Accelerating malaria prevention through enhanced analysis of transmission and RTS,S vaccination in Malawi

OVERALL SUMMARY Malaria remains stubbornly entrenched in Malawi, a poverty-stricken, ecologically diverse country in south- eastern Africa. A variety of reasons for this intransigence of malaria have emerged from our current and past ICEMR-based research:  Most severe disease and death occur in young children, but school-age children are more commonly parasitemic and represented an asymptomatic (and thus hidden) reservoir of infection  Two Anopheles species transmit the majority of Plasmodium infections, but their abundances are very heterogeneous and increasing insecticide resistance has dramatically reduced effectiveness of the most important control methods: insecticide-treated bed nets and indoor residual spraying Other studies in Malawi have shown that important Anopheles vectors have evolved to bite at places (outdoors) and times (early evening) when people are not sleeping under bed nets. In addition, a promising new anti- Plasmodium vaccine, RTS, S/AS01 (RTS, S) administered to young children, appears to be efficacious in Phase III and pilot studies in Malawi. These findings and insights are the basis for our proposed research program. Following a WHO-sponsored pilot and recommendation, RTS, S vaccination roll out is currently happening in several districts across Malawi, allowing us to study vaccination impacts on pediatric malaria risk (Epidemiology Project). A national-level distribution of new dual-insecticide bed nets (dual-AI LLIN) creates an opportunity for complementary analyses of vector and human behavior and infection patterns (Transmission Project). Multi- factorial investigations will take place at 36 sites in 7 Districts of southern Malawi comprising diverse environmental settings and three levels of transmission intensity. Analyses will assess:  Impacts of RTS, S vaccination and dual-AI LLINs on the epidemiology of uncomplicated clinical malaria, and patterns of P. falciparum infection and transmission  Long-term impact of RTS, S on the incidence and age-distribution of severe malaria  Anopheles abundance across space/time in relation to biogeographic/weather patterns and vector control  Outdoor and "awake-time" mosquito biting in relation to Plasmodium transmission and human infection  Impact of a novel transmission-blocking compound on infection in field-derived Anopheles species The Malawi ICEMR team has the capacity to sustain long-term observations of human cohorts in different transmission settings and to collect extensive ecological, entomological and parasitological data. Most of our ICEMR team have been working collaboratively for more than a decade and have developed close working relationships based on mutual respect and common goals. We have the appropriate mix of diverse training, skills, and perspectives to undertake the proposed cross-disciplinary studies.