Abstract
BackgroundAnti-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.MethodsPopulation 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).ResultsA 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.ConclusionsThe 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.
Highlights
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
The fundamental qualitative difference between combination therapy and the other policies is that CT is a strong driver of multiple drug resistance with frequency of the multi-resistant genotype usually above 50% at the end of its useful therapeutic lifespan (Figure 2A)
The multi-resistant genotype is the only one that can resist treatment under combination therapy so most resistant genotypes are multi-drug resistant under this deployment policy
Summary
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. 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 replaced by the drug in the sequence. The provision of effective anti-malarial drugs is a mainstay of public health policies aimed at reducing morbidity and mortality [3]. An alternative strategy would be to deliberately deploy multiple first-line therapy (MFT) simultaneously, resulting in malaria infections being treated with different drugs. Widespread provision of different drugs through the informal, private sector may already result in a de facto situation of MFT in many countries [8]
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