Ribavirin for treating Crimean Congo haemorrhagic fever

Abstract

BackgroundCrimean Congo haemorrhagic fever (CCHF) is a tick-borne disease that occurs in parts of Asia, Europe and Africa. Since 2000 the infection has caused epidemics in Turkey, Iran, Russia, Uganda and Pakistan. Good-quality general supportive medical care helps reduce mortality. There is uncertainty and controversy about treating CCHF with the antiviral drug ribavirin.ObjectivesTo assess the effects of ribavirin for treating people with Crimean Congo haemorrhagic fever.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register; the Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (OVID); Science Citation Index-Expanded, Social Sciences Citation index, conference proceedings (Web of Science); and CINAHL (EBSCOHost). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for trials in progress. We conducted all searches up to 16 October 2017. We also contacted experts in the field and obtained further studies from these sources.Selection criteriaWe evaluated studies assessing the use of ribavirin in people with suspected or confirmed Crimean Congo haemorrhagic fever. We included randomised control trials (RCTs); non-randomised studies (NRSs) that included more than 10 participants designed as cohort studies with comparators; and case-control studies.Data collection and analysisTwo review authors assessed eligibility, risk of bias, and extracted data. For non-randomized studies we used the ROBINS-I tool to assess risk of bias. The main effects analysis included all studies where we judged the risk of bias to be low, moderate or high. We summarized dichotomous outcomes using risk ratios (RRs) and continuous outcomes using mean differences (MDs), and used meta-analyses where appropriate. We carried out a subsidiary appraisal and analysis of studies with critical risk of bias for the primary outcome, as these are often cited to support using ribavirin.Main resultsFor the main effects analysis, five studies met our inclusion criteria: one RCT with 136 participants and four non-randomized studies with 612 participants. We excluded 18 non-randomized studies with critical risk of bias, where none had attempted to control for confounding.We do not know if ribavirin reduces mortality (1 RCT; RR 1.13, 95% confidence interval (CI) 0.29 to 4.32; 136 participants; very low-certainty evidence; 3 non-randomized studies; RR 0.72, 95% CI 0.41 to 1.28; 549 participants; very low-certainty evidence). We do not know if ribavirin reduces the length of stay in hospital (1 RCT: mean difference (MD) 0.70 days, 95% CI -0.39 to 1.79; 136 participants; and 1 non-randomized study: MD -0.80, 95% CI -2.70 to 1.10; 50 participants; very low-certainty evidence). We do not know if it reduces the risk of patients needing platelet transfusions (1 RCT: RR 1.23, 95% CI 0.77 to 1.96; 136 participants; very low-certainty evidence). For adverse effects (including haemolytic anaemia and a need to discontinue treatment), we do not know whether there is a...

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

“…There is no approved antiviral treatment. Although the antiviral drug ribavirin is widely used based on its in vitro activity, clinical evidence is inconclusive 30–36. Postexposure prophylaxis using ribavirin is controversial but recommended as a safe option for healthcare providers with high-risk/direct exposure to CCHF-infected patient fluids or tissue 15 17 37 38…”

Antivirals in medical biodefense

“…Ribavirin has been used to treat CCHF patients under compassionate use protocols with some success since 1985 [140], especially if given early in the course of the infection, but many studies with apparently beneficial results lack controls. Recent randomized clinical trials were unable to show significant beneficial effects of ribavirin versus CCHFV [70,78]. Further interesting candidates for virus-specific treatment ( Table 1) include favipiravir (T-705), which has been evaluated against a number of phleboviruses (PhleboV) and to treat CCHFV infection in rodent models [53,54,59], galidesivir (BCX4430), effective against Rift Valley fever virus (RVFV) infection in a hamster model and investigated for use by the FDA [145], 2′-fluoro-2′-deoxycytidine (2FdC), which showed protective effects against infections with PhleboV in a rodent model [134], and the FGI-106 entry inhibitor [135].…”

Recent advances in understanding Crimean–Congo hemorrhagic fever virus

“…Ribavirin, a nucleoside analog, is suggested by the World Health Organization for the treatment of CCHFV. However, clinical data supporting the use of ribavirin to treat CCHF are inconsistent; some studies report benefits whereas others report no benefit, and meta-analyses of multiple studies suggest that the efficacy of ribavirin is poor or inconclusive 69 – 71 . Notably, a placebo-controlled study failed to identify a clinical benefit of ribavirin treatment in patients with CCHF 72 .…”