Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics
Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics
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DOI：
10.1073/pnas.1611064114
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发表时间：
2017-01-10
影响因子：
11.1
通讯作者：
Burt, Austin
中科院分区：
文献类型：
--
作者：
Eckhoff, Philip A.;Wenger, Edward A.;Burt, Austin
为消除疟疾并永久消除其巨大负担而做出的新努力凸显了这样的问题：什么样的工具组合在各种情况下才足够，以及需要开发哪些新工具。基因驱动蚊子构成了一套有前途的工具，具有多种不同的可能方法，包括用引入的限制疟疾传播的基因进行种群替换，驱动Y染色体以瓦解蚊子种群，以及基因驱动破坏生育基因，从而实现种群抑制或瓦解。这些方法中的每一种最近都在实验室条件下取得了成功和进展，这就迫切需要了解如何在真实的世界中部署每一种方法以及每一种方法的潜在影响。新的分析是必要的，因为现有的基因驱动模型主要集中在非季节性或非空间动态。我们使用一个机械的，空间上明确的，随机的，以个人为基础的数学模型来模拟各种撒哈拉以南非洲环境中的每一种基因驱动方法。每种方法都表现出广泛的基因构建体参数空间区域，并成功消除了靶向载体物种引起的疟疾传播。与非季节性分析相比，在病媒种群动态中引入现实的季节性有助于基因驱动的成功。空间模拟说明了在最具挑战性的环境中对释放时间、频率和空间密度的限制。在其成功的参数空间内，每种基因驱动方法都提供了一种消除疟疾的工具，这与目前可用的任何工具都不同。如果成功的潜在障碍被克服，每一个在降低传播潜力和降低物流挑战环境中的交付要求方面都取得了很高的效率。
The renewed effort to eliminate malaria and permanently remove its tremendous burden highlights questions of what combination of tools would be sufficient in various settings and what new tools need to be developed. Gene drive mosquitoes constitute a promising set of tools, with multiple different possible approaches including population replacement with introduced genes limiting malaria transmission, driving-Y chromosomes to collapse a mosquito population, and gene drive disrupting a fertility gene and thereby achieving population suppression or collapse. Each of these approaches has had recent success and advances under laboratory conditions, raising the urgency for understanding how each could be deployed in the real world and the potential impacts of each. New analyses are needed as existing models of gene drive primarily focus on nonseasonal or nonspatial dynamics. We use a mechanistic, spatially explicit, stochastic, individual-based mathematical model to simulate each gene drive approach in a variety of sub-Saharan African settings. Each approach exhibits a broad region of gene construct parameter space with successful elimination of malaria transmission due to the targeted vector species. The introduction of realistic seasonality in vector population dynamics facilitates gene drive success compared with nonseasonal analyses. Spatial simulations illustrate constraints on release timing, frequency, and spatial density in the most challenging settings for construct success. Within its parameter space for success, each gene drive approach provides a tool for malaria elimination unlike anything presently available. Provided potential barriers to success are surmounted, each achieves high efficacy at reducing transmission potential and lower delivery requirements in logistically challenged settings.