A controlled human malaria infection model enabling evaluation of transmission-blocking interventions

Area of Science:

• * Infectious Diseases
• * Malariology
• * Clinical Trials

Background:

• * Malaria control and elimination efforts require drugs and vaccines to interrupt Plasmodium falciparum transmission.
• * Current models for early clinical evaluation of transmission-blocking interventions are limited.
• * A novel human model using controlled human malaria infection (CHMI) is introduced to assess malaria transmission from humans to Anopheles mosquitoes.

Purpose of the Study:

• * To establish and validate a new model for evaluating malaria transmission-blocking interventions.
• * To assess the safety and reproducibility of inducing Plasmodium falciparum gametocytes in healthy volunteers.
• * To evaluate the efficacy of candidate drugs in reducing gametocyte burden and transmission.

Main Methods:

• * Seventeen healthy, malaria-naive volunteers underwent CHMI with P. falciparum-infected erythrocytes.
• * Piperaquine was administered to attenuate asexual parasite replication while allowing gametocyte development.
• * Participants received either artefenomel, primaquine, or no treatment to assess gametocytocidal activity.

Main Results:

• * Plasmodium falciparum gametocytes were successfully induced in all participants, with 73% achieving transmission to mosquitoes.
• * Primaquine significantly reduced gametocyte burden, while artefenomel showed no effect compared to untreated controls.
• * The CHMI model was safe and well-tolerated, with mostly mild to moderate adverse events attributed to malaria infection.

Conclusions:

• * The developed CHMI model safely and reproducibly induces Plasmodium falciparum gametocytes at infectious densities in humans.
• * This model demonstrates significant potential for the evaluation of novel transmission-blocking interventions.
• * Further research can utilize this model to accelerate the development of tools for malaria elimination.