Zika

zika
  • 文章类型: Journal Article
    虫媒病毒疾病仍然是世界范围内重大的健康问题。世界上一半以上的人口都有患登革热的风险。如果没有疫苗或靶向治疗,最有效的预防策略是社区参与的病媒管理。m健康干预措施,像WhatsApp一样,为参与社区和促进更健康的行为提供有希望的结果。这项研究探讨了将WhatsApp纳入媒介控制活动以改善哥伦比亚虫媒病毒预防的可行性。采用混合方法评估基于WhatsApp的干预措施。WhatsApp消息被发送给45名社区妇女,为期5周,以增加她们对登革热的知识和做法,Zika,还有基孔肯雅.在社区环境中进行了前后调查和焦点小组讨论,以衡量这种干预措施的可行性和可接受性。聊天评论是为了评估用户的可用性。在45次WhatsApp聊天中,总共交换了1566条消息。这项研究报告了高接受度和良好的可用性(82%的用户使用该应用程序进行回复)。WhatsApp消息被认为很短,clear,和愉快的。用户喜欢频率,和信息的设计。前后调查表明,虫媒病毒病的知识和实践有所改善。将这些知识应用于实践的意图反映在重大改进中,特别是每周清洗一次洗衣箱(从62.1%到89.6%,p<0.008)。这项研究表明,使用WhatsApp作为额外的工具可能是可行的,可接受,和负担得起的战略,以改善在预防虫媒病毒疾病方面采用更好的做法。
    Arboviral diseases remain a significant health concern worldwide, with over half the world\'s population at risk for dengue alone. Without a vaccine or targeted treatment, the most effective strategy of prevention is vector management with community involvement. mHealth interventions, like WhatsApp, offer promising results for engaging communities and promoting healthier behaviors. This study explores the feasibility of integrating WhatsApp in vector control activities to improve arbovirus prevention in Colombia. A mixed-methods approach was employed to assess the WhatsApp-based intervention. WhatsApp messages were sent to 45 community women for 5 weeks to increase their knowledge and practices about dengue, Zika, and chikungunya. Pre-and-post surveys and focus group discussions were conducted in community settings to measure the feasibility and acceptability of this intervention. Chat reviews were done to assess the usability of users. A total of 1566 messages were exchanged in 45 WhatsApp chats. High acceptance and good usability (82% of users used the app for replying) were reported in this study. WhatsApp messages were perceived as short, clear, and enjoyable. Users liked the frequency, and design of messages. Pre- and post-surveys demonstrated improvements in the knowledge and practices of arboviral diseases. The intention to apply this knowledge in practice was reflected in a significant improvement, particularly in cleaning the laundry tank once a week (pre 62.1% to post 89.6%, p < 0.008). This study suggests that using WhatsApp as an additional tool could be a feasible, acceptable, and affordable strategy for improving the adoption of better practices in the prevention of arboviral diseases.
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  • 文章类型: Journal Article
    在2019年冠状病毒病(COVID-19)大流行之前,伊蚊传播的虫媒病毒病是浙江的重要公共卫生问题。本研究旨在调查该省伊蚊传播虫媒病毒病的流行病学特征和变化。
    进行了描述性分析,以总结2003-2022年期间伊蚊传播的虫媒病毒病的流行病学。
    共3125例,包括1,968例土著案件,在2003-2022年期间报告。大约四分之三的进口病例来自东南亚。2013-2019年年度输入病例数增加(R2=0.801,p=0.004),2019年达到峰值。与2003-2012年相比,2013-2019年所有地级市的输入性病例年平均发病率均有所增加(每10万人中0.11-0.42例,而每10万人口0-0.05),但在2020-2022年期间大幅下降(每10万人口0-0.03)。地理分布的变化是相似的,2003-2012年有33/91个县,2013-2019年有86/91个县,2020-2022年有14/91个县。2013-2019年土著病例的年平均发病率是2003-2012年的7.79倍(0.44vs.每100,000人口0.06)。在2020年至2022年之间,没有报告土著病例。在2020年之前,还注意到土著病例的地理扩展-从2003-2012年的两个县增加到2013-2019年的44个县。
    登革热,基孔肯雅热,zika病,黄热病在浙江并不流行,但在后COVID-19时代将是该省的重要公共卫生问题。
    Aedes-borne arboviral diseases were important public health problems in Zhejiang before the coronavirus disease 2019 (COVID-19) pandemic. This study was conducted to investigate the characteristics and change of the epidemiology of Aedes-borne arboviral diseases in the province.
    Descriptive analyses were conducted to summarize the epidemiology of Aedes-borne arboviral diseases during 2003-2022.
    A total of 3,125 cases, including 1,968 indigenous cases, were reported during 2003-2022. Approximately three-quarters of imported cases were infected from Southeast Asia. The number of annual imported cases increased during 2013-2019 (R2 = 0.801, p = 0.004) and peaked in 2019. When compared with 2003-2012, all prefecture-level cities witnessed an increase in the annual mean incidence of imported cases in 2013-2019 (0.11-0.42 per 100,000 population vs. 0-0.05 per 100,000 population) but a drastic decrease during 2020-2022 (0-0.03 per 100,000 population). The change in geographical distribution was similar, with 33/91 counties during 2003-2012, 86/91 during 2013-2019, and 14/91 during 2020-2022. The annual mean incidence of indigenous cases in 2013-2019 was 7.79 times that in 2003-2012 (0.44 vs. 0.06 per 100,000 population). No indigenous cases were reported between 2020-2022. Geographical extension of indigenous cases was also noted before 2020-from two counties during 2003-2012 to 44 during 2013-2019.
    Dengue, chikungunya fever, zika disease, and yellow fever are not endemic in Zhejiang but will be important public health problems for the province in the post-COVID-19 era.
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  • 文章类型: Journal Article
    背景:现有的伦理指导和法规要求强调在卫生事件中开发疫苗的过程中需要特定于妊娠的安全性和有效性数据。我们的目标是对活跃流行期间的疫苗临床试验进行系统评价。
    方法:我们搜索了在H1N1流感期间启动的II期和III期疫苗临床试验,中东呼吸综合征冠状病毒(MERS-CoV)Zika,和2009年至2019年的埃博拉病毒病(EVD)暴发。数据来自以下注册表中确定的临床试验方案:ClinicalTrials.gov,泛非临床试验注册(PACTR),以及世界卫生组织国际临床试验注册平台(ICTRP)指出的所有主要注册中心。来自注册临床试验的已发表研究通过PubMed定位。根据合格标准和妊娠结局提取数据。本研究的数据可在开放科学数据存储库中心获得:https://osf.io/nfk2p/?view_only=47deb3b206724af9b46c9c0c0083a267。
    结果:我们确定了96种疫苗临床试验方案,并在分析中纳入了84种。在筛选不相关摘要时排除了5条记录,在全文评估中排除了7例(1例用于治疗性药物试验,3只适用于老年人,3仅适用于儿童/青少年)。没有针对MERS-CoV或寨卡病毒疫苗的合格试验。总的来说,8个协议明确包括孕妇;其中,已完成3项试验,结果已发表。2项研究报告了意外怀孕和怀孕参与者的结局,10项研究报告了与妊娠相关的严重不良事件,但未提及总的意外妊娠。总共报告了411例记录的妊娠结局,来自3项符合妊娠条件的研究的293项结果。所有临床试验结果均报告了71起与妊娠有关的严重不良事件。
    结论:在爆发期间进行的疫苗临床试验中,孕妇的代表性不足,导致与妊娠相关的结局报告不足,孕妇和新生儿缺乏传染病保护。
    Existing ethics guidance and regulatory requirements emphasize the need for pregnancy-specific safety and efficacy data during the development of vaccines in health emergencies. Our objective was to conduct a systematic review of vaccine clinical trials during active epidemic periods.
    We searched for Phase II and Phase III vaccine clinical trials initiated during the H1N1 influenza, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Zika, and Ebola virus disease (EVD) outbreaks from 2009 to 2019. Data were extracted from clinical trial protocols identified in the following registries: ClinicalTrials.gov, Pan African Clinical Trial Registry (PACTR), and all primary registries indicated by the World Health Organization\'s International Clinical Trials Registry Platform (ICTRP). Published studies from registered clinical trials were located through PubMed. Data was extracted on eligibility criteria and pregnancy outcomes. Data from this study is available in the Center for Open Science Data Repository: https://osf.io/nfk2p/?view_only=47deb3b206724af9b46c9c0c0083a267.
    We identified 96 vaccine clinical trial protocols and included 84 in analysis. 5 records were excluded in screening for irrelevant abstracts, 7 were excluded in full-text assessment (1 for a therapeutic drug trial, 3 for enrolling elderly adults only, 3 for enrolling children/adolescents only). There were no eligible trials for MERS-CoV or Zika virus vaccines. Overall, 8 protocols explicitly included pregnant people; of these, 3 were completed trials with published results. Incidental pregnancies and outcomes of pregnant participants were reported in 2 studies, 10 studies reported serious adverse events related to pregnancy without mentioning total incidental pregnancies. A total of 411 recorded pregnancy outcomes were reported, with 293 from the 3 pregnancy-eligible studies with results. 71 serious adverse events pertaining to pregnancy were reported from all clinical trials with results.
    Pregnant people are underrepresented in vaccine clinical trials conducted during outbreaks, resulting in underreporting of pregnancy-related outcomes and a lack of protection for pregnant people and neonates from infectious diseases.
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  • 文章类型: Journal Article
    在急性ZIKV感染过程中,瘙痒是文献中广泛记载的主要症状。它经常与感觉异常和几种自主神经失调表现有关,提示涉及周围神经系统的病理生理机制。这项研究的目的是开发一种可能被ZIKV感染的功能性人体模型:通过使用经典方法证明角质形成细胞和诱导多能干细胞衍生的感觉神经元共培养的新型人体模型的功能辣椒素诱导和SP释放,并验证这些细胞中ZIKV进入受体的存在。根据细胞类型,TAMs家族的受体,存在/检测到TIM(TIM1、TIM3和TIM4)和DC-SIGN和RIG1。与辣椒素一起孵育的细胞导致P物质的增加。因此,这项研究证明了获得人类角质形成细胞和人类感觉神经元的共培养物的可能性,其释放物质P的方式与先前在动物模型中发表的相同,该动物模型可用作神经源性皮肤炎症的模型。ZIKV进入受体在这些细胞中表达的证明允许考虑ZIKV能够感染细胞的有效可能性。
    During the course of acute ZIKV infection, pruritus is a cardinal symptom widely documented in the literature. Its frequent association with dysesthesia and several dysautonomic manifestations, suggests a pathophysiological mechanism involving the peripheral nervous system. The aim of this study was to develop a functional human model to potentially able to be infected by ZIKV: by demonstrating the functionality on a new human model of co-culture of keratinocyte and sensory neuron derived from induced pluripotent stem cells using a classical method of capsaicin induction and SP release, and verify the presence of ZIKV entry receptor in these cells. Depending of cellular type, receptors of the TAMs family, TIMs (TIM1, TIM3 and TIM4) and DC-SIGN and RIG1 were present/detected. The cells incubations with capsaicin resulted in an increase of the substance P. Hence, this study demonstrated the possibility to obtain co-cultures of human keratinocytes and human sensory neurons that release substance P in the same way than previously published in animal models which can be used as a model of neurogenic skin inflammation. The demonstration of the expression of ZIKV entry receptors in these cells allows to considerate the potent possibility that ZIKV is able to infect cells.
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  • 文章类型: Journal Article
    背景:2015年至2016年的寨卡疫情凸显了发育残疾儿童父母在健康和社会护理服务方面的差距。作为回应,我们开发了\'Juntos\'干预措施,为先天性寨卡综合征(CZS)儿童的父母提供为期10周的社区早期干预支持小组。干预的组成部分包括参与式学习会议,实用技能获取,同行支持,和心理支持,旨在提高照顾者在照顾孩子方面的知识和信心。本研究旨在评估在哥伦比亚实施“Juntos”的可行性。方法:在2017年至2018年之间,两名辅导员向四组8-10名护理人员提供了“Juntos”。一名研究人员观察了每一组。数据来自:40个疗程的观察笔记,每届会议后举行的焦点小组讨论,对34名护理人员进行干预前问卷调查,以及与四名主持人进行的半结构化访谈,12名护理人员和3名利益相关者。我们在数据分析中使用了Bowen框架。结果:可行性评估显示,“Juntos”在目标人群中是高度可接受的和需求的。干预主要是忠实地进行的。通过提供运输成本和选择方便的地点,促进了实用性。成功实施需要额外的组织和社交媒体支持。社区卫生工作者培训可以支持融合,建立的团体可以促进方案扩展。然而,参与者认为缺乏优先次序是现有卫生系统中的一个限制。方案入学后,参与者对照顾孩子的知识和信心得到了改善。结论:“Juntos”干预表现出很高的可接受性,需求,以及支持哥伦比亚CZS儿童父母的实用性。然而,由于对CZS儿童的卫生系统支持存在差距,因此其实施面临挑战。
    Background: The 2015 - 2016 Zika epidemic highlighted gaps in health and social care services for parents of children with developmental disabilities. In response, we developed the \'Juntos\' intervention, a 10 week community-based early intervention support group for parents of children with congenital Zika syndrome (CZS). The intervention\'s components include participatory learning sessions, practical skill acquisition, peer support, and psychological support, aiming to improve caregiver\'s knowledge and confidence in caring for their children. This study aimed to evaluate the feasibility of implementing \'Juntos\' in Colombia. Methods: Two facilitators delivered \'Juntos\' to four groups of 8-10 caregivers between 2017 and 2018. One researcher observed each group. Data were collected from: observation notes from 40 sessions, focus group discussions held after each session, pre- post intervention questionnaires with 34 caregivers, and semi-structured interviews conducted with four facilitators, 12 caregivers and three stakeholders. We used the Bowen framework in data analysis. Results: The feasibility evaluation revealed that \'Juntos\' was highly acceptable and in demand among the target population. The intervention was predominantly delivered with fidelity. Practicality was facilitated by providing transport costs and selecting convenient locations. Additional organisational and social media support was required for successful implementation. Community health worker training may support integration and the established groups could facilitate programme expansion. However, participants perceived lack of prioritisation as a limitation within existing health systems. Participants\' knowledge and confidence to care for their child improved after programme enrolment. Conclusion: The \'Juntos\' intervention demonstrated high acceptability, demand, and practicality in supporting parents of children with CZS in Colombia. However, its implementation faces challenges due to existing gaps in health system support for children with CZS.
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  • 文章类型: Journal Article
    背景:诸如Google趋势和Reddit之类的资源提供了评估公众对公共卫生问题的实时兴趣的机会。尽管这些公共可用和免费资源有可能帮助优化公共卫生运动,用于此目的的利用率受到限制。
    目的:确定公众对COVID-19的早期认识是否与公众对其他具有公共卫生重要性的传染病的兴趣提高有关。
    方法:从2018年到2020年,分析了Google趋势搜索数据和Reddit评论数据中关键字“基孔肯雅”的频率,\"埃博拉病毒\",\"H1N1\",\"MERS\",\"SARS\",和\"Zika\",近几十年来,六种广为人知的流行病。在收集了这六个术语中每个术语的Google趋势相对受欢迎程度得分之后,非配对T检验用于将每个学期的2020年每周得分与其3年研究期间的平均水平进行比较。收集了这六个术语中的每个术语每月的Reddit评论数量,然后根据估计的Reddit每月评论总量进行调整,以得出相对使用量的度量。类似于Google趋势受欢迎程度得分。然后将每个搜索词的评论相对每月发生率与相应的搜索词在COVID之前的每月评论数据进行比较,再次使用不成对T检验。用Bonferroni校正先验地确定用于统计显著性的P值截止值。
    结果:GoogleTrends和Reddit数据均显示,至少在大流行的最初几个月内,每个评估的疾病术语的使用都有大幅且统计学上的显着增加。Google搜索和Reddit评论(包括任何经过评估的传染病搜索词)在2020年的头几个月中显著高于其基线使用量。都在2020年3月达到顶峰。谷歌对“SARS”和“MERS”的搜索在整个2020日历年都保持较高,正如Reddit用“埃博拉病毒”一词评论的那样,\"H1N1\",\"MERS\"和\"SARS\"(P<.001,每个每周或每月比较,分别)。
    结论:GoogleTrends和Reddit可以很容易地用于评估与公共卫生相关主题的实时普遍兴趣水平。提供一种工具,以更好地安排时间和指导需要接受目标受众的公共卫生举措。COVID-19大流行的开始与公众对其他流行性传染病的兴趣增加有关。我们已经证明,在过去的二十年中,对于流行的六种不同的传染性原因,随着COVID-19的爆发,公共利益大幅迅速上升。我们的数据表明,在最初爆发后的至少几个月里,公众可能特别接受有关这些主题的对话。公共卫生官员应考虑利用Google趋势和社交媒体数据来实时识别与公共卫生主题的参与模式,并优化公共卫生运动的时机。
    背景:
    BACKGROUND: Resources such as Google Trends and Reddit provide opportunities to gauge real-time popular interest in public health issues. Despite the potential for these publicly available and free resources to help optimize public health campaigns, use for this purpose has been limited.
    OBJECTIVE: The purpose of this study is to determine whether early public awareness of COVID-19 correlated with elevated public interest in other infectious diseases of public health importance.
    METHODS: Google Trends search data and Reddit comment data were analyzed from 2018 through 2020 for the frequency of keywords \"chikungunya,\" \"Ebola,\" \"H1N1,\" \"MERS,\" \"SARS,\" and \"Zika,\" 6 highly publicized epidemic diseases in recent decades. After collecting Google Trends relative popularity scores for each of these 6 terms, unpaired 2-tailed t tests were used to compare the 2020 weekly scores for each term to their average level over the 3-year study period. The number of Reddit comments per month with each of these 6 terms was collected and then adjusted for the total estimated Reddit monthly comment volume to derive a measure of relative use, analogous to the Google Trends popularity score. The relative monthly incidence of comments with each search term was then compared to the corresponding search term\'s pre-COVID monthly comment data, again using unpaired 2-tailed t tests. P value cutoffs for statistical significance were determined a priori with a Bonferroni correction.
    RESULTS: Google Trends and Reddit data both demonstrate large and statistically significant increases in the usage of each evaluated disease term through at least the initial months of the pandemic. Google searches and Reddit comments that included any of the evaluated infectious disease search terms rose significantly in the first months of 2020 above their baseline usage, peaking in March 2020. Google searches for \"SARS\" and \"MERS\" remained elevated for the entirety of the 2020 calendar year, as did Reddit comments with the words \"Ebola,\" \"H1N1,\" \"MERS,\" and \"SARS\" (P<.001, for each weekly or monthly comparison, respectively).
    CONCLUSIONS: Google Trends and Reddit can readily be used to evaluate real-time general interest levels in public health-related topics, providing a tool to better time and direct public health initiatives that require a receptive target audience. The start of the COVID-19 pandemic correlated with increased public interest in other epidemic infectious diseases. We have demonstrated that for 6 distinct infectious causes of epidemics over the last 2 decades, public interest rose substantially and rapidly with the outbreak of COVID-19. Our data suggests that for at least several months after the initial outbreak, the public may have been particularly receptive to dialogue on these topics. Public health officials should consider using Google Trends and social media data to identify patterns of engagement with public health topics in real time and to optimize the timing of public health campaigns.
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  • 文章类型: Randomized Controlled Trial
    背景:登革热等虫媒病毒病,Zika,基孔肯雅热是热带和亚热带地区的公共卫生威胁。在没有疫苗或特定治疗的情况下,病媒管理(在这种情况下,控制主要病媒埃及伊蚊)是预防这三种疾病的最佳做法。对矢量行为有很好的理解,生态学,人类流动和用水可以帮助设计有效的媒介控制程序。这项研究收集了有关这些因素的基线信息,以确定虫媒病毒传播风险,并评估了在哥伦比亚进行大型干预试验的要求。
    方法:在5,997个家庭中进行了基线调查,从库库塔大都市区的24个集群(平均有2000所房屋和250个家庭被检查的社区)中随机选择,哥伦比亚。该研究建立了种群特征,包括水管理和流动性以及幼虫-p指数,并在所有集群中进行了估计和比较。此外,该研究从两个来源估计疾病发病率:家庭调查中自我报告的登革热病例和国家监测系统通报的病例.
    结果:在所有24个研究集群中,发现了相似的社会和人口统计学特征,但昆虫学指标和估计的疾病发病率各不相同。昆虫学指标显示出很高的病媒侵扰:房屋指数=25.1%,集装箱指数=12.3%,Breteau指数=29.6。PupaeperpersonIndex(PPI)作为传播风险的指标显示出0.22至2.04的较大范围,表明大多数集群中的传播风险很高。用于洗衣的混凝土地面罐-主要是户外和无遮盖的-是Ae产量最高的容器。在这些容器中发现的埃及伊蚊占所有17,613只p的86.3%。此外,登革热的年发病率很高:每10万居民有841.6例自我报告病例,2019年国家监测系统通报的登革热发病率为每10万居民1,013.4例.只有2.2%的家庭使用容器水饮用。40.3%的研究人群在白天(伊蚊叮咬时)在其集群之外旅行。
    结论:Ae的生产。埃及伊蚊几乎只发生在用于洗衣的混凝土地罐(lavadero)中,主要干预目标。基线研究为哥伦比亚整群随机干预试验的设计和实施提供了必要的证据。
    Arbovirus diseases such as dengue, Zika, and chikungunya are a public health threat in tropical and subtropical areas. In the absence of a vaccine or specific treatment, vector management (in this case the control of the primary vector Aedes aegypti) is the best practice to prevent the three diseases. A good understanding of vector behaviour, ecology, human mobility and water use can help design effective vector control programmes. This study collected baseline information on these factors for identifying the arbovirus transmission risk and assessed the requirements for a large intervention trial in Colombia.
    Baseline surveys were conducted in 5,997 households, randomly selected from 24 clusters (neighbourhoods with on average 2000 houses and 250 households inspected) in the metropolitan area of Cucuta, Colombia. The study established population characteristics including water management and mobility as well as larval-pupal indices which were estimated and compared in all clusters. Additionally, the study estimated disease incidence from two sources: self-reported dengue cases in the household survey and cases notified by the national surveillance system.
    In all 24 study clusters similar social and demographic characteristics were found but the entomological indicators and estimated disease incidence rates varied. The entomological indicators showed a high vector infestation: House Index = 25.1%, Container Index = 12.3% and Breteau Index = 29.6. Pupae per person Index (PPI) as an indicator of the transmission risk showed a large range from 0.22 to 2.04 indicating a high transmission risk in most clusters. The concrete ground tanks for laundry -mostly outdoors and uncovered- were the containers with the highest production of Ae. aegypti as 86.3% of all 17,613 pupae were identified in these containers. Also, the annual incidence of dengue was high: 841.6 self-reported cases per 100,000 inhabitants and the dengue incidence notified by the National surveillance system was 1,013.4 cases per 100,000 in 2019. Only 2.2% of the households used container water for drinking. 40.3% of the study population travelled during the day (when Aedes mosquitoes bite) outside their clusters.
    The production of Ae. aegypti mosquitoes occurred almost exclusively in concrete ground tanks for laundry (lavadero), the primary intervention target. The baseline study provides necessary evidence for the design and implementation of a cluster randomized intervention trial in Colombia.
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  • 文章类型: Clinical Trial
    寨卡病毒仍然对全球健康构成威胁,因为它与严重的神经系统疾病以及缺乏疫苗和治疗有关。Sofosbuvir,一种抗丙型肝炎药物,在动物和细胞模型中显示出抗寨卡病毒的作用。因此,本研究旨在开发和验证新型LC-MS/MS方法,用于定量人血浆和脑脊液(CSF)和精液(SF)中的索非布韦及其主要代谢产物(GS-331007),并将这些方法应用于试点临床试验。样品通过液-液萃取制备,并在GeminiC18色谱柱上使用等度模式进行分离。使用配备有电喷雾电离源的三重四极质谱仪进行分析检测。索非布韦的验证范围为0.5-2,000ng/mL(血浆)和0.5-100ng/mL(CSF和SF),而对于代谢物,它们是2.0-2,000ng/mL(血浆),5.0-200ng/mL(CSF)和10-1,500ng/mL(SF)。日内和日间准确度(90.8-113.8%)和准确度(1.4-14.8%)在可接受范围内。所开发的方法满足了有关选择性的所有验证参数,基体效应,结转,线性度稀释完整性,精度,准确性和稳定性,确认该方法用于分析临床样品的适用性。
    Zika still poses a threat to global health owing to its association with serious neurological conditions and the absence of a vaccine and treatment. Sofosbuvir, an anti-hepatitis C drug, has shown anti-Zika effects in animal and cell models. Thus, this study aimed to develop and validate novel LC-MS/MS methods for the quantification of sofosbuvir and its major metabolite (GS-331007) in human plasma and cerebrospinal (CSF) and seminal fluid (SF), and apply the methods to a pilot clinical trial. The samples were prepared by liquid-liquid extraction and separated using isocratic mode on Gemini C18 columns. Analytical detection was performed using a triple quadrupole mass spectrometer equipped with an electrospray ionization source. The validated ranges for sofosbuvir were 0.5-2,000 ng/mL (plasma) and 0.5-100 ng/mL (CSF and SF), while for the metabolite they were 2.0-2,000 ng/mL (plasma), 5.0-200 ng/mL (CSF) and 10-1,500 ng/mL (SF). The intra-day and inter-day accuracies (90.8-113.8%) and precisions (1.4-14.8%) were within the acceptance range. The developed methods fulfilled all validation parameters concerning selectivity, matrix effect, carryover, linearity, dilution integrity, precision, accuracy and stability, confirming the suitability of the method for the analysis of clinical samples.
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  • 文章类型: Journal Article
    目前,主要由埃及伊蚊传播的DENV每年影响大约三分之一的人。媒介感染的时空异质性和虫媒病毒传播的强度需要能够预测爆发的监测。在这项工作中,我们使用了4年报告的登革热病例的数据,以及从安装在伊瓜苏市的大约3500个陷阱中收集的成年伊蚊的昆虫学指标,巴西,评估媒介侵染与登革热病例发生的时空关联。昆虫学(TPI,生成了ADI和MII)和昆虫病毒学(EVI)指数,目的是为当地卫生管理人员提供传播风险分层,从而可以针对病媒控制活动的区域。我们在评估中观察到了一种动态模式;然而,Ae的时空相关性较低。埃及伊蚊和登革热的发病率。独立的时间和空间效应捕获了人类虫媒病毒病例给出的信号的很大一部分。昆虫病毒学指数(EVI)在一些领域显著表明了风险,而昆虫学指标不能有效提供登革热风险警报。调查有和没有相关性的地区之间生物和非生物因素的变化应提供有关登革热当地流行病学的更多信息。
    Currently, DENV transmitted primarily by Aedes aegypti affects approximately one in three people annually. The spatio-temporal heterogeneity of vector infestation and the intensity of arbovirus transmission require surveillance capable of predicting an outbreak. In this work, we used data from 4 years of reported dengue cases and entomological indicators of adult Aedes collected from approximately 3500 traps installed in the city of Foz do Iguaçu, Brazil, to evaluate the spatial and temporal association between vector infestation and the occurrence of dengue cases. Entomological (TPI, ADI and MII) and entomo-virological (EVI) indexes were generated with the goal to provide local health managers with a transmission risk stratification that allows targeting areas for vector control activities. We observed a dynamic pattern in the evaluation; however, it was a low spatio-temporal correlation of Ae. aegypti and incidence of dengue. Independent temporal and spatial effects capture a significant portion of the signal given by human arbovirus cases. The entomo-virological index (EVI) significantly signaled risk in a few areas, whereas entomological indexes were not effective in providing dengue risk alert. Investigating the variation of biotic and abiotic factors between areas with and without correlation should provide more information about the local epidemiology of dengue.
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  • 文章类型: Journal Article
    我们旨在描述有症状的女性的不良妊娠结局,RT-PCR证实其婴儿的ZIKV感染和早期儿童结局。我们招募了有症状的孕妇,在一项前瞻性队列研究中,RT-PCR证实的ZIKV感染,和他们的婴儿在一项前瞻性儿科队列研究中。我们根据选定的神经系统定义不良妊娠和早期儿童结局,眼科,听觉,肌肉骨骼,和人体测量异常.我们使用RT-PCR和血清学测试来确定儿童的ZIKV感染状况。2016年3月10日至11月24日,我们招募了546例RT-PCR证实的ZIKV感染孕妇。可能与子宫内ZIKV暴露有关的不良妊娠和早期儿童结局的总体风险为15.7%(95%CI:12.8-19.0),分布如下:3.6%(95%CI:2.3-5.6)严重后遗症或死亡;2.7%(95%CI:1.6-4.5)主要异常;9.4%(95%CI:7.1-12.2)轻度异常。在妊娠早期发生ZIKV感染时,严重后遗症或死亡的风险更高(7.0%),与妊娠中期(2.7%)或妊娠中期(1.4%)相比(p=0.02)。在可以确定ZIKV感染状态的婴儿中,垂直传播率为3.0%(5/167)(95%CI:1.1-7.2)。在有症状的孕妇中,RT-PCR证实ZIKV感染,6.3%的胎儿和婴儿出现严重或严重妊娠或儿童早期结局.在母亲在妊娠早期感染的胎儿和婴儿中,严重的结局更常见。
    We aimed to describe adverse pregnancy outcomes among women who had symptomatic, RT-PCR-confirmed ZIKV infection and early childhood outcomes among their infants. We enrolled pregnant women with symptomatic, RT-PCR-confirmed ZIKV infection in a prospective cohort study, and their infants in a prospective pediatric cohort study. We defined adverse pregnancy and early childhood outcomes based on selected neurologic, ophthalmologic, auditory, musculoskeletal, and anthropometric abnormalities. We used RT-PCR and serologic tests to determine the ZIKV infection status of the child. Between 10 March and 24 November 2016, we enrolled 546 pregnant women with RT-PCR-confirmed ZIKV infection. The overall risk of adverse pregnancy and early childhood outcomes possibly related to in utero ZIKV exposure was 15.7% (95% CI: 12.8-19.0), distributed as follows: 3.6% (95% CI: 2.3-5.6) severe sequelae or fatality; 2.7% (95% CI: 1.6-4.5) major abnormalities; 9.4% (95% CI:7.1-12.2) mild abnormalities. The risk of severe sequelae or fatality was higher when ZIKV infection occurred during the first trimester (7.0%), compared to the second (2.7%) or third trimester (1.4%) (p = 0.02). Among the infants for whom ZIKV infection status could be determined, the vertical transmission rate was 3.0% (5/167) (95% CI: 1.1-7.2). Among pregnant women with symptomatic, RT-PCR-confirmed ZIKV infection, severe or major pregnancy or early childhood outcomes were present in 6.3% of fetuses and infants. Severe outcomes occurred more frequently in fetuses and infants whose mothers had been infected in the first trimester.
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