DEFEND · Delftia TsuruhatensTC1 Based-Intervention For Interrupting Malaria Transmission In Mosquitoes: A Novel Trial For Evaluating Alternative Tools For Control Of Vector-Borne Diseases

Malaria eradication efforts are severely hampered by the rapid emergence and spread of resistance in mosquitoes due to widespread use of insecticide-based vector-control tools. Recently, we have published a study proposing a novel malaria intervention strategy based on the use of a bacterial strain, Delftia tsuruhatensis TC1 (TC1 for short) and its secreted active component, Harmane (HA). The TC1-intervention interrupts malaria parasite development in mosquitoes without affecting mosquito survival and fitness thereby circumventing selection of resistant mosquitoes. Extensive studies to evaluate efficacy, safety and manufacturability have been successfully completed in both, laboratory and contained semi-field settings and further validate use of the TC1-intervention for malaria control. Although, WHO has established product evaluation pathways and regulatory pipelines for insecticide-based vector control tools these are not suited for TC1 and other ‘TC1-like’ control strategies which do not fall within the ‘main-stream’ conventional category of malaria vector-control tools. To date all vector control tools have been evaluated in cluster randomized control trials (RCTs) to demonstrate epidemiological benefit but RCTs are becoming increasingly difficult and extremely expensive to conduct as standard-of-care increases the heterogeneity between clusters, diminishes the effect size of novel interventions thereby requiring higher numbers of clusters to reliably power studies. An urgent need exists for rigorous and validated entomological metrics which infer epidemiological benefit. This project aims to develop a novel trial for generating the evidence base of the TC1-intervention in open-field settings at the scale of the individual mosquito, to help support the regulatory process and expedite the time between product development and widespread deployment. Additionally, this novel trial could be extrapolated to similar interventions for controlling vector-borne diseases.