Clinical characterisation of bubonic plague

Despite affecting humans for more than 5000 years, the causative agent and mode of transmission of plague were established only some 150 years ago, and there have been limited drug development activities for plague.

 The drugs currently recommended to treat plague have been approved based on experimental data alone and no pivotal clinical trials have yet been completed to demonstrate the efficacy and safety of any novel or repurposed therapeutics. 

A major barrier to conducting trials is that there is limited existing published data to support the design of a clinical trial, including the important patient outcomes that could inform endpoint selection. We therefore conducted a systematic review to summarise the available information on the clinical profile of patients with confirmed and probable bubonic plague. By synthesising data on patient demographics, signs and symptoms at baseline and follow-up, and patient outcomes, we aimed to understand whether sufficient data exists to support the design of informative clinical trials that would provide clinicians and policy-makers with the information needed to make treatment decisions for patients.

Our systematic review included 87 publications that described 1343 patients with bubonic plague. A diverse group of signs and symptoms were reported at baseline and during follow-up – the most common of which was presence of a bubo. However, other than specifying the presence of at least one bubo, limited descriptive and longitudinal information was available about the bubo. The overall case fatality ratio was 15% with a median time from first presentation to death of 1 day (ranging from 0 to 16 days).

Findings: Our study found that, based on the existing literature, there is insufficient data that can be used to develop methodologies for future trials. This not only impacts endpoint selection but the interpretation of a trial’s results challenging. Either time must be invested in to collecting robust clinical data in observational studies or developing innovative trial designs that can simultaneously collect observational and interventional data. 

This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome.

(Reference: 216273/Z/19/Z)