Insecticide mosaics and sustainability of treated nets

描述(申请人提供)：驱虫蚊帐作为一种干预措施，在疟疾死亡人数较高的撒哈拉以南非洲流行地区减少疟疾传播方面显示出巨大的希望。当低毒拟除虫菊酯进入蚊帐时，主要媒介冈比亚按蚊、按蚊和印度按蚊的雌性按蚊。Arabiens和An.Funestus要么被击退，要么被吓倒，要么在接触时被杀死。在这项建议中，我们将重点放在ITNS中对合成拟除虫菊酯的抗性进化的潜力，以干扰其使用的可持续性。我们的研究地点在肯尼亚西部，在那里，最近完成了在常年传播的全流行病地区进行的唯一大规模试验，那里大约有12万人处于蚊帐之下。这四个具体目标是：(1)利用新的分子遗传学方法和地理信息系统分析评估ITN实施对媒介种群遗传和群落结构以及抗性流行的影响。(2)实验室和野外环境下按蚊雌性对驱虫蚊帐的行为反应的量化。(3)田间环境下评价杀虫剂花叶ITN配方和轮作方案对昆虫学传播参数的影响。(4)杀虫剂马赛克和轮换对疟疾结局影响的队列流行病学分析。我们的主要假设是，杀虫剂马赛克(即，同时提供或暂时轮换的杀虫剂在净材料中)提供了在操作条件下缓和和管理抗性影响的手段。我们将通过加入低毒但针对这些媒介的高活性和可变活性的杀虫剂马赛克来制定和评估抗药性管理策略。将包括具有不同驱避性、威慑性和致命性的第一类和第二类拟除虫菊酯、类似吡丙酚的激素、低毒氨基甲酸酯丁硫丹和低毒有机磷吡咪硫磷。出于制定和评估的目的，行业合作伙伴维斯特加德-弗兰森和先正达直接参与了这些努力。

DESCRIPTION (provided by applicant): Insecticide treated bed nets (ITNs) show great promise as an intervention to reduce malaria transmission in endemic areas of subSaharan Africa, where the toll of malaria is high. When low toxicity pyrethroids are incorporated into the nets, females of the main vector species Anopheles gambiae, An. arabiensis, and An. funestus are either repelled, deterred, or are killed on contact. In this proposal, we focus on the potential for evolution of resistance to synthetic pyrethroids in ITNs to interfere with sustainability of their use. Our study site is in western Kenya, where the only large scale trial in a holoendemic area with perennial transmission was recently completed, and where approximately 120,000 people are under nets. The four specific aims are: (1) Evaluation of the effect of ITN implementation on vector population genetic and community structure and prevalence of resistance using novel molecular genetic approaches and GIS analyses. (2) Quantification of behavioral responses of Anopheles females to insecticide treated net materials in laboratory and field settings. (3) Evaluation of insecticide mosaic ITN formulations and rotation schemes on entomological transmission parameters in field settings. (4) Cohort epidemiologic analyses of the effects of insecticide mosaics and rotations on malariologic outcomes. Our primary hypothesis is that Insecticide mosaics (i.e., simultaneously presented or temporally rotated insecticides in net materials) provide the means of moderating and managing the effects of resistance under operational conditions. We will develop and evaluate resistance management strategies through incorporation of insecticide mosaics of low toxicity but high and variable activity against these vectors. Included will be both Type I and Type II pyrethroids with varying repellence, deterrence, and lethality properties, the hormone mimic pyriproxyphen, the low toxicity carbamate carbosulfan, and the low toxicity organophosphate pirimiphos-methyl. Industry partners Vestergaard-Frandsen and Syngenta are directly involved in these efforts, for formulation and evaluation purposes.