Diagnostic tests for Crimean-Congo haemorrhagic fever: a widespread tickborne disease

Abstract

Crimean-Congo haemorrhagic fever (CCHF) is a widespread tickborne disease that circulates in wild and domestic animal hosts, and causes severe and often fatal haemorrhagic fever in infected humans. Due to the lack of treatment options or vaccines, and a high fatality rate, CCHF virus (CCHFV) is considered a high-priority pathogen according to the WHO R&D Blueprint. Several commercial reverse transcriptase PCR (RT-PCR) and serological diagnostic assays for CCHFV are already available, including febrile agent panels to distinguish CCHFV from other viral haemorrhagic fever agents; however, the majority of international laboratories use inhouse assays. As CCHFV has numerous amplifying animal hosts, a cross-sectoral ‘One Health’ approach to outbreak prevention is recommended to enhance notifications and enable early warning for genetic and epidemiological shifts in the human, animal and tick populations. However, a lack of guidance for surveillance in animals, harmonisation of case identification and validated serodiagnostic kits for animal testing hinders efforts to strengthen surveillance systems. Additionally, as RT-PCR tests tend to be lineage-specific for regional circulating strains, there is a need for pan-lineage sensitive diagnostics. Adaptation of existing tests to point-of-care molecular diagnostic platforms that can be implemented in clinic or field-based settings would be of value given the potential for CCHFV outbreaks in remote or low-resource areas. Finally, improved access to clinical specimens for validation of diagnostics would help to accelerate development of new tests. These gaps should be addressed by updated target product profiles for CCHFV diagnostics.

Importance of diagnostics in epidemic and pandemic preparedness

“…Diagnostics developers had to purchase specimens without guarantee of the quality of the clinical characterisation (which is of particular importance for the Zika virus due to the high immunological cross-reactivity with dengue virus and other flaviviruses) 30. Efforts to validate diagnostic tests for the WHO R&D Blueprint pathogens CCHF and MERS-CoV have also been hampered by difficulties with sourcing of clinical specimens, as described elsewhere in this supplement 15 18…”

“…Linking diagnostics and vaccines in a common health programme would help to ensure that vaccines are delivered in a timely manner to the most at-risk populations. For pathogens with significant animal reservoirs, such as the Nipah and CCHF viruses, collection and integration of animal surveillance data may also be a necessary component of any outbreak preparedness strategy 15 17. A ‘One Health’ approach to surveillance that integrates human, animal and ecological health would provide earlier opportunities for outbreak detection and prevention; however, a number of challenges to implementing such an approach exist, including need for greater cross-sectoral communication, strengthening of laboratory networks, restructuring of existing systems, and development of shared databases, shortage of experienced personnel and limited availability of diagnostic tests suitable for animal use 37…”

“…It is vital that the current lack of rapid diagnostic tests for priority pathogens is addressed, to ensure that future outbreaks can be more effectively contained. Detailed descriptions of the diagnostic landscapes for selected WHO R&D Blueprint pathogens are provided in this supplement 15–19. Each of these pathogens presents specific challenges, due to differences in factors such as geographical location (Nipah infection primarily occurs in Asia, Middle East respiratory syndrome-coronavirus (MERS-CoV) in the Middle East and Lassa fever in Africa, while Crimean-Congo haemorrhagic fever (CCHF) is widespread) and mode of transmission (MERS-CoV in particular has a significant animal reservoir in dromedary camels, while CCHF is a tick-borne disease), among others.…”

Tick‐borne viruses: Current trends in large‐scale viral surveillance

“…The important laboratory tests used to diagnose the CCHF virus include the enzyme‐linked immunosorbent assay (ELISA), which detects IgM and IgG antibodies in the serum (Samudzi et al . 2012), RT‐PCR and qRT‐PCR for the detection of the viral genome, virus isolation by culture, and other serological diagnostic assays (Mazzola & Kelly‐Cirino 2019). Interestingly, Vanhomwegen et al .…”

An Overview of Crimean Congo Hemorrhagic Fever

“…Turnaround time for each test is specified by the manufacturer; turnaround time per result can include additional time (days to weeks) for sample transport and processing at the reference lab. Several commercial assays for PCR and serology are available (online supplementary table S1 and S2),although the majority of international laboratories use inhouse assays, likely due to an investment in tests developed from regional CCHV strains.It has also been suggested that commercial tests may be too expensive, difficult to order or not available to international customers.The majority of the inhouse assays have a publication history, several with published data on diagnostic performance or external quality assessment 12 .…”