Artemether-lumefantrine (AL) is the most widely recommended and prescribed antimalarial worldwide. Clinical trials have clearly demonstrated its safety and efficacy. Timely access to quality-assured antimalarials is vitally important, both to ensure good clinical outcomes and minimise onwards transmission of the parasite.
In recently published work , we developed a within-host model of falciparum malaria to assess the performance of AL in routine healthcare settings, where adherence to treatment may be imperfect. To do this, we utilised individual-level data on patient adherence. Here we focused on the parasitological outcomes for the patient: we now develop our investigation to quantify the impact that poor adherence has on malaria transmission. With the aid of malaria therapy data, we extend our model to include gametocyte production, explicitly modelling both the immature (sequestered) and mature parasites. With the aid of likelihood-free inference methods, we used individual-level data from clinical trials to calibrate a pharmacodynamic model, quantifying the drug action against sexual-stage parasites. Using our model, we highlight the importance of timely access to treatment by showing how delay to treatment leads to an increase in circulating gametocytes post treatment. In addition, we use adherence data for 482 patients taking a course of AL, collected in Tanzania in 2012, to assess the contribution that sub-optimal adherence makes to transmission of the malaria parasite.