224.1 🎓 醫孞生版

224.1.0.1 📌 䞀頁重點

224.1.0.1.1 Hantavirus General
  • Family: Hantaviridae (formerly Bunyaviridae); ssRNA, segmented genome (3 segments)
  • Rodent reservoirs — each hantavirus species has specific rodent host
  • Transmission: aerosolized rodent excreta inhalation (urine, feces, saliva); occasional rodent bites
  • NOT person-to-person (except Andes virus rare instances in S America)
  • 2 Major Syndromes:
    • HFRS (Hemorrhagic Fever with Renal Syndrome) — Asia + Europe (Old World hantaviruses)
    • HPS (Hantavirus Pulmonary Syndrome / Hantavirus Cardiopulmonary Syndrome) — Americas (New World hantaviruses)
224.1.0.1.2 HFRS (Asia + Europe)
  • Causative viruses:
    • Hantaan (Korea, China) — severe form
    • Seoul (worldwide, rats — urban)
    • Puumala (Europe, voles) — nephropathia epidemica, milder
    • Dobrava (Balkans) — severe
  • Clinical 5 phases:
    1. Febrile (3-7 d): fever, malaise, abdominal pain, “drunken face” facial flushing
    2. Hypotensive (hours-days): shock from vascular leak
    3. Oliguric (3-7 d): AKI, hypertension, edema, hemorrhage
    4. Polyuric (1-2 wk): recovery diuresis
    5. Convalescent (weeks-months): gradual recovery
  • Mortality: 5% Hantaan; < 1% Puumala
  • Treatment: supportive; ribavirin if severe (limited evidence)
  • Vaccine: Hantavax (Korea), inactivated, for endemic Korea + Asia
224.1.0.1.3 HPS (Americas)
  • Causative viruses:
    • Sin Nombre virus (SNV) — main USA cause
    • Black Creek Canal, Bayou, New York — other USA strains
    • Andes — S America (rare person-to-person Argentina/Chile)
    • Choclo — Panama
    • Laguna Negra — Paraguay
  • Reservoir: deer mouse (Peromyscus maniculatus) for Sin Nombre; other rodents elsewhere
  • Risk Settings:
    • Cabins, rural homes
    • Outdoor workers (camping, hunting)
    • Rodent infestation
    • USA Four Corners region historically (1993 Sin Nombre discovery)
  • Clinical:
    • Prodrome (3-5 d): fever, myalgia, malaise, headache
    • Cardiopulmonary phase: cough, dyspnea, rapid progression to severe pulmonary edema + shock (HCPS — Hantavirus Cardiopulmonary Syndrome)
    • Mortality 30-50%
  • Treatment: aggressive supportive care + ECMO for severe pulmonary failure (lifesaving)
  • No specific antiviral licensed (ribavirin tried, less effective for HPS than HFRS)

224.1.0.2 1⃣ Virology

224.1.0.2.1 Family Hantaviridae
  • ssRNA, 3-segmented genome (S, M, L)
  • Enveloped
  • 50-100 nm spherical
  • Endothelial cell tropism (vascular leak basis of disease)
224.1.0.2.2 Diversity
  • 40+ identified species
  • New species emerging
  • Each species associated with specific rodent host
224.1.0.2.3 Tropism
  • Endothelial cells
  • Causes increased vascular permeability
  • → Capillary leak + hemorrhage (HFRS) + pulmonary edema (HPS)

224.1.0.3 2⃣ HFRS (Hemorrhagic Fever with Renal Syndrome)

224.1.0.3.1 Etiology
  • Hantaan virus (Korea, China, E Russia) — severe form
  • Seoul virus (worldwide; rats — urban) — moderate
  • Puumala virus (Europe; bank voles) — milder (“nephropathia epidemica”)
  • Dobrava-Belgrade virus (Balkans + E Europe) — severe
224.1.0.3.2 Reservoir
  • Various rodents:
    • Striped field mouse (Hantaan)
    • Rat (Seoul) — urban setting
    • Bank vole (Puumala)
    • Yellow-necked mouse (Dobrava)
224.1.0.3.3 Epidemiology
  • Asia + Europe main
  • China + Korea + Russia + Europe
  • Rural + agricultural settings
  • Military (Korean War 1951 — first recognized)
  • Seasonal: spring + fall peaks
224.1.0.3.4 Clinical — 5 Phases
224.1.0.3.4.1 Phase 1: Febrile (Days 1-7)
  • Sudden fever (39-40°C)
  • Severe headache, malaise, myalgia
  • “Drunken face” facial flushing + conjunctival injection
  • Abdominal pain
  • Petechiae appear (axillary, palatal)
  • Lab: thrombocytopenia, elevated creatinine
224.1.0.3.4.2 Phase 2: Hypotensive (Hours-Days)
  • Vascular leak → shock
  • Hypotension, tachycardia
  • Capillary leak with pulmonary edema, pleural effusion
  • Hemoconcentration
  • Reversal often spontaneous within hours-days
224.1.0.3.4.3 Phase 3: Oliguric (3-7 Days)
  • Acute kidney injury (often severe)
  • Anuria possible
  • Hypertension (paradoxical)
  • Pulmonary edema
  • Hemorrhage (GI, skin)
  • Cerebral edema
  • This is the lethal phase
224.1.0.3.4.4 Phase 4: Polyuric (1-2 Weeks)
  • Diuresis (can be massive)
  • Electrolyte derangement
  • Risk of dehydration
224.1.0.3.4.5 Phase 5: Convalescent (Weeks-Months)
  • Gradual return to normal
  • Some persistent fatigue + mild renal dysfunction
224.1.0.3.5 Severity Range
  • Hantaan: mortality ~ 5%
  • Seoul: mortality 1-2%
  • Puumala (nephropathia epidemica): mortality < 1%, mild
  • Dobrava: mortality 10-15%
224.1.0.3.6 Diagnosis
  • PCR of blood (early)
  • IgM serology (high sensitivity in HFRS)
  • IgG for past exposure
  • Multiplex hantavirus serology
  • BSL-3 lab
224.1.0.3.7 Treatment
  • Supportive:
    • IV fluid management (tricky — vascular leak then oliguric phase)
    • Pressors if shock
    • Dialysis if AKI requires (~ 30%)
    • Mechanical ventilation if respiratory failure
    • Blood products if bleeding
  • Ribavirin — limited evidence; possibly reduce mortality in severe Hantaan
  • ICU monitoring
224.1.0.3.8 Vaccine
  • Hantavax (Korea) — inactivated, 2-3 dose series
  • Used in Korea + parts of China
  • Limited availability elsewhere

224.1.0.4 3⃣ HPS (Hantavirus Pulmonary Syndrome)

224.1.0.4.1 Discovery
  • 1993 USA Four Corners region (Arizona, Colorado, New Mexico, Utah)
  • Cluster of young Native Americans with rapid-onset pulmonary edema + shock
  • Sin Nombre virus identified
  • Severe presentation distinct from HFRS
224.1.0.4.2 Etiology + Reservoir
  • Sin Nombre virus (SNV) — USA main
  • Other USA: Black Creek Canal, Bayou, New York
  • S America: Andes (most severe; person-to-person Argentina/Chile rare); Choclo (Panama); Laguna Negra (Paraguay)
  • Reservoir: Deer mouse (Peromyscus maniculatus) for SNV
  • Other rodents for other strains
224.1.0.4.3 Epidemiology
  • 1993 discovery
  • USA: ~ 800 cases since 1993
  • S America: thousands of cases (more common than USA)
  • Risk:
    • Rural / cabin / outdoor settings
    • Rodent infestation
    • Cleaning rodent-contaminated areas (sweeping, vacuuming → aerosolize)
    • Camping, hunting
    • Native American reservations (USA)
    • Agricultural
224.1.0.4.4 Clinical (Rapid Progression)
224.1.0.4.4.1 Prodrome (3-5 Days)
  • Fever, malaise, severe myalgia (lower back + thighs)
  • Headache
  • Cough (often dry)
  • GI symptoms
224.1.0.4.4.2 Cardiopulmonary Phase (Sudden Deterioration)
  • Onset of dyspnea + tachypnea
  • Rapid progression within hours:
    • Severe pulmonary edema (non-cardiogenic)
    • Hypoxia
    • Cardiogenic shock (HCPS — Hantavirus Cardiopulmonary Syndrome)
    • Severe lactic acidosis
  • Hemorrhage less prominent than HFRS
  • AKI less prominent
224.1.0.4.4.3 Severity
  • Most patients require:
    • Mechanical ventilation
    • Vasopressors
    • ECMO consideration (life-saving)
  • Mortality 30-50%
224.1.0.4.5 Diagnosis
  • PCR of blood (acute)
  • IgM serology (high sensitivity)
  • BSL-3
  • Differential: ARDS from other causes, sepsis, PE
224.1.0.4.6 Treatment
  • Aggressive supportive care
  • ECMO = critical for severe (consider transferring to ECMO center)
  • Vasopressors
  • Mechanical ventilation
  • IV fluid management (cautious — pulmonary edema)
  • No specific antiviral licensed
  • Ribavirin tried in HPS — less effective than in HFRS
  • Investigational mAbs in development
224.1.0.4.7 Special: Andes Virus Person-to-Person
  • Rare documented in Argentina + Chile
  • Family + healthcare clusters
  • PPE precautions for caregivers (unique among hantaviruses)
  • Mostly mucocutaneous + close-contact transmission

224.1.0.5 4⃣ Prevention

224.1.0.5.1 Rodent Control
  • Indoor rodent exclusion (seal cracks, screens)
  • Trap + remove rodents
  • Food storage (sealed containers)
  • Trash management
  • Pet food storage
224.1.0.5.2 Avoid Aerosolization
  • Wet down rodent-infested areas before cleaning (don’t sweep / vacuum dry)
  • PPE (mask, gloves) when cleaning
  • Disinfect surfaces with bleach
  • Air out previously sealed structures (cabins) before entry
224.1.0.5.3 Travel + Outdoor
  • Cabin / camping precautions
  • Don’t pitch tent near rodent burrows
  • Store food in sealed containers
224.1.0.5.4 Healthcare PPE
  • Standard precautions for HFRS / HPS
  • Andes virus contact + droplet precautions (rare exception to no person-to-person rule)
224.1.0.5.5 Surveillance
  • 通報 mandatory many countries
  • Rodent surveillance
  • Outbreak investigation