Multi-scale mathematical modelling of parasite, drug and vaccine interactions: optimising public health and disease elimination strategies

Objectives

The overall goal of this project is to combine preclinical and clinical data from the Swiss Tropical and Public Health Institute and partners to build mathematical models to inform the development of new malaria drugs and vaccines.

Specifically, one aim is to define which type and how to use these tools within populations for malaria elimination, especially in light of drug resistance. This project will yield evidence to accelerate decisions in drug and vaccine development.

Specific objectives:

1. To elucidate the link between preclinical malaria parasite-drug dynamics and host-parasite-drug dynamics in early human clinical testing. Through model development and use of extensive preclinical and clinical data, the team will explore predictability of pharmaco-kinetic and -dynamic determinants in preclinical models for optimal human dosing.
2. To understand and optimise malaria vaccine immunogenicity and protection combining early clinical data and newly developed mathematical models. Through simulation of parasite and immune kinetic models, fitted to individual-level data, the team will evaluate kinetics resulting in longer protection.
3. To determine key vaccine, operational, population, and epidemiological determinants of public health impact when targeting malaria control and elimination, by linking models of individual immunity with population-scale models.
4. To optimise the role of new drugs and intervention strategies for malaria elimination and mitigation of drug resistance. Through the development of new models of evolution of malaria drug resistance, drug properties, operational and health system factors that limit drug resistance and assist in malaria elimination will be elucidated.
5. As an overarching aim these building blocks will be brought together by synthesising evidence from the global community and from aims 1-4 to influence the models and to guide profiles of drugs and vaccines for malaria control and elimination thus ensuring integration of the findings of the model-based research into a systematic framework for the innovation of new tools from preclinical stages to delivery.