Salmonella Typhi and antimicrobial Resistance - modelling Impact of Vaccination and antimicrobial use to control typhoid fEver (STRIVE)

The bacterium Salmonella Typhi causes typhoid fever and is responsible for >100,000 deaths annually, primarily among young children in South Asia and sub-Saharan Africa. This global public health threat will likely be exacerbated by increasing antimicrobial resistance (AMR); resistance to all antimicrobials recommended for typhoid treatment has been reported in South Asia. In 2018, the World Health Organization recommended the use of typhoid conjugate vaccines (TCVs) in endemic regions, but uptake has been limited and their long-term impact on the bacterial population structure and AMR is unclear. In addition, we urgently need data on optimal use of existing antimicrobials to maximise their clinically useful lifespan. In this fellowship, I will utilise genomic data to evaluate the impact of TCVs on bacterial populations. I will model alternative antimicrobial usage strategies that may delay the emergence of AMR in exemplar settings in Asia and Africa, leveraging phylodynamic insights from large genomic datasets to inform updated model parameterisation. Finally, I will integrate novel genomic and AMR data to model the impact of TCVs on AMR in these two settings. This will enable me to develop comprehensive, localised typhoid control strategies, and to estimate their long-term impact on AMR and bacterial populations.