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.

疟疾是一种由蚊子之间的寄生虫传播引起的传染病。在撒哈拉以南非洲，估计每年造成800,000人死亡，其中大多数是五岁以下的儿童。事实证明，这种疾病在非洲许多地方使用当前可用的工具很难控制。这些包括床网，杀虫剂和抗疟药。人们认为，即使这些工具是普遍的，在某些领域也可能无法消除。因此，正在考虑将现有策略补充的新策略。一种这样的策略是使用转基因（GM）蚊子。使用GM蚊子的策略可以分为两类 - 旨在减少蚊子人口规模的策略，以及旨在用无法传播疾病的品种替代蚊子种群的策略。前者的战略已在马来西亚开曼群岛和巴西进行了测试，以控制登革热。后一种策略是用于控制疟疾的策略，因为它在更广泛的规模上更有希望。在这里，蚊子将以一种阻止它们传播疟疾的基因进行设计。这将与有利于其跨几代的继承的基因有关。蚊子的生成时间很短 - 仅几周 - 因此抗疟疾基因可以迅速增加频率，扩散到一个人群，然后扩散到另一个人群中。这对于大规模的疟疾控制是有希望的，但质疑进行受到严格的现场试验的能力。在该项目中，伦敦帝国学院传染病流行病学系的研究人员约翰·马歇尔（John Marshall）将制定计算机模拟，以确定对疟疾控制进行GM Mosquitoes进行现场试验的最佳策略。现场试验的一个主要要求是，转基因仍然局限于其释放地点，同时也会大大降低局部疟疾的传播。在非洲海岸附近的岛屿上，正在考虑实地试验，包括科莫罗斯群岛，比科岛，圣多玛和普林斯皮。马歇尔博士将使用可用的蚊子和疟疾患病率数据量身定制其模型。然后，他将使用他的模型来确定是否可以将转基因局限于这些现场地点，在哪种释放场景下，它们将导致疟疾传播的最大减少。如果最终成功的现场试验成功，这将为更具侵入性的GM蚊子策略提供重要的授权，并有可能控制大量范围。由阿兹拉·加尼（Azra Ghani）教授领导的伦敦帝国学院的疟疾建模小组开发了覆盖非洲大陆的疟疾传播模型。马歇尔博士将使用该模型来探索GM蚊子可以作为一个联合范围内的非洲疟疾控制计划的一部分扮演的角色。转基因蚊子可以控制疟疾，因为它们可以扩散到释放部位并减少疾病传播而无需人类依从性。这项建模工作将使通用蚊子的公共卫生影响可以预测，并与疟疾干预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

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

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

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

MOESM1 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 MOESM1：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_d1
• 发表时间: 2016
• 作者: Marshall J