Surveillance to track and characterize antimalarial resistance trends in Ugandan Plasmodium falciparum parasites (STARTUP)

项目摘要/摘要： 乌干达和卢旺达的新研究报告称，PfKelch13(K13)基因突变的患病率不断上升 与青蒿素临床或体外治疗后寄生虫清除延迟有关，提示 他们担心恶性疟原虫对青蒿素的抗药性将出现在非洲，那里90%的恶性疟原虫 疟疾病例和死亡的发生，已经实现。然而，对组件的抵抗力程度 以青蒿素为基础的联合疗法(ACTs)还不是很清楚。我们正在进行的研究活动和 乌干达完善的基础设施使我们处于独特的地位，可以迅速满足以下方面的迫切需求 改进了乌干达对青蒿素和伙伴药物耐药性的监测和特征。 受益于全国80个监测点的网络和坎帕拉和 Tororo，我们将使用分子、寄生虫学和流行病学方法a)来评估来源， 青蒿素和ACT配对耐药已知标志物的流行和分布 描述有助于抗性表型建立和传播的遗传背景(S)， B)评估基因类型与药物敏感性/适合性表型之间的关系，以及c)评估 促进耐药性演变的生态和流行病学因素。抵抗重要的 毒品在地理上仍然是焦点，我们的目标是找出其出现和传播的关键驱动因素，然后 及时向公共卫生领导人通报遏制耐药性在整个非洲传播的最佳方法。

PROJECT SUMMARY/ABSTRACT: New studies in Uganda and Rwanda have reported increasing prevalence of mutations in pfkelch13 (K13) associated with delayed parasite clearance following clinical or in vitro treatment with artemisinins, suggesting that fears that resistance of Plasmodium falciparum to artemisinins will emerge in Africa, where >90% of malaria cases and deaths occur, have been realized. However, the extent of resistance to components of artemisinin-based combination therapies (ACTs) is not well understood. Our ongoing research activities and well-established infrastructure in Uganda put us in a unique position to rapidly address urgent needs for improved surveillance and characterization of resistance to artemisinins and partner drugs in Uganda. Benefitting from a network of 80 surveillance sites across the country and modern laboratories in Kampala and Tororo, we will use molecular, parasitological and epidemiological approaches a) to evaluate the origins, prevalence and distribution of known markers of artemisinin and ACT partner drug resistance and to characterize the genetic background(s) that facilitate the establishment and spread of resistance phenotypes, b) assess associations between genotypes and drug susceptibility/fitness phenotypes, and c) assess ecological and epidemiological factors that facilitate the evolution of resistance. With resistance to important drugs still geographically focal, our goal is to identify key drivers of its emergence and spread, and then to promptly inform public health leaders on the best means of blunting the spread of resistance across Africa.