Research for the Elimination of Lymphatic Filariasis

描述(申请人提供)：大约有1亿人感染了班克罗夫氏伍氏杆菌，这是一种由蚊子传播的线虫寄生虫，会在热带地区引起变形性淋巴丝虫病。改进的治疗和诊断方法导致了对淋巴丝虫病(LF)的新思考，并认识到应该有可能通过反复大规模给药(MDA)来阻断传播并消除这一重大公共卫生问题。埃及是世界上最早实施基于这一战略的消除淋巴丝虫病(PERF)国家计划的国家之一。我们目前的ICIDR致力于记录埃及PELF对哨所村庄丝虫病流行和传播的影响，并对ELF项目中监测进展的不同工具的价值进行了研究。ICIDR的这项新提议是这项工作的自然延伸。除了目前华盛顿大学、史密斯学院和艾因沙姆斯大学(开罗)的RTC具有不同科学背景(医学流行病学、免疫学、分子生物学和昆虫学)的研究人员的紧密合作小组外，新项目还在鹿特丹伊拉斯谟增加了一个强大的研究小组，他们拥有建立低频传播模型和评估控制措施影响的专业知识。新的ICIDR方案将在埃及PELF的第五轮也是最后一轮MDA(于2004年10月完成)后大约一年开始。该方案由两个相互关联的项目组成：项目1将在广泛的实地研究中使用现有的最佳诊断工具，以评估埃及是否已消除丝虫病；实地收集的材料和数据将用于项目2。项目2的重点是开发监测PELF的新工具(促进项目1的目标)。我们已经组装了一系列强大的核心，以支持这些项目并加强RTC的研究能力。我们的人员、经验和热情使我们处于进行研究的绝佳位置，这些研究应该直接有利于消除丝虫病的努力，不仅在埃及，而且在世界上许多其他地方病流行的国家。 项目1：消除淋巴丝虫病的研究(Weil，G.) 项目1说明(申请人提供)：改进的治疗方法和诊断方法导致了对淋巴丝虫病的新思考，并认识到应该有可能通过使用新的单剂量联合用药方案重复进行年度大规模给药循环来阻断传播并消除这一重大公共卫生问题。埃及是最早实施以丙二醛(丙二醛)为基础的国家消除淋巴丝虫病(PELF)计划的国家之一(2000年9月开始每年分发二乙基氨基马津和阿苯达唑)。埃及卫生和人口部于2004年10月完成了第5轮也是最后一轮中期评估。我们在本次ICIDR项目期间对哨所村庄进行的详细研究表明，MDA计划的最初几年对LF患病率(微丝虫病和循环抗原血症)和传播参数(使用小学生抗体患病率作为接触寄生虫的标志，以及通过对蚊子池中寄生虫DNA的PCR检测来估计蚊子感染率)产生了重大影响。事实上，在这些村庄，LF很可能是被MDA消灭的。新项目是这项工作的自然延伸(和重大扩展)。这个新项目利用了开罗艾因沙姆斯大学RTC强大的多学科丝虫病研究团队。ICIDR人员将与埃及卫生和人口部密切合作，通过广泛的实地研究来实施这一雄心勃勃的项目。这将是第一次尝试以这种规模严格评估国家ELF，也是第一次将国家ELF计划用作研究实验室。我们将探索处理PERF后期阶段的策略，测试消除指标，并测试埃及丝虫病已通过5轮丙二醛消除的假设。我们还将评估先进的诊断方法在检测持续传播的病灶和在丙二醛暂停后早期发现复发传播的价值。在埃及学到的经验教训将使世界各地的PELF受益。

DESCRIPTION (provided by applicant): Approximately 100 million people are infected with Wuchereria bancrofti, a mosquito-transmitted nematode parasite that causes deforming lymphatic filariasis in the tropics. Improved therapies and diagnostic methods have led to new thinking about lymphatic filariasis (LF) and the realization that it should be possible to interrupt transmission and eliminate this major public health problem by repeated cycles of mass drug administration (MDA). Egypt was one of the first countries in the world to implement a national program for elimination of lymphatic filariasis (PELF) based on this strategy. Our current ICIDR has worked to document the impact of the Egyptian PELF on filariasis prevalence and transmission in sentinel villages, and we have conducted research on the value of different tools for monitoring progress in ELF programs. This new ICIDR proposal is a natural extension of that work. In addition to the current cohesive group of researchers with different scientific backgrounds (medical epidemiology, immunology, molecular biology, and entomology) at Washington University, Smith College, and the RTC at Ain Shams University (Cairo), the new project adds a strong research group at Erasmus MC (Rotterdam) with expertise in modeling LF transmission and assessing the impact of control measures. The new ICIDR program will begin approximately one year after the 5th and final round of MDA in the Egyptian PELF (completed in October, 2004). The program is comprised of two interrelated projects: Project 1 will use the best available diagnostic tools in extensive field studies to assess whether filariasis has been eliminated in Egypt; materials and data collected in the field will be used in Project 2. Project 2 is focused on development of new tools for monitoring PELFs (promoting the objectives of Project 1). We have assembled a strong package of Cores to support these Projects and strengthen research capacity at RTC. Our personnel, experience, and enthusiasm place us in an excellent position to conduct research that should directly benefit efforts to eliminate filariasis, not only in Egypt, but also in many other endemic countries around the world. PROJECT 1: Research for the Elimination of Lymphatic Filariasis (Weil, G.) PROJECT 1 DESCRIPTION (provided by applicant): Improved therapies and diagnostic methods have led to new thinking about lymphatic filariasis and the realization that it should be possible to interrupt transmission and eliminate this major public health problem by repeated, annual cycles of mass drug administration (MDA) with new single dose combination drug regimens. Egypt was one of the first countries to implement a national program for elimination of lymphatic filariasis (PELF) based on MDA (annual distribution of diethylcarbamazine and albendazole, initiated in September 2000). The Egyptian Ministry of Health and Population (MOHP) completed its 5th and final round of MDA in October, 2004. Our detailed studies of sentinel villages during the current ICIDR project showed that the initial years of the MDA program had a major impact on LF prevalence (microfilaremia and circulating antigenemia) and transmission parameters (using antibody prevalence rates in primary school children as a marker for exposure to the parasite and PCR detection of parasite DMA in mosquito pools to estimate mosquito infection rates). Indeed, it is likely that LF was eliminated by MDA in these villages. The new project is a natural extension (and major expansion) of that work. The new project takes advantage of the strong, multidisciplinary filariasis research team at RTC, Ain Shams University in Cairo. ICIDR personnel will work closely with the Egyptian Ministry of Health and Population to carry out this ambitious project with extensive field studies. This will be the first attempt to rigorously assess a national PELF on this scale and also the first to use a national ELF program as a research laboratory. We will explore strategies for managing late stages of a PELF, test elimination indicators, and test the hypothesis that filariasis has been eliminated in Egypt by 5 rounds of MDA. We will also assess the value of advanced diagnostic methods for detecting foci of continued transmission and for early detection of resurgent transmission following suspension of MDA. Lessons learned in Egypt will benefit PELFs around the world.