Epidemiology Project

流行病学项目

• 批准号: 10381995
• 负责人: MOSES Robert KAMYA
• 金额: $ 78.38万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10381995
• 关键词: Affect; Africa South of the Sahara; Age; Anemia; Antimalarials; Area; Artemisinins; Beds; Blood; Blood specimen; Chemoprevention; Clinical; Clinical Data; Cohort Studies; Combined Modality Therapy; Country; Culicidae; Data; Disease; Entomology; Environmental Impact; Environmental Risk Factor; Epidemiology; Exposure to; Falciparum Malaria; Genetic; Genetic Polymorphism; Genotype; Household; Human; Human Genetics; Immunity; Immunology; Individual; Infection; Insecticides; Integration Host Factors; Intervention; Link; Maintenance; Malaria; Measurement; Measures; Modeling; Morbidity - disease rate; Outcome; Parasites; Plasmodium falciparum; Population; Price; Probability; Protein Microchips; Residual state; Resistance; Sampling; Serology; Site; Sporozoites; Surveillance Modeling; Time; Uganda; cohort; community intervention; density; design; epidemiologic data; experience; genome-wide; genomic data; improved; infection rate; malaria infection; member; mortality; programs; response; transmission process; vector control

Abstract The burden of falciparum malaria in sub-Saharan Africa remains unacceptably high despite significant gains in malaria control over the last 15 years. An improved ability to both predict which combinations of interventions are most likely to have the greatest benefit and to accurately evaluate their effects would be of enormous benefit. However, predictions are currently limited by gaps such as poor characterization of relationships between exposure to sporozoite-infected mosquitoes, rates of establishment of blood stage infection, and the clinical consequences of infection, including the crucial impact of antimalarial immunity. In this project, we will take advantage of unique access to linked entomologic, parasitologic, human genomic, and clinical data from intensive cohorts in different regions of Uganda. Importantly, cohorts will be established in sites where changes in community interventions are planned. Using cohort data, we will quantify the impact of environmental and host factors on the establishment and maintenance of infection, and define a serologic profile by which host immunity, a key host factor, can be measured. Central to these efforts will be our ability to detect, distinguish, and follow genetically distinct parasites in the blood of individuals over time, allowing us to accurately measure the force of infection (rate of acquisition of blood stage infections), to follow the trajectory of these infections within a host, and to relate these metrics to entomologic, epidemiologic, and clinical outcome data. We will then integrate these individual-level relationships to characterize their epidemiologic consequences and model the impact of interventions at the population level. This study has 2 aims: 1) To characterize factors determining the malarial force of infection in intensively studied cohorts at different sites in Uganda. We will derive estimates of sporozoite exposure in individuals living in malaria endemic areas, genotype parasites infecting them to derive measures of the force of infection, and evaluate human genetic polymorphisms in all cohort members using a genome-wide approach. With these data, we will determine the relationship between sporozoite exposure and the force of infection, a key relationship in predicting the effect of vector control interventions, and assess the impact of host factors including genetics, age, and recent changes in exposure on this relationship. 2) To determine factors affecting the duration, density, and clinical consequences of blood stage malaria infection in Uganda. Using quantitative PCR and parasite genotyping data, we will determine the impact of host factors such as genetics, age, and prior exposure on blood stage immunity as well as anemia. We will determine how these relationships vary in different epidemiologic settings, including before and after changes in communitywide interventions. In addition, we will define a serologic profile associated with blood stage immunity by measuring responses to P. falciparum proteins by microarray.

摘要 尽管在防治疟疾方面取得了重大进展，但撒哈拉以南非洲的恶性疟疾负担仍然高得令人无法接受。 在过去的15年里，更好地预测哪些干预组合 最有可能带来最大的好处，准确评估其影响将是巨大的 效益然而，预测目前受到差距的限制，例如对关系的描述不佳 暴露于子孢子感染的蚊子，血液阶段感染的建立率， 感染的临床后果，包括抗疟免疫的重要影响。在这个项目中，我们将 利用独特的访问链接昆虫学，寄生虫学，人类基因组学和临床数据， 乌干达不同地区的密集队列。重要的是，将在发生变化的研究中心建立队列， 在社区干预计划。使用队列数据，我们将量化环境和 宿主因素对感染建立和维持的影响，并确定宿主 免疫力是一个关键的宿主因素，可以测量。这些努力的核心将是我们探测、区分、 并随着时间的推移跟踪个体血液中遗传上不同的寄生虫，使我们能够准确测量 感染力（血液阶段感染的获得率），以跟踪这些感染的轨迹 在主机内，并将这些指标与昆虫学，流行病学和临床结果数据。我们将 然后整合这些个体水平的关系，以描述其流行病学后果和模型 干预措施在人口一级的影响。本研究有两个目的：1）表征因素 确定在乌干达不同地点深入研究的队列中疟疾感染力。 我们将估计生活在疟疾流行区的个体的子孢子暴露，基因型 寄生虫感染他们，以获得感染力的措施，并评估人类遗传 使用全基因组方法在所有群组成员中检测多态性。有了这些数据，我们将确定 子孢子暴露与感染力之间的关系，这是预测效果的关键关系 病媒控制干预措施，并评估宿主因素的影响，包括遗传学，年龄， 在这段关系上的曝光率变化。2)确定影响持续时间、密度和 乌干达血液期疟疾感染的临床后果。使用定量PCR和寄生虫 基因分型数据，我们将确定宿主因素，如遗传学，年龄和先前的暴露对 血液阶段免疫以及贫血。我们将确定这些关系如何在不同的 流行病学背景，包括社区干预措施变化前后的情况。此外，我们将 通过测量对恶性疟原虫的应答，确定与血液阶段免疫相关的血清学特征 蛋白质的微阵列。