Ribavirin for Crimean-Congo hemorrhagic fever: systematic review and meta-analysis

Abstract

BackgroundCrimean-Congo hemorrhagic fever epidemics often occur in areas where health services are limited, and result in high case fatality rates. Besides intensive care, ribavirin is often recommended. A solid evidence base for the use of this drug will help justify assuring access to the drug in areas where epidemics are common.MethodsWe carried out a systematic review of observational and experimental studies of people with suspected or confirmed Crimean-Congo hemorrhagic fever that included comparisons between patients given ribavirin and those not. We extracted data on mortality, hospital stay, and adverse events. Risk of bias was assessed using a standard checklist, and data were presented in meta-analytical graphs, stratified by study design, and GRADE tables presented. The risk of bias was summarised using the GRADE method.Results21 unique studies, including one randomised controlled trial of ribavirin, were included. Quality of the evidence was very low, with a Down and Black median score of 4 (maximum possible 33). Ribavirin treatment was not shown to be superior to no ribavirin treatment for mortality rate in a single RCT (RR: 1.13, 95%CI: 0.29 to 4.32, 136 participants, GRADE=low quality evidence); but ribavirin was associated with reduced mortality by 44% when compared to no ribavirin treatment in the pooled observational studies (RR: 0.56, 95%CI: 0.35 to 0.90, 955 participants; GRADE=very low quality evidence). Adverse events were more common with the ribavirin patients, but no severe adverse events were reported. No difference in length of hospital stay was reported.ConclusionsNo clear message of benefit is available from the current data on ribavirin as observational data are heavily confounded, and the one trial carried out has limited power. However, ribavirin could potentially have benefits in this condition and these results clearly indicate a pragmatic, randomised controlled trial in the context of good quality supportive care, is urgently needed and ethically justified.

Evaluation of cases with a preliminary diagnosis of Crimean- Congo hemorrhagic fever and comparison of characteristics in patients admitted to a secondary care hospital in Kastamonu, Turkey.

“…Although most reports claimed a therapeutic benefit about ribavirin use, the quality of the evidence was low. In general, treatment of CCHF is mainly supportive therapy 9,10,35,36 . In our study, the case who died did not receive ribarivin therapy and three of CCHF cases received oral ribavirin.…”

Crimean-Congo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity

“…However, a recent attempt to identify a benefit of ribavirin in a randomized clinical trial was unable to show that treatment significantly altered the disease (Koksal et al, 2010). A review of 21 published observational and experimental studies of ribavirin therapy concluded that, although most reports claimed a therapeutic benefit, the quality of the evidence was low (Soares-Weiser et al, 2010). The authors concluded that ''a randomized controlled trial in the context of good quality supportive care is justified.''…”

“…The use of ribavirin for the treatment of CCHF has been reviewed in detail in two recent articles (Soares-Weiser et al, 2010;Keshtkar-Jahromi et al, 2011). The drug was first employed in 1985, when it was given as postexposure prophylaxis in a nosocomial outbreak in South Africa (van de Wal et al, 1985).…”

Crimean-Congo hemorrhagic fever: Risk factors and control measures for the infection abatement

“…However, ribavirin (Virazole) is the only antiviral drug used against CCHFV, which is only effective in certain cases (61). Despite the verified insufficient efficacy of ribavirin for CCHF patients by two systematic reviews and meta-analyses, the World Health Organization has approved antiviral ribavirin for treatment of CCHFV infection based on in vitro data (7,60,62,63). Ribavirin can be taken orally and intravenously.…”