The persistence of endemic malaria infections and the increasing occurrence of antimalarial resistance necessitates the search for treatment strategies to combat and ultimately eradicate the disease. When considering treatment regimens, it also becomes important to consider the specific stages of the parasite life cycle that are affected by treatments. Of interest are the distinct within-host asexual and sexual stages which are associated with disease symptoms and transmission respectively. Ideally one should aim to target both stages to treat an ill patient and to prevent the further spread of the disease.

In this study, we investigated the use of monotherapies and dual therapy antimalarial treatment regimens by using published disease, pharmacokinetic and pharmacodynamic data and models. First, we constructed linked PKPD-disease models that contain a newly developed gametocyte description to account for observed time delays between parasite forms in clinical trial data. Candidate models were validated using clinical data to assess their ability to predict treatment outcomes in vivo, which was used to identify the most appropriate model for further analysis.

Our research also delved into the potential of a novel treatment approach. We evaluated disease outcomes in the model using a CDC-recommended administration of artesunate, used to treat severe P. falciparum malaria. We also explored the use of artemisinin-free combination therapy. This approach involved the repurposing of tafenoquine (a gametocytocidal) to target sexual forms, in combination with lumefantrine (a blood schizonticidal) to target asexual forms. Our model construction, validation, and analysis results will be presented.