A “lethal house lure” approach for the control of insecticide resistant African malaria vectors

It is now widely accepted that even with universal access and greater use of existing core malaria control measures, elimination of the disease will prove unattainable, especially in areas holoendemic for malaria. There is therefore a major public health imperative to identify new effective interventions to consolidate the major but fragile gains achieved over recent years. House improvement contributed to malaria elimination in developed countries but its potential as a vector control method remains generally underexploited in Africa. In2Care’s electrostatic charged netting is a core component of the novel In2Care® EaveTubes vector control method, which is an example prototype belonging to a new house-based intervention class defined by the Vector Control Advisory Group (VCAG) as “lethal house lure”. It is described as “Modifications made to a house to decrease exposure of inhabitants to vector”. Although a range of laboratory and semi field studies provided some evidence on its potential to reduce malaria transmission, very little is known about its mode of functioning (“modus operandi”) if deployed in mass at village level for vector control. To fill this gap in knowledge, the present PhD project was designed as part of a cluster randomized controlled trial (CRT) evaluating the epidemiological impact of this new intervention in areas highly affected by pyrethroid resistance in central Côte d’Ivoire. A series of resistance genotyping, laboratory and experimental hut studies were performed: (i) to investigate initially the dynamics of insecticide resistance and associated genetic mechanisms in Anopheles mosquitoes from the trial area and explore its entomological impact on pyrethroid-only LLINs, (ii) to select and evaluate a long-lasting insecticide for use in In2Care® EaveTubes and investigate whether the community-wide deployment of EaveTubes treated with the chosen insecticide would exert any selection pressure on mosquitoes and (iii) explore whether existing vector control technologies including new generation LLIN or IRS insecticide formulations could be adapted to serve as alternative options for delivering insecticides in EaveTubes. Resistance to insecticides from major classes was prevalent prior to the trial and was mediated primarily by target-site mutations and detoxification enzymes including cytochrome P450s and carboxylesterase. Pyrethroid resistance levels were extremely high and was shown to compromise the performance of pyrethroid-only LLIN in experimental huts. Although a wide range of insecticide classes could be deployed in EaveTubes for effective control of pyrethroid resistant mosquitoes, only the pyrethroid beta-cyfluthrin was durable and was associated with ~50% reduction in overnight mosquito survival in hut studies. However, the community-level use of beta-cyfluthrin treated EaveTubes resulted in a significant increase in the intensity of pyrethroid resistance over two years and, this was underpinned by a temporal increase in expression of metabolic genes coupled with the rise of cuticular genes over the course of the CRT. Alternative ways of delivering insecticides in EaveTubes by using netting from new generation LLIN or dipping the tube in insecticide solutions was shown to provide similar levels of control as with electrostatic netting despite low persistence. These studies demonstrate the significant malaria control potential of EaveTubes in areas with extremely high pyrethroid resistance and stress the need for further optimization of the intervention.