Table 3.
Therapeutic options for the treatment of Crimean–Congo haemorrhagic fever
| Mechanism of action | In vitro data | Animal data | Human data | |
|---|---|---|---|---|
| Standard of care | Compensates for fluid and electrolyte loss, support ventilation and treat secondary infections (Jabbari et al., 2012) | Not available | No animal data available | In a meta‐analysis compiling data of patients only provided with supportive care, 215 of 365 (68%) survived CCHF(Soares‐Weiser et al., 2010) |
| Ribavirin | Inhibits viral replication and indirectly modulates host immune response (Tam et al., 2001) | Inhibits CCHFV replication in Vero E6 cell line (Oestereich et al., 2014) |
IFNAR−/− mice (100 FFU CCHFV): Protected 1/7 (14%) when administered on 0 dpi (Oestereich et al., 2014) STAT‐1 knockout mice (10 PFU CCHFV): Protected 6/6 (100%) when daily regimen was initiated 1 hr post‐infection or 1 dpi (Bente et al., 2010). STAT‐1 knockout mice (1,000 PFU CCHFV): Protected 60% when given 1 hr post‐infection and 0% at 1 dpi (Bente et al., 2010) |
Pro‐ribavirin: Improvement in survival and disease severity (Dokuzoguz et al., 2013; Mardani et al., 2003; Ozbey et al., 2014). Anti‐ribavirin: No statistically significant improvement in outcome for CCHF patients treated with ribavirin (Ascioglu et al., 2011; Bodur et al., 2011; Ceylan et al., 2013; Elaldi et al., 2009; Koksal et al., 2010) |
| Methylprednisolone | Modulates host immune response (Tam et al., 2012) | Not available | No animal data available | 5/5 (100%) CCHF patients survived when administered doses 20–30 mg per kg/day intravenously for 5 days, after administration of IVIG and/or G‐CSF (Dilber et al., 2010) |
| Convalescent blood products | Antibody‐mediated effects (neutralization, antibody‐dependent cell cytotoxicity) | Not available | No animal data available |
1 patient treated with convalescent serum survived disease (Suleiman et al., 1980). 5/9 (56%) patients treated with hyperimmune serum survived disease (Van Eeden et al., 1985) |
| Monoclonal antibodies | Antibody‐mediated effects (neutralization, antibody‐dependent cell cytotoxicity) |
Anti‐Gc mAbs neutralized CCHFV infection of SW‐13 cells Anti‐Gn mAbs demonstrated less neutralizing activity against CCHFV in SW‐13 cells (Bertolotti‐Ciarlet et al., 2005) |
Neonatal mice: 8A1 (Anti‐Gc): 100% protection when administered 1 day before infection, 20% when administered 1 dpi 11E7 (Anti‐Gc): ~75% protection when administered 1 day before or after infection 6B12 (Anti‐Gn): 100% protection when administered 1 day before infection, ~95% protection when administered 1 dpi 10E11 (Anti‐Gn): 95% protection when administered 1 day before infection, 90% protection when administered 1 dpi (Bertolotti‐Ciarlet et al., 2005) |
Not tested in human CCHF cases |
| Favipiravir (T‐705) | Inhibits viral RNA polymerase (Janeba, 2015; Li, Chan, & Lee, 2015; Salata et al., 2015) | Inhibits CCHFV replication in Vero E6 cell line (Oestereich et al., 2014) | IFNAR−/− mice (100 FFU CCHFV): Protected 5/5 (100%) when treatment initiated up to 2 dpi (Oestereich et al., 2014) | Not tested in human CCHF cases |
| Arbidol | Inhibits viral entry (Blaising et al., 2013) | Inhibits CCHFV replication in Vero E6 cell line (Oestereich et al., 2014) |
IFNAR−/− mice (1,000 FFU CCHFV): Protected 0/5 (0%) when administered 1 day before infection (Oestereich et al., 2014) IFNAR−/− mice (10 FFU CCHFV): Protected 1/5 (20%) when administered 1 day before infection (Oestereich et al., 2014) |
Not tested in human CCHF cases |
| Chloroquine | Inhibits uncoating and post‐translational modifications, modulates host immune response (Savarino et al., 2003) | Inhibits CCHFV replication in Vero and Huh7 cell lines (Ferraris et al., 2015) | No animal data available | Not tested in human CCHF cases |
| Chlorpromazine | Inhibits formation of clathrin‐coated pits, preventing clathrin‐mediated endocytosis and viral uncoating (Wang et al., 1993) | Inhibits CCHFV in Vero and Huh7 cell lines (Ferraris et al., 2015) | No animal data available | Not tested in human CCHF cases |
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