Abstract
Resistance to antimalarial drugs is currently a growing public health problem, resulting in more cases with treatment failure. Although previous studies suggested that a concentration gradient facilitates the antibiotic resistance evolution in bacteria, no attempt has been made to investigate the roles of a concentration gradient in malaria drug resistance. Unlike the person-to-person mode of transmission of bacteria, the malaria parasites need to switch back and forth between the human and mosquito hosts to complete the life cycle and to spread the resistant alleles. Here we developed a stochastic combined within- and between-hosts evolutionary dynamics model specific to malaria parasites in order to investigate the influence of an antimalarial concentration gradient on the evolutionary dynamics of malaria drug resistance. Every stage of malaria development in both human and mosquito hosts are individually modelled using the tau-leaping algorithm. We found that the concentration gradient can accelerate antimalarial resistance evolution. The gain in resistance evolution was improved by the increase in the parasite mutation rate and the mosquito biting rate. In addition, even though the rate of resistance evolution is not sensitive to the changes in parasite reduction ratios (PRRs) of antimalarial drugs, the probability of finding the antimalarial drug resistant parasites decreases when the PRR increases.
Highlights
Resistance to antimalarial drugs is currently a growing public health problem, resulting in more cases with treatment failure
The original staircase model was used to assess the evolutionary dynamics of antibiotic resistance in bacteria
We adapted the original framework to investigate the roles of a concentration gradient in malaria drug resistance evolution in malaria parasites
Summary
Resistance to antimalarial drugs is currently a growing public health problem, resulting in more cases with treatment failure. Previous studies suggested that a concentration gradient facilitates the antibiotic resistance evolution in bacteria, no attempt has been made to investigate the roles of a concentration gradient in malaria drug resistance. Antimalarial drug resistance gives the parasite an opportunity to survive under antimalarial pressure When resistance emerges, it prolongs the illness and delays the clearance time, resulting in treatment failure. Many experimental studies have investigated the effects of the concentration gradient in the drug resistance evolution of bacteria[10,11]. Under the drug concentration gradient, the resistance to ciprofloxacin was found within 10 hours, as opposed to 25 hours with no emergence of drug resistance in the homogeneous environment[10] This demonstrated that spatial heterogeneity can accelerate the drug resistance evolution in bacteria. The analytical and numerical results of this study showed that drug concentration gradients can promote antibiotic resistance
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