Babesia canis
Edited by Fawaz Alhumaidi, Yemi Osayame, Jasmine Hinds, Quratul Ain Khanani; students of Jennifer Talbot for BI 311 General Microbiology, 2015, Boston University.
1. Classification
a. Higher order taxa
Higher order taxa: Domain - Eukarya Kingdom - Alveolata Phylum - Apicomplexa Class - Aconoidasida Family - Babesiidae Genus - Babesia Species: Babesia canis Subspecies - Babesia canis canis, Babesia canis vogeli, Babesia canis rossi
2. Description and significance
Babesia canis is characterized as a parasitic bacterial species that falls under the genus Babesia. Different strains of B. canis cause a disease called babesiosis that is highly prevalent among canines in southern and central Europe, particularly France, Portugal, and Hungary [1]. Babesiosis is distinguished by the symptoms of fatigue, vomiting, fever, pale mucous membranes, dark discoloration of urine, severe anemia and eventually death [2]. While much is known about the structure, classification and clinical impact of B. canis, more research is needed to identify reliable treatment and prevention methods for targeting the parasitic protozoa.
3. Genome structure
Although the three subspecies of B. canis are all similar morphologically due to the presence of adhesive proteins, they have small genotypic variations that make the species taxonomically different. Three subspecies of B. canis have been differentiated based on variation in genetic properties, vector transmission, pathogenicity, and geographic presence; the three strains are Babesia canis canis, Babesia canis vogeli, and Babesia canis rossi [3]. The different subspecies can vary in the chromosomal levels, ribosomal RNA, DNA sequences and coding regions. The first few chromosomes tend to be consistent in size. However, the remaining chromosomes of each species can slightly vary in size [4]. This causes a distortion in the number of chromosomes and size of the genome among all the three different subspecies. The differences in the single stranded ribosomal RNA caused the characterization of the three distinct subspecies [5]. The single stranded RNA coding regions for each of three subspecies are similar but have slight alterations due to nucleotide substitutions, deletions and insertions [6]. For example, the 18S ribosomal RNA coding region of the three species are mostly conserved but contain small variations due to substitutions, insertions and deletions. The differences in the DNA sequences can be anywhere from 18% to 31% across all the subspecies due to variations in the nucleotides [5].
4. Cell structure
B. canis is the largest species in size of the genus Babesia. It can range from 4-5 μm in length. It is pyriform in shape, which means it is pointed at one end and round at the other, similar to the shape of a pear. [7]. B. canis falls into the phylum of Apicomplexa; therefore, it is a single-celled eukaryotic intracellular parasite [8]. The organism requires the presence of adhesive proteins and contains parasitic cells called merozoites [8]. Currently, little information is available about the cell wall, plasma membrane, the internal structures and external structures.
5. Metabolic processes
Ticks are common vectors of B. canis. When an infected tick bites a canine host, it releases the parasite into its body in the form of a trophozoite. This is the initial activated, feeding stage for a protozoan parasite [9]. By the process of schizogony, a binary fission process where the nucleus divides before the cell, the trophozoite matures into a merozoite [10]. Merozoites invade the host erythrocyte, causing cell death and eventual anemia [11]. The rapid loss of many blood cells can also cause a high concentration of lactate to accumulate in the infected host. This causes to a buildup of lactic acid in the body, leading to organ failure [12]. Little is known about metabolic processes outside of the parasite direct effect on the host.
6. Ecology
The ecological niche has an impact on the phenotype of the individual subspecies of B. canis: B. canis canis, B. canis vogeli and B. canis rossi [5]. The adaptive capabilities of the subspecies in relation to a specific niche leads to phenotypic variations. B. bovis, a similar subspecies to B. canis was found to function best in a temperature of 37°C that promotes cellular development, along with a humid environment [7]. Currently, little information is available about the environmental requirements for the growth of B. canis.
7. Pathology
Infections by B. canis result in the canine disease, babesiosis. The most common signs of canine babesiosis are elevated body temperature, anemia, and hemoglobinuria [2]. The disease can present itself clinically with a combination of hemolytic complications that can result in severe renal failure and fatal shock [13]. Based on the severity of symptoms and clinical manifestations, canine babesiosis can potentially be life threatening. Cases of canine babesiosis are spreading across the world as the disease travels with their host and can easily be transmitted by vectors such as ticks and saliva. While infections caused by B. canis are generally found in domestic dogs, genotype sequencing among the three strains of B. canis has presented differences in the pathology of B. canis. B. canis rossi has been detected primarily in South Africa and is transmitted by the tick Haemaphysalis leachi, causing a lethal hemolytic version of babesiosis [14]. B. canis vogeli, more present in the Middle East, North Africa, Europe, Asia, and Australia, is transmitted by Rhipicephalus sanguineus and can cause mild to moderate clinical symptoms of babesiosis [14]. The third strain, B. canis canis, is prevalent in Europe and is transmitted by Dermacentor reticulatus, resulting in hemolytic anemia at varying levels of severity [14]. Detection and diagnosis of babesiosis utilizes microscopic identification of large eukaryotic parasites within the canine erythrocytes [15]. Further molecular characterization supports the existence of the three genetically distinct subspecies causing babesiosis, but future research aims to detect and reclassify smaller B. canis piroplasms that cause variations of the disease [15]. Due to the genetic diversity of the B.canis strains, protection against and treatment for infection must be highly specified.
8. Current Research
Current research regarding B. canis, although limited, aims to further characterize the microorganism. In 2017, a study was conducted regarding B. canis that examined the changes the microorganism undergoes as a parasite [16]. The procedures involved two groups of tissue infected with B. canis: a non-treated group and an imidocarb dipropionate-treated group [16]. After cells died they were observed under a light microscope that showed that B. canis exhibits changes in morphology from a large-like Babesia structure to a smaller-like Babesia structure that takes place postmortem [16]. Another current study examined the transmission of B. canis from ticks to animals [17]. Researchers conducted an experiment to see how the tick transmits B. canis to dogs as a function of time of infestation [17]. It was concluded that B. canis transmission occurs as early as 8 to 24 hours after tick infestation, highlighting the predicted timeline of infection [17]. As past research has focused on the effect of B. canis in dogs, current research also seeks to uncover its effects in other animals such as cats [3]. In a set of cats infected with B. canis, researchers amplified and sequenced the 18S rRNA gene, then phylogenetically analyzed the gene, where it was indicated that the symptoms of the infection in cats were caused by B. canis [3]. Additionally, based on phylogenetic comparisons of 18S rRNA, a novel feline genotype of B. canis was identified that is different from the B. canis subspecies in dogs, with the new subspecies being B. canis subsp. presentii [3]. As this paper has shown the difference between dogs and cats, there exists great genetic diversity of the B.canis strains, and as so, protection against and treatment for infection must be highly specified to target the different genotypes. A current study has found that the traditional therapy for the treatment of human Babesia infections has been the combination of clindamycin and quinine, yet, in recent years, it has become visible that some patients have not responded to this treatment [18]. Due to the diversity of Babesia, this research also suggests the use of Atovaquone as a better targeted treatment for patients with babesiosis who have either failed standard therapy or have become intolerant to traditional therapy [18].
9. References
[1] De Marco, M. del M. F., Hernández-Triana, L. M., Phipps, L. P., Hansford, K., Mitchell, E. S., Cull, B., … Johnson, N. (2017). Emergence of Babesia canis in southern England. Parasites & Vectors, 10, 241. http://doi.org/10.1186/s13071-017-2178-5
[2] Torbica, G., Bedrica, L., Samardzija, M., Lipar, M., Ljubojevic, D., Kreszinger, M., . . . Harapin, I. (2013). Canine babesiosis treatment with three different medicines. Acta Veterinaria Acta Veterinaria (Beograd), 63(2-3), 279-290. doi:10.2298/avb1303279t
[3] Baneth, G., Kenny, M. J., Tasker, S., Anug, Y., Shkap, V., Levy, A., & Shaw, S. E. (2004). Infection with a Proposed New Subspecies of Babesia canis, Babesia canis subsp. presentii, in Domestic Cats. Journal of Clinical Microbiology, 42(1), 99-105. doi:10.1128/jcm.42.1.99-105.2004
[4] Depoix D., Carcy B., Jumas-Bilak E., Pages M., Precigout E., Schetters TP., Ravel C. & Gorenflot A. (2002). Chromosome number, genome size and polymorphism of European and South African isolates of large Babesia parasites that infect dogs. Parasitology Research, 125(Pt 4), 313-321.
[5] Zahler, M., Schein, E., Rinder, H., & Gothe, R. (1998). Characteristic genotypes discriminate between Babesia canis isolates of differing vector specificity and pathogenicity to dogs. Parasitology Research, 84(7), 544-548.
[6] Cacciò, S. M., Antunovic, B., Moretti, A., Mangili, V., Marinculic, A., Baric, R. R., . . . Pieniazek, N. J. (2002). Molecular characterisation of Babesia canis canis and Babesia canis vogeli from naturally infected European dogs. Veterinary Parasitology, 106(4), 285-292. doi:10.1016/s0304-4017(02)00112-7
[7] Dalgliesh, R. J., & Stewart, N. P. (1982). Some effects of time, temperature and feeding on infection rates with Babesia bovis and Babesia bigemina in Boophilus microplus larvae. International journal for parasitology, 12(4), 323-326.
[8] Yang Y., Murciano B., Moubri K., Cibrelus P., Schetters T., Gorenflot A., Delbecq S. & Roumestand C. (2012). Structural and Functional Characterization of Bc28.1, Major Erythrocyte-binding Protein from Babesia canis Merozoite Surface, Journal of Biological Chemistry, 287(12), 9495-9508. DOI: 10.1074/jbc.M111.260745
[9] Yaeger, Robert G. (1996). "Protozoa: Structure, Classification, Growth, and Development". Medical Microbiology. University of Texas Medical Branch at Galveston.
[10] Irwin, P. J. (2009). Canine babesiosis: From molecular taxonomy to control. Parasites & Vectors, 2(Suppl 1). doi:10.1186/1756-3305-2-s1-s4
[11] Zhou, M., Cao, S., Luo, Y., Liu, M., Wang, G., Moumouni, P. F. A., … Xuan, X. (2016). Molecular identification and antigenic characterization of a merozoite surface antigen and a secreted antigen of Babesia canis (BcMSA1 and BcSA1). Parasites & Vectors, 9, 257. http://doi.org/10.1186/s13071-016-1518-1
[12] Nel, M., Lobetti, R. G., Keller, N., & Thompson, P. N. (2004). Prognostic Value of Blood Lactate, Blood Glucose, and Hematocrit in Canine Babesiosis. Journal of Veterinary Internal Medicine, 18(4), 471-476. doi:10.1111/j.1939-1676.2004.tb02569.x
[13] Bourdoiseau, G. (2006). Canine babesiosis in France. Veterinary Parasitology, 138(1-2), 118-125. doi:10.1016/j.vetpar.2006.01.046
[14] Ćoralić, A., Gabrielli, S., Zahirović, A., Stojanović, N. M., Milardi, G. L., Jažić, A., . . . Otašević, S. (2018). First molecular detection of Babesia canis in dogs from Bosnia and Herzegovina. Ticks and Tick-borne Diseases, 9(2), 363-368. doi:10.1016/j.ttbdis.2017.11.013
[15] Birkenheuer, A., Neel, J., Ruslander, D., Levy, M., & Breitschwerdt, E. (2004). Detection and molecular characterization of a novel large Babesia species in a dog. Veterinary Parasitology, 124(3-4), 151-160. doi:10.1016/j.vetpar.2004.07.008
[16] Huber, D., Beck, A., Anzulović, Ž., Jurković, D., Polkinghorne, A., Baneth, G., & Beck, R. (2017). Microscopic and molecular analysis of Babesia canis in archived and diagnostic specimens reveal the impact of anti-parasitic treatment and postmortem changes on pathogen detection. Parasites & vectors, 10(1), 495.
[17] Varloud, M., Liebenberg, J., & Fourie, J. (2018). Early Babesia canis transmission in dogs within 24 h and 8 h of infestation with infected pre-activated male Dermacentor reticulatus ticks. Parasites & vectors, 11(1), 41.
[18] Wittner, M., Lederman, J., Tanowitz, H. B., Rosenbaum, G. S., & Weiss, L. M. (1996). Atovaquone in the treatment of Babesia microti infections in hamsters. The American journal of tropical medicine and hygiene, 55(2), 219-222.
[19] Salem, N., & Farg, H. (2014, February). Clinical, Hematologic, and Molecular Findings in Naturally Occurring Babesia canis vogeli in Egyptian Dogs [Digital image]. Retrieved November 27, 2018, from https://www.researchgate.net/figure/Giemsa-stained-blood-smear-of-infected-dog-showing-the-pear-shaped-large-B-canis-inside_fig1_261295582
[20] Oosthuizen, Marinda C, et al. Identification of a Novel Babesia Sp. from a Sable Antelope (Hippotragus Niger Harris, 1838). Aug. 2008. (for tree photo)
[21] Walker, A. R. (2012, April 10). Babesia canis piroplasm stage infecting red blood cells of a dog. Giemsa stained. [Digital image]. Retrieved November 27, 2018, from https://commons.wikimedia.org/wiki/File:Babesia-canis-dog.jpg
