Evaluating Re-active Surveillance Strategies for Malaria Elimination in Swaziland

描述（由申请人提供）：我的目标是通过临床护理和以患者为导向的疟疾研究来改善儿童的健康，从而在儿科传染病领域获得有价值的职业生涯。我之所以被疟疾所吸引，是因为这种疾病给儿童带来了巨大的全球负担，也是因为最近对消灭疟疾的兴趣带来了令人兴奋的问题，即各国如何能够阻断传播。我特别感兴趣的是反应性监测，这是一项对索引病例周围的社区成员进行筛查的战略，以此作为识别和锁定使传播持续下去的无症状携带者的一种方式。基于我的奖学金研究，重点是监测疟疾的消除，并建立在现有的基础设施和与斯威士兰国家疟疾控制计划的合作，我提出了以下具体目标：1）比较混合PCR与快速诊断测试（RDT）以改进继发性疟疾感染的检测，2）确定与反应性监测中继发感染检测相关的流行病学因素，3）建立并测试一个模型，利用RDT预测热点位置，PCR、流行病学数据和疟疾血清学。这些发现将有助于指导反应性监测的最佳做法，澄清使用哪种诊断测试，何时调查指示病例，以及在这些调查期间应该筛查社区中的哪些人。改进对热点的预测还将使各国能够预测潜在的疫情，将有限的资源用于剩余的疫源地，并最终阻断疟疾传播。 拟议的项目还将使我能够收集必要的初步数据，以便随后提交R01报告，以测试针对这些监测方法（例如筛查和治疗、大规模药物管理或密集室内滞留喷洒）确定的热点采取的重点干预措施的有效性。进行这些群集随机临床试验将是我过去许多积极和富有成效的研究、计划和临床经验的顶峰。然而，为了实现这一职业目标和我的K23的目标，我需要额外的培训，指导和经验的两个主要领域：1）临床和流行病学研究的高级技能，以及2）疟疾诊断和监测实验室检测的专业知识。在这份建议书中，我提出了一个详细的职业发展计划，其中包括在这些领域的导师，在临床研究硕士学位，并在UCSF和斯威士兰的实际实验室经验。从这次培训中获得的技能和经验将使我能够独立设计临床试验，并成功地竞争R01资金。 我组建了一个经验丰富、资源充足的导师团队，致力于拟议的项目和我的职业发展。此外，我已经有了与我的导师和合作者的生产力的跟踪记录。我得到了UCSF的全力支持，我的家乡机构，在生物医学科学，临床和转化研究以及全球健康方面拥有丰富而持久的卓越传统。在加州大学旧金山分校和通过我的导师团队提供的培训和研究机会无疑将为我作为一个独立的疟疾研究人员的成功职业生涯做好准备，解决疟疾消除的临床和流行病学挑战，并最终有助于改善儿童和目前受疟疾威胁的更大人群的健康。 公共卫生相关性：疟疾造成的全球疾病负担巨大。拟议的研究计划将在斯威士兰进行，斯威士兰是一个致力于消除疟疾的南部非洲国家，并将严格评估反应性监测，这是一项对已知疟疾病例社区进行筛查的战略，以确定其他病例和热点。这些结果将有助于将未来的研究和疟疾干预措施集中在斯威士兰和许多其他国家，以消除疟疾。

DESCRIPTION (provided by applicant): My goal is to have a rewarding career in pediatric infectious diseases by improving the health of children through clinical care and patient oriented malaria research. I became drawn to malaria because of the tremendous global burden of this disease in children and because recent interest in malaria elimination has brought forth exciting questions on how countries can interrupt transmission. I am particularly interested in re-active surveillance, a strategy whereby community members around index cases are screened as a way to identify and target asymptomatic carriers that perpetuate transmission. Building on my fellowship research which focused on surveillance for malaria elimination, and building on existing infrastructure and collaboration with the Swaziland National Malaria Control Program, I propose the following specific aims: 1) Compare pooled PCR to rapid diagnostic test (RDT) for improved detection of secondary malaria infections, 2) Identify epidemiological factors associated with the detection of secondary infections in re-active surveillance, and 3) Build and test a model for predicting the location of hot spots utilizing RDT, PCR, epidemiological data, and malaria serology. These findings will help guide best practices for re-active surveillance, clarifying which diagnostic test to use, when to investigate an index case, and who in the community should be screened during these investigations. Improved prediction of hot spots will also enable countries to anticipate potential outbreaks, target limited resources to remaining foci, and ultimately interrupt malaria transmission. The proposed project will also enable me to collect the preliminary data necessary for a subsequent R01 submission to test the effectiveness of focal interventions targeting hot spots identified by these surveillance methods (e.g. screening and treatment, mass drug administration, or intensive indoor residual spraying). To perform these cluster-randomized clinical trials would be the culmination of many positive and productive research, programmatic, and clinical experiences that I have had in the past. However, in order to achieve this career goal and the aims of my K23, there are two major areas where I require additional training, mentoring, and experience: 1) Advanced skills in clinical and epidemiologic research, and 2) Expertise in malaria diagnostic and surveillance laboratory assays. In this proposal, I present a detailed career development plan that includes mentorship in these areas, a Master's in Clinical Research, and practical laboratory experience at UCSF and in Swaziland. The skills and experience acquired from this training will enable me to independently design a clinical trial and compete successfully for R01 funding. I have assembled a highly experienced and well-resourced mentorship team that is committed to the proposed project and my career development. Furthermore, I already have a track record of productivity with my mentors and collaborators. I have full and enthusiastic support from UCSF, my home institution, which has a rich and enduring tradition of excellence in biomedical science, clinical and translational research, and global health. The training and research opportunities available at UCSF and through my mentorship team will no doubt prepare me for a successful career as an independent malaria researcher, addressing clinical and epidemiologic challenges of malaria elimination, and ultimately contributing to improved health of children and larger populations currently threatened by malaria. PUBLIC HEALTH RELEVANCE: The global burden of disease caused by malaria is tremendous. The proposed research program will take place in Swaziland, a country in southern Africa endeavoring to eliminate malaria, and will critically evaluate re-active surveillance, a strategy whereby the communities of known malaria cases are screened as a way to identify other cases and hot spots. The results will help to focus future research and malaria interventions in Swaziland and many other countries aiming to eliminate malaria.