Uganda International Center for Excellence in Research

乌干达国际卓越研究中心

基本信息

批准号：
10927878
负责人：
Heinrich Feldmann
金额：
$ 72.38万
依托单位：
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10927878
关键词：
Africa Animal Model Animals Antibody Response Arenavirus Arthropods Bacteria Biological Assay Cell Culture System Circulation Collaborations Collection Communities Coronavirus Crimean-Congo Hemorrhagic Fever Virus Culicidae Data Development Disease Ecology Ensure Enzyme-Linked Immunosorbent Assay Epidemiology Equipment Etiology Fever Filovirus Flavivirus Funding Health Housekeeping Gene Human Immunocompetent In Vitro Infection International Intervention Laboratories Link Livestock Maintenance Measures Microbiology Modeling Modernization Molecular National Institute of Allergy and Infectious Disease Orthobunyavirus Participant Population Population Surveillance Postbaccalaureate Prevalence Process Public Health Quantitative Reverse Transcriptase PCR Research Research Institute Research Personnel Research Project Grants Resources Rift Valley Fever Rift Valley fever virus Risk Assessment Risk Factors Rodent Role Sampling Serology Serology test Serum Site Surveillance Program Therapeutic Ticks Tissue Sample Training Training and Education Uganda United States National Institutes of Health Vaccines Vector-transmitted infectious disease Viral Virus Wages Work Zoonoses clinically relevant cohort detection assay field study global health in vivo insight interest internal control international center mouse model nonhuman primate operation pathogen pathogenic bacteria postgraduate education programs screening seropositive tick-borne pathogen training opportunity transmission process vaccine platform vector vector-borne pathogen

项目摘要

Emerging/re-emerging zoonotic diseases are a major global health problem. Linking comprehensive pathogen surveillance of arthropod/vector populations in Uganda with public health surveillance at the regional and international level will make an important contribution to human and animal health in East Africa and the One World One Health concept in general. There will be a focus on rodent- and tick-borne pathogens potentially causing disease in humans, wildlife, and livestock. A more comprehensive understanding of the ecology of known and unknown rodent-borne zoonotic pathogens is essential for a risk assessment for local and global human and animal health. The establishment of emerging/re-emerging virus program on the campus of the Uganda Virus Research Institute (UVRI), Entebbe, Uganda is ongoing. We have procured most of the necessary equipment for the UVRI site; further equipment will be purchased when needed. Over the previous and current funding period we have refined molecular and serological detection assays for several pathogens including arenaviruses, bunyaviruses, coronaviruses filoviruses, and flaviviruses. In this fiscal year, efforts were directed towards making the laboratory fully operational. Several key pieces of equipment were installed or have been ordered and we continue to purchase necessary equipment. We have established task-orders with UVRI to pay for staff salary, utilities and maintenance of the laboratory space. We have also begun research at the Uganda ICER site directed towards serological screening of vector-borne pathogens in livestock and in humans. We have established a collaboration with researchers at the Ugandan National Livestock Resource Research Institute to conduct field sampling programs in which serum from livestock in several districts throughout Uganda was collected. At the ICER laboratory, these samples were processed to screen for vector-borne diseases via qRT-PCR and ELISA. High seropositivity for Crimean-Congo hemorrhagic fever virus and Rift Valley Fever Virus was measured in several livestock cohorts (unpublished data) adding to our understanding of the disease prevalence in these regions. In parallel to these efforts, we have established a collaboration with researchers at UVRI to conduct rodent trapping at homesites in association with our livestock sampling efforts. We are collecting serum and tissue samples to screen for rodent-borne pathogens. Lastly, we have also established a research project with NIH researcher, Dr. Steven Reynolds who leads the Rakai Community Cohort which for years has conducted community surveillance and serum collection from thousands of participants living in the Rakai district of Uganda. We are using serum from this cohort to screen for serological evidence of infection with a variety of vector-borne diseases. These data will be used in conjunction with the wealth of demographic data collected by the Rakai Community Cohort project to identify risk factors for infection. Cumulatively, our project aims to investigate rodent, livestock and human samples to build a comprehensive understanding of disease circulation in Uganda. These collaborative projects will continue into next fiscal year and these data will support Ugandan public health efforts to mitigate these public health burdens. As part of our focus on training, during this fiscal year, we have had a post-baccalaureate trainee at the laboratory who has worked to establish the serological assays and has begun using these assays for the human samples. We have also hired a local laboratory manager who will be responsible for ensuring successful operation of the laboratory. We continue to advance our molecular and serological assays that will be deployed to Uganda as soon as the lab space at UVRI is available and functional (Lombe et al., Sci Rep 2021). We have developed multiplex qRT-PCR assays for the screening of tick, mosquito, rodent and livestock samples for pathogens of interest along with internal housekeeping genes for internal controls (Hawman et al., unpublished). We have also developed serological assays to measure antibody responses to various pathogens that will be utilized in Uganda (Lombe et al., Sci Rep 2021; Hawman et al., unpublished). At RML we continue to advance vaccine platforms for CCHFV (Hawman et al., Nat Microbiol 2021; Leventhal et al., eBioMed 2022) and other pathogens endemic in these regions. We have developed an immunocompetent mouse model for CCHFV (Hawman et al., eLife 2021) and are currently using this mouse model along with the established non-human primate model to evaluate countermeasures for CCHFV.

新兴/重新出现的人畜共患病是全球主要的健康问题。将乌干达节肢动物/载体种群的全面病原体监测与区域和国际水平的公共卫生监测联系起来将为东非的人类和动物健康做出重要贡献，而总体上，一个世界一个健康概念。将关注啮齿动物和tick虫病原体，可能导致人类，野生动植物和牲畜疾病。对已知和未知啮齿动物的人畜共患病原体的生态学更全面的了解对于对本地和全球人类和动物健康的风险评估至关重要。在乌干达的乌干达病毒研究所（UVRI）校园内建立新兴/重新出现的病毒计划正在进行中。我们为UVRI站点采购了大多数必要的设备；需要在需要时购买更多设备。在过去和当前的融资期间，我们对包括体育症病毒，Bunyaviruses，冠状病毒和黄病毒在内的几种病原体进行了分子和血清学检测测定。在这个财政年度，努力致力于使实验室完全运营。安装了几个关键设备或已订购，我们继续购买必要的设备。我们已经建立了使用UVRI的任务，以支付员工工资，公用事业和实验室空间的维护。我们还开始在乌干达ICER网站上进行研究，该网站针对牲畜和人类的血清学筛查。我们已经与乌干达国家牲畜资源研究所的研究人员建立了合作，以开展现场抽样计划，该计划收集了整个乌干达的几个地区的牲畜血清。在ICER实验室，对这些样品进行处理以通过QRT-PCR和ELISA筛选媒介传播疾病。在几个牲畜队列（未发表的数据）中测量了克里米亚 - 隆戈出血病毒和裂谷发烧病毒的高血清阳性病毒，这增加了我们对这些地区疾病患病率的理解。与这些努力并行，我们与UVRI的研究人员建立了合作，以与我们的牲畜抽样工作有关，在家里进行啮齿动物捕获。我们正在收集血清和组织样品，以筛选啮齿动物的病原体。最后，我们还与NIH研究人员史蒂文·雷诺兹（Steven Reynolds）博士建立了一个研究项目，他领导了Rakai社区队列，该研究多年来一直在乌干达Rakai区的成千上万的参与者进行了社区监视和血清收集。我们正在使用该队列中的血清来筛选有各种载体疾病感染的血清学证据。这些数据将与Rakai社区队列项目收集的大量人口统计数据一起使用，以识别感染的危险因素。累积地，我们的项目旨在调查啮齿动物，牲畜和人类样本，以对乌干达的疾病循环进行全面的了解。这些协作项目将持续到下一个财政年度，这些数据将支持乌干达的公共卫生努力减轻这些公共卫生负担。作为我们对培训的关注的一部分，在这个财政年度，我们在实验室有一名后掌库的学员，他一直在努力建立血清学分析，并开始使用这些测定法作为人类样本。我们还雇用了一位当地的实验室经理，该经理将负责确保实验室成功运营。我们将继续推进分子和血清学测定法，该分子和血清学测定将在UVRI的实验室空间及其功能（Lombe等，SCI REP 2021）后立即部署到乌干达。我们已经开发了多重QRT-PCR分析，用于筛查tick，蚊子，啮齿动物和牲畜样品，以供感兴趣的病原体以及内部管家内部控制基因（Hawman等人，未发表）。我们还开发了血清学分析，以测量乌干达将使用的各种病原体的抗体反应（Lombe等，Sci Rep 2021； Hawman等人，未发表）。在RML，我们继续推进CCHFV的疫苗平台（Hawman等，Nat Microbiol 2021； Leventhal等人，Ebiomed 2022）和其他病原体在这些地区中的特有。我们为CCHFV开发了一种免疫能力的小鼠模型（Hawman等，Elife 2021），目前正在使用该小鼠模型以及已建立的非人类灵长类动物模型来评估CCHFV的对策。