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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI089674-03
Application #
8378693
Study Section
Special Emphasis Panel (ZAI1-AWA-M)
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$268,647
Indirect Cost
$26,792
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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

Showing the most recent 10 out of 156 publications