Minimally Invasive Tissue Sampling (MITS) in Lassa Fever - A postmortem Study at the Irrua Specialist Teaching Hospital

拉沙热的微创组织取样 (MITS) - 伊鲁阿专业教学医院的尸检研究

• 批准号: 461730290
• 负责人: Professor Dr. Stephan Günther
• 金额: --
• 依托单位: Institute of Lassa Fever Control
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/461730290?language=en
• 关键词: Minimally; Invasive; Tissue; Sampling; MITS

Lassa virus (LASV) is a negative-strand RNA virus that causes a viral haemmorhagic fever, Lassa fever (LF). The zoonotic virus may be transmitted to humans via spillover from the zoonotic reservoir and via human-to-human transmission. LASV causes up to 300,000 LF cases annually in the West African countries of Nigeria, Sierra Leone, Guinea, and Liberia, with up to 6,000 deaths per year. The natural host of LASV is the rat Mastomys natalensis. Most human cases are thought to be transmitted through contact with these rodents or their excreta. The virus can cause severe, highly heterogeneous disease in humans, characterised by high fever, immune dysregulation, coagulation disorders and multi-organ failure. The lethal course is often associated with neurological manifestations (coma, seizures), acute kidney damage and haemorrhage. The pathophysiological processes and the final mechanisms leading to death are poorly understood. The overall aim of this proposal is therefore to understand the cause and mechanisms of LF using state-of-the-art post-mortem macro- and microscopic as well as immunological and molecular biological methods in a lethal LF course. For this purpose, a special facility for performing ultrasound-guided, minimally invasive tissue sampling (MITS) on patients with pathogens of risk group 4 / LF was established in Nigeria, between January and March 2022 at the Irrua Specialist Teaching Hospital (ISTH), in collaboration with the Bernhard Nocht Institute for Tropical Medicine (BNITM) and the Institute of Legal Medicine of the University Medical Center Hamburg-Eppendorf (ILM, UKE), and two training exchanges were organised in Germany. The project will take place at ISTH, Irrua, Nigeria in cooperation with BNITM, Hamburg, Germany and the ILM, UKE, Hamburg, Germany. The main objective is to determine the pathophysiological mechanisms leading to death from LASV infection using morphological, histopathological, immunological and virological parameters by MITS. Our proposal is divided into four workpackages (WP). WP1 is the execution of the MITS procedure on deceased LF patients. Through the application, whole-body ultrasound diagnostics will be performed, and ultrasound-guided biopsies and samples of tissues and body fluids will be obtained, which will then be processed for further analysis in the other workpackages. WP2 and WP 3 will be used to analyse the obtained post-mortem biopsy samples with regard to histopathological, virological and laboratory-chemical characteristics or parameters, and to evaluate and record pre- and post-mortem medical records or data. WP4 will focus on community engagement and capacity building by educating on the utility and importance of MITS and conventional autopsy to understand LF and ultimately reduce morbidity. In perspective, the MITS procedure should be extended to full conventional autopsy under appropriate safety precautions.

LASSA病毒（LASV）是一种阴性链RNA病毒，可引起病毒性出血热，LASSA热（LF）。人畜共患病病毒可以通过人畜共患病和人类到人类传播传播给人类。 LASV每年在尼日利亚，塞拉利昂，几内亚和利比里亚的西非国家每年造成多达30万LF病例，每年死亡多达6,000例。 LASV的天然寄主是大鼠乳鼠纳塔尔氏菌。人们认为大多数人案件是通过与这些啮齿动物或其排泄物接触而传播的。该病毒可能引起人类严重，高度异质性疾病，其特征是高烧，免疫失调，凝结疾病和多器官衰竭。致命的病程通常与神经系统表现（昏迷，癫痫发作），急性肾脏损伤和出血有关。鲜为人知的病理生理过程和导致死亡的最终机制。因此，该提案的总体目的是使用最先进的后宏观和微观和微观和免疫学和分子生物学方法来理解LF的原因和机制。为此目的，在尼日利亚，在尼日利亚，在Irrua专业教学医院（ISTH）之间在尼日利亚建立了一个针对患有风险4 / LF病原体病原体的患者的特殊设施，该设施与伯纳德·诺奇（Bernhard Nocht Nocht）的医学中心（Bernhard Nocht Institution）在尼日利亚建立了4 / LF的病原体（MIT）。汉堡 - 埃潘多夫（ILM，UKE）和两次在德国组织了两次培训交流。该项目将与BNITM，汉堡，德国和ILM，UKE，汉堡，德国合作在尼日利亚Irua，尼日利亚的Isth举行。主要目的是通过MITS使用形态学，组织病理学，免疫学和病毒学参数来确定导致LASV感染死亡的病理生理机制。我们的建议分为四个工件包（WP）。 WP1是对已故LF患者的MITS程序的执行。通过应用，将进行全身超声诊断，并将获得超声引导的活检以及组织和体液的样品，然后将处理其他工作包中的进一步分析。 WP2和WP 3将用于分析有关组织病理学，病毒学和实验室化学特征或参数的验尸后活检样本，并评估和记录验尸前和验尸后医疗记录或数据。 WP4将通过教育MITS和常规尸检以了解LF并最终降低发病率的效用和重要性，将重点放在社区参与和能力建设上。从角度来看，在适当的安全预防措施下，应将MITS程序扩展到完全常规的尸检。