Mathematical Modelling to Guide Drug Development for Malaria Elimination
Authors: Hannah C. Slater, Lucy C. Okell, Azra C. Ghani
Mathematical models of the dynamics of a drug within the host are now frequently used to guide drug development. These generally focus on assessing the efficacy and duration of response to guide patient therapy. Increasingly, antimalarial drugs are used at the population level, to clear infections, provide chemoprevention, and to reduce onward transmission of infection. However, there is less clarity on the extent to which different drug properties are important for these different uses. In addition, the emergence of drug resistance poses new threats to longer-term use and highlights the need for rational drug development. Here, we argue that integrating within-host pharmacokinetic and pharmacodynamic (PK/PD) models with mathematical models for the population-level transmission of malaria is key to guiding optimal drug design to aid malaria elimination.
Trends
Antimalarial drugs are now being utilized in various ways beyond their primary purpose of treating the disease. One emerging application is their use in reducing malaria transmission within communities.
Different antimalarial drugs possess unique characteristics, such as their effectiveness in killing asexual parasites, duration of action, ability to target gametocytes and mosquitoes, impact on liver-stage activity (particularly for Plasmodium vivax), recommended dosage schedules, and potential toxicity.
To maximize their effectiveness, it is crucial to strategically combine these drug attributes based on a quantitative understanding of their properties and intended usage goals.
When aiming to reduce malaria transmission, an individual patient-focused approach becomes less significant, and instead, a population-level perspective becomes crucial.
To effectively combine antimalarial drugs with other malaria control measures and achieve significant reductions in transmission, it is essential to employ rational approaches. However, due to the challenge of testing all possible intervention combinations across various settings, transmission models informed by field data are relied upon to guide decision-making.
Keywords
malaria; Plasmodium falciparum; Plasmodium vivax; mathematical modelling; drug development; drug-based strategies
Citation: Hannah C. Slater, Lucy C. Okell, Azra C. Ghani Mathematical Modelling to Guide Drug Development for Malaria Elimination http://dx.doi.org/10.1016/j.pt.2016.09.004
Available online: 7 October 2016
Copyright: © 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Acknowledgments
We acknowledge support from the Medicines for Malaria Venture and the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement. H.S. acknowledges support from an Imperial College Junior Research Fellowship. L.O. acknowledges support from a Royal Society Fellowship.
