DEFEND

The challenge

Around 280 million malaria infections occurred in 2024 in sub-Saharan Africa, leading to at least 600,000 deaths, most of them of children. Mosquito vectors have long been targeted in malaria control strategies, but these require the use of powerful chemicals and drive the development of insecticide resistance.

Alternative strategies are being investigated, including genetically modified mosquitoes resistant to infection with malaria parasites and the release of mosquitoes carrying Wolbachia bacteria, which disrupt parasite development.

Another bacterium found in some wild mosquito populations, Delftia tsuruhatensis TC1, has also been found to kill malaria parasites without affecting mosquito survival. The supernatant (liquid floating on the surface) collected from cultured TC1 cells is also highly toxic to malaria parasites. The lethal compound in it, harmane, is active at extremely low concentrations and does not appear to harm either people or pollinators such as bees.

The project

The DEFEND project is advancing the clinical development of TC1-based transmission-blocking strategies and exploring novel approaches to regulatory approval to accelerate their introduction.

Studies to date, including laboratory evaluations and enclosed field studies (in a ‘MosquitoSphere’ in Burkina Faso), have generated highly encouraging findings, setting the stage for a large-scale efficacy trial. However, the TC1 intervention is unusual and demonstrating health impact in a trial setting is challenging. A cluster-randomised trial to demonstrate effects on community malaria burden would need to be very large and would be costly and time-consuming.

The project is therefore exploring an alternative approach, based on assessing TC1’s impact at the individual mosquito level. In areas of Burkina Faso and Senegal, traps are being used to capture mosquitoes around houses and the numbers infected with malaria parasites are being counted. The number of infected mosquitoes in areas where TC1 has been introduced will be compared with the numbers in control areas. Measured effects on parasite carriage will be used to infer the likely impact of TC1 introduction on malaria burden in local populations. 

At the same time, the project team is working on a new type of feeder that will attract mosquitoes, infect them with TC1, or ensure the uptake of harmane. Community consultations are being arranged to assess the acceptability of the approach and any possible obstacles to its use. 

A further critical strand of the project involves dialogue with national regulatory agencies and global policymaking groups to determine which evidence on impact and safety is needed to support licensing and policy recommendations.    

Impact

The DEFEND project is advancing the development of an environmentally friendly vector-focused approach to control malaria. It will:

• Reveal whether TC1 and/or harmane reduce carriage of malaria parasites in mosquitoes in real-world settings.
• Provide an estimate of the impact of their use on the community burden of malaria.
• Map out a path to regulatory approval and policy recommendations that could be followed by other similar interventions.

Ultimately, the DEFEND project could add to the basket of interventions available to control one of the most important causes of death in young children in sub-Saharan Africa.