Efficacy of antibiotic medication strategy following a bioterrorist attack involving Francisella tularensis

Abstract

Francisella tularensis is a virulent bacterium which hijacks the host’s immune response, turning cells usually tasked with killing foreign organisms as nutrient-rich receptacles for rapid multiplication. It is designated a Tier 1 Select Agent by the US CDC due to its potential to cause widespread mortality upon deliberate release. In this study, the key biological mechanisms of host infection are modelled as a continuous-time Markov chain (CTMC) and solved via discrete event simulation (DES). The efficacy of various medication strategies at the behest of public health authorities are investigated. Without treatment, the median lethal dose – not previously considered in humans – is estimated at approximately 1,000 organisms. Results suggest that fatality can be averted if antibiotics are administered for at least 7 days, no later than 10 days post exposure. In a mass casualty setting, this can reduce symptomatic cases by 18% from the baseline involving no medication. Reductions of 59% are possible if medication can be disseminated no later than 5 days post exposure, mitigating otherwise severe pressure on healthcare services. Novel use of CTMC and DES highlight the potential for OR in the field of immunology, where further opportunities may present in a post COVID-19 world.

Keywords:

• Bioterrorism
• tularaemia
• operational research
• Markov models
• discrete event simulation

Acknowledgements

The authors are grateful to the anonymous reviewers whose helpful and constructive comments have improved the legibility and quality of this article.

Disclosure statement

The authors declare that they have no competing interests. No specific funding was received for this study.

Author contributions

RW conceived the study, developed the model, produced the outputs, and wrote the manuscript. RW and IH designed the study, undertook the literature review, and reviewed the manuscript.