Lymphatic Filariasis Transmission and Elimination in Papua New Guinea

描述（由申请人提供）：在非洲、亚洲和太平洋地区的80个中低收入国家中，有超过10亿人面临淋巴丝虫病（LF）的风险，这是一种蚊子寄生虫“被忽视的热带疾病”（NTD），可导致象皮病、男性生殖器畸形和四肢疼痛肿胀。在过去10年中，全球一直在努力消除班氏吴策线虫（Wb）引起的LF，目标日期为2020年（世卫组织）。该战略依赖于对捐赠的抗丝虫药物进行重复的年度大规模药物管理（MDA）（5-7年的MDA与阿苯达唑加乙胺嗪或伊维菌素），目的是将血源性微丝蚴（MF）的储存减少到低于当地蚊子媒介持续传播所需的水平。然而，最近的观察表明，消除LF的进展停滞不前，在许多地区难以确定。本申请将解决两个主要缺陷。首先是缺乏强有力的监测和评价方法，无法就以下问题作出知情决策：a）是否应继续使用或停止使用MDA; B）病媒控制措施（如长效杀虫剂处理过的蚊帐; LLIN）如何利用MDA加速消除。现有的国家LF消除计划是基于WHO推荐的Binax快速卡片测试，该测试检测血液中的成人Wb抗原。虽然这种卡测试是快速和方便的，它往往产生高假阳性和假阴性率后MDA相比，寄生虫学试验，更敏感的寄生虫抗原特异性血清学试验。第二个缺陷是缺乏可靠的定量数据来评估将使用LLIN的病媒控制与MDA相结合以减少LF传播的相对附加效益。在本申请中，我们结合了联合收割机>25年的经验和对大量样品档案的访问，这些样品是在使用NIH的同事提供的新抗原研究巴布亚新几内亚（PNG）的LF传播中获得的，并且最近在PNG引入了LLIN用于在疟疾和LF的媒介相同的地方病地区进行疟疾控制。本研究a）描述了LF消除的关键变量和监测工具，B）使用MDA量化LLIN对LF消除计划的影响，以及c）在LF消除监测期间将LF传播的昆虫学和人类标志物联系起来。本研究中测试的有效的LF消除监测工具和战略对于实现和维持巴布亚新几内亚的LF消除以及消除LF全球计划（GPELF）所述的2020年目标至关重要。 公共卫生相关性：很难确定消除LF的进展，因为对以下方面决策所需的最佳监测工具了解不多：a）是否应继续使用或停止使用MDA，以及B）病媒控制措施（如杀虫剂处理过的蚊帐; LLIN）如何使用MDA加速消除LF。这一区域办事处1的应用将测试巴布亚新几内亚社区的淋巴丝虫病监测工具和战略，这些社区接受有和没有LLIN的大规模药物管理。本研究中测试的有效的LF消除监测工具和战略对于实现和维持巴布亚新几内亚的LF消除以及消除LF全球计划（GPELF）所述的2020年目标至关重要。

DESCRIPTION (provided by applicant): More than a billion people in 80 mid- and low-income countries of Africa, Asia and the Pacific are at risk for lymphatic filariasis (LF), a mosquito bore parasitic worm "Neglected Tropical Disease" (NTD) that causes elephantiasis, disfigurement of the male genitalia and painful swelling of the extremities. For the past 10 years there has been intense global effort to eliminate LF due to Wuchereria bancrofti (Wb) with a target date of 2020 (WHO). The strategy relies on repeated annual mass drug administration (MDA) of donated anti-filarial drugs (5-7 years of MDA with albendazole plus diethylcarbamazine or ivermectin) with the aim to reduce the reservoir of blood borne microfilaria (MF) below a level required for continuing transmission by local mosquito vectors. However, recent observations indicate that progress toward LF elimination is stalled and difficult to ascertain in many areas. This application will address two major deficiencies. The first is a lack of robust methods for monitoring and evaluation that allow for informed decision making with respect to a) whether MDA should be continued or stopped and b) how vector control measures (such as long lasting insecticide treated bednets; LLIN) will accelerate elimination using MDA. Existing national LF elimination programs are based on the WHO recommended Binax rapid card test, which detects adult Wb antigen in the blood. Although this card test is rapid and convenient, it often produces high false positive and false negative rates following MDA when compared to parasitological assays, more sensitive parasite-antigen specific serological assays. The second deficiency is lack of robust quantitative data assessing of the relative added benefit of combining vector control using LLIN with MDA to reduce LF transmission. In the current application we combine >25 years experience and access to a large archive of samples obtained in studying LF transmission in Papua New Guinea (PNG) using novel antigens provided by colleagues at NIH and the recent introduction of LLINs in PNG for malaria control in a endemic area where the vectors for malaria and LF are the same. This study a) characterizes the critical variables and monitoring tools for LF elimination, b) quantifies the impact of LLIN on LF elimination programs using MDA, and c) links entomological and human markers of LF transmission during LF elimination monitoring. Effective LF elimination monitoring tools and strategies as tested in this study are essential to achieving and maintaining LF elimination in PNG and the stated 2020 goals of the Global Program for the Elimination of LF (GPELF). PUBLIC HEALTH RELEVANCE: Progress toward LF elimination is difficult to ascertain due to poor understanding of the optimal monitoring tools needed to inform decision making with respect to a) whether MDA should be continued or stopped and b) how vector control measures (such as insecticide treated bednets; LLIN) will accelerate elimination using MDA. This RO1 application will test lymphatic filariasis monitoring tools and strategies in Papua New Guinea communities receiving mass drug administration with and without LLIN. Effective LF elimination monitoring tools and strategies as tested in this study are essential to achieving and maintaining LF elimination in PNG and the stated 2020 goals of the Global Program for the Elimination of LF (GPELF).