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

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.

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Comparative Study of Highly Pathogenic Avian Infl uenza Strains Isolated in Ukraine in 2005 and 2008

Agricultural science and practice ◽

10.15407/agrisp1.01.068 ◽

2014 ◽

Vol 1 (1) ◽

pp. 68-71

Author(s):

A. Gerilovych ◽

B. Stegniy ◽

A. Stegniy ◽

M. Stegniy ◽

K. Smietanka ◽

...

Keyword(s):

Western Europe ◽

Rna Extraction ◽

Experimental Studies ◽

Molecular Characteristics ◽

Eastern European ◽

Highly Pathogenic ◽

Genetic Lineages ◽

Phylogenetic Studies ◽

Polymerase Chain ◽

Pathogenic H5n1

Objective. To research the molecular characteristics of two HPAI strains – A/Ch/Syvash/02/05/H5N1 and A/Ch/Krasnogvardeysk/58/08/H5N1, which were identifi ed as representatives of the highly pathogenic H5N1 viruses. Methods. RNA extraction, real-time polymerase chain reaction (PCR). Results. The phylogenetic studies revealed that the above mentioned strains belong to two various genetic lineages originated from the Eastern European strains isolated in 2005, but differ from the viruses introduced to the Central and Western Europe in 2005/2006, and also the lineages consisting of H5N1 viruses isolated in the Europe and Middle East in late 2007. Conclusions. Relying on experimental studies, it can be concluded that the strains of A/Ch/Syvash/02/05/H5N1 and A/Ch/Krasnogvardeysk/58/08/H5N1 are highly pathogenic.

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Bacteremia Among Febrile Patients Attending Selected Healthcare Facilities in Ibadan, Nigeria

Clinical Infectious Diseases ◽

10.1093/cid/ciz516 ◽

2019 ◽

Vol 69 (Supplement_6) ◽

pp. S466-S473 ◽

Cited By ~ 4

Author(s):

Oluwafemi Popoola ◽

Aderemi Kehinde ◽

Veronica Ogunleye ◽

Oluwafemi J Adewusi ◽

Trevor Toy ◽

...

Keyword(s):

Antimicrobial Susceptibility ◽

Bacterial Infections ◽

Common Species ◽

Epidemiological Studies ◽

Multidrug Resistant ◽

African Countries ◽

Healthcare Facilities ◽

Relative Contribution ◽

Polymerase Chain ◽

Ibadan Nigeria

Abstract Background The relative contribution of bacterial infections to febrile disease is poorly understood in many African countries due to diagnostic limitations. This study screened pediatric and adult patients attending 4 healthcare facilities in Ibadan, Nigeria, for bacteremia and malaria parasitemia. Methods Febrile patients underwent clinical diagnosis, malaria parasite testing, and blood culture. Bacteria from positive blood cultures were isolated and speciated using biochemical and serological methods, and Salmonella subtyping was performed by polymerase chain reaction. Antimicrobial susceptibility was tested by disk diffusion. Results A total of 682 patients were recruited between 16 June and 16 October 2017; 467 (68.5%) were <18 years of age. Bacterial pathogens were cultured from the blood of 117 (17.2%) patients, with Staphylococcus aureus (69 [59.0%]) and Salmonella enterica (34 [29.1%]) being the most common species recovered. Twenty-seven (79.4%) of the Salmonella isolates were serovar Typhi and the other 7 belonged to nontyphoidal Salmonella serovarieties. Thirty-four individuals were found to be coinfected with Plasmodium falciparum and bacteria. Five (14.7%) of these coinfections were with Salmonella, all in children aged <5 years. Antimicrobial susceptibility testing revealed that most of the Salmonella and Staphylococcus isolates were multidrug resistant. Conclusions The study demonstrates that bacteria were commonly recovered from febrile patients with or without malaria in this location. Focused and extended epidemiological studies are needed for the introduction of typhoid conjugate vaccines that have the potential to prevent a major cause of severe community-acquired febrile diseases in our locality.

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Development of a capture sequencing assay for enhanced detection and genotyping of tick-borne pathogens

Scientific Reports ◽

10.1038/s41598-021-91956-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Komal Jain ◽

Teresa Tagliafierro ◽

Adriana Marques ◽

Santiago Sanchez-Vicente ◽

Alper Gokden ◽

...

Keyword(s):

High Throughput ◽

High Throughput Sequencing ◽

Fold Increase ◽

The United States ◽

Genomic Research ◽

Babesia Microti ◽

Hybridization Capture ◽

Mouse Tissues ◽

Genome Analyses ◽

Capture Sequencing

AbstractInadequate sensitivity has been the primary limitation for implementing high-throughput sequencing for studies of tick-borne agents. Here we describe the development of TBDCapSeq, a sequencing assay that uses hybridization capture probes that cover the complete genomes of the eleven most common tick-borne agents found in the United States. The probes are used for solution-based capture and enrichment of pathogen nucleic acid followed by high-throughput sequencing. We evaluated the performance of TBDCapSeq to surveil samples that included human whole blood, mouse tissues, and field-collected ticks. For Borrelia burgdorferi and Babesia microti, the sensitivity of TBDCapSeq was comparable and occasionally exceeded the performance of agent-specific quantitative PCR and resulted in 25 to > 10,000-fold increase in pathogen reads when compared to standard unbiased sequencing. TBDCapSeq also enabled genome analyses directly within vertebrate and tick hosts. The implementation of TBDCapSeq could have major impact in studies of tick-borne pathogens by improving detection and facilitating genomic research that was previously unachievable with standard sequencing approaches.

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Fibrinolysis: A Primordial System Linked to the Immune Response

International Journal of Molecular Sciences ◽

10.3390/ijms22073406 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3406

Author(s):

Robert L. Medcalf ◽

Charithani B. Keragala

Keyword(s):

Binding Sites ◽

Defense Mechanisms ◽

Immune Cell ◽

Immune Defense ◽

Surface Proteins ◽

Cell Behavior ◽

Phylogenetic Studies ◽

Blood Clots ◽

Lower Vertebrates ◽

Almost All

The fibrinolytic system provides an essential means to remove fibrin deposits and blood clots. The actual protease responsible for this is plasmin, formed from its precursor, plasminogen. Fibrin is heralded as it most renowned substrate but for many years plasmin has been known to cleave many other substrates, and to also activate other proteolytic systems. Recent clinical studies have shown that the promotion of plasmin can lead to an immunosuppressed phenotype, in part via its ability to modulate cytokine expression. Almost all immune cells harbor at least one of a dozen plasminogen receptors that allows plasmin formation on the cell surface that in turn modulates immune cell behavior. Similarly, a multitude of pathogens can also express their own plasminogen activators, or contain surface proteins that provide binding sites host plasminogen. Plasmin formed under these circumstances also empowers these pathogens to modulate host immune defense mechanisms. Phylogenetic studies have revealed that the plasminogen activating system predates the appearance of fibrin, indicating that plasmin did not evolve as a fibrinolytic protease but perhaps has its roots as an immune modifying protease. While its fibrin removing capacity became apparent in lower vertebrates these primitive under-appreciated immune modifying functions still remain and are now becoming more recognised.

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Superior real-time polymerase chain reaction detection of Babesia microti parasites in whole blood utilizing high-copy BMN antigens as amplification targets

Transfusion ◽

10.1111/trf.14642 ◽

2018 ◽

Vol 58 (8) ◽

pp. 1924-1932 ◽

Cited By ~ 7

Author(s):

Bryan Grabias ◽

Jean Clement ◽

Peter J. Krause ◽

Timothy Lepore ◽

Sanjai Kumar

Keyword(s):

Polymerase Chain Reaction ◽

Real Time ◽

Whole Blood ◽

Babesia Microti ◽

Polymerase Chain Reaction Detection ◽

Chain Reaction ◽

Polymerase Chain

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Anaplasma marginale(Rickettsiales: Anaplasmataceae): recent advances in defining host–pathogen adaptations of a tick-borne rickettsia

Parasitology ◽

10.1017/s0031182003004700 ◽

2004 ◽

Vol 129 (S1) ◽

pp. S285-S300 ◽

Cited By ~ 161

Author(s):

K. M. KOCAN ◽

J. DE LA FUENTE ◽

E. F. BLOUIN ◽

J. C. GARCIA-GARCIA

Keyword(s):

Antigenic Variation ◽

Control Strategies ◽

Anaplasma Marginale ◽

Surface Proteins ◽

Host Cells ◽

Developmental Cycle ◽

Persistent Infections ◽

Phylogenetic Studies ◽

Major Surface Proteins ◽

Major Surface

The tick-borne intracellular pathogenAnaplasma marginale(Rickettsiales: Anaplasmataceae) develops persistent infections in cattle and tick hosts. While erythrocytes appear to be the only site of infection in cattle,A. marginaleundergoes a complex developmental cycle in ticks and transmission occurs via salivary glands during feeding. Many geographic isolates occur that vary in genotype, antigenic composition, morphology and infectivity for ticks. In this chapter we review recent research on the host–vector–pathogen interactions ofA. marginale. Major surface proteins (MSPs) play a crucial role in the interaction ofA. marginalewith host cells. The MSP1a protein, which is an adhesin for bovine erythrocytes and tick cells, is differentially regulated and affects infection and transmission ofA. marginalebyDermacentorspp. ticks. MSP2 undergoes antigenic variation and selection in cattle and ticks, and contributes to the maintenance of persistent infections. Phylogenetic studies ofA. marginalegeographic isolates usingmsp4andmsp1α provide information about the biogeography and evolution ofA. marginale:msp1α genotypes evolve under positive selection pressure. Isolates ofA. marginaleare maintained by independent transmission events and a mechanism of infection exclusion in cattle and ticks allows for only the infection of one isolate per animal. Prospects for development of control strategies by use of pathogen and tick-derived antigens are discussed. TheA. marginale/vector/host studies described herein could serve as a model for research on other tick-borne rickettsiae.

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Clofazimine, a Promising Drug for the Treatment of Babesia microti Infection in Severely Immunocompromised Hosts

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa195 ◽

2020 ◽

Vol 222 (6) ◽

pp. 1027-1036 ◽

Cited By ~ 1

Author(s):

Bumduuren Tuvshintulga ◽

Edouard Vannier ◽

Dickson S Tayebwa ◽

Sambuu Gantuya ◽

Thillaiampalam Sivakumar ◽

...

Keyword(s):

Antimicrobial Agents ◽

Severe Combined Immunodeficiency ◽

Immunocompromised Host ◽

The United States ◽

Babesia Microti ◽

Radical Cure ◽

Nested Polymerase Chain Reaction ◽

Resistant Tuberculosis ◽

Rising Incidence ◽

Immunocompromised Hosts

Abstract Background Persistent and relapsing babesiosis caused by Babesia microti often occurs in immunocompromised patients, and has been associated with resistance to antimicrobial agents such as atovaquone. Given the rising incidence of babesiosis in the United States, novel drugs are urgently needed. In the current study, we tested whether clofazimine (CFZ), an antibiotic used to treat leprosy and drug-resistant tuberculosis, is effective against B. microti. Methods Mice with severe combined immunodeficiency were infected with 107B. microti–infected erythrocytes. Parasites were detected by means of microscopic examination of Giemsa-stained blood smears or nested polymerase chain reaction. CFZ was administered orally. Results Uninterrupted monotherapy with CFZ curtailed the rise of parasitemia and achieved radical cure. B. microti parasites and B. microti DNA were cleared by days 10 and 50 of therapy, respectively. A 7-day administration of CFZ delayed the rise of parasitemia by 22 days. This rise was caused by B. microti isolates that did not carry mutations in the cytochrome b gene. Accordingly, a 14-day administration of CFZ was sufficient to resolve high-grade parasitemia caused by atovaquone-resistant B. microti parasites. Conclusions Clofazimine is effective against B. microti infection in the immunocompromised host. Additional preclinical studies are required to identify the minimal dose and dosage of CFZ for babesiosis.

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Current Avenues for COVID-19 Serology

Annals of the National Academy of Medical Sciences (India) ◽

10.1055/s-0040-1713709 ◽

2020 ◽

Vol 56 (02) ◽

pp. 087-090

Author(s):

Saumya Srivastava ◽

Vidhi Jain ◽

Vijaya Lakshmi Nag ◽

Sanjeev Misra ◽

Kuldeep Singh

Keyword(s):

Polymerase Chain Reaction ◽

Gold Standard ◽

Diagnostic Tests ◽

Immune Status ◽

Contact Tracing ◽

Great Promise ◽

Rt Pcr ◽

Chain Reaction ◽

Diagnostic Assays ◽

Polymerase Chain

AbstractDevelopment of rapid, reliable, and easy diagnostic tests with high-throughput is the need of the hour for laboratories combating the COVID-19 pandemic. While real-time polymerase chain reaction (RT-PCR) is the gold standard for diagnosing active infections, it is expensive and time-consuming. Serological diagnostic assays with a premise to aid rapid contact tracing, immune status determination, and identification of potential convalescent plasma donors hold great promise. Timely diagnosis, effective treatment, and future prevention are key to management of COVID-19.

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Molecular detection and prevalence of feline hemotropic mycoplasmas in Istanbul, Turkey

Acta Parasitologica ◽

10.1515/ap-2016-0022 ◽

2016 ◽

Vol 61 (1) ◽

Cited By ~ 1

Author(s):

Handan Cetinkaya ◽

Damla Haktanir ◽

Seckin Arun ◽

Cem Vurusaner

Keyword(s):

Molecular Detection ◽

Fragment Length Polymorphism ◽

Common Species ◽

Mycoplasma Species ◽

Pcr Assay ◽

Blood Samples ◽

Total Prevalence ◽

Polymerase Chain ◽

First Time ◽

Candidatus Mycoplasma Turicensis

AbstractThe aim of this study was to investigate Mycoplasma spp. species in blood samples of the domestic cats from the province of Istanbul, Turkey. Three hundred eighty four blood samples of client-owned cats were used for the identification of Mycoplasma haemofelis (Mhf), Candidatus Mycoplasma haemominutum (CMhm) and Candidatus Mycoplasma turicensis (CMt) by Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) assays. Out of 384 blood samples, 74 (19.3%) were positive for one of Mycoplasma species. The total prevalence of Mhf, CMhm and CMt infections was 9.9%, 17.7% and 0.8% respectively. The most common species was CMhm. Co-infections were mostly with Mhf/CMhm and the frequency was 8.1%. Two cats were infected with three species. The current study was the first molecular prevalence study of hemotropic mycoplasmas in Istanbul, reporting the presence of CMt for the first time in Turkey. Prevalence of feline mycoplasma was notably high in Istanbul and PCR assay could be preferred rather than the microscopic examination for the diagnosis.

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