Optimal trial design for a confined release of malaria-refractory transgenic mosquitoes

抗疟疾转基因蚊子有限释放的最佳试验设计

• 批准号: MR/J012254/1
• 负责人: John Marshall
• 金额: $ 36.33万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ012254%2F1
• 关键词: Optimal; trial; design; confined; release

Malaria is an infectious disease caused by a parasite spread between people by mosquitoes. In sub-Saharan Africa, it causes an estimated 800,000 deaths per year, most of whom are children under the age of five. The disease is proving very difficult to control in many parts of Africa using tools that are currently available. These include bed nets, insecticides and antimalarial drugs. It is thought that, even if these tools are widespread, elimination may not be possible in some areas. Consequently, new strategies are being considered that will complement existing ones. One such strategy is the use of genetically modified (GM) mosquitoes. Strategies using GM mosquitoes can be grouped into two categories - those aiming to reduce mosquito population size, and those aiming to replace mosquito populations with varieties unable to transmit diseases. The former strategy has been tested in the Cayman Islands, Malaysia and Brazil to control dengue fever. The latter strategy is being considered for malaria control because it is more promising on a wider scale. Here, mosquitoes would be engineered with a gene that prevents them from transmitting malaria. This would be linked to a gene that favors its inheritance across generations. Mosquitoes have a short generation time - just a few weeks - and so the antimalarial gene could quickly increase in frequency, spreading into one population and then into another. This is promising for wide-scale malaria control, but draws into question the ability to conduct a confined field trial.In this project, Dr John Marshall, a researcher in the Department of Infectious Disease Epidemiology at Imperial College London, will develop a computer simulation to determine the optimal strategy for conducting a field trial of GM mosquitoes for malaria control. One major requirement for a field trial is that transgenes remain confined to their release site while also causing a significant reduction in local malaria transmission. Field trials are being considered on islands off the coast of Africa, including the Comoros Islands, Bioko Island, and Sao Tome and Principe. Dr Marshall will tailor his models to these locations using available mosquito and malaria prevalence data. He will then use his model to determine whether transgenes can be confined to these field sites, and under what release scenarios they will cause a maximal reduction in malaria transmission.If a confined field trial is eventually successful, this will provide an important mandate for more invasive GM mosquito strategies with the potential to control malaria on a much wider scale. The malaria modelling group at Imperial College London, led by Professor Azra Ghani, has developed a model of malaria transmission covering the African continent. Dr Marshall will use this model to explore the role that GM mosquitoes could play as part of a combined, Africa-wide malaria control program. GM mosquitoes hold great promise for malaria control because they can spread beyond their release site and reduce disease transmission without requiring human compliance. This modelling work will allow the public health impact of GM mosquitoes to be predicted and compared against other combinations of malaria interventions.

疟疾是一种传染病，由蚊子在人与人之间传播的寄生虫引起。在撒哈拉以南非洲，估计每年造成80万人死亡，其中大多数是五岁以下的儿童。事实证明，在非洲许多地区，使用目前可用的工具很难控制这种疾病。这些药物包括蚊帐、杀虫剂和抗疟疾药物。人们认为，即使这些工具被广泛使用，在某些地区也可能无法根除。因此，正在考虑将补充现有战略的新战略。一种这样的策略是使用转基因蚊子。使用转基因蚊子的策略可以分为两类--旨在减少蚊子种群数量的策略，以及旨在用不能传播疾病的品种取代蚊子种群的策略。前一种策略已经在开曼群岛、马来西亚和巴西进行了试验，以控制登革热。后一种战略正在被考虑用于疟疾控制，因为它在更广泛的范围内更有希望。在这里，蚊子将被改造成一种基因，防止它们传播疟疾。这可能与一种有利于其世代遗传的基因有关。蚊子的世代时间很短，只有几周，因此抗疟疾基因可能会迅速增加频率，传播到一个种群，然后传播到另一个种群。这对大规模疟疾控制是有希望的，但引发了对进行有限田间试验的能力的质疑。在这个项目中，伦敦帝国理工学院传染病流行病学系的研究员约翰·马歇尔博士将开发一个计算机模拟，以确定进行转基因蚊子田间试验以控制疟疾的最佳策略。实地试验的一个主要要求是转基因仍然局限在其释放地点，同时也导致当地疟疾传播的显着减少。正在考虑在非洲沿海岛屿上进行实地试验，包括科摩罗群岛、比奥科岛以及圣多美和普林西比。马歇尔博士将利用现有的蚊子和疟疾流行数据为这些地区量身定做他的模型。然后，他将使用他的模型来确定是否可以将转基因限制在这些田间地点，以及在什么释放情景下，它们将最大限度地减少疟疾传播。如果有限的田间试验最终成功，这将为更具侵入性的转基因蚊子战略提供重要授权，有可能在更广泛的范围内控制疟疾。由阿兹拉·加尼教授领导的伦敦帝国理工学院疟疾建模小组开发了一个覆盖非洲大陆的疟疾传播模型。马歇尔博士将利用这一模型来探索转基因蚊子在非洲联合疟疾控制计划中可能发挥的作用。转基因蚊子在疟疾控制方面有着巨大的希望，因为它们可以在释放地点以外传播，减少疾病传播，而不需要人类的服从。这项建模工作将能够预测转基因蚊子对公共卫生的影响，并将其与疟疾干预措施的其他组合进行比较。

项目成果

Medusa: a novel gene drive system for confined suppression of insect populations.

美杜莎：一种用于有限抑制昆虫种群的新型基因驱动系统。

• DOI: 10.1371/journal.pone.0102694
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Marshall JM

The importance of mosquito behavioural adaptations to malaria control in Africa.

• DOI: 10.1111/evo.12063
• 发表时间: 2013-04
• 期刊: Evolution; international journal of organic evolution
• 作者: Gatton ML;Chitnis N;Churcher T;Donnelly MJ;Ghani AC;Godfray HC;Gould F;Hastings I;Marshall J;Ranson H;Rowland M;Shaman J;Lindsay SW
• 通讯作者: Lindsay SW

MOESM3 of Key traveller groups of relevance to spatial malaria transmission: a survey of movement patterns in four sub-Saharan African countries

与空间疟疾传播相关的主要旅行者群体的 MOESM3：对四个撒哈拉以南非洲国家的流动模式的调查

• DOI: 10.6084/m9.figshare.c.3618116_d4
• 发表时间: 2016
• 作者: Marshall J

Contributions of Women with Children and Youth Workers to Spatial Malaria Transmission in Sub-Saharan Africa

带儿童的妇女和青年工人对撒哈拉以南非洲疟疾空间传播的贡献

• 期刊: Under review
• 作者: Marshall JM

Key traveller groups of relevance to spatial malaria transmission: a survey of movement patterns in four sub-Saharan African countries.

• DOI: 10.1186/s12936-016-1252-3
• 发表时间: 2016-04-12
• 期刊: Malaria journal
• 影响因子: 3
• 作者: Marshall JM;Touré M;Ouédraogo AL;Ndhlovu M;Kiware SS;Rezai A;Nkhama E;Griffin JT;Hollingsworth TD;Doumbia S;Govella NJ;Ferguson NM;Ghani AC
• 通讯作者: Ghani AC