Tafenoquine for Relapsing Babesiosis: A Case Series.

BACKGROUND: Relapsing babesiosis often occurs in highly immunocompromised patients and has been attributed to the acquisition of resistance against drugs commonly used for treatment such as atovaquone, azithromycin, and clindamycin. Tafenoquine, which is approved for malaria prophylaxis and presumptive antirelapse treatment of Plasmodium vivax malaria, has shown activity against Babesia microti in several animal models of acute infection and in a single human case of relapsing babesiosis. Here, we report 5 cases of relapsing babesiosis treated with tafenoquine, including the previous case, and begin to define the conditions for optimal use of tafenoquine in relapsing babesiosis. METHODS: A definitive diagnosis of babesiosis was made by microscopic examination of Giemsa-stained thin blood smears or a real-time polymerase chain reaction (PCR) that targets the parasite 18S rRNA gene. Clearance of B. microti infection was ascertained by use of blood smear and real-time PCR. RESULTS: Tafenoquine was initiated with a loading dose of 600 mg. A weekly maintenance dose consisted of 200 mg or 300 mg; the lower dose was associated with a delayed clearance of B. microti. In 2 cases, all antimicrobial agents but tafenoquine were discontinued prior to clearance of infection. In 2 other cases, clearance was achieved while tafenoquine was administered along with other antimicrobial agents. In 3 of these 4 cases, tafenoquine was used in combination with atovaquone-proguanil. Other agents included atovaquone, azithromycin, and/or clindamycin. In 1 case, tafenoquine was administered alone and failed to prevent relapse. CONCLUSIONS: Tafenoquine can be a useful adjunct for the treatment of highly immunocompromised patients experiencing relapsing babesiosis caused by B. microti.

Disparities Associated With Total Joint Arthroplasty Transfusion Rates.

BACKGROUND: Infections, readmissions, and mortalities after total joint arthroplasty (TJA) are serious complications, and transfusions have been associated with increased complication rates following TJA. Certain populations, including women, Black patients, patients who have public insurance and older adults have higher risks of transfusion. Recently, there has been a decline in transfusion rates and a greater emphasis on equity in medicine. This study examined whether disparities in transfusion rates still exist and what variables influence rates over time. METHODS: We used a health care system database to identify 5,435 total knee arthroplasty (TKA) and 2,105 total hip arthroplasty (THA) patients from 2013 to 2021. Transfusion rates were 2.9 and 3.1% in the TKA and THA arthroplasty groups, respectively. White race represented 67.1 and 69.8% of the TKA and THA groups, respectively. Fisher exact and Wilcoxon rank sum tests were used to compare categorical and continuous variables. Multivariable logistic regressions were performed to predict transfusion rates within 5 days of surgery and adjust for potential confounders. RESULTS: Transfusion rates declined over time. However, Black patients had a higher rate of transfusion than White patients despite similar hemoglobin levels, 5.1 versus 1.8% (P < .001) in the TKA group and 4.1 versus 2.7% (P = .103) in the THA group. Following adjustment, the biggest factor associated with a higher transfusion risk in the TKA group was being Black (adjusted odds ratio = 2.2, 95% confidence interval = 1.55 to 3.13). CONCLUSIONS: Transfusion rates for TJA patients are declining; however, Black patients continued to receive transfusions at higher rates in patients receiving TKA.

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.

Broad Antimicrobial Resistance in a Case of Relapsing Babesiosis Successfully Treated With Tafenoquine.

We describe a case of relapsing babesiosis in an immunocompromised patient. A point mutation in the Babesia microti 23S rRNA gene predicted resistance to azithromycin and clindamycin, whereas an amino acid change in the parasite cytochrome b predicted resistance to atovaquone. Following initiation of tafenoquine, symptoms and parasitemia resolved.

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.

Transfusion-transmitted Babesia spp.: a changing landscape of epidemiology, regulation, and risk mitigation.

Babesia spp. are tick-borne parasites with a global distribution and diversity of vertebrate hosts. Over the next several decades, climate change is expected to impact humans, vectors, and vertebrate hosts and change the epidemiology of Babesia. Although humans are dead-end hosts for tick-transmitted Babesia, human-to-human transmission of Babesia spp. from transfusion of red blood cells and whole blood-derived platelet concentrates has been reported. In most patients, transfusion-transmitted Babesia (TTB) results in a moderate-to-severe illness. Currently, in North America, most cases of TTB have been described in the United States. TTB cases outside North America are rare, but case numbers may change over time with increased recognition of babesiosis and as the epidemiology of Babesia is impacted by climate change. Therefore, TTB is a concern of microbiologists working in blood operator settings, as well as in clinical settings where transfusion occurs. Microbiologists play an important role in deploying blood donor screening assays in Babesia endemic regions, identifying changing risks for Babesia in non-endemic areas, investigating recipients of blood products for TTB, and drafting TTB policies and guidelines. In this review, we provide an overview of the clinical presentation and epidemiology of TTB. We identify approaches and technologies to reduce the risk of collecting blood products from Babesia-infected donors and describe how investigations of TTB are undertaken. We also describe how microbiologists in Babesia non-endemic regions can assess for changing risks of TTB and decide when to focus on laboratory-test-based approaches or pathogen reduction to reduce TTB risk.

Lack of Demographic Information in Total Hip Arthroplasty/Total Knee Arthroplasty Randomized Controlled Trial Publications.

BACKGROUND: The impact of social determinants of health (SDOH) has been documented in orthopaedic literature. However, there is a lack of data on the inclusion of these variables in orthopaedic studies. Our aim was to investigate how many total hip arthroplasties and total knee arthroplasties randomized controlled trials report SDOH variables such as race, ethnicity, insurance, income, and education within the manuscript. METHODS: A systematic review was conducted on a PubMed search for randomized controlled trials published from 2017 to 2019 in the Journal of Bone and Joint Surgery, Journal of Arthroplasty, Clinical Orthopaedics and Related Research, and Osteoarthritis and Cartilage. Data collected included publication year, type of surgery, and the inclusion of race, ethnicity, insurance, income, and education. RESULTS: Of the 72 manuscripts included in the study, 5.6% of the manuscripts mentioned race, 4.2% included race within the demographic table, and 1.4% included ethnicity in the demographic table. Overall, only 5 studies discussed any one of the variables studied and none included any SDOH variables in their multivariable regressions. There were no statistically significant differences on inclusion across journal year (P value = .78), journal name (P value = 1.00), or surgery type (P value = .555). CONCLUSION: Our findings identify a major shortcoming in the inclusion of SDOH variables in total knee arthroplasty/total hip arthroplasty publications. Their exclusion may be indirectly perpetuating disparities if research that does not use representative patient samples is used in creating health policies and national standards. LEVEL OF EVIDENCE: Level V.

Disparities in Elective and Nonelective Total Hip Arthroplasty.

BACKGROUND: Prior studies have shown disparities in utilization of primary and revision total hip arthroplasty (THA). However, little is known about patient population differences associated with elective and nonelective surgery. Therefore, the aim of this study was to explore factors that influence primary utilization and revision risk of THA based on surgery indication. METHODS: Data were obtained from 7,543 patients who had a primary THA from 2014 to 2020 in a database, which consists of multiple health partner systems in Louisiana and Texas. Of these patients, 602 patients (8%) underwent nonelective THA. THA was classified as "elective" or "nonelective" if the patient had a diagnosis of hip osteoarthritis or femoral neck fracture, respectively. RESULTS: After multivariable logistic regression, nonelective THA was associated with alcohol dependence, lower body mass index (BMI), women, and increased age and number of comorbid conditions. No racial or ethnic differences were observed for the utilization of primary THA. Of the 262 patients who underwent revision surgery, patients who underwent THA for nonelective etiologies had an increased odds of revision within 3 years of primary THA (odds ratio (OR) = 1.66, 95% Confidence Interval (CI) = 1.06-2.58, P-value = .025). After multivariable logistic regression, patients who had tobacco usage (adjusted odds ratio (aOR) = 1.36, 95% CI = 1.04-1.78, P-value = .024), alcohol dependence (aOR = 2.46, 95% CI = 1.45-4.15, P-value = .001), and public insurance (OR = 2.08, 95% CI = 1.18-3.70, P-value = .026) had an increased risk of reoperation. CONCLUSION: Demographic and social factors impact the utilization of elective and nonelective primary THA and subsequent revision surgery. Orthopaedic surgeons should focus on preoperative counseling for tobacco and alcohol cessation as these are modifiable risk factors to directly decrease reoperation risk.

Severity of Chronic Venous Insufficiency on Primary Total Knee Arthroplasty Outcomes.

BACKGROUND: More than 700,000 people in the United States undergo total knee arthroplasty (TKA) each year. Chronic venous insufficiency (CVI) affects 5% to 30% of adults, sometimes resulting in leg ulceration. These CVI cases in TKAs have been associated with worse outcomes; however, we found no study differentiating CVI severity. METHODS: This retrospective study analyzed TKA outcomes at one institution from 2011 to 2021 using patient-specific codes. Analyses included short-term complications (< 90 days postoperative), long-term complications (< 2 years), and CVI status (yes/no; simple/complex/unclassified). Complex CVI consisted of pain, ulceration, inflammation, and/or other complications. Revisions within 2 years and readmissions within 90 days post-TKA were assessed. Composite complications included short-term and long-term complications, revisions, and readmissions. Multivariable logistic regressions predicted complication (any/long/short) as a function of CVI status (yes/no; simple/complex) and potential confounding variables. Of 7,665 patients, 741 (9.7%) had CVI. Among CVI patients, 247 (33.3%) had simple CVI, 233 (31.4%) had complex CVI, and 261 (35.2%) had unclassified CVI. RESULTS: There was no difference in CVI versus control in composite complications (P = .722), short-term complications (P = .786), long-term complications (P = .15), revisions (P = .964), or readmissions (P = .438) postadjustment. Composite complication rates were 14.0% without CVI, 16.7% with complex CVI, and 9.3% with simple CVI. Complication rates differed between simple and complex CVI (P = .035). CONCLUSION: Overall, CVI did not affect postoperative complications versus control. Patients who have complex CVI are at higher risk for post-TKA complications compared to those who have simple CVI.

Risk of Infection Following Gunshot Wound Fractures to the Foot and Ankle: A Multicenter Retrospective Study.

The purpose of this multicenter retrospective chart review was to describe demographics, fracture and wound characteristics, and treatments for foot and/or ankle fractures caused by gunshot wounds (GSWs) and identify factors that increase risk of infection in adults treated at 5 urban level 1 trauma centers in South and Midwest regions of the United States. A total of 244 patients sustained GSW-related fractures of the foot/ankle during 2007-2017, of whom 179 had ≥30 days of follow-up data after the initial injury. Most patients were male (95.1%; 232/244) with an average age of 31.2 years. On average, patients sustained 1.3 GSWs (range 1-5) to the foot/ankle. Most GSWs were categorized as low energy (85.1%; 171/201) and the majority (58.2%; 142/244) had retained bullet fragments. Antibiotics were administered at initial presentation to 78.7% (192/244) of patients and 41.8% (102/244) were managed operatively at the time of initial injury. Nerve injury, vascular injury, and infection were documented in, respectively, 8.6% (21/243), 6.6% (16/243), and 17.2% (42/244) of all cases. Multivariable analysis revealed that high-energy injuries and retained bullet fragments increased the risk of infection by 3-fold (odds ratio 3.09, 95% confidence interval 1.16-8.27, p = .025) and 3.5-fold (OR 3.48, 95% CI1.40-8.67; p = .008), respectively. Side of injury, primary injury region, and vascular injury were not significant predictors of infection risk. Further research should examine whether retained bullet fragments are directly associated with infection risk and support the development of guidelines regarding the management of patients with GSW-related fractures to the ankle/foot.

How do surgeons decide when to treat proximal humerus fractures with operative versus nonoperative management?

PURPOSE: The objective of this study was to determine the underlying factors that drive the decision for surgeons to pursue operative versus nonoperative management for proximal humerus fractures (PHF) and if fellowship training had an impact on these decisions. METHODS: An electronic survey was distributed to members of the Orthopaedic Trauma Association and the American Shoulder and Elbow Surgeons Society to assess differences in patient selection for operative versus nonoperative management of PHF. Descriptive statistics were reported for all respondents. RESULTS: A total of 250 fellowship trained Orthopaedic Surgeons responded to the online survey. A greater proportion of trauma surgeons preferred nonoperative management for displaced PHF fractures in patients over the age of 70. Operative management was preferred for older patients with fracture dislocations (98%), limited humeral head bone subchondral bone (78%), and intraarticular head split (79%). Similar proportions of trauma surgeons and shoulder surgeons cited that acquiring a CT was crucial to distinguish between operative and nonoperative management. CONCLUSION: We found that surgeons base their decisions on when to operate primarily on patient's comorbidities, age, and the amount of fracture displacement when treating younger patients. Further, we found a greater proportion of trauma surgeons elected to proceed with nonoperative management in patients older than the age of 70 years old as compared to shoulder surgeons.

Frequency and Geographic Distribution of Borrelia miyamotoi, Borrelia burgdorferi, and Babesia microti Infections in New England Residents.

BACKGROUND: Borrelia miyamotoi is a relapsing fever spirochete that relatively recently has been reported to infect humans. It causes an acute undifferentiated febrile illness that can include meningoencephalitis and relapsing fever. Like Borrelia burgdorferi, it is transmitted by Ixodes scapularis ticks in the northeastern United States and by Ixodes pacificus ticks in the western United States. Despite reports of clinical cases from North America, Europe, and Asia, the prevalence, geographic range, and pattern of expansion of human B. miyamotoi infection are uncertain. To better understand these characteristics of B. miyamotoi in relation to other tickborne infections, we carried out a cross-sectional seroprevalence study across New England that surveyed B. miyamotoi, B. burgdorferi, and Babesia microti infections. METHODS: We measured specific antibodies against B. miyamotoi, B. burgdorferi, and B. microti among individuals living in 5 New England states in 2018. RESULTS: Analysis of 1153 serum samples collected at 11 catchment sites showed that the average seroprevalence for B. miyamotoi was 2.8% (range, 0.6%-5.2%), which was less than that of B. burgdorferi (11.0%; range, 6.8%-15.6%) and B. microti (10.0%; range, 6.5%-13.6%). Antibody screening within county residence in New England showed varying levels of seroprevalence for these pathogens but did not reveal a vectoral geographical pattern of distribution. CONCLUSIONS: Human infections caused by B. miyamotoi, B. burgdorferi, and B. microti are widespread with varying prevalence throughout New England.

Epidemiology of Hospitalized Patients with Babesiosis, United States, 2010-2016.

Babesia spp. are tickborne parasites that cause the clinical infection babesiosis, which has an increasing incidence in the United States. We performed an analysis of hospitalizations in the United States during 2010-2016 in which babesiosis was listed as a diagnosis. We used the National Inpatient Sample database to characterize the epidemiology of Babesia-associated admissions, reflecting severe Babesia-related disease. Over a 7-year period, a total of 7,818 hospitalizations listed babesiosis as a primary or secondary admitting diagnosis. Hospitalizations were seasonal (71.2% occurred during June-August) and situated overwhelmingly in the Northeast and Midwest. The patients were predominantly male and of advanced age, which is consistent with the expected epidemiology. Despite a higher severity of illness in more than (58.5%), the mortality rate was low (1.6%). Comparison with state reporting data suggests that the number of hospitalized persons with babesiosis increased modestly during the observation period.

Understanding postoperative rehabilitation preferences in operatively managed proximal humerus fractures: do trauma and shoulder surgeons differ?

BACKGROUND: Proximal humerus fractures (PHFs) are common, and their incidence is increasing as the population ages. Despite this, postoperative rehabilitation remains unstandardized and little is known about surgeon preferences. The aim of this study was to assess differences in postoperative rehabilitation preferences and patient education between orthopedic trauma and shoulder surgeons. METHODS: An electronic survey was distributed to members of the Orthopaedic Trauma Association and the American Shoulder and Elbow Surgeons to assess differences in postoperative rehabilitation preferences and patient counseling. Descriptive statistics were reported for all respondents, trauma surgeons, and shoulder surgeons. Chi-square and unpaired 2-sample t tests were used to compare responses. Multinomial regression was used to further elucidate the influence of fellowship training independent of confounding characteristics. RESULTS: A total of 293 surgeons completed the survey, including 172 shoulder and 78 trauma surgeons. A greater proportion of trauma surgeons preferred an immediate weightbearing status after arthroplasty compared to shoulder surgeons (45% vs. 19%, P = .003), but not after open reduction and internal fixation (ORIF) (62% vs. 75%, P = .412). A greater proportion of shoulder surgeons preferred home exercise therapy taught by the physician or using a handout following reverse shoulder arthroplasty (RSA) (21% vs. 2%, P = .009). A greater proportion of trauma surgeons began passive range of motion (ROM) <2 weeks after 2-part fractures (70% vs. 41%, P < .001). Conversely, a greater proportion of shoulder surgeons began passive ROM between 2 and 6 weeks for 2-part (57% vs. 24%, P < .001) and 4-part fractures (65% vs. 43%, P = .020). On multinomial regression analysis, fellowship training in shoulder surgery was associated with preference for a nonweightbearing duration of >12 weeks vs. 6-12 weeks after ORIF. Similarly, fellowship training in shoulder surgery was associated with increased odds of preferring a nonweightbearing duration of <6 weeks vs. no restrictions and >12 weeks vs. 6-12 weeks after arthroplasty. Training in shoulder surgery was associated with greater odds of preferring a nonweightbearing duration prior to beginning passive ROM of 2-6 weeks vs. <2 weeks or >6 weeks for 2-part fractures, but not 4-part fractures. CONCLUSION: Trauma surgeons have a more aggressive approach to rehabilitation following operative PHF repair compared to shoulder surgeons regarding time to weightbearing status and passive ROM. Given the increasing incidence of PHFs and substantial variations in reported treatment outcomes, differences in rehabilitation after PHF treatment should be further evaluated to determine the role it may play in the outcomes of treatment studies.

Factors influencing surgical management of proximal humerus fractures: do shoulder and trauma surgeons differ?

BACKGROUND: Proximal humerus fractures (PHFs) are managed with open reduction and internal fixation (ORIF), hemiarthroplasty (HA), reverse shoulder arthroplasty (RSA), or nonoperatively. Given the mixed results in the literature, the optimal treatment is unclear to surgeons. The purpose of this study was to survey orthopedic shoulder and trauma surgeons to identify the patient- and fracture-related characteristics that influence surgical decision-making. METHODS: We distributed a 23-question closed-response email survey to members of the American Shoulder and Elbow Surgeons and Orthopaedic Trauma Association. Questions posed to respondents included demographics, surgical planning, indications for ORIF and arthroplasty, and the use of surgical augmentation with ORIF. Numerical and multiple-choice responses were compared between shoulder and trauma surgeons using unpaired t-tests and χ2 tests, respectively. RESULTS: Respondents included 172 shoulder and 78 trauma surgeons. When surgery is indicated, most shoulder and trauma surgeons treat 2-part (69%) and 3-part (53%) PHFs with ORIF. Indications for managing PHFs with arthroplasty instead of ORIF include an intra-articular fracture (82%), bone quality (76%), age (72%), and previous rotator cuff dysfunction (70%). In patients older than 50 years, 90% of respondents cited a head-split fracture as an indication for arthroplasty. Both shoulder and trauma surgeons preferred RSA for treating PHFs presenting with a head-split fracture in an elderly patient (94%), pre-existing rotator cuff tear (84%), and pre-existing glenohumeral arthritis with an intact cuff (75%). Similarly, both groups preferred ORIF for PHFs in young patients with a fracture dislocation (94%). In contrast, although most trauma surgeons preferred to manage PHFs in low functioning patients with a significantly displaced fracture or nonreconstructable injury nonoperatively (84% and 86%, respectively), shoulder surgeons preferred either RSA (44% and 46%, respectively) or nonoperative treatment (54% and 49%, respectively) (P < .001). Similarly, although trauma surgeons preferred to manage PHFs in young patients with a head-split fracture or limited humeral head subchondral bone with ORIF (98% and 87%, respectively), shoulder surgeons preferred either ORIF (54% and 62%, respectively) or HA (43% and 34%, respectively) (P < .001). CONCLUSIONS: ORIF and HA are preferred for treating simple PHFs in young patients with good bone quality or fracture dislocations, whereas RSA and nonoperative management are preferred for complex fractures in elderly patients with poor bone quality, rotator cuff dysfunction, or osteoarthritis. The preferred management differed between shoulder and trauma surgeons for half of the common PHF presentations, highlighting the need for future research.

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.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Tick hypersensitivity and human tick-borne diseases.

Immune-mediated hypersensitivity reactions to ticks and other arthropods are well documented. Hypersensitivity to ixodid (hard bodied) ticks is especially important because they transmit infection to humans throughout the world and are responsible for most vector-borne diseases in the United States. The causative pathogens of these diseases are transmitted in tick saliva that is secreted into the host while taking a blood meal. Tick salivary proteins inhibit blood coagulation, block the local itch response and impair host anti-tick immune responses, which allows completion of the blood meal. Anti-tick host immune responses are heightened upon repeated tick exposure and have the potential to abrogate tick salivary protein function, interfere with the blood meal and prevent pathogen transmission. Although there have been relatively few tick bite hypersensitivity studies in humans compared with those in domestic animals and laboratory animal models, areas of human investigation have included local hypersensitivity reactions at the site of tick attachment and generalized hypersensitivity reactions. Progress in the development of anti-tick vaccines for humans has been slow due to the complexities of such vaccines but has recently accelerated. This approach holds great promise for future prevention of tick-borne diseases.