Babesia microti: Pathogen Genomics, Genetic Variability, Immunodominant Antigens, and Pathogenesis

Abstract

More than 100 Babesia spp. tick-borne parasites are known to infect mammalian and avian hosts. Babesia belong to Order Piroplasmid ranked in the Phylum Apicomplexa. Recent phylogenetic studies have revealed that of the three genera that constitute Piroplasmida, Babesia and Theileria are polyphyletic while Cytauxzoon is nested within a clade of Theileria. Several Babesia spp. and sub-types have been found to cause human disease. Babesia microti, the most common species that infects humans, is endemic in the Northeastern and upper Midwestern United States and is sporadically reported elsewhere in the world. Most infections are transmitted by Ixodid (hard-bodied) ticks, although they occasionally can be spread through blood transfusion and rarely via perinatal transmission and organ transplantation. Babesiosis most often presents as a mild to moderate disease, however infection severity ranges from asymptomatic to lethal. Diagnosis is usually confirmed by blood smear or polymerase chain reaction (PCR). Treatment consists of atovaquone and azithromycin or clindamycin and quinine and usually is effective but may be problematic in immunocompromised hosts. There is no human Babesia vaccine. B. microti genomics studies have only recently been initiated, however they already have yielded important new insights regarding the pathogen, population structure, and pathogenesis. Continued genomic research holds great promise for improving the diagnosis, management, and prevention of human babesiosis, and in particular, the identification of lineage-specific families of cell-surface proteins with potential roles in cytoadherence, immune evasion and pathogenesis.

Keywords: Babesia microti; biomarkers; genomics; pathogen; population genetics; tick-borne diseases.

FIGURE 1

Geographic range of Ixodes-tick vectors and location of human babesiosis reports. The lighter colors represent the geographical range of several Ixodes tick species known or suspected to transmit Babesia parasites to humans but where human babesiosis is rare (<5 cases), unreported or absent. Ixodes ricinus and Ixodes persulcatus are sympatric in southern Finland, Estonia, Latvia, and northwestern Russia, while I. persulcatus and Ixodes ovatus are both enzootic in Hokkaido in northern Japan. The darker colors represent regions where human babesiosis is endemic or sporadic (defined by ≥5 cases). Circles indicate single cases, except in three locations (Mexico, Montenegro, and eastern Poland) where all patients at these locations were reported from the same hospital. Colors indicate Babesia species: red for B. microti, orange for B. duncani, blue for B. divergens, green for B. venatorum, pink for B. crassa like agent, black for KO-1, yellow for Babesia spp. XXB/HangZhou, and white for undetermined Babesia spp. The map does not show asymptomatic cases and travel-associated cases [adapted from Vannier and Krause (2012) and (Ryan et al., 2019) from The New England Journal of Medicine, Edouard Vannier, PhD., and Peter J. Krause, M. D., Human Babesiosis, 366, 2399. Copyright (2012) Massachusetts Medical Society. Reprinted with permission.

FIGURE 2

Developmental stages of intraerythrocytic Babesia microti parasite by Giemsa-stained thin blood microscopy. (A) Ring form with cytoplasm stained blue; (B) mature trophozoite with two small nuclei; (C) a tetrad (Maltese cross); and (D) an extracellular form. 1000× magnification. Adapted from Vannier and Krause (2012) (From The New England Journal of Medicine, Edouard Vannier, PhD., and Peter J. Krause, M. D., Human Babesiosis, 366, 2399. Copyright (2012) Massachusetts Medical Society. Reprinted with permission).

FIGURE 3

Genomics-based approaches for Babesia microti detection, molecular surveillance, understanding pathogenesis and developing therapeutics.