Trial reportThe Journal of infectious diseases2021
A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite-Induced Controlled Malaria Infection.
Trial report in The Journal of infectious diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03454048 (Controlled Human Malaria Infection Study to Assess Gametocytemia and Mosquito Transmissibility in Participants Challenged With Plasmodium Falciparum by Sporozoite or Blood Stage Challenge to Establish a Model for the Evaluation of Transmission-blocking Interventions), which is not on this map. Cited by 19 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.
Controlled Human Malaria Infection Study to Assess Gametocytemia and Mosquito Transmissibility in Participants Challenged With Plasmodium Falciparum by Sporozoite or Blood Stage Challenge to Establish a Model for the Evaluation of Transmission-blocking Interventions
Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Transmissibility of a new Plasmodium falciparum 3D7 bank for use in malaria volunteer infection studies evaluating transmission blocking interventions.Scientific reports · 2025Trial
- The Effect of Artemether-Lumefantrine Combined with a Single Dose of Primaquine onTropical medicine and infectious disease · 2026Article
- An all-in-one pipeline for the in vitro discovery and in vivo testing of Plasmodium falciparum malaria transmission blocking drugs.Nature communications · 2025Article
- Controlled human malaria infection: overview and potential application in the evaluation of transmission-blocking interventions in malaria-endemic areas.Malaria journal · 2025Review
- Controlled human malaria infection studies: insights into recent advances and key immunological and ethical implementation lessons.Frontiers in immunology · 2025Review
- Plasmodium falciparum gametocyte production correlates with genetic markers of parasite replication but is not influenced by experimental exposure to mosquito biting.EBioMedicine · 2024Article
- Article
- Genetic complexity alters drug susceptibility of asexual and gametocyte stages ofAntimicrobial agents and chemotherapy · 2024Article
- Plasmodium falciparum gametocyte carriage in longitudinally monitored incident infections is associated with duration of infection and human host factors.Scientific reports · 2023Article
- A Critical Review on Human Malaria and Schistosomiasis Vaccines: Current State, Recent Advancements, and Developments.Vaccines · 2023Review
- Article
- Safety, Tolerability, and Parasite Clearance Kinetics in Controlled Human Malaria Infection after Direct Venous Inoculation of Plasmodium falciparum Sporozoites: A Model for Evaluating New Blood-Stage Antimalarial Drugs.The American journal of tropical medicine and hygiene · 2022Article
- Controlled Human Infection Models To Accelerate Vaccine Development.Clinical microbiology reviews · 2022Review
- Controlled human malaria infections by mosquito bites induce more severe clinical symptoms than asexual blood-stage challenge infections.EBioMedicine · 2022Article
- The acquisition of humoral immune responses targetingFrontiers in immunology · 2022Article
- Quantifying Reductions inFrontiers in immunology · 2022Article
- Gametocyte carriage after seasonal malaria chemoprevention in Plasmodium falciparum infected asymptomatic children.Malaria journal · 2021Article
- Development and evaluation of a new Plasmodium falciparum 3D7 blood stage malaria cell bank for use in malaria volunteer infection studies.Malaria journal · 2021Article
- Novel Method for the Separation of Male and Female Gametocytes of the Malaria ParasitemSphere · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFor malaria elimination efforts, it is important to better understand parasite transmission to mosquitoes and develop models for early-clinical evaluation of transmission-blocking interventions.
methodsIn a randomized open-label trial, 24 participants were infected by bites from Plasmodium falciparum 3D7-infected mosquitoes (mosquito bite [MB]; n = 12) or by induced blood-stage malaria (IBSM) with the same parasite line (n = 12). After subcurative piperaquine treatment, asexual parasite and gametocytes kinetics were assessed, and mosquito feeding experiments were performed.
resultsStudy procedures were well tolerated. The median peak gametocyte density was 1304/mL (interquartile range, 308-1607/mL) after IBSM, compared with 14/mL (10-64/mL) after MB inoculation (P < .001), despite similar peak asexual parasite densities (P = .48). Peak gametocyte density was correlated with preceding pfap2-g transcripts, indicative of gametocyte commitment (ρ = 0.62; P = .002). Direct feeding assays resulted in mosquito infections from 9 of 12 participants after IBSM versus 0 of 12 after MB inoculation (P < .001).
conclusionsWe observed a striking effect of inoculation method on gametocyte production, suggesting higher gametocyte commitment after IBSM. Our direct comparison of MB and IBSM establishes the controlled human malaria infection transmission model, using intravenous administration of P. falciparum-infected erythrocytes as a model for early-clinical evaluation of interventions that aim to interrupt malaria transmission. CLINICAL
trial registrationNCT03454048.
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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.