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Bourbon Virus Infection
Cardiovascular Presentations
Abdominal aortic aneurysm
Acute coronary syndrome (NSTEMI)
Acute coronary syndrome (STEMI)
Acute decompensated heart failure
Acute limb ischemia
Acute mesenteric ischemia
Aortic dissection
Aortic stenosis
Atrial fibrillation and flutter
Bradyarrhythmia and heart block
Cardiac arrest
Deep vein thrombosis
Myocarditis
Pericarditis
Pulmonary embolism
Stable angina
Superficial thrombophlebitis
Superior vena cava syndrome
Supraventricular tachycardia
Syncope (cardiogenic)
Unstable angina
Ventricular tachycardia
Respiratory Presentations
Acute bronchitis
Acute respiratory failure
Aspiration pneumonia
Asthma exacerbation
Bronchiolitis
Community-acquired pneumonia
COVID-19 pneumonia
COPD exacerbation
Croup
Croup (laryngotracheobronchitis)
Epiglottitis
Hemothorax
Hospital-acquired pneumonia
Pleural effusion
Pneumothorax (traumatic)
Pulmonary contusion
Spontaneous pneumothorax
Neurological Presentations
Bell's palsy
Benign paroxysmal positional vertigo
Brain abscess
Cauda equina syndrome
Cervical radiculopathy
Concussion (mild traumatic brain injury)
Encephalitis
Guillain-Barré syndrome
Hemorrhagic stroke (intracerebral)
Ischemic stroke
Lumbar radiculopathy
Malignant spinal cord compression
Migraine
Peripheral neuropathy (acute)
Retropharyngeal abscess
Schizophrenia (acute exacerbation)
Seizure (breakthrough:known epilepsy)
Seizure (first-time)
Spinal cord injury
Status epilepticus
Subarachnoid hemorrhage
Tension headache
Transient ischemic attack
Traumatic brain injury (moderate-severe)
Vestibular neuritis
Viral meningitis
Gastrointestinal Presentations
Acute appendicitis
Acute cholecystitis
Acute diverticulitis
Acute pancreatitis
Anal fissure
Choledocholithiasis and cholangitis
Clostridioides difficile colitis
Gastritis
Gastroenteritis (viral and bacterial)
Gastroesophageal reflux disease
Incarcerated or strangulated hernia
Inflammatory bowel disease flare
Large bowel obstruction
Lower GI hemorrhage
Peptic ulcer disease
Perforated viscus
Small bowel obstruction
Upper GI hemorrhage
Genitourinary and Reproductive Presentations
Acute prostatitis
Acute urinary retention
Ectopic pregnancy
Epididymitis
Orchitis
Ovarian torsion
Paraphimosis
Pelvic inflammatory disease
Priapism
Pyelonephritis
Renal laceration
Ruptured ovarian cyst
Testicular torsion
Tubo-ovarian abscess
Urinary tract infection (uncomplicated)
Urolithiasis (renal colic)
Vaginal bleeding (non-pregnant)
Infectious Disease Presentations
Acute sinusitis
Acute tonsillitis
Acute upper respiratory infection
Animal bite
Bacterial meningitis
Cellulitis
Conjunctivitis (bacterial)
Dental abscess
Endocarditis
Febrile neutropenia
Fournier gangrene
Hand-foot-mouth disease
Hepatitis (acute)
Herpes zoster
HIV-related illness
Human bite
Impetigo
Infected diabetic foot ulcer
Infectious mononucleosis
Influenza
Necrotizing fasciitis
Osteomyelitis
Otitis externa
Parasitic infection
Periorbital cellulitis
Peritonsillar abscess
Scabies
Sepsis
Septic arthritis
Spontaneous bacterial peritonitis
Tick-borne illness (Lyme disease)
Tinea infection
Tuberculosis
Viral exanthem
Wound infection
Trauma Presentations
Achilles tendon rupture
ACL and mceniscus tear
Ankle fracture
Ankle sprain
Burn
Calcaneus fracture
Cervical spine fracture
Clavicle fracture
Dental avulsion
Distal radius fracture
Drowning
Elbow fracture and dislocation
Electrical injury
Facial bone fracture
Facial laceration
Femur fracture
Fingertip amputation
Forearm fracture (radius and ulna)
Frostbite
Hand:finger laceration
Heat exhaustion
Heat stroke
Hip fracture
Humeral shaft fracture
Knee dislocation
Knee sprain
Lightning injury
Mandible fracture
Metacarpal fracture
Metatarsal fracture
Muscle strain
Nasal fracture
Non-accidental trauma
Orbital fracture
Patella fracture
Phalanx fracture (finger)
Proximal humerus fracture
Pulmonary contusion
Rib fracture
Rotator cuff tear (acute traumatic)
Scalp laceration
Scaphoid fracture
Shoulder dislocation
Skull fracture
Splenic laceration
Sternal fracture
Supracondylar pediatric fracture
Tendon laceration (hand:wrist)
Thoracic and lumbar spine fracture
Tibia:fibula fracture
Tibial plateau fracture
Toe fracture
Traumatic epistaxis
Traumatic hyphema
Toxicologic Presentations
Acetaminophen toxicity
Alcohol intoxication
Alcohol withdrawal
Anticholinergic toxicity
Anticoagulant overdose
Benzodiazepine overdose
Benzodiazepine:sedative overdose
Beta-blocker and calcium channel blocker toxicity
Carbon monoxide poisoning
Caustic ingestion
Digoxin toxicity
Drug eruption
Foreign body ingestion
Opioid intoxication
Opioid overdose
Opioid withdrawal
Organophosphate
Salicylate toxicity
Serotonin syndrome
Stimulant intoxication (cocaine, methamphetamine)
Tricyclic antidepressant overdose
Psychiatric Presentations
Acute anxiety
Acute psychosis
Agitation:behavioral emergency
Bipolar disorder
Conversion disorder
Major depressive episode
Neuroleptic malignant syndrome
Suicidal ideation and attempt
Musculoskeletal and Rheumatologic Presentations
Acute low back pain (mechanical)
Bursitis
Cervical radiculopathy
Costochondritis
Gout (acute)
Lumbar radiculopathy
Pseudogout
Tendinitis
Dermatology Presentations
Acute eczema (Eczema acute flare)
Allergic contact dermatitis
Erythema multiforme
Henoch-Schönlein purpura
Pressure injury
Psoriasis (acute flare)
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Urticaria (acute)
Environmental and Exposure Presentations
Envenomation (snake, spider, insect)
High-altitude illness
Hypothermia
Hematologic and Oncologic Presentations
Acute chest syndrome
Coagulopathy
Hyperviscosity syndrome
Sickle cell crisis (vaso-occlusive)
Symptomatic anemia
Thrombocytopenia (severe)
Tumor lysis syndrome
Pediatric-Specific Presentations
Bronchiolitis
Croup
Emergency delivery
Febrile seizure
Kawasaki disease
Neonatal jaundice
Neonatal sepsis
Nursemaid's elbow
Pediatric fever 0 to 28 days
Pediatric fever 29 to 60 days
Pediatric fever 61 to 90 days
Pyloric stenosis
Slipped capital femoral epiphysis
Intussusception
Endocrine and Metabolic Presentations
Adrenal crisis
Diabetic ketoacidosis
Hypercalcemia
Hyperosmolar hyperglycemic state
Hypertensive emergency
Hypertensive urgency
Hypoglycemia
Myasthenia gravis crisis
Myxedema coma
Severe hyperkalemia
Severe hyponatremia
Thyroid storm
ENT and Maxillofacial Presentations
Acute laryngitis
Acute otitis media
Acute pharyngitis
Cerumen impaction
Epistaxis (anterior)
Nasal foreign body
Otitis externa
Tympanic membrane perforation
Ophthalmologic Presentations
Acute angle-closure glaucoma
Central retinal artery occlusion
Chemical eye injury
Corneal abrasion
Corneal ulcer
Globe rupture
Ocular foreign body
Orbital cellulitis
Retinal detachment
Obstetric Presentations
Hyperemesis gravidarum
Painful vaginal bleeding in pregnancy
Placenta previa
Placental abruption
Preeclampsia:eclampsia
Preterm labor
Threatened:inevitable:incomplete abortion
Systemic and Miscellaneous Presentations
Anaphylaxis
Angioedema
Cannabis-induced hyperemesis
Bourbon Virus Infection
POCUS
Procedures
Calculators
Resuscitation
ECG Guide
Back
Clinical Assessment Checklist
Browse categories and answer follow-up questions to refine your symptom profile.
Approach to the Critical Patient
Immediate priorities
Airway and breathing threats
▶
Signs of respiratory failure requiring escalation
▶
SpO2 < 90% on room air
Respiratory rate > 30 per minute
Altered mental status suggesting severe systemic illness
▶
GCS < 13 consider ICU level care
Meningoencephalitis features
If hemodynamic instability, initiate resuscitation immediately
▶
MAP < 65 mmHg trigger
IV access and fluid bolus
Circulation and shock threats
▶
Septic shock physiology from multiorgan failure
▶
SBP < 90 mmHg
Lactate >= 2 mmol/l
Thrombocytopenic bleeding risk
▶
Platelet count < 20 x10^9/l
Active mucosal or visceral bleeding
DIC screen urgently if severe cytopenias
▶
PT/INR prolonged
Fibrinogen declining
Critical recognition
High-suspicion trigger for Bourbon virus infection
▶
Acute febrile illness with leukopenia and thrombocytopenia
▶
Tick exposure in endemic area (central, eastern, southern US)
Season: spring through fall
Failure to improve on empiric doxycycline within 48 to 72 hours
▶
Should raise suspicion for viral tick-borne illness
Heartland virus is key co-differential
Confirm isolation contact with state health department and CDC
▶
RT-PCR testing coordination required
Commercial testing not routinely available
Monitoring and targets
Monitoring bundle for admitted patients
▶
Continuous cardiac monitoring for arrhythmia from electrolyte derangements
▶
Potassium and magnesium replacement targets
QTc monitoring if medications used
Serial CBC every 12 to 24 hours for cytopenia trajectory
▶
Thrombocytopenia nadir surveillance
Leukopenia depth and trend
Hepatic transaminase trend every 24 to 48 hours
▶
AST and ALT elevation indicates hepatic involvement
Coagulopathy risk increases with hepatic dysfunction
Fluid balance and renal function daily
▶
Urine output target >= 0.5 ml/kg/hour
Creatinine trend for multiorgan failure
Consult triggers
Consultation needs in severe illness
▶
Infectious disease consultation for all suspected cases
▶
Guidance on diagnostic pathway and CDC coordination
Compassionate antiviral access discussion
ICU/critical care for hemodynamic instability or multiorgan failure
▶
Vasopressor requirement
ARDS or respiratory failure
Hematology if severe thrombocytopenia with bleeding
▶
Platelet transfusion threshold guidance
DIC management support
History
Presentation pattern
Core symptom complex
▶
Fever
▶
Typically high-grade and acute onset
Onset days after tick bite
Fatigue and malaise
▶
Prominent constitutional symptom
Often severe and debilitating
Headache
▶
Assess for meningismus to exclude meningoencephalitis
Photophobia or neck stiffness as red flags
Myalgias and arthralgias
▶
Diffuse body aches
Differentiates from isolated musculoskeletal cause
Gastrointestinal symptoms
▶
Nausea and vomiting
▶
Severity and duration
Ability to maintain hydration
Anorexia and diarrhea
▶
Dehydration risk assessment
Abdominal pain suggests hepatosplenomegaly
Dermatologic symptoms
▶
Rash character and distribution
▶
Maculopapular pattern reported in some cases
Absence of eschar makes Rickettsia parkeri less likely
Petechiae or purpura
▶
Suggests thrombocytopenia with bleeding risk
Mucosal bleeding noted
Exposure and tick history
Tick exposure history
▶
Specific tick bite recall
▶
Date and location of bite
Tick identification if possible (Lone Star tick: Amblyomma americanum)
Outdoor activity in endemic regions
▶
Midwest: Kansas, Missouri, Oklahoma
Southern and eastern US states
Season of exposure
▶
Spring through fall peak tick activity
Peak Lone Star tick season late spring to summer
Tick prevention measures
▶
Repellent use (DEET, permethrin)
Protective clothing usage
Tick checks after outdoor activity
Risk factors
Host risk factors
▶
Immunocompromised state
▶
Transplant recipients
Biologic agents or chronic steroids
Primary immunodeficiency (type I/II interferon pathway defects)
HIV infection
Splenectomy history
▶
Impairs clearance of tick-borne pathogens
More severe thrombocytopenia management challenges
Chronic liver disease
▶
Confounds transaminase interpretation
Coagulopathy risk compounded
Occupational and recreational exposures
▶
Farming, forestry, agriculture, landscaping
Hunting and camping in wooded brushy areas
Yard work in endemic states
Important negatives and clues
Features suggesting alternative tick-borne diagnosis
▶
Erythema migrans rash suggests Lyme disease
Eschar at bite site suggests Rickettsia parkeri or RMSF
Hemolysis and anemia suggest babesiosis
Morulae visible on blood smear suggests ehrlichiosis or anaplasmosis
Response to empiric doxycycline
▶
Improvement within 24 to 48 hours favors bacterial tick-borne illness
No improvement by 48 to 72 hours raises suspicion for viral etiology (BRBV, Heartland)
Key clinical decision branch point
Severity and complication clues
High-risk features
▶
Rapid progression to multiorgan dysfunction
▶
Index case: death within approximately 11 days of symptom onset
Liver and spleen are major target organs
Prior tick-borne illness history
▶
Possible prior subclinical exposure
Seroprevalence approximately 0.6% in Missouri and North Carolina
Immunocompromised baseline
▶
Intact interferon signaling critical for viral containment
Mouse models confirm type I/II interferon pathway importance
Physical Exam
Vitals and general
Vital sign assessment
▶
Temperature
▶
High-grade fever typical
Hypothermia in severe sepsis-like state
Heart rate
▶
Tachycardia from fever and systemic illness
Hemodynamic compromise trigger if HR > 120 with hypotension
Blood pressure
▶
Hypotension SBP < 90 mmHg
MAP < 65 mmHg as ICU trigger
Respiratory rate
▶
Elevated from systemic illness or early ARDS
> 30 per minute as severity marker
Oxygen saturation
▶
Room air baseline
Decline suggests pulmonary involvement
Skin and tick bite site
Dermatologic findings
▶
Maculopapular rash
▶
Distribution pattern
Presence or absence on palms and soles
Petechiae and purpura
▶
Thrombocytopenic bleeding manifestation
Distal extremities and dependent areas
Tick bite site inspection
▶
Embedded tick removal if present
Eschar presence or absence
Local inflammation or erythema
Head, eyes, ears, nose, throat
HEENT findings
▶
Conjunctival injection
▶
Bilateral injection common with systemic viral illness
Petechiae in conjunctivae if thrombocytopenic
Pharyngeal erythema
▶
Viral pharyngitis component
Exudate absent distinguishes from bacterial pharyngitis
Meningeal signs
▶
Nuchal rigidity assessment
Kernig and Brudzinski signs
Lymph nodes and abdomen
Lymphadenopathy
▶
Regional nodes near bite site
▶
Tender lymphadenopathy
Size and consistency
Generalized lymphadenopathy
▶
Systemic viral illness response
Cervical, axillary, inguinal
Abdominal findings
▶
Hepatomegaly
▶
Right upper quadrant tenderness
Hepatic involvement prominent in animal models
Splenomegaly
▶
Spleen is major target organ per mouse model data
Left upper quadrant fullness or tenderness
Peritoneal signs absent in uncomplicated cases
▶
Presence suggests alternative or complication
Neurological exam
Mental status assessment
▶
GCS or AVPU
▶
Altered mentation raises meningoencephalitis concern
Delirium in severe illness
Focal neurological deficit screening
▶
Cranial nerve assessment
Motor and sensory symmetry
Meningismus
▶
Neck stiffness
Photophobia and phonophobia
PITFALLS
Diagnostic pitfalls to avoid
▶
Assuming doxycycline response is occurring without objective reassessment
▶
Formal reassessment at 48 to 72 hours required
Fever curve and cytopenia trend as objective markers
Missing concurrent infection
▶
Co-infection with ehrlichiosis and BRBV possible
Dual pathogen testing warranted
Attributing cytopenias to medication effect
▶
Drug-induced cytopenias possible but tick-borne illness must be excluded first
Peripheral smear review essential
Differential Diagnosis
Life-threatening mimics
Bacterial tick-borne illnesses requiring immediate doxycycline
▶
Ehrlichiosis (Ehrlichia chaffeensis)
▶
ICD-10 A77.40
Same vector (Lone Star tick) and geography
Morulae in monocytes on peripheral smear
Responds to doxycycline within 24 to 48 hours
Anaplasmosis (Anaplasma phagocytophilum)
▶
ICD-10 A77.49
Ixodes tick vector in most regions
Morulae in granulocytes on smear
Responds to doxycycline
Rocky Mountain spotted fever (Rickettsia rickettsii)
▶
ICD-10 A77.0
More prominent rash on palms and soles
Fatal without doxycycline; start empirically
Viral tick-borne illnesses
▶
Heartland virus disease
▶
ICD-10 A93.8
Nearly identical presentation and same vector
No specific treatment; overlaps clinically with BRBV
Powassan virus encephalitis
▶
Ixodes tick vector
Meningoencephalitis predominates
Rapid neurologic deterioration
Colorado tick fever
▶
Western US geographic distribution distinguishes
Biphasic fever pattern
Leukopenia present
Common mimics
Systemic viral syndromes
▶
Influenza
▶
ICD-10 J11.1
Seasonal pattern; no tick exposure required
Leukopenia can occur
Epstein-Barr virus (infectious mononucleosis)
▶
Prominent pharyngitis and splenomegaly
Monospot and EBV serology
CMV disease
▶
Immunocompromised host pattern
CMV serology and PCR
Dengue fever
▶
Travel to tropical or subtropical regions
Thrombocytopenia and leukopenia similar
Other tick-borne illnesses
▶
Babesiosis (Babesia microti)
▶
ICD-10 B60.00
Hemolytic anemia distinguishes from BRBV
Ring forms on peripheral smear
Ixodes tick vector
Lyme disease (Borrelia burgdorferi)
▶
ICD-10 A69.2
Erythema migrans rash distinguishes
Cytopenias less prominent
Bourbon virus specific ICD coding
Coding context
▶
Bourbon virus infection: ICD-10 A93.8 (other specified arthropod-borne viral fevers)
▶
No dedicated ICD-10 code given emerging status
SNOMED CT: novel tick-borne viral fever
Differentiation from Heartland virus requires molecular testing
▶
Both classified under A93.8 in current coding
RT-PCR and serology distinguishes
Laboratory Tests
Core cytopenias and organ function
Complete blood count with differential
▶
Leukopenia
▶
Lymphopenia predominant pattern
Hallmark finding in BRBV infection
Nadir monitoring every 12 to 24 hours
Thrombocytopenia
▶
Hallmark finding in BRBV infection
Monitor for platelet count < 50 x10^9/l as significant threshold
Count < 20 x10^9/l as transfusion consideration threshold
Anemia
▶
Evaluate for hemolytic component to differentiate from babesiosis
Normochromic normocytic pattern with systemic illness
Comprehensive metabolic panel
▶
Hepatic transaminases
▶
AST and ALT elevation indicates hepatic involvement
Typically moderate elevation in reported cases
Renal function
▶
Creatinine and BUN for multiorgan failure surveillance
Acute kidney injury from systemic inflammation
Electrolytes
▶
Hyponatremia from systemic illness
Potassium and magnesium for arrhythmia risk
Coagulation and hemolysis labs
Coagulation studies
▶
PT and INR
▶
Prolongation suggests hepatic dysfunction or early DIC
Serial monitoring in severe illness
Fibrinogen
▶
Low fibrinogen confirms DIC
Target replacement > 1.5 g/l in active DIC
D-dimer
▶
Elevation supports DIC diagnosis
Highly sensitive but low specificity in febrile illness
Hemolysis evaluation
▶
LDH
▶
Elevated in hemolysis and organ damage
Differentiates from thrombotic microangiopathy
Haptoglobin
▶
Low level confirms hemolysis
Distinguish from babesiosis pattern
Reticulocyte count
▶
Elevated in hemolytic anemia
Absent in non-hemolytic cytopenias of BRBV
Infection differentiation labs
Peripheral blood smear
▶
Morulae evaluation
▶
Absence of morulae in BRBV (present in ehrlichiosis and anaplasmosis)
Essential early test in undifferentiated tick-borne illness
Ring forms evaluation
▶
Absence distinguishes from babesiosis
Intraerythrocytic inclusions in babesiosis
Red blood cell morphology
▶
Schistocytes suggest TTP or TMA
Normal morphology in BRBV
Blood cultures
▶
Two sets prior to empiric antibiotics when feasible
▶
Rules out bacteremia as co-diagnosis
Limited yield if antibiotics started
Procalcitonin
▶
Elevation suggests bacterial co-infection or superinfection
Typically low-normal in pure viral illness
Not definitive for exclusion
Lactate and perfusion
Lactate measurement
▶
>= 2 mmol/l as hypoperfusion marker
▶
Repeat within 2 to 4 hours if elevated
Clearance target with resuscitation
Elevated lactate in multiorgan failure
▶
Hepatic lactate clearance impaired with liver involvement
ICU escalation trigger if persistent elevation
Urinalysis
▶
Proteinuria and hematuria in renal involvement
▶
Microscopy for casts in AKI
Myoglobinuria from rhabdomyolysis if severe myalgias
Diagnostic Tests
Scoring Systems
Risk stratification considerations
▶
No validated BRBV-specific severity score exists
▶
Emerging disease with limited case series data
Clinical trajectory and cytopenia depth guide severity
qSOFA as general sepsis screen
▶
Respiratory rate >= 22 per minute
SBP <= 100 mmHg
Altered mental status
Screening only; not BRBV specific
NEWS (National Early Warning Score) adapted use
▶
Aggregate vital sign deterioration tracking
Serial scoring over 24 to 48 hours
Cytopenia severity markers as functional severity score
▶
Platelet < 100 x10^9/l: moderate severity threshold
Platelet < 20 x10^9/l: severe bleeding risk threshold
WBC < 2.0 x10^9/l: significant leukopenia threshold
MRI
MRI brain indications
▶
Altered mental status or focal neurological signs
▶
Meningoencephalitis evaluation
Encephalopathy pattern assessment
Protocol considerations
▶
MRI with and without gadolinium contrast
DWI for acute ischemic changes from DIC
Expected findings in encephalitis
▶
T2/FLAIR signal change in limbic or cortical regions
Leptomeningeal enhancement if meningitic
Contraindications
▶
Hemodynamically unstable patient (CT preferred)
Non-compatible implants
MRI abdomen (limited role)
▶
Not primary imaging modality for BRBV
▶
CT abdomen preferred for hepatosplenomegaly evaluation
MRI liver if contrast reaction or chronic liver disease
CT
CT head indications
▶
Altered mental status before lumbar puncture
▶
Exclude mass lesion or herniation risk
Non-contrast CT initial study
Focal neurological deficit
▶
Ischemic or hemorrhagic complication from DIC
CT angiography if large vessel concern
CT chest indications
▶
Respiratory symptoms or hypoxemia
▶
Bilateral infiltrates suggest ARDS
Pleural effusion evaluation
Differentiation from bacterial pneumonia
▶
Consolidation pattern
Air space disease distribution
CT abdomen and pelvis
▶
Hepatosplenomegaly confirmation
▶
Liver and spleen size measurement
Splenic enlargement prominent in BRBV animal models
Abdominal pain evaluation
▶
Splenic infarct or hemorrhage in severe thrombocytopenia
Lymphadenopathy distribution
Contrast considerations
▶
Renal function assessment before contrast
Allergy pre-medication if prior reaction
Ultrasound
Abdominal ultrasound
▶
Hepatosplenomegaly evaluation
▶
Liver size and echogenicity
Spleen size measurement (normal < 12 cm longitudinal)
Periportal lymphadenopathy
▶
Mesenteric node enlargement
Associated with viral systemic illness
POCUS in critically ill
▶
Rapid bedside hepatosplenic assessment
Ascites detection if severe systemic illness
Cardiac POCUS
▶
Gross LV function assessment
▶
Shock differential evaluation
Pericardial effusion screen
IVC assessment for fluid responsiveness
▶
Integrate with clinical exam
Limited in spontaneously breathing patients
Lung ultrasound if respiratory compromise
▶
B-lines for pulmonary edema or ARDS
▶
Bilateral dependent pattern
Consolidation detection
Pleural effusion identification
▶
Anechoic fluid collection
Thoracentesis guidance if large effusion
Disposition
Admission indications
Criteria warranting hospital admission
▶
Significant cytopenias
▶
Platelet count < 100 x10^9/l
WBC < 3.0 x10^9/l
Systemic toxicity
▶
Fever with inability to maintain oral hydration
Persistent vomiting
Anorexia with dehydration
Organ involvement evidence
▶
Transaminase elevation > 3 times upper limit of normal
Renal impairment
Coagulopathy
Immunocompromised host
▶
Lower threshold for admission in all immunocompromised patients
Interferon pathway defects risk severe disease
Empiric doxycycline indication until BRBV confirmed
▶
All undifferentiated tick-borne febrile illness with cytopenias
▶
Covers ehrlichiosis and anaplasmosis empirically
Continued until bacterial tick-borne illness excluded
ICU indications
Critical illness criteria
▶
Hemodynamic instability
▶
Vasopressor requirement
MAP < 65 mmHg despite fluid resuscitation
Respiratory failure
▶
SpO2 < 90% requiring supplemental oxygen escalation
ARDS pattern on imaging
Severe thrombocytopenic bleeding
▶
Intracranial hemorrhage concern
Gastrointestinal hemorrhage
Multiorgan failure
▶
Hepatic and renal failure concurrent
DIC with active bleeding
Altered mental status
▶
Meningoencephalitis
GCS < 13
Discharge criteria and follow-up
Copy
Outpatient management criteria (very limited for confirmed BRBV)
▶
Mild illness with stable cytopenias
▶
Platelet > 100 x10^9/l
Able to maintain oral hydration
No high-risk features
▶
Immunocompetent host
No organ involvement on labs
Reliable follow-up plan
▶
Repeat CBC within 48 to 72 hours
Clear return precautions provided
Follow-up requirements
▶
CBC and metabolic panel repeat within 48 to 72 hours
▶
Cytopenia nadir may be delayed
Recovery confirmation required
Infectious disease outpatient follow-up
▶
Convalescent serology at 2 to 4 weeks
CDC case reporting coordination
State health department notification mandatory
▶
Bourbon virus is a reportable novel pathogen
Coordinate diagnostic testing through public health channels
Treatment
Supportive care fundamentals
Fluid resuscitation and hydration
▶
IV crystalloid for dehydration or hemodynamic instability
▶
Normal saline or lactated Ringer's 500 ml bolus
Reassess after each bolus for response
Avoid fluid overload in ARDS pattern
Oral rehydration when tolerated
▶
Adequate hydration with fever and vomiting losses
Electrolyte replenishment
Antipyretics and symptom management
▶
Acetaminophen for fever and myalgias
▶
650 to 1000 mg PO or PR every 6 hours
Maximum 4 g per 24 hours in adults
Hepatic dose reduction if transaminase elevation severe
Avoid NSAIDs
▶
Renal function impairment risk
Platelet dysfunction with thrombocytopenia
Antiemetics for nausea and vomiting
▶
Ondansetron 4 to 8 mg IV or PO every 6 to 8 hours
Metoclopramide 10 mg IV or PO every 6 hours as alternative
Empiric antimicrobial therapy
Doxycycline empiric coverage
▶
Indication: undifferentiated tick-borne febrile illness with cytopenias
▶
Covers ehrlichiosis and anaplasmosis pending diagnostics
Start immediately without waiting for results (ACEP Level B)
Dosing: doxycycline 100 mg IV or PO every 12 hours
▶
IV formulation preferred in critically ill or vomiting patients
PO when oral route tolerated and stable
Duration: continue until bacterial tick-borne illness excluded
▶
Minimum 5 to 7 days if ehrlichiosis or anaplasmosis confirmed
If BRBV confirmed as sole pathogen, doxycycline can be discontinued
No activity against BRBV itself
▶
Pure supportive care once viral etiology established
Doxycycline does not alter BRBV course
Antiviral considerations
No FDA-approved antiviral therapy for BRBV
▶
Investigational agents with preclinical data only
▶
Evidence from animal models; no human clinical trial data
Class IIb recommendation based on expert opinion and case basis
Favipiravir
▶
Mechanism: RNA-dependent RNA polymerase inhibitor
▶
Prevented mortality in Ifnar1-/- mouse model
Prophylactic or therapeutic up to 3 days post-infection in mice
Human use: investigational; compassionate use discussion with CDC
▶
No established human dosing for BRBV
Available under EUA or compassionate protocols in select scenarios
Molnupiravir
▶
Mechanism: nucleoside analogue RNA mutagen
▶
In vitro and in vivo efficacy demonstrated in mouse models
Therapeutic benefit when started 24 to 48 hours post-infection
Improved thrombocytopenia and reduced liver/spleen pathology in mice
Human use: requires compassionate use and infectious disease guidance
▶
FDA approval exists for COVID-19; not indicated for BRBV
Coordinate with CDC for off-label consideration
Ribavirin
▶
Mechanism: nucleoside analogue with broad antiviral activity
▶
Inhibited BRBV in cell culture (in vitro data only)
No animal in vivo BRBV efficacy data published
Human use: case-by-case basis with infectious disease and CDC input
▶
Hemolytic anemia side effect relevant in cytopenic patient
Monitor CBC closely if used
Hematologic support
Platelet transfusion
▶
Threshold for prophylactic transfusion
▶
Platelet count < 10 x10^9/l with no active bleeding
Platelet count < 20 x10^9/l with bleeding risk
Threshold for therapeutic transfusion with active bleeding
▶
Maintain platelet > 50 x10^9/l for major bleeding
Maintain > 100 x10^9/l for intracranial hemorrhage
Avoid antiplatelet agents and anticoagulants in thrombocytopenia
▶
Aspirin, NSAIDs, and P2Y12 inhibitors withheld
LMWH and heparin held unless life-threatening thrombosis
Red blood cell transfusion
▶
Threshold: hemoglobin < 70 g/l in stable patient
▶
Higher threshold < 80 g/l if cardiac or respiratory compromise
Symptom-guided transfusion in rapidly declining anemia
DIC management
▶
Fresh frozen plasma for coagulopathy with active bleeding
▶
15 ml/kg IV
Target INR < 1.5 for invasive procedures
Cryoprecipitate if fibrinogen < 1.5 g/l
▶
1 pool (5 units) IV
Recheck fibrinogen after transfusion
ICU-level interventions
Vasopressor support for septic shock physiology
▶
Norepinephrine first-line vasopressor
▶
Start 0.01 to 0.03 mcg/kg/minute IV infusion
Titrate to MAP >= 65 mmHg
Maximum dose typically 0.5 to 1.0 mcg/kg/minute before adding second agent
Vasopressin as adjunct
▶
0.03 to 0.04 units/minute fixed dose
Added when norepinephrine dose escalating
Respiratory support escalation
▶
Supplemental oxygen titrated to SpO2 92 to 96%
▶
Nasal cannula or face mask first
High-flow nasal cannula if escalating requirement
Invasive mechanical ventilation for respiratory failure
▶
Lung-protective strategy for ARDS pattern
Tidal volume 6 ml/kg ideal body weight
Plateau pressure < 30 cmH2O
Special Populations
Pregnancy
Pregnancy considerations
▶
Risk data in pregnancy
▶
No published human cases in pregnancy; evidence extrapolated
Immunologic changes of pregnancy may alter viral course
Thrombocytopenia management overlaps with gestational thrombocytopenia
Diagnostic approach in pregnancy
▶
RT-PCR testing remains primary diagnostic modality
Ultrasound preferred over CT for abdominal evaluation
CT with shielding if clinically required for brain or chest
Treatment modifications in pregnancy
▶
Doxycycline: avoid after first trimester risk of fetal dental staining
▶
In severe tick-borne illness, benefit-risk favors treatment regardless
Class D designation; use when ehrlichiosis or anaplasmosis cannot be excluded
Acetaminophen preferred antipyretic
NSAIDs avoided especially third trimester
Fetal monitoring
▶
Fetal heart rate monitoring when viable gestation
Obstetric consultation for all admitted pregnant patients
Fever reduction important to reduce fetal tachycardia
Geriatric
Older adult features
▶
Atypical presentation risk
▶
Afebrile presentation possible despite infection
Delirium may be presenting symptom
Falls from weakness and fatigue
Comorbidity burden
▶
Polypharmacy interactions with antivirals
Chronic liver or renal disease alters drug dosing
Pre-existing cytopenias may obscure diagnosis
Doxycycline dosing in geriatric patients
▶
Standard dosing 100 mg IV or PO every 12 hours
Renal adjustment not required for doxycycline
Monitor for Clostridioides difficile in antibiotic-treated older adults
Disposition bias toward admission
▶
Lower threshold for admission in frail patients
Limited home supports increase risk of decompensation
Swallow evaluation if aspiration risk from weakness
Pediatrics
Pediatric considerations
▶
Case data in children
▶
Very limited pediatric-specific BRBV case reports
Seroprevalence data include children in endemic areas
Severity and natural history in children not well characterized
Diagnostic approach in children
▶
RT-PCR and serology as in adults; coordinate with CDC
Peripheral smear essential to exclude ehrlichiosis and anaplasmosis
Empiric doxycycline despite age in severe tick-borne febrile illness
Doxycycline dosing in children
▶
Weight-based: 2.2 mg/kg per dose IV or PO every 12 hours
Maximum dose 100 mg per dose
AAP and ACEP support doxycycline use in children with suspected tick-borne illness regardless of age
Supportive care differences
▶
Fluid resuscitation 20 ml/kg IV bolus isotonic crystalloid
Repeat bolus and reassess for fluid overload
Platelet transfusion thresholds similar to adults adjusted for weight
Fever and antipyretics
▶
Acetaminophen 15 mg/kg per dose PO or PR every 6 hours
Ibuprofen avoided due to platelet dysfunction with thrombocytopenia
Avoid aspirin (Reye syndrome risk)
Background
Epidemiology
Discovery and case history
▶
First isolated 2014 from a fatal case in Bourbon County, Kansas
▶
Index case: adult male with tick exposure who died within 11 days
Novel virus identified by next-generation sequencing
Subsequent case reports from limited US states
▶
Cases confirmed in Kansas, Missouri, Oklahoma
Sporadic cases in other Midwestern and southern states
Total reported cases remain very small (dozens as of 2024)
Seroprevalence data suggest underdiagnosis
▶
Approximately 0.6% seroprevalence in Missouri
Approximately 0.6% seroprevalence in North Carolina
True burden likely much higher than recognized cases
Vector and geographic distribution
▶
Primary vector: Lone Star tick (Amblyomma americanum)
▶
Highly aggressive human-biting tick
Range covers central, eastern, and southern United States
Seasonal exposure pattern
▶
Spring through fall peak tick activity
Peak human cases correspond to peak Lone Star tick season
Endemic states include Kansas, Missouri, Oklahoma, Arkansas, and surrounding states
▶
Range expanding as A. americanum range expands northward
Climate change may extend endemic zone
Mortality and morbidity
▶
Case-fatality rate unknown due to underdiagnosis of mild cases
▶
Index case and subsequent severe cases were fatal
Mild self-limited cases likely exist but undetected
Immunocompromised hosts at highest risk for fatal disease
▶
Interferon-deficient mouse models uniformly fatal
Intact innate immunity essential for survival
Pathophysiology
Viral classification and structure
▶
Family: Orthomyxoviridae, genus Thogotovirus
▶
Segmented negative-sense RNA virus
Related to Thogoto virus and Dhori virus
Transmission: tick bite from Amblyomma americanum
▶
Viral replication in tick salivary glands
Inoculation at bite site during tick feeding
Incubation period: not precisely defined
▶
Estimated days after tick bite based on index case
Precise range unknown due to limited case data
Immune evasion and innate immunity
▶
Type I and type II interferon signaling critical for viral control
▶
Ifnar1-deficient mice uniformly succumb to infection
Wild-type mice survive with intact interferon response
Clinical correlate: immunocompromised hosts at severe disease risk
Target organs
▶
Liver: hepatitis pattern with transaminase elevation
Spleen: prominent pathology in animal models
Bone marrow: cytopenia production from direct or immune-mediated suppression
Mechanisms of cytopenias
▶
Leukopenia pathogenesis
▶
Lymphopenia from lymphocyte trafficking or destruction
Direct marrow suppression possible
Inflammatory cytokine-mediated redistribution
Thrombocytopenia pathogenesis
▶
Viral suppression of megakaryocyte production
Immune-mediated platelet destruction
Splenic sequestration from splenomegaly
Multiorgan failure pathway
▶
Cytokine storm in severe cases
Direct viral cytopathic effect on hepatocytes
DIC from systemic endothelial activation
Therapeutic Considerations
Empiric antibiotic strategy rationale
▶
Doxycycline empirically treats the two most common differentials
▶
Ehrlichiosis: same vector, same geography, fatal without treatment
Anaplasmosis: similar presentation, doxycycline responsive
Clinical benefit of empiric doxycycline outweighs risk
▶
ACEP Level B recommendation for empiric treatment in tick-borne febrile illness
No harm in treating with doxycycline if ultimately viral etiology
Reassessment at 48 to 72 hours is the key decision branch
▶
Response to doxycycline suggests bacterial etiology
Non-response mandates viral illness workup and coordination with CDC
Antiviral drug pipeline
▶
No approved agent; investigational options limited
▶
Favipiravir has strongest animal efficacy data for BRBV
Molnupiravir shows in vitro and in vivo promise
Ribavirin has cell culture activity; less in vivo data
Compassionate use pathway
▶
Contact CDC Emergency Operations Center for guidance
State health department coordination required
Informed consent for investigational use
Public health considerations
▶
Mandatory case reporting to state health department
▶
Novel pathogen; each case contributes to epidemiologic understanding
CDC coordinates laboratory testing and case surveillance
No vaccine available
▶
Tick avoidance is only prevention strategy
DEET, permethrin-treated clothing, tick checks after outdoor activity
No evidence of human-to-human transmission
▶
Standard contact precautions sufficient
No isolation beyond standard precautions required
Patient Discharge Instructions
copy discharge instructions
Copy
Bourbon virus infection home care instructions
▶
Rest and activity
▶
Rest until fever resolves and energy returns
Avoid strenuous activity until CBC normalizes
Return to activity gradually under physician guidance
Hydration
▶
Drink plenty of fluids (water, electrolyte drinks)
Aim for clear to pale yellow urine as hydration marker
Seek care if unable to keep fluids down
Medications
▶
Take all prescribed antibiotics (doxycycline) exactly as directed
Complete full course even if feeling better
Acetaminophen for fever and pain as directed on packaging
Avoid ibuprofen and aspirin until cleared by physician
Tick prevention
▶
Use DEET-based repellent on exposed skin
Apply permethrin to clothing and gear
Wear long sleeves and pants in wooded or brushy areas
Check entire body for ticks after outdoor activity
Remove ticks promptly with fine-tipped tweezers
Required follow-up appointments
▶
Blood test repeat (CBC) within 48 to 72 hours of discharge
▶
Blood counts may continue to drop before recovery
Confirm platelet and white cell recovery
Infectious disease follow-up appointment scheduled
▶
Convalescent blood test for Bourbon virus confirmation at 2 to 4 weeks
State health department may contact for case investigation
Primary care or emergency return if symptoms worsen
Warning signs requiring immediate return to emergency department
▶
Difficulty breathing or shortness of breath
Unusual bleeding
▶
Blood in urine or stool
Nosebleed that will not stop
Vomiting blood
Severe headache or stiff neck
Confusion, unusual behavior, or difficulty waking
Persistent high fever unresponsive to acetaminophen
Fainting or near-fainting
Severe abdominal pain
Skin turning yellow (jaundice)
References
Guidelines and key sources
Foundational BRBV publications
▶
Kosoy OI et al (2015) - original Bourbon virus isolation and characterization, Emerging Infectious Diseases
▶
Index fatal case in Bourbon County, Kansas, 2014
Thogotovirus classification confirmed
Savage HM et al (2017) - Amblyomma americanum as vector, PLOS ONE
▶
Vector competence confirmed in laboratory studies
Geographic distribution implications
Brault AC et al - additional case series and seroprevalence studies
▶
Seroprevalence approximately 0.6% in Missouri and North Carolina
Suggests significant underdiagnosis
Antiviral preclinical data
▶
Favipiravir mouse model efficacy study (Thogotovirus model)
▶
Prophylactic and early therapeutic benefit in Ifnar1-deficient mice
Class IIb evidence basis for compassionate use consideration
Molnupiravir in vitro and in vivo BRBV efficacy
▶
Improved thrombocytopenia and hepatosplenic pathology
Therapeutic window 24 to 48 hours post-infection in mice
Ribavirin cell culture inhibitory activity
▶
In vitro data; no published human trial for BRBV
Tick-borne illness guidelines and standards
▶
ACEP clinical policy on tick-borne illness management
▶
Level B recommendation for empiric doxycycline in undifferentiated tick-borne febrile illness
Level C for antiviral considerations in emerging viral tick-borne pathogens
CDC Bourbon virus resources and case reporting guidance
▶
www.cdc.gov/ncezid/dvbd/bourbon
Emergency Operations Center for compassionate antiviral access
IDSA tick-borne illness clinical practice guidance
▶
Diagnostic and treatment recommendations for ehrlichiosis and anaplasmosis
Applicable empiric management prior to BRBV confirmation
Coding references
▶
ICD-10 A93.8: other specified arthropod-borne viral fevers (applied to BRBV)
ICD-10 A77.40: ehrlichiosis (key differential)
ICD-10 B60.00: babesiosis (key differential)
SNOMED CT: emerging tick-borne viral fever concept
SymptomDx is an educational tool for medical professionals. It does not replace clinical judgment. Verify all clinical data and drug dosages with authoritative sources.
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Management Protocols
Bourbon Virus Infection