RARE DISEASE
Babesiosis
Babesiosis
Babesiosis
Drug discovery
1
drug
With orphan designation
Overview
Babesiosis is a tick-borne parasitic infection caused by Babesia species, primarily B. microti in the US. Transmitted by Ixodes ticks, it presents with nonspecific flu-like symptoms but can cause severe complications (hemolytic anemia, organ failure) in immunocompromised, asplenic, or elderly patients. Diagnosis relies on blood smear/PCR, and first-line treatment combines atovaquone with azithromycin [1][3][13]. Transfusion-related transmission remains a public health concern [1][11].
Therapies
First-line: Atovaquone + azithromycin (7–10 days for immunocompetent; extended courses for immunocompromised) [1][3][13].
Alternative: Clindamycin + quinine (reserved for severe cases due to adverse effects) [1][18].
Emerging therapies: Tafenoquine + atovaquone shows promise in preclinical models [8].
Categories: rare infectious diseases
Research Papers
1,445 drug discovery papers about Babesiosis, with 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,445 drug discovery papers about Babesiosis, with 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
vaccines
2026-05-27 | Six Decades of Global Research on Bovine Babesiosis Vaccines: A Comprehensive Systematic Review and Meta-Analysis.
Bovine babesiosis is a tick-borne disease that poses significant economic losses to global cattle production, and diverse vaccine platforms have been developed to combat it. This work critically evaluates global research on bovine babesiosis vaccines, integrating historical milestones with recent advances in antigen discovery and immunization approaches and assessing their protective efficacy through meta-analysis. Using comprehensive database searches, we identified 413 publications on bovine babesiosis vaccines, of which 168 met the inclusion criteria, spanning from 1960 to August 2025. Analysis revealed that B. bovis dominated the research output, followed by B. bigemina and B. divergens. Five key methodological approaches emerged: field trials, controlled experiments, immunogenicity assessments, in vitro assays, and in silico antigen analyses, with a notable shift toward immunogenicity and computational studies post-2000. Frequently studied antigens included RAP-1, MSA-2c, AMA-1, 11C5, and 12D3 (B. bovis); RAP-1 and GP45 (B. bigemina); and Bd37 (B. divergens). Geographically, research was concentrated in the United States, Australia, Argentina, Mexico, and France, which were identified as the top contributors in that order, primarily focusing on live and recombinant vaccines, with minimal African participation despite high cattle populations. Bibliometric analysis showed increasing publication output, with leading journals such as Veterinary Parasitology, Infection and Immunity, and Parasites & Vectors as the top three. Thematic evolution highlighted a transition from live vaccines to recombinant and multi-epitope strategies, with increasing emphasis on conserved antigens and novel platforms. However, more field evaluations are required to determine whether these new technologies can achieve protective efficacy comparable to that of live vaccines. This work underscores the need for sustained investment, intersectoral collaboration, and validation using standardized and comparable metrics in field trials to translate laboratory innovations into effective, safe, and globally accessible vaccines against bovine babesiosis.
2026-05-22 | Computational immunoinformatics and molecular modeling approaches for designing a multi-epitope vaccine against Babesia microti.
Babesia microti is an emerging tick-transmitted agent causing babesiosis in humans, becoming a major concern to public health due to the lack of a vaccine. In silico methods such as reverse vaccinology and immunoinformatics offer a convenient tool for identifying promising vaccine targets. Using computational immunoinformatics and molecular modelling tools, the current study aims to develop a multi-epitope vaccination against B. microti. For identifying the antigenic proteins, subtractive proteomics, NCBI, and PPGA were used, whereas for their screening, ProtParam (ExPASy), VaxiJen 2.0, AllerTOP v2.0, and BLASTp were utilized. For B-cell epitope prediction, IEDB (BepiPred 2.0) was used, and for T-cell epitope prediction, NetMHCpan 4.1 was used, along with other characteristics such as antigenicity, allergenicity, toxicity, and solubility, which were predicted later. A multi-epitope vaccine construct was designed using the selected epitopes linked together with the help of EAAAK and GPGPG linkers, with β-defensin as an adjuvant. For structural modeling and refinement, Scratch Protein Predictor and GalaxyRefine were used, followed by validation using PROCHECK. Further, molecular docking was done using ClusPro, while molecular dynamics simulations were done using AMBER 22. In addition, immune simulation and cloning were conducted. From a total of 3601 proteins, four non-homologous and non-allergenic proteins were selected for use in the design process, from which a total of seven epitopes were selected (MHC class I - 4; MHC class II - 3). Structural analysis of the designed vaccine revealed good stability, which further increased when the vaccine was modified using disulfide bonds. Population coverage revealed that the vaccine had good global coverage (99.74%). Docking revealed good binding of the designed vaccine with the toll-like receptors TLR-2 and TLR-4. Analysis of molecular dynamics and binding energies of TLR-2 (-135.11 kcal/mol), and TLR-4 (-157.27 kcal/mol) receptors further supported the stability of complexes. In summary, the in silico and biophysical studies show that the designed multi-epitope vaccine for B. microti may have desirable stability, immunogenicity, and positive interaction with TLR-2 and TLR-4 receptors. Nevertheless, experimental validation is needed to establish its safety and effectiveness.
2026-03-14 | Comparative Analysis of the EF-1α Intergenic Region in Babesia divergens Isolates: Insights into TA Repeat Variation and Potential Regulatory Implications.
Babesia divergens, a zoonotic tick-borne pathogen, causes bovine and human babesiosis in Europe. The Elongation Factor 1 alpha (EF-1α) protein is important in many cellular processes and has emerged as a possible target for subunit vaccine development against parasitic infections, and its intergenic region (IG) is an important tool for genetic manipulation of Babesia parasites. While the EF-1α locus of B. divergens has been described, structural variation between isolates was poorly defined. In order to fill this gap, we performed a comparative analysis of the EF-1α-IG in B. divergens human (Rouen 87 and Spanish sample) and bovine (Türkiye) host isolates. Our findings revealed both conserved and variable elements, particularly in TA nucleotide repeat numbers and IG sequence length. The Spanish isolate exhibited the highest TA repeat expansion, whereas the Rouen 87 strain had the shortest IG. Given the known role of repeat-rich promoter elements in gene regulation, these differences may influence EF-1α transcription. Additionally, these findings provide insights into the evolutionary divergence of B. divergens and its host adaptation mechanisms. This study establishes a foundation for future gene editing and transfection strategies, where selecting intergenic sequences with varying TA repeats could optimize transfection efficiency and explain phenotypic differences between isolates from different hosts or regions.
2026-03-11 | Molecular interactions between ticks (Ixodidae) and cattle: Salivary proteins, host immune modulation, and pathogen transmission.
Ticks (Ixodidae) are major ectoparasites of cattle and highly effective vectors of pathogens responsible for babesiosis, theileriosis, and anaplasmosis. Their capacity to remain attached and blood feed for prolonged periods is underpinned by a finely regulated molecular dialogue at the tick cattle skin interface, driven primarily by the continuous injection of saliva throughout feeding. Tick saliva is a complex and dynamically regulated mixture of proteins, peptides, and small molecules that counter host hemostatic, inflammatory, and immune defenses, thereby ensuring uninterrupted blood uptake and creating a permissive microenvironment for pathogen establishment. Increasing evidence indicates that saliva is not merely a passive vehicle for pathogen delivery but actively promotes saliva-assisted transmission (SAT), whereby saliva-mediated immunomodulation enhances pathogen transmission efficiency and early infection success at the bite site. At the gene and pathway level, cattle responses to tick feeding involve extensive reprogramming of innate and adaptive immune networks in the skin, characterized by suppression or redirection of inflammatory signaling, antigen presentation, and effector mechanisms that would otherwise limit feeding and pathogen survival. Concurrently, the remarkable diversity of the tick sialome shaped by feeding stage specific expression and extensive functional redundancy provides multiple molecular routes to inhibit coagulation, neutralize inflammatory mediators, and modulate leukocyte recruitment, complicating efforts to link individual salivary molecules to discrete host outcomes. Together, these mechanistic insights provide a foundation for translational advances in veterinary medicine, including anti-tick vaccines that target conserved tick molecules to reduce infestation and potentially disrupt pathogen transmission. This review synthesizes current knowledge on (i) the molecular composition and functional classes of tick salivary factors relevant to cattle, (ii) cattle immune gene and pathway modulation at tick bite sites, and (iii) saliva-driven mechanisms that facilitate tick-borne pathogen transmission, while highlighting key knowledge gaps and priorities for next generation control strategies.
2026-02-27 | Effect of Weak Vaccination on the Outbreak of the Babesiosis-Bovine Epidemic Model
The mathematical model of bovine babesiosis with vaccination helps researchers understand disease spread, assess vaccine effectiveness, and make predictions to guide the development of vaccination strategies that protect cattle. This model uses a number known as the basic reproduction number $ \mathcal{R}_{0} $ to predict the spread of a disease in herds of cattle. The model predicts that the illness will eventually go spread if $ \mathcal{R}_{0}<1 $. It is predicted that the Babesiosis bovine disease will extinct persist if $ \mathcal{R}_{0}>1$.Knowing this makes it easier to create immunization plans that work. To combat babesiosis, a serious disease that is spread by ticks to cattle, a vaccination is desperately needed. Some further discussion on the optimal amount of bovine vaccination is discussed. Some numerical simulations are utilized to validate the theoretical results.
cell therapies
2026-07-20 | Comprehensive treatment of canine babesiosis with extracorporeal blood purification
The purpose of the research is to evaluate plasmapheresis in combination therapy for canine babesiosis and to assess its efficacy. Materials and methods. The efficacy of babesiosis treatment in spontaneously infected dogs was determined. Dogs with babesiosis were treated with imidocarb dipropionate, and plasmapheresis, an extracorporeal blood purification method, was used in addition to common symptomatic therapy. Results and discussion. It was established that plasmapheresis in combination therapy for canine babesiosis is an effective, minimally invasive, and non-traumatic procedure that accelerates recovery and restoration of the body and improves kidney, liver, and cardiovascular function. The recovery rate with this therapy is 2-3 times higher than the standard approach. The procedure is effective for multiple organ failure, chronic diseases, and for the prevention of complications associated with the past disease.
2026-05-01 | A50-06 A Case of Coinfection of Babesiosis and Lyme Disease in a Patient With No Risk Factors or Exposure
Abstract We present a case of a co-infection of babesiosis and Lyme disease. 89-year-old female with a medical history of hypertension, mitral valve prolapse, and cognitive impairment was admitted to the emergency department after a fall. Laboratory tests revealed markedly elevated creatine kinase (CK) levels at 3,217 U/L, thrombocytopenia with a platelet count of 125 x 10^9/L, elevated liver enzymes (AST 134 U/L and ALT 114 U/L), and significantly high total bilirubin at 134 µmol/L. Imaging, including CT scans of the head, cervical spine, abdomen, and pelvis, showed no acute structural abnormalities. A peripheral blood smear identified intra-erythrocytic rings, suggesting babesiosis. The initial parasitemia was 12%, and the patient was started on Azithromycin and Atovaquone with a decrease in parasitemia to 6.6%. After 48 hours of treatment, a rebound increase in parasitemia to 10%, worsening anemia, and pulmonary edema were noted prompting exchange transfusion. Serological tests for Lyme disease were positive, while Anaplasma, Ehrlichia, and Rickettsia serologies were negative. Treatment for Lyme disease was initiated with doxycycline. Her hospital course was complicated with acute hypoxic respiratory failure due to pneumonia and acute kidney injury (AKI) which was further exacerbated by acute diastolic heart failure. Following improvement in liver function tests, thrombocytopenia, and anemia, she was discharged to a subacute rehabilitation facility with a 14-day course of antibiotics per Infectious disease recommendations. Outpatient follow-up was arranged to monitor her recovery and manage her ongoing health issues. The diagnosis of babesiosis can be challenging due to its symptom overlap with other febrile illnesses and the variability in clinical presentation. In our case, the patient presented with a fall, and her review of systems was limited in the setting of cognitive impairment. High suspicion in endemic areas with the detection of intra-erythrocytic rings on a peripheral blood smear remains key for diagnosis. There is a strong correlation between the degree of parasitemia and morbidity with previous studies reporting severe outcomes and complications if parasitemia is between 4 and 10%. Red cell exchange transfusion (RCE) has been shown to reduce parasite burden with some studies questioning its superiority over microbiological treatment. In our case, there was a transient reduction in parasitemia with a rebound increase and worsening clinical status necessitating RCE. This case underscores the diagnostic and therapeutic challenges posed by the co-infection of babesiosis and Lyme disease, particularly in elderly patients with multiple comorbidities. This abstract is funded by: SELF
2026-03-30 | Red Blood Cell Exchange Transfusion for Severe Babesiosis.
Babesiosis is a worldwide emerging tick-borne disease with an expanding geographic range in the US, Europe, and Asia. Red blood cell exchange transfusion (ET) is often used as an adjunctive treatment for severe illness from babesiosis, particularly in patients with high parasitemia, acute organ injury, or severe hemolytic anemia. Data supporting its clinical effectiveness, however, are lacking. To test whether ET improves clinical outcomes among hospitalized adult patients with severe babesiosis. This target trial emulation used data from a multicenter cohort study of 3233 consecutive adults hospitalized with babesiosis from 2010 to 2024 at 82 sites across the northeastern US. Patients were eligible if they had parasitemia greater than 10%, or 5% to 10% with either acute organ injury or severe hemolytic anemia. Data were analyzed from April to August 2025. Treatment with ET in the first 7 days of hospitalization. A composite of in-hospital death or 30-day readmission. Outcomes were compared between patients who received ET within the first 7 days of admission and those who did not. The analysis used logistic regression, with inverse probability of treatment weighting (IPTW) to adjust for potential confounders. The analysis included 629 patients (median [IQR] age, 71 [63-79] years; 446 male [70.9%]), among whom 209 (33.2%) received ET in the first 7 days of hospitalization. Patients treated with ET were more severely ill at baseline than those not treated with ET (median parasitemia, 14.0% vs 7.2%); however, severity of illness characteristics were well balanced after applying IPTW. In the main analysis, the primary end point occurred in 3.6% of patients who received ET and in 9.8% who did not (adjusted odds ratio, 0.22; 95% CI, 0.09-0.51). The benefit of ET was confirmed in multiple sensitivity analyses. This multicenter cohort study found that among severely ill adults hospitalized with babesiosis, the adjusted risk of in-hospital death or 30-day readmission was nearly 5-fold lower in those treated with ET vs those not treated with ET. These data support ET for severely ill patients with babesiosis, although the findings may be susceptible to unmeasured confounding. Further research is needed to identify which patients are most likely to benefit.
2026-03-01 | 413: AFEBRILE BUT INFECTED: SEVERE BABESIOSIS REQUIRING EXCHANGE TRANSFUSION IN AN ELDERLY PATIENT
Introduction: Babesiosis is a tickborne illness endemic to the Northeastern United States with testing often performed on locals with fever, anemia, thrombocytopenia, and transaminitis. Babesia may be overlooked without known exposure or typical clinical features. Prognosis ranges from asymptomatic to death with increased risk of severe disease with age >50. There is limited data supporting red blood cell (RBC) exchange transfusion in babesiosis and the effect on time to parasite clearance is not well defined. Description: An 84-year-old immunocompetent female presented to a Massachusetts emergency department with several days of subjective fevers, malaise, anorexia, dyspnea, and encephalopathy. She had relocated from Florida 6 weeks prior. She was afebrile and mildly hypoxic with acute severe anemia, thrombocytopenia, transaminitis, and hyperbilirubinemia, and was admitted for heart failure exacerbation. Within 2 days of hospitalization, anemia worsened requiring multiple RBC transfusions, and workup was consistent with hemolytic anemia. Given peripheral smear with rare schistocytes, new acute kidney injury, and encephalopathy, thrombotic thrombocytopenic purpura (TTP) was suspected. Over the next 24 hours, she was transferred to the ICU for undifferentiated shock requiring pressors and completed plasma exchange (TPE) for presumed TTP pending further testing. Within 12 hours of TPE, peripheral smear revealed 10-15% intraerythrocytic parasites consistent with babesiosis (later confirmed with babesia PCR). Despite severe illness, she remained afebrile. Treatment with atovaquone, azithromycin, and RBC exchange was immediately initiated with post-procedure parasitemia of 2.9%. On further investigation, the patient had been exposed to dogs that frequented wooded areas on Long Island prior to hospitalization. Time to parasite clearance was 3 days with significant clinical improvement before discharge. Discussion: Babesiosis can cause life-threatening illness that mimics TTP in the absence of acute fever in geriatric patients. Workup for babesiosis should not be delayed in afebrile patients with hemolytic anemia, thrombocytopenia, transaminitis, and any travel to endemic areas despite lack of confirmed tick exposure. In cases with high-grade parasitemia and shock, exchange transfusion should be considered.
2025-10-07 | Severe Babesiosis in an Asplenic Patient Treated with Red Cell Exchange: Highlighting the Critical Need for Evidence-Based Guidelines – A Case Report and Literature Review
Background: This report details a rare case of fulminant babesiosis in a splenectomized patient, emphasizing key diagnostic and therapeutic dilemmas. Babesiosis is a globally emerging tick-borne disease caused by the protozoan Babesia, posing a significant public health burden with mortality reportedly greater than 20% in immunocompromised individuals and those with transfusion-acquired infections. Splenectomized individuals are especially vulnerable to life-threatening Babesia infections, often manifesting as a more hazardous course requiring aggressive treatment. Case Presentation: A 62-year-old pre-diabetic male with a history of traumatic total splenectomy presented with three days of high-grade fever, chills, bodyache, weakness, and near-syncopal episodes. Laboratory evaluations indicated anemia, haptoglobinemia, thrombocytopenia, leukocytosis, elevated creatinine and blood urea nitrogen, hepatic transaminitis, hyperbilirubinemia, and hypoalbuminemia. A peripheral blood smear confirmed the diagnosis, revealing extra- and intra-corpuscular Babesia microti with prominent vacuoles and ring forms, with a high parasitemia level of 17.6%. The patient was diagnosed with severe babesiosis complicated by multi-organ failure - including acute kidney injury and liver failure. Antiparasitic therapy with atovaquone and azithromycin was instituted. Additionally, the patient required multiple red blood cell exchange (RCE) transfusions with 12 units of packed red blood cells (PRBCs), to reduce the parasitemia down to a safer level (4%) leading to gradual clinical stabilization over the next few days. Discussion: This case emphasizes the importance of high clinical suspicion and prompt diagnosis of babesiosis in susceptible patient groups, such as asplenic patients, presenting with unexplained fever, especially with hemolytic anemia or multi-organ dysfunction. Diagnosis relies on blood smear microscopy or polymerase chain reaction (PCR) test. Standard treatment combines atovaquone and azithromycin, or clindamycin and quinine. Exchange transfusion is typically recommended for severe babesiosis, especially for parasitemia exceeding 10% or organ dysfunction, to reduce parasite burden and clear out harmful toxins. While high parasitemia strongly correlates with disease severity, the definitive clinical benefit of RCE, particularly when compared to antibiotic therapy alone, is a topic of ongoing debate in the literature. The optimal administration and precise indications for RCE are not well studied, with current guidelines based on weak evidence and vaguely-defined criteria. RCE predisposes to potentially serious complications including transient hypotension, dyselectrolytemia, transfusion reactions, transfusion-related infections, fluid overload, and acute respiratory distress syndrome (ARDS). As babesiosis cases continue to rise in endemic regions of the US, targeted research is urgently needed to determine definitive effectiveness of RCE and to develop clear, evidence-based guidelines for its use in severe cases, ensuring safe patient outcomes.
small molecules
2026-09-26 | RMF-Activated Superparamagnetic Iron Oxide Nanoparticles Trigger Macrophage-Dependent Protection Against Babesia microti Infection.
Babesiosis is an emerging tick-borne zoonosis hampered by drug-resistant Babesia parasites and the absence of vaccines. Rotating magnetic field-activated superparamagnetic iron oxide nanoparticles (RMF-SPIONs) exert anti-tumor and antibacterial effects, yet their efficacy against intraerythrocytic protozoa, including Babesia microti, is unclear. We established murine B. microti and Plasmodium yoelii infection models, using immunodeficient mouse strains and immune cell depletion approaches to dissect the antiparasitic mechanism, alongside cytokine detection, long-term physiological observation and parasite rechallenge assays. RMF-SPION therapy markedly inhibited B. microti proliferation but showed no efficacy against P. yoelii. Macrophages served as the key effector cells through IL-12 secretion, while NK cells likely played auxiliary regulatory roles in this system. Convalescent mice developed strain-specific premunition, though latent infection induced chronic inflammation and visceral lesions. In conclusion, RMF-SPIONs selectively activate macrophages to eliminate B. microti. Combining natural premunition with macrophage-targeted activation likely provides a non-chemical strategy against drug-resistant babesiosis.
2026-09-26 | Molecular Detection of Tick-Borne Parasitic Pathogens in Ticks Collected from Animal Hosts in Chuy Province, Kyrgyzstan.
Tick-borne parasitic diseases pose important threats to veterinary and public health, particularly in countries with livestock-dependent economies such as Kyrgyzstan. However, molecular epidemiological data on tick-borne pathogens in Kyrgyzstan is limited. This study investigated the prevalence, genetic diversity, and host-tick-pathogen associations in Chuy Province, Kyrgyzstan. A total of 494 ticks belonging to 6 genera and 10 species were collected from various animal hosts in eight survey areas in central-northern Chuy Province and analyzed using polymerase chain reaction, Sanger sequencing, and phylogenetic analysis. Of the 494 ticks, 35 (7.1%) were infected, including 15 (3.0%) with Babesia species and 20 (4.0%) with Theileria species. The highest positive rates were observed in Rhipicephalus annulatus (13.8%) and Haemaphysalis punctata (12.4%). Molecular analysis identified 4 Babesia species (B. caballi, B. major, B. bigemina, B. occultans) and 2 Theileria species (T. orientalis, T. ovis). Ticks collected from horses had the highest infection rates and greatest diversity of pathogens. T. orientalis was the most common pathogen. T. ovis was exclusively found in ticks collected from sheep. Phylogenetic analysis confirmed that the isolates were closely related to strains circulating in neighboring Central Asian and Eurasian countries. The findings provide foundational data for developing region-specific vector control measures.
2026-09-26 | Multilocus Characterization Reveals Two Geographically Structured Babesia Lineages in Sheep from Southern and Southeastern Kazakhstan.
In Kazakhstan, despite the diversity of ixodid ticks and extensive livestock movement throughout Central Asia, ovine Babesia infections are poorly characterized. The objective of this study was to determine the occurrence, genetic diversity and geographic distribution of Babesia spp. in sheep from southern and southeastern Kazakhstan. A total of 1458 blood samples from 51 settlements across five regions were screened by nested PCR targeting mitochondrial cytb. Positive samples were characterized by Sanger sequencing, with additional multilocus analysis based on 18S rRNA and mitochondrial cox1 sequences. Babesia DNA was detected in 75/1458 samples (5.1%), with variation in PCR positivity among regions. Positive samples occurred in Turkestan (3.6%), Jambyl (7.2%), and Almaty (21.2%), but not in Kyzylorda or Jetisu. Phylogenetic analyses identified two geographically structured lineages. Nine Turkestan samples formed a lineage related to the Babesia sp. Xinjiang/Dunhuang group and were provisionally designated Babesia sp. TRK. The remaining 66 samples formed a B. motasi lineage comprising five cytb genotypes and showing closer affinity to the Lintan/Tianzhu group than to the Hebei/Ningxian group. Despite high 18S rRNA identity with B. motasi, mitochondrial markers revealed substantial divergence. The findings of the current study expand understanding of ovine Babesia diversity in Central Asia and emphasize the need for genomic characterization to resolve the taxonomic status of the detected lineages.
2026-09-26 | Identification of Small-Molecule Inhibitors of Babesia bovis by High-Throughput SYBR Green I Screening.
Background: Bovine babesiosis, caused by Babesia bovis, remains a major constraint to cattle production in endemic regions, while the current control relies on only a few drugs with concerns over resistance and residues. Methods: This study screened 9600 chemically diverse compounds from the Drug Discovery Initiative, University of Tokyo, against B. bovis using a 96-well SYBR Green I high-throughput assay at 1 µM. Primary hits were subjected to dose-response testing to determine IC50 values, followed by Madin-Darby bovine kidney cell cytotoxicity assays for selectivity index calculation. Combination effects with diminazene aceturate were assessed using combination indices, whereby three compounds were selected for in silico ADME, drug-likeness and target prediction analyses. DDI-1101229 was further assessed by exploratory docking against BbHT1 and BbCDPK4. Results and Conclusions: Eight compounds showed ≥50% inhibition in the primary screen. DDI-1101229, DDI-8231037 and DDI-15106103 showed sub-micromolar activity (IC50 = 0.27-0.68 µM), selectivity indices > 14.7 and strong synergy with diminazene aceturate (CI < 0.4). Overall, this study identified selective, chemically diverse non-diamidine and non-imidazoline small-molecule inhibitors of B. bovis, highlighting alternative chemotypes with antibabesial activity.
2026-09-21 | Epizootic monitoring and testing of etiotropic pathogenetic therapy for bovine babesiosis in the Caspian region of the Russian Federation
The purpose of the research is to conduct an epizootic analysis of the spread of babesiosis in cattle in the Caspian region of the Republic of Dagestan, to study the seasonal dynamics of tick parasitism, which are vectors of the disease, and to identify methods and means for etiotropic and pathogenetic therapy. Materials and methods. The study was conducted from April to October 2025 at the farms of the Chokh Agricultural Company in the Gunib District. A comparative efficacy study was conducted under production conditions in 100 cattle of different age groups and breeds with varying disease severity, using spontaneous babesiosis. Animals in the first control group (n = 50) were given 5% DAC based on diminazene diaceturate at a dose of 2.5 mg/kg of body weight. Animals in the second experimental group were given 5% neosidin based on diminazene diaceturate and phenazone at a dose of 2.5 mg/kg by active substanse in combination with doxycycline 200 at a dose of 1 ml/10 kg of body weight. Symptomatic and pathogenetic agents were used as indicated. In the region, the disease is recorded in April-May, primarily in the lowland zone of the republic. The epizootic situation of bovine babesiosis was determined on three farms in the Gunibsky District; 900 animals were examined. Results and discussion. Based on blood tests, babesiosis was diagnosed in 201 (22.3%) cattle. The highest percentage of animals infected with babesiosis was found in dairy farm No. 2 – Tugay, with 81 heads (27.0%), dairy farm No. 1 – Altav, with 57 heads (19.0%), and the lowest was found in dairy farm No. 3 – Ullubiyevka, with 63 heads (21.0%). Three species of ticks were found to infect cattle: Boophilus annulatus (Curtice, 1891) (49.28%), Rhipicephalus bursa (Canestrini and Fanzago, 1878) (8.51%), and Ixodes ricinus (0.35%). For etiotropic therapy, diminazene diaceturate-based medications (DAC 5% and Neosidin-M 5%) were used in combination with symptomatic and pathogenetic agents based on clinical signs. Efficacy rates were 92.0% and 98.0%, respectively.
proteins
2026-05-21 | Immunity beyond borders: non-lethal Plasmodium confers cross-protection against lethal Babesia via macrophage activation.
In co-endemic regions, hosts are concurrently infected by related apicomplexan hemoparasites, Plasmodium and the zoonotic pathogen Babesia. This study investigates how Plasmodium berghei XAT-Babesia rodhaini co-infection modulates host immunity, dissecting the contributions of innate and adaptive immune cells. Disease progression was assessed by survival, parasitemia, body weight, and hematological parameters. Splenic histopathology and qPCR were used to evaluate tissue damage and parasite burden. Immune responses were analyzed by cytokine, antibody measurement, and flow cytometry. Adaptive immunity was examined using SCID mice, and the roles of innate effectors were determined through selective depletion of NK cells and macrophages. P. berghei XAT infection elicited robust, heterologous protection significantly reducing parasitemia and splenic damage. This was linked with potent pro-inflammatory cytokines (IFN-γ, IL-12p70, and TNF-α), balanced by increased IL-10 levels, alongside increased ROS/NO production. While co-infected SCID mice, and NK depletion retained protection, macrophage depletion eliminated cross-protection and altered microbicidal cytokine and ROS/NO profiles. Flow cytometry confirmed expansion of the splenic macrophages in protected mice. These findings demonstrate that cross-protection is mediated by a macrophage-driven innate response. Protection was associated with IFN-γ-driven pro-inflammatory responses and ROS/NO production, balanced by IL-10 to limit immunopathology. This "protective homeostasis" highlights macrophage-targeted immunomodulation as a promising strategy for multivalent vaccines against apicomplexan parasites. Future research is warranted to elucidate macrophage activation and polarization dynamics underlying this protection.
2026-04-30 | Molecular characterization and functional analysis of thioredoxin peroxidase-2 from Babesia duncani.
Human babesiosis caused by Babesia duncani is an emerging zoonotic disease that poses a growing threat to public health. Since the first reported case in 1991, knowledge of this pathogen has remained limited. Recent completion of the B. duncani genome sequence has accelerated research aimed at elucidating its molecular biology. During its intraerythrocytic life cycle, B. duncani is exposed to oxidative stress generated by redox reactions. In this study, we identified and characterized an antioxidant enzyme from B. duncani-thioredoxin peroxidase-2 (BdTPx-2), a member of the peroxiredoxin family. BdTPx-2 gene was amplified from both cDNA and gDNA of B. duncani, revealing an open reading frame of 792 bp with no introns. The native form, cellular localization, and immunogenicity of BdTPx-2 were determined using polyclonal antibodies raised against recombinant BdTPx-2 (rBdTPx-2) and sera from B. duncani-infected mice. Antioxidant activity was assessed using a mixed-function oxidation (MFO) assay. BdTPx-2 was recognized by sera from mice infected with B. duncani or B. microti, dogs infected with B. gibsoni, and water buffalo infected with B. orientalis, indicating that TPx-2 is conserved and exhibits cross-reactivity among Babesia species. A native protein of approximately 35 kDa was specifically detected in B. duncani lysates. The MFO assay demonstrated that BdTPx-2 inhibits the oxidation of plasmid DNA by a DTT/FeCl₃ mixture, preventing its conversion from the supercoiled to the nicked form. In BALB/c mice immunized with rBdTPx-2 and subsequently challenged with Babesia, parasite burden was significantly reduced, accompanied by elevated levels of the proinflammatory cytokine IFN-γ, suggesting a protective immune response induced by rBdTPx-2. This work characterizes TPx-2 as an antioxidant enzyme in B. duncani and provides insights into a key mechanism by which the parasite defends against oxidative stress during its intraerythrocytic stage.
2025-07-10 | Rhipicephalus microplus voraxin-alpha contains B-cell epitopes that reduce ticks' biological fitness in immunized cattle.
Rhipicephalus microplus ticks are a serious pest of cattle in tropical and subtropical regions, mainly due to the losses they cause by reducing meat and milk production, as well as causing hide damage, in addition to their role as vectors of babesiosis and anaplasmosis. Integrated tick control must include the use of anti-tick vaccines to reduce tick populations and mitigate the ecological impact associated with the extensive use of acaricides. To develop improved vaccines, evaluation of new tick antigens is essential. Voraxin, mainly described as a testes-derived protein, is transferred from males to females during copulation, and it is crucial for stimulating engorgement in female ticks and for the development of their organs. In this study, R. microplus voraxin-alpha (voraxin-α) was amplified and sequenced, four peptides with predicted B-cell epitopes were designed and their immunogenic properties were evaluated. Each peptide was mixed with a commercial adjuvant and inoculated into two cattle from a tick-free region to corroborate if they were truly immunogenic. The antibody responses to each peptide were assessed using indirect ELISA. Two peptides were immunogenic and were selected for further testing involving immunization and experimental infestation with 10,000 larvae and two cattle per evaluated peptide. Immunization with peptide 3 reduced tick survival in 17 %, oviposition in 14 % and egg hatching in 22 %, while peptide 4 impaired oviposition in 18 % and egg hatching in 18 %. No effect on weight was observed. In conclusion, ticks fed on cattle producing specific antibodies against voraxin-α B-cell epitopes, have a reduced survival, oviposition and fertility, which are important biological parameters, related to tick fitness. Vaccine trials are required to evaluate this antigen as a vaccine candidate against R. microplus.
2025-04-28 | ves1α genes expression is the major determinant of Babesia bovis-infected erythrocytes cytoadhesion to endothelial cells.
Babesia bovis causes the most pathogenic form of babesiosis in cattle, resulting in high mortality in naive adults. This parasite invades red blood cells (RBCs) within the bovine hosts where they multiply and produce clinical disease. Babesia bovis exports numerous proteins into invaded RBCs changing its properties. Thus, the infected RBCs (iRBCs) are capable to cytoadhere in the microvasculature of internal organs and brain, leading to respiratory distress, neurologic signs, and mortality. Variant Erythrocyte Surface Antigen 1 (VESA1) is one of those exported proteins by B. bovis which represents a major virulence factor due to its central role in immune evasion by antigenic variation and intravascular parasite sequestration. VESA1 is a heterodimer protein encoded by ves1α and ves1β multigene family and localized on the ridges, the focal point for cytoadhesion. To gain further insights into the molecular mechanisms of cytoadhesion of B. bovis, we panned the parasites with bovine brain microvasculature endothelial cells, which resulted in obtaining several clones with different cytoadherence abilities. The transcriptome analysis of 2 high and 2 low cytoadherent clones revealed that ves1α sequences were diversified, likely resulting from genomic recombination. On the other hand, ves1β sequences were almost identical among these 4 clones. Insertion and expression of ves1α of a clone with high binding into ef-1α locus of a low binding clone increased cytoadherence confirming the role of ves1α suggested by our transcriptome data. Whole genome sequencing of cytoadherent clones revealed active locus of ves1 on chromosome 2. These results suggest that VESA1a proteins encoded by ves1α genes determine the cytoadherence strength of B. bovis and they are in the active site for recombination.
2025-03-06 | Molecular identification of a thioredoxin peroxidase in Babesia gibsoni with potential against oxidative stress.
Babesia gibsoni is the infectious agent of canine babesiosis, a vector-borne infection that poses a global threat to the canine health. As B. gibsoni is an erythrocytic intracellular parasite, the completion of its genome and transcriptome sequencing and analysis facilitates the elucidation of the mechanism of B. gibsoni residue in the erythrocyte. The main function of red blood cells (RBCs) is oxygen delivery; thus, B. gibsoni may be exposed to high levels of oxidative stress. To date, no report is available on the mechanism by which B. gibsoni survives oxidative stress inside the RBCs. In this study, the thioredoxin peroxidase, an important type of peroxidoxin, was identified from B. gibsoni, with 255 amino acids and a molecular weight of 27.7 kDa. There are two conserved "VCP" domains at the N- and C-termini, respectively, indicating that this gene was a 2-Cys peroxiredoxin belonging to the PTZ00137 superfamily. It was named BgTPx-2 and was detected to be located in the B. gibsoni-infected erythrocytes through an indirect immunofluorescence assay using the polyclonal antibody against the recombinant TPx-2. Additionally, its antioxidant activity was analyzed by mixed-function oxidation assay, and BgTPx-2 could protect the pBluescript SK ( +) plasmid from oxidative damage, suggesting an antioxidant function of BgTPx-2. Moreover, the immunogenicity of BgTPx-2 was tested by Western blotting and ELISA using the serum of beagle dogs infected with B. gibsoni, and the positive serum exhibited a detectable and significant antibody response against BgTPx-2 on day 4 and day 9 post-infection, respectively.
other
2026-08-26 | Genetic characterization of natural resistance to ticks and babesiosis in cattle: Implications for safer food production
Background: Tick-borne hemoparasitic diseases remain a major limiting factor affecting livestock productivity. They affect animal health, productivity, and the safety of animal-derived products. Excessive use of antiparasitic agents may result in the accumulation of drug residues in animal-derived products, which may compromise food safety. Therefore, discovering genetic basis of the natural resistance in livestock is an important area of agricultural biotechnology. Objective: The aim of this study was to identify genetic structures associated with natural resistance to ticks in cattle and to evaluate their potential application in marker-assisted selection for breeding disease-resistant cattle. Methods: The informativeness of selected SSR markers was assessed using PIC, RP, EMR, and MI indices. QTL mapping and population genetic analyses were performed to identify genetic structures associated with resistance. Results: The selected SSR markers exhibited moderate-to-high polymorphism and high informativeness. TGLA53, SPS115, and ILSTS006 were identified as the most informative markers. QTL mapping identified three genetic structures associated with resistance, of which the most prominent was characterized by multilocus control, high allelic diversity, and a high level of heterozygosity. Conclusion: The results obtained show that the use of multilocus genetic structures of resistance in marker selection may support the development of cattle populations with greater resistance to tick-borne diseases and potentially reduce reliance on chemical interventions, thereby contributing to safer and more sustainable animal-derived food production. Novelty of the Study: This study is distinguished by the integrated application of SSR marker informativeness analysis, QTL mapping, and population genetic analysis to evaluate natural genetic resistance to ticks and bovine babesiosis. The findings provide a scientific basis for marker-assisted breeding strategies aimed at improving livestock health and supporting the sustainable production of safe animal-derived foods. Keywords: bovine babesiosis, tick resistance, quantitative trait loci, SSR markers, marker-assisted selection, food safety.
2026-08-07 | Disruption of the CD47-SIRPα Axis Causes Profound Reduction of Parasitaemia in Mice Infected With Babesia microti.
Human babesiosis is an emerging disease in North America caused by the red blood cell (RBC)-infecting parasite Babesia microti. Despite a rise in clinical cases in recent years, the pathogenesis and host immune response to B. microti infection remain unclear. CD47 is a 'marker of self' transmembrane glycoprotein expressed on cell membranes that inhibits phagocytosis through interactions with macrophage signal-regulatory protein alpha (SIRPα). We posit that disruption of CD47-SIRPα signalling will induce macrophage uptake of Babesia-infected RBCs and reduce parasitaemia in susceptible hosts. To evaluate this, we compared the in vivo clearance of B. microti in CD47 knockout (CD47-/-) mice and wild-type C57BL/6J mice. Our results showed pronounced differences in infection kinetics between the two mouse strains. C57BL/6J mice showed steadily increasing parasitaemia that peaked at an average of 12%, whereas CD47-/- mice exhibited parasitaemia that never exceeded 1.5% throughout infection. Parasitaemia became undetectable by Day 21 in C57BL/6J and by Day 16 in CD47-/- mice, indicating resolution of infection. These results imply that, in the absence of CD47, growth of B. microti is diminished due to more efficient phagocytosis of infected RBCs by macrophages. We propose that CD47-SIRPα signalling plays a key role in the innate response to Babesia and suggest CD47 modulation as a new therapeutic target for the treatment of babesiosis.
2026-06-24 | Liver histopathology in dogs with naturally acquired Babesia rossi infection.
In sub-Saharan Africa, canine babesiosis, the most significant tick-borne disease in dogs, is primarily caused by the highly virulent intra-erythrocytic protozoan Babesia rossi, transmitted by ixodid ticks. The disease presents in two forms: uncomplicated and complicated. The former is characterized by hemolysis, while the latter involves severe systemic inflammation and multiple organ dysfunction, leading to high morbidity and mortality. Building on recent evidence of severe immunoinflammatory disruption in the spleen, lung, and bone marrow, this study examines liver histopathology in fatal Babesia rossi infection to determine whether the frequent hyperbilirubinemia and icterus of complicated babesiosis reflect primary hepatic injury or secondary systemic effects. Liver samples from 10 dogs that succumbed to Babesia rossi infection were compared with samples from four healthy control dogs. Significant hematological changes included reduced red cell count, hematocrit, and platelet concentration, while biochemical alterations showed increased serum ALT and urea. Key histopathological findings in the livers of Babesia-infected dogs showed severe diffuse dilation of the spaces of Disse, cholestasis, and hypertrophy of Kupffer cells containing bile and hemosiderin pigments. Additional findings included erythropoiesis, congestion, and widespread mononuclear inflammation, predominantly involving monocytes and macrophages with fewer lymphocytes and plasma cells, present in both intravascular and interstitial areas. Centrilobular hepatocytes exhibited coagulative necrosis or prominent hydropic vacuolation, likely attributable to severe hemolysis and resulting hypoxia, similar to findings reported in human malaria and sepsis. These observations improve understanding of the pathomechanisms underlying fatal babesiosis in dogs, particularly its effects on the liver, and may help refine targeted treatment strategies.
2026-03-30 | Thromboinflammation in dogs with virulent babesiosis.
Babesia rossi infection in dogs is associated with severe hemostatic dysregulation and systemic inflammation. The close interplay between innate immunity and coagulation in pathological states, including acute infections, may lead to thrombus formation, termed thromboinflammation, and has been proposed to underlie disease severity and poor outcomes. The objectives of this study were to investigate the presence of thromboinflammation in dogs with B. rossi infection by characterizing the overall hemostatic state, using thromboelastography (TEG) and plasma-based assays, and the systemic inflammatory response using acute phase reactants as markers, and further to determine whether, if present, thromboinflammation was associated with disease severity. Ninety-seven dogs naturally infected with B. rossi and 15 healthy control dogs were included. Diagnosis of babesiosis was confirmed by reverse line blot polymerase chain reaction. Blood samples were collected at presentation, prior to any treatment. Hemostatic function was assessed using TEG, routine coagulation assays, coagulation factor activity, and fibrinolysis markers. C-reactive protein (CRP) and serum amyloid A (SAA) were measured as markers of systemic inflammation. Twelve of the Babesia-infected dogs died (12%). Babesia-infected dogs demonstrated hemostatic abnormalities marked by severe thrombocytopenia and a procoagulant state, including platelet activation, preserved clot strength, and elevated fibrinogen concentrations. Thromboelastography further revealed delayed clot initiation and propagation with maintained clot firmness, whereas conventional assays showed prolonged prothrombin time and activated partial thromboplastin time, along with markedly reduced coagulation factor activities in non-survivors. Minimal fibrinolysis was observed on TEG and was associated with elevated α2-antiplasmin activity and the presence of fibrin microthrombi in multiple organs. Markedly elevated CRP and SAA concentrations confirmed the simultaneous presence of systemic inflammation. B. rossi infection in dogs induced thromboinflammation characterized by thrombocytopenia, platelet activation, coagulation factor consumption, fibrinolytic shutdown and systemic inflammation. Thromboinflammation may drive endothelial injury, microthrombosis, and an increased risk of organ failure and death. Future therapeutic interventions targeting thromboinflammation may improve patient outcomes.
2025-11-17 | Genetic diversity of BoLA-DRB3 and its association with Anaplasma marginale and Babesia spp. infections in creole cattle of northeastern Colombia.
The BoLA-DRB3 gene is one of the most polymorphic loci in cattle, with alleles associated with susceptibility or resistance to several infectious diseases, including leukosis, mastitis, and hemotropic infections. In this study, we assessed the genetic diversity of the BoLA-DRB3 gene in three Colombian Creole cattle breeds and examined its association with natural infections by Anaplasma marginale and Babesia spp. in northeastern Colombia. A total of 97 animals (Chino - CrChi, n = 34; Casanareño - CrCAS-, n = 32; Sanmartinero - CrSM-, n = 31) from Arauca, Casanare, Meta, and Santander departments were genotyped using PCR-direct sequencing of the second exon of the BoLA-DRB3 gene. Overall genetic diversity was moderate, with a nucleotide diversity of π = 0.086, a mean pairwise distance of 18.97, and 62 segregating sites. Among the breeds, CrCAS showed the highest diversity, followed by CrChi and CrSM. We identified 35 BoLA-DRB3 alleles, 34 of which were previously reported in the IPD-MHC database, while one was novel. The CrChi population showed significant deviation from Hardy-Weinberg equilibrium. Two alleles, BoLA-DRB3*001:01 and BoLA-DRB3*025:01:01, were significantly associated with reduced risk of B. bigemina infection in CrSM, whereas BoLA-DRB3*048:02 was linked to increased susceptibility to B. bovis in CrChi. This study confirms the high genetic variability of Colombian Creole cattle breeds. The high frequency of alleles associated with B. bigemina infection in CrSM highlights its potential as a genetic reservoir for future studies evaluating the heritability and functionality of these alleles. In contrast, the elevated frequency of a susceptibility-associated allele for B. bovis infection in CrChi, together with evidence of inbreeding, underscores the urgent need for targeted conservation and breeding strategies to preserve genetic diversity and reduce disease vulnerability to infectious diseases in this breed.
vaccines
2026-05-27 | Six Decades of Global Research on Bovine Babesiosis Vaccines: A Comprehensive Systematic Review and Meta-Analysis.
Bovine babesiosis is a tick-borne disease that poses significant economic losses to global cattle production, and diverse vaccine platforms have been developed to combat it. This work critically evaluates global research on bovine babesiosis vaccines, integrating historical milestones with recent advances in antigen discovery and immunization approaches and assessing their protective efficacy through meta-analysis. Using comprehensive database searches, we identified 413 publications on bovine babesiosis vaccines, of which 168 met the inclusion criteria, spanning from 1960 to August 2025. Analysis revealed that B. bovis dominated the research output, followed by B. bigemina and B. divergens. Five key methodological approaches emerged: field trials, controlled experiments, immunogenicity assessments, in vitro assays, and in silico antigen analyses, with a notable shift toward immunogenicity and computational studies post-2000. Frequently studied antigens included RAP-1, MSA-2c, AMA-1, 11C5, and 12D3 (B. bovis); RAP-1 and GP45 (B. bigemina); and Bd37 (B. divergens). Geographically, research was concentrated in the United States, Australia, Argentina, Mexico, and France, which were identified as the top contributors in that order, primarily focusing on live and recombinant vaccines, with minimal African participation despite high cattle populations. Bibliometric analysis showed increasing publication output, with leading journals such as Veterinary Parasitology, Infection and Immunity, and Parasites & Vectors as the top three. Thematic evolution highlighted a transition from live vaccines to recombinant and multi-epitope strategies, with increasing emphasis on conserved antigens and novel platforms. However, more field evaluations are required to determine whether these new technologies can achieve protective efficacy comparable to that of live vaccines. This work underscores the need for sustained investment, intersectoral collaboration, and validation using standardized and comparable metrics in field trials to translate laboratory innovations into effective, safe, and globally accessible vaccines against bovine babesiosis.
2026-05-22 | Computational immunoinformatics and molecular modeling approaches for designing a multi-epitope vaccine against Babesia microti.
Babesia microti is an emerging tick-transmitted agent causing babesiosis in humans, becoming a major concern to public health due to the lack of a vaccine. In silico methods such as reverse vaccinology and immunoinformatics offer a convenient tool for identifying promising vaccine targets. Using computational immunoinformatics and molecular modelling tools, the current study aims to develop a multi-epitope vaccination against B. microti. For identifying the antigenic proteins, subtractive proteomics, NCBI, and PPGA were used, whereas for their screening, ProtParam (ExPASy), VaxiJen 2.0, AllerTOP v2.0, and BLASTp were utilized. For B-cell epitope prediction, IEDB (BepiPred 2.0) was used, and for T-cell epitope prediction, NetMHCpan 4.1 was used, along with other characteristics such as antigenicity, allergenicity, toxicity, and solubility, which were predicted later. A multi-epitope vaccine construct was designed using the selected epitopes linked together with the help of EAAAK and GPGPG linkers, with β-defensin as an adjuvant. For structural modeling and refinement, Scratch Protein Predictor and GalaxyRefine were used, followed by validation using PROCHECK. Further, molecular docking was done using ClusPro, while molecular dynamics simulations were done using AMBER 22. In addition, immune simulation and cloning were conducted. From a total of 3601 proteins, four non-homologous and non-allergenic proteins were selected for use in the design process, from which a total of seven epitopes were selected (MHC class I - 4; MHC class II - 3). Structural analysis of the designed vaccine revealed good stability, which further increased when the vaccine was modified using disulfide bonds. Population coverage revealed that the vaccine had good global coverage (99.74%). Docking revealed good binding of the designed vaccine with the toll-like receptors TLR-2 and TLR-4. Analysis of molecular dynamics and binding energies of TLR-2 (-135.11 kcal/mol), and TLR-4 (-157.27 kcal/mol) receptors further supported the stability of complexes. In summary, the in silico and biophysical studies show that the designed multi-epitope vaccine for B. microti may have desirable stability, immunogenicity, and positive interaction with TLR-2 and TLR-4 receptors. Nevertheless, experimental validation is needed to establish its safety and effectiveness.
2026-03-14 | Comparative Analysis of the EF-1α Intergenic Region in Babesia divergens Isolates: Insights into TA Repeat Variation and Potential Regulatory Implications.
Babesia divergens, a zoonotic tick-borne pathogen, causes bovine and human babesiosis in Europe. The Elongation Factor 1 alpha (EF-1α) protein is important in many cellular processes and has emerged as a possible target for subunit vaccine development against parasitic infections, and its intergenic region (IG) is an important tool for genetic manipulation of Babesia parasites. While the EF-1α locus of B. divergens has been described, structural variation between isolates was poorly defined. In order to fill this gap, we performed a comparative analysis of the EF-1α-IG in B. divergens human (Rouen 87 and Spanish sample) and bovine (Türkiye) host isolates. Our findings revealed both conserved and variable elements, particularly in TA nucleotide repeat numbers and IG sequence length. The Spanish isolate exhibited the highest TA repeat expansion, whereas the Rouen 87 strain had the shortest IG. Given the known role of repeat-rich promoter elements in gene regulation, these differences may influence EF-1α transcription. Additionally, these findings provide insights into the evolutionary divergence of B. divergens and its host adaptation mechanisms. This study establishes a foundation for future gene editing and transfection strategies, where selecting intergenic sequences with varying TA repeats could optimize transfection efficiency and explain phenotypic differences between isolates from different hosts or regions.
2026-03-11 | Molecular interactions between ticks (Ixodidae) and cattle: Salivary proteins, host immune modulation, and pathogen transmission.
Ticks (Ixodidae) are major ectoparasites of cattle and highly effective vectors of pathogens responsible for babesiosis, theileriosis, and anaplasmosis. Their capacity to remain attached and blood feed for prolonged periods is underpinned by a finely regulated molecular dialogue at the tick cattle skin interface, driven primarily by the continuous injection of saliva throughout feeding. Tick saliva is a complex and dynamically regulated mixture of proteins, peptides, and small molecules that counter host hemostatic, inflammatory, and immune defenses, thereby ensuring uninterrupted blood uptake and creating a permissive microenvironment for pathogen establishment. Increasing evidence indicates that saliva is not merely a passive vehicle for pathogen delivery but actively promotes saliva-assisted transmission (SAT), whereby saliva-mediated immunomodulation enhances pathogen transmission efficiency and early infection success at the bite site. At the gene and pathway level, cattle responses to tick feeding involve extensive reprogramming of innate and adaptive immune networks in the skin, characterized by suppression or redirection of inflammatory signaling, antigen presentation, and effector mechanisms that would otherwise limit feeding and pathogen survival. Concurrently, the remarkable diversity of the tick sialome shaped by feeding stage specific expression and extensive functional redundancy provides multiple molecular routes to inhibit coagulation, neutralize inflammatory mediators, and modulate leukocyte recruitment, complicating efforts to link individual salivary molecules to discrete host outcomes. Together, these mechanistic insights provide a foundation for translational advances in veterinary medicine, including anti-tick vaccines that target conserved tick molecules to reduce infestation and potentially disrupt pathogen transmission. This review synthesizes current knowledge on (i) the molecular composition and functional classes of tick salivary factors relevant to cattle, (ii) cattle immune gene and pathway modulation at tick bite sites, and (iii) saliva-driven mechanisms that facilitate tick-borne pathogen transmission, while highlighting key knowledge gaps and priorities for next generation control strategies.
2026-02-27 | Effect of Weak Vaccination on the Outbreak of the Babesiosis-Bovine Epidemic Model
The mathematical model of bovine babesiosis with vaccination helps researchers understand disease spread, assess vaccine effectiveness, and make predictions to guide the development of vaccination strategies that protect cattle. This model uses a number known as the basic reproduction number $ \mathcal{R}_{0} $ to predict the spread of a disease in herds of cattle. The model predicts that the illness will eventually go spread if $ \mathcal{R}_{0}<1 $. It is predicted that the Babesiosis bovine disease will extinct persist if $ \mathcal{R}_{0}>1$.Knowing this makes it easier to create immunization plans that work. To combat babesiosis, a serious disease that is spread by ticks to cattle, a vaccination is desperately needed. Some further discussion on the optimal amount of bovine vaccination is discussed. Some numerical simulations are utilized to validate the theoretical results.
cell therapies
2026-07-20 | Comprehensive treatment of canine babesiosis with extracorporeal blood purification
The purpose of the research is to evaluate plasmapheresis in combination therapy for canine babesiosis and to assess its efficacy. Materials and methods. The efficacy of babesiosis treatment in spontaneously infected dogs was determined. Dogs with babesiosis were treated with imidocarb dipropionate, and plasmapheresis, an extracorporeal blood purification method, was used in addition to common symptomatic therapy. Results and discussion. It was established that plasmapheresis in combination therapy for canine babesiosis is an effective, minimally invasive, and non-traumatic procedure that accelerates recovery and restoration of the body and improves kidney, liver, and cardiovascular function. The recovery rate with this therapy is 2-3 times higher than the standard approach. The procedure is effective for multiple organ failure, chronic diseases, and for the prevention of complications associated with the past disease.
2026-05-01 | A50-06 A Case of Coinfection of Babesiosis and Lyme Disease in a Patient With No Risk Factors or Exposure
Abstract We present a case of a co-infection of babesiosis and Lyme disease. 89-year-old female with a medical history of hypertension, mitral valve prolapse, and cognitive impairment was admitted to the emergency department after a fall. Laboratory tests revealed markedly elevated creatine kinase (CK) levels at 3,217 U/L, thrombocytopenia with a platelet count of 125 x 10^9/L, elevated liver enzymes (AST 134 U/L and ALT 114 U/L), and significantly high total bilirubin at 134 µmol/L. Imaging, including CT scans of the head, cervical spine, abdomen, and pelvis, showed no acute structural abnormalities. A peripheral blood smear identified intra-erythrocytic rings, suggesting babesiosis. The initial parasitemia was 12%, and the patient was started on Azithromycin and Atovaquone with a decrease in parasitemia to 6.6%. After 48 hours of treatment, a rebound increase in parasitemia to 10%, worsening anemia, and pulmonary edema were noted prompting exchange transfusion. Serological tests for Lyme disease were positive, while Anaplasma, Ehrlichia, and Rickettsia serologies were negative. Treatment for Lyme disease was initiated with doxycycline. Her hospital course was complicated with acute hypoxic respiratory failure due to pneumonia and acute kidney injury (AKI) which was further exacerbated by acute diastolic heart failure. Following improvement in liver function tests, thrombocytopenia, and anemia, she was discharged to a subacute rehabilitation facility with a 14-day course of antibiotics per Infectious disease recommendations. Outpatient follow-up was arranged to monitor her recovery and manage her ongoing health issues. The diagnosis of babesiosis can be challenging due to its symptom overlap with other febrile illnesses and the variability in clinical presentation. In our case, the patient presented with a fall, and her review of systems was limited in the setting of cognitive impairment. High suspicion in endemic areas with the detection of intra-erythrocytic rings on a peripheral blood smear remains key for diagnosis. There is a strong correlation between the degree of parasitemia and morbidity with previous studies reporting severe outcomes and complications if parasitemia is between 4 and 10%. Red cell exchange transfusion (RCE) has been shown to reduce parasite burden with some studies questioning its superiority over microbiological treatment. In our case, there was a transient reduction in parasitemia with a rebound increase and worsening clinical status necessitating RCE. This case underscores the diagnostic and therapeutic challenges posed by the co-infection of babesiosis and Lyme disease, particularly in elderly patients with multiple comorbidities. This abstract is funded by: SELF
2026-03-30 | Red Blood Cell Exchange Transfusion for Severe Babesiosis.
Babesiosis is a worldwide emerging tick-borne disease with an expanding geographic range in the US, Europe, and Asia. Red blood cell exchange transfusion (ET) is often used as an adjunctive treatment for severe illness from babesiosis, particularly in patients with high parasitemia, acute organ injury, or severe hemolytic anemia. Data supporting its clinical effectiveness, however, are lacking. To test whether ET improves clinical outcomes among hospitalized adult patients with severe babesiosis. This target trial emulation used data from a multicenter cohort study of 3233 consecutive adults hospitalized with babesiosis from 2010 to 2024 at 82 sites across the northeastern US. Patients were eligible if they had parasitemia greater than 10%, or 5% to 10% with either acute organ injury or severe hemolytic anemia. Data were analyzed from April to August 2025. Treatment with ET in the first 7 days of hospitalization. A composite of in-hospital death or 30-day readmission. Outcomes were compared between patients who received ET within the first 7 days of admission and those who did not. The analysis used logistic regression, with inverse probability of treatment weighting (IPTW) to adjust for potential confounders. The analysis included 629 patients (median [IQR] age, 71 [63-79] years; 446 male [70.9%]), among whom 209 (33.2%) received ET in the first 7 days of hospitalization. Patients treated with ET were more severely ill at baseline than those not treated with ET (median parasitemia, 14.0% vs 7.2%); however, severity of illness characteristics were well balanced after applying IPTW. In the main analysis, the primary end point occurred in 3.6% of patients who received ET and in 9.8% who did not (adjusted odds ratio, 0.22; 95% CI, 0.09-0.51). The benefit of ET was confirmed in multiple sensitivity analyses. This multicenter cohort study found that among severely ill adults hospitalized with babesiosis, the adjusted risk of in-hospital death or 30-day readmission was nearly 5-fold lower in those treated with ET vs those not treated with ET. These data support ET for severely ill patients with babesiosis, although the findings may be susceptible to unmeasured confounding. Further research is needed to identify which patients are most likely to benefit.
2026-03-01 | 413: AFEBRILE BUT INFECTED: SEVERE BABESIOSIS REQUIRING EXCHANGE TRANSFUSION IN AN ELDERLY PATIENT
Introduction: Babesiosis is a tickborne illness endemic to the Northeastern United States with testing often performed on locals with fever, anemia, thrombocytopenia, and transaminitis. Babesia may be overlooked without known exposure or typical clinical features. Prognosis ranges from asymptomatic to death with increased risk of severe disease with age >50. There is limited data supporting red blood cell (RBC) exchange transfusion in babesiosis and the effect on time to parasite clearance is not well defined. Description: An 84-year-old immunocompetent female presented to a Massachusetts emergency department with several days of subjective fevers, malaise, anorexia, dyspnea, and encephalopathy. She had relocated from Florida 6 weeks prior. She was afebrile and mildly hypoxic with acute severe anemia, thrombocytopenia, transaminitis, and hyperbilirubinemia, and was admitted for heart failure exacerbation. Within 2 days of hospitalization, anemia worsened requiring multiple RBC transfusions, and workup was consistent with hemolytic anemia. Given peripheral smear with rare schistocytes, new acute kidney injury, and encephalopathy, thrombotic thrombocytopenic purpura (TTP) was suspected. Over the next 24 hours, she was transferred to the ICU for undifferentiated shock requiring pressors and completed plasma exchange (TPE) for presumed TTP pending further testing. Within 12 hours of TPE, peripheral smear revealed 10-15% intraerythrocytic parasites consistent with babesiosis (later confirmed with babesia PCR). Despite severe illness, she remained afebrile. Treatment with atovaquone, azithromycin, and RBC exchange was immediately initiated with post-procedure parasitemia of 2.9%. On further investigation, the patient had been exposed to dogs that frequented wooded areas on Long Island prior to hospitalization. Time to parasite clearance was 3 days with significant clinical improvement before discharge. Discussion: Babesiosis can cause life-threatening illness that mimics TTP in the absence of acute fever in geriatric patients. Workup for babesiosis should not be delayed in afebrile patients with hemolytic anemia, thrombocytopenia, transaminitis, and any travel to endemic areas despite lack of confirmed tick exposure. In cases with high-grade parasitemia and shock, exchange transfusion should be considered.
2025-10-07 | Severe Babesiosis in an Asplenic Patient Treated with Red Cell Exchange: Highlighting the Critical Need for Evidence-Based Guidelines – A Case Report and Literature Review
Background: This report details a rare case of fulminant babesiosis in a splenectomized patient, emphasizing key diagnostic and therapeutic dilemmas. Babesiosis is a globally emerging tick-borne disease caused by the protozoan Babesia, posing a significant public health burden with mortality reportedly greater than 20% in immunocompromised individuals and those with transfusion-acquired infections. Splenectomized individuals are especially vulnerable to life-threatening Babesia infections, often manifesting as a more hazardous course requiring aggressive treatment. Case Presentation: A 62-year-old pre-diabetic male with a history of traumatic total splenectomy presented with three days of high-grade fever, chills, bodyache, weakness, and near-syncopal episodes. Laboratory evaluations indicated anemia, haptoglobinemia, thrombocytopenia, leukocytosis, elevated creatinine and blood urea nitrogen, hepatic transaminitis, hyperbilirubinemia, and hypoalbuminemia. A peripheral blood smear confirmed the diagnosis, revealing extra- and intra-corpuscular Babesia microti with prominent vacuoles and ring forms, with a high parasitemia level of 17.6%. The patient was diagnosed with severe babesiosis complicated by multi-organ failure - including acute kidney injury and liver failure. Antiparasitic therapy with atovaquone and azithromycin was instituted. Additionally, the patient required multiple red blood cell exchange (RCE) transfusions with 12 units of packed red blood cells (PRBCs), to reduce the parasitemia down to a safer level (4%) leading to gradual clinical stabilization over the next few days. Discussion: This case emphasizes the importance of high clinical suspicion and prompt diagnosis of babesiosis in susceptible patient groups, such as asplenic patients, presenting with unexplained fever, especially with hemolytic anemia or multi-organ dysfunction. Diagnosis relies on blood smear microscopy or polymerase chain reaction (PCR) test. Standard treatment combines atovaquone and azithromycin, or clindamycin and quinine. Exchange transfusion is typically recommended for severe babesiosis, especially for parasitemia exceeding 10% or organ dysfunction, to reduce parasite burden and clear out harmful toxins. While high parasitemia strongly correlates with disease severity, the definitive clinical benefit of RCE, particularly when compared to antibiotic therapy alone, is a topic of ongoing debate in the literature. The optimal administration and precise indications for RCE are not well studied, with current guidelines based on weak evidence and vaguely-defined criteria. RCE predisposes to potentially serious complications including transient hypotension, dyselectrolytemia, transfusion reactions, transfusion-related infections, fluid overload, and acute respiratory distress syndrome (ARDS). As babesiosis cases continue to rise in endemic regions of the US, targeted research is urgently needed to determine definitive effectiveness of RCE and to develop clear, evidence-based guidelines for its use in severe cases, ensuring safe patient outcomes.
small molecules
2026-09-26 | RMF-Activated Superparamagnetic Iron Oxide Nanoparticles Trigger Macrophage-Dependent Protection Against Babesia microti Infection.
Babesiosis is an emerging tick-borne zoonosis hampered by drug-resistant Babesia parasites and the absence of vaccines. Rotating magnetic field-activated superparamagnetic iron oxide nanoparticles (RMF-SPIONs) exert anti-tumor and antibacterial effects, yet their efficacy against intraerythrocytic protozoa, including Babesia microti, is unclear. We established murine B. microti and Plasmodium yoelii infection models, using immunodeficient mouse strains and immune cell depletion approaches to dissect the antiparasitic mechanism, alongside cytokine detection, long-term physiological observation and parasite rechallenge assays. RMF-SPION therapy markedly inhibited B. microti proliferation but showed no efficacy against P. yoelii. Macrophages served as the key effector cells through IL-12 secretion, while NK cells likely played auxiliary regulatory roles in this system. Convalescent mice developed strain-specific premunition, though latent infection induced chronic inflammation and visceral lesions. In conclusion, RMF-SPIONs selectively activate macrophages to eliminate B. microti. Combining natural premunition with macrophage-targeted activation likely provides a non-chemical strategy against drug-resistant babesiosis.
2026-09-26 | Molecular Detection of Tick-Borne Parasitic Pathogens in Ticks Collected from Animal Hosts in Chuy Province, Kyrgyzstan.
Tick-borne parasitic diseases pose important threats to veterinary and public health, particularly in countries with livestock-dependent economies such as Kyrgyzstan. However, molecular epidemiological data on tick-borne pathogens in Kyrgyzstan is limited. This study investigated the prevalence, genetic diversity, and host-tick-pathogen associations in Chuy Province, Kyrgyzstan. A total of 494 ticks belonging to 6 genera and 10 species were collected from various animal hosts in eight survey areas in central-northern Chuy Province and analyzed using polymerase chain reaction, Sanger sequencing, and phylogenetic analysis. Of the 494 ticks, 35 (7.1%) were infected, including 15 (3.0%) with Babesia species and 20 (4.0%) with Theileria species. The highest positive rates were observed in Rhipicephalus annulatus (13.8%) and Haemaphysalis punctata (12.4%). Molecular analysis identified 4 Babesia species (B. caballi, B. major, B. bigemina, B. occultans) and 2 Theileria species (T. orientalis, T. ovis). Ticks collected from horses had the highest infection rates and greatest diversity of pathogens. T. orientalis was the most common pathogen. T. ovis was exclusively found in ticks collected from sheep. Phylogenetic analysis confirmed that the isolates were closely related to strains circulating in neighboring Central Asian and Eurasian countries. The findings provide foundational data for developing region-specific vector control measures.
2026-09-26 | Multilocus Characterization Reveals Two Geographically Structured Babesia Lineages in Sheep from Southern and Southeastern Kazakhstan.
In Kazakhstan, despite the diversity of ixodid ticks and extensive livestock movement throughout Central Asia, ovine Babesia infections are poorly characterized. The objective of this study was to determine the occurrence, genetic diversity and geographic distribution of Babesia spp. in sheep from southern and southeastern Kazakhstan. A total of 1458 blood samples from 51 settlements across five regions were screened by nested PCR targeting mitochondrial cytb. Positive samples were characterized by Sanger sequencing, with additional multilocus analysis based on 18S rRNA and mitochondrial cox1 sequences. Babesia DNA was detected in 75/1458 samples (5.1%), with variation in PCR positivity among regions. Positive samples occurred in Turkestan (3.6%), Jambyl (7.2%), and Almaty (21.2%), but not in Kyzylorda or Jetisu. Phylogenetic analyses identified two geographically structured lineages. Nine Turkestan samples formed a lineage related to the Babesia sp. Xinjiang/Dunhuang group and were provisionally designated Babesia sp. TRK. The remaining 66 samples formed a B. motasi lineage comprising five cytb genotypes and showing closer affinity to the Lintan/Tianzhu group than to the Hebei/Ningxian group. Despite high 18S rRNA identity with B. motasi, mitochondrial markers revealed substantial divergence. The findings of the current study expand understanding of ovine Babesia diversity in Central Asia and emphasize the need for genomic characterization to resolve the taxonomic status of the detected lineages.
2026-09-26 | Identification of Small-Molecule Inhibitors of Babesia bovis by High-Throughput SYBR Green I Screening.
Background: Bovine babesiosis, caused by Babesia bovis, remains a major constraint to cattle production in endemic regions, while the current control relies on only a few drugs with concerns over resistance and residues. Methods: This study screened 9600 chemically diverse compounds from the Drug Discovery Initiative, University of Tokyo, against B. bovis using a 96-well SYBR Green I high-throughput assay at 1 µM. Primary hits were subjected to dose-response testing to determine IC50 values, followed by Madin-Darby bovine kidney cell cytotoxicity assays for selectivity index calculation. Combination effects with diminazene aceturate were assessed using combination indices, whereby three compounds were selected for in silico ADME, drug-likeness and target prediction analyses. DDI-1101229 was further assessed by exploratory docking against BbHT1 and BbCDPK4. Results and Conclusions: Eight compounds showed ≥50% inhibition in the primary screen. DDI-1101229, DDI-8231037 and DDI-15106103 showed sub-micromolar activity (IC50 = 0.27-0.68 µM), selectivity indices > 14.7 and strong synergy with diminazene aceturate (CI < 0.4). Overall, this study identified selective, chemically diverse non-diamidine and non-imidazoline small-molecule inhibitors of B. bovis, highlighting alternative chemotypes with antibabesial activity.
2026-09-21 | Epizootic monitoring and testing of etiotropic pathogenetic therapy for bovine babesiosis in the Caspian region of the Russian Federation
The purpose of the research is to conduct an epizootic analysis of the spread of babesiosis in cattle in the Caspian region of the Republic of Dagestan, to study the seasonal dynamics of tick parasitism, which are vectors of the disease, and to identify methods and means for etiotropic and pathogenetic therapy. Materials and methods. The study was conducted from April to October 2025 at the farms of the Chokh Agricultural Company in the Gunib District. A comparative efficacy study was conducted under production conditions in 100 cattle of different age groups and breeds with varying disease severity, using spontaneous babesiosis. Animals in the first control group (n = 50) were given 5% DAC based on diminazene diaceturate at a dose of 2.5 mg/kg of body weight. Animals in the second experimental group were given 5% neosidin based on diminazene diaceturate and phenazone at a dose of 2.5 mg/kg by active substanse in combination with doxycycline 200 at a dose of 1 ml/10 kg of body weight. Symptomatic and pathogenetic agents were used as indicated. In the region, the disease is recorded in April-May, primarily in the lowland zone of the republic. The epizootic situation of bovine babesiosis was determined on three farms in the Gunibsky District; 900 animals were examined. Results and discussion. Based on blood tests, babesiosis was diagnosed in 201 (22.3%) cattle. The highest percentage of animals infected with babesiosis was found in dairy farm No. 2 – Tugay, with 81 heads (27.0%), dairy farm No. 1 – Altav, with 57 heads (19.0%), and the lowest was found in dairy farm No. 3 – Ullubiyevka, with 63 heads (21.0%). Three species of ticks were found to infect cattle: Boophilus annulatus (Curtice, 1891) (49.28%), Rhipicephalus bursa (Canestrini and Fanzago, 1878) (8.51%), and Ixodes ricinus (0.35%). For etiotropic therapy, diminazene diaceturate-based medications (DAC 5% and Neosidin-M 5%) were used in combination with symptomatic and pathogenetic agents based on clinical signs. Efficacy rates were 92.0% and 98.0%, respectively.
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2026-05-21 | Immunity beyond borders: non-lethal Plasmodium confers cross-protection against lethal Babesia via macrophage activation.
In co-endemic regions, hosts are concurrently infected by related apicomplexan hemoparasites, Plasmodium and the zoonotic pathogen Babesia. This study investigates how Plasmodium berghei XAT-Babesia rodhaini co-infection modulates host immunity, dissecting the contributions of innate and adaptive immune cells. Disease progression was assessed by survival, parasitemia, body weight, and hematological parameters. Splenic histopathology and qPCR were used to evaluate tissue damage and parasite burden. Immune responses were analyzed by cytokine, antibody measurement, and flow cytometry. Adaptive immunity was examined using SCID mice, and the roles of innate effectors were determined through selective depletion of NK cells and macrophages. P. berghei XAT infection elicited robust, heterologous protection significantly reducing parasitemia and splenic damage. This was linked with potent pro-inflammatory cytokines (IFN-γ, IL-12p70, and TNF-α), balanced by increased IL-10 levels, alongside increased ROS/NO production. While co-infected SCID mice, and NK depletion retained protection, macrophage depletion eliminated cross-protection and altered microbicidal cytokine and ROS/NO profiles. Flow cytometry confirmed expansion of the splenic macrophages in protected mice. These findings demonstrate that cross-protection is mediated by a macrophage-driven innate response. Protection was associated with IFN-γ-driven pro-inflammatory responses and ROS/NO production, balanced by IL-10 to limit immunopathology. This "protective homeostasis" highlights macrophage-targeted immunomodulation as a promising strategy for multivalent vaccines against apicomplexan parasites. Future research is warranted to elucidate macrophage activation and polarization dynamics underlying this protection.
2026-04-30 | Molecular characterization and functional analysis of thioredoxin peroxidase-2 from Babesia duncani.
Human babesiosis caused by Babesia duncani is an emerging zoonotic disease that poses a growing threat to public health. Since the first reported case in 1991, knowledge of this pathogen has remained limited. Recent completion of the B. duncani genome sequence has accelerated research aimed at elucidating its molecular biology. During its intraerythrocytic life cycle, B. duncani is exposed to oxidative stress generated by redox reactions. In this study, we identified and characterized an antioxidant enzyme from B. duncani-thioredoxin peroxidase-2 (BdTPx-2), a member of the peroxiredoxin family. BdTPx-2 gene was amplified from both cDNA and gDNA of B. duncani, revealing an open reading frame of 792 bp with no introns. The native form, cellular localization, and immunogenicity of BdTPx-2 were determined using polyclonal antibodies raised against recombinant BdTPx-2 (rBdTPx-2) and sera from B. duncani-infected mice. Antioxidant activity was assessed using a mixed-function oxidation (MFO) assay. BdTPx-2 was recognized by sera from mice infected with B. duncani or B. microti, dogs infected with B. gibsoni, and water buffalo infected with B. orientalis, indicating that TPx-2 is conserved and exhibits cross-reactivity among Babesia species. A native protein of approximately 35 kDa was specifically detected in B. duncani lysates. The MFO assay demonstrated that BdTPx-2 inhibits the oxidation of plasmid DNA by a DTT/FeCl₃ mixture, preventing its conversion from the supercoiled to the nicked form. In BALB/c mice immunized with rBdTPx-2 and subsequently challenged with Babesia, parasite burden was significantly reduced, accompanied by elevated levels of the proinflammatory cytokine IFN-γ, suggesting a protective immune response induced by rBdTPx-2. This work characterizes TPx-2 as an antioxidant enzyme in B. duncani and provides insights into a key mechanism by which the parasite defends against oxidative stress during its intraerythrocytic stage.
2025-07-10 | Rhipicephalus microplus voraxin-alpha contains B-cell epitopes that reduce ticks' biological fitness in immunized cattle.
Rhipicephalus microplus ticks are a serious pest of cattle in tropical and subtropical regions, mainly due to the losses they cause by reducing meat and milk production, as well as causing hide damage, in addition to their role as vectors of babesiosis and anaplasmosis. Integrated tick control must include the use of anti-tick vaccines to reduce tick populations and mitigate the ecological impact associated with the extensive use of acaricides. To develop improved vaccines, evaluation of new tick antigens is essential. Voraxin, mainly described as a testes-derived protein, is transferred from males to females during copulation, and it is crucial for stimulating engorgement in female ticks and for the development of their organs. In this study, R. microplus voraxin-alpha (voraxin-α) was amplified and sequenced, four peptides with predicted B-cell epitopes were designed and their immunogenic properties were evaluated. Each peptide was mixed with a commercial adjuvant and inoculated into two cattle from a tick-free region to corroborate if they were truly immunogenic. The antibody responses to each peptide were assessed using indirect ELISA. Two peptides were immunogenic and were selected for further testing involving immunization and experimental infestation with 10,000 larvae and two cattle per evaluated peptide. Immunization with peptide 3 reduced tick survival in 17 %, oviposition in 14 % and egg hatching in 22 %, while peptide 4 impaired oviposition in 18 % and egg hatching in 18 %. No effect on weight was observed. In conclusion, ticks fed on cattle producing specific antibodies against voraxin-α B-cell epitopes, have a reduced survival, oviposition and fertility, which are important biological parameters, related to tick fitness. Vaccine trials are required to evaluate this antigen as a vaccine candidate against R. microplus.
2025-04-28 | ves1α genes expression is the major determinant of Babesia bovis-infected erythrocytes cytoadhesion to endothelial cells.
Babesia bovis causes the most pathogenic form of babesiosis in cattle, resulting in high mortality in naive adults. This parasite invades red blood cells (RBCs) within the bovine hosts where they multiply and produce clinical disease. Babesia bovis exports numerous proteins into invaded RBCs changing its properties. Thus, the infected RBCs (iRBCs) are capable to cytoadhere in the microvasculature of internal organs and brain, leading to respiratory distress, neurologic signs, and mortality. Variant Erythrocyte Surface Antigen 1 (VESA1) is one of those exported proteins by B. bovis which represents a major virulence factor due to its central role in immune evasion by antigenic variation and intravascular parasite sequestration. VESA1 is a heterodimer protein encoded by ves1α and ves1β multigene family and localized on the ridges, the focal point for cytoadhesion. To gain further insights into the molecular mechanisms of cytoadhesion of B. bovis, we panned the parasites with bovine brain microvasculature endothelial cells, which resulted in obtaining several clones with different cytoadherence abilities. The transcriptome analysis of 2 high and 2 low cytoadherent clones revealed that ves1α sequences were diversified, likely resulting from genomic recombination. On the other hand, ves1β sequences were almost identical among these 4 clones. Insertion and expression of ves1α of a clone with high binding into ef-1α locus of a low binding clone increased cytoadherence confirming the role of ves1α suggested by our transcriptome data. Whole genome sequencing of cytoadherent clones revealed active locus of ves1 on chromosome 2. These results suggest that VESA1a proteins encoded by ves1α genes determine the cytoadherence strength of B. bovis and they are in the active site for recombination.
2025-03-06 | Molecular identification of a thioredoxin peroxidase in Babesia gibsoni with potential against oxidative stress.
Babesia gibsoni is the infectious agent of canine babesiosis, a vector-borne infection that poses a global threat to the canine health. As B. gibsoni is an erythrocytic intracellular parasite, the completion of its genome and transcriptome sequencing and analysis facilitates the elucidation of the mechanism of B. gibsoni residue in the erythrocyte. The main function of red blood cells (RBCs) is oxygen delivery; thus, B. gibsoni may be exposed to high levels of oxidative stress. To date, no report is available on the mechanism by which B. gibsoni survives oxidative stress inside the RBCs. In this study, the thioredoxin peroxidase, an important type of peroxidoxin, was identified from B. gibsoni, with 255 amino acids and a molecular weight of 27.7 kDa. There are two conserved "VCP" domains at the N- and C-termini, respectively, indicating that this gene was a 2-Cys peroxiredoxin belonging to the PTZ00137 superfamily. It was named BgTPx-2 and was detected to be located in the B. gibsoni-infected erythrocytes through an indirect immunofluorescence assay using the polyclonal antibody against the recombinant TPx-2. Additionally, its antioxidant activity was analyzed by mixed-function oxidation assay, and BgTPx-2 could protect the pBluescript SK ( +) plasmid from oxidative damage, suggesting an antioxidant function of BgTPx-2. Moreover, the immunogenicity of BgTPx-2 was tested by Western blotting and ELISA using the serum of beagle dogs infected with B. gibsoni, and the positive serum exhibited a detectable and significant antibody response against BgTPx-2 on day 4 and day 9 post-infection, respectively.
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2026-08-26 | Genetic characterization of natural resistance to ticks and babesiosis in cattle: Implications for safer food production
Background: Tick-borne hemoparasitic diseases remain a major limiting factor affecting livestock productivity. They affect animal health, productivity, and the safety of animal-derived products. Excessive use of antiparasitic agents may result in the accumulation of drug residues in animal-derived products, which may compromise food safety. Therefore, discovering genetic basis of the natural resistance in livestock is an important area of agricultural biotechnology. Objective: The aim of this study was to identify genetic structures associated with natural resistance to ticks in cattle and to evaluate their potential application in marker-assisted selection for breeding disease-resistant cattle. Methods: The informativeness of selected SSR markers was assessed using PIC, RP, EMR, and MI indices. QTL mapping and population genetic analyses were performed to identify genetic structures associated with resistance. Results: The selected SSR markers exhibited moderate-to-high polymorphism and high informativeness. TGLA53, SPS115, and ILSTS006 were identified as the most informative markers. QTL mapping identified three genetic structures associated with resistance, of which the most prominent was characterized by multilocus control, high allelic diversity, and a high level of heterozygosity. Conclusion: The results obtained show that the use of multilocus genetic structures of resistance in marker selection may support the development of cattle populations with greater resistance to tick-borne diseases and potentially reduce reliance on chemical interventions, thereby contributing to safer and more sustainable animal-derived food production. Novelty of the Study: This study is distinguished by the integrated application of SSR marker informativeness analysis, QTL mapping, and population genetic analysis to evaluate natural genetic resistance to ticks and bovine babesiosis. The findings provide a scientific basis for marker-assisted breeding strategies aimed at improving livestock health and supporting the sustainable production of safe animal-derived foods. Keywords: bovine babesiosis, tick resistance, quantitative trait loci, SSR markers, marker-assisted selection, food safety.
2026-08-07 | Disruption of the CD47-SIRPα Axis Causes Profound Reduction of Parasitaemia in Mice Infected With Babesia microti.
Human babesiosis is an emerging disease in North America caused by the red blood cell (RBC)-infecting parasite Babesia microti. Despite a rise in clinical cases in recent years, the pathogenesis and host immune response to B. microti infection remain unclear. CD47 is a 'marker of self' transmembrane glycoprotein expressed on cell membranes that inhibits phagocytosis through interactions with macrophage signal-regulatory protein alpha (SIRPα). We posit that disruption of CD47-SIRPα signalling will induce macrophage uptake of Babesia-infected RBCs and reduce parasitaemia in susceptible hosts. To evaluate this, we compared the in vivo clearance of B. microti in CD47 knockout (CD47-/-) mice and wild-type C57BL/6J mice. Our results showed pronounced differences in infection kinetics between the two mouse strains. C57BL/6J mice showed steadily increasing parasitaemia that peaked at an average of 12%, whereas CD47-/- mice exhibited parasitaemia that never exceeded 1.5% throughout infection. Parasitaemia became undetectable by Day 21 in C57BL/6J and by Day 16 in CD47-/- mice, indicating resolution of infection. These results imply that, in the absence of CD47, growth of B. microti is diminished due to more efficient phagocytosis of infected RBCs by macrophages. We propose that CD47-SIRPα signalling plays a key role in the innate response to Babesia and suggest CD47 modulation as a new therapeutic target for the treatment of babesiosis.
2026-06-24 | Liver histopathology in dogs with naturally acquired Babesia rossi infection.
In sub-Saharan Africa, canine babesiosis, the most significant tick-borne disease in dogs, is primarily caused by the highly virulent intra-erythrocytic protozoan Babesia rossi, transmitted by ixodid ticks. The disease presents in two forms: uncomplicated and complicated. The former is characterized by hemolysis, while the latter involves severe systemic inflammation and multiple organ dysfunction, leading to high morbidity and mortality. Building on recent evidence of severe immunoinflammatory disruption in the spleen, lung, and bone marrow, this study examines liver histopathology in fatal Babesia rossi infection to determine whether the frequent hyperbilirubinemia and icterus of complicated babesiosis reflect primary hepatic injury or secondary systemic effects. Liver samples from 10 dogs that succumbed to Babesia rossi infection were compared with samples from four healthy control dogs. Significant hematological changes included reduced red cell count, hematocrit, and platelet concentration, while biochemical alterations showed increased serum ALT and urea. Key histopathological findings in the livers of Babesia-infected dogs showed severe diffuse dilation of the spaces of Disse, cholestasis, and hypertrophy of Kupffer cells containing bile and hemosiderin pigments. Additional findings included erythropoiesis, congestion, and widespread mononuclear inflammation, predominantly involving monocytes and macrophages with fewer lymphocytes and plasma cells, present in both intravascular and interstitial areas. Centrilobular hepatocytes exhibited coagulative necrosis or prominent hydropic vacuolation, likely attributable to severe hemolysis and resulting hypoxia, similar to findings reported in human malaria and sepsis. These observations improve understanding of the pathomechanisms underlying fatal babesiosis in dogs, particularly its effects on the liver, and may help refine targeted treatment strategies.
2026-03-30 | Thromboinflammation in dogs with virulent babesiosis.
Babesia rossi infection in dogs is associated with severe hemostatic dysregulation and systemic inflammation. The close interplay between innate immunity and coagulation in pathological states, including acute infections, may lead to thrombus formation, termed thromboinflammation, and has been proposed to underlie disease severity and poor outcomes. The objectives of this study were to investigate the presence of thromboinflammation in dogs with B. rossi infection by characterizing the overall hemostatic state, using thromboelastography (TEG) and plasma-based assays, and the systemic inflammatory response using acute phase reactants as markers, and further to determine whether, if present, thromboinflammation was associated with disease severity. Ninety-seven dogs naturally infected with B. rossi and 15 healthy control dogs were included. Diagnosis of babesiosis was confirmed by reverse line blot polymerase chain reaction. Blood samples were collected at presentation, prior to any treatment. Hemostatic function was assessed using TEG, routine coagulation assays, coagulation factor activity, and fibrinolysis markers. C-reactive protein (CRP) and serum amyloid A (SAA) were measured as markers of systemic inflammation. Twelve of the Babesia-infected dogs died (12%). Babesia-infected dogs demonstrated hemostatic abnormalities marked by severe thrombocytopenia and a procoagulant state, including platelet activation, preserved clot strength, and elevated fibrinogen concentrations. Thromboelastography further revealed delayed clot initiation and propagation with maintained clot firmness, whereas conventional assays showed prolonged prothrombin time and activated partial thromboplastin time, along with markedly reduced coagulation factor activities in non-survivors. Minimal fibrinolysis was observed on TEG and was associated with elevated α2-antiplasmin activity and the presence of fibrin microthrombi in multiple organs. Markedly elevated CRP and SAA concentrations confirmed the simultaneous presence of systemic inflammation. B. rossi infection in dogs induced thromboinflammation characterized by thrombocytopenia, platelet activation, coagulation factor consumption, fibrinolytic shutdown and systemic inflammation. Thromboinflammation may drive endothelial injury, microthrombosis, and an increased risk of organ failure and death. Future therapeutic interventions targeting thromboinflammation may improve patient outcomes.
2025-11-17 | Genetic diversity of BoLA-DRB3 and its association with Anaplasma marginale and Babesia spp. infections in creole cattle of northeastern Colombia.
The BoLA-DRB3 gene is one of the most polymorphic loci in cattle, with alleles associated with susceptibility or resistance to several infectious diseases, including leukosis, mastitis, and hemotropic infections. In this study, we assessed the genetic diversity of the BoLA-DRB3 gene in three Colombian Creole cattle breeds and examined its association with natural infections by Anaplasma marginale and Babesia spp. in northeastern Colombia. A total of 97 animals (Chino - CrChi, n = 34; Casanareño - CrCAS-, n = 32; Sanmartinero - CrSM-, n = 31) from Arauca, Casanare, Meta, and Santander departments were genotyped using PCR-direct sequencing of the second exon of the BoLA-DRB3 gene. Overall genetic diversity was moderate, with a nucleotide diversity of π = 0.086, a mean pairwise distance of 18.97, and 62 segregating sites. Among the breeds, CrCAS showed the highest diversity, followed by CrChi and CrSM. We identified 35 BoLA-DRB3 alleles, 34 of which were previously reported in the IPD-MHC database, while one was novel. The CrChi population showed significant deviation from Hardy-Weinberg equilibrium. Two alleles, BoLA-DRB3*001:01 and BoLA-DRB3*025:01:01, were significantly associated with reduced risk of B. bigemina infection in CrSM, whereas BoLA-DRB3*048:02 was linked to increased susceptibility to B. bovis in CrChi. This study confirms the high genetic variability of Colombian Creole cattle breeds. The high frequency of alleles associated with B. bigemina infection in CrSM highlights its potential as a genetic reservoir for future studies evaluating the heritability and functionality of these alleles. In contrast, the elevated frequency of a susceptibility-associated allele for B. bovis infection in CrChi, together with evidence of inbreeding, underscores the urgent need for targeted conservation and breeding strategies to preserve genetic diversity and reduce disease vulnerability to infectious diseases in this breed.
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Drug Discovery Landscape
1 orphan drug designation for Babesiosis.
1 orphan drug designation for Babesiosis.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Tafenoquine | small molecules | FDA | 60 Degrees Pharmaceuticals, Inc. |
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