containing vaccine. Based on global estimates from the World Health Organization/United Nations Children's Fund in 2022, Nigeria has the highest number of zero-dose children, with >2.3 million unvaccinated.
Methods: We used data from the 2021 Nigeria Multiple Indicator Cluster Survey/National Immunization Coverage Survey to identify zero-dose and underimmunized children. Geospatial modeling techniques were employed to determine the prevalence of zero-dose children and predict risk areas with underimmunized children at a high resolution (1 × 1 km).
Results: Zero-dose and underimmunized children are more prevalent in socially deprived groups. Univariate and multivariate bayesian analyses showed positive correlations between the prevalence of zero-dose and underimmunized children and factors such as stunting, contraceptive prevalence, and literacy. The prevalence of zero-dose and underimmunized children varies significantly by region and ethnicity, with higher rates observed in the country's northern parts. Significant heterogeneity in the distribution of undervaccinated children was observed.
Conclusions: Nigeria needs to enhance its immunization system and coverage. Geospatial modeling can help deliver vaccines effectively to underserved communities. By adopting this approach, countries can ensure equitable vaccine access and contribute to global vaccination objectives.
{"title":"High-Resolution Geospatial Mapping of Zero-Dose and Underimmunized Children Following Nigeria's 2021 Multiple Indicator Cluster Survey/National Immunization Coverage Survey.","authors":"Anne Eudes Jean Baptiste, John Wagai, Susan Hahné, Adeyemi Adeniran, Richard Ipuragboma Koko, Stijn de Vos, Messeret Shibeshi, E A M Sanders, Balcha Masresha, Eelko Hak","doi":"10.1093/infdis/jiad476","DOIUrl":"10.1093/infdis/jiad476","url":null,"abstract":"<p><strong>Background: </strong>\"Zero-dose\" children are those who are without any routine vaccination or are lacking the first dose of the diphtheria, tetanus, and pertussis-containing vaccine. Based on global estimates from the World Health Organization/United Nations Children's Fund in 2022, Nigeria has the highest number of zero-dose children, with >2.3 million unvaccinated.</p><p><strong>Methods: </strong>We used data from the 2021 Nigeria Multiple Indicator Cluster Survey/National Immunization Coverage Survey to identify zero-dose and underimmunized children. Geospatial modeling techniques were employed to determine the prevalence of zero-dose children and predict risk areas with underimmunized children at a high resolution (1 × 1 km).</p><p><strong>Results: </strong>Zero-dose and underimmunized children are more prevalent in socially deprived groups. Univariate and multivariate bayesian analyses showed positive correlations between the prevalence of zero-dose and underimmunized children and factors such as stunting, contraceptive prevalence, and literacy. The prevalence of zero-dose and underimmunized children varies significantly by region and ethnicity, with higher rates observed in the country's northern parts. Significant heterogeneity in the distribution of undervaccinated children was observed.</p><p><strong>Conclusions: </strong>Nigeria needs to enhance its immunization system and coverage. Geospatial modeling can help deliver vaccines effectively to underserved communities. By adopting this approach, countries can ensure equitable vaccine access and contribute to global vaccination objectives.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nienke H van Teijlingen, Marleen Y van Smoorenburg, Ramin Sarrami-Forooshani, Esther M Zijlstra-Willems, John L van Hamme, Hanneke Borgdorff, Janneke H H M van de Wijgert, Elisabeth van Leeuwen, Joris A M van der Post, Karin Strijbis, Carla M S Ribeiro, Teunis B H Geijtenbeek
Dysbiosis of the vaginal microbiome poses a serious risk for sexual human immunodeficiency virus type 1 (HIV-1) transmission. Prevotella spp are abundant during vaginal dysbiosis and associated with enhanced HIV-1 susceptibility; however, underlying mechanisms remain unclear. Here, we investigated the direct effect of vaginal bacteria on HIV-1 susceptibility of vaginal CD4+ T cells. Notably, pre-exposure to Prevotella timonensis enhanced HIV-1 uptake by vaginal T cells, leading to increased viral fusion and enhanced virus production. Pre-exposure to antiretroviral inhibitors abolished P timonensis-enhanced infection. Our study shows that the vaginal microbiome directly affects mucosal CD4+ T-cell susceptibility, emphasizing importance of vaginal dysbiosis diagnosis and treatment.
阴道微生物群失调对人类免疫缺陷病毒 1 型(HIV-1)的性传播构成严重威胁。在阴道菌群失调期间,普雷沃特氏菌大量存在,并与 HIV-1 易感性增强有关;然而,其潜在机制仍不清楚。在此,我们研究了阴道细菌对阴道 CD4+ T 细胞的 HIV-1 易感性的直接影响。值得注意的是,预先暴露于Prevotella timonensis会增强阴道T细胞对HIV-1的摄取,导致病毒融合增加和病毒生成增强。而预先暴露于抗逆转录病毒抑制剂则会消除P timonensis增强感染的作用。我们的研究表明,阴道微生物群直接影响粘膜 CD4+ T 细胞的易感性,这强调了阴道菌群失调诊断和治疗的重要性。
{"title":"Prevotella timonensis Bacteria Associated With Vaginal Dysbiosis Enhance Human Immunodeficiency Virus Type 1 Susceptibility Of Vaginal CD4+ T Cells.","authors":"Nienke H van Teijlingen, Marleen Y van Smoorenburg, Ramin Sarrami-Forooshani, Esther M Zijlstra-Willems, John L van Hamme, Hanneke Borgdorff, Janneke H H M van de Wijgert, Elisabeth van Leeuwen, Joris A M van der Post, Karin Strijbis, Carla M S Ribeiro, Teunis B H Geijtenbeek","doi":"10.1093/infdis/jiae166","DOIUrl":"https://doi.org/10.1093/infdis/jiae166","url":null,"abstract":"<p><p>Dysbiosis of the vaginal microbiome poses a serious risk for sexual human immunodeficiency virus type 1 (HIV-1) transmission. Prevotella spp are abundant during vaginal dysbiosis and associated with enhanced HIV-1 susceptibility; however, underlying mechanisms remain unclear. Here, we investigated the direct effect of vaginal bacteria on HIV-1 susceptibility of vaginal CD4+ T cells. Notably, pre-exposure to Prevotella timonensis enhanced HIV-1 uptake by vaginal T cells, leading to increased viral fusion and enhanced virus production. Pre-exposure to antiretroviral inhibitors abolished P timonensis-enhanced infection. Our study shows that the vaginal microbiome directly affects mucosal CD4+ T-cell susceptibility, emphasizing importance of vaginal dysbiosis diagnosis and treatment.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141769061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alba Marín-Moreno, Fabienne Reine, Laetitia Herzog, Naima Aron, Florence Jaffrézic, Jean-Luc Vilotte, Human Rezaei, Olivier Andréoletti, Davy Martin, Vincent Béringue
Background: Atypical/Nor98 scrapie (AS) is an idiopathic infectious prion disease affecting sheep and goats. Recent findings suggest that zoonotic prions from classical bovine spongiform encephalopathy (C-BSE) may copropagate with atypical/Nor98 prions in AS sheep brains. Investigating the risk AS poses to humans is crucial.
Methods: To assess the risk of sheep/goat-to-human transmission of AS, we serially inoculated brain tissue from field and laboratory isolates into transgenic mice overexpressing human prion protein (Met129 allele). We studied clinical outcomes as well as presence of prions in brains and spleens.
Results: No transmission occurred on the primary passage, with no clinical disease or pathological prion protein in brains and spleens. On subsequent passages, 1 isolate gradually adapted, manifesting as prions with a phenotype resembling those causing MM1-type sporadic Creutzfeldt-Jakob disease in humans. However, further characterization using in vivo and in vitro techniques confirmed both prion agents as different strains, revealing a case of phenotypic convergence. Importantly, no C-BSE prions emerged in these mice, especially in the spleen, which is more permissive than the brain for C-BSE cross-species transmission.
Conclusions: The results obtained suggest a low zoonotic potential for AS. Rare adaptation may allow the emergence of prions phenotypically resembling those spontaneously forming in humans.
{"title":"Assessment of the Zoonotic Potential of Atypical Scrapie Prions in Humanized Mice Reveals Rare Phenotypic Convergence but Not Identity With Sporadic Creutzfeldt-Jakob Disease Prions.","authors":"Alba Marín-Moreno, Fabienne Reine, Laetitia Herzog, Naima Aron, Florence Jaffrézic, Jean-Luc Vilotte, Human Rezaei, Olivier Andréoletti, Davy Martin, Vincent Béringue","doi":"10.1093/infdis/jiae093","DOIUrl":"10.1093/infdis/jiae093","url":null,"abstract":"<p><strong>Background: </strong>Atypical/Nor98 scrapie (AS) is an idiopathic infectious prion disease affecting sheep and goats. Recent findings suggest that zoonotic prions from classical bovine spongiform encephalopathy (C-BSE) may copropagate with atypical/Nor98 prions in AS sheep brains. Investigating the risk AS poses to humans is crucial.</p><p><strong>Methods: </strong>To assess the risk of sheep/goat-to-human transmission of AS, we serially inoculated brain tissue from field and laboratory isolates into transgenic mice overexpressing human prion protein (Met129 allele). We studied clinical outcomes as well as presence of prions in brains and spleens.</p><p><strong>Results: </strong>No transmission occurred on the primary passage, with no clinical disease or pathological prion protein in brains and spleens. On subsequent passages, 1 isolate gradually adapted, manifesting as prions with a phenotype resembling those causing MM1-type sporadic Creutzfeldt-Jakob disease in humans. However, further characterization using in vivo and in vitro techniques confirmed both prion agents as different strains, revealing a case of phenotypic convergence. Importantly, no C-BSE prions emerged in these mice, especially in the spleen, which is more permissive than the brain for C-BSE cross-species transmission.</p><p><strong>Conclusions: </strong>The results obtained suggest a low zoonotic potential for AS. Rare adaptation may allow the emergence of prions phenotypically resembling those spontaneously forming in humans.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: We aimed to analyze the clinical characteristics of peripheral Epstein-Barr virus (EBV)-infected lymphocyte subtypes in children with chronic active EBV infection (CAEBV).
Methods: The levels of peripheral EBV infection of CD4+ T cells, CD8+ T cells, and CD56+ natural killer (NK) cells were determined by flow cytometry and quantitative polymerase chain reaction (qPCR) in patients with CAEBV from July 2017 to July 2022.
Results: In total, 112 children with CAEBV were evaluated. Of these, CD4+ type, CD8+ type, and CD56+ type were defined in 44, 21, and 47 patients, respectively. Patients with CD8+ T-cell type had a significantly higher frequency of rash, while hepatomegaly was more common in patients with CD4+ T-cell type. Generally, patients with CD8+ T-cell type had the lowest overall survival rate (P = .017). Patients treated with chemotherapy and hematopoietic stem cell transplantation (HSCT) had a better prognosis (P = .001). In multivariate analysis, rash, hemophagocytic lymphohistiocytosis, CD8+ T-cell type, and no decrease of plasma EBV-DNA after treatment were independent indicators of poor prognosis (P = .002, .024, .022, and .012, respectively).
Conclusions: In children with CAEBV, rash was more frequent in patients with CD8+ T-cell type, whereas patients with CD4+ T-cell type were more likely to develop hepatomegaly. Patients with CD8+ T-cell type had a poor prognosis despite receiving chemotherapy or further HSCT.
背景:我们旨在分析慢性活动性EBV感染(CAEBV)患儿外周EBV感染淋巴细胞亚型的临床特征:我们旨在分析慢性活动性EB病毒感染(CAEBV)患儿外周EB病毒(EBV)感染淋巴细胞亚型的临床特征:2017年7月至2022年7月,通过流式细胞术和定量聚合酶链反应(qPCR)测定CAEBV患者CD4+ T细胞、CD8+ T细胞和CD56+自然杀伤(NK)细胞的外周EBV感染水平:共对112名CAEBV患儿进行了评估。其中,CD4+型、CD8+型和CD56+型患者分别为44人、21人和47人。CD8+ T 细胞型患者出现皮疹的频率明显更高,而 CD4+ T 细胞型患者肝肿大更为常见。一般来说,CD8+ T细胞型患者的总生存率最低(P = .017)。接受化疗和造血干细胞移植(HSCT)治疗的患者预后较好(P = .001)。在多变量分析中,皮疹、嗜血细胞淋巴组织细胞增多症、CD8+ T细胞类型和治疗后血浆EBV-DNA无下降是预后不良的独立指标(P = .002、.024、.022和.012):结论:在CAEBV患儿中,CD8+ T细胞型患者更易出现皮疹,而CD4+ T细胞型患者更易出现肝肿大。CD8+ T细胞型患者尽管接受了化疗或进一步造血干细胞移植,但预后较差。
{"title":"Clinical Characteristics of Peripheral Lymphocyte Subtypes in Chronic Active Epstein-Barr Virus Infection.","authors":"Ang Wei, Wenxin Ou, Yunze Zhao, Honghao Ma, Liping Zhang, Hongyun Lian, Xiaoxi Zhao, Qing Zhang, Dong Wang, Zhigang Li, Tianyou Wang, Rui Zhang","doi":"10.1093/infdis/jiad435","DOIUrl":"10.1093/infdis/jiad435","url":null,"abstract":"<p><strong>Background: </strong>We aimed to analyze the clinical characteristics of peripheral Epstein-Barr virus (EBV)-infected lymphocyte subtypes in children with chronic active EBV infection (CAEBV).</p><p><strong>Methods: </strong>The levels of peripheral EBV infection of CD4+ T cells, CD8+ T cells, and CD56+ natural killer (NK) cells were determined by flow cytometry and quantitative polymerase chain reaction (qPCR) in patients with CAEBV from July 2017 to July 2022.</p><p><strong>Results: </strong>In total, 112 children with CAEBV were evaluated. Of these, CD4+ type, CD8+ type, and CD56+ type were defined in 44, 21, and 47 patients, respectively. Patients with CD8+ T-cell type had a significantly higher frequency of rash, while hepatomegaly was more common in patients with CD4+ T-cell type. Generally, patients with CD8+ T-cell type had the lowest overall survival rate (P = .017). Patients treated with chemotherapy and hematopoietic stem cell transplantation (HSCT) had a better prognosis (P = .001). In multivariate analysis, rash, hemophagocytic lymphohistiocytosis, CD8+ T-cell type, and no decrease of plasma EBV-DNA after treatment were independent indicators of poor prognosis (P = .002, .024, .022, and .012, respectively).</p><p><strong>Conclusions: </strong>In children with CAEBV, rash was more frequent in patients with CD8+ T-cell type, whereas patients with CD4+ T-cell type were more likely to develop hepatomegaly. Patients with CD8+ T-cell type had a poor prognosis despite receiving chemotherapy or further HSCT.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rachel M Burdorf, Shuntai Zhou, Claire Amon, Nathan Long, Collin S Hill, Lily Adams, Gerald Tegha, Maganizo B Chagomerana, Allan Jumbe, Madalitso Maliwichi, Shaphil Wallie, Yijia Li, Ronald Swanstrom, Mina C Hosseinipour
Background: The association between low-frequency human immunodeficiency virus type 1 (HIV-1) drug resistance mutations (DRMs) and treatment failure (TF) is controversial. We explore this association using next-generation sequencing (NGS) methods that accurately sample low-frequency DRMs.
Methods: We enrolled women with HIV-1 in Malawi who were either antiretroviral therapy (ART) naive (cohort A), had ART failure (cohort B), or had discontinued ART (cohort C). At entry, cohorts A and C began a nonnucleoside reverse transcriptase inhibitor-based regimen and cohort B started a protease inhibitor-based regimen. We used Primer ID MiSeq to identify regimen-relevant DRMs in entry and TF plasma samples, and a Cox proportional hazards model to calculate hazard ratios (HRs) for entry DRMs. Low-frequency DRMs were defined as ≤20%.
Results: We sequenced 360 participants. Cohort B and C participants were more likely to have TF than cohort A participants. The presence of K103N at entry significantly increased TF risk among A and C participants at both high and low frequency, with HRs of 3.12 (95% confidence interval [CI], 1.58-6.18) and 2.38 (95% CI, 1.00-5.67), respectively. At TF, 45% of participants showed selection of DRMs while in the remaining participants there was an apparent lack of selective pressure from ART.
Conclusions: Using accurate NGS for DRM detection may benefit an additional 10% of patients by identifying low-frequency K103N mutations.
背景:低频人类免疫缺陷病毒 1 型(HIV-1)耐药突变(DRMs)与治疗失败(TF)之间的关联存在争议。我们使用能准确采样低频 DRMs 的下一代测序(NGS)方法探讨了这种关联:我们在马拉维招募了感染 HIV-1 的女性患者,她们要么是抗逆转录病毒疗法 (ART) 天真者(队列 A),要么是抗逆转录病毒疗法失败者(队列 B),要么是中断抗逆转录病毒疗法者(队列 C)。入组时,A 组和 C 组开始采用非核苷类逆转录酶抑制剂治疗方案,B 组开始采用蛋白酶抑制剂治疗方案。我们使用 Primer ID MiSeq 在入组样本和 TF 血浆样本中识别与治疗方案相关的 DRMs,并使用 Cox 比例危险模型计算入组 DRMs 的危险比 (HRs)。低频DRM定义为≤20%:我们对 360 名参与者进行了测序。与队列 A 的参与者相比,队列 B 和队列 C 的参与者更有可能患有 TF。在 A 组和 C 组参与者中,K103N 的高频和低频出现会显著增加 TF 风险,HR 分别为 3.12(95% 置信区间 [CI],1.58-6.18)和 2.38(95% 置信区间,1.00-5.67)。在TF时,45%的参与者表现出DRMs的选择性,而在其余参与者中,明显缺乏ART的选择性压力:结论:使用准确的 NGS 检测 DRM 可通过识别低频 K103N 突变使另外 10% 的患者受益。
{"title":"Impact of Low-Frequency Human Immunodeficiency Virus Type 1 Drug Resistance Mutations on Antiretroviral Therapy Outcomes.","authors":"Rachel M Burdorf, Shuntai Zhou, Claire Amon, Nathan Long, Collin S Hill, Lily Adams, Gerald Tegha, Maganizo B Chagomerana, Allan Jumbe, Madalitso Maliwichi, Shaphil Wallie, Yijia Li, Ronald Swanstrom, Mina C Hosseinipour","doi":"10.1093/infdis/jiae131","DOIUrl":"10.1093/infdis/jiae131","url":null,"abstract":"<p><strong>Background: </strong>The association between low-frequency human immunodeficiency virus type 1 (HIV-1) drug resistance mutations (DRMs) and treatment failure (TF) is controversial. We explore this association using next-generation sequencing (NGS) methods that accurately sample low-frequency DRMs.</p><p><strong>Methods: </strong>We enrolled women with HIV-1 in Malawi who were either antiretroviral therapy (ART) naive (cohort A), had ART failure (cohort B), or had discontinued ART (cohort C). At entry, cohorts A and C began a nonnucleoside reverse transcriptase inhibitor-based regimen and cohort B started a protease inhibitor-based regimen. We used Primer ID MiSeq to identify regimen-relevant DRMs in entry and TF plasma samples, and a Cox proportional hazards model to calculate hazard ratios (HRs) for entry DRMs. Low-frequency DRMs were defined as ≤20%.</p><p><strong>Results: </strong>We sequenced 360 participants. Cohort B and C participants were more likely to have TF than cohort A participants. The presence of K103N at entry significantly increased TF risk among A and C participants at both high and low frequency, with HRs of 3.12 (95% confidence interval [CI], 1.58-6.18) and 2.38 (95% CI, 1.00-5.67), respectively. At TF, 45% of participants showed selection of DRMs while in the remaining participants there was an apparent lack of selective pressure from ART.</p><p><strong>Conclusions: </strong>Using accurate NGS for DRM detection may benefit an additional 10% of patients by identifying low-frequency K103N mutations.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The coronavirus disease 2019 (COVID-19) pandemic has been called the deadliest disease event in history. In this study, we compared the cause-specific mortality rate of the Spanish flu (1918-1920) with that of COVID-19 (2020-2022) in the Netherlands. During the periods of exposure, about 50 000 people died of COVID-19 and 32 000 people of the Spanish flu. In absolute numbers, COVID-19 seems to be deadlier than Spanish flu. However, the crude mortality rates for COVID-19 and Spanish flu were 287 and 486 per 100 000 inhabitants, respectively. Comparing age-standardized mortality rates, there would have been 28 COVID-19- and 194 Spanish flu-related deaths in 1918-1920, or 214 Spanish flu- and 98 COVID-19-related deaths in 2020-2022 per 100 000 inhabitants per year. Thus, taking the population differences into account, the Spanish flu would have been deadlier than COVID-19.
{"title":"Mortality Rates of the Spanish Flu and Coronavirus Disease 2019 in the Netherlands: A Historical Comparison.","authors":"Peter Harteloh, Rob van Mechelen","doi":"10.1093/infdis/jiae071","DOIUrl":"10.1093/infdis/jiae071","url":null,"abstract":"<p><p>The coronavirus disease 2019 (COVID-19) pandemic has been called the deadliest disease event in history. In this study, we compared the cause-specific mortality rate of the Spanish flu (1918-1920) with that of COVID-19 (2020-2022) in the Netherlands. During the periods of exposure, about 50 000 people died of COVID-19 and 32 000 people of the Spanish flu. In absolute numbers, COVID-19 seems to be deadlier than Spanish flu. However, the crude mortality rates for COVID-19 and Spanish flu were 287 and 486 per 100 000 inhabitants, respectively. Comparing age-standardized mortality rates, there would have been 28 COVID-19- and 194 Spanish flu-related deaths in 1918-1920, or 214 Spanish flu- and 98 COVID-19-related deaths in 2020-2022 per 100 000 inhabitants per year. Thus, taking the population differences into account, the Spanish flu would have been deadlier than COVID-19.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Regulatory T (Treg) cells are involved in the antiviral immune response in patients with coronavirus disease 2019 (COVID-19); however, whether Treg cells are involved in the neutralizing antibody (nAb) response remains unclear. Here, we found that individuals who recovered from mild but not severe COVID-19 had significantly greater frequencies of Treg cells and lower frequencies of CXCR3+ circulating T follicular helper (cTfh) cells than healthy controls. Furthermore, the frequencies of Treg and CXCR3+ cTfh cells were negatively and positively correlated with the nAb responses, respectively, and Treg cells was inversely associated with CXCR3+ cTfh cells in individuals who recovered from mild COVID-19 but not in those with severe disease. Mechanistically, Treg cells inhibited memory B-cell differentiation and antibody production by limiting the activation and proliferation of cTfh cells, especially CXCR3+ cTfh cells, and functional molecule expression. This study provides novel insight showing that mild COVID-19 elicits concerted nAb responses, which are shaped by both Treg and Tfh cells.
{"title":"Regulatory T and CXCR3+ Circulating Tfh Cells Concordantly Shape the Neutralizing Antibody Responses in Individuals Who Have Recovered from Mild COVID-19.","authors":"Xingyu Zheng, Rui Lu, Dong Pan, Liting Peng, Rongzhang He, Yabin Hu, Jun Chen, Jinyong Tang, Xiaohan Rong, Shishan Teng, You Wang, Fen Liu, Tianyi Xie, Chanfeng Wu, Yinggen Tang, Wenpei Liu, Xiaowang Qu","doi":"10.1093/infdis/jiae061","DOIUrl":"10.1093/infdis/jiae061","url":null,"abstract":"<p><p>Regulatory T (Treg) cells are involved in the antiviral immune response in patients with coronavirus disease 2019 (COVID-19); however, whether Treg cells are involved in the neutralizing antibody (nAb) response remains unclear. Here, we found that individuals who recovered from mild but not severe COVID-19 had significantly greater frequencies of Treg cells and lower frequencies of CXCR3+ circulating T follicular helper (cTfh) cells than healthy controls. Furthermore, the frequencies of Treg and CXCR3+ cTfh cells were negatively and positively correlated with the nAb responses, respectively, and Treg cells was inversely associated with CXCR3+ cTfh cells in individuals who recovered from mild COVID-19 but not in those with severe disease. Mechanistically, Treg cells inhibited memory B-cell differentiation and antibody production by limiting the activation and proliferation of cTfh cells, especially CXCR3+ cTfh cells, and functional molecule expression. This study provides novel insight showing that mild COVID-19 elicits concerted nAb responses, which are shaped by both Treg and Tfh cells.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Supeng Yin, Mengmeng Yuan, Sirui Zhang, Hongdan Chen, Jing Zhou, Tongyu He, Gang Li, Yanlan Yu, Fan Zhang, Ming Li, Yan Zhao
The subtilisin-like protease-1 (SspA-1) plays an important role in the pathogenesis of a highly virulent strain of Streptococcus suis 2. However, the mechanism of SspA-1-triggered excessive inflammatory response is still unknown. In this study, we demonstrated that activation of type I IFN signaling is required for SspA-1-induced excessive proinflammatory cytokine production. Further experiments showed that the TLR2 endosomal pathway mediates SspA-1-induced type I IFN signaling and the inflammatory response. Finally, we mapped the major signaling components of the related pathway and found that the TIR adaptor proteins Mal, TRAM, and MyD88 and the downstream activation of IRF1 and IRF7 were involved in this pathway. These results explain the molecular mechanism by which SspA-1 triggers an excessive inflammatory response and reveal a novel effect of type I IFN in S. suis 2 infection, possibly providing further insights into the pathogenesis of this highly virulent S. suis 2 strain.
在高致病性猪链球菌 2 株的致病过程中,枯草蛋白样蛋白酶-1(SspA-1)发挥了重要作用。然而,SspA-1 引发过度炎症反应的机制仍不清楚。在这项研究中,我们证明了 SspA-1 诱导的过度促炎细胞因子的产生需要 I 型 IFN 信号的激活。进一步的实验表明,TLR2 内体通路介导了 SspA-1 诱导的 I 型 IFN 信号转导和炎症反应。最后,我们绘制了相关通路的主要信号成分图,发现 TIR 适应蛋白 Mal、TRAM 和 MyD88 以及 IRF1 和 IRF7 的下游激活参与了这一通路。这些结果解释了SspA-1引发过度炎症反应的分子机制,并揭示了I型IFN在猪流感病毒2型感染中的新作用,可能为进一步了解猪流感病毒2型这一高致病性菌株的发病机制提供了线索。
{"title":"Streptococcus suis Serotype 2 Type IV Secretion Effector SspA-1 Induces Proinflammatory Cytokine Production via TLR2 Endosomal and Type I Interferon Signaling.","authors":"Supeng Yin, Mengmeng Yuan, Sirui Zhang, Hongdan Chen, Jing Zhou, Tongyu He, Gang Li, Yanlan Yu, Fan Zhang, Ming Li, Yan Zhao","doi":"10.1093/infdis/jiad454","DOIUrl":"10.1093/infdis/jiad454","url":null,"abstract":"<p><p>The subtilisin-like protease-1 (SspA-1) plays an important role in the pathogenesis of a highly virulent strain of Streptococcus suis 2. However, the mechanism of SspA-1-triggered excessive inflammatory response is still unknown. In this study, we demonstrated that activation of type I IFN signaling is required for SspA-1-induced excessive proinflammatory cytokine production. Further experiments showed that the TLR2 endosomal pathway mediates SspA-1-induced type I IFN signaling and the inflammatory response. Finally, we mapped the major signaling components of the related pathway and found that the TIR adaptor proteins Mal, TRAM, and MyD88 and the downstream activation of IRF1 and IRF7 were involved in this pathway. These results explain the molecular mechanism by which SspA-1 triggers an excessive inflammatory response and reveal a novel effect of type I IFN in S. suis 2 infection, possibly providing further insights into the pathogenesis of this highly virulent S. suis 2 strain.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lara I Allen, Hannah Fraser, Jack Stone, Andrew McAuley, Kirsten M A Trayner, Rebecca Metcalfe, S Erica Peters, Sharon J Hutchinson, Peter Vickerman, Matthew Hickman
Background: A human immunodeficiency virus (HIV) outbreak was identified among people who inject drugs (PWID) in Glasgow in 2015, with >150 diagnoses by the end of 2019. The outbreak response involved scaling up HIV testing and improving HIV treatment initiation and retention.
Methods: We parameterized and calibrated a dynamic, deterministic model of HIV transmission among PWID in Glasgow to epidemiological data. We use this model to evaluate HIV testing and treatment interventions. We present results in terms of relative changes in HIV prevalence, incidence, and cases averted.
Results: If the improvements in both testing and treatment had not occurred, we predict that HIV prevalence would have reached 17.8% (95% credible interval [CrI], 14.1%-22.6%) by the beginning of 2020, compared to 5.9% (95% CrI, 4.7%-7.4%) with the improvements. If the improvements had been made on detection of the outbreak in 2015, we predict that peak incidence would have been 26.2% (95% CrI, 8.8%-49.3%) lower and 62.7% (95% CrI, 43.6%-76.6%) of the outbreak cases could have been averted. The outbreak could have been avoided if the improvements had already been in place.
Conclusions: Our modeling suggests that the HIV testing and treatment interventions successfully brought the HIV outbreak in Glasgow under control by the beginning of 2020.
背景:2015 年,在格拉斯哥的注射吸毒者(PWID)中发现了人类免疫缺陷病毒(HIV)疫情,到 2019 年底,确诊人数超过 150 人。疫情应对措施包括扩大 HIV 检测范围、改善 HIV 治疗的启动和保留:方法:我们根据流行病学数据对格拉斯哥吸毒者中 HIV 传播的动态确定性模型进行了参数化和校准。我们使用该模型来评估 HIV 检测和治疗干预措施。我们以 HIV 感染率、发病率和避免病例的相对变化来呈现结果:结果:如果没有检测和治疗方面的改进,我们预测到 2020 年初,HIV 感染率将达到 17.8%(95% 可信区间 [CrI],14.1%-22.6%),而改进后的感染率为 5.9%(95% 可信区间 [CrI],4.7%-7.4%)。如果在 2015 年检测到疫情时就做出改进,我们预测发病高峰将降低 26.2%(95% 置信度,8.8%-49.3%),62.7%(95% 置信度,43.6%-76.6%)的疫情病例本可避免。如果改进措施已经到位,疫情本可以避免:我们的模型表明,艾滋病检测和治疗干预措施在 2020 年初成功控制了格拉斯哥的艾滋病疫情。
{"title":"Testing and Treatment Interventions in Community Settings Key to Controlling a Recent Human Immunodeficiency Virus Outbreak Among People Who Inject Drugs in Glasgow: A Modeling Study.","authors":"Lara I Allen, Hannah Fraser, Jack Stone, Andrew McAuley, Kirsten M A Trayner, Rebecca Metcalfe, S Erica Peters, Sharon J Hutchinson, Peter Vickerman, Matthew Hickman","doi":"10.1093/infdis/jiae206","DOIUrl":"10.1093/infdis/jiae206","url":null,"abstract":"<p><strong>Background: </strong>A human immunodeficiency virus (HIV) outbreak was identified among people who inject drugs (PWID) in Glasgow in 2015, with >150 diagnoses by the end of 2019. The outbreak response involved scaling up HIV testing and improving HIV treatment initiation and retention.</p><p><strong>Methods: </strong>We parameterized and calibrated a dynamic, deterministic model of HIV transmission among PWID in Glasgow to epidemiological data. We use this model to evaluate HIV testing and treatment interventions. We present results in terms of relative changes in HIV prevalence, incidence, and cases averted.</p><p><strong>Results: </strong>If the improvements in both testing and treatment had not occurred, we predict that HIV prevalence would have reached 17.8% (95% credible interval [CrI], 14.1%-22.6%) by the beginning of 2020, compared to 5.9% (95% CrI, 4.7%-7.4%) with the improvements. If the improvements had been made on detection of the outbreak in 2015, we predict that peak incidence would have been 26.2% (95% CrI, 8.8%-49.3%) lower and 62.7% (95% CrI, 43.6%-76.6%) of the outbreak cases could have been averted. The outbreak could have been avoided if the improvements had already been in place.</p><p><strong>Conclusions: </strong>Our modeling suggests that the HIV testing and treatment interventions successfully brought the HIV outbreak in Glasgow under control by the beginning of 2020.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11272080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}