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

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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.