Detect

The challenge

Crimean-Congo haemorrhagic fever (CCHF) is a severe tick-borne viral disease with a case fatality rate of up to 40%. Around 3 billion people are estimated to be at risk, with CCHF endemic across large parts of Africa, the Balkans, the Middle East and Asia, and its geographical range continuing to expand. The World Health Organization (WHO) has identified CCHF as a priority disease because of its epidemic potential and the urgent need for improved diagnostics.

CCHF can progress rapidly from non-specific febrile symptoms to severe bleeding, organ failure and death. However, these early symptoms are difficult to distinguish from other common febrile illnesses, making laboratory confirmation essential. Current diagnosis relies on testing samples to reference laboratories, with samples often needing to be transported and results taking 2–5 days or longer. This delay is particularly critical for CCHF, where patients can deteriorate rapidly and early clinical decisions are important.

Delayed diagnosis can affect patient triage and supportive care, but also delays the implementation of infection prevention and control measures needed to reduce the risk of person-to-person and healthcare-associated transmission. These challenges are even greater in rural and resource-limited settings, where many outbreaks occur and access to molecular testing may be limited.

There is therefore an urgent need for an accurate, easy-to-use rapid diagnostic test that can bring CCHF diagnosis closer to the patient, enabling clinical and infection-control decisions to be made within minutes rather than days.

About the project

DETECT is an MRC-funded programme led by LSTM that is turning an academic proof-of-concept into a rapid diagnostic designed for real-world use in CCHF-endemic settings. The programme builds on earlier LSTM research that developed a prototype lateral flow test capable of detecting CCHF viral antigen directly in blood. DETECT was established to take the crucial next step: moving beyond demonstrating that the technology works to developing a robust, scalable and clinically validated diagnostic that can ultimately reach patients. Working closely with Global Access Diagnostics (GADx), and with clinical, laboratory and public health partners in CCHF-endemic countries, DETECT is progressing the test through the full translational pathway. This includes optimisation to commercial standards, design lock, scale-up of manufacturing under quality-controlled processes, evaluation across CCHF viral diversity, and prospective clinical evaluation using different sample types directly at the point of care. The programme is therefore addressing not only whether the test can detect CCHF, but whether it can be manufactured consistently at scale and perform where it is ultimately intended to be used. The ambition is to replace a diagnostic pathway that can take days with an accurate, easy-to-use test that can identify CCHF in approximately 30 minutes, without dependence on specialist molecular laboratories.

Our strategies and approaches

Developing a test that addresses CCHF genetic diversity

The substantial genetic diversity of CCHF virus is a major challenge for diagnostic development, as a test must be able to detect the different viral lineages circulating across endemic regions. DETECT has addressed this challenge from the outset by designing and evaluating the test against the breadth of CCHF genetic diversity. The team has produced recombinant CCHF nucleoproteins representing lineages I–VII, which have been used to evaluate and optimise the ability of the RDT to recognise antigen across all viral lineages. This is complemented by close collaboration with the UK Health Security Agency (UKHSA) to evaluate the analytical sensitivity of the test against CCHF virus isolates. This work requires highly specialised facilities because CCHF virus is a Containment Level 4 (CL4) pathogen, making comprehensive evaluation considerably more challenging than for many other infectious diseases. Clinical evaluation in endemic settings provides a further layer of evidence by assessing the test against viruses circulating in patients. Sequencing undertaken through the project has differentiated two CCHF viral subclades circulating in Türkiye that had not previously been reported, generating new information on local viral diversity while also allowing us to investigate whether genetic variation influences diagnostic performance.

Moving from prototype to a scalable diagnostic

A major focus of DETECT is turning a successful academic proof of concept into a diagnostic that can reach patients. Achieving this requires more than demonstrating good diagnostic performance: the test must remain accurate and robust as it moves from laboratory development to scaled manufacture, while being simple and practical to use in the settings where CCHF cases occur. DETECT brings together LSTM, commercial manufacturers, Ministries of Health, clinical partners and end users throughout the development pathway. Through successive rounds of optimisation, manufacturing development and clinical evaluation, the original academic prototype has progressed to a design-locked product developed to commercial manufacturing and quality standards. Working directly with healthcare teams in affected countries has also ensured that the test is developed around the practical requirements of those who will ultimately use it. By addressing diagnostic performance, manufacturability, quality and end-user requirements together, DETECT is building the evidence and product readiness needed for regulatory approval, sustainable manufacture and future deployment at scale.

Evaluating the test in real-world settings

Evaluating diagnostics for CCHF is particularly challenging. As a high-containment pathogen, access to well-characterised clinical samples is limited, and prospective studies depend on outbreaks and seasonal transmission. Building strong partnerships with clinicians, laboratories and public health institutions in affected countries has therefore been fundamental to ensuring that DETECT is evaluated where CCHF cases occur and in the patients for whom the test is being developed. Retrospective evaluation using stored clinical samples from Türkiye and Iraq provided the first evidence of performance in patients and was used to further optimise the test before moving into prospective studies. The programme has since progressed to evaluation using fresh clinical samples and, now, point-of-care testing at the bedside using capillary blood. This is a major step towards the ultimate aim of DETECT: bringing CCHF diagnosis to the patient and reducing the time from clinical presentation to a diagnostic result from days to less than 30 minutes.

Key findings and impact

DETECT has generated strong evidence that a rapid, point-of-care approach to CCHF diagnosis is achievable. Analytical and clinical evaluations have demonstrated that the test fulfils the WHO Target Product Profile requirements for CCHF rapid diagnostic tests, providing an important benchmark for its progression towards implementation.

The analytical programme has demonstrated detection across the major CCHF viral lineages (I–VII), alongside good specificity against other febrile illnesses. The test performed at the highest sensitivity in patients with higher viral loads and more severe disease, supporting its potential to rapidly identify clinically important cases.

Most importantly, DETECT has moved the technology beyond proof of concept, progressing from an academic prototype through optimisation, clinical validation, design lock and manufacturing scale-up to a manufacturable diagnostic now being evaluated at the patient’s bedside. This progression represents a major translational achievement, turning promising academic research into a diagnostic designed for manufacture at scale and real-world use, while generating the clinical, manufacturing and implementation evidence needed to support regulatory progression and future deployment in CCHF-affected settings.

Our partners

The programme lead at LSTM is Dr Ana Isabel Cubas Atienzar.

Global Access Diagnostics (GADx); the Ministry of Health CCHF National Reference Laboratory, Ankara, Türkiye; and clinical and laboratory partners across Türkiye, including Ondokuz Mayis University, Sivas Cumhuriyet University, Kastamonu Training and Research Hospital, Gaziosmanpaşa University, Atatürk University and Erzurum City Hospital, as well as the Central Public Health Laboratory in Baghdad, Iraq.