The study was published yesterday in Science Translational Medicine.
The researchers developed a mathematical model to assess the relationship between piperaquine concentrations in patient plasma and the risk among healthy males of acquiring a malaria infection. Piperaquine concentrations of 6.7 ng/mL and 20 ng/mL were found to reduce the risk of acquiring a malaria infection by 50 per cent and 95 per cent, respectively.
Simulations were used to translate the results from the studied male population to a population of children. This showed that increasing the dose in children could potentially decrease the yearly incidence of malaria from 6 per cent to 2 per cent, during preventive treatment under certain conditions – a relative decrease of 70 per cent.
The modelling and simulation of vulnerable populations such as children and pregnant women is a valuable method, since actual dosing studies on these groups are difficult to perform.
The researchers also used mathematical models to investigate the consequence of a potential emerging resistance to piperaquine. These simulations indicated that even moderate resistance to piperaquine can be expected to drastically compromise the usefulness of piperaquine in preventive therapy. A doubling of the piperaquine concentration needed to reduce the risk of a malaria infection by 50 per cent would increase the yearly incidence from 2% to 10% under similar conditions. This emphasizes the need for a correct use of piperaquine, in order to minimize the risk for development of widespread resistance.