Medlock Jan, Luz Paula M, Struchiner Claudio J, Galvani Alison P
Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Am Nat. 2009 Oct;174(4):565-77. doi: 10.1086/605403.
Dengue is a major public health concern in the tropics and subtropics. Innovative transgenic strategies to render Aedes aegypti mosquitoes, the primary vector of dengue, incompetent for dengue transmission are under development. We modeled the evolutionary impact of different transgenic mosquito strategies on dengue-induced mortality, that is, dengue virulence, to both humans and mosquitoes. This model incorporates various evolutionary trade-offs in dengue virus epidemiological traits, for example, a trade-off between dengue transmission rate and its virulence to humans. Our results indicate that strategies that block transmission or reduce mosquito biting impose selection on dengue virulence in humans. This selection can be for either higher or lower virulence, depending on the interaction between the effect of the transgene and the trade-offs in epidemiological traits, highlighting the need for detailed quantitative data to understand more fully the impact of mosquito transgenesis on dengue virulence. Dengue virulence in mosquitoes can be selected on by transgenic strategies of blocking transmission, decreased mosquito biting, increased mosquito background mortality, and increased mosquito infection-induced mortality. Our results suggest that dengue control strategies that raise mosquito background mortality or mosquito infection-induced mortality pose less risk of causing increased virulence to humans than strategies that block transmission or reduce mosquito biting.
登革热是热带和亚热带地区主要的公共卫生问题。目前正在研发创新的转基因策略，以使登革热的主要传播媒介埃及伊蚊无法传播登革热。我们模拟了不同转基因蚊子策略对登革热所致死亡率（即登革热对人类和蚊子的毒力）的进化影响。该模型纳入了登革热病毒流行病学特征中的各种进化权衡，例如，登革热传播率与其对人类毒力之间的权衡。我们的结果表明，阻断传播或减少蚊子叮咬的策略会对人类登革热毒力产生选择作用。这种选择可能导致毒力升高或降低，具体取决于转基因效应与流行病学特征权衡之间的相互作用，这凸显了需要详细的定量数据来更全面地了解蚊子转基因对登革热毒力的影响。阻断传播转基因策略、减少蚊子叮咬、增加蚊子本底死亡率以及增加蚊子感染所致死亡率等转基因策略，均可对蚊子的登革热毒力产生选择作用。我们的结果表明，与阻断传播或减少蚊子叮咬的策略相比，提高蚊子本底死亡率或蚊子感染所致死亡率的登革热控制策略导致人类毒力增加的风险更低。
