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Iranian Journal of Parasitology 2024Bovine babesiosis, a global disease, has not been studied so far in Kashmir valley, which is having temperate type of climate as compared to rest of India having...
BACKGROUND
Bovine babesiosis, a global disease, has not been studied so far in Kashmir valley, which is having temperate type of climate as compared to rest of India having tropical to sub-tropical climate, so we felt the need to investigate it.
METHODS
To diagnose the babesiosis in clinically suspected cattle (n=450), peripheral blood film examination and PCR tests using generic and species-specific primers targeting / genera and , as well as , respectively were conducted. Four PCR products were sequenced and subjected to BLASTn analysis. Ticks were collected from the clinically suspected animals and identified as per the standard morphological keys.
RESULTS
The prevalence of babesiosis among suspected cattle in central Kashmir by peripheral blood film examination and PCR technique was 11.11% and 33.62%, respectively. The gene of Isolate B1 of spp. showed 99.0 to 100% nucleotide sequence homology with gene of different isolates of registered in the GenBank, while as gene of Isolate Z showed 98.5 to 99.2% and 93.1 to 93.9% nucleotide sequence homology with gene of different isolates of spp. and , respectively registered in the GenBank. spp. and spp. were the two major tick genera identified in the present study.
CONCLUSION
Bovine Babesiosis in Kashmir is attributed to , and some other spp. or strains which needs further investigation. To our knowledge, this is the first report of from northern India in cattle.
PubMed: 38654941
DOI: 10.18502/ijpa.v19i1.15211 -
MedRxiv : the Preprint Server For... Mar 2024Human babesiosis is a rapidly emerging and potentially fatal tick-borne disease caused by intraerythrocytic apicomplexan parasites of the genus. Among the various...
UNLABELLED
Human babesiosis is a rapidly emerging and potentially fatal tick-borne disease caused by intraerythrocytic apicomplexan parasites of the genus. Among the various species of that infect humans, has been found to cause severe and life-threatening infections. Detection of active infection is critical for accurate diagnosis and effective management of the disease. While molecular assays for the detection of infection in blood are available, a reliable strategy to detect biomarkers of active infection has not yet been developed. Here, we report the development of the first antigen capture assays that rely on the detection of two -exported immunodominant antigens, BdV234 and BdV38. The assays were validated using blood samples from cultured parasites in human erythrocytes and -infected laboratory mice at different parasitemia levels and following therapy. The assays display high specificity with no cross-reactivity with , , MO1, or The assay also demonstrates high sensitivity, detecting as low as 115 infected erythrocytes/µl of blood. Screening of 1,731 blood samples from diverse biorepositories, including previously identified Lyme and/or positive human samples and new specimens from field mice, showed no evidence of infection in these samples. The assays could be useful in diverse diagnostic scenarios, including point-of-care testing for early infection detection in patients, field tests for screening reservoir hosts, and high-throughput screening such as blood collected for transfusion.
SHORT SUMMARY
We developed two ELISA-based assays, BdACA38 and BdACA234, for detecting , a potentially fatal tick-borne parasite causing human babesiosis. The assays target two immunodominant antigens, BdV234 and BdV38, demonstrating high specificity (no cross-reactivity with other species or ) and sensitivity (detecting as low as 115 infected erythrocytes/µl). The assays were validated using in vitro-cultured parasites and infected mice. Screening diverse blood samples showed no evidence of active infection among 1,731 human and field mice blood samples collected from the north-eastern, midwestern, and western US. These assays offer potential in diverse diagnostic scenarios, including early patient detection, reservoir animal screening, and transfusion-transmitted babesiosis prevention.
PubMed: 38585766
DOI: 10.1101/2024.03.25.24304816 -
Inhibition of malaria and babesiosis parasites by putative red blood cell targeting small molecules.Frontiers in Cellular and Infection... 2024Chemotherapies for malaria and babesiosis frequently succumb to the emergence of pathogen-related drug-resistance. Host-targeted therapies are thought to be less...
BACKGROUND
Chemotherapies for malaria and babesiosis frequently succumb to the emergence of pathogen-related drug-resistance. Host-targeted therapies are thought to be less susceptible to resistance but are seldom considered for treatment of these diseases.
METHODS
Our overall objective was to systematically assess small molecules for host cell-targeting activity to restrict proliferation of intracellular parasites. We carried out a literature survey to identify small molecules annotated for host factors implicated in infection. Alongside , we implemented parasite susceptibility assays also in the zoonotic parasite and the veterinary parasite . We additionally carried out assays to test directly for action on RBCs apart from the parasites. To distinguish specific host-targeting antiparasitic activity from erythrotoxicity, we measured phosphatidylserine exposure and hemolysis stimulated by small molecules in uninfected RBCs.
RESULTS
We identified diverse RBC target-annotated inhibitors with -specific, specific, and broad-spectrum antiparasitic activity. The anticancer MEK-targeting drug trametinib is shown here to act with submicromolar activity to block proliferation of spp. in RBCs. Some inhibitors exhibit antimalarial activity with transient exposure to RBCs prior to infection with parasites, providing evidence for host-targeting activity distinct from direct inhibition of the parasite.
CONCLUSIONS
We report here characterization of small molecules for antiproliferative and host cell-targeting activity for malaria and babesiosis parasites. This resource is relevant for assessment of physiological RBC-parasite interactions and may inform drug development and repurposing efforts.
Topics: Animals; Humans; Parasites; Babesiosis; Malaria; Erythrocytes; Plasmodium; Malaria, Falciparum; Babesia; Antimalarials; Plasmodium falciparum
PubMed: 38572319
DOI: 10.3389/fcimb.2024.1304839 -
Open Forum Infectious Diseases Feb 2024Today only indirect fluorescent antibody assays (IFAs) are commercially available to detect antibodies against in humans. IFA is subjective and requires highly...
BACKGROUND
Today only indirect fluorescent antibody assays (IFAs) are commercially available to detect antibodies against in humans. IFA is subjective and requires highly experienced staff. We have therefore developed an enzyme-linked immunosorbent assay (ELISA)-based method for measuring anti- immunoglobulin G antibodies in human blood samples.
METHODS
Crude merozoite extract from in vitro cultures of a new isolate was used in ELISA to detect antibodies in different sets of samples: -positive samples, healthy individuals, tick-bitten individuals including follow-up samples 3 months later, positive control samples from patients with an active infection, and samples from malaria-endemic regions. As a reference, IFA was used to detect antibodies in the tick-bitten samples. Western blot was used to evaluate reactions against specific bands in extracts with/without parasites.
RESULTS
Using IFA as the reference method, the sensitivity and specificity of the ELISA were 86% (12/14) and 100% (52/52). There was a very high correlation ( = -0.84; = .0004) between IFA dilution factors and ELISA absorbances among the samples classified as positive. Five percent of the -positive samples were judged as weakly positive and 5% as strongly positive in our ELISA. Western blot showed that the immunodominant antigens (∼120 kDa) were from merozoites and not from erythrocytes.
CONCLUSIONS
This ELISA can detect antibodies directed against and it can be a useful and easy assay to handle compared with IFA. The ELISA can also measure high and low levels of antibodies, which could give insight into the recency of a infection.
PubMed: 38328497
DOI: 10.1093/ofid/ofae028 -
BioRxiv : the Preprint Server For... Jan 2024Babesiosis, caused by protozoan parasites of the genus , is an emerging tick-borne disease of significance for both human and animal health. parasites infect...
Babesiosis, caused by protozoan parasites of the genus , is an emerging tick-borne disease of significance for both human and animal health. parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of various species underscores the ongoing risk of new zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental shifts impacting the distribution and transmission dynamics of parasites, their vectors, and reservoir hosts. One such species, MO1, previously implicated in severe cases of human babesiosis in the midwestern United States, was initially considered closely related to , the predominant agent of human babesiosis in Europe. Yet, uncertainties persist regarding whether these pathogens represent distinct variants of the same species or are entirely separate species. We show that although both MO1 and share similar genome sizes, comprising three nuclear chromosomes, one linear mitochondrial chromosome, and one circular apicoplast chromosome, major differences exist in terms of genomic sequence divergence, gene functions, transcription profiles, replication rates and susceptibility to antiparasitic drugs. Furthermore, both pathogens have evolved distinct classes of multigene families, crucial for their pathogenicity and adaptation to specific mammalian hosts. Leveraging genomic information for MO1, , and other members of the Babesiidae family within Apicomplexa provides valuable insights into the evolution, diversity, and virulence of these parasites. This knowledge serves as a critical tool in preemptively addressing the emergence and rapid transmission of more virulent strains.
PubMed: 38293033
DOI: 10.1101/2024.01.17.575932 -
Frontiers in Cellular and Infection... 2023is an emerging tick-borne pathogen considered as the principal causative agent of bovine babesiosis in Europe with a notable zoonotic risk to human health. Despite its...
is an emerging tick-borne pathogen considered as the principal causative agent of bovine babesiosis in Europe with a notable zoonotic risk to human health. Despite its increasing impact, considerable gaps persist in our understanding of the molecular interactions between this parasite and its hosts. In this study, we address the current limitation of functional genomic tools in and introduce a stable transfection system specific to this parasite. We define the parameters for a drug selection system -WR99210 and evaluate different transfection protocols for highly efficient generation of transgenic parasites expressing GFP. We proved that plasmid delivery into bovine erythrocytes prior to their infection is the most optimal transfection approach for , providing novel evidence of parasites' ability to spontaneously uptake external DNA from erythrocytes cytoplasm. Furthermore, we validated the bidirectional and symmetrical activity of promoter, enabling simultaneous expression of external genes. Lastly, we generated a knockout line by targeting a gene locus. The observed dispensability of this gene in intraerythrocytic parasite development makes it a suitable recipient locus for further transgenic application. The platform for genetic manipulations presented herein serves as the initial step towards developing advanced functional genomic tools enabling the discovery of molecules involved in host-vector-pathogen interactions.
Topics: Humans; Babesia; Babesiosis; Transfection; Gene Targeting; Erythrocytes
PubMed: 38156314
DOI: 10.3389/fcimb.2023.1278041 -
Ticks and Tick-borne Diseases Jan 2024Babesiosis, a disease in humans and animals is caused by piroplasms from the genus Babesia and is transmitted by ixodid ticks. Bovine babesiosis, commonly called...
Babesiosis, a disease in humans and animals is caused by piroplasms from the genus Babesia and is transmitted by ixodid ticks. Bovine babesiosis, commonly called redwater fever, is reported in cattle from many regions of the British Isles. The presence of Babesia in questing ticks in the United Kingdom (UK) and its potential impact on public and animal health has not been widely studied. Therefore, this study aimed to assess the presence of Babesia spp. in England and Wales using ticks collected over a six-year period. Questing Ixodes ricinus nymphs were collected at 20 recreational areas between 2014 and 2019 and screened for Babesia. Of 3912 nymphs tested, Babesia spp. were detected in 15, giving an overall prevalence of 0.38% [95%CI: 0.21-0.63%]. A number of Babesia species were identified including B. venatorum (n = 9), B. divergens/capreoli (n = 5) and B. odocoilei-like species (n = 1). Based on the low prevalence of Babesia detected in questing I. ricinus nymphs in the recreational areas studied, the likelihood of exposure to Babesia-infected ticks is lower compared to other pathogens more widely studied in the UK (e.g. Borrelia burgdorferi s.l.). However, localized areas of elevated risk may occur in pockets in England and Wales.
Topics: Animals; Humans; Cattle; Ixodes; Babesia; Babesiosis; Wales; England; Nymph
PubMed: 38061320
DOI: 10.1016/j.ttbdis.2023.102291 -
Frontiers in Pharmacology 2023FLLL-32, a synthetic analog of curcumin, is a potent inhibitor of STAT3's constitutive activation in a variety of cancer cells, and its anticancer properties have been...
FLLL-32, a synthetic analog of curcumin, is a potent inhibitor of STAT3's constitutive activation in a variety of cancer cells, and its anticancer properties have been demonstrated both and . It is also suggested that it might have other pharmacological activities including activity against different parasites. This study therefore investigated the antiparasitic activity of FLLL-32 against four pathogenic species, , , , and , and one species, . anti-Babesia microti activity of FLLL-32 was also evaluated in mice. The FLLL-32, in the growth inhibition assay with a concentration range (0.005-50 μM), was tested for it's activity against these pathogens. The reverse transcription PCR (RT-PCR) assay was used to evaluate the possible effects of FLLL-32 treatment on the mRNA transcription of the target genes including and . The growth of , , , , and was significantly inhibited in a dose-dependent manner (in all cases, < 0.05). FLLL-32 exhibits the highest inhibitory effects on growth , and it's IC value against this species was 9.57 μM. The RT-PCR results showed that FLLL-32 inhibited the transcription of the gene. , the FLLL-32 showed significant inhibition ( < 0.05) of parasitemia in infected mice with results comparable to that of diminazene aceturate. Parasitemia level in -infected mice treated with FLLL-32 from day 12 post infection (pi) was reduced to reach zero level at day 16 pi when compared to the infected non-treated mice. The present study demonstrated the antibabesial properties of FLLL-32 and suggested it's usage in the treatment of babesiosis especially when utilized in combination therapy with other antibabesial drugs.
PubMed: 38027032
DOI: 10.3389/fphar.2023.1278451 -
Animals : An Open Access Journal From... Oct 2023Invasive species have a detrimental impact on native populations, particularly in island ecosystems, and they pose a potential zoonotic and wildlife threat. Black rats...
Invasive species have a detrimental impact on native populations, particularly in island ecosystems, and they pose a potential zoonotic and wildlife threat. Black rats () are invasive species that disrupt native flora and fauna on islands and serve as potential competent reservoirs for various pathogens and parasites. Microparasites screening was conducted in rat populations from small islands in central Italy (the Pontine Islands and Pianosa) with the aim of assessing the role of rats in maintaining infections, particularly in cases where key reservoir hosts were scarce or absent. We focused on microparasites of zoonotic and veterinary relevance. A total of 53 rats was kill-trapped and target tissues were analysed with molecular techniques. We observed the absence or very low prevalence of spp., while was found in rats from all locations, marking the first recorded instance of in wild rats. Data from Pianosa strongly suggest the presence of an autochthonous cycle in the Tuscan archipelago islands. was absent from all islands, even in areas where dogs, the main reservoirs, were present. was only recorded on the Pontine Islands, where genotyping is needed to shed light on infection dynamics. This study confirms that invasive species, such as rats, may be responsible for maintaining an increased parasitological threat to fauna and human communities in certain ecosystems.
PubMed: 37894002
DOI: 10.3390/ani13203279 -
Veterinary Microbiology Nov 2023Ticks are the main vectors for the transmission of bacterial, protist and viral pathogens in Europe affecting wildlife and domestic animals. However, some of them are... (Review)
Review
Exploring the diversity of tick-borne pathogens: The case of bacteria (Anaplasma, Rickettsia, Coxiella and Borrelia) protozoa (Babesia and Theileria) and viruses (Orthonairovirus, tick-borne encephalitis virus and louping ill virus) in the European continent.
Ticks are the main vectors for the transmission of bacterial, protist and viral pathogens in Europe affecting wildlife and domestic animals. However, some of them are zoonotic and can cause serious, sometimes fatal, problems in human health. A systematic review in PubMed/MEDLINE database was conducted to determine the spatial distribution and host and tick species ranges of a selection of tick-borne bacteria (Anaplasma spp., Borrelia spp., Coxiella spp., and Rickettsia spp.), protists (Babesia spp. and Theileria spp.), and viruses (Orthonairovirus, and flaviviruses tick-borne encephalitis virus and louping ill virus) on the European continent in a five-year period (November 2017 - November 2022). Only studies using PCR methods were selected, retrieving a total of 429 articles. Overall, up to 85 species of the selected tick-borne pathogens were reported from 36 European countries, and Anaplasma spp. was described in 37% (159/429) of the articles, followed by Babesia spp. (34%, 148/429), Borrelia spp. (34%, 147/429), Rickettsia spp. (33%, 142/429), Theileria spp. (11%, 47/429), tick-borne flaviviruses (9%, 37/429), Orthonairovirus (7%, 28/429) and Coxiella spp. (5%, 20/429). Host and tick ranges included 97 and 50 species, respectively. The highest tick-borne pathogen diversity was detected in domestic animals, and 12 species were shared between humans, wildlife, and domestic hosts, highlighting the following zoonotic species: Anaplasma phagocytophilum, Babesia divergens, Babesia microti, Borrelia afzelii, Borrelia burgdorferi s.s., Borrelia garinii, Borrelia miyamotoi, Crimean-Congo hemorrhagic fever virus, Coxiella burnetii, Rickettsia monacensis and tick-borne encephalitis virus. These results contribute to the implementation of effective interventions for the surveillance and control of tick-borne diseases.
Topics: Animals; Humans; Babesia; Encephalitis Viruses, Tick-Borne; Anaplasma; Theileria; Coxiella; Ixodes; Borrelia; Rickettsia; Animals, Domestic; Tick-Borne Diseases; Animals, Wild
PubMed: 37866329
DOI: 10.1016/j.vetmic.2023.109892