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Hantavirus (HFRS)
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
Hantavirus (HFRS)
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
Life-threatening presentations requiring immediate action
▶
Hemodynamic shock
▶
SBP < 90 mmHg in hypotensive phase (days 3–6)
MAP < 65 mmHg
Leading cause of death in HFRS
Oliguric renal failure
▶
Urine output < 400 mL/24 hours
30% of patients develop severe oliguria
Severe hyperkalemia risk
Active hemorrhage
▶
Petechiae, epistaxis, GI bleeding, intracranial hemorrhage
DIC with platelet < 50 x10^9/L
Respiratory failure
▶
Pulmonary edema in oliguric phase
ARDS in multiorgan dysfunction
Altered mental status
▶
Cerebral edema
Toxic encephalopathy
Initial stabilization steps
▶
IV access x2 large bore
▶
Fluid resuscitation titrated to phase
Avoid fluid overload during oliguria
Continuous cardiorespiratory monitoring
▶
Urine output monitoring every hour
Serial electrolytes every 6–12 hours
If refractory hypotension, initiate norepinephrine
▶
Target MAP >= 65 mmHg
Vasopressin as adjunct if norepinephrine dose escalating
Phase-based management framework
Five clinical phases of HFRS
▶
Febrile phase (days 1–7)
▶
Fever, headache, myalgia, thrombocytopenia onset
Initiate supportive care and monitoring
Hypotensive phase (days 3–6)
▶
Sudden BP drop, capillary leak, hemoconcentration
Aggressive but titrated volume resuscitation
Oliguric phase (days 5–12)
▶
AKI peak, fluid restriction, hyperkalemia management
Dialysis threshold assessment
Diuretic phase (days 10–21)
▶
Polyuria up to 3–6 L/day
Aggressive electrolyte and fluid repletion
Convalescent phase (weeks to months)
▶
Gradual renal recovery
Outpatient nephrology follow-up
Consultation and escalation triggers
Mandatory early consultations
▶
Nephrology
▶
Creatinine rising to > 350 micromol/L
Oliguria unresponsive to cautious fluid challenge
Hyperkalemia > 6 mmol/L
Infectious disease
▶
Diagnostic confirmation of hantavirus
Ribavirin consideration for Hantaan virus exposure
Critical care / ICU
▶
Vasopressor requirement
Mechanical ventilation for ARDS
Multiorgan dysfunction syndrome
Cardiology
▶
Troponin elevation or ECG changes suggesting myocarditis
History
Exposure and epidemiological history
Critical exposure window
▶
Incubation period 2–6 weeks before symptom onset
▶
Rural or outdoor activity during this period
Contact with rodent droppings, urine, or nests
High-risk activities
▶
Farming, forestry, military exercises, hiking
Cleaning rodent-infested barns, sheds, or cabins
Pest control work without respiratory protection
Transmission route
▶
Inhalation of aerosolized rodent excreta (primary)
No human-to-human transmission for HFRS-causing viruses
Geographic exposure
▶
Endemic regions: China, Korea, Balkans, Scandinavia, Russia
Recent flooding events increase rodent displacement and risk
Spring and autumn peaks correlate with rodent population dynamics
Symptom timeline
Classic presentation sequence
▶
Acute high fever (often > 39°C)
▶
Headache and myalgia
Nausea, vomiting, abdominal pain
Fever duration approximately 7 days
▶
Oliguria appearance around day 6
Polyuria onset approximately day 9
Decreased or absent urine output
▶
Dark or bloody urine
Back and flank pain
No coryza, no sore throat
▶
Absence helps distinguish from typical viral URI
Important negative finding
Associated symptoms and red flags
Hemorrhagic manifestations
▶
Petechiae (axillae, trunk)
▶
Epistaxis
Gingival bleeding or melena
Menorrhagia in female patients
Ocular symptoms
▶
Blurred vision or transient myopia
▶
Present in up to 70% of Puumala virus cases
Usually resolves with recovery
Respiratory symptoms
▶
Cough, dyspnea, chest tightness
▶
More than 50% of HFRS patients have respiratory involvement
GI symptoms mimicking acute abdomen
▶
Severe abdominal pain
▶
Can mimic appendicitis or pancreatitis
HFRS abdominal pain from retroperitoneal edema
Risk factors
Host and demographic risk factors
▶
Male sex
▶
Male-to-female ratio approximately 2.6:1
Age > 50 years
▶
Older age independently associated with mortality
Smoking
▶
Risk factor for Puumala virus infection and more severe disease
Comorbidities increasing mortality
▶
Hypertension
Diabetes mellitus
Pre-existing chronic kidney disease
Occupational and behavioral risks
▶
Rural residence in endemic areas
Pet or laboratory rats (Seoul virus transmission)
Immunosuppression may alter disease course
Physical Exam
Vital signs and general appearance
Vital sign profile
▶
High fever (> 39°C) in febrile phase
▶
Temperature may normalize abruptly at onset of hypotensive phase
Relative bradycardia despite fever
▶
Present in 80% of Puumala virus patients
Hallmark finding — paradoxical bradycardia with fever
Hypotension in hypotensive phase
▶
SBP < 90 mmHg
Capillary leak physiology
Tachycardia in shock states
▶
Weak pulses, delayed capillary refill
General appearance
▶
Flushed facies
▶
Facial flushing is classic in febrile phase
Periorbital edema
Signs of fluid overload in oliguric phase
▶
Peripheral edema
Pulmonary crackles
Skin and mucous membranes
Hemorrhagic skin findings
▶
Petechiae distribution
▶
Axillae, trunk, and extremities
Palatal petechiae possible
Conjunctival injection or hemorrhage
▶
Scleral icterus rare but reported
Volume status assessment
▶
Dry mucous membranes in febrile or hypotensive phase
▶
Peripheral edema in oliguric phase
Paradoxical: volume-depleted then volume-overloaded
Abdominal and renal exam
Abdominal tenderness
▶
Diffuse tenderness
▶
Flank and costovertebral angle tenderness prominent
Hepatomegaly possible
Mimics surgical abdomen
▶
Peritonism may be absent despite severe pain
Neurologic assessment
▶
Altered sensorium in severe cases
▶
Cerebral edema from capillary leak
Toxic encephalopathy
Pulmonary exam
Respiratory findings
▶
Crackles suggesting pulmonary edema
▶
Oliguric phase fluid redistribution
Bilateral interstitial pattern
Decreased breath sounds at bases
▶
Pleural effusion in Balkan HFRS cases (~50%)
Oxygen saturation monitoring
▶
SpO2 < 94% triggers supplemental oxygen
Declining SpO2 signals impending respiratory failure
PITFALLS
Common diagnostic errors
▶
Misidentified as acute abdomen
▶
Surgical consultation before hantavirus considered
Abdominal pain from retroperitoneal not intraperitoneal cause
Bradycardia misinterpreted
▶
May be incorrectly attributed to treatment effect or drug
Actually reflects autonomic dysfunction from hantavirus
Thrombocytopenia attributed to sepsis or drug
▶
HFRS thrombocytopenia is immunopathological
Do not withhold diagnosis while awaiting blood cultures
Differential Diagnosis
Life-threatening mimics
Leptospirosis
▶
ICD-10 A27.9
▶
Closest clinical mimic: fever, AKI, thrombocytopenia
Leptospirosis more commonly shows higher bilirubin and more shock
Weil disease distinction: pronounced jaundice and renal failure
Sepsis with multiorgan failure
▶
ICD-10 A41.9
▶
Fever, hypotension, AKI, thrombocytopenia
Blood cultures positive in bacterial sepsis; negative in HFRS
Crimean-Congo hemorrhagic fever
▶
ICD-10 A98.0
▶
Fever plus hemorrhage plus thrombocytopenia
Overlapping endemic regions (Balkans)
Tick exposure history versus rodent exposure history
Thrombotic microangiopathy
▶
TTP/HUS: ICD-10 M31.1 / D59.3
▶
Thrombocytopenia plus AKI plus microangiopathic hemolysis
ADAMTS13 deficiency in TTP; STEC in HUS
Infectious mimics
Dengue and arboviral infections
▶
ICD-10 A90–A92
▶
Fever plus thrombocytopenia
Typically no significant AKI
Travel to tropical endemic region
Rickettsiosis
▶
Scrub typhus (ICD-10 A75.3), RMSF (ICD-10 A77.0)
▶
Fever, rash, thrombocytopenia
Eschar in scrub typhus; tick exposure in RMSF
Acute glomerulonephritis
▶
ICD-10 N00
▶
Hematuria, proteinuria, AKI, hypertension
No systemic viral prodrome or thrombocytopenia
Non-infectious mimics
Acute pancreatitis
▶
ICD-10 K85
▶
Severe abdominal pain, nausea, vomiting
Amylase and lipase markedly elevated versus mild in HFRS
HELLP syndrome in pregnancy
▶
ICD-10 O14.2
▶
Thrombocytopenia, hypertension, renal dysfunction
Pregnancy-specific context required
Acute abdomen
▶
Appendicitis, ruptured viscus
▶
HFRS abdominal pain can mimic precisely
Absence of peritonism on exam, imaging showing renal enlargement
Laboratory Tests
Core diagnostic labs
Complete blood count
▶
Thrombocytopenia present in 95% of HFRS patients
▶
Platelet nadir typically < 100 x10^9/L
Platelet < 50 x10^9/L associated with worse outcomes and higher creatinine
Leukocytosis in 55% of patients
▶
Left shift possible
Immunoblasts on peripheral smear are a clue
Elevated hematocrit or hemoglobin
▶
Hemoconcentration from plasma leak in hypotensive phase
Basic metabolic panel
▶
Creatinine and BUN
▶
Peaks days 5–9 of illness
Creatinine may reach > 800 micromol/L in severe cases
Potassium
▶
Hyperkalemia during oliguric phase
Hypokalemia during diuretic phase — replacement required
Sodium
▶
Hyponatremia <= 133 mmol/L predicts development of oliguric ARF
Monitor closely throughout all phases
Liver function tests
▶
AST and ALT elevated in most cases
▶
LDH elevated, reflecting tissue injury
Severe hepatic failure uncommon
Inflammatory and coagulation markers
Inflammatory markers
▶
CRP markedly elevated (99% of patients)
▶
Limited specificity for hantavirus versus other infections
Procalcitonin elevated (91% of patients)
▶
Can complicate differentiation from bacterial sepsis
Clinical and epidemiological context essential
Coagulation studies
▶
PT and aPTT prolonged in severe disease
▶
DIC panel when hemorrhagic manifestations present
Fibrinogen, D-dimer, antithrombin
Platelet trend
▶
Serial monitoring every 12–24 hours in acute phase
Urinalysis and serologic confirmation
Urinalysis
▶
Proteinuria present — highly supportive of HFRS
▶
Hematuria on dipstick
Rapid bedside clue when combined with fever and thrombocytopenia
Hantavirus serologic testing
▶
IgM EIA against hantavirus nucleocapsid protein
▶
Gold standard for acute confirmation
Typically positive at symptom onset
Send on any febrile patient with AKI and thrombocytopenia in endemic area
IgG EIA
▶
Used for confirmation and convalescent serology
Four-fold rise between acute and convalescent samples
RT-qPCR (S segment)
▶
Sensitive and specific
Detects viral RNA before antibody seroconversion
Buffy coat preferred specimen over plasma
Can remain positive for weeks after symptom resolution
Additional labs
Arterial blood gas
▶
Metabolic acidosis in oliguric phase
▶
PaO2 mmHg for respiratory failure assessment
Bicarbonate depletion from renal tubular loss
Lactate
▶
>= 2 mmol/L indicates hypoperfusion
▶
Repeat within 2–4 hours if elevated
Blood cultures
▶
Send before empiric antibiotics if bacterial sepsis considered
▶
Expected to be negative in HFRS
Troponin
▶
Elevated in myocarditis complication
▶
ECG abnormalities in 18–50% depending on strain and cohort
Diagnostic Tests
Scoring Systems
No validated HFRS-specific clinical scoring system exists
▶
Risk stratification based on clinical phase and severity markers
▶
Severity markers: platelet < 50 x10^9/L, creatinine > 350 micromol/L, shock
Multiorgan dysfunction (liver + kidney + coagulation) = ICU level care
Hemorrhage risk assessment
▶
Platelet nadir and coagulation profile
Active bleeding site identification
AKI staging using KDIGO criteria
▶
Stage 1: creatinine 1.5–1.9x baseline or rise > 26.5 micromol/L in 48 hours
Stage 2: creatinine 2.0–2.9x baseline
Stage 3: creatinine >= 3x baseline or >= 353.6 micromol/L or RRT initiated
MRI
Cardiac MRI indications in HFRS
▶
Suspected hantavirus-induced myocarditis
▶
Troponin elevation plus chest pain or ECG changes
Can detect myocardial edema (T2 mapping) and late gadolinium enhancement
CMR is the gold standard for myocarditis diagnosis
Late gadolinium enhancement pattern
▶
Non-ischemic (mid-myocardial or epicardial) distribution
Distinguishes myocarditis from ischemic injury
Timing considerations
▶
Defer MRI until hemodynamically stable
Gadolinium use with eGFR < 30: gadolinium-based agents increase NSF risk
Brain MRI if encephalopathy suspected
▶
Cerebral edema on DWI or FLAIR
▶
Posterior reversible encephalopathy syndrome (PRES) pattern reported
MRI superior to CT for posterior fossa and cortical lesions
CT
CT abdomen and pelvis
▶
Indications
▶
Severe abdominal pain requiring surgical exclusion
Suspected retroperitoneal hemorrhage
Expected findings in HFRS
▶
Bilateral renal enlargement
Perirenal fluid collections
Retroperitoneal hemorrhage in severe cases
Absence of surgical pathology (no perforation, no abscess)
CT findings supporting HFRS diagnosis over acute abdomen
▶
Large edematous kidneys with perirenal stranding
No free air, no bowel obstruction
Chest CT
▶
Interstitial infiltrates and bilateral pleural effusions
▶
Present in approximately 50% of Balkan HFRS cases
Differentiate pulmonary edema from ARDS pattern
Pulmonary edema
▶
Ground-glass opacification with perihilar predominance
Septal thickening
Ultrasound
Renal ultrasound
▶
First-line imaging for renal assessment
▶
Bilateral renal enlargement (kidneys > 12 cm in HFRS)
Increased cortical echogenicity reflecting edema and injury
Perirenal fluid collection
Rule out obstructive uropathy
▶
No hydronephrosis differentiates from obstruction
HFRS causes non-obstructive AKI
Subcapsular hematoma detection
▶
Spontaneous perinephric hemorrhage complication
Focused cardiac ultrasound
▶
Left ventricular function assessment
▶
Myocarditis: reduced EF
Pericardial effusion
Volume status assessment
▶
IVC collapsibility index for fluid responsiveness
Wall motion abnormalities in severe cases
Point-of-care lung ultrasound
▶
B-lines indicating pulmonary edema
▶
Bilateral distribution
Guides fluid management in oliguric phase
Pleural effusion
▶
Anechoic basal collections
Guides drainage decision if hemodynamically impactful
Disposition
ICU admission criteria
Mandatory ICU admission
▶
Hemodynamic shock requiring vasopressors
▶
Norepinephrine or vasopressin initiation
Respiratory failure requiring mechanical ventilation
▶
ARDS pattern on imaging
SpO2 < 90% despite high-flow oxygen
Severe AKI requiring renal replacement therapy
▶
Required in approximately 15% of Dobrava virus cases
Required in < 5% of Puumala virus cases
Multiorgan dysfunction syndrome
▶
Liver failure, DIC, cardiac compromise
General ward admission criteria
Ward-level admission
▶
Confirmed or suspected HFRS with any of the following
▶
Oliguria (urine output < 400 mL/day) or rising creatinine
Platelet < 100 x10^9/L
Inability to maintain oral hydration
Active hemorrhagic manifestations (epistaxis, GI bleeding)
Hypotension without vasopressor requirement
Severe abdominal pain requiring monitoring
30–50% of confirmed HFRS cases in Europe require hospitalization
Transfer criteria
Transfer to higher level of care
▶
Vasopressor need at a facility without ICU
▶
Stabilize then transfer with intensive monitoring
Need for CRRT not available at initial facility
▶
Nephrology center with dialysis access
Diagnostic uncertainty requiring ID or nephrology expertise
Discharge criteria
Copy
Safe for discharge when
▶
Hemodynamically stable
▶
BP normalized, no vasopressor dependence
Transitioning to diuretic or convalescent phase
▶
Urine output increasing, creatinine downtrending
Platelet count recovering (> 100 x10^9/L)
▶
No active hemorrhage
Tolerating oral intake
▶
Adequate outpatient follow-up arranged
Renal function recovering to near baseline
Follow-up planning
Copy
Mandatory outpatient follow-up
▶
Renal function check within 1–2 weeks post-discharge
▶
Creatinine, eGFR, urinalysis
Some patients develop chronic kidney disease
Ophthalmology if visual symptoms persist
▶
Transient myopia usually resolves spontaneously
Notify public health authorities
▶
Reportable disease in most countries
Exposure site investigation and rodent control
Treatment
Fluid management by phase
Febrile phase fluid strategy
▶
IV or oral hydration to maintain euvolemia
▶
Normal saline or lactated Ringer's
Target urine output 0.5–1 mL/kg/hour
Monitor for transition to capillary leak
Hypotensive phase fluid strategy
▶
Careful IV crystalloid resuscitation
▶
Crystalloid boluses 250–500 mL, reassess after each
Goal MAP >= 65 mmHg
Avoid excessive fluid — worsens pulmonary edema in oliguric phase
Vasopressors for refractory hypotension
▶
Norepinephrine: start 0.1–0.2 mcg/kg/min IV infusion
▶
Titrate 0.02–0.05 mcg/kg/min every 5–15 minutes
Target MAP >= 65 mmHg
Maximum dose 3 mcg/kg/min before adding second agent
Vasopressin adjunct: 0.03–0.04 units/min fixed dose
▶
Add when norepinephrine dose > 0.25 mcg/kg/min
Oliguric phase fluid strategy
▶
Fluid restriction
▶
Input equals output plus insensible losses (~500 mL/day)
Daily weights to guide restriction
Restrict sodium and potassium in diet
Indications for renal replacement therapy
▶
Refractory hyperkalemia > 6.5 mmol/L
Severe acidosis: pH < 7.15 or bicarbonate < 10 mmol/L
Volume overload with pulmonary edema refractory to diuretics
Uremic symptoms (encephalopathy, pericarditis)
BUN > 35 mmol/L in context of oliguric AKI
Diuretic phase fluid strategy
▶
Aggressive fluid and electrolyte repletion
▶
Match urine output with IV or oral fluids
Potassium replacement: IV or oral based on severity
Sodium monitoring — hyponatremia and hypernatremia both possible
Renal replacement therapy
Hemodialysis or CRRT selection
▶
CRRT preferred in hemodynamically unstable patients
▶
CVVHDF or CVVHF modality
Continuous filtration avoids large fluid shifts
Intermittent hemodialysis in hemodynamically stable patients
▶
3–4 sessions per week if chronic
Single session if acute hyperkalemia management
Duration
▶
Most HFRS AKI is reversible
Discontinue when urine output recovering and renal function improving
Antiviral therapy
Ribavirin — not routinely recommended
▶
Evidence for Hantaan virus (HTNV) in China
▶
One controlled trial showed reduced mortality (HTNV)
Dose if used: 33 mg/kg IV loading dose, then 16 mg/kg IV every 6 hours x4 days, then 8 mg/kg IV every 8 hours x6 days
Total course 10 days
Ineffective against Puumala virus (PUUV)
▶
Not recommended for European HFRS
No FDA or EMA approval for HFRS indication
Consult infectious disease before use
Supportive medications
Analgesia and antipyresis
▶
Acetaminophen preferred
▶
For fever and pain management
Avoid NSAIDs: nephrotoxic, inhibit platelet function
Avoid aspirin: platelet dysfunction in thrombocytopenic patient
Nephrotoxin avoidance
▶
Avoid aminoglycosides
▶
Use alternative antibiotics if bacterial coinfection suspected
Avoid contrast agents for imaging when possible
▶
Use ultrasound or non-contrast CT first
Avoid ACE inhibitors and ARBs during AKI
Hemorrhage management
▶
Platelet transfusion for active bleeding with platelet < 50 x10^9/L
▶
Threshold may be higher (< 100 x10^9/L) for invasive procedures
FFP and cryoprecipitate for DIC with active hemorrhage
▶
Avoid anticoagulants given hemorrhagic diathesis
Blood product transfusion
▶
pRBC for hemoglobin < 70–80 g/L or symptomatic anemia
Electrolyte management
Hyperkalemia management (oliguric phase)
▶
Potassium > 6 mmol/L with ECG changes
▶
Calcium gluconate 1 g IV over 5–10 minutes (membrane stabilization)
Sodium bicarbonate 50–100 mmol IV for metabolic acidosis correction
Insulin 10 units IV + dextrose 50% 50 mL IV
Kayexalate (sodium polystyrene sulfonate) 15–30 g orally or PR
Dialysis for refractory hyperkalemia
Hyponatremia management (febrile phase)
▶
Mild hyponatremia (Na 130–133 mmol/L): fluid restriction
▶
Monitor closely — predicts oliguric AKI development
Severe hyponatremia (Na < 125 mmol/L): hypertonic saline cautiously
▶
Correct at rate < 10 mmol/L per 24 hours to avoid osmotic demyelination
Special Populations
Pregnancy
HFRS in pregnancy overview
▶
Rare but reported — especially Puumala virus in Scandinavia
▶
Can be confused with HELLP syndrome or preeclampsia
Shared features: thrombocytopenia, hypertension, AKI, elevated LFTs
Distinguishing features from HELLP
▶
Exposure history to rodents
Fever and myalgia prominent in HFRS
Serology confirms diagnosis
Fetal risks
▶
Maternal AKI and hypotension increase fetal compromise risk
▶
Continuous fetal monitoring in hospital
Obstetrics consultation mandatory
Hantavirus RNA detected in placenta in some cases
▶
Vertical transmission not confirmed but cannot be excluded
Treatment modifications
▶
Ribavirin contraindicated in pregnancy
▶
Category X teratogen — avoid entirely
Treatment is supportive only
Vasopressors
▶
Norepinephrine preferred over phenylephrine for maternal hemodynamics
Use lowest effective dose
Fluid management
▶
Same phase-based principles apply
Extra caution with fluid overload — worsens uteroplacental flow
Geriatric
Age-related risks
▶
Older age independently associated with mortality in HFRS
▶
Reduced physiologic reserve for hemodynamic instability
Baseline CKD common — AKI superimposed on chronic disease
Comorbidity burden
▶
Hypertension and diabetes worsen outcomes
Polypharmacy — review all nephrotoxic medications on admission
Presentation differences
▶
Atypical or blunted fever response
▶
May present with confusion as dominant feature
Lower threshold to test for HFRS in unexplained AKI with thrombocytopenia
Dehydration and malnutrition at baseline
▶
Exacerbate capillary leak and oliguria severity
Management modifications
▶
More conservative fluid resuscitation
▶
Higher risk of pulmonary edema from cardiac diastolic dysfunction
Frequent reassessment of volume status
Earlier dialysis threshold
▶
Less renal reserve to tolerate prolonged severe AKI
Acetaminophen dose reduction
▶
Maximum 2 g/day if malnutrition or hepatic impairment
Pediatrics
Epidemiology in children
▶
HFRS less common in children than adults
▶
Puumala virus causes milder pediatric disease
Hantaan and Dobrava can cause severe pediatric disease in Asia and Balkans
Clinical course generally milder in young children
▶
Fatality rare with Puumala virus in children
Presentation differences
▶
Abdominal pain may dominate
▶
Misdiagnosed as appendicitis or mesenteric adenitis
Maintain high suspicion in endemic area with rodent exposure
Thrombocytopenia and hematuria similar to adult pattern
▶
Renal manifestations may be less severe
Dosing considerations
▶
Fluid resuscitation: 10–20 mL/kg isotonic crystalloid boluses
▶
Reassess after each bolus
Same oliguric phase fluid restriction principles apply (weight-based)
Norepinephrine: 0.1–2 mcg/kg/min IV
▶
Titrate to MAP appropriate for age
Ribavirin in children (if considered for HTNV)
▶
Weight-based dosing: consult infectious disease
Avoid in prepubertal girls if possible given teratogenic risk to future pregnancy
Background
Epidemiology
Global burden and distribution
▶
Approximately 150,000–200,000 cases of HFRS globally per year
▶
90% of cases occur in China (Hantaan and Seoul viruses)
Europe primarily affected by Puumala and Dobrava viruses
Case fatality rates by viral species
▶
Puumala (nephropathia epidemica): CFR approximately 1%
Seoul virus: CFR approximately 1%
Hantaan virus: CFR 5–15%
Dobrava virus: CFR 5–12%
Seasonal distribution
▶
Spring and autumn peaks in Europe (correlate with rodent population cycles)
China has two seasonal peaks: spring-summer (Hantaan) and winter (Seoul)
Demographic distribution
▶
Male predominance: male-to-female ratio approximately 2.6:1
Peak incidence in adults aged 20–50 years in occupational exposure settings
Natural reservoir and transmission
▶
Striped field mouse (Apodemus agrarius): Hantaan and Dobrava-Belgrade viruses
▶
Bank vole (Myodes glareolus): Puumala virus
Brown rat (Rattus norvegicus): Seoul virus
Transmission exclusively via inhalation of aerosolized infected rodent excreta
▶
No human-to-human transmission established for HFRS hantaviruses
Incubation period 2–6 weeks
Pathophysiology
Viral mechanism
▶
Hantaviruses target endothelial cells (primary)
▶
Integrin beta-3 is the cellular receptor
Capillary leak syndrome from endothelial dysfunction
No direct cytopathic effect — immunopathological injury
Immune response drives pathology
▶
CD8+ T-cell response peaks at symptom onset
Immunoblast production (visible on smear)
Cytokine storm contributes to capillary permeability
Renal pathophysiology
▶
Tubulointerstitial nephritis predominant histology
▶
Intense mononuclear infiltrate
Tubular epithelial cell apoptosis
Hemorrhagic necrosis in severe Hantaan and Dobrava cases
Glomerular involvement secondary
▶
Mesangial expansion, immune complex deposition
Proteinuria and hematuria
Acute tubular necrosis in severe oliguric phase
▶
Reversible in majority of cases
Thrombocytopenia mechanism
▶
Platelet activation and consumption
▶
Endothelial injury triggers platelet adhesion
Immune-mediated platelet destruction
Bone marrow suppression in severe disease
▶
Contributes to nadir
Therapeutic Considerations
No approved specific antiviral treatment for HFRS
▶
Supportive care is the cornerstone of management
▶
Phase-matched fluid management is most critical intervention
Avoidance of nephrotoxins
Ribavirin
▶
Showed mortality benefit in one Chinese RCT for HTNV
Not effective for Puumala virus (European HFRS)
Not routinely recommended; consult ID if considering
Investigational approaches
▶
Icatibant (bradykinin B2 receptor antagonist): compassionate use in severe European HFRS
Based on hypothesis that bradykinin contributes to capillary leak
No randomized controlled trial data for HFRS
Future therapeutic directions
▶
Monoclonal antibodies targeting hantavirus envelope glycoproteins
▶
Neutralizing antibodies in preclinical development
Hantavirus vaccines
▶
Inactivated vaccines available in China and Korea
Not approved in North America or Western Europe
Prevention and public health
▶
Rodent control measures reduce transmission
▶
Seal entry points in homes and storage buildings
Use N95 respirator when cleaning rodent-infested areas
Wet-mop rather than sweep or vacuum contaminated areas
No post-exposure prophylaxis established
Patient Discharge Instructions
copy discharge instructions
Copy
What you have been diagnosed with
▶
Hemorrhagic Fever with Renal Syndrome (HFRS)
▶
A viral infection caused by hantavirus
Spread by breathing in dust contaminated with rodent droppings, urine, or saliva
Not spread from person to person
Your kidneys were affected by this infection
▶
Your kidney function is improving but needs time to fully recover
▶
Recovery may take weeks to months
You may have more urine than usual for a week or two — this is normal
Drink plenty of fluids during the high-urination phase
Medications and activity
▶
Avoid anti-inflammatory pain medicines (ibuprofen, naproxen, aspirin)
▶
These can harm your kidneys
Use acetaminophen (Tylenol) for pain or fever
Avoid any new medications without checking with your doctor first
▶
Many medications are processed by the kidneys
No strenuous activity until cleared by your doctor
▶
Fatigue is common during recovery
Follow-up appointments are essential
▶
Blood and urine tests within 1–2 weeks to check kidney function
▶
Your doctor needs to see how your kidneys are recovering
If you had vision changes (blurry vision), see an eye doctor
▶
Usually resolves on its own
Return to the emergency department immediately if you develop
▶
Decreased urine output or no urine
▶
Dark, bloody, or foamy urine
Worsening shortness of breath
▶
Unable to lie flat due to breathing difficulty
Persistent vomiting or inability to drink fluids
▶
Signs of dehydration: dizziness, dry mouth, fast heart rate
New bleeding
▶
Nosebleeds, blood in stool, unusual bruising
Confusion, fainting, or severe weakness
Protecting yourself and others
▶
Do not clean rodent-infested areas without respiratory protection (N95 mask)
▶
Wet surfaces before cleaning (wet-mop, do not sweep)
Seal holes and gaps in your home to prevent rodent entry
Wash hands thoroughly after any outdoor activity in endemic areas
Inform public health authorities — your case must be reported
References
Guidelines and key sources
Vial PA, Ferrés M, Vial C, et al.
▶
Hantavirus in Humans: A Review of Clinical Aspects and Management
▶
The Lancet Infectious Diseases 2023
PMID 37105214
Abdoler EA, Malani PN.
▶
What Is Hantavirus?
▶
JAMA 2025
jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2025.5014
Avšič-Županc T, Saksida A, Korva M.
▶
Hantavirus Infections
▶
Clinical Microbiology and Infection 2019
PMID 24750436
Watson DC, Sargianou M, Papa A, et al.
▶
Epidemiology of Hantavirus Infections in Humans: A Comprehensive Global Overview
▶
Critical Reviews in Microbiology 2014
PMID 23607444
Pal E, Korva M, Resman Rus K, et al.
▶
Sequential Assessment of Clinical and Laboratory Parameters in Patients With HFRS
▶
PLoS One 2018
PMID 29791494
Supplementary references
Kitterer D, Greulich S, Grün S, et al.
▶
Electrocardiographic Abnormalities and Relative Bradycardia in Hantavirus-Induced Nephropathia Epidemica
▶
European Journal of Internal Medicine 2016
PMID 27296590
Koehler FC, Di Cristanziano V, Späth MR, et al.
▶
The Kidney in Hantavirus Infection
▶
Clinical Kidney Journal 2022
PMID 35756741
Sehgal A, Mehta S, Sahay K, et al.
▶
Hemorrhagic Fever With Renal Syndrome in Asia
▶
Viruses 2023
PMID 36851775
Rigby I, Michelen M, Dagens A, et al.
▶
Standard of Care for Viral Haemorrhagic Fevers: A Systematic Review
▶
Lancet Infectious Diseases 2023
PMID 36758568
Krumm P, Zitzelsberger T, Gawaz M, Greulich S.
▶
Young Patient With Hantavirus-Induced Myocarditis Detected by CMR
▶
BMC Infectious Diseases 2019
PMID 30612548
Ji H, Li K, Shang M, Wang Z, Liu Q.
▶
The 2016 Severe Floods and Incidence of HFRS in the Yangtze River Basin
▶
JAMA Network Open 2024
jamanetworkopen.com/fullarticle/10.1001/jamanetworkopen.2024.29682
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
Hantavirus (HFRS)