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10 pages, 1909 KiB

Open AccessEditor’s ChoiceArticle

Initiated Babesia ovata Sexual Stages under In Vitro Conditions Were Recognized by Anti-CCp2 Antibodies, Showing Changes in the DNA Content by Imaging Flow Cytometry

by Thu-Thuy Nguyen, Minh-Anh Dang-Trinh, Luna Higuchi, Juan Mosqueda, Hassan Hakimi, Masahito Asada, Junya Yamagishi, Rika Umemiya-Shirafuji and Shin-ichiro Kawazu

Pathogens 2019, 8(3), 104; https://doi.org/10.3390/pathogens8030104 - 17 Jul 2019

Cited by 6 | Viewed by 4513

Abstract

Sexual stage induction under in vitro conditions is useful for biological and molecular studies of Babesia parasites. Therefore, in the present study, we induced B. ovata tick stages using the chemical inducers: xanthurenic acid (XA), dithiothreitol (DTT) and tris (2-carboxyethyl) phosphine (TCEP) at [...] Read more.

Sexual stage induction under in vitro conditions is useful for biological and molecular studies of Babesia parasites. Therefore, in the present study, we induced B. ovata tick stages using the chemical inducers: xanthurenic acid (XA), dithiothreitol (DTT) and tris (2-carboxyethyl) phosphine (TCEP) at 27 °C or 37 °C conditions. Cultures at low temperature (27 °C) or treated with XA/TCEP induced a large number of extra-erythrocytic merozoites, which transformed into round shape cells at 12–24 h post-induction (pi). However, typical forms of tick stages (aggregation forms and the spiky forms/ray bodies) were only observed in the cultures treated with 40 mM or 60 mM of DTT during 3–6 h pi. The induced cells were recognized by anti-CCp2 rabbit antisera. DNA content of the cell population treated with 40 mM of DTT was analyzed by imaging flow cytometry at 0, 12 and 48 h pi. The results indicated that the parasite population with diploid-like double DNA content increased at 48 h pi. Our observations on morphological and changes in the DNA content provide useful information for understanding the life cycle of B. ovata under in vitro conditions, which will facilitate further studies on basic biology and the development of transmission blocking vaccines against bovine babesiosis. Full article

(This article belongs to the Special Issue Persistence in Babesia)

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Review

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14 pages, 260 KiB

Open AccessReview

Diagnostic Tools for the Identification of Babesia sp. in Persistently Infected Cattle

by J. Antonio Alvarez, Carmen Rojas and Julio V. Figueroa

Pathogens 2019, 8(3), 143; https://doi.org/10.3390/pathogens8030143 - 09 Sep 2019

Cited by 42 | Viewed by 5387

Abstract

Bovine babesiosis is a tick-borne disease of cattle caused by the protozoan parasites of the genus Babesia. Babesia bovis, Babesia bigemina and Babesia divergens are considered by International health authorities (OIE) as the principal species of Babesia that cause bovine babesiosis. [...] Read more.

Bovine babesiosis is a tick-borne disease of cattle caused by the protozoan parasites of the genus Babesia. Babesia bovis, Babesia bigemina and Babesia divergens are considered by International health authorities (OIE) as the principal species of Babesia that cause bovine babesiosis. Animals that recover from a babesial primo infection may remain as persistent carriers with no clinical signs of disease and can be the source of infection for ticks that are able to acquire Babesia parasites from infected cattle and to transmit Babesia parasites to susceptible cattle. Several procedures that have been developed for parasite detection and diagnosis of this infectious carrier state constitute the basis for this review: A brief description of the direct microscopic detection of Babesia-infected erytrocytes; PCR-based diagnostic assays, which are very sensitive particularly in detecting Babesia in carrier cattle; in-vitro culture methods, used to demonstrate presence of carrier infections of Babesia sp.; animal inoculation, particularly for B. divergens isolation are discussed. Alternatively, persistently infected animals can be tested for specific antibabesial antibodies by using indirect serological assays. Serological procedures are not necessarily consistent in identifying persistently infected animals and have the disadvantage of presenting with cross reactions between antibodies to Babesia sp. Full article

(This article belongs to the Special Issue Persistence in Babesia)

7 pages, 536 KiB

Open AccessReview

Babesia microti—Borrelia burgdorferi Coinfection

by Nikhat Parveen and Purnima Bhanot

Pathogens 2019, 8(3), 117; https://doi.org/10.3390/pathogens8030117 - 31 Jul 2019

Cited by 20 | Viewed by 5599

Abstract

The incidence and geographic distribution of human babesiosis is growing in the U.S. Its major causative agent is the protozoan parasite, Babesia microti. B. microti is transmitted to humans primarily through the bite of Ixodes scapularis ticks, which are vectors for a [...] Read more.

The incidence and geographic distribution of human babesiosis is growing in the U.S. Its major causative agent is the protozoan parasite, Babesia microti. B. microti is transmitted to humans primarily through the bite of Ixodes scapularis ticks, which are vectors for a number of other pathogens. Other routes of B. microti transmission are blood transfusion and in rare cases of mother-to-foetus transmission, through the placenta. This review discusses the current literature on mammalian coinfection with B. microti and Borrelia burgdorferi, the causative agent Lyme disease. Full article

(This article belongs to the Special Issue Persistence in Babesia)

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12 pages, 1321 KiB

Open AccessEditor’s ChoiceReview

Persistence of Babesia microti Infection in Humans

by Evan M. Bloch, Sanjai Kumar and Peter J. Krause

Pathogens 2019, 8(3), 102; https://doi.org/10.3390/pathogens8030102 - 17 Jul 2019

Cited by 63 | Viewed by 18270

Abstract

Persistent infection is a characteristic feature of babesiosis, a worldwide, emerging tick-borne disease caused by members of the genus Babesia. Persistence of Babesia infection in reservoir hosts increases the probability of survival and transmission of these pathogens. Laboratory tools to detect Babesia in [...] Read more.

Persistent infection is a characteristic feature of babesiosis, a worldwide, emerging tick-borne disease caused by members of the genus Babesia. Persistence of Babesia infection in reservoir hosts increases the probability of survival and transmission of these pathogens. Laboratory tools to detect Babesia in red blood cells include microscopic detection using peripheral blood smears, nucleic acid detection (polymerase chain reaction and transcription mediated amplification), antigen detection, and antibody detection. Babesia microti, the major cause of human babesiosis, can asymptomatically infect immunocompetent individuals for up to two years. Chronically infected blood donors may transmit the pathogen to another person through blood transfusion. Transfusion-transmitted babesiosis causes severe complications and death in about a fifth of cases. Immunocompromised patients, including those with asplenia, HIV/AIDS, malignancy, or on immunosuppressive drugs, often experience severe disease that may relapse up to two years later despite anti-Babesia therapy. Persistent Babesia infection is promoted by Babesia immune evasive strategies and impaired host immune mechanisms. The health burden of persistent and recrudescent babesiosis can be minimized by development of novel therapeutic measures, such as new anti-parasitic drugs or drug combinations, improved anti-parasitic drug duration strategies, or immunoglobulin preparations; and novel preventive approaches, including early detection methods, tick-avoidance, and blood donor screening. Full article

(This article belongs to the Special Issue Persistence in Babesia)

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13 pages, 1885 KiB

Open AccessReview

Interplay between Attenuation- and Virulence-Factors of Babesia bovis and Their Contribution to the Establishment of Persistent Infections in Cattle

by Gina M. Gallego-Lopez, Brian M. Cooke and Carlos E. Suarez

Pathogens 2019, 8(3), 97; https://doi.org/10.3390/pathogens8030097 - 04 Jul 2019

Cited by 8 | Viewed by 9156

Abstract

Bovine babesiosis is an acute and persistent tick-borne global disease caused mainly by the intraerythrocytic apicomplexan parasites Babesia bovis and B. bigemina. B. bovis infected erythrocytes sequester in blood capillaries of the host (cytoadhesion), causing malaria-like neurological signs. Cytoadhesion and antigenic variation [...] Read more.

Bovine babesiosis is an acute and persistent tick-borne global disease caused mainly by the intraerythrocytic apicomplexan parasites Babesia bovis and B. bigemina. B. bovis infected erythrocytes sequester in blood capillaries of the host (cytoadhesion), causing malaria-like neurological signs. Cytoadhesion and antigenic variation in B. bovis are linked to the expression of members of the Variant Erythrocyte Surface Antigen (VESA) gene family. Animals that survive acute B. bovis infection and those vaccinated with attenuated strains remain persistently infected, suggesting that B. bovis parasites use immune escape mechanisms. However, attenuated B. bovis parasites do not cause neurological signs in vaccinated animals, indicating that virulence or attenuation factors play roles in modulating parasite virulence phenotypes. Artificial overexpression of the SBP2t11 protein, a defined attenuation factor, was associated with reduced cytoadhesion, suggesting a role for this protein as a key modulator of virulence in the parasite. Hereby, we propose a model that might be functional in the modulation of B. bovis virulence and persistence that relies on the interplay among SBP2t, VESA proteins, cytoadhesion, and the immune responses of the host. Elucidation of mechanisms used by the parasite to establish persistent infection will likely contribute to the design of new methods for the control of bovine babesiosis. Full article

(This article belongs to the Special Issue Persistence in Babesia)

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8 pages, 1402 KiB

Open AccessReview

Babesia divergens: A Drive to Survive

by Cheryl A Lobo, Jeny R Cursino-Santos, Manpreet Singh and Marilis Rodriguez

Pathogens 2019, 8(3), 95; https://doi.org/10.3390/pathogens8030095 - 02 Jul 2019

Cited by 16 | Viewed by 5479

Abstract

Babesia divergens is an obligate intracellular protozoan parasite that causes zoonotic disease. Central to its pathogenesis is the ability of the parasite to invade host red blood cells of diverse species, and, once in the host blood stream, to manipulate the composition of [...] Read more.

Babesia divergens is an obligate intracellular protozoan parasite that causes zoonotic disease. Central to its pathogenesis is the ability of the parasite to invade host red blood cells of diverse species, and, once in the host blood stream, to manipulate the composition of its population to allow it to endure unfavorable conditions. Here we will review key in vitro studies relating to the survival strategies that B. divergens adopts during its intraerythrocytic development to persist and how proliferation is restored in the parasite population once optimum conditions return. Full article

(This article belongs to the Special Issue Persistence in Babesia)

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15 pages, 15915 KiB

Open AccessReview

Mechanisms Involved in the Persistence of Babesia canis Infection in Dogs

by Theo Schetters

Pathogens 2019, 8(3), 94; https://doi.org/10.3390/pathogens8030094 - 29 Jun 2019

Cited by 15 | Viewed by 8210

Abstract

Dogs that are infected with Babesia canis parasites usually show severe clinical signs, yet often very few parasites are detectable in the blood circulation. The results showed that large numbers of B. canis-infected red blood cells accumulate in the microvasculature of infected [...] Read more.

Dogs that are infected with Babesia canis parasites usually show severe clinical signs, yet often very few parasites are detectable in the blood circulation. The results showed that large numbers of B. canis-infected red blood cells accumulate in the microvasculature of infected subjects. The initial process leading to the attachment of infected erythrocytes to the endothelial cells of small capillaries (sequestration) appears to involve the interaction of parasite molecules at the erythrocyte surface with ligands on the endothelial cells. Since parasites continue to develop in the sequestered erythrocyte, it would be expected that the infected erythrocyte is destroyed when the mature parasites escape the host cell, which would make it hard to explain accumulation of infected erythrocytes at the initial site of attachment. Apparently, additional processes are triggered that lead to consolidation of parasite sequestration. One possible explanation is that after initial attachment of an infected erythrocyte to the wall of a blood capillary, the coagulation system is involved in the trapping of infected and uninfected erythrocytes. The data further suggest that newly formed parasites subsequently infect normal red blood cells that are also trapped in the capillary, which finally leads to capillaries that appear to be loaded with infected erythrocytes. Full article

(This article belongs to the Special Issue Persistence in Babesia)

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15 pages, 1425 KiB

Open AccessEditor’s ChoiceReview

Variable and Variant Protein Multigene Families in Babesia bovis Persistence

by David R. Allred

Pathogens 2019, 8(2), 76; https://doi.org/10.3390/pathogens8020076 - 11 Jun 2019

Cited by 18 | Viewed by 4025

Abstract

Cattle infected with Babesia bovis face a bifurcated fate: Either die of the severe acute infection, or survive and carry for many years a highly persistent but generally asymptomatic infection. In this review, the author describes known and potential contributions of three variable [...] Read more.

Cattle infected with Babesia bovis face a bifurcated fate: Either die of the severe acute infection, or survive and carry for many years a highly persistent but generally asymptomatic infection. In this review, the author describes known and potential contributions of three variable or highly variant multigene-encoded families of proteins to persistence in the bovine host, and the mechanisms by which variability arises among these families. Ramifications arising from this variability are discussed. Full article

(This article belongs to the Special Issue Persistence in Babesia)

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