Abstract

Drug resistance has rendered most of the antimalarial drugs ineffective. In addition, utilization of some of the antimalarial drugs has been limited by their toxic effects due to prolonged treatment regimens. The long treatment period affects compliance, which contributes to the development of drug resistance. As such, malaria continues to be a major health problem in resource-constrained regions of the world. This has necessitated the search for new antimalarial drugs. Several natural products and synthetic compounds have exhibited potent antimalarial activity in vitro and in mouse studies. On the other hand, there is a paucity of new chemical entities being developed into antimalarial products, thus pointing to the existence of potentially distinct disconnects between pre-clinical and clinical development. Lack of relevant models in pre-clinical development to provide reasonable prior dose estimates that would be optimally safe and efficacious during clinical evaluation in patients is one of the main impediments. In this review, we discuss the limitations of the in vitro and in vivo models of antimalarial drug efficacy studies and highlight the relevance of the Plasmodium knowlesi–baboon (Papio anubis) malaria model in strengthening the antimalarial drug development pipeline. Plasmodium knowlesi–baboon model provides an opportunity for fast tracking the translation of pre-clinical findings to the clinical phase, thus bridging the wide gap between mice and humans in the antimalarial drugs development pipeline. This review suggests the utilization of the Plasmodium knowlesi–baboon model in translational research to support accelerated antimalarial drug discovery and development.

Key words: Malaria, Antimalarial drug development, Translational research, Plasmodium knowlesi, Baboon