Ensemble modeling highlights importance of understanding parasite-host behavior in preclinical antimalarial drug development.

ABSTRACT: Emerging drug resistance and high-attrition rates in early and late stage drug development necessitate accelerated development of antimalarial compounds. However, systematic and meaningful translation of drug efficacy and host-parasite dynamics between preclinical testing stages is missing. We developed an ensemble of mathematical within-host parasite growth and antimalarial action models, fitted to extensive data from four antimalarials with different modes of action, to assess host-parasite interactions in two preclinical drug testing systems of murine parasite P. berghei in mice, and human parasite P. falciparum in immune-deficient mice. We find properties of the host-parasite system, namely resource availability, parasite maturation and virulence, drive P. berghei dynamics and drug eff

SUBMITTER: Burgert L 

PROVIDER: S-EPMC7064600 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature