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.

The biology of intraerythrocytic Babesia parasites presents unique challenges for the diagnosis of human babesiosis. Antibody-based assays are highly sensitive but fail to detect early stage Babesia infections prior to seroconversion (window period) and cannot distinguish between an active infection and a previously resolved infection. On the other hand, nucleic acid-based tests (NAT) may lack the sensitivity to detect window cases when parasite burden is below detection limits and asymptomatic low-grade infections. Recent technological advances have improved the sensitivity, specificity and high throughput of NAT and the antibody-based detection of Babesia. Some of these advances include genomics approaches for the identification of novel high-copy-number targets for NAT and immunodominant antigens for superior antigen and antibody-based assays for Babesia. Future advances would also rely on next generation sequencing and CRISPR technology to improve Babesia detection. This review article will discuss the historical perspective and current status of technologies for the detection of Babesia microti, the most common Babesia species causing human babesiosis in the United States, and their implications for early diagnosis of acute babesiosis, blood safety and surveillance studies to monitor areas of expansion and emergence and spread of Babesia species and their genetic variants in the United States and globally.

Malaria vaccines that disrupt the Plasmodium life cycle in mosquitoes and reduce parasite transmission in endemic areas are termed transmission-blocking vaccines (TBVs). Despite decades of research, there are only a few Plasmodium falciparum antigens that indisputably and reproducibly demonstrate transmission-blocking immunity. So far, only two TBV candidates have advanced to phase 1/2 clinical testing with limited success. By applying an unbiased transcriptomics-based approach, we have identified Pf77 and male development gene 1 (PfMDV-1) as two P. falciparum TBV antigens that, upon immunization, induced antibodies that caused reductions in oocyst counts in Anopheles mosquito midguts in a standard membrane feeding assay. In-depth studies were performed to characterize the genetic diversity of, stage-specific expression by, and natural immunity to these two molecules to evaluate their suitability as TBV candidates. Pf77 and PfMDV-1 display limited antigenic polymorphism, are pan-developmentally expressed within the parasite, and induce naturally occurring antibodies in Ghanaian adults, which raises the prospect of natural boosting of vaccine-induced immune response in endemic regions. Together, these biological properties suggest that Pf77 and PfMDV-1 may warrant further investigation as TBV candidates.