The impact of antimalarials and insecticide resistance on malaria transmission in Uganda

乌干达抗疟药和杀虫剂耐药性对疟疾传播的影响

• 批准号: 9789714
• 负责人: Melissa D Conrad
• 金额: $ 14.12万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-21 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789714
• 关键词: Africa South of the Sahara; Anopheles gambiae; Anti-malarial drug resistance; Biological Assay; Biology; Blood; Characteristics; Clinical; Clinical Research; Consumption; Culicidae; Data; Data Analyses; Development; Development Plans; Disease; Drug resistance; Entomology; Female; Genes; Genotype; Goals; Human; Immune response; Infection; Infrastructure; Innate Immune Response; Insecticide Resistance; Insecticides; Intervention; Laboratories; Learning; Malaria; Markov chain Monte Carlo methodology; Measures; Membrane; Mentors; Midgut; Modeling; Molecular; Molecular Epidemiology; Natural Immunity; Oocysts; Parasites; Parasitology; Patients; Pharmaceutical Preparations; Plasmodium falciparum; Policies; Policy Maker; Prevalence; Process; Research; Research Personnel; Research Technics; Resistance; Resistance profile; Resources; Sex Ratio; Site; Source; Sporozoites; Techniques; Testing; Training; Uganda; Universities; Vaccination; Variant; Work; career; career development; clinical infrastructure; density; drug sensitivity; experimental study; feeding; improved; malaria infection; malaria transmission; molecular marker; skills; transmission process; vector; vector control; vector mosquito

PROJECT SUMMARY Eliminating malaria in high transmission settings where asymptomatic infections are prevalent will require improved interventions to treat malaria, control vectors, and also decrease transmission to mosquitoes. However, our understanding of what factors govern the efficiency of malaria transmission is incomplete, limiting our ability to accurately predict the impacts of transmission-reducing interventions. We hypothesize that parasite and mosquito factors are associated with the likelihood of malaria transmission to mosquitoes. To test this hypothesis, we will utilize our well-established clinical and entomology infrastructure in Tororo, Uganda to infect field-collected and colony anopheline mosquitoes with blood from P. falciparum-infected Ugandans using membrane feeding assays. We will then analyze the prevalence and intensity of malaria infection in mosquitoes in relation to measured parasite and vector characteristics. Among the characteristics we will investigate are gametocyte density, multiplicity of infection and sex ratio, parasite drug resistance and genotypes, and mosquito insecticide resistance and genotypes. Using Bayesian Markov Chain Monte Carlo techniques, we will fit models to our data, allowing explicit estimation of parameters related to infectiousness needed to reproduce the observed data, allowing us to test our hypotheses regarding variation in infectiousness, measure the magnitude of these effects, and identify putative sources of the variation, information that will be essential to inform policy decisions that will facilitate the control and eventual elimination of malaria. Specifically, our results will help us to prioritize control measures directed toward parasites (drugs) and mosquitoes (insecticides) in Uganda. The PI of this project will greatly benefit from the infrastructure for clinical and entomology research already established in her field sites in Uganda as part of years of collaborative work between UCSF and Makerere University. This infrastructure includes clinical facilities, molecular and parasitology laboratories, and an insectary. In addition, a team of exceptional mentors and collaborators has been assembled to provide expertise in all aspects of her proposed research. This project will allow the PI to broaden her research to the study of malaria transmission, an ideal focus for the establishment of an independent career. As part of her comprehensive career development plan, she will learn new research techniques, project management, and other essential skills for a successful career as an independent researcher.

项目总结