Babesiosis is attracting increasing attention as a worldwide emerging zoonosis. The first case of human babesiosis in Europe was described in the late 1950s and since then more than 60 cases have been reported in Europe. While the disease is relatively rare in Europe, it is significant because the majority of cases present as life-threatening fulminant infections, mainly in immunocompromised patients. Although appearing clinically similar to human babesiosis elsewhere, particularly in the USA, most European forms of the disease are distinct entities, especially concerning epidemiology, human susceptibility to infection and clinical management. This paper describes the history of the disease and reviews all published cases that have occurred in Europe with regard to the identity and genetic characteristics of the etiological agents, pathogenesis, aspects of epidemiology including the eco-epidemiology of the vectors, the clinical courses of infection, diagnostic tools and clinical management and treatment.

Multiple interactions between parasite ligands and their receptors on the human erythrocyte are a condition of successful Plasmodium falciparum invasion. The identification and characterization of these receptors presents a major challenge in the effort to understand the mechanism of invasion and to develop the means to prevent it. We describe here a novel member of the reticulocyte-binding family homolog (RH) of P. falciparum, PfRH5, and show that it binds to a previously unrecognized receptor on the RBC. PfRH5 is expressed as a 63 kDa protein and localized at the apical end of the invasive merozoite. We have expressed a fragment of PfRH5 which contains the RBC-binding domain and exhibits the same pattern of interactions with the RBC as the parent protein. Attachment is inhibited if the target cells are exposed to high concentrations of trypsin, but not to lower concentrations or to chymotrypsin or neuraminidase. We have determined the affinity, copy number and apparent molecular mass of the receptor protein. Thus, we have shown that PfRH5 is a novel erythrocyte-binding ligand and the identification and partial characterization of the new RBC receptor may indicate the existence of an unrecognized P. falciparum invasion pathway

Babesiosis is considered an emerging disease because its incidence has significantly increased in the last 30 years, providing evidence of the expanding range of this rare but potentially life-threatening zoonotic disease. Babesia divergens is a causative agent of babesiosis in humans and cattle in Europe. The recently sequenced genome of B. divergens revealed over 3,741 protein coding-genes and the 10.7-Mb high-quality draft become the first reference tool to study the genome structure of B. divergens. Now, by exploiting this sequence data and using new computational tools and assembly strategies, we have significantly improved the quality of the B. divergens genome. The new assembly shows better continuity and has a higher correspondence to B. bovis chromosomes. Moreover, we present a differential expression analysis using RNA sequencing of the two different stages of the asexual lifecycle of B. divergens: the free merozoite capable of invading erythrocytes and the intraerythrocytic parasite stage that remains within the erythrocyte until egress. Comparison of mRNA levels of both stages identified 1,441 differentially expressed genes. From these, around half were upregulated and the other half downregulated in the intraerythrocytic stage. Orthogonal validation by real-time quantitative reverse transcription PCR confirmed the differential expression. A moderately increased expression level of genes, putatively involved in the invasion and egress processes, were revealed in the intraerythrocytic stage compared with the free merozoite. On the basis of these results and in the absence of molecular models of invasion and egress for B. divergens, we have proposed the identified genes as putative molecular players in the invasion and egress processes. Our results contribute to an understanding of key parasitic strategies and pathogenesis and could be a valuable genomic resource to exploit for the design of diagnostic methods, drugs and vaccines to improve the control of babesiosis. Babesiosis has long been recognized as an economically important disease of cattle, but only in the last 40 years has Babesia been recognized as an important pathogen in humans. Babesiosis in humans is caused by one of several species (B. microti, B. divergens, B. duncani and B. venatorum). The complete Babesia lifecycle requires two hosts, the ixodid ticks and a vertebrate host. It is the parasite's ability to first recognize and then invade host erythrocytes that is central to the pathogenesis of babesiosis. Once inside the cell, the parasite begins a cycle of maturation and growth, resulting in merozoites that egress from the red blood cells (RBCs) and seek new, uninfected RBCs to invade, perpetuating the infection. To better understand this asexual lifecycle, the authors focused on the parasite genome and transcriptome of the asexual erythrocytic forms of B. divergens. Through this functional and comparative genomic approach, the authors have identified genes putatively involved in invasion, gliding motility, moving junction formation and egress, providing new insights into the molecular mechanisms of these processes necessary for B. divergens to survive and propagate during its life cycle.

Babesiosis is a malaria-like disease in humans and animals that is caused by Babesia species, which are tick-transmitted apicomplexan pathogens. Babesia duncani causes severe to lethal infection in humans, but despite the risk that this parasite poses as an emerging pathogen, little is known about its biology, metabolic requirements or pathogenesis. Unlike other apicomplexan parasites that infect red blood cells, B. duncani can be continuously cultured in vitro in human erythrocytes and can infect mice resulting in fulminant babesiosis and death. We report comprehensive, detailed molecular, genomic, transcriptomic and epigenetic analyses to gain insights into the biology of B. duncani. We completed the assembly, 3D structure and annotation of its nuclear genome, and analysed its transcriptomic and epigenetics profiles during its asexual life cycle stages in human erythrocytes. We used RNA-seq data to produce an atlas of parasite metabolism during its intraerythrocytic life cycle. Characterization of the B. duncani genome, epigenome and transcriptome identified classes of candidate virulence factors, antigens for diagnosis of active infection and several attractive drug targets. Furthermore, metabolic reconstitutions from genome annotation and in vitro efficacy studies identified antifolates, pyrimethamine and WR-99210 as potent inhibitors of B. duncani to establish a pipeline of small molecules that could be developed as effective therapies for the treatment of human babesiosis.

Multiple parasite ligand-erythrocyte receptor interactions must occur for successful Babesia and Plasmodium invasion of the human red cell. One such parasite ligand is the apical membrane antigen 1 (AMA1) which is a conserved apicomplexan protein present in the micronemes and then secreted onto the surface of the merozoite. Much evidence exists for a vital role for AMA1 in host cell invasion; however, its interaction with the host erythrocyte has remained controversial. In this paper, we present a detailed characterization of a Babesia divergens homolog of AMA1 (BdAMA1), and taking advantage of the relatively high amounts of native BdAMA1 available from the parasite culture system, show that proteolytic products of native BdAMA1 bind to a trypsin- and chymotrypsin-sensitive receptor on the red blood cell. Moreover, immuno-electron microscopic images of the B. divergens merozoite captured during invasion offer additional evidence of the presence of BdAMA1 on the red cell membrane. Given the importance of AMA1 in invasion and the central role invasion plays in pathogenesis, these studies have implications both for novel drug design and for the development of new vaccine approaches aimed at interfering with AMA1 function.