Evaluation of Malaria Parasite Transmission Competency Using a Nanozyme-Based Immunodiagnostic Targeting Female Gamete Antigen Release.

Abstract

Preventing malaria parasite transmission to the mosquito vector is a key elimination challenge that could benefit from a diagnostic test that can identify transmission-competent individuals. Only sexual parasite forms, called gametocytes, which activate into gametes (gametogenesis) upon mosquito uptake or blood sampling are responsible for transmission. Herein, we devised a nanozyme-based immunoassay to detect the <i>Plasmodium falciparum</i> female gametocyte activation antigen <i>Pf</i>G377, which is released during gametogenesis. Initial validation of our nanozyme assay with cultured parasites demonstrated that levels of <i>Pf</i>G377 were higher in supernatants of activated versus nonactivated cultures and those treated with transmission blocking drugs. To define the field potential of this approach, patient samples from a clinical transmission-focused trial were used, including those receiving treatment with the gametocytocidal drug primaquine (PQ) that sterilizes gametocytes and blocks transmission. PQ-treated patient samples showed significantly lower signals of <i>Pf</i>G377 2 days after treatment, consistent with an inability of PQ-treated gametocytes to activate and release antigen upon blood sampling. This study serves as a pathfinder for field transmission rapid diagnostics to detect transmission-competent individuals, which could help revive malaria elimination strategies.