221.1 🎓 醫學生版

221.1.0.1 📌 一頁重點

221.1.0.1.1 Yellow Fever (YF)

• Virus: ssRNA flavivirus
• Vectors: Aedes aegypti (urban), Haemagogus + Sabethes (sylvatic)
• Reservoir: monkeys + humans
• Geography: sub-Saharan Africa + S America endemic; not Asia (mystery — competent vectors present)
• Clinical:
  • Asymptomatic / mild (most): 3-day febrile illness
  • Severe: 15-25% develop biphasic illness — initial improvement → toxic phase with hepatic + renal failure + hemorrhage (mortality 20-50%)
  • “Yellow” fever: jaundice (hence name)
• Diagnosis: PCR (early) + IgM serology
• Treatment: supportive
• Vaccine: YF-17D (live attenuated) — single dose, lifelong protection (>10 yr per WHO 2024); routine in endemic + travelers; rare YEL-AVD (vaccine-associated viscerotropic disease, especially elderly)

221.1.0.1.2 Japanese Encephalitis (JE)

• Virus: ssRNA flavivirus
• Vectors: Culex tritaeniorhynchus (rice paddy mosquito)
• Reservoir: pigs (amplifying) + waterbirds (maintenance)
• Geography: Asia + N Australia rural endemic; especially India + China + SE Asia
• Burden: ~ 70,000 cases/yr globally; mortality 25%; sequelae in 50% survivors
• Clinical:
  • Asymptomatic / mild (99% — only 1% develop neurological disease)
  • Encephalitis (severe): fever + altered mental status + seizures + focal neurological signs + extrapyramidal movement
  • Children + elderly mortality higher
• Diagnosis: CSF JE PCR + IgM; serum IgM
• Treatment: supportive
• Vaccines:
  • JE-VC (Ixiaro) — inactivated, 2-dose series (USA + EU)
  • SA 14-14-2 live attenuated (China + Asia mass campaigns)
  • CD-JEVAX (chimeric live attenuated, single dose)
  • Routine pediatric in endemic Asia + travelers
• Taiwan: vaccination universal pediatric; sporadic adult cases

221.1.0.1.3 West Nile Virus (WNV)

• Virus: ssRNA flavivirus
• Vectors: Culex mosquitoes
• Reservoir: birds (especially corvids — crows, jays, ravens) + humans dead-end host
• Geography: USA + Canada + Europe + parts of Africa + Middle East + Asia + Australia (worldwide expanded since 1999 NYC introduction)
• Burden USA: 2700+ cases + 200+ deaths in 2023; annual epidemic
• Clinical:
  • Asymptomatic (~ 80%)
  • West Nile Fever (20%): febrile illness with rash + LAP + myalgia
  • Neuroinvasive Disease (< 1% — but mortality 10-20%): meningitis, encephalitis, acute flaccid paralysis (polio-like — anterior horn cell)
  • Elderly highest risk for severe (CD4 not relevant; age + comorbidities)
• Diagnosis: CSF WNV PCR + IgM; serum IgM
• Treatment: supportive; IVIG investigational
• Prevention: mosquito control + DEET; no licensed human vaccine (equine vaccines available)

221.1.0.1.4 Tick-Borne Encephalitis (TBE)

• Flavivirus
• Ixodes ricinus / persulcatus tick
• Europe + Russia + Asia
• Biphasic: fever → encephalitis after 1-2 wk asymptomatic
• TBE vaccine in endemic regions (FSME-IMMUN, Encepur)
• Treatment: supportive

221.1.0.1.5 Powassan Virus

• Emerging tick-borne flavivirus
• USA Northeast + Great Lakes + Russia/Asia
• Ixodes scapularis / cookei tick
• Transmits within 15 minutes (vs Lyme 36-48 hr)
• Severe encephalitis (mortality 10-15%)
• Climate change driving expansion
• No vaccine; supportive

221.1.0.1.6 Other Flaviviruses

• Murray Valley encephalitis (Australia)
• St. Louis encephalitis (Americas)
• Usutu virus (Europe)
• Kyasanur Forest disease (India)
• Omsk hemorrhagic fever (Russia)

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221.1.0.2 1️⃣ Yellow Fever

221.1.0.2.1 Epidemiology

• Sub-Saharan Africa: > 90% global burden (Nigeria, Cameroon, DRC, etc.)
• South America: Brazil + Peru + Colombia + Venezuela + Bolivia
• Asia + Pacific: not endemic (mystery — competent vectors present; theories: immunity from dengue cross-protection, behavioral, ecological)
• 200,000+ cases + 30,000+ deaths/yr (WHO estimates; mostly Africa)
• 2016-2018 Angola + DRC outbreak (largest in decades)
• 2019-2023 Brazil sylvatic outbreaks

221.1.0.2.2 Vectors + Cycles

221.1.0.2.2.1 Urban Cycle

• Aedes aegypti
• Human-mosquito-human
• Major outbreaks
• Cities

221.1.0.2.2.2 Sylvatic Cycle

• Haemagogus, Sabethes (S America), Aedes africanus (Africa)
• Monkey-mosquito-monkey
• Forest workers (loggers, farmers) get bitten

221.1.0.2.2.3 Intermediate (Savanna) Cycle

• Africa: Aedes spp.
• Both monkeys + humans

221.1.0.2.3 Clinical

221.1.0.2.3.1 Phase 1: Febrile (Days 1-3)

• High fever, severe headache, backache, myalgia
• Faget sign (relative bradycardia)
• Nausea, vomiting
• Self-limited in most

221.1.0.2.3.2 Phase 2: Remission (Day 3-4)

• Brief defervescence + improvement
• ~ 85% recover

221.1.0.2.3.3 Phase 3: Toxic (Day 4+)

• 15-25% enter toxic phase
• Jaundice (hence “yellow”)
• Hemorrhage (gums, GI, ecchymoses)
• Black vomit (hematemesis)
• AKI
• Encephalopathy
• Multi-organ failure
• Mortality 20-50%

221.1.0.2.4 Diagnosis

• PCR of blood (acute, first 5-7 days)
• IgM ELISA after day 5
• PRNT for confirmation
• Clinical context in endemic

221.1.0.2.5 Treatment

• Supportive (no specific antiviral)
• Hospitalization
• Fluid + electrolyte
• Transfusion for severe bleeding
• ICU + dialysis if needed
• Liver transplant rare success

221.1.0.2.6 Vaccine — YF-17D

• Live attenuated, single dose
• Developed 1937 (Theiler — Nobel Prize)
• Lifelong protection (WHO 2024 — no boosters needed for most travelers)

• 95% efficacy

• International Certificate of Vaccination required for travel to + from endemic countries
• 11 yr historic boost requirement removed (2016)

221.1.0.2.7 Adverse Events

• Mild reaction common (fever, malaise)
• YEL-AVD (Vaccine-Associated Viscerotropic Disease):
  • Rare (0.3-0.4 per 100,000 vaccinations)
  • Severe organ failure mimicking yellow fever
  • Elderly (≥ 60 yr) highest risk
  • Mortality 60%+
• YEL-AND (Vaccine-Associated Neurological Disease):
  • Even rarer
  • Encephalitis, GBS
  • Recovery usually
• Avoid in: immunocompromised, pregnancy (case-by-case for travel), allergy egg

221.1.0.2.8 Endemic Childhood Immunization

• WHO routine pediatric (12-15 mo) in endemic countries
• Mass vaccination campaigns for outbreaks
• Cabotegravir LA + ART for outbreak control

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221.1.0.3 2️⃣ Japanese Encephalitis (JE)

221.1.0.3.1 Epidemiology

• Asia + N Australia rural endemic
• India + China + SE Asia + Korea + Japan + Indonesia
• ~ 68,000 cases globally/yr
• Mortality 25%
• 50% of survivors have neurological sequelae
• Children + elderly highest risk
• Rice paddy areas + rainy season

221.1.0.3.2 Vectors + Reservoir

• Culex tritaeniorhynchus (rice paddy mosquito; outdoor evening biter)
• Pigs amplifying host (high viremia)
• Waterbirds (egrets, herons) maintenance host
• Humans dead-end

221.1.0.3.3 Clinical

221.1.0.3.3.1 Asymptomatic / Mild (99%)

• Brief febrile illness or asymptomatic

221.1.0.3.3.2 Encephalitis (1%)

• Fever + altered mental status
• Seizures
• Extrapyramidal movement (cogwheel rigidity, masked face, tremor — parkinsonism-like)
• Focal neurological signs
• Cranial nerve palsies
• Coma

221.1.0.3.4 Severity

• Mortality 25% in encephalitic cases
• 50% sequelae: motor weakness, cognitive impairment, behavior change

221.1.0.3.5 Diagnosis

• CSF JE PCR + IgM
• Serum IgM
• Imaging: MRI thalamic + basal ganglia + cerebellar lesions

221.1.0.3.6 Treatment

• Supportive
• Anticonvulsants
• ICU
• No specific antiviral

221.1.0.3.7 Vaccines

221.1.0.3.7.1 JE-VC (Ixiaro, IXIARO)

• Inactivated cell-culture derived
• 2-dose series (0 + 28 d)
• USA + EU + travelers
• Adult only (≥ 18 yr; some countries pediatric formulations)
• Booster q1-5 yr based on exposure
• Safety profile excellent

221.1.0.3.7.2 SA 14-14-2 Live Attenuated

• China + Asia mass campaigns
• Cheaper, mass deployment
• Pediatric primary
• Single dose

221.1.0.3.7.3 CD-JEVAX (Chimeric)

• Yellow fever 17D backbone + JE
• Live attenuated
• Single dose
• Approved Australia + others

221.1.0.3.8 Prevention

• Mosquito avoidance (evening DEET, bed nets)
• Avoid rice paddy areas at dusk
• Vaccination for travelers > 1 month in endemic + rural; outbreak response
• 公費 routine pediatric in endemic Asia + Taiwan

221.1.0.3.9 Taiwan

• 公費 pediatric routine
• Sporadic adult cases (rural, agricultural exposure)
• Vector control ongoing

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221.1.0.4 3️⃣ West Nile Virus (WNV)

221.1.0.4.1 Epidemiology

• 1937 Uganda (named after West Nile district)
• 1999 NYC introduction to USA (crow die-off + human encephalitis cluster)
• Spread across USA + Canada
• Now worldwide except Antarctica
• USA 2023: 2700+ cases + 200+ deaths
• Annual seasonal epidemic (summer + fall)
• Europe + Russia + Middle East + Africa + Australia

221.1.0.4.2 Vectors + Reservoir

• Culex mosquitoes (multiple species)
• Birds (especially corvids — crows, jays, ravens) = reservoir
• Crows die from WNV (used as sentinel surveillance)
• Humans + horses = dead-end hosts

221.1.0.4.3 Other Transmission Routes

• Blood transfusion (now screened)
• Organ transplant
• Vertical (rare)
• Breast milk (theoretical)
• Lab exposures

221.1.0.4.4 Clinical

221.1.0.4.4.1 Asymptomatic (80%)

221.1.0.4.4.2 West Nile Fever (20%)

• Fever, fatigue, headache, myalgia, arthralgia
• Maculopapular rash (often trunk, fading)
• LAP
• Self-limited 1-2 weeks
• Fatigue may persist months

221.1.0.4.4.3 Neuroinvasive Disease (< 1% — but ~ 30-40% of reported cases)

• Higher in elderly + immunocompromise + organ transplant
• Meningitis: fever + headache + meningismus
• Encephalitis: + altered mental status + seizures + focal signs
• Acute Flaccid Paralysis: anterior horn cell involvement, polio-like, asymmetric
• Movement disorders (tremor, parkinsonism)
• Mortality 10-20% of neuroinvasive
• Long-term sequelae common in survivors

221.1.0.4.5 Diagnosis

• CSF WNV PCR (low sens in late infection — Ab clears virus)
• CSF IgM (high sens, definitive diagnostic in CSF)
• Serum IgM (positive 8 days post-onset, persists year)
• Quantitative PCR of blood (early)
• Cross-reactivity with other flaviviruses (Zika, dengue, JE) — PRNT for confirmation

221.1.0.4.6 Treatment

• Supportive
• No specific antiviral
• IVIG investigational (positive results in HIG-WNV study small)
• ICU for severe neuroinvasive
• Long rehabilitation for sequelae

221.1.0.4.7 Prevention

• Mosquito control (Culex)
• DEET + protective clothing
• Reduce outdoor activity dusk/dawn
• Window screens
• Blood + organ donor screening (USA)
• No licensed human vaccine (equine vaccines effective)
• Several human vaccines in trials

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221.1.0.5 4️⃣ Tick-Borne Encephalitis (TBE)

221.1.0.5.1 Epidemiology

• Europe + Russia + Asia
• Ixodes ricinus (W Europe) + Ixodes persulcatus (E Europe + Asia)
• Spring + summer + fall
• Increasing incidence (climate change + outdoor activities)

221.1.0.5.2 Reservoir

• Small mammals (rodents, hedgehogs, deer)
• Birds

221.1.0.5.3 Clinical (Biphasic)

221.1.0.5.3.1 Phase 1: Febrile (Days 1-7)

• Fever, headache, myalgia, fatigue
• 1-2 wk asymptomatic interval

221.1.0.5.3.2 Phase 2: CNS

• 1-2 wk after first phase
• Meningitis (mild)
• Encephalitis (severe)
• Myelitis (motor weakness)
• 50% sequelae

221.1.0.5.4 Severity

• Western strains: mortality 1-2%, fewer sequelae
• Eastern strains: mortality 20%+, more sequelae

221.1.0.5.5 Treatment

• Supportive
• No antiviral

221.1.0.5.6 Vaccines

• FSME-IMMUN, Encepur, TicoVac — inactivated, 3-dose series + boosters
• Routine in endemic Europe (Austria, Germany, Russia, Czech, Switzerland)
• Travelers to endemic areas

221.1.0.5.7 Prevention

• Tick avoidance
• Permethrin clothing
• DEET
• Tick checks
• Remove ticks promptly

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221.1.0.6 5️⃣ Powassan Virus

221.1.0.6.1 Epidemiology

• Ixodes scapularis / cookei tick
• USA Northeast + Great Lakes + Wisconsin + Minnesota
• Russia + Asia (Eurasian lineage)
• 2024-2025 USA increasing cases

221.1.0.6.2 Unique Features

• Transmits within 15 minutes of tick attachment (vs Lyme 36-48 hr)
• Severe disease prevalent
• Mortality 10-15%; long sequelae in 50% survivors

221.1.0.6.3 Clinical

• Encephalitis primarily
• Meningitis
• Acute flaccid paralysis

221.1.0.6.4 Diagnosis

• CSF Powassan PCR + IgM
• Serum IgM
• Cross-reactivity considerations

221.1.0.6.5 Treatment

• Supportive
• IVIG investigational
• No specific antiviral

221.1.0.6.6 Prevention

• Tick avoidance (especially relevant since transmits quickly)
• No vaccine

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221.1.0.7 6️⃣ Other Flaviviruses

221.1.0.7.1 Murray Valley Encephalitis (Australia)

• Northern Australia + PNG
• Culex mosquito
• Rare but severe encephalitis
• Mortality 15-25%

221.1.0.7.2 St. Louis Encephalitis (Americas)

• USA + Central + South America
• Culex mosquito
• Less common since WNV epidemic
• Mostly mild

221.1.0.7.3 Usutu Virus (Europe)

• Africa origin, spread Europe 2000s
• Culex mosquito
• Bird die-offs (blackbirds)
• Rare human disease
• Cross-reacts with WNV

221.1.0.7.4 Kyasanur Forest Disease (KFD, India)

• Tick-borne flavivirus (Haemaphysalis spinigera)
• Forest monkey reservoir + human
• Hemorrhagic fever
• Vaccine available (limited supply)

221.1.0.7.5 Omsk Hemorrhagic Fever (Russia)

• Tick + muskrat reservoir
• Mortality 1-3%

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