Policy options for deploying anti-malarial drugs in endemic countries: a population genetics approach

Background: Anti-malarial drugs are constantly exposed to the threat of evolving drug resistance so good stewardship of existing therapy is an essential component of public health policy. However, the widespread availability of numerous different drugs through informal providers could undermine official drug deployment policies. A policy of multiple first-line therapy (MFT) is compared with the conventional policy of sequential drug deployment, i.e., where one drug is used until resistance evolves and then replaced by the next drug in the sequence. Methods: Population genetic models of drug resistance are used to make the comparison; this methodology explicitly tracks the genetics of drug resistance (including, importantly, recombination in the sexual stage, intrahost dynamics, and direction of linkage disequilibrium). Results: A policy of MFT outlasts sequential application providing drug usages are low to moderate, and appears not to drive widespread multi-drug resistance. Inadequate dosing is an even more potent driver of drug resistance than the MFT/sequential policy decision. Conclusions: The provision of MFT as a deliberate policy can be encouraged provided overall treatment rates are low or moderate (less than around half of malaria infections are treated) and the ad hoc provision of MFT through the private sector may be tolerated. This must be fully supported by education to ensure people take adequate doses of each of the drugs.