ICF: Development of a rapid diagnostic test to identify Crimean-Congo Haemorrhagic Fever at the point-of-care

Crimean-Congo haemorrhagic fever (CCHF) is a World Health Organisation (WHO)-listed priority disease due to its high mortality and lack of vaccines and effective treatment and diagnostics. Patients with CCHF have a high mortality and there is only one antiviral used that may only be effective if given early in disease. However, the current turnaround of test results for CCHF diagnosis is slow with a 2-5-day delay causing reduced treatment efficacy and poor patient recovery. The development of rapid diagnostic tests (RDTs) for rapid diagnosis of CCHF has been identified as a priority by the WHO. This proposal seeks to address this need and the Liverpool School of Tropical Medicine (LSTM) in collaboration with Global Access Diagnostics (GADx) have achieved the development of the first RDT prototype to diagnose CCHF with a sensitivity and specificity that fulfils the recommendations from WHO for RDTs.

LSTM in collaboration with GADx will optimise the RDT to refine sensitivity and specificity within an ISO-accredited environment. GADx will perform up-scale of manufacturing techniques including bulk conjugations and use quality control systems within their Quality Management System to ensure that the RDT preserves its original performance between batches and when manufactured at commercial volumes. We will do a market scoping exercise to identify the customers and pull through mechanisms to market for this important RDT. We will design-lock the product with all the kit components for evaluation. Firstly, we will perform analytical evaluations across all CCHF viral lineages with UK Health Security Agency (UKHSA) and following this we will evaluate the RDT in banked samples at the Ministry of Health (MoH) in Turkey and the Centers for Disease Control and Prevention (CDC) in Iraq. Also, in collaboration with the MoH, LSTM will set up clinical trials for diagnostic evaluation of the RDT among 492 patients attending secondary health clinics in CCHF hyperendemic regions in Turkey. Data from these trials will be used for preparation of regulatory submission under UKCA marking.

Crimean-Congo haemorrhagic fever (CCHF) is a WHO-listed priority disease due to the high fatality rate, lack of vaccines and effective treatment and diagnostics. Ribavirin may be an effective antiviral if administered early in disease course, however, the current diagnosis is deficient with the turnaround of results of 2-5 days leading to poor patient outcomes. The development of rapid diagnostic tests (RDTs) has been identified as of high priority by the WHO. This proposal seeks to address this need and the Liverpool School of Tropical Medicine (LSTM) in collaboration with Global Access Diagnostics (GADx) have achieved the development of the first RDT prototype to detect CCHF viral antigens with a sensitivity and specificity that exceeds the minimum recommended in the WHO target product profile (TPP).

The prototype RDT has completed Phase 0 (proof of concept) and entered Phase 1 (feasibility) of product development and this proposal aims to progress the RDT through the next phases, completion of Phase 1, optimisation and design-lock (Phase 2), upscale to manufacturing volumes within GADx Quality Management System (Phase 3), verification and validation and clinical trials for regulatory submission (Phase 4). LSTM in collaboration with GADx will optimise the RDT to refine the sensitivity and specificity and produce a design-locked RDT kit with all the components. We will perform analytical testing of the RDT at LSTM for specificity and interference testing and at the Biosafety Level 4 laboratories of UKHSA for analytical sensitivity among all CCHF lineages. The clinical performance will be first evaluated in retrospective samples at the Ministry of Health (MoH) in Turkey and Iraq CDC. This will follow with clinical trials at the point-of-care among 492 patients attending secondary health clinics in CCHF hyperendemic regions in Turkey, data of which will be compatible with regulatory submission for UKCA marking.