Ribavirin for patients with Crimean-Congo haemorrhagic fever: a systematic review and meta-analysis

Background: Crimean-Congo haemorrhagic fever (CCHF) is a potentially fatal tick-borne infection. The virus is widely distributed around the world and reports of sporadic cases and outbreaks have recently increased significantly. Some authors have proposed that ribavirin improves survival in CCHF and this view appears to be widely accepted. Methods: We evaluated the efficacy of ribavirin in reducing mortality by conducting a systematic review and meta-analysis. We included randomized controlled trials and observational studies that compared the outcomes of CCHF patients who were treated with ribavirin with those of patients that were not treated. The main endpoint we assessed was survival. We also evaluated secondary endpoints, i.e. adverse events, length of stay in the hospital, time taken for laboratory values to return to normal and requirement for blood products. A pooled estimate of the relative risks for survival from each study was obtained by using random effects models. Results: One randomized controlled trial and seven observational studies met our inclusion criteria. Most observational studies suffered from different types of bias due to inappropriate selection of controls. Compilation of data from all included studies showed that ribavirin did not improve survival in CCHF (relative risk 1.06, 95% confidence interval 0.97-1.16). Analysis of secondary endpoints did not suggest a clinically significant beneficial effect either. Conclusions: Our systematic review and meta-analysis revealed that the available data in the literature are inadequate to support a claim of efficacy of ribavirin in CCHF. We believe a real uncertainty exists over the benefit of ribavirin in the treatment of CCHF, which necessitates the urgent conduct of a randomized placebo-controlled trial.