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

拉沙病毒（LASV）是一种负链RNA病毒，引起病毒性出血热，即拉沙热（LF）。人畜共患病毒可通过人畜共患水库的溢出和人与人之间的传播传播给人类。在尼日利亚、塞拉利昂、几内亚和利比里亚等西非国家，LASV每年造成多达30万例LF病例，每年造成多达6000人死亡。LASV的天然宿主是大鼠Mastomys natalensis。大多数人间病例被认为是通过接触这些啮齿动物或其排泄物传播的。该病毒可在人类中引起严重的、高度异质性的疾病，其特征是高烧、免疫失调、凝血障碍和多器官衰竭。致死过程通常伴有神经系统症状（昏迷、癫痫发作）、急性肾损伤和出血。导致死亡的病理生理过程和最终机制尚不清楚。因此，本提案的总体目标是利用最先进的死后宏观和微观以及免疫学和分子生物学方法来了解LF致死过程中的原因和机制。为此，与Bernhard Nocht热带医学研究所（BNITM）和汉堡-埃本多夫大学医学中心法律医学研究所（ILM，英国大学）合作，于2022年1月至3月在尼日利亚的Irrua专科教学医院（ISTH）建立了一个特殊设施，用于对4 / LF危险组病原体患者进行超声引导、微创组织取样（MITS）。在德国组织了两次培训交流。该项目将在尼日利亚Irrua的ISTH与德国汉堡的BNITM和德国汉堡的ILM合作进行。主要目的是利用MITS的形态学、组织病理学、免疫学和病毒学参数来确定LASV感染导致死亡的病理生理机制。我们的提案分为四个工作包（WP）。WP1是对已故LF患者执行MITS程序。通过该应用程序，将进行全身超声诊断，并将获得超声引导下的活组织检查和组织和体液样本，然后将对其进行处理，以便在其他工作包中进行进一步分析。WP2和WP 3将用于分析获得的死后活检样本的组织病理学、病毒学和实验室化学特征或参数，并评估和记录死前和死后的医疗记录或数据。WP4将重点关注社区参与和能力建设，教育人们了解低度脑病和常规解剖的效用和重要性，并最终降低发病率。从长远来看，在适当的安全预防措施下，MITS程序应扩展到完全的常规尸检。

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.