Crimean–Congo haemorrhagic fever virus: Past, present and future insights for animal modelling and medical countermeasures

Crimean-Congo haemorrhagic fever (CCHF) is a widespread tick-borne viral zoonosis with a case-fatality rate ranging from 9% to 50% in humans. Although a licensed vaccine to prevent infection by the CCHF virus (CCHFV) exists, its ability to induce neutralizing antibodies is limited and its efficacy against CCHFV remains undetermined. In addition, controlling CCHF infections by eradication of the tick reservoir has been ineffective, both economically and logistically, and the treatment options for CCHF remain limited. In this review, we first critically discuss the existing animal models to evaluate therapeutics for CCHF. We then review the therapeutic options for CCHF that have been investigated in human cases, followed by investigational drugs that have been evaluated in pre-clinical studies. We highlight the importance of understanding human prognostic factors in developing an animal model for CCHF that recapitulates hallmarks of human disease and its implication for selecting therapeutic candidates.