PROJECT SUMMARY/ABSTRACT The impact of climate change, including the increased frequency of weather extremes such as flooding, on the incidence of malaria and other vector-borne diseases is an issue of substantial public health importance. Therefore, there is an urgent need to develop effective mitigation and control strategies. In May 2020, we piloted a post-flood malaria chemoprevention intervention in rural western Uganda. When compared to two neighboring villages where no intervention was deployed, we estimated a 53% reduction (aRR 0.47, 95% CI 0.34 – 0.62, p<.01) in malaria incidence in the six months post-intervention. Building on these results, the scientific aim of this proposal is to evaluate the effectiveness of a targeted, time-limited malaria chemoprevention intervention with and without larval source management (LSM) to reduce excess disease burden in a perennial, high- transmission setting following severe flooding. Our premise is that the intervention will reduce the parasite reservoir during the critical “rebound” period, when vectors are re-establishing habitats thereby maintaining relatively low levels of transmission until conditions have returned to the pre-flood baseline. Specifically, we will: Aim 1: Determine the effectiveness of chemoprevention with or without peri-domestic larvicide application to reduce the incidence of P. falciparum malaria after severe flooding. We will conduct a cluster randomized trial in 50 villages (144 clusters) in rural western Uganda, where flooding relatively predictable, to compare: (i) LLIN distribution (control), (ii) LLIN distribution plus three, monthly rounds of DP provided to children ≤12 years of age (DP), and (iii) LLIN+DP with three months of bi-weekly application of larvicide in the peri- domestic space (DP+Bti). Hypothesis: Chemoprevention will achieve a sustained (≥6 months) reduction in malaria incidence of ≥30% compared to the control arm without the emergence of artemisinin resistance. Aim 2: Elucidate the evolution of vector populations, feeding behaviors, and sporozoite rate in affected villages up to one year after flooding. We will perform weekly surveillance for adult and juvenile Anopheles mosquitoes in sentinel households and within the peri-domestic space. Collected mosquitoes will be counted, and identified to species and tested for the presence of P. falciparum sporozoites. Hypothesis: Flooding will create innumerable small pools favored by An. gambiae complex resulting in predominance of An. gambiae s.s. with potential for emergence of An. arabiensis as important vector in setting of widespread LLIN use.23 Aim 3: Evaluate the relative cost-effectiveness of chemoprevention (Aim 3A) and assess social and economic impacts on households (Aim 3B). We will conduct baseline and longitudinal quantitative surveys in sample clusters to evaluate impacts of the interventions on (i) economic activities and income, (ii) health seeking and expenditures, and (iii) mental health and well-being. These data will inform a cost effectiveness analysis of chemoprevention compared to the control (i.e., relative cost per case averted). Hypothesis: Chemoprevention will mitigate negative effects of malaria in the aftermath of a flood.

PROJECT NARRATIVE The impact of global climate change, including the increased frequency of weather extremes such as flooding, on the incidence of malaria and other vector-borne diseases is an issue of substantial public health importance. Thus, there is an urgent need not only to elucidate the changes in the ecological, biological, and social factors that impact malaria transmission in the post-flood environment, but also to develop effective mitigation and control strategies. Therefore, the scientific aim of this proposal is to evaluate the effectiveness of a targeted, time-limited malaria chemoprevention intervention with and without larval source management (LSM) to reduce excess malaria burden in a perennial, high-transmission setting following severe flooding.