Hantavirus Infections

汉坦病毒感染
  • 文章类型: Journal Article
    汉坦病毒是在美洲引起汉坦病毒心肺综合症(HCPS)的人畜共患因子,巴西在南美确诊的HCPS病例数中排名第一。在这项研究中,我们通过将Kermack-McCormickSIR模型与细胞自动机模型(CA)结合来模拟高致死汉坦病毒在自然宿主中的每月传播,因此,同时评估宿主群体中的细胞内和细胞间感染动力学,使用最近汇编的主要宿主物种丰度和确认的汉坦病毒感染死亡数据。对于两种宿主物种来说,我们的模型预测感染面积会增加,迄今为止尚未确认病例的22个城市预计在未来十年内至少有一例病例,11个城市的感染率下降。我们的发现支持现有的研究,并揭示了汉坦病毒可能在公认的震中传播的新领域。突出时空趋势和潜在扩展,我们强调,由于普遍的栖息地碎片化和农业扩张,风险增加。持续的预防工作和“一个健康”行动至关重要,特别是在新确定的高风险城市。
    Hantaviruses are zoonotic agents responsible for causing Hantavirus Cardiopulmonary Syndrome (HCPS) in the Americas, with Brazil ranking first in number of confirmed HCPS cases in South America. In this study, we simulate the monthly spread of highly lethal hantavirus in natural hosts by conjugating a Kermack-McCormick SIR model with a cellular automata model (CA), therefore simultaneously evaluating both in-cell and between-cell infection dynamics in host populations, using recently compiled data on main host species abundances and confirmed deaths by hantavirus infection. For both host species, our models predict an increase in the area of infection, with 22 municipalities where no cases have been confirmed to date expected to have at least one case in the next decade, and a reduction in infection in 11 municipalities. Our findings support existing research and reveal new areas where hantavirus is likely to spread within recognized epicenters. Highlighting spatial-temporal trends and potential expansion, we emphasize the increased risk due to pervasive habitat fragmentation and agricultural expansion. Consistent prevention efforts and One Health actions are crucial, especially in newly identified high-risk municipalities.
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  • 文章类型: Journal Article
    我们调查了台湾一家饲养啮齿动物养殖场工人的2例急性病例和1例先前的汉城汉坦病毒感染病例。在测试的饲养大鼠中,汉坦病毒IgG的患病率为37.5%。采取适当的预防措施,包括使用消毒协议和个人防护设备,对降低风险至关重要。
    We investigated 2 acute cases and 1 previous case of Seoul hantavirus infection in workers in a feeder rodent breeding farm in Taiwan. Prevalence of hantavirus IgG among the tested feeder rats was 37.5%. Appropriate prevention measures, including using disinfection protocols and personal protective equipment, are crucial to lowering risk.
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  • 文章类型: Journal Article
    汉坦病毒是属于布尼亚病毒科的单链RNA病毒,在世界范围内引起汉坦病毒心肺综合征(HCPS)和肾综合征出血热(HFRS)。目前,没有有效的疫苗接种或治疗方法可用于治疗汉坦病毒,因此,迫切需要研究以制定该疾病的治疗方法。计算疫苗设计目前是一个高度准确的,设计针对不同疾病的有效疫苗的时间和成本效益方法。在目前的研究中,我们入围了高抗原蛋白,即,信封,和来自汉坦病毒蛋白质组的核蛋白,并经过高抗原表位的选择,设计下一代多表位疫苗构建体。一种高度抗原性和稳定的佐剂与免疫表位(T细胞,B细胞,和HTL)来设计Env-Vac,NP-Vac,和Com-Vac结构,表现出更强的抗原性,非过敏性,和良好的理化性质。此外,预测了3D结构,对接分析揭示了与人Toll样受体3(TLR3)的强相互作用以启动免疫级联反应.为Env-Vac计算的总自由能,NP-Vac,Com-Vac为-50.02千卡/摩尔,-24.13kcal/mol,和-62.30千卡/摩尔,分别。硅克隆,结果表明Env-Vac的CAI值,NP-Vac,和Com-Vac分别为0.957、0.954和0.956,而其相应的GC含量为65.1%,64.0%,和63.6%。此外,三剂量注射的免疫模拟结果释放了显著水平的IgG,IgM,白细胞介素,和细胞因子,以及随着时间的推移抗原清除,在接受疫苗和两次加强剂量后。我们针对汉坦病毒的疫苗被发现具有高度免疫原性,诱导强大的免疫反应,需要临床使用的实验验证。
    Hantaviruses are single-stranded RNA viruses belonging to the family Bunyaviridae that causes hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS) worldwide. Currently, there is no effective vaccination or therapy available for the treatment of hantavirus, hence there is a dire need for research to formulate therapeutics for the disease. Computational vaccine designing is currently a highly accurate, time and cost-effective approach for designing effective vaccines against different diseases. In the current study, we shortlisted highly antigenic proteins i.e., envelope, and nucleoprotein from the proteome of hantavirus and subjected to the selection of highly antigenic epitopes to design of next-generation multi-epitope vaccine constructs. A highly antigenic and stable adjuvant was attached to the immune epitopes (T-cell, B-cell, and HTL) to design Env-Vac, NP-Vac, and Com-Vac constructs, which exhibit stronger antigenic, non-allergenic, and favorable physiochemical properties. Moreover, the 3D structures were predicted and docking analysis revealed robust interactions with the human Toll-like receptor 3 (TLR3) to initiate the immune cascade. The total free energy calculated for Env-Vac, NP-Vac, and Com-Vac was -50.02 kcal/mol, -24.13 kcal/mol, and -62.30 kcal/mol, respectively. In silico cloning, results demonstrated a CAI value for the Env-Vac, NP-Vac, and Com-Vac of 0.957, 0.954, and 0.956, respectively, while their corresponding GC contents were 65.1%, 64.0%, and 63.6%. In addition, the immune simulation results from three doses of shots released significant levels of IgG, IgM, interleukins, and cytokines, as well as antigen clearance over time, after receiving the vaccine and two booster doses. Our vaccines against Hantavirus were found to be highly immunogenic, inducing a robust immune response that demands experimental validation for clinical usage.
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  • 文章类型: Journal Article
    汉坦病毒科内的正坦病毒属中的病毒会引起人类汉坦病毒感染,并对公众健康构成威胁。北海道病毒(HOKV),正坦病毒puumalaense(Puumala病毒;PUUV)的基因型,最初是在Tobetsu发现的,北海道,日本。尽管它与PUUV的原型在遗传上有关,HOKV的进化途径尚不清楚。我们于2022年在Tobetsu的森林中进行了实地调查,并捕获了44只啮齿动物。从5只病毒RNA阳性啮齿动物(4只Myodesrufocanusbedefordiae和1种Apodemusspeciosus)获得了HOKV的完整编码基因组序列。系统发育分析揭示了与M.rufocanus相关的正交病毒的系统发育与地理起源之间的密切关系。正交病毒S段的系统发育树和Myodes物种的细胞色素b基因的比较表明,由于遗传分离和宿主转换,与Myodes相关的正交病毒在Myodes啮齿动物物种中进化。
    Viruses in the genus Orthohantavirus within the family Hantaviridae cause human hantavirus infections and represent a threat to public health. Hokkaido virus (HOKV), a genotype of Orthohantavirus puumalaense (Puumala virus; PUUV), was first identified in Tobetsu, Hokkaido, Japan. Although it is genetically related to the prototype of PUUV, the evolutionary pathway of HOKV is unclear. We conducted a field survey in a forest in Tobetsu in 2022 and captured 44 rodents. Complete coding genome sequences of HOKVs were obtained from five viral-RNA-positive rodents (four Myodes rufocanus bedfordiae and one Apodemus speciosus). Phylogenetic analysis revealed a close relationship between the phylogenies and geographical origins of M. rufocanus-related orthohantaviruses. Comparison of the phylogenetic trees of the S segments of orthohantaviruses and the cytochrome b genes of Myodes species suggested that Myodes-related orthohantaviruses evolved in Myodes rodent species as a result of genetic isolation and host switching.
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  • 文章类型: Journal Article
    背景:有记录的最大的肾综合征出血热暴发发生在Primorje-GorskiKotar县,克罗地亚,2021年,这标志着在该县北部已知的流行地区之外记录的首次汉坦病毒感染病例。目的:确定导致疫情蔓延的因素,并比较流行和新感染地区汉坦病毒感染的危险因素。方法与结果:PuumalaIgM/IgG抗体阳性确诊189例(93.6%),使用结构化问卷通过临床和流行病学数据确定了13例可能病例(6.4%).在有临床资料的179例病例中,59例(33.0%)住院。3例接受血液透析,没有死亡报告。在170个有暴露信息的案例中,66(38.8%)报告了职业风险。县北部的病例更有可能在早春感染(OR27.1,95%CI2.93-250.7),报告看到啮齿动物(OR6.5;95CI2.3-18.4),并且知道患有肾综合征出血热(HFRS)(OR3.0;95CI1.2-8.0)的人比该县南部的病例要多。克罗地亚森林有限公司的数据表明,2020年山毛榉种子的异常良好产量可能导致2021年啮齿动物数量增加。然而,平均温度,降雨,2021年的湿度数据并未说明与往年的显着差异(Kruskal-Wallisp=0.837,p=0.999,p=0.108)。结论:2021年HFRS爆发可能是由丰富的啮齿动物种群和啮齿动物宿主中的病毒传播推动的。人类活动,环境因素,随之而来的动物与人类的相互作用已经将汉坦病毒感染从克罗地亚的山区传播到了一个以前没有流行的地中海气候的沿海地区。
    Background: The largest documented outbreak of hemorrhagic fever with renal syndrome occurred in Primorje-Gorski Kotar County, Croatia, in 2021, marking the first-time cases of hantavirus infection recorded outside of the known endemic region in the north of the county. Aim: To identify the factors contributing to the spread of the outbreak and to compare risk factors for acquiring hantavirus infection in the endemic and newly affected regions. Methods and Results: A total of 189 cases were confirmed by positive Puumala IgM/IgG antibodies (93.6%), and 13 probable cases were identified by clinical and epidemiological data (6.4%) using a structured questionnaire. Of the 179 cases with available clinical data, 59 (33.0%) were hospitalized. Three cases received hemodialysis, and no deaths were reported. Among 170 cases with information on exposures, 66 (38.8%) reported occupational risk. Cases in the northern part of county were more likely to have been infected in early spring (OR 27.1, 95% CI 2.93-250.7), to report seeing a rodent (OR 6.5; 95%CI 2.3-18.4), and to know someone with hemorrhagic fever with renal syndrome (HFRS) (OR 3.0; 95%CI 1.2-8.0) than cases from the southern part of the county. Data from Croatian Forests Ltd. suggested that an unusually good production of beech seeds in 2020 may have contributed to an increased rodent population in 2021. However, average temperature, rainfall, and humidity data from 2021 did not illustrate a significant difference from previous years (Kruskal-Wallis p = 0.837, p = 0.999, p = 0.108). Conclusion: The 2021 HFRS outbreak was likely fueled by an abundant rodent population and virus transmission in rodent hosts. Human activity, environmental factors, and the ensuing animal-human interactions have spread hantavirus infection from Croatia\'s mountainous region to a previously nonendemic coastal area with a Mediterranean climate.
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  • 文章类型: Journal Article
    2022年,在卡宴周围非正式定居点的患者中报告了四例汉坦病毒肺综合征(HPS)的严重病例,法属圭亚那的主要城市。法国公共卫生署委托区域卫生署(RHA)评估HPS确诊病例附近汉坦病毒感染的血清阳性率。RHA随后委托法国红十字会(FRC)移动公共卫生团队,由卫生调解员向生活在非正式住区的人口提供环境卫生问题方面的支持,以方便调查。这项研究的目的是描述为提高调查效率而设立的健康中介活动。
    健康调解小组由HPS专业的病毒学家和感染学家专门培训。他们在调查的各个步骤中帮助调查小组和卫生工作者。然后在结果部分中描述这些干预措施。
    调查发生在11月之间2022年和2023年3月在三个社区。在前期调查活动中,调解员提高了343人对HPS的认识,其中319人(93%)计划参与调查。总之,274人最终参与了调查,包括,即,居住在三个有关定居点的估计人口的30.8%。抗汉坦病毒IgG阳性患者的全球比例为5.1%。卫生调解员小组支持以下步骤:初步会议和培训模块,确定资源人员,实地访问以及提高认识和宣传运动(调查前);关于非正式住区的实地数据收集(每次调查)和个人结果的交流,公众反馈会议(调查后)。
    调解员的参与可能是对生活在被调查社区中的社会弱势群体的公共卫生反应成功的一个因素。初步的预防活动有助于提高对健康风险的认识并招募参与者。健康调解和外展活动似乎是影响非正规住区居民的疾病的流行病学实地调查的相关工具。
    UNASSIGNED: In 2022, four severe cases of Hantavirus pulmonary syndrome (HPS) were reported in patients from informal settlements around Cayenne, the main city in French Guiana. Regional Health Agency (RHA) was commissioned by the French Public Health Agency to estimate the seroprevalence of Hantavirus infections in the neighborhoods of confirmed cases of HPS. RHA then commissioned the French Red Cross (FRC) mobile public health team, providing support in environmental health issues to the population living in informal settlements by health mediators, to facilitate the investigation. The objective of this study was to describe the health mediators\' activities set up to improve the efficiency of the investigation.
    UNASSIGNED: The health mediators\' team was specifically trained by virologist and infectiologist specialized in HPS. They helped the investigating team and health workers at various steps of the investigation. These interventions are then described in the results section.
    UNASSIGNED: The investigation took place between Nov. 2022 and March 2023 in three neighborhoods. During the pre-investigation activities, the mediators raised awareness about HPS of 343 people, among whom 319 (93%) planned to participate in the investigation. Altogether, 274 people finally participated in the investigation, including, i.e., 30.8% of the estimated population living in the three concerned settlements. The global proportion of patients with positive IgG anti-Hantavirus was 5.1%. The health mediators team supported the following steps: preliminary meetings and training modules, identification of resource persons, field visits and awareness and information campaigns (pre-investigation); on field data collection in informal settlements (per-investigation) and communication of individual results, public feedback meeting (post-investigation).
    UNASSIGNED: The involvement of mediators was probably a factor in the success of the public health response to socially vulnerable people living in the investigated neighborhoods. The preliminary prevention activities helped to raise awareness of the health risk and to enroll participants. Health mediation and outreach activities seem relevant tools of epidemiological field investigations in diseases affecting inhabitants of informal settlements.
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  • 文章类型: Journal Article
    在阿根廷东北部,很少有汉坦病毒肺综合征的报道。然而,邻近地区发病率较高,暗示漏报。我们评估了整个Misiones省小型啮齿动物中抗正坦病毒抗体的存在。在Misiones的保护区发现了受感染的Akodonaffinismontensis和Oligoryzomysnigripes本地啮齿动物。
    Few cases of hantavirus pulmonary syndrome have been reported in northeastern Argentina. However, neighboring areas show a higher incidence, suggesting underreporting. We evaluated the presence of antibodies against orthohantavirus in small rodents throughout Misiones province. Infected Akodon affinis montensis and Oligoryzomys nigripes native rodents were found in protected areas of Misiones.
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  • 文章类型: Journal Article
    正坦病毒感染的实验室诊断主要基于血清学。然而,为了确诊的血清学诊断,评估后续血清样本是必不可少的,这是耗时的,并导致延迟。实时逆转录聚合酶链反应(RT-PCR)测试,如果是积极的,提供即时和明确的诊断,并准确识别病原体,其中血清学的辨别性质是次优的。我们重新评估了2014年7月至2016年4月在Twente和Achterhoek的荷兰地区的疑似正坦病毒临床病例的血清中是否存在Puumala正坦病毒(PUUV),图拉正坦病毒(TULV),和首尔正州病毒(SEOV)RNA。PUUVRNA检测到的血清总数(n=85)的11%,在50%的抗PUUV/TULVIgM阳性血清中(n=16),并且在1.4%的血清中抗PUUV/TULVIgM阴性或不确定(n=69)。没有发现存在TULV或SEOV病毒RNA的证据。基于这些发现,我们提出了两种算法来实现实时RT-PCR检测在常规的正畸病毒诊断,这可以最佳地为临床医生提供早期确诊的诊断,并可以防止可能的进一步侵入性测试和治疗。
    目的:将实时逆转录聚合酶链反应试验添加到常规的正坦病毒诊断中可能比单独使用标准血清学试验更好地帮助临床决策。临床医生和临床微生物学家对这一优势的认识可能最终导致过度住院和不必要的侵入性诊断程序的减少。
    Laboratory diagnosis of orthohantavirus infection is primarily based on serology. However, for a confirmed serological diagnosis, evaluation of a follow-up serum sample is essential, which is time consuming and causes delay. Real-time reverse transcription polymerase chain reaction (RT-PCR) tests, if positive, provide an immediate and definitive diagnosis, and accurately identify the causative agent, where the discriminative nature of serology is suboptimal. We re-evaluated sera from orthohantavirus-suspected clinical cases in the Dutch regions of Twente and Achterhoek from July 2014 to April 2016 for the presence of Puumala orthohantavirus (PUUV), Tula orthohantavirus (TULV), and Seoul orthohantavirus (SEOV) RNA. PUUV RNA was detected in 11% of the total number (n = 85) of sera tested, in 50% of sera positive for anti-PUUV/TULV IgM (n = 16), and in 1.4% of sera negative or indeterminate for anti-PUUV/TULV IgM (n = 69). No evidence was found for the presence of TULV or SEOV viral RNA. Based on these findings, we propose two algorithms to implement real-time RT-PCR testing in routine orthohantavirus diagnostics, which optimally provide clinicians with early confirmed diagnoses and could prevent possible further invasive testing and treatment.
    OBJECTIVE: The addition of a real-time reverse transcription polymerase chain reaction test to routine orthohantavirus diagnostics may better aid clinical decision making than the use of standard serology tests alone. Awareness by clinicians and clinical microbiologists of this advantage may ultimately lead to a reduction in over-hospitalization and unnecessary invasive diagnostic procedures.
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  • 文章类型: Journal Article
    背景:汉坦病毒,一种人畜共患病原体,导致严重的综合征,如肾综合征出血热(HFRS),有时对人类是致命的。考虑到检测汉坦病毒抗原的重要性,免疫传感器的构建是必不可少的。骆驼纳米体(VHHs)的结构和功能特征鼓励它们在纳米生物技术领域的应用,治疗学,诊断,和基础研究。因此,这项研究旨在使用金纳米粒子(AuNPs)和VHHs标准化稳定的生物缀合物,为了开发用于汉坦病毒感染诊断的免疫生物传感器。
    方法:进行固定金属亲和层析(IMAC)以获得纯化的重组抗汉坦病毒核衣壳纳米抗体(抗prNΔ85VHH),而AuNP被合成用于生物缀合。采用紫外可见分光光度法和透射电子显微镜(TEM)分析来表征AuNP。
    结果:生物缀合稳定性参数(VHH-AuNP),通过分光光度法分析,结果表明,理想的pH值和VHH浓度分别为7.4和50μg/mL,分别,加入1MNaCl后,诱导AuNP聚集。在生物缀合之前和之后进行的TEM显示均匀,同质,分散良好,和球形AuNP,平均直径为~14±0.57nm。此外,高分辨率图像显示AuNPs表面上有一层薄薄的白色光晕,表明AuNP被蛋白质覆盖。在固定阶段进行了生物传感器模拟测试(类似斑点印迹[DB-like]),以验证来自Araucária汉坦病毒株(prNΔ85)的重组核衣壳蛋白的结合和检测极限。
    结论:使用AuNP/VHH生物缀合物,在反应的5~10分钟之间,以剂量依赖性方式检测到特异性相互作用.观察到该测试足够灵敏以检测浓度高达25ng/μL的prNΔ85。考虑到纳米结构的生物系统,如与AuNP缀合的抗体是开发化学和生物传感器的有用工具,生物缀合物的稳定性表明检测抗原的熟练程度。获得的实验结果将用于将来的免疫斑点测定或侧流免疫色谱分析以检测汉坦病毒。
    BACKGROUND: Hantavirus, a zoonotic pathogen, causes severe syndromes like hemorrhagic fever with renal syndrome (HFRS), sometimes fatal in humans. Considering the importance of detecting the hantavirus antigen, the construction of an immunosensor is essential. The structural and functional characteristics of camelid nanobodies (VHHs) encourage their application in the areas of nanobiotechnology, therapeutics, diagnostics, and basic research. Therefore, this study aimed to standardize stable bioconjugates using gold nanoparticles (AuNPs) and VHHs, in order to develop immunobiosensors for the diagnosis of hantavirus infection.
    METHODS: Immobilized metal affinity chromatography (IMAC) was performed to obtain purified recombinant anti-hantavirus nucleocapsid nanobodies (anti-prNΔ85 VHH), while AuNPs were synthesized for bioconjugation. UV-visible spectrophotometry and transmission electron microscopy (TEM) analysis were employed to characterize AuNPs.
    RESULTS: The bioconjugation stability parameters (VHH-AuNPs), analyzed by spectrophotometry, showed that the ideal pH value and VHH concentration were obtained at 7.4 and 50 μg/mL, respectively, after addition of 1 M NaCl, which induces AuNP aggregation. TEM performed before and after bioconjugation showed uniform, homogeneous, well-dispersed, and spherical AuNPs with an average diameter of ~ 14 ± 0.57 nm. Furthermore, high-resolution images revealed a thin white halo on the surface of the AuNPs, indicating the coating of the AuNPs with protein. A biosensor simulation test (dot blot-like [DB-like]) was performed in stationary phase to verify the binding and detection limits of the recombinant nucleocapsid protein from the Araucária hantavirus strain (prN∆85).
    CONCLUSIONS: Using AuNPs/VHH bioconjugates, a specific interaction was detected between 5 and 10 min of reaction in a dose-dependent manner. It was observed that this test was sensitive enough to detect prNΔ85 at concentrations up to 25 ng/μL. Considering that nanostructured biological systems such as antibodies conjugated with AuNPs are useful tools for the development of chemical and biological sensors, the stability of the bioconjugate indicates proficiency in detecting antigens. The experimental results obtained will be used in a future immunospot assay or lateral flow immunochromatography analysis for hantavirus detection.
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  • 文章类型: Journal Article
    我们调查了奥地利370例汉坦病毒感染患者(ICU入院率7.8%),发现2例侵袭性肺曲霉病(累积发生率7%);1例患者死亡。汉坦病毒相关的肺曲霉病可能会使患有肾综合征出血热的危重患者的病程复杂化。
    We investigated a cohort of 370 patients in Austria with hantavirus infections (7.8% ICU admission rate) and detected 2 cases (cumulative incidence 7%) of invasive pulmonary aspergillosis; 1 patient died. Hantavirus-associated pulmonary aspergillosis may complicate the course of critically ill patients who have hemorrhagic fever with renal syndrome.
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