由tick传播的齿丛寄生虫引起的牛babesia牛babesia的全球影响,Babesiabigemina和Babesiadivergens被大大低估了。这些寄生虫在牛红细胞(RBC)中无性繁殖,在其tick虫载体中进行有性生殖(Rhipicephalusspp。对于B.bovis和B.bigemina,和蓖麻梭菌为B.divergens),并具有跨卵巢传播模式。巴贝斯虫寄生虫可导致成年幼稚牛的急性和持续性感染,可在没有明显临床症状的情况下发生。但是由牛芽孢杆菌引起的感染与更严重的疾病和死亡率增加有关,被认为是牛巴贝斯虫病中毒性最强的病原体。此外,由B.divergens引起的babesiosis具有重要的人畜共患潜力。由B.bovis和B.bigemina引起的疾病是可以控制的,至少在某种程度上,使用包含减毒活寄生虫的治疗剂或疫苗,但是这些方法在安全性方面受到限制,易于部署和长期功效,迫切需要改进控制措施。此外,由于气候变化和其他快速变化的环境因素,蜱虫栖息地的扩大使这些寄生虫的有效控制变得复杂。虽然引起持续感染的能力促进了寄生虫在流行地区的传播和持续存在,它还突出了它们逃避宿主免疫反应的能力。目前,受感染的牛在急性和慢性感染中存活的免疫反应机制仍然知之甚少,保证进一步的研究。同样,缺乏导致有性生殖和蜱期寄生虫发育过程的分子细节,这种蜱特异性分子可以成为使用替代传播阻断疫苗控制的目标。在这次审查中,我们确定并检查了巴贝斯虫寄生虫生命周期的关键阶段,包括对传输的滴答向量的依赖,寄生虫在蜱中肠的有性繁殖,牛红细胞的寄生虫依赖性入侵和入侵,脾脏在清除感染的红细胞(IRBCs)中的作用,以及与年龄相关的抗病性,作为制定改进控制措施的机会。集成的新研究方法的可用性,包括“组学”(如基因组学,转录组学,和蛋白质组学),基因修饰,细胞粘附试验,用于体外诱导性阶段寄生虫的RBC入侵测定和方法将加速我们对寄生虫脆弱性的理解。Further,产生关于这些漏洞的新知识,以及充分利用现有知识,通过填补重要的研究空白,应该导致开发下一代疫苗来控制急性疾病和寄生虫传播。需要创造性和有效地利用当前和未来的技术和计算资源,面对这些高度进化的寄生虫带来的众多挑战,改善对这种疾病的控制。总的来说,牛babesiosis被认为是一种全球性疾病,给畜牧业生产和人类生计带来沉重负担,但在世界许多地区,它在很大程度上仍然是一种控制不佳的疾病。最近,在我们对巴贝虫寄生虫的基本生物学和宿主-寄生虫相互作用的理解方面取得了重要进展,然而,仍然需要大量的基础和转化研究来实现对这一重要疾病的有效控制,并改善动物和人类的健康。
The global impact of bovine babesiosis caused by the tick-borne apicomplexan parasites Babesia bovis, Babesia bigemina and Babesia divergens is vastly underappreciated. These parasites invade and multiply asexually in bovine red blood cells (RBCs), undergo sexual reproduction in their tick vectors (Rhipicephalus spp. for B. bovis and B. bigemina, and Ixodes ricinus for B. divergens) and have a trans-ovarial mode of transmission. Babesia parasites can cause acute and persistent infections to adult naïve cattle that can occur without evident clinical signs, but infections caused by B. bovis are associated with more severe disease and increased mortality, and are considered to be the most virulent agent of bovine babesiosis. In addition, babesiosis caused by B. divergens has an important zoonotic potential. The disease caused by B. bovis and B. bigemina can be controlled, at least in part, using therapeutic agents or vaccines comprising live-attenuated parasites, but these methods are limited in terms of their safety, ease of deployability and long-term efficacy, and improved control measures are urgently needed. In addition, expansion of tick habitats due to climate change and other rapidly changing environmental factors complicate efficient control of these parasites. While the ability to cause persistent infections facilitates transmission and persistence of the parasite in endemic regions, it also highlights their capacity to evade the host immune responses. Currently, the mechanisms of immune responses used by infected bovines to survive acute and chronic infections remain poorly understood, warranting further research. Similarly, molecular details on the processes leading to sexual reproduction and the development of tick-stage parasites are lacking, and such tick-specific molecules can be targets for control using alternative transmission blocking vaccines. In this review, we identify and examine key phases in the life-cycle of Babesia parasites, including dependence on a tick vector for transmission, sexual reproduction of the parasite in the midgut of the tick, parasite-dependent invasion and egression of bovine RBCs, the role of the spleen in the clearance of infected RBCs (IRBCs), and age-related disease resistance in cattle, as opportunities for developing improved control measures. The availability of integrated novel research approaches including \"omics\" (such as genomics, transcriptomics, and proteomics), gene modification, cytoadhesion assays, RBC invasion assays and methods for in vitro induction of sexual-stage parasites will accelerate our understanding of parasite vulnerabilities. Further, producing new knowledge on these vulnerabilities, as well as taking full advantage of existing knowledge, by filling important research gaps should result in the development of next-generation vaccines to control acute disease and parasite transmission. Creative and effective use of current and future technical and computational resources are needed, in the face of the numerous challenges imposed by these highly evolved parasites, for improving the control of this disease. Overall, bovine babesiosis is recognised as a global disease that imposes a serious burden on livestock production and human livelihood, but it largely remains a poorly controlled disease in many areas of the world. Recently, important progress has been made in our understanding of the basic biology and host-parasite interactions of Babesia parasites, yet a good deal of basic and translational research is still needed to achieve effective control of this important disease and to improve animal and human health.