Among our best tools for the control of malaria are effective antimalarial drugs and insecticides, but these are jeopardized by increasing resistance of malaria parasites and anopheline mosquitoes. Parasite and mosquito resistance are partially characterized, and assays are available to identify certain genotypes associated with resistance. However, additional studies to identify novel markers of resistance, especially to newer drugs and insecticides, are needed. This project will utilize available tools to conduct efficient surveys of the prevalence of known resistance markers across Uganda, develop new tools to improve surveillance methods, search for new markers to allow us to track the development of resistance to newer drugs and insecticides, and identify associations between specific intervenfions and the development of resistance. We hypothesize that benefits of current malaria control measures will be challenged by increasing resistance in malaria parasites and anopheline vectors. We further hypothesize that the rate of resistance development will vary depending on the level of malaria transmission and extent of implementation of control measures. We will test these hypotheses with serial surveys for parasite and mosquito resistance mediators at sites with varied malaria transmission intensity. We also predict that newer agents will select for not-yet-described resistance mediators. We will search for these novel mediators of resistance in samples under drug and insecticide selection pressure.
Our specific aims will be: 1) to compare the prevalence of molecular markers of antimalarial drug resistance by serial surveillance at diverse sites in Uganda with varied implementation of control measures, 2) to compare the prevalence of molecular markers of anopheline insecticide resistance by serial surveillance at diverse sites in Uganda with varied implementation of control measures, and 3) to improve surveillance tools and search for novel mediators of antimalarial and insecticide resistance using transcriptome and high throughput sequencing techniques. We anficlpate that this project will offer a detailed characterization of the progression of resistance to drugs and insecticides in Uganda over time and also help us to identify novel mechanisms of resistance.
Among our best tools for the control of malaria are effecfive drugs and insecticides. However, effective drugs and insecticides are jeopardized by increasing resistance. This project will utilize samples of malaria parasites and mosquitoes collected at mulfiple locafions in Uganda to better characterize the nature of resistance, and thereby improve the ability to circumvent resistance and best control malaria.
|Tatem, Andrew J; Jia, Peng; Ordanovich, Dariya et al. (2017) The geography of imported malaria to non-endemic countries: a meta-analysis of nationally reported statistics. Lancet Infect Dis 17:98-107|
|Tukwasibwe, Stephen; Tumwebaze, Patrick; Conrad, Melissa et al. (2017) Drug resistance mediating Plasmodium falciparum polymorphisms and clinical presentations of parasitaemic children in Uganda. Malar J 16:125|
|Williams, Claire R; Baccarella, Alyssa; Parrish, Jay Z et al. (2017) Empirical assessment of analysis workflows for differential expression analysis of human samples using RNA-Seq. BMC Bioinformatics 18:38|
|Farrington, Lila; Vance, Hilary; Rek, John et al. (2017) Both inflammatory and regulatory cytokine responses to malaria are blunted with increasing age in highly exposed children. Malar J 16:499|
|Lloyd, Christopher T; Sorichetta, Alessandro; Tatem, Andrew J (2017) High resolution global gridded data for use in population studies. Sci Data 4:170001|
|Tejedor-Garavito, Natalia; Dlamini, Nomcebo; Pindolia, Deepa et al. (2017) Travel patterns and demographic characteristics of malaria cases in Swaziland, 2010-2014. Malar J 16:359|
|Mugenyi, L; Abrams, S; Hens, N (2017) Estimating age-time-dependent malaria force of infection accounting for unobserved heterogeneity. Epidemiol Infect 145:2545-2562|
|Martins, Walter Fabricio Silva; Subramaniam, Krishanthi; Steen, Keith et al. (2017) Detection and quantitation of copy number variation in the voltage-gated sodium channel gene of the mosquito Culex quinquefasciatus. Sci Rep 7:5821|
|Isaacs, Alison T; Lynd, Amy; Donnelly, Martin J (2017) Insecticide-induced leg loss does not eliminate biting and reproduction in Anopheles gambiae mosquitoes. Sci Rep 7:46674|
|Taylor, Aimee R; Flegg, Jennifer A; Holmes, Chris C et al. (2017) Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine Exert Inverse Selective Pressure on Plasmodium Falciparum Drug Sensitivity-Associated Haplotypes in Uganda. Open Forum Infect Dis 4:ofw229|
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