Immunotherapy
One trial found that immunotherapy, via passive simultaneous transfer of two different specific immunoglobulin preparations (intramuscular CCHF-bulin and intravenous CCHF-venin) prepared from the plasma of CCHF survivor donors boosted with a dose of CCHF vaccine, resulted in the recovery of all seven patients with severe CCHF.[101]Vassilenko SM, Vassilev TL, Bozadjiev LG, et al. Specific intravenous immunoglobulin for Crimean-Congo haemorrhagic fever. Lancet. 1990;335:791-2.
http://www.ncbi.nlm.nih.gov/pubmed/1969533?tool=bestpractice.com
Investigators subsequently suggested that the intravenous preparation be used for the treatment of CCHF.[64]European Centre for Disease Prevention and Control. Meeting report: consultation on Crimean-Congo haemorragic fever prevention and control. September 2008 [internet publication].
https://www.ecdc.europa.eu/en/publications-data/consultation-crimean-congo-haemorragic-fever-prevention-and-control
[102]Dimitrov DS. Antibodies to CCHFV for prophylaxis and treatment. In: Ergonul O, Whitehouse CA, eds. Crimean Congo hemorrhagic fever: a global perspective. Dordrecht: Springer; 2007:261-9. Another study suggested prompt administration of CCHF virus hyperimmunoglobulin may be an alternative treatment approach, especially for high-risk individuals.[40]Ergonul O. Crimean-Congo hemorrhagic fever. In: Ergonul O, Can F, Akova M, Madoff L, eds. Emerging infectious diseases: clinical case studies. London: Academic Press; 2014:136-49.[103]Kubar A, Haciomeroglu M, Ozkul A, et al. Prompt administration of Crimean-Congo hemorrhagic fever (CCHF) virus hyperimmunoglobulin in patients diagnosed with CCHF and viral load monitorization by reverse transcriptase-PCR. Jpn J Infect Dis. 2011;64:439-43.
http://www.ncbi.nlm.nih.gov/pubmed/21937830?tool=bestpractice.com
Further studies are needed to determine whether these treatments have a role in the management of CCHF.
Corticosteroids
Corticosteroids have been found to be beneficial in one observational study and one small case series. Corticosteroids were found to decrease mortality in patients with severe disease in the observational study.[79]Dokuzoguz B, Celikbas AK, Gök ŞE, et al. Severity scoring index for Crimean-Congo hemorrhagic fever and the impact of ribavirin and corticosteroids on fatality. Clin Infect Dis. 2013;57:1270-4.
http://cid.oxfordjournals.org/content/57/9/1270.long
http://www.ncbi.nlm.nih.gov/pubmed/23946218?tool=bestpractice.com
In the case series, all six patients survived when corticosteroids were added to standard treatment early in the disease course.[104]Jabbari A, Besharat S, Abbasi A, et al. Crimean-Congo hemorrhagic fever: case series from a medical center in Golestan province, Northeast of Iran (2004). Indian J Med Sci. 2006 Aug;60(8):327-9.
http://www.ncbi.nlm.nih.gov/pubmed/16864919?tool=bestpractice.com
One clinical trial involving 35 people with CCHF revealed the beneficial use of corticosteroids in addition to other treatments in patients with severe thrombocytopenia.[105]Sharifi-Mood B, Alavi-Naini R, Metanat M, et al. Efficacy of high-dose methylprednisolone in patients with Crimean-Congo haemorrhagic fever and severe thrombocytopenia. Trop Doct. 2013 Apr;43(2):49-53.
https://journals.sagepub.com/doi/10.1177/0049475513486642
http://www.ncbi.nlm.nih.gov/pubmed/23796671?tool=bestpractice.com
Another study revealed the efficacy of corticosteroids on the clinical outcome of five patients with CCHF.[106]Dilber E, Cakir M, Erduran E, et al. High-dose methylprednisolone in children with Crimean-Congo haemorrhagic fever. Trop Doct. 2010 Jan;40(1):27-30.
https://journals.sagepub.com/doi/10.1258/td.2009.090069
http://www.ncbi.nlm.nih.gov/pubmed/20075424?tool=bestpractice.com
Adjuvant use of corticosteroids may be useful for decreasing the acute inflammatory response caused by the course of the disease.[107]Fabara SP, Ortiz JF, Smith DW, et al. Crimean-Congo Hemorrhagic Fever Beyond Ribavirin: A Systematic Review. Cureus. 2021 Sep;13(9):e17842.
https://www.doi.org/10.7759/cureus.17842
http://www.ncbi.nlm.nih.gov/pubmed/34557373?tool=bestpractice.com
[108]Arab-Bafrani Z, Jabbari A, Mostakhdem Hashemi M, et al. Identification of the crucial parameters regarding the efficacy of ribavirin therapy in Crimean-Congo haemorrhagic fever (CCHF) patients: a systematic review and meta-analysis. J Antimicrob Chemother. 2019 Dec 1;74(12):3432-9.
https://academic.oup.com/jac/article/74/12/3432/5542609
http://www.ncbi.nlm.nih.gov/pubmed/31369086?tool=bestpractice.com
Further studies are needed to further clarify role of corticosteroids in the management of CCHF.
Favipiravir
Animal studies have shown the antiviral agent favipiravir to be effective in the treatment of CCHF, either alone or in combination with ribavirin.[109]Oestereich L, Rieger T, Neumann M, et al. Evaluation of antiviral efficacy of ribavirin, arbidol, and T-705 (favipiravir) in a mouse model for Crimean-Congo hemorrhagic fever. PLoS Negl Trop Dis. 2014;8:e2804.
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002804
http://www.ncbi.nlm.nih.gov/pubmed/24786461?tool=bestpractice.com
[110]Hawman DW, Haddock E, Meade-White K, et al. Efficacy of favipiravir (T-705) against Crimean-Congo hemorrhagic fever virus infection in cynomolgus macaques. Antiviral Res. 2020 Sep;181:104858.
http://www.ncbi.nlm.nih.gov/pubmed/32645335?tool=bestpractice.com
[111]Tipih T, Meade-White K, Rao D, et al. Favipiravir and Ribavirin protect immunocompetent mice from lethal CCHFV infection. Antiviral Res. 2023 Oct;218:105703.
https://www.doi.org/10.1016/j.antiviral.2023.105703
http://www.ncbi.nlm.nih.gov/pubmed/37611878?tool=bestpractice.com
[112]Wang Q, Cao R, Li L, et al. In vitro and in vivo efficacy of a novel nucleoside analog H44 against Crimean-Congo hemorrhagic fever virus. Antiviral Res. 2022 Mar;199:105273.
https://www.doi.org/10.1016/j.antiviral.2022.105273
http://www.ncbi.nlm.nih.gov/pubmed/35257725?tool=bestpractice.com
[113]Hawman DW, Haddock E, Meade-White K, et al. Favipiravir (T-705) but not ribavirin is effective against two distinct strains of Crimean-Congo hemorrhagic fever virus in mice. Antiviral Res. 2018 Sep;157:18-26.
https://www.doi.org/10.1016/j.antiviral.2018.06.013
http://www.ncbi.nlm.nih.gov/pubmed/29936152?tool=bestpractice.com
Plasma exchange
Therapeutic plasma exchange was associated with decreased mortality rates and may be a useful adjunct to antiviral therapy in patients with severe disease. However, evidence is limited (case reports and one small clinical trial).[114]Kurnaz F, Metan G, Coskun R, et al. A case of Crimean-Congo haemorrhagic fever successfully treated with therapeutic plasma exchange and ribavirin. Trop Doct. 2011 Jul;41(3):181-2.
https://www.doi.org/10.1258/td.2011.100470
http://www.ncbi.nlm.nih.gov/pubmed/21565949?tool=bestpractice.com
[115]Beştepe Dursun Z, Korkmaz S, Türe Z, et al. Efficacy of therapeutic plasma exchange in patients with Crimean-Congo hemorrhagic fever. J Clin Apher. 2021 Jun;36(3):390-7.
https://www.doi.org/10.1002/jca.21875
http://www.ncbi.nlm.nih.gov/pubmed/33485278?tool=bestpractice.com
[116]Gayretli Aydin ZG, Yesilbas O, Reis GP, et al. The first pediatric case of hemophagocytic lymphohistiocytosis secondary to Crimean-Congo haemorrhagic fever successfully treated with therapeutic plasma exchange accompanying ribavirin and intravenous immunoglobulin. J Clin Apher. 2021 Oct;36(5):780-4.
https://www.doi.org/10.1002/jca.21915
http://www.ncbi.nlm.nih.gov/pubmed/34061376?tool=bestpractice.com
[117]Ture Z, Kalin-Unuvar G. A case of Crimean Congo hemorrhagic fever complicated with acute pulmonary embolism. J Med Virol. 2021 Jun;93(6):3925-8.
https://www.doi.org/10.1002/jmv.26358
http://www.ncbi.nlm.nih.gov/pubmed/32716057?tool=bestpractice.com
[118]Meço BC, Memikoğlu O, Ilhan O, et al. Double filtration plasmapheresis for a case of Crimean-Congo hemorrhagic fever. Transfus Apher Sci. 2013 Jun;48(3):331-4.
https://www.doi.org/10.1016/j.transci.2013.04.011
http://www.ncbi.nlm.nih.gov/pubmed/23619328?tool=bestpractice.com
[119]Perk O, Emeksiz S, Ozcan S, et al. Crimean-Congo hemorrhagic fever: a pediatric case responding to plasmapheresis treatment. Transfus Apher Sci. 2021 Dec;60(6):103215.
https://www.doi.org/10.1016/j.transci.2021.103215
http://www.ncbi.nlm.nih.gov/pubmed/34366235?tool=bestpractice.com
Further studies are needed to determine whether this treatment has a role in the management of CCHF.