at the Doctoral Program in Complexity Sciences

João Sequeira

Transition from endemic behavior to eradication of malaria due to combined drug therapies: an agent-model approach

We propose an agent-based model describing a susceptible-infectious-susceptible (SIS) system of humans and mosquitoes to predict malaria epidemiological scenarios in realistic biological conditions. Emphasis is given to the transition from endemic behavior to eradication of malaria transmission induced by combined drug therapies acting on both the gametocytemia reduction and on the selective mosquito mortality during parasite development in the mosquito. Our mathematical framework enables to uncover the critical values of the parameters characterizing the effect of each drug therapy.

Moreover, our results provide quantitative evidence of what was up to now only partially assumed with empirical support: interventions combining gametocytemia reduction through the use of gametocidal drugs, with the selective action of ivermectin during parasite development in the mosquito, may actively promote disease eradication in the long run. In the agent model, the main properties of human-mosquito interactions are implemented as parameters and the model is validated by comparing simulations with real data of malaria incidence collected in the endemic malaria region of Chimoio in Mozambique.

Time series of weekly malaria incidence, comparing empirical data against data from one realization of the agent model.

We present numerical evidence that in communities of individuals having an affinity varying within a broad range of values, disease transmission may increase up to 300%. Moreover, our findings provide new insight into how to combine different strategies for the prevention of malaria transmission. In particular, we uncover a relationship between the level of heterogeneity and the level of conventional and unconventional anti-malarial drug administration (ivermectin and gametocidal agents), which, when taken together, will define a control parameter, tuning between disease persistence and elimination.

The basic reproduction number and the annual entomological inoculation rate, both as a function of the ivermectin probability and heterogeneous affinity.

Finally, we also provide evidence that the entomological inoculation rate, as well as the product between parasite and sporozoite rates are both good indicators of malaria incidence in the presence of heterogeneity in disease transmission and may configure a possible improvement in that setting, upon classical standard measures such as the basic reproductive number.


  • João Sequeira; Jorge Louçã; António M. Mendes; Pedro Lind. A Model for Assessing the Quantitative Effects of Heterogeneous Affinity in Malaria Transmission along with Ivermectin Mass Administration. Applied Sciences, Ed. MDPI AG, 10(23), 8696, 4 December 2020. Access here.
  • João Sequeira; Jorge Louçã; António M. Mendes; Pedro Lind. Transition from endemic behavior to eradication of malaria due to combined drug therapies: an agent-model approach. Journal of Theoretical Biology, Ed. Academic Press, Vol.484, 7 January 2020. Access here.