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Transfusion-transmitted spp.: a changing landscape of epidemiology, regulation, and risk mitigation.Journal of Clinical Microbiology Oct 2023spp. are tick-borne parasites with a global distribution and diversity of vertebrate hosts. Over the next several decades, climate change is expected to impact humans,... (Review)
Review
spp. are tick-borne parasites with a global distribution and diversity of vertebrate hosts. Over the next several decades, climate change is expected to impact humans, vectors, and vertebrate hosts and change the epidemiology of . Although humans are dead-end hosts for tick-transmitted , human-to-human transmission of spp. from transfusion of red blood cells and whole blood-derived platelet concentrates has been reported. In most patients, transfusion-transmitted (TTB) results in a moderate-to-severe illness. Currently, in North America, most cases of TTB have been described in the United States. TTB cases outside North America are rare, but case numbers may change over time with increased recognition of babesiosis and as the epidemiology of is impacted by climate change. Therefore, TTB is a concern of microbiologists working in blood operator settings, as well as in clinical settings where transfusion occurs. Microbiologists play an important role in deploying blood donor screening assays in endemic regions, identifying changing risks for in non-endemic areas, investigating recipients of blood products for TTB, and drafting TTB policies and guidelines. In this review, we provide an overview of the clinical presentation and epidemiology of TTB. We identify approaches and technologies to reduce the risk of collecting blood products from -infected donors and describe how investigations of TTB are undertaken. We also describe how microbiologists in non-endemic regions can assess for changing risks of TTB and decide when to focus on laboratory-test-based approaches or pathogen reduction to reduce TTB risk.
Topics: Humans; United States; Babesia; Babesia microti; Blood Transfusion; Babesiosis; Blood Donors
PubMed: 37750699
DOI: 10.1128/jcm.01268-22 -
Frontiers in Microbiology 2021The apicomplexan is a main pathogenic parasite causing human babesiosis, which is one of the most widely distributed tick-borne diseases in humans. Pyruvate kinase...
The apicomplexan is a main pathogenic parasite causing human babesiosis, which is one of the most widely distributed tick-borne diseases in humans. Pyruvate kinase (PYK) plays a central metabolic regulatory role in most living organisms and catalyzes the essentially irreversible step in glycolysis that converts phosphoenolpyruvate (PEP) to pyruvate. Hence, PYK is recognized as an attractive therapeutic target in cancer and human pathogens such as apicomplexans. In this study, we cloned, expressed, and purified PYK I (BmPYKI). Western blotting illustrated that anti-rBmPYKI antibody could specifically recognize the native BmPYKI protein in the lysate of with a 54-kDa band, which is consistent with the predicted size. In addition, the enzymatic activity of the purified recombinant PYKI (rPYKI) was tested under a range of pH values. The results showed that the maximum catalytic activity could be achieved at pH 7.0. The saturation curves for substrates demonstrated that the value for PEP was 0.655 ± 0.117 mM and that for ADP was 0.388 ± 0.087 mM. We further investigated the effect of 13 compounds on rBmPYKI. Kinetic analysis indicated that six inhibitors (tannic acid, shikonin, apigenin, PKM2 inhibitor, rosiglitazone, and pioglitazone) could significantly inhibit the catalytic activity of PYKI, among which tannic acid is the most efficient inhibitor with an IC value 0.49 μM. Besides, four inhibitors (tannic acid, apigenin, shikonin, and PKM2 inhibitor) could significantly decrease the growth of -cultured with IC values of 0.77, 2.10, 1.73, and 1.15 μM. Overall, the present study provides a theoretical basis for the design and development of new anti- drugs.
PubMed: 34603237
DOI: 10.3389/fmicb.2021.710678 -
CMAJ : Canadian Medical Association... Oct 2021
Topics: Aged; Animals; Anti-Bacterial Agents; Babesia microti; Babesiosis; Host-Parasite Interactions; Humans; Lyme Disease; Male
PubMed: 34663609
DOI: 10.1503/cmaj.201983-f -
Animals : An Open Access Journal From... Jun 2021(Aconoidasida: Piroplasmida) (Franca, 1910) is an emerging tick-borne parasite with rodents serving as the considered reservoir host. However, the distribution of in...
(Aconoidasida: Piroplasmida) (Franca, 1910) is an emerging tick-borne parasite with rodents serving as the considered reservoir host. However, the distribution of in Europe is insufficiently characterized. Based on the sample of 1180 rodents from 19 study sites in Lithuania, the objectives of this study were: (1) to investigate the presence of parasites in eight species of rodents, (2) to determine the prevalence of parasites in rodents from different habitats, and (3) to characterize the detected strains using partial sequencing of the 18S rRNR gene. DNA was detected in 2.8% rodents. The highest prevalence of was found in (14.5%) and (7.1%) followed by (2.3%), (2.2%) and (1.3%). In , was identified for the first time. The prevalence of -infected rodents was higher in the meadow (5.67%) than in the ecotone (1.69%) and forest (0.31%) habitats. The sequence analysis of the partial 18S rRNA gene reveals that isolates derived from rodents were 99-100% identical to human pathogenic 'Jena/Germany' strain.
PubMed: 34200491
DOI: 10.3390/ani11061707 -
Frontiers in Microbiology 2017The apicomplexan is the primary causative agent of human babesiosis, one of the most broadly distributed tick-borne diseases worldwide. undergoes a complex lifecycle...
The apicomplexan is the primary causative agent of human babesiosis, one of the most broadly distributed tick-borne diseases worldwide. undergoes a complex lifecycle within both the mammalian host and the tick vector, and employs several different specific molecular mechanisms to enter host cells. Enolase, the key glycolytic enzyme in intracellular glucose metabolism, can also be expressed on the parasite's outer surface, binds to human plasminogen, and coordinates apicomplexan parasite invasion of host cells, however, it lacks sorting sequences or lipoprotein anchor sites. In the present study, we isolated the coding gene of enolase (BmEno), expressed it within and purified the recombinant BmEno protein (rBmEno). Consequently, we confirmed cytoplasmic and surface localization of BmEno via immunofluorescence, and demonstrated that rBmEno catalyzes the dehydration of 2-phospho-D-glycerate to phosphoenolpyruvate. Moreover, our results showed that rBmEno binds to human plasminogen, and that the lysine analog ε-aminocaproic acid significantly inhibited this binding. Furthermore plasminogen bound to rBmEno converts to active plasmin. Additionally, actively immunizing mice with rBmEno could evoke a partial protective immunity against infection following challenge. In conclusion, enolase is a multifunctional cytoplasmic protein which is also expressed at the parasitic outer surface, facilitates binding to host plasminogen, and could partially protect hosts against parasite infection.
PubMed: 28443086
DOI: 10.3389/fmicb.2017.00622 -
Clinical Microbiology Reviews Jan 2011Babesia spp. are intraerythrocytic protozoan parasites of animals and humans that cause babesiosis, a zoonotic disease transmitted primarily by tick vectors. Although a... (Review)
Review
Babesia spp. are intraerythrocytic protozoan parasites of animals and humans that cause babesiosis, a zoonotic disease transmitted primarily by tick vectors. Although a variety of species or types of Babesia have been described in the literature as causing infection in humans, the rodent parasite Babesia microti has emerged as the focal point of human disease, especially in the United States. Not only has B. microti become established as a public health concern, this agent is increasingly being transmitted by blood transfusion: estimates suggest that between 70 and 100 cases of transfusion-transmitted Babesia (TTB) have occurred over the last 30 years. A recent upsurge in TTB cases attributable to B. microti, coupled with at least 12 fatalities in transfusion recipients diagnosed with babesiosis, has elevated TTB to a key policy issue in transfusion medicine. Despite clarity on a need to mitigate transmission risk, few options are currently available to prevent the transmission of B. microti by blood transfusion. Future mitigation efforts may stress serological screening of blood donors in regionalized areas of endemicity, with adjunct nucleic acid testing during the summer months, when acute infections are prevalent. However, several hurdles remain, including the absence of a licensed blood screening assay and a thorough cost-benefit analysis of proposed interventions. Despite current obstacles, continued discussion of TTB without proactive intervention is no longer a viable alternative.
Topics: Animals; Babesia microti; Babesiosis; Humans; Iatrogenic Disease; Transfusion Reaction; United States
PubMed: 21233506
DOI: 10.1128/CMR.00022-10 -
Parasites & Vectors Aug 2023The protozoan parasite Babesia microti that causes the zoonotic disease babesiosis resides in the erythrocytes of its mammalian host during its life-cycle. No effective...
BACKGROUND
The protozoan parasite Babesia microti that causes the zoonotic disease babesiosis resides in the erythrocytes of its mammalian host during its life-cycle. No effective vaccines are currently available to prevent Babesia microti infections.
METHODS
We previously identified a highly seroactive antigen, named Bm8, as a B. microti conserved erythrocyte membrane-associated antigen, by high-throughput protein chip screening. Bioinformatic and phylogenetic analysis showed that this membrane-associated protein is conserved among apicomplexan hemoprotozoa, such as members of genera Babesia, Plasmodium and Theileria. We obtained the recombinant protein Bm8 (rBm8) by prokaryotic expression and purification.
RESULTS
Immunofluorescence assays confirmed that Bm8 and its Plasmodium homolog were principally localized in the cytoplasm of the parasite. rBm8 protein was specifically recognized by the sera of mice infected with B. microti or P. berghei. Also, mice immunized with Bm8 polypeptide had a decreased parasite burden after B. microti or P. berghei infection.
CONCLUSIONS
Passive immunization with Bm8 antisera could protect mice against B. microti or P. berghei infection to a certain extent. These results lead us to hypothesize that the B. microti conserved erythrocyte membrane-associated protein Bm8 could serve as a novel broad-spectrum parasite vaccine candidate since it elicits a protective immune response against Babesiosis and Plasmodium infection.
Topics: Animals; Mice; Babesia microti; Babesia; Babesiosis; Phylogeny; Malaria; Membrane Proteins; Gastropoda; Mammals
PubMed: 37649042
DOI: 10.1186/s13071-023-05825-x -
PLoS Neglected Tropical Diseases Jan 2023Babesiosis is an emerging infectious disease caused by intraerythrocytic Babesia parasites that can cause severe disease and death. While blood type is known to affect...
BACKGROUND
Babesiosis is an emerging infectious disease caused by intraerythrocytic Babesia parasites that can cause severe disease and death. While blood type is known to affect the mortality of Plasmodium falciparum malaria patients, associations between red blood cell (RBC) antigens and Babesia microti infection and disease severity are lacking.
METHODS
We evaluated RhD and ABO blood types of Babesia-infected (18S rRNA reactive) blood donors in 10 endemic states in the Northeastern and northern Midwestern United States. We also assessed possible associations between RhD and ABO blood types and disease severity among hospitalized babesiosis patients in Connecticut.
RESULTS
A total of 768 Babesia-infected blood donors were analyzed, of which 750 (97.7%) had detectable B. microti-specific antibodies. B. microti-infected blood donors were more likely to be RhD- (OR of 1.22, p-value 0.024) than RhD+ donors. Hospitalized RhD- babesiosis patients were more likely than RhD+ patients to have high peak parasitemia (p-value 0.017), which is a marker for disease severity. No differences in RhD+ blood type were noted between residents of the Northeast (OR of 0.82, p-value 0.033) and the Midwest (OR of 0.74, p-value 0.23). Overall, ABO blood type was not associated with blood donor B. microti infection, however, B. microti-infected donors in Maine and New Jersey were more likely to be blood type B compared to non-type B (OR 2.49 [p = 0.008] and 2.07 [p = 0.009], respectively), while infected donors from Pennsylvania were less likely to be type B compared to non-type B (OR 0.32 [p = 0.02]).
CONCLUSIONS
People expressing RhD antigen may have a decreased risk of B. microti infection and babesiosis severity. The association of B antigen with B. microti infection is less clear because the antigen appeared to be less prevalent in infected Pennsylvania blood donors but more prevalent in Maine and New Jersey infected donors. Future studies should quantify associations between B. microti genotypes, RBC antigens, and the frequency and severity of B. microti infection to increase our understanding of human Babesia pathogenesis and improve antibody, vaccine, and RBC exchange transfusion strategies.
Topics: Humans; Babesiosis; Babesia microti; Connecticut; Blood Donors; Maine
PubMed: 36696414
DOI: 10.1371/journal.pntd.0011060 -
Frontiers in Cellular and Infection... 2022Babesiosis poses a serious threat to immunocompromised individuals and the major etiological species of for human babesiosis is . Merozoites are a critical stage in the...
Babesiosis poses a serious threat to immunocompromised individuals and the major etiological species of for human babesiosis is . Merozoites are a critical stage in the life cycle of . Several merozoite proteins have been demonstrated to play important roles in this process; however, most of the merozoite proteins of remain unknown. In the present study, we identified a novel merozoite protein of with similar structure to the thioredoxin (Trx)-like domain of the Trx family, which was named as Trx-like protein (TLP). Western blot assays demonstrated that this protein was expressed by during the erythrocytic infection process, and its expression peaked on day 7 post-infection . Immunofluorescence assay further showed that this protein is mainly expressed in merozoites. TLP hold both heparin- and erythrocyte-binding properties, which are critical functions of invasion-related proteins. Immunization with recombinant TLP imparted significant protection against infection in mice. Taken together, these results suggest that the novel merozoite protein, TLP, is an important pathogenic molecule of and may be a possible target for the design of babesiosis control strategy.
Topics: Animals; Babesia microti; Babesiosis; Mice; Protozoan Proteins; Thioredoxins; Virulence
PubMed: 35252036
DOI: 10.3389/fcimb.2022.826818 -
Scientific Reports Jun 2020Babesia microti is an intraerythrocytic parasite and the primary causative agent of human babesiosis. It is transmitted by Ixodes ticks, transfusion of blood and blood...
Babesia microti is an intraerythrocytic parasite and the primary causative agent of human babesiosis. It is transmitted by Ixodes ticks, transfusion of blood and blood products, organ donation, and perinatally. Despite its global public health impact, limited progress has been made to identify and characterize immunodominant B. microti antigens for diagnostic and vaccine use. Using genome-wide immunoscreening, we identified 56 B. microti antigens, including some previously uncharacterized antigens. Thirty of the most immunodominant B. microti antigens were expressed as recombinant proteins in E. coli. Among these, the combined use of two novel antigens and one previously described antigen provided 96% sensitivity and 100% specificity in identifying B. microti antibody containing sera in an ELISA. Using extensive computational sequence and bioinformatics analyses and cellular localization studies, we have clarified the domain architectures, potential biological functions, and evolutionary relationships of the most immunodominant B. microti antigens. Notably, we found that the BMN-family antigens are not monophyletic as currently annotated, but rather can be categorized into two evolutionary unrelated groups of BMN proteins respectively defined by two structurally distinct classes of extracellular domains. Our studies have enhanced the repertoire of immunodominant B. microti antigens, and assigned potential biological function to these antigens, which can be evaluated to develop novel assays and candidate vaccines.
Topics: Amino Acid Sequence; Animals; Antibodies, Protozoan; Antigens, Protozoan; Babesia microti; Babesiosis; Case-Control Studies; Computational Biology; Genetic Variation; Genome; Humans; Immunodominant Epitopes; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Peptide Library; Recombinant Proteins; Sequence Homology
PubMed: 32533024
DOI: 10.1038/s41598-020-66273-6