Babesiosis

Abstract

Babesia spp. are protozoan parasites defining separate lineages in the Apicomplexa phylum and phylogenetically closely related to Theileria, and less closely to Plasmodium species. These parasites are transmitted primarily by ticks to a wide range of domestic and wild animals as well as humans, where they develop within the host red blood cells to cause the pathological symptoms associated with babesiosis. The widespread distribution of these parasites throughout the world, their recognition as emerging pathogens and the major economic and health impacts of babesiosis have stimulated major research efforts to understand the basic biology, pathogenesis, evolution and transmission patterns of these organisms.

Key Concepts

  • Babesia spp. parasites are the causative agents of babesiosis in wild and domestic animals, as well as humans.
  • Babesia spp. are transmitted by ticks to mammals and birds, and reproduce asexually within host red blood cells.
  • Babesiosis has major health and economic impacts.
  • There are over 100 species of Babesia parasites, with several known to cause disease in humans.
  • Babesia spp. belong to at least two distinct branches, with one capable of transovarial transmission and the other only of transstadial transmission.

Keywords: parasitology; Apicomplexa; tick‐transmitted disease; babesiosis; emerging disease

Figure 1. Current taxonomic classification of most common Babesia pathogens of animals and humans.
Figure 2. Giemsa‐stained blood smear from a human babesiosis patient with high B. microti parasitaemia. ER: early ring forms represent early stages detected in an infected red blood cell following merozoite invasion. R: ring stage forms of B. microti consist of normal ring‐like forms as well as rings with long extensions. M: Meront form of B. microti following division of the mother parasite into four merozoites.
close

References

Al‐Khedery B and Allred DR (2006) Antigenic variation in Babesia bovis occurs through segmental gene conversion of the ves multigene family, within a bidirectional site of transcription. Molecular Microbiology 59: 402–414.

Allred DR (2007) Dynamics of anemia progression and recovery in Babesia bigemina infection is unrelated to initiating parasite burden. Veterinary Parasitology 146: 170–174.

Alzan HF, Lau AO, Knowles DP, et al. (2016) Expression of 6‐cys gene superfamily defines Babesia bovis sexual stage development within Rhipicephalus microplus. PLoS One 11 (9): e0163791.

Asada M, Yahata K, Hakimi H, et al. (2015) Transfection of Babesia bovis by double selection with WR99210 and blasticidin‐S and its application for functional analysis of thioredoxin peroxidase‐1. PLoS One 10 (5): e0125993.

Bastos RG, Suarez CE, Laughery JM, et al. (2013) Differential expression of three members of the multidomain adhesion CCp family in Babesia bigemina, Babesia bovis and Theileria equi. PLoS One 8 (7): e67765.

Becker CA, Malandrin L, Larcher T, et al. (2013) Validation of BdCCp2 as a marker for Babesia divergens sexual stages in ticks. Experimental Parasitology 133 (1): 51–56.

Berman KH, Blue DE, Smith DS, Kwo PY and Liangpunsakul S (2009) Fatal case of babesiosis in postliver transplant patient. Transplantation 87 (3): 452–453.

Birkenheuer AJ, Levy MG and Breitschwerdt EB (2004) Efficacy of combined atovaquone and azithromycin for therapy of chronic Babesia gibsoni (Asian genotype) infections in dogs. Journal of Veterinary Internal Medicine 18 (4): 494–498.

Bosman AM, Oosthuizen MC, Venter EH, et al. (2013) Babesia lengau associated with cerebral and haemolytic babesiosis in two domestic cats. Parasites & Vectors 6: 128.

Brayton KA, Lau AOT, Herndon DR, et al. (2007) Genome sequence of Babesia bovis and comparative analysis of apicomplexan hemoprotozoa. PLoS Pathogens 3: e148.

Brennan MB, Herwaldt BL, Kazmierczak JJ, et al. (2016) Transmission of Babesia microti parasites by solid organ transplantation. Emerging Infectious Diseases 22 (11): 1869–1876.

Camacho‐Nuez M, Hernandez‐Silva DJ, Castaneda‐Ortiz EJ, et al. (2017) Hap2, a novel gene in Babesia bigemina is expressed in tick stages, and specific antibodies block zygote formation. Parasites & Vectors 10 (1): 568.

Canto GJ, Figueroa JV, Ramos JA, et al. (2006) Evaluation of cattle inoculated with Babesia bovis clones adhesive in vitro to bovine brain endothelial cells. Annals of the New York Academy of Sciences 1081: 397–404.

Checa R, Montoya A, Ortega N, et al. (2017) Efficacy, safety and tolerance of imidocarb dipropionate versus atovaquone or buparvaquone plus azithromycin used to treat sick dogs naturally infected with the Babesia microti‐like piroplasm. Parasites & Vectors 10 (1): 145.

Clark IA, Alleva LM, Mills AC and Cowden WB (2004) Pathogenesis of malaria and clinically similar conditions. Clinical Microbiology Reviews 17 (3): 509–539.

Conrad PA, Kjemtrup AM, Carreno RA, et al. (2006) Description of Babesia duncani n.sp. (Apicomplexa: Babesiidae) from humans and its differentiation from other piroplasms. International Journal for Parasitology 36: 779–789.

Cornillot E, Hadj‐Kaddour K, Dassouli A, et al. (2012) Sequencing of the smallest apicomplexan genome from the human pathogen Babesia microti. Nucleic Acids Research 40 (18): 9102–9114.

Cornillot E, Dassouli A, Garg A, et al. (2013) Whole genome mapping and re‐organization of the nuclear and mitochondrial genomes of Babesia microti isolates. PLoS One 8 (9): e72657.

Cursino‐Santos JR, Singh M, Pham P, Rodriguez M and Lobo CA (2016) Babesia divergens builds a complex population structure composed of specific ratios of infected cells to ensure a prompt response to changing environmental conditions. Cellular Microbiology 18: 859–874.

Franssen FFJ, Gaffar FR, Yatsuda AP and de Vries E (2003) Characterisation of erythrocyte invasion by Babesia bovis merozoites efficiently released from their host cell after high‐voltage pulsing. Microbes and Infection 5: 365–372.

Gaffar FR, Yatsuda AP, Franssen FFJ and de Vries E (2004) Erythrocyte invasion by Babesia bovis merozoites is inhibited by polyclonal antisera directed against peptides derived from a homologue of Plasmodium falciparum apical membrane antigen 1. Infection and Immunity 72: 2947–2955.

Garg A, Stein A, Zhao W, et al. (2014) Sequence and annotation of the apicoplast genome of the human pathogen Babesia microti. PLoS One 9 (10): e107939.

Hermance ME and Thangamani S (2017) Powassan virus: an emerging arbovirus of public health concern in North America. Vector Borne and Zoonotic Diseases 17 (7): 453–462.

Jackson AP, Otto TD, Darby A, et al. (2014) The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host‐parasite interaction. Nucleic Acids Research 42 (11): 7113–7131.

Jacobson LS (2006) The South African form of severe and complicated canine babesiosis: clinical advances 1994–2004. Veterinary Parasitology 138 (1‐2): 126–139.

Jalovecka M, Bonsergent C, Hajdusek O, Kopacek P and Malandrin L (2016) Stimulation and quantification of Babesia divergens gametocytogenesis. Parasites & Vectors 9 (1): 439.

Johnson TL, Graham CB, Boegler KA, et al. (2017) Prevalence and diversity of tick‐borne pathogens in nymphal Ixodes scapularis (Acari: Ixodidae) in Eastern National Parks. Journal of Medical Entomology 54 (3): 742–751.

Lack JB, Reichard MV and Van Den Bussche RA (2012) Phylogeny and evolution of the Piroplasmida as inferred from 18S rRNA sequences. International Journal for Parasitology 42 (4): 353–363.

Lawres LA, Garg A, Kumar V, et al. (2016) Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin‐like quinolone and atovaquone. Journal of Experimental Medicine 213 (7): 1307–1318.

LeRoith T, Berens SJ, Brayton KA, et al. (2006) The Babesia bovis merozoite surface antigen 1 hypervariable region induces surface‐reactive antibodies that block merozoite invasion. Infection and Immunity 74: 3663–3667.

Lobo CA (2005) Babesia divergens and Plasmodium falciparum use common receptors, glycophorins A and B, to invade the human red blood cell. Infection and Immunity 73 (1): 649–651.

Mathe A, Voros K, Papp L and Reiczigel J (2006) Clinical manifestations of canine babesiosis in Hungary (63 cases). Acta Veterinaria Hungarica 54 (3): 367–385.

Meissner EG, McGillicuddy JW, Squires J, et al. (2017) Across state lines: fulminant Babesia microti infection in a liver transplant recipient. Transplant Infectious Disease 19 (5): e12741.

Moritz ED, Winton CS, Tonnetti L, et al. (2016) Screening for Babesia microti in the U.S. Blood Supply. New England Journal of Medicine 375 (23): 2236–2245.

Mosqueda J, Falcon A, Alvarez JA, et al. (2004) Babesia bigemina sexual stages are induced in vitro and are specifically recognized by antibodies in the midgut of infected Boophilus microplus ticks. International Journal for Parasitology 34: 1229–1236.

O'Connor RM and Allred DR (2000) Selection of Babesia bovis‐infected erythrocytes for adhesion to endothelial cells co‐selects for altered variant erythrocyte surface antigen isoforms. Journal of Immunology 164: 2037–2045.

O'Donoghue P (2017) Haemoprotozoa: making biological sense of molecular phylogenies. International Journal for Parasitology: Parasites and Wildlife 6 (3): 241–256.

Pellé KG, Jiang RHY, Mantel P‐Y, et al. (2015) Shared elements of host‐targeting pathways among apicomplexan parasites of differing lifestyles. Cellular Microbiology 17 (11): 1618–1639.

Repnik U, Gangopadhyay P, Bietz S, et al. (2015) The apicomplexan parasite Babesia divergens internalizes band 3, glycophorin A and spectrin during invasion of human red blood cells. Cellular Microbiology 17 (7): 1052–1068.

Schetters TP, Kleuskens J, Scholtes N and Gorenflot A (1998) Parasite localization and dissemination in the Babesia‐infected host. Annals of Tropical Medicine and Parasitology 92 (4): 513–519.

Schetters TPM, Kleuskens JAGM, Van De Crommert J, et al. (2009) Systemic inflammatory responses in dogs experimentally infected with Babesia canis; a haematologic study. Veterinary Parasitology 162: 7–15.

Schnittger L, Rodriguez AE, Florin‐Christensen M and Morrison DA (2012) Babesia: a world emerging. Infection, Genetics and Evolution 12 (8): 1788–1809.

Silva JC, Cornillot E, McCracken C, et al. (2016) Genome‐wide diversity and gene expression profiling of Babesia microti isolates identify polymorphic genes that mediate host‐pathogen interactions. Scientific Reports 6: 35284.

Simon JA, Marrotte RR, Desrosiers N, et al. (2014) Climate change and habitat fragmentation drive the occurrence of Borrelia burgdorferi, the agent of Lyme disease, at the northeastern limit of its distribution. Evolutionary Applications 7: 750–764.

Sondgeroth KS, McElwain TF, Allen AJ, Chen JV and Lau A (2013) Loss of neurovirulence is associated with reduction of cerebral capillary sequestration during acute Babesia bovis infection. Parasites & Vectors 6 (1): 181.

Suarez CE, Laughery JM, Schneider DA, Sondgeroth KS and McElwain TF (2012) Acute and persistent infection by a transfected Mo7 strain of Babesia bovis. Molecular and Biochemical Parasitology 185: 52–57.

Vannier EG, Diuk‐Wasser MA, Ben Mamoun C and Krause PJ (2015) Babesiosis. Infectious Disease Clinics of North America 29 (2): 357–370.

Wang X, Bouchut A, Xiao Y‐P, Al‐Khedery B and Allred DR (2012) Characterization of the unusual bidirectional ves promoters driving VESA1 expression and associated with antigenic variation in Babesia bovis. Eukaryotic Cell 11: 260–269.

Zintl A, McGrath G, O'Grady L, et al. (2014) Changing incidence of bovine babesiosis in Ireland. Irish Veterinary Journal 67 (1): 19.

Further Reading

Alzan HF et al. (2017) Geno‐ and phenotypic characteristics of a transfected Babesia bovis 6‐Cys‐E knockout clonal line. Parasites & Vectors 10: 214.

Asada M, Goto Y, Yahata K, et al. (2012) Gliding motility of Babesia bovis merozoites visualized by time‐lapse video microscopy. PLoS One 7: e35227.

Ather I, Pourafshar N, Schain D, Gupte A and Casey MJ (2017) Babesiosis: an unusual cause of sepsis after kidney transplantation and review of the literature. Transplant Infectious Disease 19: e12740.

Becker CAM, Malandrin L, Depoix D, et al. (2010) Identification of three CCp genes in Babesia divergens: novel markers for sexual stages parasites. Molecular and Biochemical Parasitology 174: 36–43.

Cornillot E, Dassouli A, Pachikara N, et al. (2016) A targeted immunomic approach identifies diagnostic antigens in the human pathogen Babesia microti. Transfusion 56 (8): 2085–2099.

Fang DC and McCullough J (2016) Transfusion‐transmitted Babesia microti. Transfusion Medicine Reviews 30 (3): 132–138.

Hussein HE, Bastos RG, Schneider DA, et al. (2017) The Babesia bovis hap2 gene is not required for blood stage replication, but expressed upon in vitro sexual stage induction. PLoS Neglected Tropical Diseases 11 (10): e0005965.

Lubin AS, Snydman DR and Miller KB (2011) Persistent babesiosis in a stem cell transplant recipient. Leukemia Research 35 (6): e77.

Mosqueda J, McElwain TF and Palmer GH (2002) Babesia bovis merozoite surface antigen 2 proteins are expressed on the merozoite and sporozoite surface, and specific antibodies inhibit attachment and invasion of erythrocytes. Infection and Immunity 70: 6448–6455.

de Rezende J, Rangel CP, McIntosh D, et al. (2015) In vitro cultivation and cryopreservation of Babesia bigemina sporokinetes in hemocytes of Rhipicephalus microplus. Veterinary Parasitology 212: 400–403.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Mamoun, Choukri B, and Allred, David R(Apr 2018) Babesiosis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001945.pub2]