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.
|Wilding, C S; Weetman, D; Rippon, E J et al. (2015) Parallel evolution or purifying selection, not introgression, explains similarity in the pyrethroid detoxification linked GSTE4 of Anopheles gambiae and An. arabiensis. Mol Genet Genomics 290:201-15|
|Nankoberanyi, Sheila; Mbogo, George W; LeClair, Norbert P et al. (2014) Validation of the ligase detection reaction fluorescent microsphere assay for the detection of Plasmodium falciparum resistance mediating polymorphisms in Uganda. Malar J 13:95|
|Tatem, Andrew J; Huang, Zhuojie; Narib, Clothilde et al. (2014) Integrating rapid risk mapping and mobile phone call record data for strategic malaria elimination planning. Malar J 13:52|
|Perkins, T Alex; Garcia, Andres J; Paz-Soldán, Valerie A et al. (2014) Theory and data for simulating fine-scale human movement in an urban environment. J R Soc Interface 11:|
|Conrad, Melissa D; Bigira, Victor; Kapisi, James et al. (2014) Polymorphisms in K13 and falcipain-2 associated with artemisinin resistance are not prevalent in Plasmodium falciparum isolated from Ugandan children. PLoS One 9:e105690|
|Tatem, Andrew J (2014) Mapping population and pathogen movements. Int Health 6:5-11|
|Johnston, Geoffrey L; Gething, Peter W; Hay, Simon I et al. (2014) Modeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination. PLoS Comput Biol 10:e1003434|
|Deville, Pierre; Linard, Catherine; Martin, Samuel et al. (2014) Dynamic population mapping using mobile phone data. Proc Natl Acad Sci U S A 111:15888-93|
|Tatem, Andrew J (2014) Mapping the denominator: spatial demography in the measurement of progress. Int Health 6:153-5|
|Gething, Peter W; Battle, Katherine E; Bhatt, Samir et al. (2014) Declining malaria in Africa: improving the measurement of progress. Malar J 13:39|
Showing the most recent 10 out of 40 publications