Modeling of leishmaniasis infection dynamics: novel application to the design of effective therapies

Four biologically significant variables were chosen to develop a differential equation model based on the GMA power-law formalism. Parameters were determined to minimize error in the model dynamics and time series experimental data. Subsequently, the model robustness was tested and the model predictions were verified by comparing them with experimental observations made in different experimental conditions. The model obtained helps to quantify relationships between the selected variables, leads to a better understanding of disease progression, and aids in the identification of crucial points for introducing therapeutic methods.Our model can be used to identify the biological factors that must be changed to minimize parasite load in the host body, and contributes to the design of effective therapies.The WHO considers leishmaniasis as one of the six most important tropical diseases worldwide [1]. It is caused by parasites of the genus Leishmania that are passed to humans and animals by sandflies of the subfamily Phlebotominae [2]. Leishmaniasis, which is endemic in 88 countries, has an annual incidence of two million cases and is estimated to cause over 50,000 deaths per year [3]. The disease has three main forms: cutaneous leishmaniasis, mucocutaneous leishmaniasis and visceral leishmaniasis. Visceral leishmaniasis, the most severe form of the disease, is also known as "kala azar", "black fever" or "dumdum fever". It especially affects hosts with weak immune systems, such as children or adults suffering from malnutrition or HIV. The human immune response that limits leishmaniasis is mediated by Th1 cells that activate macrophages to kill the parasite (cellular immunity). When cellular immunity is deficient, an expansion of Th2 cells occurs which allows the parasite to survive within the monocytes and fosters disease development [4]. After an incubation period that varies from ten days to two years [3], typical symptoms are fever, diarrhea, body weight loss, lymphaden