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Table 1.  

Neurologic symptom No. (%) patients Peak parasitemia, no. (%) patients p value
<1.0%, n = 45 1.0%–10.0%, n = 81 >10.0%, n = 37
Headache 52 (31.9) 14 (31.1) 28 (34.6) 10 (27.0) 0.711
Confusion/delirium 27 (16.6) 2 (4.4) 13 (16.1) 12 (32.4) 0.003
Impaired consciousness 24 (14.7) 4 (8.9) 9 (11.1) 11 (29.7) 0.018
Ataxia/gait disorder 17 (10.4) 3 (6.7) 10 (12.4) 4 (10.8) 0.632
Vision impairment 10 (6.1) 5 (11.1) 4 (4.9) 1 (2.7) 0.266
Acute syncope 6 (3.7) 2 (4.4) 4 (4.9) 0 (0.0) 0.482
Language deficit 5 (3.1) 0 (0.0) 5 (6.2) 0 (0.0) 0.106
Nerve pain 4 (2.5) 1 (2.2) 2 (2.5) 1 (2.7) 1.000
Focal weakness 3 (1.8) 1 (2.2) 1 (1.2) 1 (2.7) 0.794
Tremor 3 (1.8) 1 (2.2) 2 (2.5) 0 (0.0) 1.000
Seizure 2 (1.3) 1 (2.2) 0 (0.0) 1 (2.7) 0.252

Table 1. Neurologic symptoms during hospital admissions for babesiosis in patients admitted to Yale-New Haven Hospital, New Haven, Connecticut, USA, January 2011–October 2021*

*Total sample (n = 163); Column percentages do not sum to 100% due to many patients being affected by multiple neurologic conditions throughout hospitalization. Boldface type indicates statistical significance.

Table 2.  

Imaging No. (%) patients
Neuroimaging modality  
   Computed tomography 28 (17.2)
   Magnetic resonance imaging 7 (4.3)
   Electroencephalogram 2 (1.2)
Indication  
   Altered mental status/confusion 15 (9.2)
   Headache 8 (4.9)
   Fever 5 (3.1)
   Evaluate CNS abnormalities 3 (1.8)
   Weakness 3 (1.8)
   Dizziness 1 (0.6)
   Dysphagia, slurred speech 1 (0.6)
   Fall 1 (0.6)
   Head injury 1 (0.6)
   Visual changes 1 (0.6)
   Syncope 1 (0.6)
   Numbness 1 (0.6)
   Fatigue 1 (0.6)
   Seizure 1 (0.6)
Findings  
   Nonspecific white matter changes 23 (14.1)
   Volume loss 14 (8.6)
   Acute changes 2 (1.2)
   Evidence of previous stroke 3 (1.8)

Table 2. Imaging indications and findings in patients with neurologic symptoms associated with babesiosis admitted to Yale-New Haven Hospital, New Haven, Connecticut, USA, January 2011–October 2021*

*Total sample consisted of 163 patients. Neuroimaging modalities and indications sum to >33 because some patients received multiple imaging modalities or had multiple indications. CNS, central nervous system.

Table 3.  

Laboratory result, median (IQR) Reference range Headache Confusion/delirium Impaired consciousness
Yes,
n = 52
No,
n = 111
p value† Yes,
n = 27
No,
n = 136
p value† Yes,
n = 24
No,
n = 139
p value†
Hematologic function                    
   Lowest hematocrit M, 40%–52%;
F, 37%–53%
25.9 (16.2–35.6) 26.0 (19.4­–32.6) 0.581 24.0 (16.5–31.5) 26.4 (18.8–34) 0.088 23.6 (15.7–31.5) 26.4 (18.9–33.9) 0.024
   Lowest platelet count 150–400 × 109/L 78.5
82.0 (23.0–141.0) 0.881 68.0
82.0
0.339 59.5
84.0 (17.0–151.0) 0.084
Hepatic function                    
   Highest AST 3–40 U/L 66.0 (25.5–106.5) 76.0 (38.0–114.0) 0.277 76.0 (42.0–110.0) 75.5 (32.5–118.5) 0.813 81.0 (48.0–114.0) 75.0 (33.0–117.0) 0.909
   Highest ALT 3–40 U/L 61.0 (10.0–112.0) 63.0
0.809 54.0
63.5 (12.5–114.5) 0.568 49.0
63.0 (13.0–113.0) 0.441
Renal function                    
   Highest BUN 7–20 mg/dL 17.0 (4.5–29.5) 24.0
0.002 31.0
20.0 (5.5–34.5) 0.025 33.0
20.0 (5.0–35.0) 0.005
   Highest creatinine 0.5–1.2 mg/dL 1.00 (0.96–1.40) 1.1 (0.3–1.9) 0.091 1.5 (0.7–2.3) 1.0 (0.5–1.5) <0.001 1.5 (0.3–2.7) 1.0 (0.5–1.5) 0.002
   Lowest GFR ≥60 mL/min 76.0 (37.5–114.5) 67.0 (21.0–113.0) 0.007 46.0 (3.0–89.0) 73.0 (33.5–112.5) <0.001 47.0 (1.0–93.0) 73.0 (33.0–113.0) 0.003

Table 3. Laboratory result comparisons by neurologic symptoms in patients with babesiosis admitted to Yale-New Haven Hospital, New Haven, Connecticut, USA, January 2011–October 2021*

*Boldface indicates significance. ALT, alanine transaminase; AST, aspartate transaminase; BUN, blood urea nitrogen; GFR, glomerular filtration rate; IQR, interquartile range. †By Wilcoxon 2-sample test.

Table 4.  

Comorbid condition Confusion/delirium, no. (%) Adjusted odds of confusion/delirium Impaired consciousness, no. (%) Adjusted odds of impaired consciousness
OR (95% CI) p value OR (95% CI) p value
Diabetes mellitus            
No 140 (13.6) 1.00   140 (10.7)    
Yes 23 (34.8) 3.04 (1.11–8.34) 0.031 23 (39.1) 5.36 (1.98–14.48) <0.001
Stroke/transient ischemic attack            
No 150 (14.7)          
Yes 13 (38.5) 3.06 (0.88–10.66) 0.079      

Table 4. Associations between comorbid conditions and neurologic symptoms in patients with babesiosis admitted to Yale-New Haven Hospital, New Haven, Connecticut, USA, January 2011–October 2021*

*Univariate logistic regression models tested associations between the following comorbid conditions and the 3 most frequent neurologic symptoms (headache, confusion/delirium, impaired consciousness): cardiac disorder, hypertension, diabetes mellitus, immunocompromised status, stroke/transient ischemic attack, obesity, chronic kidney disease, migraine, and malignancy. Variables that were significant in unadjusted univariate analysis were entered into a multivariate model for each neurologic symptom. The significance level for univariate and multivariate analysis was set to p<0.05. Boldface indicates statistical significance.

CME / ABIM MOC

Neurologic Complications of Babesiosis

  • Authors: Sara Locke, BA; Jane O’Bryan, MPH; Adeel S. Zubair, MD; Melissa Rethana, MD; Anne Spichler Moffarah, MD, PhD; Peter J. Krause, MD; Shelli F. Farhadian, MD, PhD
  • CME / ABIM MOC Released: 5/16/2023
  • Valid for credit through: 5/19/2024, 11:59 PM EST
Start Activity

  • Credits Available

    Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 1.00 ABIM MOC points

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for infectious disease clinicians, neurologists, internists, and other clinicians caring for patients with neurologic complications of babesiosis.

The goal of this activity is for learners to be better able to describe the type and frequency of neurologic complications of babesiosis and risk factors predisposing patients to neurologic complications, on the basis of a record review of all 163 adult patients admitted to Yale-New Haven Hospital in New Haven, Connecticut, from January 2011 to October 2021 for laboratory-confirmed babesiosis.

Upon completion of this activity, participants will:

  • Assess the type and frequency of neurologic complications of babesiosis, on the basis of a record review of all adult patients admitted to Yale-New Haven Hospital from January 2011 to October 2021 for laboratory-confirmed babesiosis
  • Evaluate the risk factors predisposing patients to neurologic complications of babesiosis and outcomes, on the basis of a record review of all adult patients admitted to Yale-New Haven Hospital from January 2011 to October 2021 for laboratory-confirmed babesiosis
  • Determine the clinical implications of the type and frequency of neurologic complications of babesiosis and risk factors predisposing patients to neurologic complications, on the basis of a record review of all adult patients admitted to Yale-New Haven Hospital from January 2011 to October 2021 for laboratory-confirmed babesiosis


Disclosures

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All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated. Others involved in the planning of this activity have no relevant financial relationships.


Faculty

  • Sara Locke, BA

    Yale School of Medicine
    New Haven, Connecticut

  • Jane O’Bryan, MPH

    Frank H. Netter MD School of Medicine
    Quinnipiac University
    North Haven, Connecticut
    Yale School of Medicine
    New Haven, Connecticut

  • Adeel S. Zubair, MD

    Department of Neurology
    Yale School of Medicine
    New Haven, Connecticut

  • Melissa Rethana, MD

    Department of Neurology
    Yale School of Medicine
    New Haven, Connecticut

  • Anne Spichler-Moffarah, MD, PhD

    Yale University School of Public Health
    Yale School of Medicine
    New Haven, Connecticut

  • Peter J. Krause, MD

    Department of Medicine
    Section of Infectious Diseases
    Yale School of Medicine
    Yale University School of Public Health
    New Haven, Connecticut

  • Shelli F. Farhadian, MD, PhD

    Department of Medicine
    Section of Infectious Diseases
    Department of Neurology
    Yale School of Medicine
    New Haven, Connecticut

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has no relevant financial relationships.

Editor

  • Cheryl Salerno, BA

    Copyeditor 
    Emerging Infectious Diseases

Compliance Reviewer

  • Yaisanet Oyola, MD

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Yaisanet Oyola, MD, has no relevant financial relationships.


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    For Physicians

  • Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1.0 MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

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CME / ABIM MOC

Neurologic Complications of Babesiosis

Authors: Sara Locke, BA; Jane O’Bryan, MPH; Adeel S. Zubair, MD; Melissa Rethana, MD; Anne Spichler Moffarah, MD, PhD; Peter J. Krause, MD; Shelli F. Farhadian, MD, PhDFaculty and Disclosures

CME / ABIM MOC Released: 5/16/2023

Valid for credit through: 5/19/2024, 11:59 PM EST

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Abstract and Introduction

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.

Introduction

Babesiosis is an emerging parasitic infection with global distribution. The infection is caused by intraerythrocytic protozoa of the genus Babesia. During the past 2 decades, the incidence of babesiosis has increased, particularly in the northeastern and northern midwestern United States. The Centers for Disease Control and Prevention reported an increased babesiosis incidence in Connecticut, USA, from 2011 (2.1 cases/100,000 persons) to 2019 (9 cases/100,000 persons), more than 10 times the incidence reported nationally during that time period[1]. More than 100 species of Babesia have been described in wild and domestic animals. The predominant species causing human disease in the United States is B. microti[1–3]. The disease is transmitted primarily through the bite of an infected ixodid tick, which is capable of transmitting several pathogens at the same time, including Borrelia burgdorferi, the cause of Lyme disease[2–5]. Babesiosis is less commonly transmitted via blood transfusion, organ transplantation, or through the placenta[2,3,6].

Although most persons with babesiosis experience nonspecific influenza-like symptoms, more severe and prolonged disease can occur in persons >50 years of age; those who are immunocompromised due to asplenia, cancer, or HIV/AIDS or who are receiving immunosuppressive drugs; and those who have chronic heart, lung, renal, or liver disease[2,7,8]. Severe infection is associated with high-grade parasitemia and organ failure (e.g., acute respiratory distress syndrome, congestive heart failure, severe hemolytic anemia, or renal failure) and death[2,8–11]. Little has been published about babesiosis-induced central nervous system dysfunction[12,13]. Neurologic complications include headache, syncope, neuropathy, retinal nerve infarcts, and altered state of consciousness[9,12,14–20]. The full spectrum of neurologic complications and underlying pathophysiology are poorly understood, as are factors that predispose patients to neurologic complications.

We conducted this study to investigate the type and frequency of neurologic complications of babesiosis in a group of hospitalized patients and to assess risk factors that predispose patients to neurologic complications. We hypothesized that patients with a diagnosis of babesiosis commonly experience neurologic system manifestations and that those symptoms are most frequent in patients with severe babesiosis. Accordingly, we conducted a retrospective medical record review of all adult patients admitted to Yale-New Haven Hospital (YNHH) in New Haven, Connecticut, USA, during 2011–2021 with laboratory-confirmed babesiosis.