Molecular epidemiology network for promotion and support of delivery of life vaccines against Theileria parva and Theileria annulata infection in Eastern and Northern Africa

热带环形泰勒虫病（Theileria annulata）和东海岸热（ECF），由T。parva）是疾病流行地区畜牧业发展的主要制约因素。目前，泰勒虫病的管理依赖于化疗、使用杀螨剂控制蜱虫以及在一定程度上免疫接种。经过近世纪的杀螨剂利用，现在很清楚，这本身不能提供一个可持续的解决方案，以控制泰勒虫病。感染和治疗疫苗接种（ITM）是一种可供选择的控制ECF的方法，包括接种活T。parva子孢子，同时用长效剂量的土霉素治疗。最近首次成功大规模部署的原始三价Muguga鸡尾酒（TV）版本的ITM没有明显的突破性感染的牧民系统在坦桑尼亚重新希望更广泛的部署。我们目前正在支持ITM部署，方法是使用包含TV的稳定剂的遗传组成标记，评估疫苗接种是否诱导可能导致疾病问题加重的外来寄生虫基因型的持续性蜱传播性感染（携带状态）。我们建议继续与DFG合作，为更广泛地部署信息技术管理奠定基础。特别是，我们将解决的问题，在何种程度上的基因库的牛和非洲水牛衍生的T。在坦桑尼亚以及在苏丹南部和乌干达中部部署的新目标地区，小蜜蜂种群是分开的。此外，我们还建议在开发广泛保护性的多表位亚单位疫苗中弥合宿主遗传学差距。并进一步探讨了基于T.被细小病毒感染的B淋巴细胞T. annulata的基础上接种的减毒疟原虫感染的白细胞已建立在埃及和苏丹在第2阶段。该项目的目的是：（i）确定减毒疫苗是否可以在埃及和苏丹的野外条件下保护动物免受热带泰勒虫病的侵害，（ii）评估减毒疫苗是否可以通过与亚单位疫苗结合来改进，（iii）评估候选T.特别令人感兴趣的是苏丹南部的情况，在那里我们最近首次证明了T. annulata培养疫苗的地理传播，该疫苗基于第2阶段鉴定的减毒标记物的上调和下调，（iv）实现减毒活疫苗的设计、开发和安全标准的循证声明。parva朝向南苏丹北部（Marcellino et al，2016）。后者特别有趣，因为它使南苏丹成为世界上唯一一个T。annulata和T.两种情况都有，初步数据表明在某些畜群中共存。我们建议评估这种共存对免疫试验结果的影响。

Tropical theileriosis (Theileria annulata) and East Coast fever (ECF, caused by T. parva) are major constraints for development of livestock where the diseases are endemic. Currently, management of theileriosis relies on chemotherapy, tick control using acaricides and to a certain degree immunization. After nearly a century of acaricide utilization, it is now clear that this alone cannot provide a sustainable solution to the control of theileriosis. Infection and treatment vaccination (ITM) for control of ECF is an alternative control method involving inoculation with live T. parva sporozoites and simultaneous treatment with a long-acting dose of oxytetracycline. The recent first successful large scale deployment of the orginal trivalent Muguga cocktail (TV) version of ITM without apparent breakthrough infections in pastoralist systems in Tanzania has renewed the desire for more extensive deployment. We are currently supporting ITM deployment by using markers for the genetic composition of stabilates comprising the TV to assess if vaccination induces a persistent, tick transmissible infection (carrier state) with foreign parasite genotpyes that could result in enhanced disease problems. We propose to continue our DFG collaboration to set the stage for wider deployment of ITM. In particular, we will address the issue of to what extent the gene pools of cattle and African buffalo-derived T. parva populations are separate, both in Tanzania and in the new target regions for deployment in Southern Sudan and Central Uganda. In addition, we also propose to bridge the host genetics gap in the development of broadly protective multi-epitope subunit vaccines against T. parva and further explore a vaccination strategy based on T. parva-infected B-lymphocytes. A live vaccine for T. annulata based on inoculation of attenuated schizont-infected leukocytes has been established in Egypt and Sudan in phase 2. The aim of the project is to: (i) ascertain whether attenuated vaccines can protect animals from tropical theileriosis under field conditions in Egypt and Sudan, (ii) assess whether attenuated vaccines can be improved by combining them with subunit vaccines, (iii) assess attenuation of candidate T. annulata culture vaccines based on the up- and down-regulation of attenuation markers identified in phase 2, (iv) achieve an evidence-based statement of the design, development and safety criteria of attenuated live vaccines.Of particular interest is the situation in Southern Sudan where we have recently demonstrated for the first time the geographical spread of T. parva towards the north of South Sudan (Marcellino et al, 2016). The latter is particular interesting since it makes South Sudan unique as the only country in the world where T. annulata and T. parva both occur and there is preliminary data suggesting co-existence in certain herds. We propose to assess the impact of this co-existence on the outcome of immunization trials.