Immunology and Pathogenesis

疟疾仍然是非洲公共卫生的主要威胁。然而，新的和扩大的重点是 主要利益攸关方，包括非洲国家元首、政府和非政府组织 包括主要的慈善组织和公共卫生界的领导人已经改变了 从关注疟疾控制到关注区域消除和最终的国际对话 根除疟疾。实现这些目标将需要多方面的方法，最好地利用 现有的工具，将需要开发新的工具，包括疫苗和新药。同样 重要的是针对具体的微环境调整干预措施及其实施 遍及非洲的地方病。在拟议的工作中，西非的四个地点每个都有一个独特的 流行病学和生态环境将在强度和 感染流行情况、媒介蚊子种群动态，包括杀虫剂抗药性、疾病 病因学，侧重于宿主因素和免疫反应以及药物的出现和传播 抵抗。支持这一提议的假设是寄生虫、人类和媒介的组合 在个人和更广泛的社区中，因素决定了疾病的结局。这两个 生态环境和寄生虫影响着个体和人群的疾病结局 水平，这项建议试图理解这些外部因素与 宿主、寄生虫和媒介种群的潜在遗传决定因素。在两个方面都取得了进展 过去一年对寄主、寄生虫和病媒生物学进行调查的执行能力和工具 五年使我们能够以前所未有的方式进行这些研究。了解这些 关系对于评估当前干预措施的有效性和在翻译 预防和治疗该病及其传播的新工具。

Malaria remains a major threat to public health in Africa. However, renewed and expanded emphasis by the major stakeholders including African heads of state, governmental and non-governmental organizations including major philanthropic organizations and leaders in the public health community have changed the international conversation from a focus on malaria control to a focus on regional elimination and eventual eradication of malaria. Accomplishing these goals will require a multifaceted approach, making best use of existing tools and will require the development of new tools including vaccines and new drugs. Equally important will be the tailoring of the interventions and their implementation to the specific microenvironments throughout endemic Africa. In the proposed work, four sites in West Africa each with a unique epidemiological and ecological environment will be compared and contrasted with regard to intensity and prevalence of infection, vector mosquito population dynamics, including insecticide resistance, disease pathogenesis with a focus on host factors and the immune response and the emergence and spread of drug resistance. The hypothesis underlying this proposal is that a combination of parasite, human and vector factors determine the disease outcome in the individual and more broadly in the community. Both the ecological environment and the parasite modulate the disease outcome on an individual and population level, and this proposal seeks to understand the relationship between these external factors and the underlying genetic determinants in the host, parasite and vector populations. Advances both in implementation capacity and in tools for the interrogation of host, parasite and vector biology over the last five years has enabled us to undertake these studies in an unprecedented manner. Understanding these relationships is critical to both the evaluation of current intervention effectiveness and in the translation of new tools for prevention and treatment of the disease and its transmission.