We request a one-year extension to our ongoing cohort study, entitled """"""""Clinical and molecular studies of drug resistant malaria."""""""" Therapy for malaria in Africa has changed greatly in recent years, with adoption of new artemisinin-based combination therapy (ACT) as the standard treatment for uncomplicated malaria in most countries. However, our appreciation of the relative efficacies and safeties of leading ACTs remains ncomplete. In this study we continue to compare the efficacy and safety of the two leading ACTs, artesunate/amodiaquine and artemether/lumefantrine, using a novel longitudinal format. A project extension is requested to allow acrual of additional sample size for adequate comparison of efficacy and safety. In addition, added sample size will facilitate exploration of secondary clinical outcomes and molecular aims. We continue to test the hypotheses stated in our initial application, that longitudinal evaluation will identify important differences between the efficacies and selective pressures of leading antimalarial combination therapies and that identifiable parasite and host polymorphisms will help predict outcomes after antimalarial therapy. In addition, with our extension we will emphasize studies of safety, hypothesizing that longitudinal evaluation will identify important differences in the tolerability and safety of study regimens. Our project includes clinical studies at our established study site in Kampala, Uganda and related molecular studies in Kampala and San Francisco. Since initiation of our clinical trial in November, 2004 our project has been highly successful in working toward our aims, which will continue to be (1) to compare the efficacies of combination antimalarial therapies using a longitudinal design, (2) to follow plasmodial genetic polymorphisms as longitudinal markers of antimalarial drug resistance, and (3) to evaluate the roles of host genetic polymorphisms in antimalarial drug resistance and the incidence of clinical malaria. We anticipate that the experiments designed to achieve these aims will contribute to improved management of malaria and to a better understanding of the genetic factors that impact upon responses to therapy for this disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
4U01AI052142-06
Application #
7505105
Study Section
Special Emphasis Panel (NSS)
Program Officer
Rosenthal, Steven R
Project Start
2002-07-01
Project End
2010-02-28
Budget Start
2008-03-15
Budget End
2010-02-28
Support Year
6
Fiscal Year
2008
Total Cost
$428,734
Indirect Cost
Name
University of California San Francisco
Department
Pediatrics
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Gantt, Soren; Huang, Meei-Li; Magaret, Amalia et al. (2013) An artesunate-containing antimalarial treatment regimen did not suppress cytomegalovirus viremia. J Clin Virol 58:276-8
Ruel, Theodore D; Boivin, Michael J; Boal, Hannah E et al. (2012) Neurocognitive and motor deficits in HIV-infected Ugandan children with high CD4 cell counts. Clin Infect Dis 54:1001-9
Gupta, Vinay; Perez-Perez, Guillermo I; Dorsey, Grant et al. (2012) The seroprevalence of Helicobacter pylori and its relationship to malaria in Ugandan children. Trans R Soc Trop Med Hyg 106:35-42
Yeka, Adoke; Gasasira, Anne; Mpimbaza, Arthur et al. (2012) Malaria in Uganda: challenges to control on the long road to elimination: I. Epidemiology and current control efforts. Acta Trop 121:184-95
Baliraine, Frederick N; Rosenthal, Philip J (2011) Prolonged selection of pfmdr1 polymorphisms after treatment of falciparum malaria with artemether-lumefantrine in Uganda. J Infect Dis 204:1120-4
Greenhouse, Bryan; Ho, Benjamin; Hubbard, Alan et al. (2011) Antibodies to Plasmodium falciparum antigens predict a higher risk of malaria but protection from symptoms once parasitemic. J Infect Dis 204:19-26
Baliraine, Frederick N; Nsobya, Samuel L; Achan, Jane et al. (2011) Limited ability of Plasmodium falciparum pfcrt, pfmdr1, and pfnhe1 polymorphisms to predict quinine in vitro sensitivity or clinical effectiveness in Uganda. Antimicrob Agents Chemother 55:615-22
Clark, Tamara D; Njama-Meya, Denise; Nzarubara, Bridget et al. (2010) Incidence of malaria and efficacy of combination antimalarial therapies over 4 years in an urban cohort of Ugandan children. PLoS One 5:e11759
Gasasira, Anne F; Kamya, Moses R; Ochong, Edwin O et al. (2010) Effect of trimethoprim-sulphamethoxazole on the risk of malaria in HIV-infected Ugandan children living in an area of widespread antifolate resistance. Malar J 9:177
Nsobya, Samuel L; Kiggundu, Moses; Nanyunja, Sarah et al. (2010) In vitro sensitivities of Plasmodium falciparum to different antimalarial drugs in Uganda. Antimicrob Agents Chemother 54:1200-6

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