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.

Babesia in North America: An Update.

Canine babesiosis results from infection of 1 of 5 identified protozoal species in the United States (Babesia conradae, Babesia sp. "coco," Babesia gibsoni, Babesia vogeli, and Babesia vulpes). They are part of the Apicomplexa family of protozoa and are obligate intraerythrocytic parasites. Domestic and wild canids are suspected of being intermediate hosts. This updated article aims to provide practical guidance about the clinical manifestations of disease, treatment options, and outcomes. In addition, the authors hope to provide some clarity about the taxonomy and nomenclature of these organisms, as they have undergone multiple changes since their initial discovery.

Prognostic markers and their discriminant score in predicting the outcome of Babesia gibsoni infection.

BACKGROUND: We aimed to identify prognostic markers and their discriminant score in predicting the lethal outcome of canine Babesia gibsoni. METHODS: Blood samples were collected from 108 client-owned dogs with clinical signs commensurate with babesiosis to analyze haematological, biochemical, haemostatic, antioxidant profile and thiobarbituric acid reactive substance levels. Samples were screened for Babesia infection (microscopic and molecular techniques). Babesiosis-affected dogs were classified into survivors and non-survivors, and 30 healthy dogs were used in the control group. RESULTS: Haemoglobin, thrombocytes, catalase, urea, creatinine, alanine aminotransferase (ALT), alkaline phosphatase, lactate and reticulocytes were highly correlated to survival. Receiver operating characteristics analysis revealed urea, ALT and lactate as specific prognostic markers for the disease. The formula for calculation of discriminant scores (Di) for lethal outcome of the disease was generated with cut-off score 0.141. The scoring system was 79% sensitive and 83% specific in predicting the lethal outcome of the disease. CONCLUSIONS: A scoring system developed from the prognosticating markers may aid in predicting the outcome of Babesia gibsoni infection on the day of presentation itself enabling intensive care for those animals with a cut-off score more than 0.141.

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.

Powassan virus encephalitis, severe babesiosis and lyme carditis in a single patient.

Ixodes scapularis is responsible for transmission of Borrelia burgdorferi, B. miyamotoi, Babesia microti, Anaplasma phagocytophilum and Powassan virus to humans. We present a case of an 87-year-old man who presented with fever and altered mental status. Initial workup revealed haemolytic anaemia, thrombocytopenia, mild hepatitis and acute kidney injury. Patient tested positive for B. burgdorferi and Babesia microti, and was started on doxycycline, atovaquone and azithromycin. He also underwent exchange transfusion twice. After some initial improvement, patient had acute deterioration of mental status and appearance of neurological findings like myoclonus and tremors. Therefore, testing for arboviruses was done and results were positive for Powassan virus. During a protracted course of hospitalisation, patient required intubation for respiratory failure and temporary pacemaker for unstable arrythmias from Lyme carditis. Patient developed permanent neurological deficits even after recovery from the acute illness.

Safety and effectiveness of apheresis in the treatment of infectious diseases: A systematic review.

OBJECTIVES: Apheresis has been used as adjunctive treatment of severe falciparum malaria, loiasis and babesiosis. This systematic review aimed to investigate the safety and efficacy of apheresis in the treatment of these conditions. METHODS: MEDLINE, PUBMED, EMBASE and CINAHL databases were searched to identify studies published between January 1969 and March 2018 involving patients treated using apheresis for severe falciparum malaria, loiasis or babesiosis. Data extracted included details about the apheresis intervention, populations, study methods and outcomes relating to efficacy and safety. RESULTS: A total of 67 publications met the inclusion criteria and were included in the data synthesis, 36 for malaria (70 cases), 17 for babesiosis (22 cases) and 14 for loiasis (34 cases). Publications were case reports, case series, and cohort studies; there were no randomised controlled trials identified. Potential publication bias was considered to be high. CONCLUSIONS: Systematic review of the literature suggests that apheresis may be a useful adjunct in the treatment of patients hospitalised for babesiosis, and prior to chemotherapy in loiasis with microfilarial count >8000 parasites/mL. Data does not support the use of apheresis in patients with severe falciparum malaria.

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.

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.

Lyme borreliosis and other tick-borne diseases. Guidelines from the French Scientific Societies (I): prevention, epidemiology, diagnosis.

Lyme borreliosis is transmitted en France by the tick Ixodes ricinus, endemic in metropolitan France. In the absence of vaccine licensed for use in humans, primary prevention mostly relies on mechanical protection (clothes covering most parts of the body) that may be completed by chemical protection (repulsives). Secondary prevention relies on early detection of ticks after exposure, and mechanical extraction. There is currently no situation in France when prophylactic antibiotics would be recommended. The incidence of Lyme borreliosis in France, estimated through a network of general practitioners (réseau Sentinelles), and nationwide coding system for hospital stays, has not significantly changed between 2009 and 2017, with a mean incidence estimated at 53 cases/100,000 inhabitants/year, leading to 1.3 hospital admission/100,000 inhabitants/year. Other tick-borne diseases are much more seldom in France: tick-borne encephalitis (around 20 cases/year), spotted-fever rickettsiosis (primarily mediterranean spotted fever, around 10 cases/year), tularemia (50-100 cases/year, of which 20% are transmitted by ticks), human granulocytic anaplasmosis (<10 cases/year), and babesiosis (<5 cases/year). The main circumstances of diagnosis for Lyme borreliosis are cutaneous manifestations (primarily erythema migrans, much more rarely borrelial lymphocytoma and atrophic chronic acrodermatitis), neurological (<15% of cases, mostly meningoradiculitis and cranial nerve palsy, especially facial nerve) and rheumatologic (mostly knee monoarthritis, with recurrences). Cardiac and ophtalmologic manifestations are very rarely encountered.

Babesiosis as a cause of acute respiratory distress syndrome: a series of eight cases.

OBJECTIVES: The characteristics of patients with Acute Respiratory Distress Syndrome (ARDS) as a complication of Babesia microti infection have not been systematically described. METHODS: Adult patients admitted to the medical intensive care unit (MICU) of a tertiary care hospital in the Lower Hudson Valley of New York from 1/1/2008 to 8/1/2016 were evaluated for ARDS complicating babesiosis. RESULTS: Of 22 patients with babesiosis in the MICU, eight (36.4%; 95% CI: 19.7-57.0%) had ARDS. Six patients (75%) developed ARDS following initiation of anti-babesia drug therapy; however, the mean duration of symptoms in these patients exceeded that of patients who developed ARDS prior to initiation of treatment (7.50 ± 3.83d vs. 4.50 ± 0.71d, p = 0.34). Three patients (37.5%; 95% CI: 13.7-69.4%) expired without recovery from ARDS. In comparison, the mortality rate for the 14 MICU babesiosis patients without ARDS was 14.3% (p = 0.31). There was a trend toward younger age in survivors relative to non-survivors (mean age 54.6 ± 13.8y vs. 74.0 ± 6.24y, p = 0.07). Three of the five survivors did not require mechanical ventilation. The mean sequential organ failure assessment score of non-survivors was significantly higher than that of survivors (12.3 ± 1.15 vs. 6.0 ± 1.4, p = 0.0006). CONCLUSION: Among 22 critically ill adult patients with B. microti infection, ARDS developed in eight (35.4%), and three (37.5%) expired without resolution of the ARDS. ARDS often followed the initiation of anti-babesia drug therapy, raising the question of whether the death of the parasite per se contributed to its development. However, this observation was confounded by the longer duration of symptoms preceding initiation of drug therapy.

Optimizing exchange transfusion for patients with severe Babesia divergens babesiosis: Therapeutically-Rational Exchange (T-REX) of M antigen-negative and/or S antigen-negative red blood cells should be evaluated now.

Babesia divergens is an intraerythrocytic parasite, which is the major cause of babesiosis in Europe. For years, clinicians have been publishing stunning case reports that describe how some - but not all - conventional red blood cell (RBC) exchange transfusions have saved the lives of severely ill babesiosis patients. Due to markedly different patient outcomes, clinicians agree that new treatments and additional studies are needed. Here we argue that we should evaluate "therapeutically-rational exchange" (T-REX) in which the RBCs used to replace Babesia-parasitized RBCs are special disease-resistant RBC genetic variants (instead of the nondescript, "standard issue" RBCs used in conventional exchanges). T-REX seems prudent because with conventional exchange only some units of "standard issue" RBCs may be disease-resistant, while other units may not protect or may even promote disease. The random selection of RBCs for conventional RBC exchange may explain why clinical outcomes can vary dramatically. Fortunately, researchers have found that M antigen-negative (M-) and S antigen-negative (S-) RBCs resist invasion by B. divergens. Thus, we recommend evaluating T-REX of RBC variants that are B. divergens invasion-resistant: RBCs that are (1) M-, (2) S-, or (3) both M- and S-. By using only Babesia-resistant RBCs, T-REX eliminates the risk of unintentionally infusing Babesia-susceptible RBCs that might increase the severity of babesiosis. Because the T-REX variation of the conventional RBC exchange procedure is feasible, safe, and biologically plausible, we feel T-REX of Babesia-resistant RBCs should now be evaluated.

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.

Tick-Borne Illnesses in the United States.

Close interaction with nature can lead to tick-borne illnesses, which are seen most frequently in primary care clinics when patients present symptoms. Considerable morbidity can result from untreated infections. Fortunately, these illnesses are often easily managed when diagnosed early.