Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA): 2020 Guideline on Diagnosis and Management of Babesiosis.

The purpose of this guideline is to provide evidence-based guidance for the most effective strategies for the diagnosis and management of babesiosis. The diagnosis and treatment of co-infection with babesiosis and Lyme disease will be addressed in a separate Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR) guideline [1]. Recommendations for the diagnosis and treatment of human granulocytic anaplasmosis can be found in the recent rickettsial disease guideline developed by the Centers for Disease Control and Prevention [2]. The target audience for the babesiosis guideline includes primary care physicians and specialists caring for this condition, such as infectious diseases specialists, emergency physicians, intensivists, internists, pediatricians, hematologists, and transfusion medicine specialists.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA): 2020 Guideline on Diagnosis and Management of Babesiosis.

The purpose of this guideline is to provide evidence-based guidance for the most effective strategies for the diagnosis and management of babesiosis. The diagnosis and treatment of co-infection with babesiosis and Lyme disease will be addressed in a separate Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR) guideline [1]. Recommendations for the diagnosis and treatment of human granulocytic anaplasmosis can be found in the recent rickettsial disease guideline developed by the Centers for Disease Control and Prevention [2]. The target audience for the babesiosis guideline includes primary care physicians and specialists caring for this condition, such as infectious diseases specialists, emergency physicians, intensivists, internists, pediatricians, hematologists, and transfusion medicine specialists.

Parasite burden and red blood cell exchange transfusion for babesiosis.

BACKGROUND: The association between parasite burden and end-organ dysfunction in subjects with Babesia microti infection has not been extensively studied, nor has the optimal role of red blood cell exchange (RCE) transfusion in babesiosis treatment. This retrospective chart review evaluates the associations between parasitemia, end-organ dysfunction, and outcomes in babesiosis patients treated with antimicrobial agents and RCE compared to those treated with antimicrobial agents alone. MATERIALS AND METHODS: We evaluated adults (≥18 years of age) with laboratory-confirmed babesiosis who were admitted between 2011 and 2017 to Yale New Haven Hospital, located in a Babesia-endemic region of the Northeastern United States. Patient demographics, parasitemia levels, clinical and laboratory indicators of end-organ dysfunction, and outcomes were examined. RESULTS: Ninety-one subjects (mean age 65.1 years, 69.2% male) were studied. Subjects were stratified according to peak parasitemia: <1% (n = 34), 1-5% (n = 24), 5-10% (n = 15), and >10% (n = 18). Laboratory measures indicating degrees of hemolysis, coagulopathy, and pulmonary, renal and hepatic dysfunction differed significantly across peak parasitemia levels. Median length of hospital stay increased with each successive peak parasitemia level (P < .001). These results indicate a strong association between peak parasitemia level and disease severity. Nineteen subjects underwent RCE, all with peak parasitemia ≥9% and some degree of end-organ dysfunction. CONCLUSIONS: Babesia microti parasitemia is closely associated with disease severity, though not all subjects with end-organ dysfunction had high-grade parasitemia. Our data suggest that the use of parasitemia >10%, coupled with clinical status, is a reasonable indicator for RCE in babesiosis patients.

Human babesiosis: recent advances and future challenges.

PURPOSE OF REVIEW: As human babesiosis caused by apicomplexan parasites of the Babesia genus is associated with transfusion-transmitted illness and relapsing disease in immunosuppressed populations, it is important to report novel findings relating to parasite biology that may be responsible for such pathology. Blood screening tools recently licensed by the FDA are also described to allow understanding of their impact on keeping the blood supply well tolerated. RECENT FINDINGS: Reports of tick-borne cases within new geographical regions such as the Pacific Northwest of the USA, through Eastern Europe and into China are also on the rise. Novel features of the parasite lifecycle that underlie the basis of parasite persistence have recently been characterized. These merit consideration in deployment of both detection, treatment and mitigation tools such as pathogen inactivation technology. The impact of new blood donor screening tests in reducing transfusion transmitted babesiosis is discussed. SUMMARY: New Babesia species have been identified globally, suggesting that the epidemiology of this disease is rapidly changing, making it clear that human babesiosis is a serious public health concern that requires close monitoring and effective intervention measures. Unlike other erythrocytic parasites, Babesia exploits unconventional lifecycle strategies that permit host cycles of different lengths to ensure survival in hostile environments. With the licensure of new blood screening tests, incidence of transfusion transmission babesiosis has decreased.

Adjunctive treatment of clinically severe babesiosis with red blood cell exchange: a case series of nineteen patients.

BACKGROUND: Infection with the protozoan parasite Babesia, the causative agent of babesiosis, can result in asymptomatic to life-threatening illness. Severe cases of babesiosis are characterized by high levels of parasitemia (>4%-10%) and commonly treated with adjunctive red blood cell exchange (RCE) in addition to antimicrobial therapy. The efficacy of RCE in this context is unknown. STUDY DESIGN AND METHODS: Blood bank records were examined for requests for RCE during a 10-year period from 2007 to 2017. Relevant clinical and laboratory variables were extracted from medical records from presentation to 35 days after RCE and analyzed in univariate and multivariate models. RESULTS: Nineteen cases of babesiosis were identified in which RCE was performed. The median age of patients was 77 years, 74% of whom were male. A total of 37% of patients were asplenic. RCE was performed on average 1.3 days after presentation, with procedural urgency driven mainly by the level of parasitemia. Mean pre- and post-RCE levels of parasitemia were 12.9 and 3.4%, respectively, resulting in a mean percent reduction in parasitemia of 75%. Preprocedural parasitemia (p = 0.047) and age (p = 0.028) were both significant predictors of postprocedural hospital length of stay (post-RCE LOS). Neither postprocedural parasitemia (p = 0.12) nor percent reduction in parasitemia (p = 0.72) correlated with post-RCE LOS. Four patients died, none of whom were asplenic. Mortality was not correlated with hematologic, parasitologic, or clinical variables analyzed. CONCLUSIONS: Reduction in the level of parasitemia is the only known benefit of RCE in severe babesiosis.

Repeat exchange transfusion for treatment of severe babesiosis.

We report a case of severe babesiosis presenting with 43% parasitemia in a 73-year-old splenectomized woman on etanercept for rheumatoid arthritis. She initially was treated aggressively with clindamycin and quinine and exchange transfusion. Despite a post-exchange drop in parasitemia to 7.6%, it rebounded to 11.4% on hospital day 5 accompanied by new onset high fevers and hypoxia. She improved after a second exchange transfusion and ultimately resolved her infection after 12 weeks of antibabesial antibiotics. Although exchange transfusion is commonly used in immunocompromised hosts, there is a dearth of information about repeat exchange transfusion, including the risk for and outcome of repeat exchange. We performed a literature search for other cases of repeat exchange transfusion for severe Babesia microti infection and compared our case with those in other published reports.

Transfusion-transmitted babesiosis leading to severe hemolysis in two patients with sickle cell anemia.

The intracellular parasites Babesia microti and Babesia duncani can be transmitted by blood transfusion and cause severe life-threatening hemolytic anemia in high-risk patients, including those with sickle cell disease. The rarity of the diagnosis, as well as its similar clinical presentation to delayed hemolytic transfusion reaction, may lead to a delay in diagnosis, as well as inappropriate treatment with steroids or other immunosuppressive agents. The morbidity caused by this disease in especially vulnerable populations justifies the need for a universal blood-screening program in endemic areas.

The use of cytapheresis in the treatment of infectious diseases.

Cytapheresis (removal of cellular blood components) has been employed for treatment of infectious diseases since the 1960s. Techniques have included thrombocytapheresis (buffy coat apheresis) for loiasis, erythrocytapheresis for malaria and babesiosis, and leukocytapheresis for pertussis-associated lymphocytosis. Published data on these applications is largely limited to case level data and small observational studies; as such, recommendations for or against the use of cytapheresis in the treatment of infections have been extrapolated from these limited (and at times flawed) data sets. Consequently, utilization of cytapheresis in many instances is not uniform between institutions, and typically occurs at the discretion of treating medical teams. This review revisits the existing literature on the use of cytapheresis in the treatment of four infections (loasis, malaria, babesiosis, and pertussis) and examines the rationale underlying current treatment recommendations concerning its use.

Unusual Complications From Babesia Infection: Splenic Infarction and Splenic Rupture in Two Separate Patients.

BACKGROUND: Babesiosis is a zoonotic parasitic infection transmitted by the tick, Ixodes scapularis. Splenic infarct and rupture are infrequent complications of Babesia parasitemia, and have not been previously reported in the emergency medicine literature. CASE REPORT: We present two separate cases seen within 1 month at our institution: a case of splenic rupture and another case of splenic infarction due to Babesia parasitemia. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Babesia infection in humans is increasingly prevalent in both the United States and worldwide, and clinical manifestations can range from subclinical to fulminant infections. An unusual but potentially fatal complication of babesiosis is splenic infarctions and rupture. Due to the endemicity of this parasite, a careful history and level of suspicion will enable the emergency physician to consider and test for babesiosis in patients with splenic injuries and without obvious traditional risk factors.

Babesia parasitemia rebound after red blood cell exchange.

Babesiosis is an increasingly recognized disease which may benefit from therapeutic apheresis (Category II/Grade 2C). Vulnerable populations include the splenectomized, those aged >50, those with malignancies, and the immunocompromised. In the setting of parasite levels > 10%, significant anemia, renal impairment, pulmonary compromise, or hepatic dysfunction, RBC exchange can rapidly reduce parasite burdens and decrease the bioavailability of proinflammatory cytokines. No previous report has shown such a rapid rebound in parasitemia despite adequate organism removal. Herein, we report a case of severe babesiosis in a splenectomized 56 year old male with a past medical history significant for benign multiple sclerosis. Following a week of flu-like symptoms, the patient presented to an outside hospital with anemia, elevated bilirubin, thrombocytopenia, and 15% of his RBCs containing Babesia forms on a peripheral smear. Despite initiation of appropriate antimicrobials, subsequent transfer to our facility revealed worsening parasitemia (25%), tachypnea, and hypoxia. An emergent two volume RBC exchange was performed, resulting in 15% post-exchange parasitemia. Twelve hours later, the parasitic burden had climbed to 30%. A second RBC exchange reduced the parasite burden to 1.5%. His post-procedural course was significant for diminishing periodic increases in parasitemia despite continued antimicrobial therapy. Rapid increases in parasitic burden following RBC exchanges can occur and post-procedural surveillance of parasitemia should be closely monitored to expedite additional exchanges.

Severe Babesia microti infection in an American immunocompetent patient diagnosed in Spain.

We report a severe Babesia microti infection in an immunocompetent patient diagnosed in Spain. A 66-year-old woman coming from USA presented with fever, thrombocytopenia, and multiorgan failure. Intraerythrocytic parasites were observed in Giemsa-stained peripheral blood smears and B. microti was first suspected by optical microscopy and afterward confirmed by specific polymerase chain reaction (PCR). Patient received antibiotic therapy, vital support measures and one red blood cell (RBC) exchange procedure. After 15 days, patient recovered and she was transferred to her reference hospital. This case report highlights the importance of clinical suspicion by physicians in non-endemic areas to diagnose this entity, the differential diagnosis with malaria infection, and the indication of RBC exchange as a therapeutic apheresis modality in the management of severe forms.

Apheresis for babesiosis: Therapeutic parasite reduction or removal of harmful toxins or both?

Babesiosis is a potentially life-threatening illness caused by intraerythrocytic protozoan parasites of the genus Babesia that are transmitted most commonly by Ixodes ticks, and rarely from blood transfusion or congenitally. Clinical presentations of babesiosis include asymptomatic infection, mild to moderate disease, or severe disease. Antibiotics such as atovaquone plus azithromycin or clindamycin and quinine can be used effectively to treat this disease in most cases, however in high risk populations, the mortality rate can be as high as 20% despite therapy. Therapeutic exchange transfusion has been used in severe babesiosis and is of apparent therapeutic benefit. It is not entirely clear through what mechanism therapeutic exchange transfusion may help patients. Data suggests that in addition to parasite load reduction, it is possible that therapeutic exchange transfusion removes toxins generated by babesia infection. There are many remaining questions that need to be addressed regarding exchange transfusion for babesiosis. J. Clin. Apheresis 31:454-458, 2016. © 2015 Wiley Periodicals, Inc.

Role of therapeutic apheresis in infectious and inflammatory diseases: Current knowledge and unanswered questions.

Apheresis can remove pathogens and mediators that contribute to pathogenic inflammatory responses in diseases not generally considered to be "Hematologic." Erythrocytapheresis can remove intracellular pathogens such as Babesiosis. Plasmapheresis can remove mediators of the inflammatory response in conditions such as sepsis, chronic autoimmune urticaria and malignant pertussis. Leukapheresis can remove potentially harmful leukocytes in Crohn's Disease and malignant pertussis. While apheresis can remove all of these substances, the clinical efficacy and pathophysiologic changes that occur during apheresis in these conditions are largely unknown. Hence, the clinical utility of apheresis in these conditions is largely unknown and research in these areas has the potential to benefit many patients with a variety of diseases.

Out with the bad and in with the good; red cell exchange, white cell reduction, and platelet reduction.

Automated techniques for red cell [red blood cell (RBC)] exchange or depletion of malignant cells from the peripheral blood have allowed patients with life-threatening conditions to survive long enough to receive definitive treatment. Examples of such conditions include acute chest syndrome in sickle cell disease (SCD) or acute respiratory insufficiency due to leukostasis in acute leukemia. Conversely, other patients with SCD undergo RBC exchanges on a chronic basis to maintain a reasonable quality of life and prevent another stroke. In this review, we will discuss the techniques as well as indications for RBC exchange, leukocytapheresis, and thrombocytapheresis. To illustrate the uses of these therapeutic apheresis procedures, the authors included a summary of the most common diagnoses that comprise their use.

Severe babesiosis presenting as acute respiratory distress syndrome in an immunocompetent patient.

Babesiosis is a tick-borne illness caused by the intraerythrocytic parasite Babesia microti. Adult respiratory distress syndrome (ARDS) is a complication of B. microti infection and generally presents later in the course of the disease. We present a case of babesiosis presenting with ARDS. A 59-year-old male with history of hypertension and atrial fibrillation presented with one day of progressive shortness of breath. The patient returned from a trip to Massachusetts one day prior. On arrival to the emergency department (ED) the patient was noted to be febrile with tachycardia, tachypnea, and hypoxia and was intubated for respiratory failure. A computed tomography angiography (CTA) was negative for pulmonary embolism and showed bilateral infiltrates. The Berlin criteria for severe ARDS were met. Tick-borne illness was suspected and Wright-Giemsa stained thin blood smear confirmed the diagnosis of babesiosis. The patient was treated with atovaquone and azithromycin for seven days and was successfully extubated on day four of hospitalization. He continued to clinically improve and was discharged home four days later. The case highlights the importance of physicians being aware of the manifold ways in which babesiosis can manifest.

Equine piroplasmosis.

Equine piroplasmosis, caused by the parasites Theileria equi and Babesia caballi, is a globally important disease, affecting a large percentage of the world's horses. This article serves as a review of these divergent parasites. Discussed are the clinical presentation of disease, diagnosis, and treatment. Special attention is given to the current disease status specifically in North America.

Tick-borne diseases in the North Sea region-A comprehensive overview and recommendations for diagnostics and treatment.

As part of the NorthTick project, co-funded by the European Union through the European Regional Development Fund and the North Sea Region Programme, specialists in the field of tick-borne diseases from seven North Sea countries co-operated with patient organisations and governmental health care institutions to provide this comprehensive overview of diagnostics and treatment recommendations in the region for Lyme borreliosis, Borrelia miyamotoi infection, tick-borne encephalitis, human granulocytic anaplasmosis, rickettsiosis, neoehrlichiosis and babesiosis. The main conclusion is that the recommendations in these northern countries are essentially the same, with very few differences. This overview presents the current diagnostics and provides useful clinical guidance.

Human babesiosis in Europe: what clinicians need to know.

Although best known as an animal disease, human babesiosis is attracting increasing attention as a worldwide emerging zoonosis. Humans are commonly infected by the bite of ixodid ticks. Rare ways of transmission are transplacental, perinatal and transfusion-associated. Infection of the human host can cause a very severe host-mediated pathology including fever, and hemolysis leading to anemia, hyperbilirubinuria, hemoglobinuria and possible organ failure. In recent years, apparently owing to increased medical awareness and better diagnostic methods, the number of reported cases in humans is rising steadily worldwide. Hitherto unknown zoonotic Babesia spp. are now being reported from geographic areas where babesiosis was not previously known to occur and the growing numbers of travelers and immunocompromised individuals suggest that the frequency of cases in Europe will also continue to rise. Our review is intended to provide clinicians with practical information on the clinical management of this rare, but potentially life-threatening zoonotic disease. It covers epidemiology, phylogeny, diagnostics and treatment of human babesiosis and the potential risk of transfusion-transmitted disease with a special focus on the European situation.