Mentoring and patient-oriented research in malaria

 描述(申请人提供)：尽管在过去30年里，我们对疟疾生物学的了解取得了显著进展，但在马拉维和其他撒哈拉以南非洲国家，消除疟疾仍然遥不可及。申请者的学术生涯专注于使用遗传学和流行病学来解决与治疗和预防疟疾相关的关键公共卫生问题，并培训美国和马拉维的研究人员为此目的进行以患者为导向的疟疾研究。这一K24奖项建立在她的总体目标之上，即利用转化研究来改善疟疾的治疗和预防，并将使她和她的学员为制定在马拉维和整个撒哈拉以南非洲消除疟疾的战略做好准备。这项提案的具体研究目标侧重于在两个脆弱人群中预防疟疾的干预措施：孕妇及其婴儿，他们的疟疾风险众所周知，但对他们来说，预防战略不足；学龄儿童，这是一个新发现的疟疾感染率较高的人群。孕妇通常在怀孕期间接受两到三次间歇治疗，以预防疟疾，但由于普遍存在耐药性，目前使用的药物的疗效受到影响，迫切需要新的战略。申请人和她的团队最近在马拉维完成了一项试验，将间歇预防性治疗与持续预防疟疾进行比较，以预防怀孕期间的疟疾。在这项提案中，将分析临床、分子、基因组和免疫学数据，以检验这样一种假设，即孕期预防疟疾的间歇治疗和持续预防将对孕产妇和新生儿的结局、母亲在随后怀孕时对疟疾的易感性以及婴儿对疟疾的免疫力产生不同的影响。为了进一步调查疟疾感染的负担和学龄儿童的传播潜力，申请人在正在进行的横断面研究中增加了基于学校的调查。他们将检验这样一个假设，即携带疟疾感染的高风险儿童，包括配子细胞，可以通过基于学校的干预措施接触到。申请者将利用这一奖项的职业发展部分来丰富她的知识基础和国际伙伴关系，使她能够扩大她的研究范围，并在马拉维制定新的干预措施。这项建议包括一项综合的、全面的指导计划，以培训美国和马拉维的研究人员在以患者为导向的研究中取得成功所需的技术、科学和专业技能。申请者和她的研究团队努力设计假设驱动的研究，导致基于证据的干预措施，以改善疟疾患者的健康，并为帮助根除疟疾贡献科学见解。

 DESCRIPTION (provided by applicant): Despite remarkable advances in our understanding of the biology of malaria over the last 30 years, malaria elimination remains elusive in Malawi, among other sub-Saharan African countries. The applicant has focused her academic career on using genetics and epidemiology to address key public health questions related to treating and preventing malaria, and to training U.S.- and Malawi-based investigators to conduct patient- oriented malaria research to this end. This K24 award builds on her overarching goal of using translational research to improve malaria treatment and prevention now and will prepare her and her trainees to develop strategies for malaria elimination in Malawi and throughout sub-Saharan Africa. The specific research aims of this proposal focus on interventions to prevent malaria in two vulnerable populations: pregnant women and their babies, in whom the malaria risk is well known but for whom preventive strategies are inadequate, and school-age children, a population newly recognized to suffer from high rates of malaria infection. Pregnant women routinely receive intermittent treatment two to three times during pregnancy to prevent malaria, but the efficacy of currently used medication is compromised due to widespread resistance and new strategies are urgently needed. The applicant and her team recently completed a trial comparing intermittent preventive treatment to continuous prophylaxis to prevent malaria during pregnancy in Malawi. In this proposal, clinical, molecular, genomic and immunological data will be analyzed to test the hypothesis that intermittent treatment and continuous prophylaxis to prevent malaria during pregnancy will have different effects on maternal and neonatal outcomes, maternal susceptibility to malaria in subsequent pregnancies and infant immunity to malaria. To further investigate the burden of malaria infection and transmission potential in school-age children, the applicant has added school-based surveys to on-going cross-sectional studies. They will test the hypothesis that children at high risk of carrying malaria infection, including gametocytes, can be reached through school-based interventions. The applicant will take advantage of the career development components of this award to enrich her knowledge base and international partnerships that will allow her to expand the scope of her research and develop new interventions in Malawi. This proposal includes an integrated, comprehensive mentoring plan to train U.S.- and Malawi-based investigators in the technical, scientific and professional skills required to succeed in patient-oriented research. The applicant and her research team strive to design hypothesis-driven studies that lead to evidence-based interventions to improve the health of those who suffer from malaria and contribute scientific insight to help eradicate malaria.