Bovine Babesiosis

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Parasitic Pathogens".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 24873

Special Issue Editors


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Guest Editor
Animal Disease Research Unit, ARS-USDA, and Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-6630, USA
Interests: ticks and tick-borne diseases of livestock; vaccine development and molecular biology of apicomplexan parasites; diagnostics of babesiosis in livestock
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Guest Editor
Department of Veterinary Microbiology and Pathology, Washington State University, USA
Interests: diagnosis of Babesia and Theileria parasites; tick–host–pathogen interactions; immunology; innate and cellular immune responses to apicomplexan hemoparasites; vaccine development

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Guest Editor
Animal Disease Research Unit, ARS-USDA, Pullman, WA, USA
Interests: tick-borne pathogens, vector competence, tick-parasite interaction

Special Issue Information

Dear Colleagues,

Bovine babesiosis, also known as cattle tick fever, is an economically important tick-borne disease that affects bovines in tropical and subtropical areas worldwide. The tick-borne apicomplexan hemoparasites Babesia bovis, B. bigemina, B. divergens, and B. orientalis are the main causative agents of bovine babesiosis, which is characterized by high fever, profound anemia, and high mortality in naïve bovines. 

The use of acaricides to decrease tick infestation, and the utilization of live, blood-based, attenuated Babesia vaccines combined with anti-Babesia drugs are currently the only available alternatives to mitigate acute disease in endemic countries, such as Mexico, Israel, Brazil, Australia, and Argentina, among others. Despite their relative efficacy, these control strategies present both technical and logistical limitations, and novel, sustainable approaches are urgently needed to control the acute disease in endemic areas and to prevent parasite emergence in non-endemic regions.

Development of protective immunity to Babesia parasites is associated with early production of the pro-inflammatory cytokines IL-12 and IFNγ, in contrast to the anti-inflammatory cytokines IL-10 and IL-4. This kinetics of cytokine production is particularly important for survival of acutely infected animals. In addition, young calves, less than 6-month old, do not succumb to acute disease, but become chronically infected for life. These observations set the basis for vaccine development; however, additional studies are needed to fully elucidate the immune mechanisms of protection during bovine babesiosis, to understand mechanisms involved in parasite escape from the immune system, and to identify Babesia protective antigens. Of particular interest for pathogenesis, cytoadhesion of parasitized red blood cells (RBC) in the brain capillaries is observed in most cases of B. bovis infection, a condition known as cerebral babesiosis that resembles cerebral malaria, which ultimately leads to death.

Great advances in our understanding of the B. bovis and B. bigemina lifecycle have been made in recent years due to the development of genetic tools to transfect and edit the genomes of these parasites, and the use of in vitro models for sexual stage induction. These advances allowed better knowledge of the role played by several molecules during asexual and sexual stages of the parasites. However, key specific molecules for parasite invasion of and egression from RBC, markers for development of sexual stages, and mechanisms of parasite survival in the tick hemolymph and salivary glands still remain unknown.       

Altogether, this clearly demonstrates that additional studies focused on disease mechanisms, protective immunity, development of novel vaccines, tick-parasite-host interactions, parasite transmission, and novel anti-Babesia drugs, among other areas, are needed and remain of pivotal importance for the field of bovine babesiosis. Therefore, the goal of this current issue is to serve as a platform to present such studies and start filling knowledge gaps to better understand the disease and develop strategies to improve the control of bovine babesiosis. We will consider all types of articles for publication, including short reports, original research articles and reviews, and very much look forward to receiving contributions for this special issue of Pathogens.

Dr. Carlos E. Suarez
Dr. Reginaldo G. Bastos
Dr. Massaro W. Ueti
Guest Editors

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Keywords

  • Bovine babesiosis
  • Babesia bovis
  • Babesia bigemina
  • Babesia-tick-host interations
  • Babesia transfection
  • Babesia vaccines
  • Babesia diagnostics
  • Babesicidal drugs
  • Babesia gene editing
  • Babesia pathology

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Published Papers (8 papers)

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Research

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10 pages, 1924 KiB  
Article
Establishment of Babesia bovis In Vitro Culture Using Medium Free of Animal Products
by Jesús A. Álvarez Martínez, Julio V. Figueroa Millán, Massaro W. Ueti and Carmen Rojas-Martínez
Pathogens 2021, 10(6), 770; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10060770 - 19 Jun 2021
Cited by 2 | Viewed by 2374
Abstract
Babesia bovis, an etiological agent of bovine babesiosis, causes a significant burden to the cattle industry worldwide. The most efficient method to mitigate bovine babesiosis is a live vaccine produced by serial passage in splenectomized cattle. However, there are several concerns regarding [...] Read more.
Babesia bovis, an etiological agent of bovine babesiosis, causes a significant burden to the cattle industry worldwide. The most efficient method to mitigate bovine babesiosis is a live vaccine produced by serial passage in splenectomized cattle. However, there are several concerns regarding live vaccine production, including variation between batches and the use of many animals. In this study, we report a B. bovis-SF strain continuously cultured in a medium free of components of animal origin enriched with a chemically defined lipid mixture (CD lipid mixture) and the use of a perfusion bioreactor to harvest a large amount of B. bovis. Six culture media were compared, including VP-SFM, CD-CHO, CD-Hydrolyzed, CD-CHO, SFM, and ADMEM/F12. We found that the VP-SFM medium performed the best for B. bovis growth, with a maximum percentage of parasitized erythrocytes (PPE) of 8.6%. The effect of six dilutions of a commercial mixture of CD lipids added to VP-SFM showed that the CD lipid mixture at a dilution of 1:100 had the best B. bovis growth curve, with a maximum PPE of 13.9%. Propagation of the in vitro B. bovis culture was scaled up in a perfusion bioreactor using VP-SFM with a CD lipid mixture, and the PPE reached over 32%. The continuous in vitro B. bovis culture in a medium free of animal origin components could potentially reduce and replace the use of animals to produce a reagent for diagnostics and live vaccines to control bovine babesiosis. Full article
(This article belongs to the Special Issue Bovine Babesiosis)
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11 pages, 822 KiB  
Communication
A Comparative Genomic Study of Attenuated and Virulent Strains of Babesia bigemina
by Bernardo Sachman-Ruiz, Luis Lozano, José J. Lira, Grecia Martínez, Carmen Rojas, J. Antonio Álvarez and Julio V. Figueroa
Pathogens 2021, 10(3), 318; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10030318 - 08 Mar 2021
Cited by 6 | Viewed by 1991
Abstract
Cattle babesiosis is a socio-economically important tick-borne disease caused by Apicomplexa protozoa of the genus Babesia that are obligate intraerythrocytic parasites. The pathogenicity of Babesia parasites for cattle is determined by the interaction with the host immune system and the presence of the [...] Read more.
Cattle babesiosis is a socio-economically important tick-borne disease caused by Apicomplexa protozoa of the genus Babesia that are obligate intraerythrocytic parasites. The pathogenicity of Babesia parasites for cattle is determined by the interaction with the host immune system and the presence of the parasite’s virulence genes. A Babesia bigemina strain that has been maintained under a microaerophilic stationary phase in in vitro culture conditions for several years in the laboratory lost virulence for the bovine host and the capacity for being transmitted by the tick vector. In this study, we compared the virulome of the in vitro culture attenuated Babesia bigemina strain (S) and the virulent tick transmitted parental Mexican B. bigemina strain (M). Preliminary results obtained by using the Basic Local Alignment Search Tool (BLAST) showed that out of 27 virulence genes described and analyzed in the B. bigemina virulent tick transmitted strain, only five were fully identified in the attenuated laboratory strain. In all cases, the identity and coverture of the identified genes of the wildtype strain were higher than those of the laboratory strain. This finding is putatively associated with the continuous partial loss of virulence genes in the laboratory strain after several passages of the parasite population under optimal in vitro growth conditions. The loss of virulence factors might be reflected in the absence of symptoms of the disease in cattle inoculated with the attenuated strain despite the presence of infection in the bovine host cells. Full article
(This article belongs to the Special Issue Bovine Babesiosis)
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16 pages, 4030 KiB  
Article
Experimental Infection of Calves with Transfected Attenuated Babesia bovis Expressing the Rhipicephalus microplus Bm86 Antigen and eGFP Marker: Preliminary Studies towards a Dual Anti-Tick/Babesia Vaccine
by Monica L. Mazuz, Jacob M. Laughery, Benjamin Lebovitz, Daniel Yasur-Landau, Assael Rot, Reginaldo G. Bastos, Nir Edery, Ludmila Fleiderovitz, Maayan Margalit Levi and Carlos E. Suarez
Pathogens 2021, 10(2), 135; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10020135 - 29 Jan 2021
Cited by 6 | Viewed by 2690
Abstract
Bovine babesiosis, caused by Babesia bovis and B. bigemina, is a major tick-borne disease of cattle with global economic impact. The disease can be prevented using integrated control measures including attenuated Babesia vaccines, babesicidal drugs, and tick control approaches. Vaccination of cattle [...] Read more.
Bovine babesiosis, caused by Babesia bovis and B. bigemina, is a major tick-borne disease of cattle with global economic impact. The disease can be prevented using integrated control measures including attenuated Babesia vaccines, babesicidal drugs, and tick control approaches. Vaccination of cattle with the Rhipicephalus microplus Bm86-based recombinant vaccine reduces the fitness of R. microplus and R. annulatus, but several booster inoculations are required to maintain protection. Herein, we generated a stable transfected strain of B. bovis expressing an enhanced GFP (eGFP) and a chimeric version of Bm86 (B. bovis/Bm86/eGFP). The eGFP was expressed in the parasite cytoplasm, whereas Bm86 was displayed on the surface of merozoites. Three splenectomized calves experimentally infected with B. bovis/Bm86/eGFP showed mild signs of acute disease and developed long-lasting antibody responses to B. bovis and native Bm86. No evidence of sequestration of parasites in the cerebral capillaries was found upon postmortem analysis, confirming attenuation of the strain. This is the first report of transfected B. bovis expressing the tick antigen Bm86 on the merozoite surface that elicits an antibody response to native Bm86. These results represent a proof of concept for a novel live, attenuated, tagged dual-vaccine approach to attempt simultaneous control of babesiosis and tick infestation. Full article
(This article belongs to the Special Issue Bovine Babesiosis)
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14 pages, 1507 KiB  
Article
N-Glycosylation in Piroplasmids: Diversity within Simplicity
by Monica Florin-Christensen, Anabel E. Rodriguez, Carlos E. Suárez, Massaro W. Ueti, Fernando O. Delgado, Ignacio Echaide and Leonhard Schnittger
Pathogens 2021, 10(1), 50; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10010050 - 08 Jan 2021
Cited by 5 | Viewed by 2939
Abstract
N-glycosylation has remained mostly unexplored in Piroplasmida, an order of tick-transmitted pathogens of veterinary and medical relevance. Analysis of 11 piroplasmid genomes revealed three distinct scenarios regarding N-glycosylation: Babesia sensu stricto (s.s.) species add one or two N-acetylglucosamine (NAcGlc) molecules [...] Read more.
N-glycosylation has remained mostly unexplored in Piroplasmida, an order of tick-transmitted pathogens of veterinary and medical relevance. Analysis of 11 piroplasmid genomes revealed three distinct scenarios regarding N-glycosylation: Babesia sensu stricto (s.s.) species add one or two N-acetylglucosamine (NAcGlc) molecules to proteins; Theileria equi and Cytauxzoon felis add (NAcGlc)2-mannose, while B. microti and Theileria s.s. synthesize dolichol-P-P-NAcGlc and dolichol-P-P-(NAcGlc)2 without subsequent transfer to proteins. All piroplasmids possess the gene complement needed for the synthesis of the N-glycosylation substrates, dolichol-P and sugar nucleotides. The oligosaccharyl transferase of Babesia species, T. equi and C. felis, is predicted to be composed of only two subunits, STT3 and Ost1. Occurrence of short N-glycans in B. bovis merozoites was experimentally demonstrated by fluorescence microscopy using a NAcGlc-specific lectin. In vitro growth of B. bovis was significantly impaired by tunicamycin, an inhibitor of N-glycosylation, indicating a relevant role for N-glycosylation in this pathogen. Finally, genes coding for N-glycosylation enzymes and substrate biosynthesis are transcribed in B. bovis blood and tick stages, suggesting that this pathway is biologically relevant throughout the parasite life cycle. Elucidation of the role/s exerted by N-glycans will increase our understanding of these successful parasites, for which improved control measures are needed. Full article
(This article belongs to the Special Issue Bovine Babesiosis)
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11 pages, 1971 KiB  
Article
Genetic Diversity of Babesia bovis MSA-1, MSA-2b and MSA-2c in China
by Jinming Wang, Jifei Yang, Shandian Gao, Xiaoxing Wang, Hao Sun, Zhaoyong Lv, Youquan Li, Aihong Liu, Junlong Liu, Jianxun Luo, Guiquan Guan and Hong Yin
Pathogens 2020, 9(6), 473; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9060473 - 15 Jun 2020
Cited by 6 | Viewed by 2413
Abstract
The apicomplexan parasite Babesia bovis is a tick-borne intracellular hemoprotozoan parasite that is widespread across China. Genetic diversity is an important strategy used by parasites to escape the immune responses of their hosts. In our present study, 575 blood samples, collected from cattle [...] Read more.
The apicomplexan parasite Babesia bovis is a tick-borne intracellular hemoprotozoan parasite that is widespread across China. Genetic diversity is an important strategy used by parasites to escape the immune responses of their hosts. In our present study, 575 blood samples, collected from cattle in 10 provinces, were initially screened using a nested PCR (polymerase chain reaction) for detection of B. bovis infection. To perform genetic diversity analyses, positive samples were further amplified to obtain sequences of three B. bovis merozoite surface antigen genes (MSA-1, MSA-2b, MSA-2c). The results of the nested PCR approach showed that an average of 8.9% (51/575) of cattle were positive for B. bovis infection. Phylogenetic analyses of the predicted amino acid sequences revealed that unique antigen variants were formed only by Chinese isolates. Our findings provide vital information for understanding the genetic diversity of B. bovis in China. Full article
(This article belongs to the Special Issue Bovine Babesiosis)
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Review

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23 pages, 746 KiB  
Review
Bovine Babesiosis in Turkey: Impact, Current Gaps, and Opportunities for Intervention
by Sezayi Ozubek, Reginaldo G. Bastos, Heba F. Alzan, Abdullah Inci, Munir Aktas and Carlos E. Suarez
Pathogens 2020, 9(12), 1041; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9121041 - 11 Dec 2020
Cited by 28 | Viewed by 4306
Abstract
Bovine babesiosis is a global tick-borne disease that causes important cattle losses and has potential zoonotic implications. The impact of bovine babesiosis in Turkey remains poorly characterized, but several Babesia spp., including B. bovis, B. bigemina, and B. divergens, among [...] Read more.
Bovine babesiosis is a global tick-borne disease that causes important cattle losses and has potential zoonotic implications. The impact of bovine babesiosis in Turkey remains poorly characterized, but several Babesia spp., including B. bovis, B. bigemina, and B. divergens, among others and competent tick vectors, except Rhipicephalus microplus, have been recently identified in the country. Bovine babesiosis has been reported in all provinces but is more prevalent in central and highly humid areas in low and medium altitude regions of the country housing approximately 70% of the cattle population. Current control measures include acaricides and babesicidal drugs, but not live vaccines. Despite the perceived relevant impact of bovine babesiosis in Turkey, basic research programs focused on developing in vitro cultures of parasites, point-of-care diagnostic methods, vaccine development, “omics” analysis, and gene manipulation techniques of local Babesia strains are scarce. Additionally, no effective and coordinated control efforts managed by a central animal health authority have been established to date. Development of state-of-the-art research programs in bovine babesiosis to address current gaps in knowledge and implementation of long-term plans to control the disease will surely result in important economic, nutritional, and public health benefits for the country and the region. Full article
(This article belongs to the Special Issue Bovine Babesiosis)
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23 pages, 944 KiB  
Review
Research on Integrated Management for Cattle Fever Ticks and Bovine Babesiosis in the United States and Mexico: Current Status and Opportunities for Binational Coordination
by Maria D. Esteve-Gasent, Roger I. Rodríguez-Vivas, Raúl F. Medina, Dee Ellis, Andy Schwartz, Baltazar Cortés Garcia, Carrie Hunt, Mackenzie Tietjen, Denise Bonilla, Don Thomas, Linda L. Logan, Hallie Hasel, Jesús A. Alvarez Martínez, Jesús J. Hernández-Escareño, Juan Mosqueda Gualito, Miguel A. Alonso Díaz, Rodrigo Rosario-Cruz, Noé Soberanes Céspedes, Octavio Merino Charrez, Tami Howard, Victoria M. Chávez Niño and Adalberto A. Pérez de Leónadd Show full author list remove Hide full author list
Pathogens 2020, 9(11), 871; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens9110871 - 23 Oct 2020
Cited by 27 | Viewed by 4675
Abstract
Bovine babesiosis is a reportable transboundary animal disease caused by Babesia bovis and Babesiabigemina in the Americas where these apicomplexan protozoa are transmitted by the invasive cattle fever ticks Rhipicephalus (Boophilus) microplus and Rhipicephalus(Boophilus) annulatus. In countries like Mexico where [...] Read more.
Bovine babesiosis is a reportable transboundary animal disease caused by Babesia bovis and Babesiabigemina in the Americas where these apicomplexan protozoa are transmitted by the invasive cattle fever ticks Rhipicephalus (Boophilus) microplus and Rhipicephalus(Boophilus) annulatus. In countries like Mexico where cattle fever ticks remain endemic, bovine babesiosis is detrimental to cattle health and results in a significant economic cost to the livestock industry. These cattle disease vectors continue to threaten the U.S. cattle industry despite their elimination through efforts of the Cattle Fever Tick Eradication Program. Mexico and the U.S. share a common interest in managing cattle fever ticks through their economically important binational cattle trade. Here, we report the outcomes of a meeting where stakeholders from Mexico and the U.S. representing the livestock and pharmaceutical industry, regulatory agencies, and research institutions gathered to discuss research and knowledge gaps requiring attention to advance progressive management strategies for bovine babesiosis and cattle fever ticks. Research recommendations and other actionable activities reflect commitment among meeting participants to seize opportunities for collaborative efforts. Addressing these research gaps is expected to yield scientific knowledge benefitting the interdependent livestock industries of Mexico and the U.S. through its translation into enhanced biosecurity against the economic and animal health impacts of bovine babesiosis and cattle fever ticks. Full article
(This article belongs to the Special Issue Bovine Babesiosis)
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Other

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13 pages, 1366 KiB  
Case Report
First Autochthonous Report on Cattle Babesia naoakii in Central Java, Indonesia, and Identification of Haemaphysalis bispinosa Ticks in the Investigated Area
by Penny Humaidah Hamid, Muhammad Cahyadi, April Hari Wardhana, Dyah Haryuningtyas Sawitri, Nadya Nurvita R. Setya, Titis Insyariati, Heri Kurnianto and Carlos R. Hermosilla
Pathogens 2023, 12(1), 59; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12010059 - 29 Dec 2022
Cited by 6 | Viewed by 1833
Abstract
In tropical countries, clinical bovine babesiosis is a tick-borne disease primarily caused by Babesia bovis and Babesia bigemina. Here, we investigated 11 cattle with presumptive diagnosis of clinical babesiosis in Boyolali district, Central Java, Indonesia. The majority of the animals were anemic, [...] Read more.
In tropical countries, clinical bovine babesiosis is a tick-borne disease primarily caused by Babesia bovis and Babesia bigemina. Here, we investigated 11 cattle with presumptive diagnosis of clinical babesiosis in Boyolali district, Central Java, Indonesia. The majority of the animals were anemic, as evidenced by lower hematocrit, hemoglobin concentration, and red blood cell counts than the normal ranges. Blood DNA was analyzed by a PCR assay targeting the 18S rRNA-ITS region of babesial origin, and the results confirmed that the cattle were infected with Babesia species. The sequencing and phylogenetic analyses demonstrated that the animals were infected with Babesia naoakii. This is the first report of B. naoakii in Indonesia and of B. naoakii-induced clinical bovine babesiosis outside of Sri Lanka. B. naoakii causes a persistent infection, as indicated by positive PCR results for serial blood samples of the circulatory system taken two weeks after treatment. Consequently, subclinical or newly recovered cattle may serve as potential intermediate hosts and infect ticks as definitive hosts to complete the life cycle. To identify potential tick vectors, we collected ticks from cattle, including 11 animals with clinical babesiosis. Based on the morphology and the mitochondrial cytochrome c oxidase subunit 1 (COX1) of collected ticks, we found that all of the collected ticks were Haemaphysalis bispinosa, identifying this tick species as a potential vector of B. naoakii in Indonesia. In this study, the evaluation of local farmers’ awareness and practices regarding tick-borne diseases is presented, as disease prevention is also reliant on the implementation of strategies for vector control. Since livestock activities in Java represent the country’s busiest animal trade, thereby the spread of disease to other regions is possible through anthropogenic factors. In conclusion, B. naoakii is a causative pathogen of clinical bovine babesiosis autochthonously occurred in this report and further research on B. naoakii-infection is required in other regions of the country. The prompt treatment of the disease seemed crucial for animal survival, which implies the necessity of early diagnosis and a sensitive detection method. Full article
(This article belongs to the Special Issue Bovine Babesiosis)
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