monkeypox (Mpox)

  • 文章类型: Journal Article
    将基于实验室的数字检测的高灵敏度和特异性与现场护理(POC)技术的易用性和可负担性相结合的诊断方法可以彻底改变疾病诊断。在传染病诊断中尤其如此,快速准确的病原体检测对于遏制疾病传播至关重要。我们开创了一个创新的无标签数字检测平台,利用干涉反射成像传感器(IRIS)技术。IRIS利用光学透明薄膜的光干涉,通过在散粒噪声受限的操作中利用光干扰和信号平均的功率来消除对复杂的光学共振来增强信号的需要,以实现几乎无限的灵敏度。在我们最新的作品中,我们通过允许从单个图像构建目标纳米粒子(整个病毒)的光学特征,进一步改进了我们以前的“单粒子”IRIS(SP-IRIS)技术。这个新平台,\'像素多样性\'IRIS(PD-IRIS),消除了对z扫描采集的需要,在SP-IRIS中需要,一个耗时且昂贵的过程,并使我们的技术更适用于POC设置。使用PD-IRIS,我们定量检测了猴痘病毒(MPXV),猴痘(Mpox)感染的病原体。MPXV被抗A29单克隆抗体(mAb69-126-3)捕获在传感器芯片上的蛋白G斑点上,并在200PFU/ml(〜3.3atomolar)的检测限(LOD)下进行检测。PD-IRIS优于基于实验室的ELISA(LOD-1800PFU/mL)作为比较。使用单纯疱疹病毒证明了PD-IRIS在MPXV检测中的特异性,1型(HSV-1),牛痘病毒(CPXV)。这项工作确立了PD-IRIS的有效性,并为其在POC的临床诊断中的进展开辟了可能性。此外,PD-IRIS是一种模块化技术,可适用于病原体的多重检测,其中高亲和力配体可结合其表面抗原以将其捕获在传感器表面上。
    Diagnostic approaches that combine the high sensitivity and specificity of laboratory-based digital detection with the ease of use and affordability of point-of-care (POC) technologies could revolutionize disease diagnostics. This is especially true in infectious disease diagnostics, where rapid and accurate pathogen detection is critical to curbing the spread of disease. We have pioneered an innovative label-free digital detection platform that utilizes Interferometric Reflectance Imaging Sensor (IRIS) technology. IRIS leverages light interference from an optically transparent thin film, eliminating the need for complex optical resonances to enhance the signal by harnessing light interference and the power of signal averaging in shot-noise-limited operation to achieve virtually unlimited sensitivity. In our latest work, we have further improved our previous \'Single-Particle\' IRIS (SP-IRIS) technology by allowing the construction of the optical signature of target nanoparticles (whole virus) from a single image. This new platform, \'Pixel-Diversity\' IRIS (PD-IRIS), eliminated the need for z-scan acquisition, required in SP-IRIS, a time-consuming and expensive process, and made our technology more applicable to POC settings. Using PD-IRIS, we quantitatively detected the Monkeypox virus (MPXV), the etiological agent for Monkeypox (Mpox) infection. MPXV was captured by anti-A29 monoclonal antibody (mAb 69-126-3) on Protein G spots on the sensor chips and were detected at a limit-of-detection (LOD) - of 200 PFU/ml (~3.3 attomolar). PD-IRIS was superior to the laboratory-based ELISA (LOD - 1800 PFU/mL) used as a comparator. The specificity of PD-IRIS in MPXV detection was demonstrated using Herpes simplex virus, type 1 (HSV-1), and Cowpox virus (CPXV). This work establishes the effectiveness of PD-IRIS and opens possibilities for its advancement in clinical diagnostics of Mpox at POC. Moreover, PD-IRIS is a modular technology that can be adapted for the multiplex detection of pathogens for which high-affinity ligands are available that can bind their surface antigens to capture them on the sensor surface.
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  • 文章类型: Journal Article
    最近在全球范围内观察到人类猴痘(水痘)的发病率增加,包括喀麦隆。确保卫生系统的有效准备和干预,我们试图评估水痘传播的知识,预防,以及喀麦隆医护人员(HCWs)的反应。
    使用美国疾病控制和预防中心(US-CDC)关于Mpox的标准问卷改编的21项问题,对喀麦隆的HCWs进行了横断面在线调查。Mpox的总体知识通过累积评分进行评估,并归类为优秀(≥80%,17/21)或良好(≥70%,≥15/21)知识。回归分析用于确定Mpox知识的预测因子。
    这项调查招募了377名参与者,但只分析了342名参与者的反应.总的来说,50.6%是女性参与者,年龄在30岁或以下的占59.6%。大多数参与者是医生(50.3%);大多数在中央级医院工作(25.1%),有1-5年的经验(70.7%)。共有高达92.7%的人知道天花,以社交媒体(58.7%)和广播/电视(49.2%)为主要来源。平均知识得分为14.0±3.0(4至20),只有12.9%具有良好的知识(≥80%),42.1%具有良好的水痘知识。年轻的年龄(26-30岁)与良好的知识有关,而工作场所类型与良好的水痘知识相关(aOR[95%CI]:4.01[1.43-11.24])。不同专业类别的水痘治疗/管理知识普遍较差。
    在不同的专业人士中,HCWs中的Mpox知识是不合格的。因此,为了对水痘和类似新出现的病原体进行最佳准备和立即干预,应在鼓励科学文献和组织社交媒体网站的同时,为HCW组织能力增强计划。
    An increased incidence of human Monkeypox (Mpox) cases was recently observed worldwide, including in Cameroon. To ensure efficient preparedness and interventions in the health system, we sought to assess the knowledge of Mpox\'s transmission, prevention, and response among healthcare workers (HCWs) in Cameroon.
    A cross-sectional online survey was conducted among HCWs in Cameroon using 21-item questions adapted from the United States Centers for Disease Control and Prevention (US-CDC) standard questionnaire on Mpox. The overall knowledge of Mpox was assessed by cumulative score and categorized as excellent (≥80%, 17/21) or good (≥70%, ≥15/21) knowledge. The regression analysis was used to identify the predictors of Mpox knowledge.
    The survey enrolled 377 participants, but only responses from 342 participants were analyzed. Overall, 50.6% were female participants, and 59.6% aged 30 years or younger. The majority of the participants were medical doctors (50.3%); most worked in central-level hospitals (25.1%) and had 1-5 years of experience (70.7%). A total of up to 92.7% were aware of Mpox, with social media (58.7%) and radio/television (49.2%) as the main sources. The mean knowledge score was 14.0 ± 3.0 (4 to 20), with only 12.9% having excellent knowledge (≥80%) and 42.1% having good knowledge of Mpox. Younger age (26-30 years old) was associated with good knowledge, while workplace type was associated with excellent knowledge of Mpox (aOR [95% CI]: 4.01 [1.43-11.24]). Knowledge of treatment/management of Mpox was generally poor across the different professional categories.
    Knowledge of Mpox among HCWs is substandard across different professionals. Thus, for optimal preparedness and immediate interventions for Mpox and similar emerging pathogens, capacity-strengthening programs should be organized for HCWs while encouraging scientific literature and organizational social media websites.
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  • 文章类型: Journal Article
    患有人类免疫缺陷病毒(HIV)的人是受当前猴痘病毒爆发影响最大的人,该病毒于2022年5月首次宣布。在这里,我们报告了一组HIV-1感染个体在接受非复制后的泛痘特异性T细胞反应,来自巴伐利亚北欧的减毒天花疫苗JYNNEOS。皮内(i.d.)和皮下(s.c.)疫苗接种是安全的,没有重大副作用。节省剂量的i.d.疫苗接种优于s.c.疫苗接种并促进T细胞多功能性,肠归巢标记α4β7整合素在淋巴细胞上的表达。CD4T细胞计数≤500/mm3血液的HIV-1感染个体需要至少加强疫苗接种才能表现出有效的病毒特异性T细胞反应。加强后Th1反应的大小与接种者的CD4T细胞计数直接相关。有必要对更多参与者进行进一步的研究,以证实和扩大我们的观察结果。
    People living with human immunodeficiency virus (HIV) are the individuals most affected by the current Monkeypox virus outbreak that was first announced in May 2022. Here we report Pan-pox-specific T-cell responses in a cohort of HIV-1-infected individuals after receiving the nonreplicative, attenuated smallpox vaccine JYNNEOS from Bavarian Nordic. Intradermal (i.d.) and subcutaneous (s.c.) vaccination was safe without major side effects. Dose-sparing i.d. vaccination was superior to s.c. vaccination and promoted T-cell polyfunctionality, and the expression of the gut-homing marker α4β7 integrin on lymphocytes. HIV-1-infected individuals with CD4 T-cell counts ≤500/mm3 blood required at least a booster vaccination to exhibit efficient virus-specific T-cell responses. The magnitude of the Th1 response after this booster directly correlated with the CD4 T-cell count of the vaccinees. Further studies with a larger number of participants are warranted to confirm and expand our observations.
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  • 文章类型: Journal Article
    背景:最近在非流行地区再次出现猴痘(水痘)流行,这引起了人们对潜在全球爆发的担忧。痘病毒(MPV)是一种天花样病毒,属于正痘病毒属(家族:Poxviridae)。尽管研究表明MPV感染抑制了Toll样受体-3和肿瘤坏死因子-α相关的信号通路,MPV是否调节其他免疫相关途径尚不清楚.
    方法:在本研究中,两种不同的时间模式用于建立MPV感染的人永生上皮癌细胞系(HeLa)。选择孵育的这两个持续时间2和12小时以鉴定受MPV感染影响的共调节的基因和途径。
    结果:使用基因本体框架,京都基因百科全书和基因组数据库,和MetaCore软件产生了有价值的见解。具体来说,发现各种途径在感染MPV2和12小时的HeLa细胞中富集。这些途径包括Notch,CD40,CD95,缺氧诱导因子-1-α,白细胞介素(IL)-1,IL-6,磷酸肌醇3-激酶,核因子-κB,丝裂原活化蛋白激酶,和氧化应激诱导的信号通路。代谢和病毒复制周期的簇和途径与2小时感染组显著相关。基于诸如HSPG2、RHPN2、MYL1、ASPHD2、CA9、VIPR1、SNX12、MGC2752、SLC25A1、PEX19和AREG的基因的调节来鉴定这种关联。此外,发现与免疫和细胞运动相关的簇和途径与12小时感染组相关.这种关联是基于基因如C1orf21,C19orf48,HRK,IL8,GULP1,SCAND2,ATP5C1,FEZ1,SGSH,TACC2、CYP4X1、MMP1、CPB1、P2RY13、WDR27、PRPF4和ENDOD1。
    结论:这项研究可以提高我们对水痘的病理生理学和感染后后遗症的潜在机制的理解。我们的发现为MPV感染的各种模式提供了有价值的见解。
    BACKGROUND: The recent re-emergence of the monkeypox (mpox) epidemic in nonendemic regions has raised concerns regarding a potential global outbreak. The mpox virus (MPV) is a smallpox-like virus belonging to the genus Orthopoxvirus (family: Poxviridae). Although studies suggest that MPV infection suppresses the Toll-like receptor-3- and tumor necrosis factor-α-related signaling pathways, whether MPV regulates other immune-related pathways remains unclear.
    METHODS: In this study, two distinct temporal patterns were used for establishing an MPV-infected human immortal epithelial cancer cell line (HeLa). These two durations 2 and 12 h of incubation were selected to identify the coregulated genes and pathways affected by MPV infection.
    RESULTS: The use of the Gene Ontology framework, Kyoto Encyclopedia of Genes and Genome database, and MetaCore software yielded valuable insights. Specifically, various pathways were found to be enriched in HeLa cells infected with MPV for 2 and 12 h. These pathways included Notch, CD40, CD95, hypoxia-inducible factor-1-α, interleukin (IL)- 1, IL-6, phosphoinositide 3-kinase, nuclear factor-κB, mitogen-activated protein kinase, and oxidative stress-induced signalling pathways. Clusters and pathways of metabolism and viral replication cycles were significantly associated with the 2-hour infection group. This association was identified based on the regulation of genes such as HSPG2, RHPN2, MYL1, ASPHD2, CA9, VIPR1, SNX12, MGC2752, SLC25A1, PEX19, and AREG. Furthermore, clusters and pathways related to immunity and cell movement were found to be associated with the 12-hour infection group. This association was identified based on the regulation of genes such as C1orf21, C19orf48, HRK, IL8, GULP1, SCAND2, ATP5C1, FEZ1, SGSH, TACC2, CYP4X1, MMP1, CPB1, P2RY13, WDR27, PRPF4, and ENDOD1.
    CONCLUSIONS: This study can improve our understanding of the mechanisms underlying the pathophysiology and post-infection sequelae of mpox. Our findings provide valuable insights into the various modes of MPV infection.
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  • 文章类型: Journal Article
    猴痘(Mpox)是一种新兴的人畜共患疾病,具有严重并发症的潜力。早期识别和诊断对于及时治疗至关重要,控制它的传播,并降低人与人之间传播的风险。这项研究旨在开发一种临床诊断工具,并描述在墨西哥西北部非流行地区爆发期间19例经PCR确认的水痘病例的临床和社会人口统计学特征。患者的中位年龄为35岁,大多数是男性。痘痘阳性患者通常报告发热等症状,腰痛,和虚弱,除了经历痛苦的溃疡和艾滋病毒感染者(PLWH)的高频率的艾滋病毒感染。设计了两个使用逻辑回归的诊断模型,最佳模型的预测精度为0.92(95%CI:0.8-1),敏感性为0.86,特异性为0.93。最佳模型的高预测值和准确性凸显了其在临床环境中显着改善早期水痘诊断和治疗的潜力,帮助控制未来的疫情。
    Monkeypox (Mpox) is an emerging zoonotic disease with the potential for severe complications. Early identification and diagnosis are essential to prompt treatment, control its spread, and reduce the risk of human-to-human transmission. This study aimed to develop a clinical diagnostic tool and describe the clinical and sociodemographic features of 19 PCR-confirmed Mpox cases during an outbreak in a nonendemic region of northwestern Mexico. The median age of patients was 35 years, and most were male. Mpox-positive patients commonly reported symptoms such as fever, lumbago, and asthenia, in addition to experiencing painful ulcers and a high frequency of HIV infection among people living with HIV (PLWH). Two diagnostic models using logistic regression were devised, with the best model exhibiting a prediction accuracy of 0.92 (95% CI: 0.8-1), a sensitivity of 0.86, and a specificity of 0.93. The high predictive values and accuracy of the top-performing model highlight its potential to significantly improve early Mpox diagnosis and treatment in clinical settings, aiding in the control of future outbreaks.
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  • 文章类型: Journal Article
    虽然痘病毒(MPXV)诊断仅在专业实验室进行,2022年全球出现的水痘病例表明需要更容易获得的诊断.许多实验室已经建立了具有快速核酸提取和PCR的自动化随机存取平台,提供更快、更方便的测试。在这项研究中,我们在NeuMoDx分子系统上采用了以前发表的通用MPXV-PCR作为实验室开发的测试(LDT),并从患者材料中分离了MPXV克隆.为了减少传染性物质的处理,我们评估了用于样品预处理的病毒裂解缓冲液(VLB)。我们进一步比较了MPXV-LDT-PCR与传统的实时PCR,使用阳性拭子确定其敏感性和特异性,并使用外部质量评估样本评估其性能。用50%VLB预处理样品使MPXV感染性降低约200倍,同时保持PCR灵敏度。该测定显示出100%的灵敏度和特异性,在测试的样品中没有交叉反应性,并且以262GE/mL的检测限进行。总之,该测定的周转时间少于2小时,可以很容易地转移到其他自动化PCR平台,为开发针对即将到来的大流行的快速检测方法提供了基础。
    While Mpox virus (MPXV) diagnostics were performed in specialized laboratories only, the global emergence of Mpox cases in 2022 revealed the need for a more readily available diagnostic. Automated random-access platforms with fast nucleic acid extraction and PCR have become established in many laboratories, providing faster and more accessible testing. In this study, we adapted a previously published generic MPXV-PCR as a lab-developed test (LDT) on a NeuMoDx Molecular System and isolated MPXV clones from patient materials. To reduce the handling of infectious material, we evaluated a viral lysis buffer (VLB) for sample pretreatment. We further compared the MPXV-LDT-PCR to conventional real-time PCR, determined its sensitivity and specificity using positive swabs, and assessed its performance using external quality assessment samples. Pretreatment of samples with 50% VLB reduced MPXV infectivity by approximately 200-fold while maintaining PCR sensitivity. The assay demonstrated a sensitivity and specificity of 100% with no cross-reactivity in the samples tested and performed with a limit of detection of 262 GE/mL. In summary, the assay had a turnaround time of fewer than 2 h and can easily be transferred to other automated PCR platforms, providing a basis for developing rapid assays for upcoming pandemics.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Case Reports
    在最近的2022年水痘全球疫情中,病例大多记录在MSM中。近14%的病例报告直肠炎。在这项研究中,4例因严重直肠炎需要住院治疗的水痘确诊病例的临床特征为,病毒学,微生物,内窥镜,和组织学方面。该研究首次显示与痘病毒直肠感染相关的淋巴滤泡病变的存在。
    In the recent 2022 monkeypox (Mpox) global outbreak, cases have been mostly documented among men who have sex with men. Proctitis was reported in almost 14% of cases. In this study, four Mpox-confirmed cases requiring hospitalizations for severe proctitis were characterized by clinical, virological, microbiological, endoscopic, and histological aspects. The study showed the presence of lymphofollicular lesions associated with Mpox virus rectal infection for the first time.
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  • 文章类型: Journal Article
    背景:男男性行为者(MSM)已被推荐用于有针对性的猴痘疫苗接种。我们旨在调查中国MSM的猴痘意识,并探讨猴痘疫苗接种犹豫的相关性。
    方法:我们于2022年8月10日至9月9日进行了横断面调查。收集≥18岁MSM人群猴痘相关意识和对猴痘疫苗接种的态度。采用多因素logistic回归分析评价疫苗接种犹豫的相关性。评估了亚组之间对艾滋病毒状况的认识差异。
    结果:共纳入1090名MSM(年龄:中位数30岁,IQR,25-35;HIV感染:53.12%)。只有13.85%的受访者表示猴痘疫苗接种有较高的犹豫。犹豫与没有固定收入(AOR,2.46,95%CI,1.48-4.11),以下不常见的信息(有时,3.01、1.55-5.83;很少或从不,5.66,2.58-12.45),对猴痘流行缺乏担忧(1.78,1.11-2.87)。认为HIV感染病例所占比例较小的参与者(1.62,1.01-2.60),不同意猴痘病毒可以在精液中检测到(2.21,1.26-3.88),并且认为复制能力强(1.84,1.14-2.96)或复制缺陷型(4.80,2.26-10.21)不适合HIV感染者的猴痘疫苗通常比较犹豫.与未感染HIV的MSM相比,HIV感染的MSM支持更多的疫苗接种推广。
    结论:中国的MSM对猴痘疫苗接种的犹豫程度较低。疫苗的安全性和可负担性,和信息的可用性是减少犹豫的重要方面。应鼓励关于疫苗接种益处的教育,以促进未来的疫苗接种计划。本文受版权保护。保留所有权利。
    Men who have sex with men (MSM) have been recommended for targeted monkeypox vaccination. We aimed to investigate monkeypox awareness and explore the correlates of monkeypox vaccination hesitancy among MSM in China. We conducted a cross-sectional survey from August 10 to September 9, 2022. Awareness related to monkeypox and attitude toward monkeypox vaccination among MSM aged ≥18 years were collected. Multivariable logistic regression was applied to evaluate correlates of vaccination hesitancy. The discrepancy in awareness between subgroups regarding HIV status was assessed. A total of 1090 MSM were included (age: median 30 years, interquartile range [IQR], 25-35; HIV-infected: 53.12%). Only 13.85% of respondents expressed high monkeypox vaccination hesitancy. Hesitancy was associated with no fixed income (adjuster odds ratio [aOR], 2.46, 95% confidence interval [CI], 1.48-4.11), infrequent information following (sometimes, 3.01, 1.55-5.83; seldom or never, 5.66, 2.58-12.45), and lack of worries about monkeypox endemic (1.78, 1.11-2.87). Participants who believed that HIV-infected cases accounted for a smaller proportion (1.62, 1.01-2.60), disagreed that monkeypox virus could be detected in semen (2.21, 1.26-3.88), and considered either replication-competent (1.84, 1.14-2.96) or replication-deficient (4.80, 2.26-10.21) monkeypox vaccine unsuitable for HIV-infected people were generally more hesitant. Compared with HIV-uninfected MSM, HIV-infected MSM supported more for vaccination promotion. MSM in China had low hesitancy toward monkeypox vaccination. Safety and affordability of vaccine and availability of information were essential aspects to reduce hesitancy. Education on vaccination benefits should be encouraged to promote future vaccination plans.
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