Current status of experimental models for the study of malaria

Abstract

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.

Methylene Blue-Based Combination Therapy with Amodiaquine Prevents Severe Malaria in an Experimental Rodent Model

“…In vivo pre-clinical studies allow for evaluation of in vivo drug activity, pharmacodynamics and pharmacokinetics and toxicities. However, the results obtained may vary between humans and other species [ 66 ]. A dose of 500 mg of methylene blue led to an average maximum concentration (C max ) of 1600 ng/mL in plasma and an elimination half-life time (t 1/2 ) of 7.2 h in humans [ 67 ].…”

The Potential of Human Defensin 5 (HD5) as a Novel Strategy for Malaria Control: Inhibition of Plasmodium Development in Anopheles

“…The animal model of An. stephensi and Plasmodium yoelii that infect rodents (mice) was often used to study the relationship between the vector and the disease (Simwela and Waters, 2022). Based on the above analysis, it is wondering that whether HD5 can regulate the innate immunity of An.…”

A stochastic model for malaria and its behavior under insecticide‐treated nets

“…19 introduced a stochastic model for malaria by introducing Brownian motion into fluctuations around the steady‐state point. We refer to recent articles regarding models for malaria 20,21,22,23,24,25,26 …”

“…We refer to recent articles regarding models for malaria. 20,21,22,23,24,25,26 There are many other different approaches of introducing randomness via stochasticity, but the one that is presented in this paper is different compared with the mentioned ones.…”