Abstract
The spread of drug resistance represents a significant challenge to many disease control efforts. The evolution of resistance is a complex process influenced by transmission dynamics between hosts as well as infection dynamics within these hosts. This study aims to investigate how these two processes combine to impact the evolution of resistance in malaria parasites. We introduce a stochastic modelling framework combining an epidemiological model of Plasmodium transmission and an explicit within-human infection model for two competing strains. Immunity, treatment and resistance costs are included in the within-host model. We show that the spread of resistance is generally less likely in areas of intense transmission, and therefore of increased competition between strains, an effect exacerbated when costs of resistance are higher. We also illustrate how treatment influences the spread of resistance, with a trade-off between slowing resistance and curbing disease incidence. We show that treatment coverage has a stronger impact on disease prevalence, whereas treatment efficacy primarily affects resistance spread, suggesting that coverage should constitute the primary focus of control efforts. Finally, we illustrate the importance of feedbacks between modelling scales. Overall, our results underline the importance of concomitantly modelling the evolution of resistance within and between hosts.
Highlights
Antimalarial drugs, along with vector control, are an essential pillar of malaria control throughout malaria-endemic areas [1]
We find that in high transmission settings, the proportion of resistant parasites in the simulated population after 5 years is lower (F 1⁄4 13.12, p, 0.001, logit-transformed data) than in low transmission settings, the effect remains relatively weak with the default value of the cost of resistance (f2 1⁄4 0.01)
We introduced in this study a model combining within-host and between-hosts modelling scales, and we have shown that the dynamics of two competing strains, sensitive and resistant, depend on specific assumptions at each of these scales and on interactions between dynamics across scales
Summary
Antimalarial drugs, along with vector control, are an essential pillar of malaria control throughout malaria-endemic areas [1]. Several pharmaceutical compounds have been promoted as first-line defences against Plasmodium in a number of large-scale control efforts. Their efficacy, has systematically been compromised after several years of intense usage owing to the appearance and spread of parasite strains resistant to each of these drugs [2,3,4]. Given the current importance of artemisinin-based combination therapies in the worldwide fight against malaria, the selection and spread of these (at least partially) resistant strains would have potentially dramatic consequences for malaria control [3]
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