首页 > 最新文献

Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America最新文献

英文 中文
Model-Based Meta-analysis of Rifampicin Exposure and Mortality in Indonesian Tuberculous Meningitis Trials. 印度尼西亚结核性脑膜炎试验中利福平暴露与死亡率的基于模型的meta分析。
Elin M Svensson, Sofiati Dian, Lindsey Te Brake, Ahmad Rizal Ganiem, Vycke Yunivita, Arjan van Laarhoven, Reinout Van Crevel, Rovina Ruslami, Rob E Aarnoutse

Background: Intensified antimicrobial treatment with higher rifampicin doses may improve outcome of tuberculous meningitis, but the desirable exposure and necessary dose are unknown. Our objective was to characterize the relationship between rifampicin exposures and mortality in order to identify optimal dosing for tuberculous meningitis.

Methods: An individual patient meta-analysis was performed on data from 3 Indonesian randomized controlled phase 2 trials comparing oral rifampicin 450 mg (~10 mg/kg) to intensified regimens including 750-1350 mg orally, or a 600-mg intravenous infusion. Pharmacokinetic data from plasma and cerebrospinal fluid (CSF) were analyzed with nonlinear mixed-effects modeling. Six-month survival was described with parametric time-to-event models.

Results: Pharmacokinetic analyses included 133 individuals (1150 concentration measurements, 170 from CSF). The final model featured 2 disposition compartments, saturable clearance, and autoinduction. Rifampicin CSF concentrations were described by a partition coefficient (5.5%; 95% confidence interval [CI], 4.5%-6.4%) and half-life for distribution plasma to CSF (2.1 hours; 95% CI, 1.3-2.9 hours). Higher CSF protein concentration increased the partition coefficient. Survival of 148 individuals (58 died, 15 dropouts) was well described by an exponentially declining hazard, with lower age, higher baseline Glasgow Coma Scale score, and higher individual rifampicin plasma exposure reducing the hazard. Simulations predicted an increase in 6-month survival from approximately 50% to approximately 70% upon increasing the oral rifampicin dose from 10 to 30 mg/kg, and predicted that even higher doses would further improve survival.

Conclusions: Higher rifampicin exposure substantially decreased the risk of death, and the maximal effect was not reached within the studied range. We suggest a rifampicin dose of at least 30 mg/kg to be investigated in phase 3 clinical trials.

背景:加强抗菌治疗,提高利福平剂量可改善结核性脑膜炎的预后,但理想暴露量和必要剂量尚不清楚。我们的目的是表征利福平暴露与死亡率之间的关系,以确定结核性脑膜炎的最佳剂量。方法:对印度尼西亚3项随机对照2期试验的数据进行个体患者荟萃分析,比较口服利福平450 mg (~10 mg/kg)和强化方案,包括750-1350 mg口服或600 mg静脉输注。采用非线性混合效应模型对血浆和脑脊液的药代动力学数据进行分析。6个月生存率用参数时间-事件模型描述。结果:药代动力学分析包括133个个体(1150个浓度测量,170个来自CSF)。最终模型具有2个处置隔间,可饱和间隙和自动感应。利福平脑脊液浓度用分配系数(5.5%;95%可信区间[CI], 4.5%-6.4%)和分配血浆到脑脊液的半衰期(2.1小时;95% CI, 1.3-2.9小时)。脑脊液蛋白浓度越高,分割系数越高。148人的生存(58人死亡,15人退出)的风险呈指数下降,年龄越低,基线格拉斯哥昏迷评分越高,个体利福平血浆暴露越多,风险越低。模拟预测,将口服利福平剂量从10 mg/kg增加到30 mg/kg后,6个月生存率将从约50%增加到约70%,并预测更高剂量将进一步提高生存率。结论:较高的利福平暴露量可显著降低死亡风险,在研究范围内未达到最大效果。我们建议在3期临床试验中研究至少30 mg/kg的利福平剂量。
{"title":"Model-Based Meta-analysis of Rifampicin Exposure and Mortality in Indonesian Tuberculous Meningitis Trials.","authors":"Elin M Svensson, Sofiati Dian, Lindsey Te Brake, Ahmad Rizal Ganiem, Vycke Yunivita, Arjan van Laarhoven, Reinout Van Crevel, Rovina Ruslami, Rob E Aarnoutse","doi":"10.1093/cid/ciz1071","DOIUrl":"10.1093/cid/ciz1071","url":null,"abstract":"<p><strong>Background: </strong>Intensified antimicrobial treatment with higher rifampicin doses may improve outcome of tuberculous meningitis, but the desirable exposure and necessary dose are unknown. Our objective was to characterize the relationship between rifampicin exposures and mortality in order to identify optimal dosing for tuberculous meningitis.</p><p><strong>Methods: </strong>An individual patient meta-analysis was performed on data from 3 Indonesian randomized controlled phase 2 trials comparing oral rifampicin 450 mg (~10 mg/kg) to intensified regimens including 750-1350 mg orally, or a 600-mg intravenous infusion. Pharmacokinetic data from plasma and cerebrospinal fluid (CSF) were analyzed with nonlinear mixed-effects modeling. Six-month survival was described with parametric time-to-event models.</p><p><strong>Results: </strong>Pharmacokinetic analyses included 133 individuals (1150 concentration measurements, 170 from CSF). The final model featured 2 disposition compartments, saturable clearance, and autoinduction. Rifampicin CSF concentrations were described by a partition coefficient (5.5%; 95% confidence interval [CI], 4.5%-6.4%) and half-life for distribution plasma to CSF (2.1 hours; 95% CI, 1.3-2.9 hours). Higher CSF protein concentration increased the partition coefficient. Survival of 148 individuals (58 died, 15 dropouts) was well described by an exponentially declining hazard, with lower age, higher baseline Glasgow Coma Scale score, and higher individual rifampicin plasma exposure reducing the hazard. Simulations predicted an increase in 6-month survival from approximately 50% to approximately 70% upon increasing the oral rifampicin dose from 10 to 30 mg/kg, and predicted that even higher doses would further improve survival.</p><p><strong>Conclusions: </strong>Higher rifampicin exposure substantially decreased the risk of death, and the maximal effect was not reached within the studied range. We suggest a rifampicin dose of at least 30 mg/kg to be investigated in phase 3 clinical trials.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/cid/ciz1071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74103053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 45
Mapping the Current and Future Noncommunicable Disease Burden in Kenya by Human Immunodeficiency Virus Status: A Modeling Study. 按人体免疫缺陷病毒状况绘制肯尼亚当前和未来非传染性疾病负担图:模型研究。
Mikaela Smit, Pablo N Perez-Guzman, Kennedy K Mutai, Rachel Cassidy, Joseph Kibachio, Nduku Kilonzo, Timothy B Hallett

Background: The noncommunicable disease (NCD) burden in Kenya is not well characterized, despite estimates needed to identify future health priorities. We aimed to quantify current and future NCD burden in Kenya by human immunodeficiency virus (HIV) status.

Methods: Original systematic reviews and meta-analyses of prevalence/incidence of cardiovascular disease (CVD), chronic kidney disease, depression, diabetes, high total cholesterol, hypertension, human papillomavirus infection, and related precancerous stages in Kenya were carried out. An individual-based model was developed, simulating births, deaths, HIV disease and treatment, aforementioned NCDs, and cancers. The model was parameterized using systematic reviews and epidemiological national and regional surveillance data. NCD burden was quantified for 2018-2035 by HIV status among adults.

Results: Systematic reviews identified prevalence/incidence data for each NCD except ischemic heart disease. The model estimates that 51% of Kenyan adults currently suffer from ≥1 NCD, with a higher burden in people living with HIV (PLWH) compared to persons not living with HIV (62% vs 51%), driven by their higher age profile and partly by HIV-related risk for NCDs. Hypertension and high total cholesterol are the main NCD drivers (adult prevalence of 20.5% [5.3 million] and 9.0% [2.3 million]), with CVD and cancers the main causes of death. The burden is projected to increase by 2035 (56% in persons not living with HIV; 71% in PLWH), with population growth doubling the number of people needing services (15.4 million to 28.1 million) by 2035.

Conclusions: NCD services will need to be expanded in Kenya. Guidelines in Kenya already support provision of these among both the general and populations living with HIV; however, coverage remains low.

背景:肯尼亚的非传染性疾病 (NCD) 负担还没有得到很好的描述,尽管需要进行估算以确定未来的健康优先事项。我们的目的是根据人体免疫缺陷病毒(HIV)状况量化肯尼亚当前和未来的非传染性疾病负担:方法:我们对肯尼亚心血管疾病(CVD)、慢性肾病、抑郁症、糖尿病、高总胆固醇、高血压、人类乳头瘤病毒感染以及相关癌前病变阶段的流行率/发病率进行了原创性系统综述和荟萃分析。开发了一个基于个人的模型,模拟出生、死亡、艾滋病毒疾病和治疗、上述非传染性疾病和癌症。该模型使用系统回顾和流行病学国家和地区监测数据进行参数化。根据成人的艾滋病毒感染状况,对 2018-2035 年的非传染性疾病负担进行了量化:系统综述确定了除缺血性心脏病以外的每种非传染性疾病的流行率/发病率数据。该模型估计,目前有 51% 的肯尼亚成年人罹患≥1 种 NCD,与非 HIV 感染者相比,HIV 感染者的负担更高(62% 对 51%),这是因为他们的年龄更高,而且部分原因是与 HIV 相关的 NCD 风险。高血压和高总胆固醇是非传染性疾病的主要诱因(成人发病率分别为 20.5% [530 万] 和 9.0% [230 万]),心血管疾病和癌症是主要死因。预计到 2035 年,这一负担将加重(非艾滋病毒感染者的负担将增加 56%;艾滋病毒感染者的负担将增加 71%),到 2035 年,人口增长将使需要服务的人数增加一倍(从 1,540 万增加到 2,810 万):肯尼亚需要扩大非传染性疾病服务。肯尼亚的指导方针已经支持在普通人群和艾滋病毒感染者中提供这些服务;但是,覆盖率仍然很低。
{"title":"Mapping the Current and Future Noncommunicable Disease Burden in Kenya by Human Immunodeficiency Virus Status: A Modeling Study.","authors":"Mikaela Smit, Pablo N Perez-Guzman, Kennedy K Mutai, Rachel Cassidy, Joseph Kibachio, Nduku Kilonzo, Timothy B Hallett","doi":"10.1093/cid/ciz1103","DOIUrl":"10.1093/cid/ciz1103","url":null,"abstract":"<p><strong>Background: </strong>The noncommunicable disease (NCD) burden in Kenya is not well characterized, despite estimates needed to identify future health priorities. We aimed to quantify current and future NCD burden in Kenya by human immunodeficiency virus (HIV) status.</p><p><strong>Methods: </strong>Original systematic reviews and meta-analyses of prevalence/incidence of cardiovascular disease (CVD), chronic kidney disease, depression, diabetes, high total cholesterol, hypertension, human papillomavirus infection, and related precancerous stages in Kenya were carried out. An individual-based model was developed, simulating births, deaths, HIV disease and treatment, aforementioned NCDs, and cancers. The model was parameterized using systematic reviews and epidemiological national and regional surveillance data. NCD burden was quantified for 2018-2035 by HIV status among adults.</p><p><strong>Results: </strong>Systematic reviews identified prevalence/incidence data for each NCD except ischemic heart disease. The model estimates that 51% of Kenyan adults currently suffer from ≥1 NCD, with a higher burden in people living with HIV (PLWH) compared to persons not living with HIV (62% vs 51%), driven by their higher age profile and partly by HIV-related risk for NCDs. Hypertension and high total cholesterol are the main NCD drivers (adult prevalence of 20.5% [5.3 million] and 9.0% [2.3 million]), with CVD and cancers the main causes of death. The burden is projected to increase by 2035 (56% in persons not living with HIV; 71% in PLWH), with population growth doubling the number of people needing services (15.4 million to 28.1 million) by 2035.</p><p><strong>Conclusions: </strong>NCD services will need to be expanded in Kenya. Guidelines in Kenya already support provision of these among both the general and populations living with HIV; however, coverage remains low.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79674316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Noncommunicable Diseases: Yet Another Challenge for Human Immunodeficiency Virus Treatment and Care in Sub-Saharan Africa. 非传染性疾病:撒哈拉以南非洲地区人类免疫缺陷病毒治疗和护理面临的又一挑战。
Brian K Agan, Vincent C Marconi
{"title":"Noncommunicable Diseases: Yet Another Challenge for Human Immunodeficiency Virus Treatment and Care in Sub-Saharan Africa.","authors":"Brian K Agan, Vincent C Marconi","doi":"10.1093/cid/ciz1104","DOIUrl":"10.1093/cid/ciz1104","url":null,"abstract":"","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88188347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chlamydia and Gonorrhea Incidence and Testing among Patients in the HIV Outpatient Study, 2007-2017. 2007-2017年HIV门诊患者衣原体和淋病发病率及检测
Jun Li, C. Armon, F. Palella, R. Novak, D. Ward, S. Purinton, M. Durham, K. Buchacz
BACKGROUNDAlthough chlamydia (CT) and gonorrhea (GC) infections are increasing in the United States, there are limited data on their incidence, testing rates and associated risk factors among persons with HIV (PWH), including by anatomic site among men who have sex with men (MSM).METHODSWe analyzed 2007-2017 medical record data from HIV Outpatient Study participants in care at nine HIV clinics. We calculated CT (and GC) incidence and testing rates and assessed associations with sociodemographic and clinical factors using log-linear regression.RESULTSAmong 4,727 PWH, 397 had 881 CT infections and 331 had 861 GC infections, with incidence of 2.95 and 2.88 per 100 person-years, respectively. From 2007-2017, incidence and testing rates increased by approximately 3.0- and 1.9-fold for CT and GC, respectively. Multivariable factors associated with incident CT (GC) included younger age, MSM, and prior diagnoses of sexually transmitted diseases (STDs). Among 1,159 MSM, 583 (50.3%) had 844 CT and 843 GC tests during 2016-2017, and 26.6% of tests were 3-site (urethra, rectum, and pharynx), yielding the highest rates of CT (GC) detection. Multivariable factors associated with CT (GC) testing included younger age, non-Hispanic/Latino black race, and having prior STDs.CONCLUSIONSRecent CT and GC incidence and testing increased among PWH; however, only half of MSM were tested for CT or GC during 2016-2017 and < 1/3 of tests were 3-site. To promote sexual health and STD prevention among PWH, including MSM, research regarding the added value of CT and GC testing across three anatomic sites is needed.
背景:尽管衣原体(CT)和淋病(GC)感染在美国呈上升趋势,但关于其在HIV感染者(PWH)中的发病率、检测率和相关危险因素的数据有限,包括男男性行为者(MSM)的解剖部位。方法:我们分析了2007-2017年9家HIV诊所的HIV门诊研究参与者的医疗记录数据。我们计算了CT(和GC)的发病率和检测率,并使用对数线性回归评估了与社会人口统计学和临床因素的关联。结果4727例PWH患者中,CT感染397例(881例),GC感染331例(861例),发病率分别为2.95例/ 100人年和2.88例/ 100人年。从2007年到2017年,CT和GC的发病率和检测率分别增加了约3.0倍和1.9倍。与发生CT (GC)相关的多变量因素包括年龄较小、男男性行为和先前的性传播疾病(STDs)诊断。在1159名男男性行为者中,583名(50.3%)在2016-2017年期间进行了844次CT和843次GC检查,其中26.6%的检查是三部位(尿道、直肠和咽),CT (GC)检出率最高。与CT (GC)检测相关的多变量因素包括年龄较小、非西班牙裔/拉丁裔黑人、既往性传播疾病。结论PWH患者近期CT和GC的发病率及检测呈上升趋势;然而,在2016-2017年期间,只有一半的MSM进行了CT或GC检测,且小于1/3的检测是三部位检测。为了促进包括男男性行为者在内的PWH的性健康和性病预防,需要研究CT和GC检测在三个解剖部位的附加价值。
{"title":"Chlamydia and Gonorrhea Incidence and Testing among Patients in the HIV Outpatient Study, 2007-2017.","authors":"Jun Li, C. Armon, F. Palella, R. Novak, D. Ward, S. Purinton, M. Durham, K. Buchacz","doi":"10.1093/cid/ciz1085","DOIUrl":"https://doi.org/10.1093/cid/ciz1085","url":null,"abstract":"BACKGROUND\u0000Although chlamydia (CT) and gonorrhea (GC) infections are increasing in the United States, there are limited data on their incidence, testing rates and associated risk factors among persons with HIV (PWH), including by anatomic site among men who have sex with men (MSM).\u0000\u0000\u0000METHODS\u0000We analyzed 2007-2017 medical record data from HIV Outpatient Study participants in care at nine HIV clinics. We calculated CT (and GC) incidence and testing rates and assessed associations with sociodemographic and clinical factors using log-linear regression.\u0000\u0000\u0000RESULTS\u0000Among 4,727 PWH, 397 had 881 CT infections and 331 had 861 GC infections, with incidence of 2.95 and 2.88 per 100 person-years, respectively. From 2007-2017, incidence and testing rates increased by approximately 3.0- and 1.9-fold for CT and GC, respectively. Multivariable factors associated with incident CT (GC) included younger age, MSM, and prior diagnoses of sexually transmitted diseases (STDs). Among 1,159 MSM, 583 (50.3%) had 844 CT and 843 GC tests during 2016-2017, and 26.6% of tests were 3-site (urethra, rectum, and pharynx), yielding the highest rates of CT (GC) detection. Multivariable factors associated with CT (GC) testing included younger age, non-Hispanic/Latino black race, and having prior STDs.\u0000\u0000\u0000CONCLUSIONS\u0000Recent CT and GC incidence and testing increased among PWH; however, only half of MSM were tested for CT or GC during 2016-2017 and < 1/3 of tests were 3-site. To promote sexual health and STD prevention among PWH, including MSM, research regarding the added value of CT and GC testing across three anatomic sites is needed.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79212743","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}
引用次数: 6
Early vaccination with BCG-Denmark or BCG-Japan versus BCG-Russia to healthy newborns in Guinea-Bissau: A randomized controlled trial. 几内亚比绍健康新生儿早期接种bcg -丹麦或bcg -日本与bcg -俄罗斯:一项随机对照试验
F. Schaltz-Buchholzer, M. Bjerregaard-Andersen, C. B. Øland, C. Golding, Elise Brenno Stjernholm, I. Monteiro, P. Aaby, C. Benn
BACKGROUNDBacille Calmette-Guérin (BCG) vaccination remains a cornerstone against tuberculosis. Randomized controlled trials (RCTs) has demonstrated that BCG-Denmark lowers all-cause mortality, but a recent RCT found no effect of BCG-Russia. Observational studies indicate that the genetically divergent BCG strains have different effects.METHODSParallel-group, open-label RCT conducted at the National Hospital in Guinea-Bissau. Healthy neonates were randomized 1:1 to BCG-Denmark (2,851 randomized, 2,840 analyzed) versus BCG-Russia (2,845 randomized, 2,837 analyzed). We hypothesized that BCG-Denmark would reduce morbidity (primary outcome) and mortality while inducing more BCG reactions and Purified Protein Derivative (PPD) responses (secondary outcomes). Halfway through the trial, production of BCG-Denmark was halted, and the trial continued comparing BCG-Japan (3,191 neonates randomized, 3,184 analyzed) with BCG-Russia (3,170 randomized, 3,160 analyzed). Mortality and morbidity data were collected by telephone, at home-visits and at the National Hospital and assessed in Cox-models providing 6-week Mortality Rate Ratios (MRRs) and hospitalization Incidence Rate Ratios (IRRs).RESULTSBy age 6 weeks, there were 140 admissions among neonates vaccinated with BCG-Denmark and 130 admissions for BCG-Russia, IRR=1.08 (95% Confidence Interval: 0.84-1.37). For BCG-Japan there were 185 admissions versus 161 admissions for BCG-Russia, IRR=1.15 (0.93-1.43). The 6-week mortality did not differ, BCG-Denmark/BCG-Russia MRR=1.15 (0.74-1.81); BCG-Japan/BCG-Russia MRR=0.71 (0.43-1.19). BCG-Denmark and BCG-Japan induced more BCG scars and PPD reactions than BCG-Russia.CONCLUSIONBCG strains did not affect morbidity. BCG-Denmark and BCG-Japan were more immunogenic than BCG-Russia by the measures traditionally viewed as surrogates for successful immunization. The implications of strain differences for tuberculosis protection and overall health warrant further study.
背景:卡介苗接种仍然是防治结核病的基石。随机对照试验(RCT)表明,丹麦的bcg降低了全因死亡率,但最近的一项RCT发现俄罗斯的bcg没有效果。观察性研究表明,遗传差异的卡介苗株具有不同的效果。方法在几内亚比绍国立医院进行平行组、开放标签随机对照试验。健康新生儿按1:1随机分为bcg -丹麦组(2851名随机,2840名分析)和bcg -俄罗斯组(2845名随机,2837名分析)。我们假设BCG- denmark会降低发病率(主要结局)和死亡率,同时诱导更多的BCG反应和纯化蛋白衍生物(PPD)反应(次要结局)。试验进行到一半,bcg -丹麦的生产停止,试验继续比较bcg -日本(随机3191例,分析3184例)和bcg -俄罗斯(随机3170例,分析3160例)。通过电话、家访和国立医院收集死亡率和发病率数据,并用cox模型进行评估,提供6周死亡率比(MRRs)和住院发病率比(IRRs)。结果6周龄时,接种bcg -丹麦的新生儿入院140例,接种bcg -俄罗斯的新生儿入院130例,IRR=1.08(95%可信区间:0.84-1.37)。bcg -日本有185人,而bcg -俄罗斯有161人,IRR=1.15(0.93-1.43)。6周死亡率无差异,丹麦/俄罗斯的MRR=1.15 (0.74-1.81);bcg -日本/ bcg -俄罗斯MRR=0.71(0.43-1.19)。BCG-丹麦和BCG-日本比BCG-俄罗斯引起更多的BCG疤痕和PPD反应。结论卡介苗株对发病率无影响。通过传统上被视为成功免疫替代指标的措施,bcg -丹麦和bcg -日本比bcg -俄罗斯更具免疫原性。菌株差异对结核病保护和整体健康的影响值得进一步研究。
{"title":"Early vaccination with BCG-Denmark or BCG-Japan versus BCG-Russia to healthy newborns in Guinea-Bissau: A randomized controlled trial.","authors":"F. Schaltz-Buchholzer, M. Bjerregaard-Andersen, C. B. Øland, C. Golding, Elise Brenno Stjernholm, I. Monteiro, P. Aaby, C. Benn","doi":"10.1093/cid/ciz1080","DOIUrl":"https://doi.org/10.1093/cid/ciz1080","url":null,"abstract":"BACKGROUND\u0000Bacille Calmette-Guérin (BCG) vaccination remains a cornerstone against tuberculosis. Randomized controlled trials (RCTs) has demonstrated that BCG-Denmark lowers all-cause mortality, but a recent RCT found no effect of BCG-Russia. Observational studies indicate that the genetically divergent BCG strains have different effects.\u0000\u0000\u0000METHODS\u0000Parallel-group, open-label RCT conducted at the National Hospital in Guinea-Bissau. Healthy neonates were randomized 1:1 to BCG-Denmark (2,851 randomized, 2,840 analyzed) versus BCG-Russia (2,845 randomized, 2,837 analyzed). We hypothesized that BCG-Denmark would reduce morbidity (primary outcome) and mortality while inducing more BCG reactions and Purified Protein Derivative (PPD) responses (secondary outcomes). Halfway through the trial, production of BCG-Denmark was halted, and the trial continued comparing BCG-Japan (3,191 neonates randomized, 3,184 analyzed) with BCG-Russia (3,170 randomized, 3,160 analyzed). Mortality and morbidity data were collected by telephone, at home-visits and at the National Hospital and assessed in Cox-models providing 6-week Mortality Rate Ratios (MRRs) and hospitalization Incidence Rate Ratios (IRRs).\u0000\u0000\u0000RESULTS\u0000By age 6 weeks, there were 140 admissions among neonates vaccinated with BCG-Denmark and 130 admissions for BCG-Russia, IRR=1.08 (95% Confidence Interval: 0.84-1.37). For BCG-Japan there were 185 admissions versus 161 admissions for BCG-Russia, IRR=1.15 (0.93-1.43). The 6-week mortality did not differ, BCG-Denmark/BCG-Russia MRR=1.15 (0.74-1.81); BCG-Japan/BCG-Russia MRR=0.71 (0.43-1.19). BCG-Denmark and BCG-Japan induced more BCG scars and PPD reactions than BCG-Russia.\u0000\u0000\u0000CONCLUSION\u0000BCG strains did not affect morbidity. BCG-Denmark and BCG-Japan were more immunogenic than BCG-Russia by the measures traditionally viewed as surrogates for successful immunization. The implications of strain differences for tuberculosis protection and overall health warrant further study.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91434831","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}
引用次数: 21
Dynamics of intestinal carriage of Extended-spectrum Beta-lactamase producing Enterobacteriaceae in the Dutch general population (2014-2016). 荷兰普通人群中产广谱β -内酰胺酶肠杆菌科肠道运输动态(2014-2016)
G. van den Bunt, A. Fluit, M. Bootsma, E. V. Duijkeren, J. Scharringa, W. Pelt, M. Bonten
BACKGROUNDIn the Netherlands the prevalence of intestinal Extended-spectrum Beta-lactamase producing Enterobacteriaceae (ESBL-E) carriage in community-dwelling subjects is ~5%. Little is known about the dynamics of ESBL-E carriage.METHODSIn a nation-wide population-based study (2014-2016) with 4,177 community-dwelling subjects, fecal samples from 656 subjects were also collected after one (T=1) and six (T=2) months. Growth of ESBL-E was quantified and whole genome sequence analysis performed. Subjects were categorized as "incidental", "short-term", "long-term" carrier or as "non-carrier". Risk factors were determined by random forest models and logistic regression. Transmissibility and duration of ESBL-E carriage was quantified using a transmission model also using previous study data.RESULTSOut of 656 participants, 96 were ESBL-E carrier at T=0. Sixty-six (10.1%) subjects were "incidental carriers", 22 (3.3%) "short-term carriers", 38 (5.8%) "long-term carriers" and 530 (80.8%) "non-carrier". Risk factors for long-term carriage were travelling to Asia, swimming in sea/ocean, and not changing the kitchen towel daily. The log-transformed CFU ratio at T=0 was predictive for ESBL-E carriage at T=1 (OR: 1.3, 95%CI: 1.2-1.6) and T=2 (OR: 1.2, 95%CI: 1.1-1.4). Model simulations revealed a median decolonization rate of 2.83/year, an average duration of carriage of 0.35 years and an acquisition rate of 0.34/year. The trend of the acquisition rate during the study period was close to zero.CONCLUSIONRisk factors for long-term ESBL-E carriage were travel and hygiene related . The dynamics of ESBL-E carriage in the general Dutch population are characterized by balancing decolonization and acquisition rates.
背景在荷兰,社区居民肠道内产广谱β -内酰胺酶肠杆菌科(ESBL-E)携带的患病率为~5%。人们对ESBL-E运载的动力学知之甚少。方法2014-2016年,在全国范围内对4177名社区居民进行人群研究,分别在1个月(T=1)和6个月(T=2)后采集656名受试者的粪便样本。测定ESBL-E的生长并进行全基因组序列分析。受试者被分为“偶然”、“短期”、“长期”携带者和“非携带者”。危险因素由随机森林模型和logistic回归确定。采用传播模型和既往研究数据对ESBL-E携带的传播率和持续时间进行量化。结果656例患者中,T=0时ESBL-E携带者96例。偶发携带者66例(10.1%),22例(3.3%)。“短期承运者”38人(5.8%)“长期携带者”和530人(80.8%)“非承运人”。长期携带的危险因素是去亚洲旅行、在海里游泳、不每天更换厨房毛巾。T=0时的对数转换CFU比率可预测T=1 (OR: 1.3, 95%CI: 1.2-1.6)和T=2 (OR: 1.2, 95%CI: 1.1-1.4)时的ESBL-E携带情况。模型模拟显示,平均非殖民化率为2.83年/年,平均携带时间为0.35年,获取率为0.34年/年。在研究期间,用户获取率的趋势接近于零。结论长期携带ESBL-E的危险因素与旅行和卫生有关。荷兰一般人口中ESBL-E传播的动态特点是平衡非殖民化和获得率。
{"title":"Dynamics of intestinal carriage of Extended-spectrum Beta-lactamase producing Enterobacteriaceae in the Dutch general population (2014-2016).","authors":"G. van den Bunt, A. Fluit, M. Bootsma, E. V. Duijkeren, J. Scharringa, W. Pelt, M. Bonten","doi":"10.1093/cid/ciz1091","DOIUrl":"https://doi.org/10.1093/cid/ciz1091","url":null,"abstract":"BACKGROUND\u0000In the Netherlands the prevalence of intestinal Extended-spectrum Beta-lactamase producing Enterobacteriaceae (ESBL-E) carriage in community-dwelling subjects is ~5%. Little is known about the dynamics of ESBL-E carriage.\u0000\u0000\u0000METHODS\u0000In a nation-wide population-based study (2014-2016) with 4,177 community-dwelling subjects, fecal samples from 656 subjects were also collected after one (T=1) and six (T=2) months. Growth of ESBL-E was quantified and whole genome sequence analysis performed. Subjects were categorized as \"incidental\", \"short-term\", \"long-term\" carrier or as \"non-carrier\". Risk factors were determined by random forest models and logistic regression. Transmissibility and duration of ESBL-E carriage was quantified using a transmission model also using previous study data.\u0000\u0000\u0000RESULTS\u0000Out of 656 participants, 96 were ESBL-E carrier at T=0. Sixty-six (10.1%) subjects were \"incidental carriers\", 22 (3.3%) \"short-term carriers\", 38 (5.8%) \"long-term carriers\" and 530 (80.8%) \"non-carrier\". Risk factors for long-term carriage were travelling to Asia, swimming in sea/ocean, and not changing the kitchen towel daily. The log-transformed CFU ratio at T=0 was predictive for ESBL-E carriage at T=1 (OR: 1.3, 95%CI: 1.2-1.6) and T=2 (OR: 1.2, 95%CI: 1.1-1.4). Model simulations revealed a median decolonization rate of 2.83/year, an average duration of carriage of 0.35 years and an acquisition rate of 0.34/year. The trend of the acquisition rate during the study period was close to zero.\u0000\u0000\u0000CONCLUSION\u0000Risk factors for long-term ESBL-E carriage were travel and hygiene related . The dynamics of ESBL-E carriage in the general Dutch population are characterized by balancing decolonization and acquisition rates.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77989690","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}
引用次数: 10
Shiga Toxin-Producing Escherichia coli Infections Associated With Romaine Lettuce-United States, 2018. 2018年美国与罗马生菜有关的产志贺毒素大肠埃希氏菌感染。
Lyndsay Bottichio, Amelia Keaton, Deepam Thomas, Tara Fulton, Amanda Tiffany, Anna Frick, Mia Mattioli, Amy Kahler, Jennifer Murphy, Mark Otto, Adiam Tesfai, Angela Fields, Kelly Kline, Jennifer Fiddner, Jeffrey Higa, Amber Barnes, Francine Arroyo, Annabelle Salvatierra, April Holland, Wendy Taylor, June Nash, Bozena M Morawski, Sarah Correll, Rachel Hinnenkamp, Jeffrey Havens, Kane Patel, Morgan N Schroeder, Lori Gladney, Haley Martin, Laura Whitlock, Natasha Dowell, Corinne Newhart, Louise Francois Watkins, Vincent Hill, Susan Lance, Stic Harris, Matthew Wise, Ian Williams, Colin Basler, Laura Gieraltowski

Background: Produce-associated outbreaks of Shiga toxin-producing Escherichia coli (STEC) were first identified in 1991. In April 2018, New Jersey and Pennsylvania officials reported a cluster of STEC O157 infections associated with multiple locations of a restaurant chain. The Centers for Disease Control and Prevention (CDC) queried PulseNet, the national laboratory network for foodborne disease surveillance, for additional cases and began a national investigation.

Methods: A case was defined as an infection between 13 March and 22 August 2018 with 1 of the 22 identified outbreak-associated E. coli O157:H7 or E. coli O61 pulsed-field gel electrophoresis pattern combinations, or with a strain STEC O157 that was closely related to the main outbreak strain by whole-genome sequencing. We conducted epidemiologic and traceback investigations to identify illness subclusters and common sources. A US Food and Drug Administration-led environmental assessment, which tested water, soil, manure, compost, and scat samples, was conducted to evaluate potential sources of STEC contamination.

Results: We identified 240 case-patients from 37 states; 104 were hospitalized, 28 developed hemolytic uremic syndrome, and 5 died. Of 179 people who were interviewed, 152 (85%) reported consuming romaine lettuce in the week before illness onset. Twenty subclusters were identified. Product traceback from subcluster restaurants identified numerous romaine lettuce distributors and growers; all lettuce originated from the Yuma growing region. Water samples collected from an irrigation canal in the region yielded the outbreak strain of STEC O157.

Conclusions: We report on the largest multistate leafy greens-linked STEC O157 outbreak in several decades. The investigation highlights the complexities associated with investigating outbreaks involving widespread environmental contamination.

背景:与农产品相关的产志贺毒素大肠杆菌(STEC)疫情于 1991 年首次被发现。2018 年 4 月,新泽西州和宾夕法尼亚州官员报告了与一家连锁餐馆多个分店相关的 STEC O157 感染群。美国疾病控制和预防中心(CDC)查询了食源性疾病监测国家实验室网络 PulseNet,以了解更多病例,并开始了全国性调查:病例的定义是在 2018 年 3 月 13 日至 8 月 22 日期间感染了 22 种已确定的与疫情相关的大肠杆菌 O157:H7 或大肠杆菌 O61 脉冲场凝胶电泳模式组合中的一种,或通过全基因组测序感染了与主要疫情菌株密切相关的 STEC O157 菌株。我们开展了流行病学和溯源调查,以确定疾病亚群和共同来源。美国食品和药物管理局牵头开展了一项环境评估,对水、土壤、粪便、堆肥和粪便样本进行了检测,以评估 STEC 污染的潜在来源:我们确定了来自 37 个州的 240 名病例患者,其中 104 人住院治疗,28 人出现溶血性尿毒症,5 人死亡。在 179 名受访者中,152 人(85%)称在发病前一周食用过莴苣。确定了 20 个亚群。通过对子群餐馆的产品追踪,确定了许多莴苣经销商和种植商;所有莴苣均来自尤马种植区。从该地区一条灌溉渠中采集的水样检出了 STEC O157 暴发菌株:我们报告了几十年来最大规模的多州叶菜类 STEC O157 疫情。此次调查凸显了调查涉及广泛环境污染的疫情的复杂性。
{"title":"Shiga Toxin-Producing Escherichia coli Infections Associated With Romaine Lettuce-United States, 2018.","authors":"Lyndsay Bottichio, Amelia Keaton, Deepam Thomas, Tara Fulton, Amanda Tiffany, Anna Frick, Mia Mattioli, Amy Kahler, Jennifer Murphy, Mark Otto, Adiam Tesfai, Angela Fields, Kelly Kline, Jennifer Fiddner, Jeffrey Higa, Amber Barnes, Francine Arroyo, Annabelle Salvatierra, April Holland, Wendy Taylor, June Nash, Bozena M Morawski, Sarah Correll, Rachel Hinnenkamp, Jeffrey Havens, Kane Patel, Morgan N Schroeder, Lori Gladney, Haley Martin, Laura Whitlock, Natasha Dowell, Corinne Newhart, Louise Francois Watkins, Vincent Hill, Susan Lance, Stic Harris, Matthew Wise, Ian Williams, Colin Basler, Laura Gieraltowski","doi":"10.1093/cid/ciz1182","DOIUrl":"10.1093/cid/ciz1182","url":null,"abstract":"<p><strong>Background: </strong>Produce-associated outbreaks of Shiga toxin-producing Escherichia coli (STEC) were first identified in 1991. In April 2018, New Jersey and Pennsylvania officials reported a cluster of STEC O157 infections associated with multiple locations of a restaurant chain. The Centers for Disease Control and Prevention (CDC) queried PulseNet, the national laboratory network for foodborne disease surveillance, for additional cases and began a national investigation.</p><p><strong>Methods: </strong>A case was defined as an infection between 13 March and 22 August 2018 with 1 of the 22 identified outbreak-associated E. coli O157:H7 or E. coli O61 pulsed-field gel electrophoresis pattern combinations, or with a strain STEC O157 that was closely related to the main outbreak strain by whole-genome sequencing. We conducted epidemiologic and traceback investigations to identify illness subclusters and common sources. A US Food and Drug Administration-led environmental assessment, which tested water, soil, manure, compost, and scat samples, was conducted to evaluate potential sources of STEC contamination.</p><p><strong>Results: </strong>We identified 240 case-patients from 37 states; 104 were hospitalized, 28 developed hemolytic uremic syndrome, and 5 died. Of 179 people who were interviewed, 152 (85%) reported consuming romaine lettuce in the week before illness onset. Twenty subclusters were identified. Product traceback from subcluster restaurants identified numerous romaine lettuce distributors and growers; all lettuce originated from the Yuma growing region. Water samples collected from an irrigation canal in the region yielded the outbreak strain of STEC O157.</p><p><strong>Conclusions: </strong>We report on the largest multistate leafy greens-linked STEC O157 outbreak in several decades. The investigation highlights the complexities associated with investigating outbreaks involving widespread environmental contamination.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78085390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of a Novel Antimicrobial Surface Coating on Healthcare-Associated Infections and Environmental Bioburden at Two Urban Hospitals. 一种新型抗菌表面涂层对两家城市医院医疗相关感染和环境生物负担的影响
K. Ellingson, K. Pogreba-Brown, C. Gerba, S. Elliott
BACKGROUNDApproximately 1 in 25 people admitted to a hospital in the United States will suffer a healthcare-associated infection (HAI). Environmental contamination of hospital surfaces contributes to HAI transmission. We investigated the impact of an antimicrobial surface coating on HAIs and environmental bioburden at two urban hospitals.METHODSA transparent antimicrobial surface coating was applied to patient rooms and common areas in three units at each hospital. Longitudinal regression models were used to compare changes in hospital-onset multidrug-resistant organism bloodstream infection (MDRO-BSI) and Clostridium difficile infection (CDI) rates in the 12 months before and after application of the surface coating. Incidence rate ratios (IRRs) were compared for units receiving the surface coating application and for contemporaneous control units. Environmental samples were collected pre- and post-application to identify bacterial colony forming units (CFU) and percent of sites positive for select clinically relevant pathogens.RESULTSAcross both hospitals, there was a 36% decline in pooled HAIs (MDRO-BSI + CDI) in units receiving surface coating application (IRR=0.64, 95% CI=0.44-0.91), and no decline in control units (IRR=1.20, 95% CI=0.92-1.55). Following the surface application, total bacterial CFU at Hospitals A and B declined by 64% and 75%, respectively; the percentage of environmental samples positive for clinically relevant pathogens also declined significantly for both hospitals.CONCLUSIONSStatistically significant reductions in HAIs and environmental bioburden occurred in units receiving the antimicrobial surface coating, suggesting the potential for improved patient outcomes and persistent reduction in environmental contamination. Future studies should assess optimal implementation methods and long-term impact.
背景:在美国,大约每25名住院患者中就有1人患有医疗保健相关感染(HAI)。医院表面的环境污染有助于HAI的传播。我们研究了抗菌表面涂层对两家城市医院HAIs和环境生物负荷的影响。方法在各医院3个科室的病房和公共区域应用透明抗菌表面涂层。采用纵向回归模型比较应用表面涂层前后12个月内医院发病的多药耐药生物血流感染(MDRO-BSI)和艰难梭菌感染(CDI)率的变化。比较了接受表面涂层应用的单元和同期控制单元的发病率比(IRRs)。在应用前和应用后收集环境样本,以确定细菌菌落形成单位(CFU)和选择临床相关病原体的阳性位点百分比。结果两家医院接受表面涂层治疗的单位合并HAIs (MDRO-BSI + CDI)下降了36% (IRR=0.64, 95% CI=0.44-0.91),而对照单位没有下降(IRR=1.20, 95% CI=0.92-1.55)。表面施用后,A医院和B医院的总细菌CFU分别下降了64%和75%;两家医院的环境样本中临床相关病原体呈阳性的百分比也显著下降。结论:在接受抗菌表面涂层的单位中,HAIs和环境生物负担显著降低,表明有可能改善患者预后并持续减少环境污染。未来的研究应评估最佳的实施方法和长期影响。
{"title":"Impact of a Novel Antimicrobial Surface Coating on Healthcare-Associated Infections and Environmental Bioburden at Two Urban Hospitals.","authors":"K. Ellingson, K. Pogreba-Brown, C. Gerba, S. Elliott","doi":"10.1093/cid/ciz1077","DOIUrl":"https://doi.org/10.1093/cid/ciz1077","url":null,"abstract":"BACKGROUND\u0000Approximately 1 in 25 people admitted to a hospital in the United States will suffer a healthcare-associated infection (HAI). Environmental contamination of hospital surfaces contributes to HAI transmission. We investigated the impact of an antimicrobial surface coating on HAIs and environmental bioburden at two urban hospitals.\u0000\u0000\u0000METHODS\u0000A transparent antimicrobial surface coating was applied to patient rooms and common areas in three units at each hospital. Longitudinal regression models were used to compare changes in hospital-onset multidrug-resistant organism bloodstream infection (MDRO-BSI) and Clostridium difficile infection (CDI) rates in the 12 months before and after application of the surface coating. Incidence rate ratios (IRRs) were compared for units receiving the surface coating application and for contemporaneous control units. Environmental samples were collected pre- and post-application to identify bacterial colony forming units (CFU) and percent of sites positive for select clinically relevant pathogens.\u0000\u0000\u0000RESULTS\u0000Across both hospitals, there was a 36% decline in pooled HAIs (MDRO-BSI + CDI) in units receiving surface coating application (IRR=0.64, 95% CI=0.44-0.91), and no decline in control units (IRR=1.20, 95% CI=0.92-1.55). Following the surface application, total bacterial CFU at Hospitals A and B declined by 64% and 75%, respectively; the percentage of environmental samples positive for clinically relevant pathogens also declined significantly for both hospitals.\u0000\u0000\u0000CONCLUSIONS\u0000Statistically significant reductions in HAIs and environmental bioburden occurred in units receiving the antimicrobial surface coating, suggesting the potential for improved patient outcomes and persistent reduction in environmental contamination. Future studies should assess optimal implementation methods and long-term impact.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78383697","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}
引用次数: 32
How much impact do antimicrobial surfaces really have on healthcare-acquired infection? 抗菌表面对医疗获得性感染的影响到底有多大?
S. Dancer
{"title":"How much impact do antimicrobial surfaces really have on healthcare-acquired infection?","authors":"S. Dancer","doi":"10.1093/cid/ciz1078","DOIUrl":"https://doi.org/10.1093/cid/ciz1078","url":null,"abstract":"","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86258484","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}
引用次数: 5
The duration, dynamics and determinants of SARS-CoV-2 antibody responses in individual healthcare workers 个体医护人员SARS-CoV-2抗体反应的持续时间、动态和决定因素
S. Lumley, Jia Wei, D. O’Donnell, N. Stoesser, P. Matthews, A. Howarth, S. Hatch, B. Marsden, S. Cox, T. James, Liam J. Peck, Thomas G Ritter, Z. de Toledo, R. Cornall, E. Jones, D. Stuart, G. Screaton, Daniela Ebner, S. Hoosdally, D. Crook, C. Conlon, K. Pouwels, A. Walker, T. Peto, T. Walker, K. Jeffery, D. Eyre
Background SARS-CoV-2 IgG antibody measurements can be used to estimate the proportion of a population exposed or infected and may be informative about the risk of future infection. Previous estimates of the duration of antibody responses vary. Methods We present 6 months of data from a longitudinal seroprevalence study of 3217 UK healthcare workers (HCWs). Serial measurements of IgG antibodies to SARS-CoV-2 nucleocapsid were obtained. Bayesian mixed linear models were used to investigate antibody waning and associations with age, gender, ethnicity, previous symptoms and PCR results. Results In this cohort of working age HCWs, antibody levels rose to a peak at 24 (95% credibility interval, CrI 19-31) days post-first positive PCR test, before beginning to fall. Considering 452 IgG seropositive HCWs over a median of 121 days (maximum 171 days) from their maximum positive IgG titre, the mean estimated antibody half-life was 85 (95%CrI, 81-90) days. The estimated mean time to loss of a positive antibody result was 137 (95%CrI 127-148) days. We observed variation between individuals; higher maximum observed IgG titres were associated with longer estimated antibody half-lives. Increasing age, Asian ethnicity and prior self-reported symptoms were independently associated with higher maximum antibody levels, and increasing age and a positive PCR test undertaken for symptoms with longer antibody half-lives. Conclusion IgG antibody levels to SARS-CoV-2 nucleocapsid wane within months, and faster in younger adults and those without symptoms. Ongoing longitudinal studies are required to track the long-term duration of antibody levels and their association with immunity to SARS-CoV-2 reinfection.
背景:SARS-CoV-2 IgG抗体测量可用于估计暴露或感染人群的比例,并可提供有关未来感染风险的信息。以往对抗体反应持续时间的估计各不相同。方法:研究人员对3217名英国医护人员(HCWs)进行了为期6个月的纵向血清患病率研究。获得了SARS-CoV-2核衣壳IgG抗体的系列测量结果。使用贝叶斯混合线性模型调查抗体减弱及其与年龄、性别、种族、既往症状和PCR结果的关系。结果在该工作年龄的医护人员队列中,抗体水平在首次PCR阳性检测后24天(95%可信区间,CrI 19-31)达到峰值,然后开始下降。考虑到452例IgG血清阳性HCWs中位时间为121天(最长时间为171天),估计抗体半衰期平均为85天(95%CrI, 81-90)天。估计失去阳性抗体结果的平均时间为137天(95%CrI 127-148)。我们观察到个体之间的差异;观察到的最大IgG滴度越高,估计的抗体半衰期越长。年龄增长、亚洲种族和先前自我报告的症状与较高的最大抗体水平、年龄增长和抗体半衰期较长的症状的PCR检测阳性独立相关。结论SARS-CoV-2核衣壳IgG抗体水平在几个月内下降,且在年轻人和无症状者中下降更快。需要进行持续的纵向研究,以跟踪抗体水平的长期持续时间及其与SARS-CoV-2再感染免疫的关系。
{"title":"The duration, dynamics and determinants of SARS-CoV-2 antibody responses in individual healthcare workers","authors":"S. Lumley, Jia Wei, D. O’Donnell, N. Stoesser, P. Matthews, A. Howarth, S. Hatch, B. Marsden, S. Cox, T. James, Liam J. Peck, Thomas G Ritter, Z. de Toledo, R. Cornall, E. Jones, D. Stuart, G. Screaton, Daniela Ebner, S. Hoosdally, D. Crook, C. Conlon, K. Pouwels, A. Walker, T. Peto, T. Walker, K. Jeffery, D. Eyre","doi":"10.1101/2020.11.02.20224824","DOIUrl":"https://doi.org/10.1101/2020.11.02.20224824","url":null,"abstract":"Background SARS-CoV-2 IgG antibody measurements can be used to estimate the proportion of a population exposed or infected and may be informative about the risk of future infection. Previous estimates of the duration of antibody responses vary. Methods We present 6 months of data from a longitudinal seroprevalence study of 3217 UK healthcare workers (HCWs). Serial measurements of IgG antibodies to SARS-CoV-2 nucleocapsid were obtained. Bayesian mixed linear models were used to investigate antibody waning and associations with age, gender, ethnicity, previous symptoms and PCR results. Results In this cohort of working age HCWs, antibody levels rose to a peak at 24 (95% credibility interval, CrI 19-31) days post-first positive PCR test, before beginning to fall. Considering 452 IgG seropositive HCWs over a median of 121 days (maximum 171 days) from their maximum positive IgG titre, the mean estimated antibody half-life was 85 (95%CrI, 81-90) days. The estimated mean time to loss of a positive antibody result was 137 (95%CrI 127-148) days. We observed variation between individuals; higher maximum observed IgG titres were associated with longer estimated antibody half-lives. Increasing age, Asian ethnicity and prior self-reported symptoms were independently associated with higher maximum antibody levels, and increasing age and a positive PCR test undertaken for symptoms with longer antibody half-lives. Conclusion IgG antibody levels to SARS-CoV-2 nucleocapsid wane within months, and faster in younger adults and those without symptoms. Ongoing longitudinal studies are required to track the long-term duration of antibody levels and their association with immunity to SARS-CoV-2 reinfection.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81547785","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}
引用次数: 110
期刊
Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1