Human Parasite and Mosquito Determinants of Plasmodium Vivax Transmission

间日疟原虫传播的人类寄生虫和蚊子决定因素

• 批准号: 8309161
• 负责人: Joseph M. Vinetz
• 金额: $ 37.07万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8309161
• 关键词: Affect; Anopheles Genus; Antibody Formation; Blocking Antibodies; Cellular Immunity; Culicidae; Drug resistance; Economics; Human; Infection; Legal patent; Malaria; Malaria Vaccines; Morbidity - disease rate; Parasites; Patients; Plasmodium falciparum; Plasmodium vivax; Predisposition; Research; Sex Ratio; Testing; cell mediated immune response; insight; mortality; patient population; response; transmission process; vector mosquito

Malaria, caused by both Plasmodium falciparum and P. vivax in the Amazon region, is responsible for enormous human suffering and human economic loss worldwide. The long-term objective of the research proposed here is to contribute towards the global control of malaria by understanding human, parasite and mosquito factors that modulate the transmission of malaria parasites from the human reservoir to mosquitoes. Despite eradication efforts since the 1950s, malaria has rebounded to levels of morbidity and mortality that are higher than ever. There is no effective malaria vaccine. Drug-resistant malaria is common and increasing not only in the lethal human malaria parasite, Plasmodium falciparum but also in the even more widespread human malaria parasite, P. vivax. A key observation we seek to explain is why patients infected with P. vivax that have patent gametocytemia only inefficiently (-50%) infected wild-caught Anopheles darlingi mosquitoes under experimental conditions. The central hypotheses ofthis project are that that human antibody responses, cell-mediated immunity, and P. vivax maturity and sex ratios may modulate parasite infectivity to mosquitoes; and that different species of neotropical anopheles mosquitoes differ in their sensitivity to P. vivax. These hypotheses will be tested in the following Specific Aims: 1) To determine the contributions and associations ofhuman humoral responses, human cell-mediated immune responses, and P. vivax gametocyte maturity and sex ratio with parasite transmission to Anopheles darlingi, in both symptomatic and asymptomatic patient populations; 2) To assess the susceptibility of colonized Anopheles darlingi and non-An darlingi potential malaria vector mosquitoes to infection by Plasmodium vivax; and 3) To determine mechanisms of transmission blocking activity in patients with naturally acquired transmission blocking antibodies. This project will provide new insights into fundamental mechanisms affecting the transmission of P. vivax from the human reservoir to natural, wild type neotropical Anopheles mosquito vectors in the Amazonian hypoendemic setting.

亚马逊地区由恶性疟原虫和杜瓦克斯疟原虫引起的疟疾，负责 全世界的巨大人类苦难和人类经济损失。这里提出的研究的长期目标是通过了解人类，寄生虫和蚊子因素来为全球疟疾的控制做出贡献，这些因素调节了疟疾寄生虫从人类储层到蚊子的传播。尽管自1950年代以来就根除了努力，但疟疾已经反弹到比以往任何时候都更高的发病率和死亡率水平。没有有效的疟疾疫苗。抗药性疟疾很常见，不仅在致命的人类疟原虫，恶性疟原虫，而且在更广泛的人类疟原虫寄生虫P. vivax中也增加。我们寻求解释的一个关键观察是，为什么在实验条件下感染了专利的野生型疾病（-50％）感染的野生动物的野生动物蚊子（-50％）的患者。该项目的中心假设是，人类抗体反应，细胞介导的免疫力以及疟原虫的成熟度和性别比例可能会调节对蚊子的寄生虫​​感染性。并且新热带蚊子的不同种类在其对维瓦克斯的敏感性方面有所不同。这些假设将在以下特定目的中进行检验：1）确定人类体液反应的贡献和关联，人类细胞介导的免疫反应以及Vivax P. vivax Gametocyte的成熟度和性别比率与寄生虫传播的寄生虫传播，以症状性和有症状性和性能为darling。无症状的患者人群； 2）评估殖民地围绕止血物的敏感性和非宠儿的潜在疟疾媒介蚊子对疟原虫的感染； 3）确定自然获得传输阻断抗体患者的传输阻断活性的机制。该项目将提供有关影响体内储层的基本机制，从人类储层传播到亚马逊性次病性环境中自然，野生型新热带蚊子媒介的传播。