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Hantavirus General
- Family: Hantaviridae (formerly Bunyaviridae); ssRNA, segmented genome (3 segments)
- Rodent reservoirs â 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) â Asia + Europe (Old World hantaviruses)
- HPS (Hantavirus Pulmonary Syndrome / Hantavirus Cardiopulmonary Syndrome) â Americas (New World hantaviruses)
HFRS (Asia + Europe)
- Causative viruses:
- Hantaan (Korea, China) â severe form
- Seoul (worldwide, rats â urban)
- Puumala (Europe, voles) â nephropathia epidemica, milder
- Dobrava (Balkans) â severe
- Clinical 5 phases:
- Febrile (3-7 d): fever, malaise, abdominal pain, âdrunken faceâ facial flushing
- Hypotensive (hours-days): shock from vascular leak
- Oliguric (3-7 d): AKI, hypertension, edema, hemorrhage
- Polyuric (1-2 wk): recovery diuresis
- 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
HPS (Americas)
- Causative viruses:
- Sin Nombre virus (SNV) â main USA cause
- Black Creek Canal, Bayou, New York â other USA strains
- Andes â S America (rare person-to-person Argentina/Chile)
- Choclo â Panama
- Laguna Negra â 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 â 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)
1ïžâ£ Virology
Family Hantaviridae
- ssRNA, 3-segmented genome (S, M, L)
- Enveloped
- 50-100 nm spherical
- Endothelial cell tropism (vascular leak basis of disease)
Diversity
- 40+ identified species
- New species emerging
- Each species associated with specific rodent host
Tropism
- Endothelial cells
- Causes increased vascular permeability
- â Capillary leak + hemorrhage (HFRS) + pulmonary edema (HPS)
2ïžâ£ HFRS (Hemorrhagic Fever with Renal Syndrome)
Etiology
- Hantaan virus (Korea, China, E Russia) â severe form
- Seoul virus (worldwide; rats â urban) â moderate
- Puumala virus (Europe; bank voles) â milder (ânephropathia epidemicaâ)
- Dobrava-Belgrade virus (Balkans + E Europe) â severe
Reservoir
- Various rodents:
- Striped field mouse (Hantaan)
- Rat (Seoul) â urban setting
- Bank vole (Puumala)
- Yellow-necked mouse (Dobrava)
Epidemiology
- Asia + Europe main
- China + Korea + Russia + Europe
- Rural + agricultural settings
- Military (Korean War 1951 â first recognized)
- Seasonal: spring + fall peaks
Clinical â 5 Phases
Phase 1: Febrile (Days 1-7)
- Sudden fever (39-40°C)
- Severe headache, malaise, myalgia
- âDrunken faceâ facial flushing + conjunctival injection
- Abdominal pain
- Petechiae appear (axillary, palatal)
- Lab: thrombocytopenia, elevated creatinine
Phase 2: Hypotensive (Hours-Days)
- Vascular leak â shock
- Hypotension, tachycardia
- Capillary leak with pulmonary edema, pleural effusion
- Hemoconcentration
- Reversal often spontaneous within hours-days
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
Phase 4: Polyuric (1-2 Weeks)
- Diuresis (can be massive)
- Electrolyte derangement
- Risk of dehydration
Phase 5: Convalescent (Weeks-Months)
- Gradual return to normal
- Some persistent fatigue + mild renal dysfunction
Severity Range
- Hantaan: mortality ~ 5%
- Seoul: mortality 1-2%
- Puumala (nephropathia epidemica): mortality < 1%, mild
- Dobrava: mortality 10-15%
Diagnosis
- PCR of blood (early)
- IgM serology (high sensitivity in HFRS)
- IgG for past exposure
- Multiplex hantavirus serology
- BSL-3 lab
Treatment
- Supportive:
- IV fluid management (tricky â vascular leak then oliguric phase)
- Pressors if shock
- Dialysis if AKI requires (~ 30%)
- Mechanical ventilation if respiratory failure
- Blood products if bleeding
- Ribavirin â limited evidence; possibly reduce mortality in severe Hantaan
- ICU monitoring
Vaccine
- Hantavax (Korea) â inactivated, 2-3 dose series
- Used in Korea + parts of China
- Limited availability elsewhere
3ïžâ£ HPS (Hantavirus Pulmonary Syndrome)
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
Etiology + Reservoir
- Sin Nombre virus (SNV) â 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
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 â aerosolize)
- Camping, hunting
- Native American reservations (USA)
- Agricultural
Clinical (Rapid Progression)
Prodrome (3-5 Days)
- Fever, malaise, severe myalgia (lower back + thighs)
- Headache
- Cough (often dry)
- GI symptoms
Cardiopulmonary Phase (Sudden Deterioration)
- Onset of dyspnea + tachypnea
- Rapid progression within hours:
- Severe pulmonary edema (non-cardiogenic)
- Hypoxia
- Cardiogenic shock (HCPS â Hantavirus Cardiopulmonary Syndrome)
- Severe lactic acidosis
- Hemorrhage less prominent than HFRS
- AKI less prominent
Severity
- Most patients require:
- Mechanical ventilation
- Vasopressors
- ECMO consideration (life-saving)
- Mortality 30-50%
Diagnosis
- PCR of blood (acute)
- IgM serology (high sensitivity)
- BSL-3
- Differential: ARDS from other causes, sepsis, PE
Treatment
- Aggressive supportive care
- ECMO = critical for severe (consider transferring to ECMO center)
- Vasopressors
- Mechanical ventilation
- IV fluid management (cautious â pulmonary edema)
- No specific antiviral licensed
- Ribavirin tried in HPS â less effective than in HFRS
- Investigational mAbs in development
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
4ïžâ£ Prevention
Rodent Control
- Indoor rodent exclusion (seal cracks, screens)
- Trap + remove rodents
- Food storage (sealed containers)
- Trash management
- Pet food storage
Avoid Aerosolization
- Wet down rodent-infested areas before cleaning (donât sweep / vacuum dry)
- PPE (mask, gloves) when cleaning
- Disinfect surfaces with bleach
- Air out previously sealed structures (cabins) before entry
Travel + Outdoor
- Cabin / camping precautions
- Donât pitch tent near rodent burrows
- Store food in sealed containers
Healthcare PPE
- Standard precautions for HFRS / HPS
- Andes virus contact + droplet precautions (rare exception to no person-to-person rule)
Surveillance
- éå ± mandatory many countries
- Rodent surveillance
- Outbreak investigation