Pathogens

Editorial

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5 pages, 223 KiB

Open AccessEditorial

Babesia and Human Babesiosis

by Estrella Montero, Jeremy Gray, Cheryl Ann Lobo and Luis Miguel González

Pathogens 2022, 11(4), 399; https://doi.org/10.3390/pathogens11040399 - 25 Mar 2022

Cited by 3 | Viewed by 2703

Abstract

Babesia is a genus of intraerythrocytic protozoan parasites belonging to the exclusively parasitic phylum Apicomplexa [...] Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

Research

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10 pages, 1552 KiB

Open AccessArticle

An Alternative Culture Medium for Continuous In Vitro Propagation of the Human Pathogen Babesia duncani in Human Erythrocytes

by Pallavi Singh, Anasuya C. Pal and Choukri Ben Mamoun

Pathogens 2022, 11(5), 599; https://doi.org/10.3390/pathogens11050599 - 20 May 2022

Cited by 9 | Viewed by 2827

Abstract

Continuous propagation of Babesia duncani in vitro in human erythrocytes and the availability of a mouse model of B. duncani lethal infection make this parasite an ideal model to study Babesia biology and pathogenesis. Two culture media, HL-1 and Claycomb, with proprietary formulations [...] Read more.

Continuous propagation of Babesia duncani in vitro in human erythrocytes and the availability of a mouse model of B. duncani lethal infection make this parasite an ideal model to study Babesia biology and pathogenesis. Two culture media, HL-1 and Claycomb, with proprietary formulations are the only culture media known to support the parasite growth in human erythrocytes; however, the HL-1 medium has been discontinued and the Claycomb medium is often unavailable leading to major interruptions in the study of this pathogen. To identify alternative media conditions, we evaluated the growth of B. duncani in various culture media with well-defined compositions. We report that the DMEM-F12 culture medium supports the continuous growth of the parasite in human erythrocytes to levels equal to those achieved in the HL-1 and Claycomb media. We generated new clones of B. duncani from the parental WA-1 clinical isolate after three consecutive subcloning events in this medium. All clones showed a multiplication rate in vitro similar to that of the WA-1 parental isolate and cause fatal infection in C3H/HeJ mice. The culture medium, which can be readily reconstituted from its individual components, and the tools and resources developed here will facilitate the study of B. duncani. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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12 pages, 976 KiB

Open AccessArticle

Babesia and Theileria Identification in Adult Ixodid Ticks from Tapada Nature Reserve, Portugal

by Nélida Fernández, Belen Revuelta, Irene Aguilar, Jorge Francisco Soares, Annetta Zintl, Jeremy Gray, Estrella Montero and Luis Miguel Gonzalez

Pathogens 2022, 11(2), 222; https://doi.org/10.3390/pathogens11020222 - 8 Feb 2022

Cited by 4 | Viewed by 2464

Abstract

This study, conducted in a nature reserve in southern Portugal, investigated the frequency and diversity of tick-borne piroplasms in six species of adult ixodid ticks removed from 71 fallow deer (Dama dama) and 12 red deer (Cervus elaphus), collected [...] Read more.

This study, conducted in a nature reserve in southern Portugal, investigated the frequency and diversity of tick-borne piroplasms in six species of adult ixodid ticks removed from 71 fallow deer (Dama dama) and 12 red deer (Cervus elaphus), collected over the period 2012–2019. The majority of 520 ticks were Ixodes ricinus (78.5%), followed by Rhipicephalus sanguineus sensu lato, Hyalomma lusitanicum, Haemaphysalis punctata, Dermacentor marginatus, and Ixodes hexagonus. The R. sanguineus ticks collected from the deer were clearly exophilic, in contrast to the endophilic species usually associated with dogs. Four tick-borne piroplasms, including Theileria spp., and the zoonotic species, Babesia divergens and Babesia microti, were detected. B. divergens 18S rDNA, identical to that of the bovine reference strain U16370 and to certain strains from red deer, was detected in I. ricinus ticks removed from fallow deer. The sporadic detection of infections in ticks removed from the same individual hosts suggests that the piroplasms were present in the ticks rather than the hosts. Theileria sp. OT3 was found in I. ricinus and, along with T. capreoli, was also detected in some of the other tick species. The natural vector and pathogenic significance of this piroplasm are unknown. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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26 pages, 359 KiB

Open AccessArticle

In Silico Survey and Characterization of Babesia microti Functional and Non-Functional Proteases

by Monica Florin-Christensen, Sarah N. Wieser, Carlos E. Suarez and Leonhard Schnittger

Pathogens 2021, 10(11), 1457; https://doi.org/10.3390/pathogens10111457 - 10 Nov 2021

Cited by 5 | Viewed by 2524

Abstract

Human babesiosis caused by the intraerythrocytic apicomplexan Babesia microti is an expanding tick-borne zoonotic disease that may cause severe symptoms and death in elderly or immunocompromised individuals. In light of an increasing resistance of B. microti to drugs, there is a lack of [...] Read more.

Human babesiosis caused by the intraerythrocytic apicomplexan Babesia microti is an expanding tick-borne zoonotic disease that may cause severe symptoms and death in elderly or immunocompromised individuals. In light of an increasing resistance of B. microti to drugs, there is a lack of therapeutic alternatives. Species-specific proteases are essential for parasite survival and possible chemotherapeutic targets. However, the repertoire of proteases in B. microti remains poorly investigated. Herein, we employed several combined bioinformatics tools and strategies to organize and identify genes encoding for the full repertoire of proteases in the B. microti genome. We identified 64 active proteases and 25 nonactive protease homologs. These proteases can be classified into cysteine (n = 28), serine (n = 21), threonine (n = 14), asparagine (n = 7), and metallopeptidases (n = 19), which, in turn, are assigned to a total of 38 peptidase families. Comparative studies between the repertoire of B. bovis and B. microti proteases revealed differences among sensu stricto and sensu lato Babesia parasites that reflect their distinct evolutionary history. Overall, this data may help direct future research towards our understanding of the biology and pathogenicity of Babesia parasites and to explore proteases as targets for developing novel therapeutic interventions. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

17 pages, 3942 KiB

Open AccessArticle

The New Human Babesia sp. FR1 Is a European Member of the Babesia sp. MO1 Clade

by Claire Bonsergent, Marie-Charlotte de Carné, Nathalie de la Cotte, François Moussel, Véronique Perronne and Laurence Malandrin

Pathogens 2021, 10(11), 1433; https://doi.org/10.3390/pathogens10111433 - 4 Nov 2021

Cited by 5 | Viewed by 4429

Abstract

In Europe, Babesia divergens is responsible for most of the severe cases of human babesiosis. In the present study, we describe a case of babesiosis in a splenectomized patient in France and report a detailed molecular characterization of the etiological agent, named Babesia [...] Read more.

In Europe, Babesia divergens is responsible for most of the severe cases of human babesiosis. In the present study, we describe a case of babesiosis in a splenectomized patient in France and report a detailed molecular characterization of the etiological agent, named Babesia sp. FR1, as well as of closely related Babesia divergens, Babesia capreoli and Babesia sp. MO1-like parasites. The analysis of the conserved 18S rRNA gene was supplemented with the analysis of more discriminant markers involved in the red blood cell invasion process: rap-1a (rhoptry-associated-protein 1) and ama-1 (apical-membrane-antigen 1). The rap-1a and ama-1 phylogenetic analyses were congruent, placing Babesia sp. FR1, the new European etiological agent, in the American cluster of Babesia sp. MO1-like parasites. Based on two additional markers, our analysis confirms the clear separation of B. divergens and B. capreoli. Babesia sp. MO1-like parasites should also be considered as a separate species, with the rabbit as its natural host, differing from those of B. divergens (cattle) and B. capreoli (roe deer). The natural host of Babesia sp. FR1 remains to be discovered. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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15 pages, 4677 KiB

Open AccessArticle

Babesia microti Immunoreactive Rhoptry-Associated Protein-1 Paralogs Are Ancestral Members of the Piroplasmid-Confined RAP-1 Family

by Reginaldo G. Bastos, Jose Thekkiniath, Choukri Ben Mamoun, Lee Fuller, Robert E. Molestina, Monica Florin-Christensen, Leonhard Schnittger, Heba F. Alzan and Carlos E. Suarez

Pathogens 2021, 10(11), 1384; https://doi.org/10.3390/pathogens10111384 - 26 Oct 2021

Cited by 7 | Viewed by 2627

Abstract

Babesia, Cytauxzoon and Theileria are tick-borne apicomplexan parasites of the order Piroplasmida, responsible for diseases in humans and animals. Members of the piroplasmid rhoptry-associated protein-1 (pRAP-1) family have a signature cysteine-rich domain and are important for parasite development. We propose that the [...] Read more.

Babesia, Cytauxzoon and Theileria are tick-borne apicomplexan parasites of the order Piroplasmida, responsible for diseases in humans and animals. Members of the piroplasmid rhoptry-associated protein-1 (pRAP-1) family have a signature cysteine-rich domain and are important for parasite development. We propose that the closely linked B. microti genes annotated as BMR1_03g00947 and BMR1_03g00960 encode two paralogue pRAP-1-like proteins named BmIPA48 and Bm960. The two genes are tandemly arranged head to tail, highly expressed in blood stage parasites, syntenic to rap-1 genes of other piroplasmids, and share large portions of an almost identical ~225 bp sequence located in their 5′ putative regulatory regions. BmIPA48 and Bm960 proteins contain a N-terminal signal peptide, share very low sequence identity (<13%) with pRAP-1 from other species, and harbor one or more transmembrane domains. Diversification of the piroplasmid-confined prap-1 family is characterized by amplification of genes, protein domains, and a high sequence polymorphism. This suggests a functional involvement of pRAP-1 at the parasite-host interface, possibly in parasite adhesion, attachment, and/or evasion of the host immune defenses. Both BmIPA48 and Bm960 are recognized by antibodies in sera from humans infected with B. microti and might be promising candidates for developing novel serodiagnosis and vaccines. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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17 pages, 6521 KiB

Open AccessArticle

Plasmepsin-like Aspartyl Proteases in Babesia

by Pavla Šnebergerová, Pavla Bartošová-Sojková, Marie Jalovecká and Daniel Sojka

Pathogens 2021, 10(10), 1241; https://doi.org/10.3390/pathogens10101241 - 26 Sep 2021

Cited by 7 | Viewed by 3093

Abstract

Apicomplexan genomes encode multiple pepsin-family aspartyl proteases (APs) that phylogenetically cluster to six independent clades (A to F). Such diversification has been powered by the function-driven evolution of the ancestral apicomplexan AP gene and is associated with the adaptation of various apicomplexan species [...] Read more.

Apicomplexan genomes encode multiple pepsin-family aspartyl proteases (APs) that phylogenetically cluster to six independent clades (A to F). Such diversification has been powered by the function-driven evolution of the ancestral apicomplexan AP gene and is associated with the adaptation of various apicomplexan species to different strategies of host infection and transmission through various invertebrate vectors. To estimate the potential roles of Babesia APs, we performed qRT-PCR-based expressional profiling of Babesia microti APs (BmASP2, 3, 5, 6), which revealed the dynamically changing mRNA levels and indicated the specific roles of individual BmASP isoenzymes throughout the life cycle of this parasite. To expand on the current knowledge on piroplasmid APs, we searched the EuPathDB and NCBI GenBank databases to identify and phylogenetically analyse the complete sets of APs encoded by the genomes of selected Babesia and Theileria species. Our results clearly determine the potential roles of identified APs by their phylogenetic relation to their homologues of known function—Plasmodium falciparum plasmepsins (PfPM I–X) and Toxoplasma gondii aspartyl proteases (TgASP1–7). Due to the analogies with plasmodial plasmepsins, piroplasmid APs represent valuable enzymatic targets that are druggable by small molecule inhibitors—candidate molecules for the yet-missing specific therapy for babesiosis. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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Review

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13 pages, 810 KiB

Open AccessReview

Major Surface Antigens in Zoonotic Babesia

by Stephane Delbecq

Pathogens 2022, 11(1), 99; https://doi.org/10.3390/pathogens11010099 - 15 Jan 2022

Cited by 8 | Viewed by 2496

Abstract

Human babesiosis results from a combination of tick tropism for humans, susceptibility of a host to sustain Babesia development, and contact with infected ticks. Climate modifications and increasing diagnostics have led to an expanded number of Babesia species responsible for human babesiosis, although, [...] Read more.

Human babesiosis results from a combination of tick tropism for humans, susceptibility of a host to sustain Babesia development, and contact with infected ticks. Climate modifications and increasing diagnostics have led to an expanded number of Babesia species responsible for human babesiosis, although, to date, most cases have been attributed to B. microti and B. divergens. These two species have been extensively studied, and in this review, we mostly focus on the antigens involved in host–parasite interactions. We present features of the major antigens, so-called Bd37 in B. divergens and BmSA1/GPI12 in B. microti, and highlight the roles of these antigens in both host cell invasion and immune response. A comparison of these antigens with the major antigens found in some other Apicomplexa species emphasizes the importance of glycosylphosphatidylinositol-anchored proteins in host–parasite relationships. GPI-anchor cleavage, which is a property of such antigens, leads to soluble and membrane-bound forms of these proteins, with potentially differential recognition by the host immune system. This mechanism is discussed as the structural basis for the protein-embedded immune escape mechanism. In conclusion, the potential consequences of such a mechanism on the management of both human and animal babesiosis is examined. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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16 pages, 1233 KiB

Open AccessReview

Technologies for Detection of Babesia microti: Advances and Challenges

by Scott Meredith, Miranda Oakley and Sanjai Kumar

Pathogens 2021, 10(12), 1563; https://doi.org/10.3390/pathogens10121563 - 30 Nov 2021

Cited by 13 | Viewed by 4055

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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24 pages, 14532 KiB

Open AccessReview

The Global Emergence of Human Babesiosis

by Abhinav Kumar, Jane O’Bryan and Peter J. Krause

Pathogens 2021, 10(11), 1447; https://doi.org/10.3390/pathogens10111447 - 6 Nov 2021

Cited by 59 | Viewed by 10385 | Correction | Correction

Abstract

Babesiosis is an emerging tick-borne disease caused by intraerythrocytic protozoa that are primarily transmitted by hard-bodied (ixodid) ticks and rarely through blood transfusion, perinatally, and organ transplantation. More than 100 Babesia species infect a wide spectrum of wild and domestic animals worldwide and [...] Read more.

Babesiosis is an emerging tick-borne disease caused by intraerythrocytic protozoa that are primarily transmitted by hard-bodied (ixodid) ticks and rarely through blood transfusion, perinatally, and organ transplantation. More than 100 Babesia species infect a wide spectrum of wild and domestic animals worldwide and six have been identified as human pathogens. Babesia microti is the predominant species that infects humans, is found throughout the world, and causes endemic disease in the United States and China. Babesia venatorum and Babesia crassa-like agent also cause endemic disease in China. Babesia divergens is the predominant species in Europe where fulminant cases have been reported sporadically. The number of B. microti infections has been increasing globally in recent decades. In the United States, more than 2000 cases are reported each year, although the actual number is thought to be much higher. In this review of the epidemiology of human babesiosis, we discuss epidemiologic tools used to monitor disease location and frequency; demographics and modes of transmission; the location of human babesiosis; the causative Babesia species in the Americas, Europe, Asia, Africa, and Australia; the primary clinical characteristics associated with each of these infections; and the increasing global health burden of this disease. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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10 pages, 562 KiB

Open AccessReview

Sickle Cell Anemia and Babesia Infection

by Divya Beri, Manpreet Singh, Marilis Rodriguez, Karina Yazdanbakhsh and Cheryl Ann Lobo

Pathogens 2021, 10(11), 1435; https://doi.org/10.3390/pathogens10111435 - 4 Nov 2021

Cited by 7 | Viewed by 5342

Abstract

Babesia is an intraerythrocytic, obligate Apicomplexan parasite that has, in the last century, been implicated in human infections via zoonosis and is now widespread, especially in parts of the USA and Europe. It is naturally transmitted by the bite of a tick, but [...] Read more.

Babesia is an intraerythrocytic, obligate Apicomplexan parasite that has, in the last century, been implicated in human infections via zoonosis and is now widespread, especially in parts of the USA and Europe. It is naturally transmitted by the bite of a tick, but transfused blood from infected donors has also proven to be a major source of transmission. When infected, most humans are clinically asymptomatic, but the parasite can prove to be lethal when it infects immunocompromised individuals. Hemolysis and anemia are two common symptoms that accompany many infectious diseases, and this is particularly true of parasitic diseases that target red cells. Clinically, this becomes an acute problem for subjects who are prone to hemolysis and depend on frequent transfusions, like patients with sickle cell anemia or thalassemia. Little is known about Babesia’s pathogenesis in these hemoglobinopathies, and most parallels are drawn from its evolutionarily related Plasmodium parasite which shares the same environmental niche, the RBCs, in the human host. In vitro as well as in vivo Babesia-infected mouse sickle cell disease (SCD) models support the inhibition of intra-erythrocytic parasite proliferation, but mechanisms driving the protection of such hemoglobinopathies against infection are not fully studied. This review provides an overview of our current knowledge of Babesia infection and hemoglobinopathies, focusing on possible mechanisms behind this parasite resistance and the clinical repercussions faced by Babesia-infected human hosts harboring mutations in their globin gene. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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13 pages, 30458 KiB

Open AccessReview

Ticks, Human Babesiosis and Climate Change

by Jeremy S. Gray and Nicholas H. Ogden

Pathogens 2021, 10(11), 1430; https://doi.org/10.3390/pathogens10111430 - 4 Nov 2021

Cited by 30 | Viewed by 3857

Abstract

The effects of current and future global warming on the distribution and activity of the primary ixodid vectors of human babesiosis (caused by Babesia divergens, B. venatorum and B. microti) are discussed. There is clear evidence that the distributions of both [...] Read more.

The effects of current and future global warming on the distribution and activity of the primary ixodid vectors of human babesiosis (caused by Babesia divergens, B. venatorum and B. microti) are discussed. There is clear evidence that the distributions of both Ixodes ricinus, the vector in Europe, and I. scapularis in North America have been impacted by the changing climate, with increasing temperatures resulting in the northwards expansion of tick populations and the occurrence of I. ricinus at higher altitudes. Ixodes persulcatus, which replaces I. ricinus in Eurasia and temperate Asia, is presumed to be the babesiosis vector in China and Japan, but this tick species has not yet been confirmed as the vector of either human or animal babesiosis. There is no definite evidence, as yet, of global warming having an effect on the occurrence of human babesiosis, but models suggest that it is only a matter of time before cases occur further north than they do at present. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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14 pages, 2018 KiB

Open AccessReview

Experimental Infection of Ticks: An Essential Tool for the Analysis of Babesia Species Biology and Transmission

by Sarah I. Bonnet and Clémence Nadal

Pathogens 2021, 10(11), 1403; https://doi.org/10.3390/pathogens10111403 - 29 Oct 2021

Cited by 12 | Viewed by 6572

Abstract

Babesiosis is one of the most important tick-borne diseases in veterinary health, impacting mainly cattle, equidae, and canidae, and limiting the development of livestock industries worldwide. In humans, babesiosis is considered to be an emerging disease mostly due to Babesia divergens in Europe [...] Read more.

Babesiosis is one of the most important tick-borne diseases in veterinary health, impacting mainly cattle, equidae, and canidae, and limiting the development of livestock industries worldwide. In humans, babesiosis is considered to be an emerging disease mostly due to Babesia divergens in Europe and Babesia microti in America. Despite this importance, our knowledge of Babesia sp. transmission by ticks is incomplete. The complexity of vectorial systems involving the vector, vertebrate host, and pathogen, as well as the complex feeding biology of ticks, may be part of the reason for the existing gaps in our knowledge. Indeed, this complexity renders the implementation of experimental systems that are as close as possible to natural conditions and allowing the study of tick-host-parasite interactions, quite difficult. However, it is unlikely that the development of more effective and sustainable control measures against babesiosis will emerge unless significant progress can be made in understanding this tripartite relationship. The various methods used to date to achieve tick transmission of Babesia spp. of medical and veterinary importance under experimental conditions are reviewed and discussed here. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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16 pages, 310 KiB

Open AccessReview

Preventing Transfusion-Transmitted Babesiosis

by Evan M. Bloch, Peter J. Krause and Laura Tonnetti

Pathogens 2021, 10(9), 1176; https://doi.org/10.3390/pathogens10091176 - 13 Sep 2021

Cited by 18 | Viewed by 3494

Abstract

Babesia are tick-borne intra-erythrocytic parasites and the causative agents of babesiosis. Babesia, which are readily transfusion transmissible, gained recognition as a major risk to the blood supply, particularly in the United States (US), where Babesia microti is endemic. Many of those infected [...] Read more.

Babesia are tick-borne intra-erythrocytic parasites and the causative agents of babesiosis. Babesia, which are readily transfusion transmissible, gained recognition as a major risk to the blood supply, particularly in the United States (US), where Babesia microti is endemic. Many of those infected with Babesia remain asymptomatic and parasitemia may persist for months or even years following infection, such that seemingly healthy blood donors are unaware of their infection. By contrast, transfusion recipients are at high risk of severe babesiosis, accounting for the high morbidity and mortality (~19%) observed in transfusion-transmitted babesiosis (TTB). An increase in cases of tick-borne babesiosis and TTB prompted over a decade-long investment in blood donor surveillance, research, and assay development to quantify and contend with TTB. This culminated in the adoption of regional blood donor testing in the US. We describe the evolution of the response to TTB in the US and offer some insight into the risk of TTB in other countries. Not only has this response advanced blood safety, it has accelerated the development of novel serological and molecular assays that may be applied broadly, affording insight into the global epidemiology and immunopathogenesis of human babesiosis. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

7 pages, 961 KiB

Open AccessReview

What Babesia microti Is Now

by Heidi K. Goethert

Pathogens 2021, 10(9), 1168; https://doi.org/10.3390/pathogens10091168 - 10 Sep 2021

Cited by 24 | Viewed by 3977

Abstract

Parasites from diverse hosts morphologically identified as Babesia microti have previously been shown to belong to a paraphyletic species complex. With a growing number of reports of B. microti-like parasites from across the world, this paper seeks to report on the current [...] Read more.

Parasites from diverse hosts morphologically identified as Babesia microti have previously been shown to belong to a paraphyletic species complex. With a growing number of reports of B. microti-like parasites from across the world, this paper seeks to report on the current knowledge of the diversity of this species complex. Phylogenetic analysis of 18S rDNA sequences obtained from GenBank shows that the diversity of the B. microti species complex has markedly increased and now encompasses at least five distinct clades. This cryptic diversity calls into question much of our current knowledge of the life cycle of these parasites, as many biological studies were conducted before DNA sequencing technology was available. In many cases, it is uncertain which B. microti-like parasite was studied because parasites from different clades may occur sympatrically and even share the same host. Progress can only be made if future studies are conducted with careful attention to parasite identification and PCR primer specificity. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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29 pages, 1649 KiB

Open AccessEditor’s ChoiceReview

Human Babesiosis in Europe

by Anke Hildebrandt, Annetta Zintl, Estrella Montero, Klaus-Peter Hunfeld and Jeremy Gray

Pathogens 2021, 10(9), 1165; https://doi.org/10.3390/pathogens10091165 - 9 Sep 2021

Cited by 59 | Viewed by 10437

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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14 pages, 3344 KiB

Open AccessReview

Semicentennial of Human Babesiosis, Nantucket Island

by Sam R. Telford III, Heidi K. Goethert and Timothy J. Lepore

Pathogens 2021, 10(9), 1159; https://doi.org/10.3390/pathogens10091159 - 9 Sep 2021

Cited by 3 | Viewed by 3609

Abstract

Fifty years ago, the index case of human babesiosis due to Babesia microti was diagnosed in a summer resident of Nantucket Island. Human babesiosis, once called “Nantucket fever” due to its seeming restriction to Nantucket and the terminal moraine islands of southern New [...] Read more.

Fifty years ago, the index case of human babesiosis due to Babesia microti was diagnosed in a summer resident of Nantucket Island. Human babesiosis, once called “Nantucket fever” due to its seeming restriction to Nantucket and the terminal moraine islands of southern New England, has emerged across the northeastern United States to commonly infect people wherever Lyme disease is endemic. We review the history of babesiosis on Nantucket, analyze its epidemiology and ecology there, provide summaries of the first case histories, and comment on its future public health burden. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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18 pages, 1665 KiB

Open AccessReview

Treatment of Human Babesiosis: Then and Now

by Isaline Renard and Choukri Ben Mamoun

Pathogens 2021, 10(9), 1120; https://doi.org/10.3390/pathogens10091120 - 1 Sep 2021

Cited by 34 | Viewed by 12068

Abstract

Babesiosis is an emerging tick-borne disease caused by apicomplexan parasites of the genus Babesia. With its increasing incidence worldwide and the risk of human-to-human transmission through blood transfusion, babesiosis is becoming a rising public health concern. The current arsenal for the treatment [...] Read more.

Babesiosis is an emerging tick-borne disease caused by apicomplexan parasites of the genus Babesia. With its increasing incidence worldwide and the risk of human-to-human transmission through blood transfusion, babesiosis is becoming a rising public health concern. The current arsenal for the treatment of human babesiosis is limited and consists of combinations of atovaquone and azithromycin or clindamycin and quinine. These combination therapies were not designed based on biological criteria unique to Babesia parasites, but were rather repurposed based on their well-established efficacy against other apicomplexan parasites. However, these compounds are associated with mild or severe adverse events and a rapid emergence of drug resistance, thus highlighting the need for new therapeutic strategies that are specifically tailored to Babesia parasites. Herein, we review ongoing babesiosis therapeutic and management strategies and their limitations, and further review current efforts to develop new, effective, and safer therapies for the treatment of this disease. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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Other

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3 pages, 223 KiB

Open AccessComment

Call for Caution to Consider Babesia bovis and Babesia bigemina as Anthropozoonotic Agents in Colombia. Comment on Kumar et al. The Global Emergence of Human Babesiosis. Pathogens 2021, 10, 1447

by Carlos Ramiro Silva-Ramos and Álvaro A. Faccini-Martínez

Pathogens 2022, 11(2), 263; https://doi.org/10.3390/pathogens11020263 - 18 Feb 2022

Cited by 3 | Viewed by 1854

Abstract

Currently, six species and two genetic variants within Babesia genus have been confirmed as human pathogens. Babesia bovis and Babesia bigemina are causative agents of bovine babesiosis, and, in spite of the worldwide distribution of those species and their vectors, no description of [...] Read more.

Currently, six species and two genetic variants within Babesia genus have been confirmed as human pathogens. Babesia bovis and Babesia bigemina are causative agents of bovine babesiosis, and, in spite of the worldwide distribution of those species and their vectors, no description of related human cases has been reported. As a contribution, we would like to address the articles which claim the alleged role of B. bovis and B. bigemina as anthropozoonotic pathogens in Colombia. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

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