Transmission

Kamuzu University Of Health Sciences, Blantyre

Investigators

Abstract

SUMMARY – PROJECT 2 Vector control, the mainstay of malaria prevention over the past few decades, has recently become less effective due in part to expanding insecticide resistance and changing mosquito behaviors involving more outdoor and early-evening/dawn biting. We have designed studies with the overall goal of understanding and overcoming the limitations of the current vector control strategies for further reductions of the burden of malaria globally, and specifically in Malawi. First, we will assess the effects of vector control interventions on population patterns of two important malaria parasite vectors, Anopheles funestus and An. arabiensis, in environmentally diverse sites with different transmission intensities, using a robust dataset from historical and prospective household-level vector sampling (Aim 1). Statistical models will also assess whether National Malaria Control Program sentinel surveillance sites are adequately representative and informative for evaluating vector control interventions nationwide. In another set of household-level studies, we will use human-landing catch methods to quantify the time of day and indoor/outdoor location when Anopheles species-specific biting behavior is occurring in different socio-ecological settings and seasons. We will then characterize the contribution of differences in the observed vector biting patterns to Plasmodium falciparum transmission (Aim 2), using concurrent measures of people's activity patterns, bed net use, infection status, and malaria incidence rate in coordination with the Epidemiology Project of this ICEMR Program. We expect these analyses will identify policy-relevant risks that could tailor implementation of existing vector control tools. These first two Aims, combined with the studies proposed in the Epidemiology Project, will provide a valuable multidisciplinary evaluation of the current malaria prevention tools used in Malawi. Our third Aim is designed to inform the development of potential future malaria prevention tools. In these proposes studies, we will assess the transmission-blocking activity of novel antimalarial compounds targeting mosquitoes under field-like conditions (Aim 3). All experiments will use field-derived, insecticide- resistant An. funestus and An. arabiensis mosquitoes, and P. falciparum parasites currently circulating in Malawi. We will initially assess compound uptake and stability under laboratory conditions and quantify P. falciparum infection in mosquitoes exposed to treated net material, either with the novel compounds alone or in combination with the insecticide deltamethrin. Additional experiments will be conducted using a screened-in experimental hut setup, which will provide results under field-like conditions. Results will be incorporated into a mathematical model of malaria transmission to evaluate the potential public health impact of antimalarial-treated nets. Taken together, the proposed research program is designed to identify components of current malaria intervention strategies that may limit their long-term effectiveness, while also assessing opportunities for improved strategies through enhanced vector surveillance and novel interventions with unique mechanisms of action.