Viral Zoonoses and Severe Febrile Illness in Northern Tanzania

坦桑尼亚北部的病毒性人畜共患病和严重发热性疾病

• 批准号: 9179924
• 负责人: Matthew P Rubach
• 金额: $ 15.04万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-06 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9179924
• 关键词: Accounting; Acquired Immunodeficiency Syndrome; Adult; Africa; Africa South of the Sahara; Animals; Antibodies; Arboviruses; Archives; Award; Bacterial Infections; Biological Assay; Blood Circulation; Blood specimen; Brucella; Catchment Area; Cessation of life; Child; Clinical Research; Collaborations; Collection; Communicable Diseases; Communities; Complex; Country; Coxiella burnetii; Cryptococcus neoformans; Data; Detection; Developing Countries; Development; Diagnosis; Diagnostic; Discipline; Disease; Distance Learning; Doctor of Philosophy; Ecology; Emerging Communicable Diseases; Enrollment; Environment; Epidemic; Epidemiologic Studies; Epidemiology; Etiology; Evaluation; Exposure to; Factor Analysis; Faculty; Fever; Funding; Goals; Gray unit of radiation dose; Health; Healthcare; Hospital Referrals; Hospitalization; Hospitals; Human; Hygiene; Infection; Infectious Disease Epidemiology; Institution; International; Investigation; K-Series Research Career Programs; Knowledge; Laboratories; Leptospira; Letters; Link; Livestock; London; Medical; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Metadata; Microbiology; Mycobacterium tuberculosis; Oligonucleotide Probes; Pathogen detection; Patients; Physicians; Plasma; Polymerase Chain Reaction; Positioning Attribute; Prevalence; Prevention; Prevention strategy; Preventive Intervention; Reovirus; Research; Research Design; Research Personnel; Research Project Grants; Resources; Risk Factors; Role; Salmonella enterica; Sampling; Schools; Security; Serotyping; Serum; Singapore; Site; Social Impacts; Source; State Government; Streptococcus pneumoniae; Syndrome; Tanzania; Technical Expertise; Techniques; Technology; Time; Training; Training Activity; Tropical Medicine; United States; United States National Institutes of Health; Universities; Viral; Viral Epidemiology; Viremia; Virus; Virus Diseases; Whole Blood; Work; Zoonoses; Zoonotic Bacterial Infection; Zoonotic Infection; base; career; career development; co-infection; cohort; disease transmission; disorder prevention; global health; improved; innovation; medical schools; meetings; mortality; next generation sequencing; novel; novel diagnostics; novel strategies; pathogen; programs; public health relevance; repository; research study; tool; transmission process

SUMMARY/ABSTRACT The objective of this proposal is to deploy standard as well as innovative diagnostic tools in order to investigate what proportion of severe febrile illness (SFI) in northern Tanzania is attributable to emerging zoonotic viral pathogens. Fever is among the most common reasons for seeking health care in less developed countries, yet up to half of patients hospitalized with fever in sub-Saharan Africa may go without a laboratory- confirmed diagnosis—this represents a serious knowledge gap that hinders disease prevention efforts. Prior research in northern Tanzania has revealed that animal-borne bacterial infections are a common cause of SFI, perhaps reflecting the effects of close interaction between humans, livestock and wildlife in many parts of sub- Saharan Africa. Yet the impact of animal-borne viral infections, such as henipa-, bunya-, corona- and reoviruses, remains unknown. An enhanced understanding of whether and which of these high-consequence viral pathogens are causing SFI is fundamental to the prevention and control of severe infectious diseases in sub-Saharan Africa and to the global health security agenda of the United States and other G7 countries. To these ends, this career development award proposes to utilize well-characterized archived blood specimens from prior fever etiology research in northern Tanzania in order to undertake the following SPECIFIC AIMS: SPECIFIC AIM 1—Establish the prevalence of exposure to zoonotic viral pathogens by performing antibody evaluations of serum from patients with SFI and from previously enrolled community-dwellers. SPECIFIC AIM 2— Establish the proportion of SFI cases with detectable viremia from select zoonotic pathogens by performing real-time polymerase chain reaction (PCR) assays on SFI patient blood samples. SPECIFIC AIM 3—Achieve enhanced viral pathogen detection and discover new viral pathogens by interrogating SFI blood samples with hybridization enrichment next-generation sequencing technology. The requisite laboratory work to achieve these SPECIFIC AIMS will be conducted at Duke-National University of Singapore Graduate Medical School (Duke-NUS) under the direction of the Candidate and the Director of the Duke-NUS Program in Emerging Infectious Disease, Lin-Fa Wang, PhD (K23 Co-Mentor), and Duke University/Duke-NUS faculty, Greg Gray, MD, MPH (K23 Co-Mentor). De-identified serum, plasma and whole blood will be utilized for these aims. These well-characterized blood specimens represent nearly 1500 patients enrolled in two febrile illness research cohorts conducted in northern Tanzania by K23 Primary Mentor, John Crump, MB ChB, MD: International Co-Studies of AIDS-Associated Co-Infections (U01 AI062563), a comprehensive fever etiology study; and The Impact and Social Ecology of Bacterial Zoonoses in Northern Tanzania (R01TW009237), an epidemiologic risk factor analysis on zoonotic causes of SFI. The Candidate, Matthew Rubach, MD, is a board-certified medical microbiologist and infectious disease physician. Dr. Rubach was stationed full-time in Moshi, Tanzania 2012-2014. He has engaged successfully in clinical research on febrile illness and the epidemiology of bacterial zoonotic infections under the mentorship of Dr. Crump and in the context of Dr. Crump's productive zoonoses research program, comprised of over 20 collaborating scholars from multiple disciplines. This institutional environment in Tanzania, the excellent mentorship team as well as directed coursework through the London School of Hygiene & Tropical Medicine MSc Epidemiology distance learning program will collectively enable the Candidate to achieve the following TRAINING OBJECTIVES: TRAINING OBJECTIVE 1—To develop further expertise in epidemiologic research, clinical research study design, and quantitative analysis (Drs. Crump & Gray; coursework). TRAINING OBJECTIVE 2 – To develop further expertise in the epidemiology of zoonotic infections (Drs. Crump & Gray; coursework). TRAINING OBJECTIVE 3—To develop further technical expertise in innovative diagnostic microbiology through mentored clinical research that utilizes novel pathogen detection and pathogen discovery laboratory techniques (Dr. Wang). Ultimately, Dr. Rubach aspires to improve infectious disease diagnostic capacity in resource-limited settings by conducting relevant clinical research as Duke University faculty stationed full-time at the KCMC- Duke University Health Research Collaboration in Moshi, Tanzania. This early career award will equip Dr. Rubach with technical expertise in innovative diagnostics that will differentiate him from his Primary Mentor and will enable Dr. Rubach to develop an independent research track with novel approaches to infectious disease diagnostics for clinical and epidemiologic research. Through the mentorship and training objectives in this proposal, Dr. Rubach will emerge with a highly unique skillset that bridges world-class infectious disease epidemiology research in the field with state-of-the-art technical expertise in diagnostic microbiology. As such, he will be well positioned to seek R01 funding support for further studies on the diagnosis, management and epidemiology of zoonotic and non-zoonotic causes of SFI.

总结/摘要 这项建议的目的是部署标准和创新的诊断工具，以便 调查坦桑尼亚北方严重发热性疾病（SFI）的比例可归因于 人畜共患病毒病原体。发烧是欠发达国家寻求医疗保健的最常见原因之一， 然而，在撒哈拉以南非洲，多达一半的发烧住院患者可能没有实验室- 确诊--这代表了严重的知识差距，阻碍了疾病预防工作。之前 坦桑尼亚北方的研究表明动物传播的细菌感染是SFI的常见原因， 这也许反映了人类、牲畜和野生动物之间密切互动的影响， 撒哈拉非洲。然而，动物传播的病毒感染，如henipa-，bunya-，corona-和 呼肠孤病毒，仍然未知。更好地了解这些高后果是否以及哪些 病毒性病原体引起的SFI是预防和控制严重传染病的根本， 撒哈拉以南非洲以及美国和其他七国集团国家的全球卫生安全议程。到 为此，该职业发展奖建议利用特征良好的存档血液标本 来自坦桑尼亚北方先前的发热病因学研究，以实现以下具体目标： 具体目标1-通过进行抗体检测， 来自SFI患者和先前登记的社区居民的血清的评价。 特定目的2-确定选择的人畜共患病中可检测到病毒血症的SFI病例的比例 通过对SFI患者血液样品进行实时聚合酶链反应（PCR）测定来检测病原体。 特定目标3-通过以下方式实现增强的病毒病原体检测并发现新的病毒病原体 用杂交富集下一代测序技术询问SFI血液样品。 实现这些特定目标所需的实验室工作将在Duke-National进行。 新加坡大学医学研究生院（Duke-NUS）在候选人和 杜克-新加坡国立大学新发传染病项目主任，Lin-Fa Wang博士（K23共同导师）， 杜克大学/杜克-新加坡国立大学教师，格雷格·格雷，医学博士，公共卫生硕士（K23共同导师）。去识别血清、血浆和 全血将用于这些目的。这些特征良好的血液样本代表了近1500个 K23 Primary在坦桑尼亚北方进行的两个发热性疾病研究队列中招募的患者 导师，John Crump，MB ChB，MD：艾滋病相关合并感染的国际合作研究（U 01 AI 062563），一项全面的发热病因学研究;以及细菌性人畜共患病在非洲的影响和社会生态学。 坦桑尼亚北方（R 01 TW 009237），SFI人兽共患原因的流行病学风险因素分析。的 候选人，马修鲁巴赫，医学博士，是一个委员会认证的医学微生物学家和传染病医生。 博士2012-2014年，Rubach全职驻扎在坦桑尼亚的莫希。他成功地从事了临床 研究发热性疾病和细菌性人畜共患传染病的流行病学。 在克博士富有成效的人畜共患病研究计划的背景下， 来自多个学科的合作学者。坦桑尼亚的这种制度环境， 导师团队以及通过卫生与热带医学的伦敦学校指导课程 MSC流行病学远程学习计划将共同使候选人实现以下目标 培训人员： 培训目标1-进一步发展流行病学研究、临床研究 设计和定量分析（Crump & Gray博士;课程）。 培训目标2 -进一步发展人畜共患病感染流行病学方面的专业知识（Drs. Crump&Gray; coursework）. 培训目标3-进一步发展创新诊断微生物学方面的技术专长 通过指导临床研究，利用新的病原体检测和病原体发现实验室 技术（王博士）。 最终，Rubach博士渴望在资源有限的国家提高传染病诊断能力。 作为杜克大学的全职教师，在KCMC进行相关的临床研究， 坦桑尼亚莫希的杜克大学健康研究合作。这个早期的职业生涯奖将装备博士。 Rubach在创新诊断方面拥有技术专长，这将使他与他的主要导师区分开来， 将使Rubach博士能够开发一个独立的研究轨道，采用新的方法来治疗传染病 用于临床和流行病学研究的诊断学。通过这方面的指导和培训目标， 鲁巴赫博士将以一种高度独特的技能出现，这种技能可以连接世界级的传染病。 该领域的流行病学研究，拥有诊断微生物学方面最先进的技术专业知识。因此，在本发明中， 他将有能力寻求R 01资金支持，以进一步研究诊断，管理和 SFI的人畜共患病和非人畜共患病原因的流行病学。