Trial reportAntimicrobial agents and chemotherapy2016
Linking Murine and Human Plasmodium falciparum Challenge Models in a Translational Path for Antimalarial Drug Development.
Trial report in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- Safety, pharmacokinetics, and antimalarial activity of the novel plasmodium eukaryotic translation elongation factor 2 inhibitor M5717: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study and volunteer infection study.The Lancet. Infectious diseases · 2021Trial
- Safety, tolerability, pharmacokinetics, and activity of the novel long-acting antimalarial DSM265: a two-part first-in-human phase 1a/1b randomised study.The Lancet. Infectious diseases · 2017Trial
- A Phase II pilot trial to evaluate safety and efficacy of ferroquine against early Plasmodium falciparum in an induced blood-stage malaria infection study.Malaria journal · 2016Trial
- Pharmacokinetics and Pharmacodynamics of Antimalarial Agents: Optimizing Combination Therapies to Overcome Resistance Mechanisms.Journal of clinical pharmacology · 2026Review
- Pharmacokinetic and pharmacodynamic modeling of anti-plasmodial drugs mefloquine plus artesunate: insights on translational application.Antimicrobial agents and chemotherapy · 2026Article
- Emerging Role of Splenic Macrophage in Malaria Pathogenesis and Immunity.Immunity, inflammation and disease · 2025Review
- The Importance of Murine Models in Determining In Vivo Pharmacokinetics, Safety, and Efficacy in Antimalarial Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Senna occidentalis (L.) Link root extract inhibits Plasmodium growth in vitro and in mice.BMC complementary medicine and therapies · 2023Article
- Methylene Blue-Based Combination Therapy with Amodiaquine Prevents Severe Malaria in an Experimental Rodent Model.Pharmaceutics · 2022Article
- Scoping Review of Antimalarial Drug Candidates in Phase I and II Drug Development.Antimicrobial agents and chemotherapy · 2022Article
- Malaria PK/PD and the Role Pharmacometrics Can Play in the Global Health Arena: Malaria Treatment Regimens for Vulnerable Populations.Clinical pharmacology and therapeutics · 2021Review
- Parasite-Host Dynamics throughout Antimalarial Drug Development Stages Complicate the Translation of Parasite Clearance.Antimicrobial agents and chemotherapy · 2021Article
- Retrospective Analysis Using Pharmacokinetic/Pharmacodynamic Modeling and Simulation Offers Improvements in Efficiency of the Design of Volunteer Infection Studies for Antimalarial Drug Development.Clinical and translational science · 2021Article
- Defining the Antimalarial Activity of Cipargamin in Healthy Volunteers Experimentally Infected with Blood-Stage Plasmodium falciparum.Antimicrobial agents and chemotherapy · 2021Article
- Liver Enzyme Elevations inThe American journal of tropical medicine and hygiene · 2020Article
- Ensemble modeling highlights importance of understanding parasite-host behavior in preclinical antimalarial drug development.Scientific reports · 2020Article
- Growth Rate of Plasmodium falciparum: Analysis of Parasite Growth Data From Malaria Volunteer Infection Studies.The Journal of infectious diseases · 2020Article
- An in vitro toolbox to accelerate anti-malarial drug discovery and development.Malaria journal · 2020Article
- Searching for Improved Flu Vaccines-The Time Is Now.The Journal of infectious diseases · 2020Article
- AttenuatedFrontiers in immunology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 7 institutions in 3 countries.
Funding
Abstract
Effective progression of candidate antimalarials is dependent on optimal dosing in clinical studies, which is determined by a sound understanding of pharmacokinetics and pharmacodynamics (PK/PD). Recently, two important translational models for antimalarials have been developed: the NOD/SCID/IL2Rγ(-/-) (NSG) model, whereby mice are engrafted with noninfected and Plasmodium falciparum-infected human erythrocytes, and the induced blood-stage malaria (IBSM) model in human volunteers. The antimalarial mefloquine was used to directly measure the PK/PD in both models, which were compared to previously published trial data for malaria patients. The clinical part was a single-center, controlled study using a blood-stage Plasmodium falciparum challenge inoculum in volunteers to characterize the effectiveness of mefloquine against early malaria. The study was conducted in three cohorts (n = 8 each) using different doses of mefloquine. The characteristic delay in onset of action of about 24 h was seen in both NSG and IBSM systems. In vivo 50% inhibitory concentrations (IC50s) were estimated at 2.0 μg/ml and 1.8 μg/ml in the NSG and IBSM models, respectively, aligning with 1.8 μg/ml reported previously for patients. In the IBSM model, the parasite reduction ratios were 157 and 195 for the 10- and 15-mg/kg doses, within the range of previously reported clinical data for patients but significantly lower than observed in the mouse model. Linking mouse and human challenge models to clinical trial data can accelerate the accrual of critical data on antimalarial drug activity. Such data can guide large clinical trials required for development of urgently needed novel antimalarial combinations. (This trial was registered at the Australian New Zealand Clinical Trials Registry [http://anzctr.org.au] under registration number ACTRN12612000323820.).
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.