Unraveling the cellular and molecular pathogenesis of bovine babesiosis: is the sky the limit?

Authors: Suarez, Carlos; ALZAN, AF - Washington State University; SILVA, MG - Washington State University; RATHINASAMY, V - Washington State University; POOLE, WA - Washington State University; COOKE, BM - Washington State University

Submitted to: International Journal for Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/21/2018
Publication Date: 1/26/2019
Citation: Suarez, C.E., Alzan, A., Silva, M., Rathinasamy, V., Poole, W., Cooke, B. 2019. Unraveling the cellular and molecular pathogenesis of bovine babesiosis: is the sky the limit? International Journal for Parasitology. 49(2):183-197. https://doi.org/10.1016/j.ijpara.2018.11.002.
DOI: https://doi.org/10.1016/j.ijpara.2018.11.002

Interpretive Summary: Bovine babesiosis is a disease with underappreciated global impact that is caused by the tick-borne apicomplexan parasites Babesia bovis, B. bigemina and B. divergens. These parasites infect and multiply in bovine red blood cells, undergo sexual reproduction in their Riphicephalus spp. tick vectors, and have a trans-ovarial mode of transmission. Babesia parasites can cause acute and persistent infections that can occur without evident clinical signs, but infections caused by B. bovis are associated with increased mortality rates and are considered to be the most virulent agent of bovine babesiosis. 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 and long-term efficacy, and improved control measures are urgently needed. In addition, the 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 demonstrates the ability of the parasites to evade the host immune responses. Currently, the mechanism 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 stages are lacking, and such, tick specific molecules can be a target for control using alternative transmission blocking vaccines. In this review, we identify and examine key phases in Babesia life-cycle, such as dependence on the tick vector, sexual reproduction in the midgut of the tick, parasite-dependent invasion and egression of bovine red blood cells, the role of spleen in the clearance of infected red blood cells (iRBC), 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 genomic, transcriptomic, proteomics), gene modification, cytoadhesion assays, red blood cell invasion assays and methods for in vitro induction of sexual stages will accelerate our understanding of parasite vulnerabilities. Further, producing new knowledge on these vulnerabilities by filling important research gaps and taking full advantage of the existing knowledge on these vulnerabilities should result in the development of next-generation vaccines to control acute disease and transmission of parasites. Creative and effective use of the current and future technical and computational resources are needed, on the face of the numerous challenges imposed by these highly evolved parasites, suggesting that the ‘sky is the limit’ in our search for improving the control of this disease. Overall, bovine babesiosis is recognized as a global disease that imposes a serious burden on livestock production and human livelihood, but it largely remains as a poorly controlled disease in many areas of the world. Recently, important progress has been made in our understanding of 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

Technical Abstract: Bovine babesiosis is a disease with underappreciated global impact that is caused by the tick-borne apicomplexan parasites Babesia bovis, B. bigemina and B. divergens. These parasites infect and multiply in bovine red blood cells, undergo sexual reproduction in their Riphicephalus spp. tick vectors, and have a trans-ovarial mode of transmission. Babesia parasites can cause acute and persistent infections that can occur without evident clinical signs, but infections caused by B. bovis are associated with increased mortality rates and are considered to be the most virulent agent of bovine babesiosis. 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 and long-term efficacy, and improved control measures are urgently needed. In addition, the 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 demonstrates the ability of the parasites to evade the host immune responses. Currently, the mechanism 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 stages are lacking, and such, tick specific molecules can be a target for control using alternative transmission blocking vaccines. In this review, we identify and examine key phases in Babesia life-cycle, such as dependence on the tick vector, sexual reproduction in the midgut of the tick, parasite-dependent invasion and egression of bovine red blood cells, the role of spleen in the clearance of infected red blood cells (iRBC), 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 genomic, transcriptomic, proteomics), gene modification, cytoadhesion assays, red blood cell invasion assays and methods for in vitro induction of sexual stages will accelerate our understanding of parasite vulnerabilities. Further, producing new knowledge on these vulnerabilities by filling important research gaps and taking full advantage of the existing knowledge on these vulnerabilities should result in the development of next-generation vaccines to control acute disease and transmission of parasites. Creative and effective use of the current and future technical and computational resources are needed, on the face of the numerous challenges imposed by these highly evolved parasites, suggesting that the ‘sky is the limit’ in our search for improving the control of this disease. Overall, bovine babesiosis is recognized as a global disease that imposes a serious burden on livestock production and human livelihood, but it largely remains as a poorly controlled disease in many areas of the world. Recently, important progress has been made in our understanding of 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