Mathematical Modeling of Malaria: Theories of Malaria Elimination

dissertation describes the development and application of a new mathematical model for simulating the progression of Plasmodium falciparum infections in individuals with no malarial acquired immunity. The model allows for stochastic simulation of asexual and sexual parasitemias as well as the onset of fever and human to mosquito infectivity on a daily time scale. The model components for the asexual and sexual stages were developed elsewhere but are here extended to allow for simulation of the full range of dynamics observed in a subset of malaria therapy patients. As a first application of the model, I calculate the human component of malarial R0, the basic reproductive number. I then compare this value to those from three other models and describe how this quantity can be used to model malaria transmission. The second application of the model incorporates the effects of drug treatment on progression of infection by utilizing modeled pharmacokinetic and pharmacodynamic properties of a variety of antimalarials. I utilize a stage specific proportional killing model for sexual stages, informed from recent in vitro data. The relationship of effect sizes to treatment coverage and type of treatment in both early and late treatment seeking settings is calculated. In the third chapter, I consider the economic and epidemiological ramifications of antimalarial and rapid diagnostic subsidization for malaria control. For the epidemiological modeling I utilize a semi-mechanistic model of the spread of drug resistanc