Journal of Infection最新文献_第5页

Effect of a campaign with oral polio vaccine on general health: A cluster-randomised trial in rural Guinea-Bissau 口服脊髓灰质炎疫苗运动对总体健康的影响：几内亚比绍农村地区的分组随机试验。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-09-30 DOI: 10.1016/j.jinf.2024.106302

Objectives

To investigate in a cluster-randomised trial whether a campaign with oral polio vaccine (C-OPV) reduced mortality and morbidity.

Methods

We randomised 222 village clusters under demographic surveillance to an intervention (health check and C-OPV) or control group (health check only). Children aged 0–8 months were eligible. In Cox proportional hazards models with age as the underlying timescale, we compared rates of non-accidental mortality/hospital admission (composite primary outcome) during 12 months of follow-up. Secondary analyses considered non-accidental admission and mortality as separate outcomes. Potential effect modifiers identified in prior studies including sex, season, and timing of the first routine OPV dose (OPV0, scheduled at birth) were assessed.

Results

Among 10,175 children (5288 in 111 intervention clusters/4887 in 111 control clusters), we observed 265 deaths/admissions during 7616 person-years at risk (intervention: 129; control: 136). C-OPV did not reduce the composite endpoint, hazard ratio (HR): 0.87, 95%CI: 0.68–1.12 or its separate components. C-OPV reduced the risk in children receiving OPV0<15 days of birth (HR=0.66, 95%CI: 0.46–0.95), but not in other children (p for interaction: 0.03). Interactions for other potential effect modifiers were not statistically significant.

Conclusions

C-OPV had no overall effect on mortality/admissions, but the effect differed by early priming with OPV0.

目的通过分组随机试验调查口服脊髓灰质炎疫苗（C-OPV）是否能降低死亡率和发病率：我们将 222 个接受人口监测的村庄集群随机分为干预组（健康检查和 C-OPV）或对照组（仅健康检查）。0-8个月大的儿童均符合条件。在以年龄为基本时间尺度的 Cox 比例危险模型中，我们比较了 12 个月随访期间的非意外死亡率/入院率（综合主要结果）。二次分析将非意外入院率和死亡率作为单独的结果。我们还评估了先前研究中发现的潜在影响因素，包括性别、季节和首次常规接种 OPV 的时间（OPV0，计划在出生时接种）：在 10,175 名儿童（111 个干预群组中的 5,288 人/111 个对照群组中的 4,887 人）中，我们观察到在 7,616 个风险年中有 265 人死亡/入院（干预群组：129 人；对照群组：136 人）。C-OPV 没有降低综合终点（危险比 (HR)：0.87，95%CI：0.68-1.12）或其单独组成部分。结论：C-OPV降低了接受OPV的儿童的风险：结论：C-OPV对死亡率/入院率没有总体影响，但效果因早期接种OPV0而异。

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引用次数: 0

Occurrence and predictors of laboratory abnormalities during outpatient parenteral antimicrobial therapy – A multicenter cohort study to inform laboratory test monitoring 门诊胃肠外抗菌治疗期间实验室异常的发生率和预测因素--一项多中心队列研究，为实验室检验监测提供依据。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-09-30 DOI: 10.1016/j.jinf.2024.106301

Objectives

Evidence on the optimal frequency of laboratory testing during outpatient parenteral antimicrobial therapy (OPAT) is lacking. Therefore, we investigated how often and when laboratory abnormalities occur during OPAT and which factors are associated with these abnormalities.

Methods

We performed a multicenter cohort study in four Dutch hospitals among adult patients receiving OPAT and collected routinely obtained laboratory test results. Incidence and incidence rates were calculated for various laboratory abnormalities. Survival analysis was performed to visualize the time to the first occurrence of laboratory abnormalities and Poisson regression analysis to compare the number of abnormalities in the first and second 30 OPAT days among patients receiving OPAT for ≥60 days. Predictors were identified using a multivariable Cox proportional hazard regression model.

Results

45.1% of 1152 included patients developed laboratory abnormalities, but only 2% led to OPAT discontinuation. Hepatotoxicity was most common (33.9 events/1000 OPAT days), with a time-dependent decrease in the occurrence of the first hepatotoxic event, while hypokalemia was rare (1.7 events/1000 OPAT days). In the subgroup of patients receiving ≥60 days of OPAT, nephrotoxicity was more common in days 31–60. We observed partly toxicity-specific associations between antibiotic type, concomitant medication, baseline laboratory values, patient characteristics, and the occurrence of laboratory abnormalities.

Conclusions

While laboratory abnormalities are frequently observed during OPAT, they rarely lead to discontinuation of OPAT. Specific patient, treatment and laboratory characteristics were associated with the occurrence of laboratory abnormalities. Based on our results, we recommend a more personalized laboratory monitoring policy with less blood sampling.

目的：关于门诊肠外抗菌治疗（OPAT）期间实验室检测的最佳频率尚缺乏证据。因此，我们对 OPAT 期间实验室异常发生的频率和时间以及与这些异常相关的因素进行了调查：我们在四家荷兰医院对接受 OPAT 治疗的成年患者进行了一项多中心队列研究，并收集了常规实验室检测结果。我们计算了各种实验室异常的发生率和发病率。对接受 OPAT≥60 天的患者进行了生存分析，以直观显示首次出现实验室异常的时间，并进行了泊松回归分析，以比较接受 OPAT 前 30 天和后 30 天的异常数量。使用多变量考克斯比例危险回归模型确定了预测因素：结果：在纳入的1152名患者中，45.1%的患者出现实验室异常，但只有2%的患者因此停用了OPAT。肝毒性最为常见（33.9 例/1000 OPAT 天），首次肝毒性事件的发生率随时间推移而下降，而低钾血症则很少见（1.7 例/1000 OPAT 天）。在接受 OPAT 治疗≥60 天的患者亚组中，肾毒性在第 31-60 天更为常见。我们观察到抗生素类型、伴随用药、基线实验室值、患者特征与实验室异常发生之间存在部分毒性特异性关联：虽然在 OPAT 期间经常会观察到实验室异常，但它们很少导致 OPAT 的中止。特定的患者、治疗和实验室特征与实验室异常的发生有关。基于我们的研究结果，我们建议采取更个性化的实验室监测政策，减少抽血次数。

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引用次数: 0

Global resurgence of pertussis: A perspective from China 百日咳在全球卷土重来：来自中国的视角。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-09-30 DOI: 10.1016/j.jinf.2024.106289

Pertussis (or whooping cough) is a highly infectious acute respiratory disease primarily caused by Bordetella pertussis, which is also one of the most important causes of infant death worldwide. The widespread use of vaccines has greatly reduced the morbidity and mortality of pertussis. However, since the 1980s, in a number of countries with high vaccine coverage, the incidence of pertussis has risen again after remaining low for many years, with outbreaks even occurring in some areas. The peak onset of pertussis is shifting from infancy to adolescence, and adolescence is becoming the main source of infection for infants. Despite the increasing incidence of pertussis, serological findings suggest that the true prevalence of the disease may be significantly underestimated. Therefore, in this narrative review, we summarize the pathogenic process and immune characteristics of bacteria, the diagnosis and treatment of diseases, as well as vaccination and prevalence of pertussis at home and abroad, and attempt to analyze the causes and influencing factors of pertussis resurgence and summarize some prevention and control strategies to assist in improving the understanding of pertussis and preventing unexpected outbreaks.

百日咳（或百日咳）是一种高度传染性的急性呼吸道疾病，主要由百日咳杆菌引起，也是全球婴儿死亡的最重要原因之一。疫苗的广泛使用大大降低了百日咳的发病率和死亡率。然而，自 20 世纪 80 年代以来，在一些疫苗覆盖率较高的国家，百日咳的发病率在多年保持低水平后再次上升，在一些地区甚至出现了爆发。百日咳的发病高峰正从婴儿期向青少年期转移，青少年正成为婴儿的主要感染源。尽管百日咳发病率不断上升，但血清学研究结果表明，该病的真实发病率可能被严重低估。因此，在这篇叙事性综述中，我们总结了百日咳的致病过程和细菌的免疫特性、疾病的诊断和治疗以及疫苗接种和国内外的流行情况，并试图分析百日咳死灰复燃的原因和影响因素，总结一些预防和控制策略，以帮助提高人们对百日咳的认识，防止意外爆发。

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引用次数: 0

Regulation of plasma soluble receptors of TNF and IL-1 in patients with COVID-19 differs from that observed in sepsis COVID-19 患者血浆中 TNF 和 IL-1 可溶性受体的调节与败血症患者不同。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-09-30 DOI: 10.1016/j.jinf.2024.106300

Objectives

IL-1α/β and TNF are closely linked to the pathology of severe COVID-19 and sepsis. The soluble forms of their receptors, functioning as decoy receptors, exhibit inhibitory effects. However, little is known about their regulation in severe bacterial and viral infections, which we aimed to investigate in this study.

Methods

The circulating soluble receptors of TNF (sTNFR1 and sTNFR2) and IL-1α/β (sIL-1R1, sIL-1R2) were evaluated in the plasma of patients with COVID-19, severe bacterial infections, and sepsis and compared with healthy controls. Additionally, IL1R1, IL1R2, TNFRSF1A, and TNFRSF1B expression was evaluated at the single cell level in PBMCs derived from COVID-19 or sepsis patients.

Results

Plasma concentrations of sIL-1R1, sTNFR1, and sTNFR2 were significantly higher in COVID-19 patients compared to healthy subjects. Notably, sIL-1R1 levels were particularly elevated in ICU COVID-19 patients, and transcriptome analysis indicated heightened IL1R1 expression in PBMCs from severe COVID-19 patients. In severe bacterial infections, only sTNFR1 and sTNFR2 exhibited increased levels compared to healthy controls. Sepsis patients had decreased sIL-1R1 plasma concentrations but elevated sIL-1R2, sTNFR1, and sTNFR2 levels compared to healthy individuals, reflecting the heightened expression due to the increased numbers of monocytes present in sepsis. Finally, elevated concentrations of sIL-1R2, sTNFR1, and sTNFR2 were moderately associated with reduced 28-day survival in sepsis patients.

Conclusion

Our study reveals distinct regulation of plasma concentrations of soluble IL-1 receptors in COVID-19 and sepsis. Moreover, soluble TNF receptors 1 and 2 consistently rise in all conditions and show a positive correlation with disease severity in sepsis.

目的：IL-1α/β 和 TNF 与严重 COVID-19 和败血症的病理学密切相关。它们的可溶性受体作为诱饵受体，具有抑制作用。然而，我们对它们在严重细菌和病毒感染中的调节作用知之甚少，本研究旨在对此进行研究：方法：评估 COVID-19、严重细菌感染和败血症患者血浆中 TNF（sTNFR1 和 sTNFR2）和 IL-1α/β （sIL-1R1、sIL-1R2）的循环可溶性受体，并与健康对照组进行比较。此外，还在 COVID-19 或败血症患者的 PBMCs 中评估了 IL1R1、IL1R2、TNFRSF1A 和 TNFRSF1B 在单细胞水平上的表达：结果：与健康人相比，COVID-19 患者血浆中 sIL-1R1、sTNFR1 和 sTNFR2 的浓度明显较高。值得注意的是，ICU COVID-19 患者的 sIL-1R1 水平特别高，转录组分析表明严重 COVID-19 患者的 PBMCs 中 IL1R1 表达增强。在严重细菌感染中，与健康对照组相比，只有 sTNFR1 和 sTNFR2 的水平有所升高。与健康人相比，败血症患者血浆中的 sIL-1R1 浓度降低，但 sIL-1R2、sTNFR1 和 sTNFR2 水平升高，这反映了败血症中单核细胞数量增加导致表达增强。最后，sIL-1R2、sTNFR1 和 sTNFR2 浓度的升高与败血症患者 28 天存活率的降低呈中度相关：我们的研究揭示了 COVID-19 和脓毒症患者血浆中可溶性 IL-1 受体浓度的不同调节方式。此外，可溶性 TNF 受体 1 和 2 在所有情况下均持续上升，并与败血症的疾病严重程度呈正相关。

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引用次数: 0

Outpatient parenteral antimicrobial therapy with carbapenems: A systematic review 使用碳青霉烯类药物的门诊外用抗菌疗法：系统综述。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-09-30 DOI: 10.1016/j.jinf.2024.106299

Objective

To review the literature on parenteral carbapenems in OPAT and present comprehensive evidence on their safety, efficacy, and stability.

Methods

A systematic review following PRISMA guidelines was conducted through 17 January 2024, using PubMed, Embase, Web of Science, Scopus, and the Cochrane Library to find relevant articles.

Results

Ertapenem (1 g QD) in OPAT showed high clinical (81–97%) and microbiological (67–90.9%) success rates. Ertapenem (1 g QD) was also comparable to piperacillin/tazobactam (3.375 g every 6 h) for complicated skin infections and superior to cefazolin (2 g every 8 h) and oxacillin (2 g every 4–6 h) for various infections. Ertapenem monotherapy, once daily, achieved an 81% clinical cure rate for urinary tract infections. Additionally, subcutaneous ertapenem in OPAT showed outcomes comparable to parenteral routes. Meropenem continuous infusion (CI) may also be considered safe and effective in selected patient populations; however, its use in OPAT as a CI is limited due to stability concerns.

Conclusion

Parenteral carbapenems are effective, and well-tolerated OPAT treatment options; nonetheless, further studies are warranted to optimize the stability and/or dosing regimens of meropenem and enable its wider use.

目的回顾有关 OPAT 中肠外碳青霉烯类药物的文献，并提供有关其安全性、有效性和稳定性的全面证据：方法：使用 PubMed、Embase、Web of Science、Scopus 和 Cochrane 图书馆查找相关文章，按照 PRISMA 指南进行了系统性综述（截至 2024 年 1 月 17 日）：厄他培南（1 克 QD）在 OPAT 中的临床成功率（81%-97%）和微生物成功率（67%-90.9%）都很高。在治疗复杂性皮肤感染方面，厄他培南（1 克 QD）的疗效与哌拉西林/他唑巴坦（3.375 克，每 6 小时一次）相当；在治疗各种感染方面，厄他培南（1 克 QD）的疗效优于头孢唑啉（2 克，每 8 小时一次）和氧西林（2 克，每 4-6 小时一次）。厄他培南单药治疗尿路感染，每日一次，临床治愈率达 81%。此外，在 OPAT 中皮下注射厄他培南的疗效与肠外途径相当。美罗培南持续输注（CI）在特定患者群体中也被认为是安全有效的；但由于稳定性问题，其在 OPAT 中作为 CI 的使用受到了限制：结论：肠外碳青霉烯类是有效且耐受性良好的 OPAT 治疗选择；然而，还需要进一步研究以优化美罗培南的稳定性和/或给药方案，使其得到更广泛的应用。

{"title":"Outpatient parenteral antimicrobial therapy with carbapenems: A systematic review","authors":"","doi":"10.1016/j.jinf.2024.106299","DOIUrl":"10.1016/j.jinf.2024.106299","url":null,"abstract":"<div><h3>Objective</h3><div>To review the literature on parenteral carbapenems in OPAT and present comprehensive evidence on their safety, efficacy, and stability.</div></div><div><h3>Methods</h3><div>A systematic review following PRISMA guidelines was conducted through 17 January 2024, using PubMed, Embase, Web of Science, Scopus, and the Cochrane Library to find relevant articles.</div></div><div><h3>Results</h3><div>Ertapenem (1 g QD) in OPAT showed high clinical (81–97%) and microbiological (67–90.9%) success rates. Ertapenem (1 g QD) was also comparable to piperacillin/tazobactam (3.375 g every 6 h) for complicated skin infections and superior to cefazolin (2 g every 8 h) and oxacillin (2 g every 4–6 h) for various infections. Ertapenem monotherapy, once daily, achieved an 81% clinical cure rate for urinary tract infections. Additionally, subcutaneous ertapenem in OPAT showed outcomes comparable to parenteral routes. Meropenem continuous infusion (CI) may also be considered safe and effective in selected patient populations; however, its use in OPAT as a CI is limited due to stability concerns.</div></div><div><h3>Conclusion</h3><div>Parenteral carbapenems are effective, and well-tolerated OPAT treatment options; nonetheless, further studies are warranted to optimize the stability and/or dosing regimens of meropenem and enable its wider use.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The persistence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis SARS-CoV-2感染后肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）的持续存在：系统回顾和荟萃分析。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-09-29 DOI: 10.1016/j.jinf.2024.106297

Objectives

Long COVID-19 (LC) patients experience a number of chronic idiopathic symptoms that are highly similar to those of post-viral myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We have therefore performed a systematic review and meta-analysis to determine the proportion of LC patients that satisfy ME/CFS diagnostic criteria.

Methods

Clinical studies published between January 2020 and May 2023 were identified using the PubMed, Web of Science, Embase and CINAHL databases. Publication inclusion/exclusion criteria were formulated using the global CoCoPop framework. Data were pooled using a random-effects model with a restricted maximum-likelihood estimator. Study quality was assessed using the Joanna Briggs Institute critical assessment tool.

Results

We identified 13 eligible studies that reported a total of 1973 LC patients. Our meta-analysis indicated that 51% (95% CI, 42%−60%) of LC patients satisfied ME/CFS diagnostic criteria, with fatigue, sleep disruption, and muscle/joint pain being the most common symptoms. Importantly, LC patients also experienced the ME/CFS hallmark symptom, post-exertional malaise.

Conclusions

Our study not only demonstrates that LC patients exhibit similar symptom clusters to ME/CFS, but that approximately half of LC patients satisfy a diagnosis of ME/CFS. Our findings suggest that current ME/CFS criteria could be adapted to the identification of a subset of LC patients that may facilitate the standardised diagnosis, management and the recruitment for clinical studies in the future.

目的：长COVID-19（LC）患者会出现一些慢性特发性症状，这些症状与病毒后肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）的症状极为相似。因此，我们进行了一项系统回顾和荟萃分析，以确定符合 ME/CFS 诊断标准的 LC 患者比例：方法：我们使用 PubMed、Web of Science、Embase 和 CINAHL 数据库对 2020 年 1 月至 2023 年 5 月间发表的临床研究进行了鉴定。采用全球 CoCoPop 框架制定了出版物纳入/排除标准。采用随机效应模型和限制性最大似然估计法对数据进行汇总。研究质量采用乔安娜-布里格斯研究所的关键评估工具进行评估：我们确定了 13 项符合条件的研究，共报告了 1,973 名 LC 患者。我们的荟萃分析表明，51%（95% CI，42%-60%）的 LC 患者符合 ME/CFS 诊断标准，疲劳、睡眠障碍和肌肉/关节疼痛是最常见的症状。重要的是，LC 患者还出现了 ME/CFS 的标志性症状--劳累后乏力：我们的研究不仅证明了 LC 患者表现出与 ME/CFS 相似的症状群，而且大约一半的 LC 患者符合 ME/CFS 的诊断标准。我们的研究结果表明，目前的ME/CFS标准可用于确定LC患者的子集，这将有助于标准化诊断、管理和未来临床研究的招募：数据可应要求提供。

{"title":"The persistence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis","authors":"","doi":"10.1016/j.jinf.2024.106297","DOIUrl":"10.1016/j.jinf.2024.106297","url":null,"abstract":"<div><h3>Objectives</h3><div>Long COVID-19 (LC) patients experience a number of chronic idiopathic symptoms that are highly similar to those of post-viral myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We have therefore performed a systematic review and meta-analysis to determine the proportion of LC patients that satisfy ME/CFS diagnostic criteria.</div></div><div><h3>Methods</h3><div>Clinical studies published between January 2020 and May 2023 were identified using the PubMed, Web of Science, Embase and CINAHL databases. Publication inclusion/exclusion criteria were formulated using the global CoCoPop framework. Data were pooled using a random-effects model with a restricted maximum-likelihood estimator. Study quality was assessed using the Joanna Briggs Institute critical assessment tool.</div></div><div><h3>Results</h3><div>We identified 13 eligible studies that reported a total of 1973 LC patients. Our meta-analysis indicated that 51% (95% CI, 42%−60%) of LC patients satisfied ME/CFS diagnostic criteria, with fatigue, sleep disruption, and muscle/joint pain being the most common symptoms. Importantly, LC patients also experienced the ME/CFS hallmark symptom, post-exertional malaise.</div></div><div><h3>Conclusions</h3><div>Our study not only demonstrates that LC patients exhibit similar symptom clusters to ME/CFS, but that approximately half of LC patients satisfy a diagnosis of ME/CFS. Our findings suggest that current ME/CFS criteria could be adapted to the identification of a subset of LC patients that may facilitate the standardised diagnosis, management and the recruitment for clinical studies in the future.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protection of vaccine boosters and prior infection against mild/asymptomatic and moderate COVID-19 infection in the UK SIREN healthcare worker cohort: October 2023 to March 2024 英国 SIREN 医护人员队列中轻度/无症状和中度 COVID-19 感染的疫苗强化剂和既往感染保护：2023 年 10 月至 2024 年 3 月。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-09-27 DOI: 10.1016/j.jinf.2024.106293

Objectives

Bivalent original/BA.4–5 and monovalent XBB.1.5 mRNA boosters were offered to UK healthcare workers (HCWs) in the autumn of 2023. We aimed to estimate booster vaccine effectiveness (VE) and post-infection immunity among the SIREN HCW cohort over the subsequent 6-month period of XBB.1.5 and JN.1 variant circulation.

Methods

Between October 2023 to March 2024, 2867 SIREN study participants tested fortnightly for SARS-CoV-2 and completed symptoms questionnaires. We used multi-state models, adjusted for vaccination, prior infection, and demographic covariates, to estimate protection against mild/asymptomatic and moderate SARS-CoV-2 infection.

Results

Half of the participants (1422) received a booster during October 2023 (280 bivalent, 1142 monovalent), and 536 (19%) had a PCR-confirmed infection over the study period. Bivalent booster VE was 15.1% (−55.4 to 53.6%) at 0–2 months and 4.2% (−46.4 to 37.3%) at 2–4 months post-vaccination. Monovalent booster VE was 44.2% (95% CI 21.7 to 60.3%) at 0–2 months, and 24.1% (−0.7 to 42.9%) at 2–4 months. VE was greater against moderate infection than against mild/asymptomatic infection, but neither booster showed evidence of protection after 4 months. Controlling for vaccination, compared to an infection >2 years prior, infection within the past 6 months was associated with 58.6% (30.3 to 75.4%) increased protection against moderate infection and 38.5% (5.8 to 59.8%) increased protection against mild/asymptomatic infection.

Conclusions

Monovalent XBB.1.5 boosters provided short-term protection against SARS-CoV-2 infection, particularly against moderate symptoms. Vaccine formulations that target the circulating variant may be suitable for inclusion in seasonal vaccination campaigns among HCWs.

目标：2023年秋季向英国医护人员（HCWs）提供二价原始/BA.4-5和单价XBB.1.5 mRNA强化疫苗。我们的目的是估算 XBB.1.5 和 JN.1 变体在随后 6 个月的流通期间在 SIREN 医护人员队列中的强化疫苗有效性 (VE) 和感染后免疫力：在 2023 年 10 月至 2024 年 3 月期间，2867 名 SIREN 研究参与者每两周进行一次 SARS-CoV-2 检测，并填写症状问卷。我们使用多状态模型，对疫苗接种、先前感染和人口统计学协变量进行了调整，以估算轻度/无症状和中度 SARS-CoV-2 感染的保护率：半数参与者（1,422 人）在 2023 年 10 月期间接种了加强剂（280 人接种了二价疫苗，1,142 人接种了一价疫苗），536 人（19%）在研究期间经 PCR 证实感染了 SARS-CoV-2。二价疫苗接种后 0-2 个月的 VE 为 15.1%（-55.4% 至 53.6%），接种后 2-4 个月的 VE 为 4.2%（-46.4% 至 37.3%）。接种后 0-2 个月和 2-4 个月，单价加强剂的 VE 分别为 44.2% (95% CI 21.7 至 60.3%)和 24.1% (-0.7 至 42.9%)。对中度感染的保护率高于对轻度/无症状感染的保护率，但两种加强剂在 4 个月后都没有显示出保护作用。在控制疫苗接种的情况下，与两年前的感染相比，过去6个月内的感染可提高58.6%（30.3%至75.4%）的中度感染保护率，提高38.5%（5.8%至59.8%）的轻度/无症状感染保护率：结论：单价XBB.1.5加强剂可在短期内预防SARS-CoV-2感染，尤其是预防中度症状。针对流行变异株的疫苗制剂可能适合纳入人机工程人员的季节性疫苗接种活动。

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引用次数: 0

Therapy modulates the response to T cell epitopes over the spectrum of tuberculosis infection 治疗可调节结核病感染范围内对 T 细胞表位的反应。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-09-27 DOI: 10.1016/j.jinf.2024.106295

Background

Identifying stage-specific antigens is essential for developing tuberculosis (TB) diagnostics and vaccines. In a low TB endemic country, we characterized, the Mycobacterium tuberculosis (Mtb)-specific immune response to a pool of Mtb-derived epitopes (ATB116), demonstrated as associated with TB disease.

Methods

In this prospective observational cross-sectional study, we enrolled healthy donors (HD), subjects with TB disease, and TB infection (TBI) at baseline and therapy completion. T-cell response after whole blood stimulation with the peptide pools was characterized by ELISA, flow cytometry, and multiplex assay.

Results

ATB116-specific IFN-γ response (by ELISA) significantly associates with Mtb regardless of infection/disease (p < 0.0001) and decreases during TB therapy (p = 0.0002). Flow cytometry confirms that ATB116-specific CD4⁺ T-cell response associated with Mtb regardless of infection/disease (p < 0.0001) and shows a significantly higher frequency of IFN-γ/IL-2 and central memory T-cells in TBI compared to TB (p = 0.016; p = 0.0242, respectively). CD4⁺ T cell-specific response decreases after TB therapy completion. The antigen-specific CD8⁺ T-cell response mirrors the CD4⁺ response. Finally, the multiplex assay analysis showed that ATB116 induces several immune factors in both TB and TBI.

Conclusion

We characterized the immune response to Mtb peptide pools that is modulated by TB therapy. These results are important for our understanding of TB immunopathogenesis and vaccine design.

背景：确定阶段特异性抗原对于开发结核病（TB）诊断和疫苗至关重要。在一个结核病低流行的国家，我们研究了结核分枝杆菌（Mtb）特异性免疫反应的特征，该免疫反应与结核病相关：在这项前瞻性观察横断面研究中，我们招募了健康供体（HD）、结核病患者和结核感染者（TBI）在基线和治疗结束时进行研究。用酶联免疫吸附试验、流式细胞术和多重检测法鉴定了多肽池刺激全血后的 T 细胞反应：结果：无论感染/患病情况如何，ATB116 特异性 IFN-γ 反应（通过酶联免疫吸附试验）都与 Mtb 显著相关（p+ T 细胞反应与 Mtb 相关，无论感染/患病情况如何（p+ T 细胞特异性反应在结核病治疗完成后下降）。抗原特异性 CD8+ T 细胞反应反映了 CD4+ 反应。最后，多重检测分析表明，ATB116 在结核病和创伤性脑损伤中都能诱导多种免疫因子：我们描述了结核病治疗对 Mtb 多肽池免疫反应的调节。这些结果对于我们了解结核病的免疫发病机制和疫苗设计非常重要：在本研究中生成和/或分析的原始数据将在 INMI 机构资料库（rawdata.inmi.it）中提供，但需注册。从按发表年份排序的文章列表中选择感兴趣的文章，即可找到相关数据。访问数据无需付费。如果应用程序出现故障，可直接通过电子邮件将请求发送至 biblioteca@inmi.it。

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引用次数: 0

Modelling the temperature dependent extrinsic incubation period of West Nile Virus using Bayesian time delay models 利用贝叶斯时间延迟模型模拟西尼罗河病毒随温度变化的外在潜伏期。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-09-27 DOI: 10.1016/j.jinf.2024.106296

West Nile Virus (WNV) is a mosquito-borne pathogen that primarily infects birds. Infections can spillover to humans and cause a spectrum of clinical symptoms, including WNV neuroinvasive disease. The extrinsic incubation period (EIP) is the time taken for a mosquito to become infectious following the ingestion of an infected blood meal. Characterising how the EIP varies with temperature is an essential part of predicting the impact and transmission dynamics of WNV. We re-analyse existing experimental data using Bayesian time delay models, allowing us to account for variation in how quickly individual mosquitoes developed disseminated WNV infections. In these experiments, cohorts of Culex pipiens mosquitoes were infected with WNV and kept under different temperature conditions, being checked for disseminated infection at defined timepoints. We find that EIPs are best described with a Weibull distribution and become shorter log-linearly with temperature. Under 18°C, less than 1% of infected Cx. pipiens had a disseminated infection after 5 days, compared to 9.73% (95% CrI: 7.97 to 11.54) at 25°C and 42.20% (95% CrI: 38.32 to 46.60) at 30°C. In the hottest experimental temperature treatment (32°C), the EIP₅₀ was estimated at 3.78 days (CrI: 3.42 to 4.15) compared to over 100 days in the coolest treatment (15°C). The variance of EIPs was found to be much larger at lower temperatures than higher temperatures, highlighting the importance of characterising the time delay distribution associated with the EIP. We additionally demonstrate a competitive advantage of WNV strain WN02 over NY99, where the former infects mosquitoes more quickly at colder temperatures than the latter. This research contributes crucial parameters to the WNV literature, providing essential insights for modellers and those planning interventions.

西尼罗河病毒（WNV）是一种由蚊子传播的病原体，主要感染鸟类。感染可波及人类，并引起一系列临床症状，包括西尼罗河病毒神经侵袭性疾病。体外潜伏期（EIP）是指蚊子在摄入受感染的血餐后产生传染性的时间。描述 EIP 如何随温度变化是预测 WNV 影响和传播动态的重要部分。我们利用贝叶斯时间延迟模型对现有实验数据进行了重新分析，使我们能够考虑到单个蚊子感染 WNV 的速度变化。在这些实验中，成群的库蚊感染了 WNV 病毒，并在不同的温度条件下饲养，在规定的时间点检查是否有传播感染。我们发现，EIPs 最适合用 Weibull 分布来描述，并随温度的升高而呈对数线性缩短。在 18ºC 温度条件下，受感染的蝰蛇在 5 天后扩散感染的比例不到 1%，而在 25ºC 温度条件下为 9.73%（95% 置信区间：7.97 至 11.54），在 30ºC 温度条件下为 42.20%（95% 置信区间：38.32 至 46.60）。在最热的实验温度处理（32ºC）中，EIP50 估计为 3.78 天（CrI：3.42 至 4.15），而在最冷的处理（15ºC）中，EIP50 超过 100 天。研究发现，低温条件下的 EIP 方差比高温条件下的 EIP 方差大得多，这突出表明了确定与 EIP 相关的时间延迟分布特征的重要性。我们还证明了 WNV 株系 WN02 相对于 NY99 的竞争优势，前者在低温下感染蚊子的速度比后者更快。这项研究为 WNV 文献提供了重要参数，为建模者和计划干预者提供了重要见解。

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引用次数: 0

Immunogenicity and safety of SARS-CoV-2 recombinant spike protein vaccine in South African people living with and without HIV-1 infection: A phase 2 randomised trial 南非 HIV-1 感染者和非 HIV-1 感染者接种 SARS-CoV-2 重组尖峰蛋白疫苗的免疫原性和安全性：2 期随机试验。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-09-27 DOI: 10.1016/j.jinf.2024.106285

Background

Response data for COVID-19 vaccines in immunosuppressed individuals are typically limited to standard dosing in small populations. Adjusting number or interval of doses may impact immune responses based on HIV status.

Methods

This phase 2 randomised, observer-blinded, placebo-controlled South African study (2019nCoV-505/NCT05112848) enrolled medically stable people living with HIV (PLWH) and HIV-uninfected participants aged 18–65 years. PLWH were randomised 1:1:1 to receive NVX-CoV2373 on day 0 (D0) and either D21 (2-Dose_D0/D21) or D70 (2-Dose_D0/D70), or on D0, D21, and D70 (3-Dose). HIV-uninfected participants were randomised 1:1 to each 2-Dose regimen. PLWH were stratified into well-controlled and less–well-controlled subgroups. The primary immunologic endpoint included serum IgG and neutralising antibody responses (per geometric mean fold rise [GMFR] in titre and seroconversion rate) to ancestral SARS-CoV-2 at D35 (2-Dose_D0/D21) and D84 (2-Dose_D0/D70 and 3-Dose). The primary safety endpoints were participants with an unsolicited adverse event through D84, at D120, and at D180, or reactogenicity ≤7 days post-vaccination.

Results

Of 288 PLWH, 98, 96, and 94 were randomised into the 2-Dose_D0/D21, 2-Dose_D0/D70, and 3-Dose groups, respectively; 96 HIV-uninfected participants were randomised to the 2-Dose_D0/D21 (n = 47) or 2-Dose_D0/D70 (n = 49) regimens. Most (>85%) of the population were SARS-CoV-2 positive at baseline. Ancestral anti-spike IgG GMFRs in PLWH and HIV-uninfected participants, respectively, were 12·4 and 12·9 (D35) and 12·2 and 13·6 (D84). Comparable outcomes occurred across dosing regimens and in well-controlled and less–well-controlled PLWH. Microneutralization GMFRs at D84 in PLWH and HIV-uninfected participants, respectively, were: 6·9 and 10·1 (2-Dose_D0/D21), 11·0 and 11·3 (2-Dose_D0/D70), and 17·2 (PLWH 3-Dose). Antibody responses against BA.1 trended similar to those against the ancestral virus. Safety outcomes were comparable among PLWH and HIV-uninfected participants.

Conclusion

This study demonstrated that NVX-CoV2373 produced consistent immunogenicity responses to SARS-CoV-2 among PLWH and HIV-uninfected participants, with no new safety signals.

背景：COVID-19疫苗在免疫抑制个体中的应答数据通常仅限于小群体中的标准剂量。根据艾滋病病毒感染状况调整剂量的数量或间隔可能会影响免疫反应：这项 2 期随机、观察者盲法、安慰剂对照南非研究（2019nCoV-505/NCT05112848）招募了年龄在 18-65 岁、病情稳定的 HIV 感染者（PLWH）和未感染 HIV 的参与者。HIV感染者按1:1:1随机分配，在第0天（D0）和第21天（2-剂量D0/D21）或第70天（2-剂量D0/D70）接受NVX-CoV2373，或在第0天、第21天和第70天（3-剂量）接受NVX-CoV2373。未感染艾滋病毒的参与者按 1:1 随机分配到每种 2 剂量方案中。艾滋病毒感染者被分为控制良好亚组和控制较差亚组。主要免疫学终点包括在D35（2-DoseD0/D21）和D84（2-DoseD0/D70和3-Dose）对祖先SARS-CoV-2的血清IgG和中和抗体反应（滴度的几何平均倍数上升[GMFR]和血清转换率）。主要安全性终点是在D84、D120和D180期间出现主动不良事件或接种后7天内出现反应性的参与者：在288名艾滋病毒感染者中，分别有98人、96人和94人被随机分配到2剂量D0/D21组、2剂量D0/D70组和3剂量组；96名未感染艾滋病毒的参与者被随机分配到2剂量D0/D21组（47人）或2剂量D0/D70组（49人）。大多数人（>85%）在基线时为 SARS-CoV-2 阳性。PLWH 和 HIV 未感染者的祖先抗尖峰抗体 IgG GMFR 分别为 12-4 和 12-9 (D35)，以及 12-2 和 13-6 (D84)。不同给药方案、控制良好和控制较差的艾滋病毒感染者的结果具有可比性。感染艾滋病毒的 PLWH 和未感染艾滋病毒的参与者在 D84 时的微中性 GMFR 分别为 6-9 和 10-1 （2-D）：6-9和10-1（2-剂量D0/D21）、11-0和11-3（2-剂量D0/D70）以及17-2（PLWH 3-剂量）。针对 BA.1 的抗体反应与针对祖先病毒的抗体反应趋势相似。感染艾滋病毒的 PLWH 和未感染艾滋病毒的参与者的安全性结果相当：这项研究表明，NVX-CoV2373 能在 PLWH 和未感染 HIV 的参与者中产生一致的针对 SARS-CoV-2 的免疫原性反应，而且没有新的安全性信号：Novavax, Inc.

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引用次数: 0