New Approaches for Addressing Outdoor/Residual Malaria Transmission (Round 15)

Opportunity:

There is critical need to develop new vector control methods to address malaria parasite transmission that occurs outdoors. Long-lasting insecticide treated nets (LLINs) and indoor residual sprays (IRS) are effective in preventing transmission within houses at night. However, individuals who spend time outdoors between evening and early morning are at risk of acquiring malaria due to a lack of effective anti-vector tools designed specifically to prevent outdoor (or what is referred to here as "residual" transmission).^[1] The term residual transmission is defined as all forms of transmission that persist after universal coverage has been achieved with effective LLIN and IRS interventions. Outdoor laborers and persons living outside enclosed structures are at greatest risk of acquiring malaria because they are not protected by LLINs and IRS interventions during times when they and malaria vectors are most active. Furthermore, National Malaria Control Programs face the threat of persistent, residual transmission despite having achieved significant reductions in malaria through the successful scaling up of LLIN and IRS activities. While these interventions remain effective against indoor-biting mosquitoes, a significant gap remains in addressing the residual transmission that occurs outside the protection of indoor-based interventions.

The diverse malaria vector species that can mediate transmission despite high coverage of LLINs and IRS all exhibit one or more of the following behavioral traits that allow them to evade fatal exposure to insecticides applied indoors:^[2]

Feeding outdoors, which attenuates personal protection and any potential for community-wide protection provided to humans sleeping under LLINs or in houses treated with IRS;
Resting outdoors, which precludes contact with insecticide treated surfaces of LLINs or walls and roofs treated with IRS;
Insecticide contact avoidance and early-exit behaviors that minimize exposure of indoor feeding vectors;
Preference for feeding upon animals rather than humans, allowing mosquitoes to minimize contact with LLINs and IRS targeted at humans and their dwellings.

The Challenge:

In many settings, residual transmission - mediated by mosquitoes exhibiting the behaviors listed above - is or will be of sufficient magnitude to render eradication of malaria infeasible with complementary diagnosis and treatment alone.^[2] Going beyond the current limitations of impact that can be achieved with effective IRS and LLINs will require new or improved vector control methods that:

Extend coverage of vector control measures to kill or repel adult mosquitoes when they bite people outdoors;
Enhance measures that kill, repel or exclude adult mosquitoes seeking to enter houses to rest after feeding outdoors;
Extend coverage of vector control measures to kill adult mosquitoes that readily feed on both livestock and human hosts;
Target source reduction efforts toward the immature stages of mosquitoes in their aquatic habitats;

What we're looking for:

We seek proposals that address the diversity of vector behaviors that contribute to residual transmission in malaria endemic settings. Preference will be given to ideas that are relevant to Foundation priority geographies: Southern Africa, the Greater Mekong Sub-region and Hispaniola and approaches that address anopheline vector behaviors or developmental stages listed above. A successful proposal will::

Include a clear statement of the hypothesis to be tested as well as the specific aims of the proposed intervention;
Describe a suitable intervention or tool that is feasible in malaria endemic, low-resource settings;
Include a description of how the proposed intervention addresses gaps in protection with existing vector control interventions or how the proposed intervention/tool(s) will complement or enhance current interventions;
Describe a path to operationalization for the proposed intervention(s) among key human populations (e.g. agricultural, forestry, and mining laborers and military personnel) in priority geographies listed above; and
Provide a clear plan to increase global access to the proposed intervention(s) to ensure that the poorest of the poor have access to any knowledge or products developed.

What we will consider funding:

A successful proposal will describe how the proposed intervention tool will address one or more of the following: 1) prevention of contact between humans and malaria vectors; 2) suppression of vector populations; and 3) a reduction in the capacity of vectors to transmit malaria parasites to humans.Preference will be given to proposals that address residual transmission among key populations in one or more of the priority geographies listed above.

Some examples of intervention tools or approaches we will consider include (but are not limited to):

Integration of personal protection products or clothing into bite-protection systems that require a minimal effort by the user;
Novel "attract, and kill" approaches;
Novel, scalable, ecologically appropriate, source reduction methods;
Integrated intervention and entomological surveillance measures that allow for the direct measurement of transmission intensity;
Approaches that target other common or shared mosquito behaviors that would reduce or eliminate vector populations.

What we will not consider funding:

Applications proposing basic research without clear relevance to the goals of this topic;
Ideas that do not specifically address malaria as the primary focus of the work;
Ideas that are not directly relevant to malaria endemic settings;
Ideas without a clearly articulated and testable hypothesis and metrics;
Ideas for which the described indicator of success cannot be demonstrated within the scope of the GCE Phase 1 award ($100,000 over 18 months);
Ideas that combine the delivery of multiple drugs or pesticide exposure without evidence of safety;
Ideas based exclusively on incremental improvements to current interventions and tools (e.g. pyrethroid-based LLIN, IRS-based approaches);
Solely infrastructure or capacity-building initiatives;
Proposals involving clinical trials in human volunteers or patients or large-scale field trials at this time (although those may be needed in the future).

Examples of research areas that will not be considered in this call for proposals include genetically modified mosquitoes, homing endonuclease gene-based approaches, Wolbachia/symbiont refactory-inducing technologies, sterile insect release approaches, biological control methods that employ predatory/larvivorous fish, and application of currently approved larvicides.

References

^[1] Durnez L., Coosemans M. Anopheles mosquitoes - New insights into malaria vectors; Chapter 21: Residual Transmission of Malaria: An Old Issue for New Approaches, book edited by Sylvie Manguin, ISBN 978-953-51-1188-7.

^[2] ^[a],^[b] Killeen GF, 2014. Characterizing, controlling and eliminating residual malaria transmission, Malar J. 2014 Aug 23; 13(1):330.