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Successful programmatic use of anti-malarials faces challenges that are not covered by standard drug development processes. The development of appropriate pragmatic dosing regimens for low-resource settings or community-based use is not formally regulated, even though these may alter factors which can substantially affect individual patient and population(More)
Mechanism-based pharmacokinetic-pharmacodynamic (PK/PD) modelling is the standard computational technique for simulating drug treatment of infectious diseases with the potential to enhance our understanding of drug treatment outcomes, drug deployment strategies, and dosing regimens. Standard methodologies assume only a single drug is used, it acts only in(More)
Effective population-level interventions against Plasmodium falciparum malaria lead to age-shifts, delayed morbidity or rebounds in morbidity and mortality whenever they are deployed in ways that do not permanently interrupt transmission. When long-term intervention programmes target specific age-groups of human hosts, the age-specific morbidity rates(More)
Pharmacological modeling of antiparasitic treatment based on a drug's pharmacokinetic and pharmacodynamic properties plays an increasingly important role in identifying optimal drug dosing regimens and predicting their potential impact on control and elimination programs. Conventional modeling of treatment relies on methods that do not distinguish between(More)
The long half-lives of malaria ‘partner’ drugs are a potent force selecting for drug resistance. Clinical trials can quantify this effect by estimating a window of selection (WoS), defined as the amount of time post-treatment when drug levels are sufficiently high that resistant parasites can re-establish an infection while preventing drug-sensitive(More)
The standard drug development process for antimalarials and other drugs uses weight-based dosing (mg/kg) to predict blood concentrations of the drug, and hence their effect. Consequently, the current World Health Organization Guidelines for the treatment of malaria [1] provide target doses and therapeutic dose ranges in mg/ kg/day. However, in resource-poor(More)
Most current antimalarial drugs are combinations of an artemisinin plus a 'partner' drug from another class, and are known as artemisinin-based combination therapies (ACTs). They are the frontline drugs in treating human malaria infections. They also have a public-health role as an essential component of recent, comprehensive scale-ups of malaria(More)
The search for highly effective anti-malarial therapies has gathered pace and recent years have seen a number of promising single and combined therapies reach the late stages of development. A key drug development challenge is the need for early assessment of the clinical utility of new drug leads as it is often unclear for developers whether efforts should(More)
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