Characterization of anti-erythrocyte and anti-platelet antibodies in hemolytic anemia and thrombocytopenia induced by Plasmodium spp. and Babesiaspp. infection in mice.

Introduction: Malaria and Babesiosis are acute zoonotic disease that caused by infection with the parasite in the phylum Apicomplexa. Severe anemia and thrombocytopenia are the most common hematological complication of malaria and babesiosis. However, the mechanisms involved have not been elucidated, and only a few researches focus on the possible role of anti-erythrocyte and anti-platelet antibodies. Methods: In this study, the Plasmodium yoelii, P. chabaudi, Babesia microti and B. rodhaini infected SCID and ICR mice. The parasitemia, survival rate, platelet count, anti-platelet antibodies, and the level of IFN-γ and interleukin (IL) -10 was tested after infection. Furthermore, the P. yoelii, P. chabaudi, B. rodhaini and B. microti infected ICR mice were treated with artesunate and diminaze, the development of the anti-erythrocyte and anti-platelet antibodies in chronic stage were examined. At last, the murine red blood cell and platelet membrane proteins probed with auto-antibodies induced by P. yoelii, P. chabaudi, B. rodhaini, and B. microti infection were characterized by proteomic analysis. Results and discussion: The high anti-platelet and anti-erythrocyte antibodies were detected in ICR mice after P. yoelii, P. chabaudi, B. rodhaini, and B. microti infection. Actin of murine erythrocyte and platelet is a common auto-antigen in Plasmodium and Babesia spp. infected mice. Our findings indicate that anti-erythrocyte and anti-platelet autoantibodies contribute to thrombocytopenia and anemia associated with Plasmodium spp. and Babesia spp. infection. This study will help to understand the mechanisms of malaria and babesiosis-related thrombocytopenia and hemolytic anemia.

Neurologic Complications of Babesiosis, United States, 2011-2021.

Babesiosis is a globally distributed parasitic infection caused by intraerythrocytic protozoa. The full spectrum of neurologic symptoms, the underlying neuropathophysiology, and neurologic risk factors are poorly understood. Our study sought to describe the type and frequency of neurologic complications of babesiosis in a group of hospitalized patients and assess risk factors that might predispose patients to neurologic complications. We reviewed medical records of adult patients who were admitted to Yale-New Haven Hospital, New Haven, Connecticut, USA, during January 2011-October 2021 with laboratory-confirmed babesiosis. More than half of the 163 patients experienced >1 neurologic symptoms during their hospital admissions. The most frequent symptoms were headache, confusion/delirium, and impaired consciousness. Neurologic symptoms were associated with high-grade parasitemia, renal failure, and history of diabetes mellitus. Clinicians working in endemic areas should recognize the range of symptoms associated with babesiosis, including neurologic.

Cardiac Complications of Human Babesiosis.

BACKGROUND: Human babesiosis is a worldwide emerging tick-borne disease caused by intraerythrocytic protozoa. Most patients experience mild to moderate illness, but life-threatening complications can occur. Although cardiac complications are common, the full spectrum of cardiac disease and the frequency, risk factors, and outcomes in patients experiencing cardiac complications are unclear. Accordingly, we carried out a record review of cardiac complications among patients with babesiosis admitted to Yale-New Haven Hospital over the last decade to better characterize cardiac complications of babesiosis. METHODS: We reviewed the medical records of all adult patients with babesiosis admitted to Yale-New Haven Hospital from January 2011 to October 2021, confirmed by identification of Babesia parasites on thin blood smear and/or by polymerase chain reaction. The presence of Lyme disease and other tick-borne disease coinfections were recorded. RESULTS: Of 163 enrolled patients, 32 (19.6%) had ≥1 cardiac complication during hospitalization. The most common cardiac complications were atrial fibrillation (9.4%), heart failure (8.6%), corrected QT interval prolongation (8.0%), and cardiac ischemia (6.8%). Neither cardiovascular disease risk factors nor preexisting cardiac conditions were significantly associated with the development of cardiac complications. The cardiac complication group had a greater prevalence of high-grade parasitemia (>10%) (P < .001), longer median length of both hospital (P < .001) and intensive care unit stay (P < .001), and a higher mortality rate (P = .02) than the group without cardiac complications. CONCLUSIONS: Cardiac complications of acute babesiosis are common and occurred in approximately one-fifth of this inpatient sample. Further investigation is needed to elucidate the relationship between babesiosis severity and cardiac outcomes.

Serum and urine profiling by high-throughput TMT-based proteomics for the investigation of renal dysfunction in canine babesiosis.

Canine babesiosis is a tick-borne disease caused by Babesia canis, with acute kidney injury as one of the common complications. In the study 8 healthy control dogs and 22 dogs with naturally occurring babesiosis were enrolled, with the aim to analyse differences in serum and urinary proteomes between healthy dogs and dogs with different degree of renal dysfunction in babesiosis using a label-based high-throughput quantitative proteomic approach. In serum, 58 proteins were found differentially abundant between healthy controls and groups of dogs with different degrees of renal dysfunction in babesiosis, while in urine there were 259 differentially abundant proteins. In addition, altered biological pathways were detected in the diseased dogs using bioinformatics tools and validation of several candidate biomarkers was performed. SIGNIFICANCE: The main aim of this comprehensive study was to perform analyses of serum and urinary proteomes of dogs with renal dysfunction in babesiosis compared to healthy dogs using, for the first time, a high-throughput proteomic method and functional enrichment analyses. Serum and urine samples of the same dogs were investigated in order to gain a more complete picture of pathologic changes taking place in renal dysfunction in babesiosis. We highlighted two putative biomarkers validated herein which could be of importance for early diagnosis of renal dysfunction in canine babesiosis, as they are easily accessible from urine and their concentration rises before the appearance of azotaemia: urinary neutrophil gelatinase-associated lipocalin (NGAL) and urinary liver-type fatty acid-binding protein (L-FABP).

[Role of systemic infections in canine kidney diseases]. / Rolle systemischer Infektionen bei Nierenerkrankungen des Hundes.

Kidney diseases represent a common problem as well as a frequent cause of death in dogs. Infectious agents may be responsible for glomerulopathies and acute kidney injuries. Many infections commonly associated with the development of immune complex glomerulonephritis in central and southern Europe are important as travel-associated diseases in Germany. These include leishmaniosis, dirofilariosis, and ehrlichiosis. Rarely, anaplasmosis, hepatozoonosis, Lyme disease as well as babesiosis caused by small Babesia spp. are detected as cause of canine immune complex glomerulonephritis in Germany. Leptospirosis, canine infectious hepatitis, and babesiosis caused by large Babesia spp. may be responsible for the development of acute kidney injuries associated with tubulointerstitial nephritis. Therefore, further diagnostics aiming at identifying potentially causative infectious agents in dogs with renal disease is important for both prognosis and therapy of the patient.

A typical babesiosis in an immunocompetent patient.

Babesiosis is a tick-borne infectious disease, caused by an intraerythrocytic parasite of the genus Babesia. It has clinical, biological and microbiological similarities with Plasmodium related infections. In rare cases, babesiosis may be complicated by hemophagocytic lymphohistiocytosis, which occurs preferentially in the immunodeficient patient. We report here the case of a non-immunocompromised patient living in Manhattan, New York hospitalized for a complicated babesiosis of a hemophagocytic lymphohistiocytosis. After 7 days of hospitalization and treatment by azithromycin 500 mg/day and atovaquone 750 mg twice a day, the patient was discharged with an improvement in clinical symptoms and biological parameters.

ULTRAMICROSCOPIC CHARACTERISTICS OF ERYTHROCYTES IN INDIVIDUALS WITH BORRELIOSIS, RHEUMATOID ARTHRITIS AND TOXOPLASMOSIS AS A MARKER, COMORBID OR CONCOMITANT PATHOLOGY FOR BABESIOSIS.

OBJECTIVE: The aim is to determine the ultramicroscopic characteristics of erythrocytes in individuals with rheumatoid arthritis, borreliosis or toxoplasmosis as a marker, comorbid or concomitant pathology for babesiosis. PATIENTS AND METHODS: Materials and methods: Blood samples from the patients with revealed borreliosis (Lyme disease) (19 cases), toxoplasmosis (15 cases), rheumatoid arthritis in the stage of exacerbation (10 cases) served as the study material (group 2). In all patients of group 2, positive results for babesiosis were obtained during the polymerase chain reaction. The group of comparative control (group 1) consisted of clinically healthy people (n=31), who underwent the blood cytological examination (light microscopy) preceding the scanning electron microscopy, followed by verification of the results by resources of molecular genetic research (polymerase chain reaction). Scanning electron microscopy was used in this study. RESULTS: Results: In patients with babesiosis and marker, comorbid and concomitant conditions for this disease (rheumatoid arthritis, borreliosis, toxoplasmosis) it was identified the specific diagnostic criteria for the presence of extraerythrocyte forms of babesia, constant number of erythrocytes and their regenerative forms, the appearance of degenerative forms of erythrocytes with their size and shape pathology. The latter lead to hemodynamic disorders, the development of ischemic and hypoxic changes in tissues of different organs of human body. CONCLUSION: Conclusions: Scanning electron microscopy of erythrocytes in patients with babesiosis and marker, comorbid and concomitant conditions for this disease (rheumatoid arthritis, borreliosis, toxoplasmosis) plays the role of an objective method of verifying the results of previous clinical and laboratory diagnosis. The use of scanning electron microscopy allow us to determine in these patients the specific diagnostic criteria for the presence of extraerythrocyte forms of babesia, constant number of erythrocytes and their regenerative forms, degenerative forms of erythrocytes with their size and shape pathology.

Babesiosis as a Cause of Atraumatic Splenic Injury: Two Case Reports and a Review of Literature.

We present two cases of Babesia-induced splenic injury at a single institution. In the late summer, two patients presented with left-sided abdominal pain radiating to the shoulder. They were both found to have hemolytic anemia, thrombocytopenia, and acute splenic infarction on imaging. Blood smears showed intracellular ring forms consistent with Babesia spp. and low parasitemia (<1%). Diagnosis was confirmed by PCR for Babesia microti. Both patients improved with azithromycin and atovaquone, without blood products or surgical intervention. Several weeks following treatment, repeat blood smears revealed no parasites. Splenic infarct and hemorrhage have been previously reported as rare complications of babesiosis. However, given the steady rise in Babesia microti cases in the USA, even these rare complications will become more prevalent. We review both the diagnosis and management of Babesia-induced splenic complications, which can be challenging in patients with low-level parasitemia. Clinicians should consider babesiosis as a cause of atraumatic splenic injury.

Babesiosis in the Emergency Department: A Case Report.

BACKGROUND: Babesiosis, a tick-borne illness spread by Ixodes scapularis, is an emerging infectious disease in the Northeastern and upper Midwestern United States. Infection can present as a flu-like illness with anemia, thrombocytopenia, and jaundice. This disease can even be fatal in the immunocompromised or highly infected patient. Co-infection with other tick-borne illnesses is common, and prompt treatment with antiprotozoal agents and antibiotics is indicated to prevent adverse outcomes. CASE REPORT: We describe a patient who presented to the emergency department with flu-like symptoms, but had history concerning for environmental exposure to babesiosis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Early detection is important to prevent severe sequalae of the disease. This is a disease that can imitate a viral syndrome but should be considered in the differential for a patient with a concerning history.

Systemic inflammatory response syndrome in dogs naturally infected with Babesia canis: Association with the parasite load and host factors.

The common signs of canine babesiosis caused by an infection with Babesia canis are fever, anorexia, lethargy, pulse alterations, anemia, and occasionally mild icterus. Dogs with these clinical signs can be divided into two groups: those with acute-phase reaction and those with systemic inflammatory response syndrome (SIRS). Factors associated with the occurrence of SIRS in canine babesiosis have not been thoroughly researched. This article outlines a cross-sectional study of 54 client-owned dogs with an acute B. canis infection, and evaluates the differences in age, gender, laboratory findings, parasite load, and seroreactivity against B. canis between the SIRS and the SIRS-free dogs. We have analyzed a complete blood count, serum biochemistry, serum amyloid A, ceruloplasmin, paraoxonase-1, serology, and PCR testing using standard methodologies. The frequency of SIRS among the investigated dogs reached 0.59. Male dogs and those seronegative against B. canis, were more frequent in the SIRS group, whilst age and parasite load could not be associated with the presence of SIRS. Dogs with SIRS had a lower count of total leukocytes, neutrophils, lymphocytes, and monocytes, and a lower concentration of iron and bilirubin compared with SIRS-free dogs. No significant differences in the concentration of acute-phase proteins have been noticed to exist between the groups of dogs. Further, the seronegative dogs had a lower count of lymphocytes and monocytes and a higher parasite load than the seroreactive dogs. Multivariate logistic regression analysis has identified leukopenia (<6 × 109/L) and monocytopenia (<0.2 × 109/L) as independent associates of SIRS in the investigated dogs, thus implying that these routine tests could be used as reliable markers for SIRS.

Babesia microti infection in a patient with multiple sclerosis treated with ocrelizumab.

Ocrelizumab is a humanized monoclonal anti-CD20 antibody approved for treatment of relapsing-remitting and primary progressive multiple sclerosis (MS). Rare parasitic infections have been reported in patients with lymphoproliferative disorders using rituximab, a chimeric anti-CD20 antibody used off-label for the treatment of MS. Here, we report a patient with MS on ocrelizumab with B-cell depletion who developed severe Babesia microti (B. microti) infection with neutropenia, hemolytic anemia, and thrombocytopenia. He recovered after prompt diagnosis and treatment. This case represents the first published occurrence of babesiosis in a patient with MS on ocrelizumab. It also adds to the accumulating evidence from databases of emergent severe or relapsing B. microti infection in patients receiving anti-CD20 antibodies. This presentation stresses the diagnostic vigilance required by MS neurologists in endemic areas to identify cases of babesiosis in patients on anti-CD20 therapy and to better counsel these individuals on their risks of B. microti infection.

Complications and risk factors regarding the outcomes of canine babesiosis in Central Europe - A retrospective analysis of 240 cases.

The purpose of this study was to investigate retrospectively the prevalence of the complicated and uncomplicated forms of babesiosis and to evaluate various laboratory and clinical parameters of dogs infected with Babesia canis in order to assess their prognostic value regarding the outcomes of the disease. Medical records, complete blood count and serum biochemical analysis from the animal hospital information system of 240 dogs were reviewed and evaluated retrospectively. Binary logistic regression analysis was used to ascertain correlations between alterations in the obtained parameters and survival probability. The results showed that creatinine levels of more than 5 mg/dL and phosphate levels of more than 3 mmol/L have a highly significant link to death (P ≤ 0.001). Albumin levels of <2.2 g/dL (P = 0.003) and a rectal body temperature below 38 °C (P ≤ 0.001) may also serve as prognostic markers for the severity of the disease. If renal involvement was present, 33.9% of the dogs died, while 40.0% of the dogs died in the presence of pancreatitis. The parameters creatinine, phosphate, albumin and rectal temperature serve as reliable predictive markers of an increased risk of death in the case of an infection with B. canis.