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Microorganisms Feb 2021The first case of human babesiosis was reported in the literature in 1957. The clinical disease has sporadically occurred as rare case reports in North America and... (Review)
Review
The first case of human babesiosis was reported in the literature in 1957. The clinical disease has sporadically occurred as rare case reports in North America and Europe in the subsequent decades. Since the new millennium, especially in the last decade, many more cases have apparently appeared not only in these regions but also in Asia, South America, and Africa. More than 20,000 cases of human babesiosis have been reported in North America alone. In several cross-sectional surveys, exposure to spp. has been demonstrated within urban and rural human populations with clinical babesiosis reported in both immunocompromised and immunocompetent humans. This review serves to highlight the widespread distribution of these tick-borne pathogens in humans, their tick vectors in readily accessible environments such as parks and recreational areas, and their phylogenetic relationships.
PubMed: 33672522
DOI: 10.3390/microorganisms9020440 -
Frontiers in Microbiology 2022is an obligate intraerythrocytic protozoan transmitted by tick. Infections caused by protozoa, including and , are shown to inhibit tumor development by activating...
is an obligate intraerythrocytic protozoan transmitted by tick. Infections caused by protozoa, including and , are shown to inhibit tumor development by activating immune responses. Th1 immune response and macrophages not only are essential key factors in infection control but also play an important role in regulating tumor development. In this study, we investigated the effects of infection on melanoma in tumor-bearing mice. The results showed that infection could inhibit the growth of melanoma, significantly enlarge the spleen size ( ≤ 0.0001), and increase the survival period (over 7 days) of tumor-bearing mice. Mouse spleen immune cell analysis revealed that -infected tumor-bearing mice could increase the number of macrophages and CD4+ T cells, as well as the proportion of CD4+ T cells and M1 macrophages in the tumor. Immunohistochemical assays showed that infection could inhibit tumor angiogenesis ( ≤ 0.0032). Meanwhile, both -infected erythrocytes and culture supernatant were observed to significantly ( ≤ 0.0021) induce the mRNA expression of iNOS, IL-6, and TNF-α in macrophages. Moreover, culture supernatant could also repolarize IL-4-induced M2 macrophages to the M1 type. Overall, exerted antitumor effects by stimulating the immune system of tumor-bearing mice and inducing the polarization of immunosuppressive M2 macrophages to pro-inflammatory M1 macrophages.
PubMed: 35814662
DOI: 10.3389/fmicb.2022.862894 -
Frontiers in Microbiology 2019Lyme disease is the most prominent tick-borne disease in the United States. Co-infections with the tick-transmitted pathogens and sensu stricto are becoming a serious...
Lyme disease is the most prominent tick-borne disease in the United States. Co-infections with the tick-transmitted pathogens and sensu stricto are becoming a serious health problem. is an extracellular spirochete that causes Lyme disease while is a protozoan that infects erythrocytes and causes babesiosis. Testing of donated blood for species is not currently mandatory due to unavailability of an FDA approved test. Transmission of this protozoan by blood transfusion often results in high morbidity and mortality in recipients. Infection of C3H/HeJ mice with and individually results in inflammatory Lyme disease and display of human babesiosis-like symptoms, respectively. Here we use this mouse model to provide a detailed investigation of the reciprocal influence of the two pathogens on each other during co-infection. We show that infection attenuates parasitemia in mice while subverts the splenic immune response, such that a marked decrease in splenic B and T cells, reduction in antibody levels and diminished functional humoral immunity, as determined by spirochete opsonophagocytosis, are observed in co-infected mice compared to only infected mice. Furthermore, immunosuppression by in co-infected mice showed an association with enhanced Lyme disease manifestations. This study demonstrates the effect of only simultaneous infection by and on each pathogen, immune response and on disease manifestations with respect to infection by the spirochete and the parasite. In our future studies, we will examine the overall effects of sequential infection by these pathogens on host immune responses and disease outcomes.
PubMed: 31354683
DOI: 10.3389/fmicb.2019.01596 -
Infection and Immunity Oct 2023an intraerythrocytic apicomplexan parasite, is the primary causative agent of human babesiosis and an emerging threat to public health in the United States and...
an intraerythrocytic apicomplexan parasite, is the primary causative agent of human babesiosis and an emerging threat to public health in the United States and elsewhere. An effective vaccine against would reduce disease severity in acute babesiosis patients and shorten the parasitemic period in asymptomatic individuals, thereby minimizing the risk of transfusion-transmitted babesiosis. Here we report on immunogenicity, protective efficacy, and correlates of immunity following immunization with four immunodominant recombinantly produced antigens-Serine Reactive Antigen 1 (SERA1), Maltese Cross Form Related Protein 1 (MCFRP1), Piroplasm β-Strand Domain 1 (PiβS1), and Alpha Helical Cell Surface Protein 1 (BAHCS1)-delivered subcutaneously in Montanide ISA 51/CpG adjuvant in three doses to BALB/c mice. Following parasite challenge, BAHCS1 led to the highest reduction in peak parasitemia (67.8%), followed by SERA1 (44.8%) and MCFRP1 (41.9%); PiβS1 (27.6%) had minimal protective effect. All four antigens induced high ELISA total IgG and each isotype; however, antibody levels did not directly correlate with anti-parasitic activity in mice. Increased prechallenge levels of some cell populations including follicular helper T cells (T) and memory B cells, along with a set of six cytokines [IL-1α, IL-2, IL-3, IL-6, IL-12(p40), and G-CSF] that belong to both innate and adaptive immune responses, were generally associated with protective immunity. Our results indicate that mechanisms driving recombinant antigen-induced immunity are complex and multifactorial. We think that BAHCS1 warrants further evaluation in preclinical studies.
Topics: Humans; Mice; Animals; United States; Babesia microti; Babesiosis; Immunodominant Epitopes; Cytokines; Immunization
PubMed: 37728332
DOI: 10.1128/iai.00162-23 -
Pathogens (Basel, Switzerland) Feb 2023Babesiosis is a tick-borne zoonotic disease, which is caused by various species of intracellular parasite. It is a problem not only for the livestock industry but also... (Review)
Review
Babesiosis is a tick-borne zoonotic disease, which is caused by various species of intracellular parasite. It is a problem not only for the livestock industry but also for global health. Significant global economic losses, in particular in cattle production, have been observed. Since the current preventive measures against babesiosis are insufficient, there is increasing pressure to develop a vaccine. In this review, we survey the achievements and recent advances in the creation of antibabesiosis vaccine. The scope of this review includes the development of a vaccine against , , , and . Here, we present different strategies in their progress and evaluation. Scientists worldwide are still trying to find new targets for a vaccine that would not only reduce symptoms among animals but also prevent the further spread of the disease. Molecular candidates for the production of a vaccine against various spp. are presented. Our study also describes the current prospects of vaccine evolution for successful parasites elimination.
PubMed: 36839572
DOI: 10.3390/pathogens12020300 -
Tropical Animal Health and Production Feb 2023Babesia microti (Apicomplexa: Piroplasmida) causes a medically important tick-borne zoonotic protozoan disease. Egyptian camels are susceptible to Babesia infection;...
Babesia microti (Apicomplexa: Piroplasmida) causes a medically important tick-borne zoonotic protozoan disease. Egyptian camels are susceptible to Babesia infection; however, just a few cases have been documented. This study aimed to identify Babesia species, specifically Babesia microti, and their genetic diversity in dromedary camels in Egypt and associated hard ticks. Blood and hard tick samples were taken from 133 infested dromedary camels slaughtered in Cairo and Giza abattoirs. The study was conducted from February to November 2021. The 18S rRNA gene was amplified by polymerase chain reaction (PCR) to identify Babesia species. Nested PCR targeting the β-tubulin gene was used to identify B. microti. The PCR results were confirmed by DNA sequencing. Phylogenetic analysis based on the ß-tubulin gene was used to detect and genotype B. microti. Three tick genera were identified in infested camels (Hyalomma, Rhipicephalus, and Amblyomma). Babesia species were detected in 3 out of 133 blood samples (2.3%), while Babesia spp. were not detected in hard ticks by using the 18S rRNA gene. B. microti was identified in 9 out of 133 blood samples (6.8%) and isolated from Rhipicephalus annulatus and Amblyomma cohaerens by the β-tubulin gene. The phylogenetic analysis of the β-tubulin gene revealed that USA-type B. microti was prevalent in Egyptian camels. The results of this study suggested that the Egyptian camels may be infected with Babesia spp. and the zoonotic B. microti strains, which pose a potential risk to public health.
Topics: Animals; Babesia microti; Camelus; Egypt; Phylogeny; Tubulin; Babesia; Babesiosis; Ixodidae; Rhipicephalus; RNA, Ribosomal, 18S
PubMed: 36808565
DOI: 10.1007/s11250-023-03507-5 -
Clinical Infectious Diseases : An... Feb 2023Human babesiosis is a worldwide emerging tick-borne disease caused by intraerythrocytic protozoa. Most patients experience mild to moderate illness, but life-threatening...
BACKGROUND
Human babesiosis is a worldwide emerging tick-borne disease caused by intraerythrocytic protozoa. Most patients experience mild to moderate illness, but life-threatening complications can occur. Although cardiac complications are common, the full spectrum of cardiac disease and the frequency, risk factors, and outcomes in patients experiencing cardiac complications are unclear. Accordingly, we carried out a record review of cardiac complications among patients with babesiosis admitted to Yale-New Haven Hospital over the last decade to better characterize cardiac complications of babesiosis.
METHODS
We reviewed the medical records of all adult patients with babesiosis admitted to Yale-New Haven Hospital from January 2011 to October 2021, confirmed by identification of Babesia parasites on thin blood smear and/or by polymerase chain reaction. The presence of Lyme disease and other tick-borne disease coinfections were recorded.
RESULTS
Of 163 enrolled patients, 32 (19.6%) had ≥1 cardiac complication during hospitalization. The most common cardiac complications were atrial fibrillation (9.4%), heart failure (8.6%), corrected QT interval prolongation (8.0%), and cardiac ischemia (6.8%). Neither cardiovascular disease risk factors nor preexisting cardiac conditions were significantly associated with the development of cardiac complications. The cardiac complication group had a greater prevalence of high-grade parasitemia (>10%) (P < .001), longer median length of both hospital (P < .001) and intensive care unit stay (P < .001), and a higher mortality rate (P = .02) than the group without cardiac complications.
CONCLUSIONS
Cardiac complications of acute babesiosis are common and occurred in approximately one-fifth of this inpatient sample. Further investigation is needed to elucidate the relationship between babesiosis severity and cardiac outcomes.
Topics: Adult; Humans; Babesia microti; Babesiosis; Heart Diseases; Lyme Disease; Tick-Borne Diseases
PubMed: 35983604
DOI: 10.1093/cid/ciac525 -
Frontiers in Immunology 2021is a protozoan that infects red blood cells. Babesiosis is becoming a new global threat impacting human health. Rhoptry neck proteins (RONs) are proteins located at the...
is a protozoan that infects red blood cells. Babesiosis is becoming a new global threat impacting human health. Rhoptry neck proteins (RONs) are proteins located at the neck of the rhoptry and studies indicate that these proteins play an important role in the process of red blood cell invasion. In the present study, we report on the bioinformatic analysis, cloning, and recombinant gene expression of two truncated rhoptry neck proteins 2 (BmRON2), as well as their potential for incorporation in a candidate vaccine for babesiosis. Western blot and immunofluorescence antibody (IFA) assays were performed to detect the presence of specific antibodies against BmRON2 in infected mice and the localization of N-BmRON2 in parasites. experiments were carried out to investigate the role of BmRON2 proteins during the invasion process and experiments to investigate immunoprotection. Homologous sequence alignment and molecular phylogenetic analysis indicated that BmRON2 showed similarities with RON2 proteins of other species. We expressed the truncated N-terminal (33-336 aa, designated rN-BmRON2) and C-terminal (915-1171 aa, designated rC-BmRON2) fragments of the BmRON2 protein, with molecular weights of 70 and 29 kDa, respectively. Western blot assays showed that the native BmRON2 protein is approximately 170 kDa, and that rN-BmRON2 was recognized by serum of mice experimentally infected with Immunofluorescence analysis indicated that the BmRON2 protein was located at the apical end of merozoites, at the opposite end of the nucleus. red blood cell invasion inhibition studies with rBmRON2 proteins showed that relative invasion rate of rN-BmRON2 and rC-BmRON2 group is 45 and 56%, respectively. Analysis of the host immune response after immunization and infection showed that both rN-BmRON2 and rC-BmRON2 enhanced the immune response, but that rN-BmRON2 conferred better protection than rC-BmRON2. In conclusion, our results indicate that truncated rhoptry neck protein 2, especially its N-terminal fragment (rN-BmRON2), plays an important role in the invasion of host red blood cells, confers immune protection, and shows good potential as a candidate vaccine against babesiosis.
Topics: Animals; Antigens, Protozoan; Babesia microti; Babesiosis; Disease Models, Animal; Erythrocytes; Fluorescent Antibody Technique; Gene Expression; Host-Parasite Interactions; Immunization; Mice; Phylogeny; Protein Transport; Protozoan Proteins; Protozoan Vaccines; Recombinant Proteins
PubMed: 33717108
DOI: 10.3389/fimmu.2021.616343 -
Diagnostics (Basel, Switzerland) May 2022Diagnosing and treating many infectious diseases depends on correctly identifying the causative pathogen. Characterization of pathogen-specific nucleic acid sequences by... (Review)
Review
Diagnosing and treating many infectious diseases depends on correctly identifying the causative pathogen. Characterization of pathogen-specific nucleic acid sequences by PCR is the most sensitive and specific method available for this purpose, although it is restricted to laboratories that have the necessary infrastructure and finance. Microscopy, rapid immunochromatographic tests for antigens, and immunoassays for detecting pathogen-specific antibodies are alternative and useful diagnostic methods with different advantages and disadvantages. Detection of ribosomal RNA molecules in the cytoplasm of bacterial and protozoan pathogens by fluorescence in-situ hybridization (FISH) using sequence-specific fluorescently labelled DNA probes, is cheaper than PCR and requires minimal equipment and infrastructure. A LED light source attached to most laboratory light microscopes can be used in place of a fluorescence microscope with a UV lamp for FISH. A FISH test hybridization can be completed in 30 min at 37 °C and the whole test in less than two hours. FISH tests can therefore be rapidly performed in both well-equipped and poorly-resourced laboratories. Highly sensitive and specific FISH tests for identifying many bacterial and protozoan pathogens that cause disease in humans, livestock and pets are reviewed, with particular reference to parasites causing malaria and babesiosis, and mycobacteria responsible for tuberculosis.
PubMed: 35626441
DOI: 10.3390/diagnostics12051286 -
Pathogens (Basel, Switzerland) Mar 2021Human babesiosis in Europe has been attributed to infection with and, to a lesser extent, with and which are all transmitted to humans through a bite of . These...
Human babesiosis in Europe has been attributed to infection with and, to a lesser extent, with and which are all transmitted to humans through a bite of . These species circulate in the Netherlands, but autochthonous human babesiosis cases have not been reported so far. To gain more insight into the natural sources of these species, their presence in reservoir hosts and in was examined. Moreover, part of the ticks were tested for co-infections with other tick borne pathogens. In a cross-sectional study, qPCR-detection was used to determine the presence of species in 4611 tissue samples from 27 mammalian species and 13 bird species. Reverse line blotting (RLB) and qPCR detection of species were used to test 25,849 questing . Fragments of the 18S rDNA and cytochrome c oxidase subunit I (COI) gene from PCR-positive isolates were sequenced for confirmation and species identification and species-specific PCR reactions were performed on samples with suspected mixed infections. was found in two widespread rodent species: and , whereas was detected in the geographically restricted and , and occasionally in free-ranging . was detected in the ubiquitous , and occasionally in free-ranging . pecies-specific PCR revealed co-infections in and resulting in higher prevalence of and than disclosed by qPCR detection, followed by 18S rDNA and COI sequencing. The non-zoonotic species found were , sp. deer clade and badger-associated species. The infection rate of zoonotic species in questing ticks was higher for clade I (2.6%) than clade X (1.9%). Co-infection of with sensu lato and in questing nymphs occurred more than expected, which reflects their mutual reservoir hosts, and suggests the possibility of co-transmission of these three pathogens to humans during a tick bite. The ubiquitous spread and abundance of and in their reservoir hosts and questing ticks imply some level of human exposure through tick bites. The restricted distribution of the wild reservoir hosts for and its low infection rate in ticks might contribute to the absence of reported autochthonous cases of human babesiosis in the Netherlands.
PubMed: 33804875
DOI: 10.3390/pathogens10040386