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Towards integrated control of East Cost fever, a devastating disease of cattle

机译：走向综合控制东方成本热，一种毁灭性的牛病

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摘要

Infection of cattle with the tick-borne apicomplexan parasite Theileria parva results in the fatal lympho-proliferative disease known as East Coast fever (ECF). ECF is considered to be one of the most devastating diseases of livestock in sub-Saharan Africa affecting all sectors of livestock production. The three-host brown ear tick, Rhipicephalus appendiculatus is the primary vector of T. parva with all tick life stages adapted to feeding on cattle. Currently, there is no effective vaccine against ECF and control of R. appendiculatus and T. parva occurs primarily through the use of disease tolerant breeds, chemotherapy and acaricide application. Widespread application of acaricides for tick and tick borne-disease control is becoming less viable due to rapid development of acaricide resistance. Alternative measures for tick control based on integrated and sustainable methods are urgently needed.udControl of the one host tick Rhipicephalus microplus through anti-tick vaccination has been shown to be viable culminating in the commercial products GavacTM and TickGardTM. Both vaccines are based on the recombinant protein Bm86 expressed as concealed antigen in the R. microplus midgut. Vaccination elicits humoral immune response targeting Bm86 during tick feeding resulting in extensive gut damage. In this thesis, anti-tick vaccines were evaluated for their ability to control R. appendiculatus tick populations and to interfere with transmission of T. parva in their natural host-pathogen-vector system.udThe R. appendiculatus homologue of Bm86, named Ra86, was examined for of its impact on nymphal and adult R. appendiculatus ticks after feeding on Ra86 vaccinated cattle. The molting success of nymphal ticks to the adult stage was significantly reduced in ticks feeding on Ra86 vaccinated animals in comparison control animals. Simulations based on our empirical data suggest that repeated Ra86 vaccinations would reduce tick populations over successive generations. This experiment showed for the first time that Ra86 based vaccination could play a part in integrated pest management and control strategies for R. appendiculatus. Reducing the nymphal population molting to adult instars has implications forudECF clinical disease severity. T. parva transmission by adult ticks is commonly associated with more severe ECF disease symptoms when compared to nymph mediated transmission. Reduction of the number of adult ticks before they can transmit T. parva may lead to diminution of the negative impact of ECF on animal productivity. Additionally, Ra86 vaccination lowered T. parva infection levels in ticks that fed on vaccinated cattle indicating that targeting the tick gut could affect the uptake of T. parva from infected cattle and/or further development within the vector.udVaccines that block parasite transmission either to- or from- the vertebrate host have been proposed for the control of numerous vector-borne diseases including ECF. Cattle were vaccinated with a multivalent recombinant antigen cocktail containing R. appendiculatus antigens TRP64, histamine binding protein (male and female variants) and subolesin. Included in this cocktail was the T. parva protein p67, located on the sporozoite surface. Transmission of T. parva sporozoites from infected ticks to the vaccinated cattle was compared to control cattle. Establishment of ECF was 20 % lower in the vaccinated animals indicating that this multivalent vaccine partially prevented disease establishment. Importantly, animals that showed no or only mild ECF symptoms after cocktail vaccination and infected tick exposure were solidly protected from lethal needle challenge with the homologous T. parva stock. This work demonstrated for the first time that transmission of T. parva can be reduced by vaccination resulting in lowering of ECF clinical cases while still advantageously enables establishment of immune protection.udCurrent experimental infection of animals with T. parva involves the needle administration of cryo-preserved isolated sporozoites. This highly artificial infection method differs from natural tick based T. parva infection in both the delivery route and the number of parasite injected over time. A reliable tick-based infection method for ECF resembling natural field situations is essential for future intervention studies. Here we show for the first time that the R. appendiculatus RAM-L tick line is a suitable tool that reproducibly delivers T. parva infectious sporozoite doses to cattle resembling endemically stable field situations. Our newly developed RAM-L tick based infection model can provide information on the potential protective capacity of experimental subunit T. parva vaccines requiring substantially smaller animal numbers than conventional field trials. Together, this work adds novel information on anti-tick and transmission blocking vaccine testing for control of R. appendiculatus and T. parva.ud
机译：the传播的apicomplexan寄生虫Theileria parva感染牛会导致致命的淋巴增生性疾病，称为东海岸热（ECF）。 ECF被认为是撒哈拉以南非洲最严重的牲畜疾病之一，影响到牲畜生产的所有部门。三宿主棕色耳tick，Rhipicephalus appendiculatus是细叶锥虫的主要媒介，其所有tick生活阶段都适合以牛为食。目前，尚无针对ECF的有效疫苗，主要通过使用耐病品种，化学疗法和杀螨剂来防治盲肠罗非鱼和细小球菌。由于对杀螨剂的快速发展，杀螨剂在tick和and传播疾病控制中的广泛应用正变得不可行。迫切需要基于集成和可持续方法的methods控制措施。 ud已证明，通过抗-疫苗接种控制一种宿主hostRhipicephalus microplus在商业产品GavacTM和TickGardTM中达到了最终目的。两种疫苗均基于在微小芽孢杆菌中肠中表达为隐蔽抗原的重组蛋白Bm86。在tick喂期间，疫苗接种引起针对Bm86的体液免疫反应，导致肠道全面受损。在本论文中，评估了抗-虫疫苗在其天然宿主-病原体-载体系统中控制阑尾tick虫tick种群和干扰小。虫传播的能力。 udBm86阑尾R同源物Ra86在以Ra86疫苗接种的牛为食后，检查了其对若虫和成年罗氏append的影响。与比较对照动物相比，以Ra86疫苗接种的动物为食的tick的成虫蜕皮成年成功率显着降低。根据我们的经验数据进行的模拟表明，重复接种Ra86疫苗将减少连续世代的tick虫种群。该实验首次表明基于Ra86的疫苗接种可在阑尾红斑病的综合害虫管理和控制策略中发挥作用。将若虫种群蜕化成成年幼虫对 udECF临床疾病严重程度具有影响。与若虫介导的传播相比，成年s虫传播的小圆球菌通常与更严重的ECF疾病症状相关。减少成年transmit传播小圆虱之前的数量可能会导致ECF对动物生产力的负面影响减少。此外，Ra86疫苗接种降低了接种牛的cattle中的小圆虫的T. parva感染水平，这表明靶向targeting肠可能会影响被感染牛的小圆虫的吸收和/或载体中的进一步发育。 udV疫苗可阻止寄生虫传播已经提出了将脊椎动物寄主或寄回脊椎动物以控制许多媒介传播疾病，包括ECF。用含有阑尾毛状芽孢杆菌抗原TRP64，组胺结合蛋白（雄性和雌性变体）和次油质蛋白的多价重组抗原混合物对牛进行疫苗接种。包含在子孢子表面上的T. parva蛋白p67包含在该鸡尾酒中。将T. parva子孢子从受感染的s传播到接种牛与对照组牛进行了比较。接种动物的ECF降低了20％，表明这种多价疫苗部分预防了疾病的建立。重要的是，在接种鸡尾酒疫苗和tick感染后没有或仅有轻度ECF症状的动物得到了可靠的保护，以免受到同源小木耳菌的致死针头攻击。这项工作首次证明，通过接种疫苗可减少小肠衣原体的传播，从而降低ECF临床病例，同时仍能有利地建立免疫保护。 ud当前的小肠衣原体实验动物感染涉及冷冻针的给药。保留的子孢子。这种高度人为的感染方法在递送途径和随时间推移注射的寄生虫数量上均不同于基于自然tick的T. parva感染。对于将来的干预研究而言，一种类似于自然场的ECF可靠的基于tick虫的感染方法至关重要。在这里，我们首次展示了阑尾R. RAM-L滴答线是一种合适的工具，可将T. parva传染性子孢子剂量可重复地输送到类似地方性稳定田地的牛身上。我们新开发的基于RAM-L壁虱的感染模型可以提供有关实验亚单位T.parva疫苗潜在保护能力的信息，这些疫苗所需动物数量要比常规田间试验少得多。在一起，这项工作增加了有关抗par虫和传播阻断疫苗测试以控制阑尾罗非鱼和细小球菌的新信息。 ud

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    Olds Cassandra Leah;

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  • 年度 2013
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  • 正文语种 {"code":"en","name":"English","id":9}
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