Current status of experimental models for the study of malaria

Infection by malaria parasites (Plasmodium spp.) remains one of the leading causes of morbidity and mortality, especially in tropical regions of the world. Despite the availability of malaria control tools such as integrated vector management and effective therapeutics, these measures have been continuously undermined by the emergence of vector resistance to insecticides or parasite resistance to frontline antimalarial drugs. Whilst the recent pilot implementation of the RTS,S malaria vaccine is indeed a remarkable feat, highly effective vaccines against malaria remain elusive. The barriers to effective vaccines result from the complexity of both the malaria parasite lifecycle and the parasite as an organism itself with consequent major gaps in our understanding of their biology. Historically and due to the practical and ethical difficulties of working with human malaria infections, research into malaria parasite biology has been extensively facilitated by animal models. Animals have been used to study disease pathogenesis, host immune responses and their (dys)regulation and further disease processes such as transmission. Moreover, animal models remain at the forefront of pre-clinical evaluations of antimalarial drugs (drug efficacy, mode of action, mode of resistance) and vaccines. In this review, we discuss commonly used animal models of malaria, the parasite species used and their advantages and limitations which hinder their extrapolation to actual human disease. We also place into this context the most recent developments such as organoid technologies and humanized mice.