Artemisinin derivatives are the first line treatment for falciparum malaria. Alarmingly, resistance to these drugs has emerged in Southeast Asia, jeopardizing malaria control. Mathematical models integrating blood antimalarial drug concentrations with the parasite-time profile of an infected individual provide an avenue to studying drug action. We have developed biologically informed within-host mathematical models for exploring treatment outcomes following artemisinin-based combination therapies. See our online tool for interactive simulations of patient parasite profiles following malaria treatments. We have expanded our model to include transmission dynamics and future developments will incorporate innate and acquired immunity. We apply state of the art Bayesian methods to validate the within-host models against data from controlled human malaria infection studies and multinational clinical trials (see ACREME website for our network of collaborators and regional partners).
- Development and validation of an in silico decision-tool to guide optimisation of intravenous artesunate dosing regimens for severe falciparum malaria patients
- Modeling the dynamics of Plasmodium falciparum gametocytes in humans during malaria infection
- Evaluating antimalarial efficacy in single-armed and comparative drug trials using competing risk survival analysis: a simulation study.
- In silico investigation of the decline in clinical efficacy of artemisinin combination therapies due to increasing artemisinin and partner drug resistance
- Investigating the efficacy of triple artemisinin-based combination therapies (TACTs) for treating Plasmodium falciparum malaria patients using mathematical modelling. Antimicrob Agents Chemother AAC.01068-18.
- Assessing the utility of an anti-malarial pharmacokinetic-pharmacodynamic model for aiding drug clinical development. Malar J 11:303.
- Population Pharmacokinetics of Intravenous Artesunate: A Pooled Analysis of Individual Data From Patients With Severe Malaria. CPT Pharmacometrics Syst Pharmacol 3:145.
- Making the Most of Clinical Data: Reviewing the Role of Pharmacokinetic-Pharmacodynamic Models of Anti-malarial Drugs. AAPS J 16:962–974.
- A Dynamic Stress Model Explains the Delayed Drug Effect in Artemisinin Treatment of Plasmodium falciparum. Antimicrob Agents Chemother 61:e00618-17.
- Parasite Strain, Host Immunity, and Circulating Blood Cells with Dead Parasites: Why Predicting Malaria Parasite Clearance Is Not a Simple Task. Antimicrob Agents Chemother 60:1172.
- A mechanistic model quantifies artemisinin-induced parasite growth retardation in blood-stage Plasmodium falciparum infection. J Theor Biol 430:117–127.
Other related Publications:
- Parasite-Host Dynamics throughout Antimalarial Drug Development Stages Complicate the Translation of Parasite Clearance
- Modelling the time course of antimalarial parasite killing: a tour of animal and human models, translation and challenges. Br J Clin Pharmacol 79:97–107.
- Statistical methods to derive efficacy estimates of anti-malarials for uncomplicated Plasmodium falciparum malaria: pitfalls and challenges. Malar J 16:430.
- Within-host modeling of blood-stage malaria. Immunol Rev 285:168–193.
- Implications of population-level immunity for the emergence of artemisinin-resistant malaria: a mathematical model. Malar J 17:279.