Time to reconsider the role of ribavirin in Lassa fever

Jul 8, 2021

Ribavirin is the only available Lassa fever–specific treatment and has been used routinely for over 25 years. However, Ribavirin is not licensed for Lassa fever, its mechanism of action is unclear, it’s expensive and hard to source, and it has well-known toxicities.

The rationale for using ribavirin in Lassa fever is primarily based on one clinical trial (McCormick et al, 1986) conducted in Sierra Leone in the late 1970s and early 1980s. We reconstructed the derivations from this trial, and identified numerous methodological flaws including comparisons between non-randomised and non-matched groups and post hoc merging of treatment groups. This trial reports a subset of a much larger dataset assembled by the Lassa treatment unit in Sierra Leone and the United States Army Medical Research and Development Command, that was until recently unavailable to the public.

Although this dataset suffers from numerous issues re-analysis of the available data suggests that ribavirin reduced mortality only in patients with serum aspartate transaminase (AST) ≥150 IU/L, with less benefit than reported by McCormick et al.

However, ribavirin appeared to increase mortality in patients with serum AST <150 IU/L. In the analysis, the only group in which ribavirin appeared protective was patients with a serum AST >300 IU/L. Ribavirin was associated with overall increased mortality, although this was attenuated after adjustment for AST. The limitations revealed by this newly available dataset, such as large amounts of missing data, unclear treatment allocation practices, imbalances in treatment groups, and errors in coding serology results, cast further doubt on the conclusions of the McCormick study.

There is therefore a compelling case to re-evaluate the role of ribavirin in the care of patients with Lassa fever. Vigorous efforts should be made to engage clinicians and patients in designing a placebo-controlled trial to assess the safety and efficacy of Ribavirin treatment in Lassa fever patients, particularly in those with milder disease (as may be indicated by an admission AST <150 IU/L) in whom the available evidence is compatible with ribavirin causing more harm than good.

Read the article on the use of Ribavirin for Lassa fever at PLOS