ArticleScientific reports2020
Ensemble modeling highlights importance of understanding parasite-host behavior in preclinical antimalarial drug development.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Pharmacokinetic and pharmacodynamic modeling of anti-plasmodial drugs mefloquine plus artesunate: insights on translational application.Antimicrobial agents and chemotherapy · 2026Article
- The Importance of Murine Models in Determining In Vivo Pharmacokinetics, Safety, and Efficacy in Antimalarial Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Plant-based nanoparticles targeting malaria management.Frontiers in pharmacology · 2024Review
- Cytotoxicity and immunological impact of Trypanosoma sp. infection on blood parameters of wild African catfish, Clarias gariepinus.Parasitology research · 2023Article
- Predicting Optimal Antimalarial Drug Combinations from a Standardized Plasmodium falciparum Humanized Mouse Model.Antimicrobial agents and chemotherapy · 2023Article
- Parasite Viability as a Measure ofAntimicrobial agents and chemotherapy · 2022Article
- Combined Transcriptome and Proteome Profiling for Role of pfEMP1 in Antimalarial Mechanism of Action of Dihydroartemisinin.Microbiology spectrum · 2021Article
- Druggable hot spots in trypanothione reductase: novel insights and opportunities for drug discovery revealed by DRUGpy.Journal of computer-aided molecular design · 2021Article
- Parasite-Host Dynamics throughout Antimalarial Drug Development Stages Complicate the Translation of Parasite Clearance.Antimicrobial agents and chemotherapy · 2021Article
- Mechanisms of artemether toxicity on single cardiomyocytes and protective effect of nanoencapsulation.British journal of pharmacology · 2020Article
- Leveraging Computational Modeling to Understand Infectious Diseases.Current pathobiology reports · 2020Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 efficacy, whereas experimental constraints primarily influence P. falciparum infection and drug efficacy. Furthermore, uninvestigated parasite behavior such as dormancy influences parasite recrudescence following non-curative treatment and requires further investigation. Taken together, host-parasite interactions should be considered for meaningful translation of pharmacodynamic properties between murine systems and for predicting human efficacious treatment.
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