Peri-domestic behaviour of African malaria vectors and the impact of insecticides

The most effective and widely used malaria vector control measures use insecticides to target the vector in the home environment and account for 60% of global investment in malaria control today. With the arrival and rapid spread of insecticide resistance in African malaria vectors, the need to find new approaches to indoor vector control has become urgent. Existing tools and the majority of new approaches for vector control are designed to target Anopheles sp. peri-domestic behaviours to deliver impact. Yet despite its importance in malaria epidemiology and control, very little is known about mosquito behaviour within the human home. Knowledge is limited to simple basics such as where mosquitoes enter and exit the house and that they rest within the home after bloodfeeding. Key questions about how they approach the house, where they fly in three-dimensional space, which sensory cues are critical and how they influence flight or entry behaviour remain unanswered. This lack of knowledge becomes even more apparent when investigating how mosquitoes interact with insecticides in the domestic environment.
Small, fast-flying and nocturnally active, Anopheles mosquito behaviour is not easily studied. Progress in this field has been hampered by the technological challenge of tracking anophelines and insight into the behaviour of anophelines will ultimately be the key to more effective vector control. Moreover, such studies are best undertaken in the mosquito's natural environment, to ensure accuracy and reliability. Tackling this challenge, we have developed robust mosquito tracking technology that overcomes many of the obstacles that prevented studies previously. Our tracking system can provide detailed visual recordings of nocturnal mosquito activity indoors, at a rural setting in the field in Tanzania, allowing detailed observation and subsequent analysis of the behaviour of wild populations of the Anopheles malaria vectors.
The project will use the tracking equipment in an experimental hut system in the field in Tanzania to deliver an evidence-based characterisation of anopheline mosquito behaviour in the human home. We will also examine how insecticide treatments deployed in the home affect behaviour to determine more precisely how existing vector control tools function and how they might be improved.
This unique collaboration utilises state-of-the-art technology deployed in a resource-poor setting to search for solutions to a disease affecting millions worldwide. Its findings will be fundamental to increasing understanding of the mechanisms of existing vector control tools, whilst potentially identifying targets for new tools in the near future.

Limited knowledge of malaria vector behaviour in the peri-domestic environment is a major obstacle to the development of better tools for vector control. We have developed robust mosquito tracking technology that overcomes many of those obstacles. The project will deploy the purpose-built and unique system in an experimental hut system at a rural setting in Tanzania, to record and analyse the behaviour of wild vector populations.
The first aim is to track and fully characterize endophilic and endophagic behaviour of Anopheles gambiae and other mosquitoes. In a specially constructed experimental hut, activity of mosquitoes responding to human volunteers will be recorded and analysed. Using human volunteers as 'bait', we will capture and describe the complete sequence of mosquito behaviour from arrival to exit, including the key events involved in orientation to, and bloodfeeding at humans. Data will be produced on entry and exit (location, timing), flight (flight type, 3D spatial location, velocity, tortuosity, saccades and other parameters) and resting (timing, location, duration) activities in periods of <3 days. We will use human volunteers of both sexes and a range of ethnicities and ages. We anticipate numerous valuable insights and the primary deliverable is detailed characterisation of Anopheles gambiae behaviour in the human home.
The second aim is to investigate behaviour in response to insecticide treatments. Here we will examine how insecticide-based interventions (long-lasting insecticide-treated bednets and durable wall linings) affect behaviour, to explore modes of action of existing tools. Fundamental to our study is the eventual translation of basic behaviour findings to design new tools; hence we will test mosquito response to a new, patent pending, LLIN design.
The findings will deliver important evidence for understanding mechanisms of existing vector control tools, whilst potentially identifying targets for new tools.

The project's primary goal is the enhancement of basic knowledge of the biology of mosquitoes, an essential step towards the rational design of effective control tools and strategies for reducing human malaria. Economic and societal impacts would impact primarily in sub-Saharan Africa, but be relevant to any malaria-endemic country. In the longer term, the same vector control tools could also be very effective against other diseases transmitted by other mosquitoes and arthropods.

Reducing the burden of malaria via improved vector control
The burden of malaria is one of mankind's greatest challenges. Globally, an estimated 3.4 billion people are at risk of malaria. In 2012, over 200 million cases and 627,000 deaths occurred, mostly in Africa where 77% were in children under 5 years of age. Global investment in malaria prevention and elimination is at an all-time high, and improved vector control tools remain a top priority if recent impacts on malaria are to be sustained. Rapidly emerging insecticide resistance represents an imminent threat. Application and usage of many insecticides and other chemical treatments, both existing and in-development, are limited for safety reasons, compromising the arsenal of tools available for improving vector control and for the management of insecticide resistance. Delivery of such new tools is a priority for WHO and the Global Malaria Action Plan.
Our proposal tackles these challenges head-on and our findings will be of immediate value and direct interest to WHO, Ministries of Health, NGOs, donor communities and the private sector, ultimately benefitting malaria-affected communities in endemic countries.

Ensuring sustainable cost-effective malaria control tools
Not all vector control tools that effectively target mosquitoes will also be suitable for deployment in disease-endemic communities, as numerous issues surrounding user perception of efficacy and benefit, as well as potential for routine, correct usage and frequency and cost of replenishment over time must all be considered. The applicants' experience in this respect will ensure that projects aims are developed, and outputs delivered, with a clear understanding of the realities and challenges of implementing effective sustainable vector control in sub-Saharan Africa.

Reducing insecticide quantities and risks
The global community is aware and highly sensitive to the risks of side-effects occurring during insecticide use. Our goal is to design tools that deliver insecticides in ways that reach the target pest species efficiently, whilst minimizing quantities of insecticide used and risks to users within and beyond the home.

Improved capacity for malaria research in Tanzania
Capacity strengthening is a cornerstone of LSTM's mission and this collaboration continues a long and productive association with many institutions in Tanzania by LSTM staff, including the PI. By undertaking virtually all of the experimental work in Tanzania, we are mutually dependent. UK partners will further ensure our commitment to colleagues in Tanzania by seeking additional training support for the PGRA, Jackline Martine, and also for other NIMR staff when future recruiting opportunities arise.