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Babesiosis is caused by intraerythrocytic protozoan parasites that are transmitted by ticks, or less commonly through blood transfusion or transplacentally. Human babesiosis was first recognized in a splenectomized patient in Europe but most cases have been reported from the northeastern and upper midwestern United States in people with an intact s...
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Context 1
... In New England, seroprevalence has varied between 0.5% and 16%. 15,19 Mild to Moderate Disease Following an incubation period of about 1 to 4 weeks after a tick bite or 1 to 9 weeks (but up to 6 months) following transfusion of contaminated blood products, a gradual onset of malaise and fatigue is accompanied by fever and one or more of the following: chills, sweats, anorexia, headache, myalgia, nausea, nonproductive cough, and arthralgia (Table 1). 18,20-29 Also reported are emotional liability and depression, Outpatient cases are from Ruebush et al, 25 Krause et al, 26 and Krause et al. 27 Inpatient cases are from White et al, 20 Krause et al, 24 Hatcher et al, 28 and Joseph et al. 18 hyperesthesia, sore throat, abdominal pain, vomiting, conjunctival injection, photo- phobia, and weight loss. ...
Citations
... Babesia is a protozoan parasite of the phylum Apicomplexa. Babesiosis is a worldwide tick-borne zoonosis caused by hemoprotozoan parasites of the genus Babesia (20). Ixodes ticks are the main vectors of Babesia spp. ...
Introduction
Ticks are important ectoparasites of livestock. Ticks and tick-borne diseases (TBDs) cause losses to the animal husbandry industry and also present a major hidden danger to public health and safety. However, the tick species and prevalence of TBDs in border regions of China, Russia, and North Korea remain unknown. The purpose of this study was to identify the tick species and tick-borne pathogens endemic in these regions.
Methods
Morphological and molecular identification of ticks was performed by microscopy and polymerase chain reaction (PCR), and the distribution of tick species, pathogen, and risk factors of infection were analyzed.
Results
In total, 1,187 ticks were collected from the border areas of 13 localities in eight cities. Five tick species were identified: Haemaphysalis longicornis (39.68%), Ixodes persulcatus (25.36%), Haemaphysalis japonica (15.50%), Dermacentor silvarum (15.42%), and Haemaphysalis concinna (4.04%). There were more female than male ticks, and nymphs were the least frequently collected. I. persulcatus was the main species in the forest environment, while H. longicornis was the main species in grasslands and animal surface. Four pathogens were detected: Rickettsia , Bartonella , Anaplasma , and Babesia .
Discussion
Pathogen detection in ticks differed significantly among the environments and between Sexes. There were significant differences in the proportion of ticks infected with Rickettsia , Bartonella , Anaplasma , and Babesia among regions, species, sexes, and environments. The results of this survey of the tick species in border areas of China, Russia, and North Korea provided a scientific basis for the prevention and control of TBDs.
... Babesia spp. -це рід паразитичних одноклітинних організмів, які належать до класу Apicomplexa і передаються іксодовими кліщами, можуть вражати різні види ссавців, включаючи людину (Vannier et al., 2015). Деякі види бабезій можуть спричиняти значні економічні збитки у тваринництві, тому надзвичайно важливими є дослідження патогенезу захворювання, епізоотології, а також розробки ефективних методів діагностики та лікування (Rashid et al., 2019). ...
This article presents the results of a study on the optimal conditions for in vitro cultivation of Babesia divergens. Cultivating species of the genus Babesia is essential for studying their biology, pathogenesis, and for developing diagnostic and therapeutic strategies. Different Babesia species require specific cultivation conditions, including optimal medium composition, serum and erythrocyte concentrations, oxygen levels, and additional nutritional components. Research on B. divergens in vitro is particularly relevant, as this species is a causative agent of human babesiosis and has limited therapeutic options available. In this study, we evaluated the effectiveness of three different media for cultivation: RPMI 1640, DMEM, and M-199. The culture was maintained by regularly replacing the medium and performing passages every two days. This process involved centrifuging the culture to remove the supernatant, transferring the infected erythrocytes into fresh medium, and adding fresh erythrocytes to achieve an optimal hematocrit concentration of 5 %. Parasitemia levels were routinely monitored by preparing blood smears from infected samples. The RPMI 1640 medium supplemented with bovine erythrocytes and 10% fetal calf serum yielded the highest parasitemia level and stable replication. The results indicated that the absence of serum adversely affected the viability of B. divergens, with parasites dying by the fourth day of culture without serum components. The optimal erythrocyte ratio was 5 %, providing a stable environment for the prolonged replication of the parasite. Regular monitoring of parasitemia showed sustained growth of B. divergens over six days, with parasitemia levels increasing from 2 % to 20 %. Confocal microscopy with fluorescent staining of genetic material confirmed active parasite growth, allowing visualization of intracellular forms. The data obtained for B. divergens emphasize the necessity of serum factors in the medium, distinguishing this species from others. This study enhances cultivation methods and may support future research aimed at understanding the biology, pathogenesis, and potential therapeutic strategies for controlling babesiosis caused by B. divergens.
... KO-1 [7], and B. divergens-like [8]. Infection with these pathogens can lead to a malaria-like illness characterized by symptoms such as high fever, anemia, hemoglobinuria, and even death, particularly for immunocompromised individuals [9]. ...
Background
Babesia duncani is a pathogen within the phylum Apicomplexa that causes human babesiosis. It poses a significant threat to public health, as it can be transmitted not only through tick bites but also via blood transfusion. Consequently, an understanding of the gene functions of this pathogen is necessary for the development of drugs and vaccines. However, the absence of conditional gene knockdown tools has hindered the research on this pathogen. The auxin-inducible degron (AID) system is a rapid, reversible conditional knockdown system widely used in gene function studies. Thus, there is an urgent need to establish the AID system in B. duncani to study essential gene functions.
Methods
The endogenous genes of the Skp1-Cullin-F-box (SCF) complex in B. duncani were identified and confirmed through multiple sequence alignment and conserved domain analysis. The expression of the F-box protein TIR1 from Oryza sativa (OsTIR1) was achieved by constructing a transgenic parasite strain using a homologous recombination strategy. Polymerase chain reaction (PCR), western blot, and indirect immunofluorescence assay (IFA) were used to confirm the correct monoclonal parasite strain. The degradation of enhanced green fluorescent protein (eGFP) tagged with an AID degron was detected through western blot and live-cell fluorescence microscopy after treatment of indole-3-acetic acid (IAA).
Results
In this study, Skp1, Cul1, and Rbx1 of the SCF complex in B. duncani were identified through sequence alignment and domain analysis. A pure BdTIR1 strain with expression of the OsTIR1 gene was constructed through homologous recombination and confirmed. This strain showed no significant differences from the wild type (WT) in terms of growth rate and proportions of different parasite forms. The eGFP tagged with an AID degron was successfully induced for degradation using 500 μM IAA. Grayscale analysis of western blot indicated a 61.3% reduction in eGFP expression levels, while fluorescence intensity analysis showed a 77.5% decrease in fluorescence intensity. Increasing the IAA concentration to 2 mM accelerated eGFP degradation and enhanced the extent of degradation.
Conclusions
This study demonstrated the functionality of the AID system in regulating protein levels by inducing rapid degradation of eGFP using IAA, providing an important research tool for studying essential gene functions related to invasion, egress, and virulence of B. duncani. Moreover, it also offers a construction strategy for apicomplexan parasites that have not developed an AID system.
Graphical Abstract
... 7, 8 The pathology in humans ranges from clinically silent infections to intense malaria-like episodes representing a fatal risk particularly for elderly or immunocompromised patients. 1 With a limited number of Babesia species known to infect humans�primarily Babesia microti in the United States 3 and Babesia divergens in Europe 1 �treatment has traditionally relied on a combination of antimalarial drugs (atovaquone) and antibiotics (azithromycin) in mild cases, while clindamycin and quinine are used in severe cases. 9 However, the emergence of drug-resistant Babesia strains 10 and recurrent infections in immunocompromised and asplenic individuals 11 underscores the urgent need for novel therapeutic approaches. ...
... 9,12−15 This need is further compounded by reports of new geographical regions affected and the identification of Babesia species as agents of severe human disease, suggesting rapid epidemiological changes. 1,16 Given the zoonotic nature of babesiosis, which affects both animals and humans, and its transmission dynamics that involve wildlife and environmental factors, the One Health approach interconnecting the health of humans, animals, and our shared environment becomes essential. 17 Proteasomes are crucial protein complexes found in all eukaryotic cells that play a significant role in degrading proteins marked by ubiquitin. ...
Tick-transmitted Babesia are a major global veterinary threat and an emerging risk to humans. Unlike their Plasmodium relatives, these erythrocyte-infecting Apicomplexa have been largely overlooked and lack specific treatment. Selective targeting of the Babesia proteasome holds promise for drug development. In this study, we screened a library of peptide epoxyketone inhibitors derived from the marine natural product carmaphycin B for their activity against Babesia. Several of these compounds showed activity against both the asexual and sexual blood stages of Plasmodium falciparum. These compounds inactivate β5 proteasome subunit activity in the lysates of Babesia divergens and Babesia microti in the low nanomolar range. Several compounds were tested with the purified B. divergens proteasome and showed IC50 values comparable to carfilzomib, an approved anticancer proteasome inhibitor. They also inhibited B. divergens growth in bovine erythrocyte cultures with solid EC50 values, but importantly, they appeared less toxic to human cells than carfilzomib. These compounds therefore offer a wider therapeutic window and provide new insights into the development of small proteasome inhibitors as selective drugs for babesiosis.
... While babesiosis has been reported in Europe, Asia, Australia, and South America, most of the cases are caused by B. microti in the Northeast and Upper Midwest of the United States [178]. Babesia species may be transmitted through blood transfusion, but B. microti is primarily transmitted to humans by Ixodes scapularis [179,180]. Once in a host, B. microti invades the erythrocytes and multiplies into daughter cells, which get released and spread to new erythrocytes [178,180]. Common symptoms of B. microti infection include fever, fatigue, chills, headache, loss of appetite, and myalgia [178,180]. ...
... Babesia species may be transmitted through blood transfusion, but B. microti is primarily transmitted to humans by Ixodes scapularis [179,180]. Once in a host, B. microti invades the erythrocytes and multiplies into daughter cells, which get released and spread to new erythrocytes [178,180]. Common symptoms of B. microti infection include fever, fatigue, chills, headache, loss of appetite, and myalgia [178,180]. B. microti infections cause severe disease in immunocompromised (HIV, immunosuppressed, or elderly patients) individuals, resulting in possible death [23,181]. ...
... Once in a host, B. microti invades the erythrocytes and multiplies into daughter cells, which get released and spread to new erythrocytes [178,180]. Common symptoms of B. microti infection include fever, fatigue, chills, headache, loss of appetite, and myalgia [178,180]. B. microti infections cause severe disease in immunocompromised (HIV, immunosuppressed, or elderly patients) individuals, resulting in possible death [23,181]. ...
Ticks are vectors of public health concern because the pathogens they transmit can cause detrimental diseases in humans. Lyme disease, tick-borne relapsing fever, human granulocytic anaplasmosis, Rocky Mountain spotted fever, tick-borne encephalitis, Crimean-Congo hemorrhagic fever, and babesiosis are some of the most common diseases caused by the pathogens transmitted by ticks. The overlap between human activities and tick habitats is growing, contributing to an increase in tick-borne disease cases. Unfortunately, pregnancy as a risk factor for tick-borne diseases is largely ignored. In this narrative review we use case reports, epidemiological studies, and animal studies to evaluate the maternal, pregnancy, and fetal outcomes caused by Lyme disease, tick-borne relapsing fever, human granulocytic anaplasmosis, Rocky Mountain spotted fever, tick-borne encephalitis, Crimean-Congo hemorrhagic fever, and babesiosis during pregnancy.
... In otherwise healthy individuals, less than 50 years of age, tick-transmitted infection frequently causes only a mild disease course or can be asymptomatic, likely often going undiagnosed. In individuals greater than 50 years of age, asplenic individuals, or those with a compromised immune system, B. microti can cause a severe infection requiring hospitalization and can be fatal [1,5,6]. Asplenia is a particularly significant risk factor for fatal disease. ...
Babesia microti is an Apicomplexan parasite that infects erythrocytes and causes the tick-transmitted infection, babesiosis. B. microti can cause a wide variety of clinical manifestations ranging from asymptomatic to severe infection and death. Some risk factors for severe disease are well-defined, an immune compromised state, age greater than 50, and asplenia. However, increasing cases of severe disease and hospitalization in otherwise healthy individuals suggests that there are unknown risk factors. The immunopathology of babesiosis is poorly described. CD4+ T cells and the spleen both play a critical role in parasite clearance, but few other factors have been found that significantly impact the course of disease. Here, we evaluated the role of several immune mediators in B. microti infection. Mice lacking TNF receptors 1 and 2, the receptors for TNFα and LTα, had a higher peak parasitemia, reduced parasite killing in infected red blood cells (iRBCs), and delayed parasite clearance compared to control mice. Mice lacking CCR2, a chemokine receptor involved in the recruitment of inflammatory monocytes, and mice lacking NADPH oxidase, which generates superoxide radicals, demonstrated reduced parasite killing but had little effect on the course of parasitemia. These results suggest that TNFR-mediated responses play an important role in limiting parasite growth, the death of parasites in iRBCs, and the clearance of iRBCs, and that the parasite killing in iRBCs is being primarily mediated by ROS and inflammatory monocytes/macrophages. By identifying factors involved in parasite killing and clearance, we can begin to identify additional risk factors for severe infection and newer therapeutic interventions.
... Human babesiosis is most commonly caused by tick bite, but it may also occur through blood transfusion, transplacental, or perinatal transmission. 18,19 In studies conducted on ticks that infect humans in the Central Anatolian region of Turkiye, B. bovis, B. ocultans Microscopic examination is widely used in laboratory diagnosis of pathogens in blood smears. However, there are serious problems such as similar morphologies of different parasites, carrier animals with low parasite counts, inability to identify parasites in acute conditions at the beginning of the disease, low sensitivity, need for an expert, and inability to identify species. ...
... Gel electrophoresis image including samples 62, 116, 118 and 130 after amplification and positive and negative controls. M: marker, PK: positive control, NK: negative control, PO: positive samples (Original)infection has generally been detected in individuals who have undergone splenectomy.18 ...
Aims: To determine the presence of Babesia species in ticks in the Ankara region and neighboring provinces; the aim of this study was to detect and distribute Babesia species using molecular methods in ticks collected from nature and hosts. Methods: Babesia was detected at the species level by conventional PCR method by DNA extraction of 191 tick samples collected from Ankara and neighboring provinces, which applied to the Parasitology National Reference Laboratory of the Ministry of Health, General Directorate of Public Health, between 2020-2021. Results: A total of 191 tick samples were examined in the study, and as a result of the conventional PCR study, 4 Babesia agents were found positive, 1 of them was Babesia bigemina (B. bigemina), 2 were Babesia ovis, 1 was Babesia spp. were determined. Conclusion: In tick-borne diseases such as Babesiosis; it should not be forgotten that ticks continue to focus some infections in nature and serve as reservoirs for disease agents in nature, and the necessary strategies for tick control should be followed.
... Mild babesiosis usually manifests with a wide range of nonspecific symptoms such as fever, sweats, fatigue, and myalgia. Several factors, including asplenia and older age, have been associated with severe presentations [3]. Previous studies have reported complications involving neurologic, cardiologic, hematologic, and splenic systems. ...
... Clinical physicians should maintain awareness of diagnostic anchoring when gathering clinical information to form a diagnosis, especially in diseases with myriad presentations. Babesiosis is a multifaceted disease that can manifest with a broad spectrum of symptoms influenced by the host's immunological status [3]. This variability in presentation underscores the challenge of accurately diagnosing Babesiosis, particularly in patients with concurrent unknown medical diseases. ...
... In this case, although the patient presented with clinical pictures suggestive of lymphoma, other potential causes of hemolytic anemia and splenic infarction were worth evaluating. Furthermore, the patient's epidemiological background, Northeastern United States, should raise concern for possible tick-borne diseases [3]. ...
Babesiosis is a tick-borne disease caused by an intraerythrocytic parasite known as Babesia spp. Its clinical presentation is often nonspecific and can range from asymptomatic to life-threatening, depending on the host’s immune status. This myriad of manifestations potentially overlaps with other familiar conditions such as hematologic malignancy. Fortunately, despite the variability of presentations, babesiosis can be effectively diagnosed by using simple and cost-effective methods like peripheral blood smears. Recognizing diverse presentations of babesiosis is crucial for accurate diagnosis and timely management. In this case, we highlight the importance of avoiding diagnostic anchoring and including babesiosis in the differential diagnosis, particularly in endemic areas and in the setting of uncommon complications such as splenic infarction.
... Babesia parasites are transmitted by ticks [4]; however, in humans, one of the primary routes of infection is through blood transfusion [5], and there have been documented cases of vertical transmission in both humans and mice [6,7]. In many cases, infected patients remain asymptomatic [5], but certain factors predispose individuals to complications from the infection [8]. The multiplication of the parasite and the subsequent release of merozoites lead to erythrocyte lysis [8][9][10], resulting in symptoms primarily characterized by anemia, fever, hemoglobinuria, and fatigue [11,12]. ...
... In many cases, infected patients remain asymptomatic [5], but certain factors predispose individuals to complications from the infection [8]. The multiplication of the parasite and the subsequent release of merozoites lead to erythrocyte lysis [8][9][10], resulting in symptoms primarily characterized by anemia, fever, hemoglobinuria, and fatigue [11,12]. Moreover, organ-related conditions can occur in patients infected with these intraerythrocytic parasites [13][14][15][16][17]. ...
... However, this treatment regimens have not consistently demonstrated effectiveness and patients with compromised immune systems may require supportive therapies, including blood transfusions [2]. Adverse effects have been reported for both therapy options, with a higher frequency observed in those receiving clindamycin/quinine [2,8]. All this is consistent with the need to develop and evaluate new compounds with anti-Babesia activity. ...
Babesiosis is a growing concern due to the increased prevalence of this infectious disease caused by Babesia protozoan parasites, affecting various animals and humans. With rising worries over medication side effects and emerging drug resistance, there is a notable shift towards researching babesiacidal agents. Antimicrobial peptides, specifically cathelicidins known for their broad-spectrum activity and immunomodulatory functions, have emerged as potential candidates. Aqui-luscidin, a cathelicidin from Crotalus aquilus, and its derivative Vcn-23, have been of interest due to their previously observed antibacterial effects and non-hemolytic activity. This work aimed to characterize the effect of these peptides against three Babesia species. Results showed Aquiluscidinʹs significant antimicrobial effects on Babesia species, reducing the B. bigemina growth rate and exhibiting IC50 values of 14.48 and 20.70 µM against B. ovata and B. bovis, respectively. However, its efficacy was impacted by serum presence in culture, and it showed no inhibition against a B. bovis strain grown in serum-supplemented medium. Conversely, Vcn-23 did not demonstrate babesiacidal activity. In conclusion, Aquiluscidin shows antibabesia activity in vitro and its efficacy is affected by the presence of serum in the culture medium. Nevertheless, this peptide represents a candidate for further investigation of its antiparasitic properties and provides insights into potential alternatives for the treatment of babesiosis.
... Las enzimas hepáticas, bilirrubina total e indirecta, nitrógeno ureico en sangre y/o creatinina sérica pueden también estar elevadas Vannier, 2015). ...
Revista GICOS. Volumen 9, Número 1 (2024): enero-abril