211.1 🎓 醫孞生版

211.1.0.1 📌 䞀頁重點

  • Enteroviruses: ssRNA Picornaviridae, > 100 serotypes
  • Groups:
    • Poliovirus (1, 2, 3) — nearly eradicated
    • Coxsackie A (24 serotypes) — herpangina, HFMD (A16)
    • Coxsackie B (6 serotypes) — myocarditis, pleurodynia, neonatal sepsis
    • Echovirus (28 serotypes) — aseptic meningitis main
    • EV-71 — severe HFMD with neurologic complications (Asia, Taiwan)
    • EV-D68 — acute flaccid myelitis + asthma exacerbation (Ch 205)
  • Transmission: fecal-oral primarily; respiratory droplet; vertical (neonatal)
  • Clinical Forms:
    • Asymptomatic (most)
    • Mild URI (common cold-like)
    • Aseptic meningitis (#1 viral meningitis cause)
    • Encephalitis (rare)
    • Hand-Foot-Mouth Disease (HFMD) — Coxsackie A16, EV-71
    • Herpangina (oral vesicles, Coxsackie A)
    • Pleurodynia (Bornholm disease) — Coxsackie B
    • Myocarditis + pericarditis — Coxsackie B mostly
    • Neonatal sepsis — severe systemic; multi-organ failure
    • Pancreatitis — Coxsackie B
    • Conjunctivitis — EV-70, Coxsackie A24
    • Acute Flaccid Myelitis (AFM) — EV-D68, EV-71 (polio-like)
  • Polio:
    • Nearly eradicated globally (WHO Global Polio Eradication Initiative)
    • 2024-2025: Pakistan + Afghanistan = only countries with wild polio (WPV1)
    • Vaccine-derived polio (cVDPV2) outbreaks in vaccine-gap regions (Africa)
    • 2022 NYS USA: paralytic case from imported cVDPV2 — wake-up call
    • 2024 wastewater surveillance UK + US detecting strains
  • Diagnosis: PCR (CSF, throat, stool, blood), serology
  • Treatment: supportive; pleconaril, pocapavir in clinical trials
  • Vaccines:
    • OPV (Oral Polio Vaccine) — live attenuated, mass administration, rare VAPP
    • IPV (Inactivated Polio Vaccine) — universal in developed countries
    • bOPV (bivalent, types 1+3 since 2016 — type 2 removed due cVDPV2 risk)
    • nOPV2 (novel oral vaccine type 2) — for cVDPV2 outbreaks
    • EV-71 vaccines (China + Taiwan licensed) for HFMD outbreaks

211.1.0.2 1⃣ Virology

  • Picornaviridae family
  • ssRNA, ~ 7-8 kb
  • Non-enveloped (resistant to alcohol, soap; environmental stability)

  • 100 human enteroviruses

  • 4 species: A, B, C, D
  • Receptors variable: CAR (coxsackie-adenovirus), DAF, PVR (poliovirus)
211.1.0.2.1 Replication
  • Fecal-oral primarily
  • Replicate in gut + tonsils
  • Viremia → spread to target organs (CNS, heart, muscle, etc.)
  • Long fecal shedding (weeks)

211.1.0.3 2⃣ Specific Diseases

211.1.0.3.1 Aseptic Meningitis
  • Enteroviruses #1 cause of viral aseptic meningitis (especially Echovirus + Coxsackie B)
  • Children + young adults
  • Summer + early fall (warm months)
  • Sx: fever + headache + meningismus + photophobia
  • LP: lymphocytic pleocytosis, normal glucose, mildly elevated protein
  • CSF PCR diagnostic
  • Self-limited 1-2 wk
  • Supportive management
211.1.0.3.2 Encephalitis (Rare)
  • Severe in immunocompromise (X-linked agammaglobulinemia — chronic enteroviral encephalitis)
  • IVIG for chronic cases
  • Pocapavir (capsid inhibitor) — investigational
211.1.0.3.3 Hand-Foot-Mouth Disease (HFMD)
  • Coxsackie A16 classic
  • EV-71 more severe (Asia, Taiwan)
  • Children < 5 yr
  • Oral vesicles + erosions
  • Vesicular rash on hands, feet, buttocks
  • Fever
  • Self-limited 7-10d in classic A16
  • EV-71 complications:
    • Brainstem encephalitis
    • Pulmonary edema
    • Myocarditis
    • High mortality in severe
  • Taiwan 1998 outbreak: 70+ pediatric deaths
  • Active surveillance + vaccine implemented
211.1.0.3.4 Herpangina
  • Coxsackie A (usually)
  • Oral vesicles (posterior pharynx) + fever
  • Often distinct from HFMD (no hands/feet involvement)
  • Self-limited
211.1.0.3.5 Pleurodynia (Bornholm Disease)
  • Coxsackie B
  • Sudden severe pleuritic chest pain + fever
  • “Devil’s grip” name
  • Adolescent + young adult
  • Self-limited 3-5 days
211.1.0.3.6 Myocarditis + Pericarditis
  • Coxsackie B mainly (also other enteroviruses)
  • Fever + chest pain + heart failure
  • Adolescent + young adult
  • Severe → cardiogenic shock + dilated cardiomyopathy
  • Treatment: supportive, immunosuppression for severe immune-mediated
  • Some progress to chronic DCM
211.1.0.3.7 Neonatal Sepsis
  • Severe systemic enterovirus < 14 days old
  • Multi-organ failure
  • Hepatic failure
  • Coagulopathy
  • Mortality 5-10% historical
  • IVIG considered (high anti-enterovirus titer)
  • Pocapavir investigational
211.1.0.3.8 Pancreatitis
  • Coxsackie B
  • Possible trigger for type 1 diabetes (autoimmune)
211.1.0.3.9 Conjunctivitis
  • EV-70 + Coxsackie A24 — “acute hemorrhagic conjunctivitis”
  • Highly contagious
  • Self-limited 1-2 wk
211.1.0.3.10 Acute Flaccid Myelitis (AFM)
  • EV-D68 + EV-71 main viruses
  • Polio-like asymmetric flaccid paralysis
  • Children, post-respiratory illness
  • 2014 + 2016 + 2018 + 2022-2024 USA outbreaks
  • MRI: cervical spinal cord gray matter lesions
  • Supportive; IVIG / steroid mixed evidence
  • 通報 CDC

211.1.0.4 3⃣ Polio (Poliomyelitis)

211.1.0.4.1 Background
  • 3 serotypes (1, 2, 3)
  • ~ 75% asymptomatic / mild
  • ~ 1% paralytic disease
  • Anterior horn cell destruction → flaccid paralysis
  • Respiratory failure in bulbar paralysis
211.1.0.4.2 Clinical
211.1.0.4.2.1 Abortive Polio (Minor Illness)
  • 1-5% of infected
  • Fever, malaise, sore throat, headache, vomiting
  • Self-limited 1-3 days
211.1.0.4.2.2 Aseptic Meningitis
  • 1% of infected
  • Same as other enteroviral meningitis
211.1.0.4.2.3 Paralytic Polio (0.1-1%)
  • Acute febrile illness → asymmetric flaccid paralysis
  • Lower extremity > upper
  • Bulbar (cranial nerve) involvement = respiratory failure
  • Permanent residual paralysis in survivors
211.1.0.4.2.4 Post-Polio Syndrome
  • 30-40 yr after acute polio
  • New weakness + fatigue + atrophy in previously affected muscles
  • 30%+ polio survivors affected
  • Mechanism: motor neuron exhaustion / loss
  • Supportive
211.1.0.4.3 Eradication Progress
  • WHO Global Polio Eradication Initiative (GPEI) since 1988
  • Type 2 wild eradicated 2015
  • Type 3 wild eradicated 2019
  • Type 1 wild remaining in Pakistan + Afghanistan only (2024-2025)
  • 2024: ~ 20-50 cases globally annually
211.1.0.4.4 Vaccine-Derived Polio (cVDPV)
  • Live OPV mutates rare to virulent + transmits
  • cVDPV2 main type (after type 2 wild eradication, OPV2 stopped 2016 but cVDPV2 from prior use)
  • Outbreaks in vaccine-gap regions (Africa)
  • 2022 NYS USA case: paralytic polio in unvaccinated adult from imported cVDPV2
  • 2022-2024 UK + USA + Israel wastewater detection — silent transmission concern
  • nOPV2 (novel OPV2 with reduced reversion potential) deployed for outbreaks 2020+
211.1.0.4.5 Vaccines
211.1.0.4.5.1 IPV (Inactivated, Salk 1955)
  • Universal in developed countries
  • 4-dose series (2, 4, 6-18 mo, 4-6 yr)
  • No risk of vaccine-derived polio
  • High individual protection but less herd immunity (no mucosal antibody)
211.1.0.4.5.2 OPV (Oral, Sabin)
  • Used in mass campaigns + endemic countries
  • Bivalent (1+3) since 2016 (bOPV)
  • Excellent mucosal immunity + herd protection
  • Rare VAPP (vaccine-associated paralytic polio) ~ 1/750,000
  • Rare cVDPV (causes outbreaks in gap regions)
211.1.0.4.5.3 nOPV2
  • Novel OPV2 with reduced reversion potential
  • WHO EUL 2020
  • Deployed for cVDPV2 outbreaks
211.1.0.4.6 Endgame
  • Synchronization of OPV cessation globally (after wild eradication)
  • IPV-only era goal
  • Surveillance for VDPV via wastewater + clinical AFP

211.1.0.5 4⃣ EV-71 + Taiwan Experience

211.1.0.5.1 Significance
  • Severe HFMD with neurologic + cardiopulmonary complications
  • 1998 Taiwan outbreak: 405 severe cases, 78 deaths (mostly pediatric)
  • Subsequent outbreaks Asia-Pacific 2000s+
211.1.0.5.2 Clinical Severity
  • Stage 1: HFMD typical
  • Stage 2: CNS involvement — meningitis, encephalitis, brainstem encephalitis, AFM
  • Stage 3: cardiopulmonary collapse — neurogenic pulmonary edema, shock
  • Stage 4: recovery or death
211.1.0.5.3 Vaccines (Taiwan + China)
  • Vigoo vaccine (China, 2015 licensed)
  • Sinovac vaccine (China, 2016 licensed)
  • National Vaccine Institute Taiwan vaccine (2023 licensed)
  • ≥ 90% efficacy against EV-71 disease + severe complications
  • Single-strain vaccines (not cross-protect against other HFMD-causing enteroviruses)

211.1.0.6 5⃣ Diagnosis

  • CSF PCR for meningitis
  • Stool / throat PCR for systemic
  • Serology (less useful)
  • Viral culture historical
  • Multiplex respiratory PCR for some

211.1.0.7 6⃣ Treatment

211.1.0.7.1 Supportive
  • Hydration, fever management, comfort care
  • Severe: ICU, ventilator, ECMO
211.1.0.7.2 Antivirals (Investigational)
  • Pleconaril — capsid inhibitor, in trials, limited approval
  • Pocapavir — investigational
  • IVIG for severe / immunocompromise / neonatal
  • No FDA-approved specific antiviral
211.1.0.7.3 EV-71 Severe Disease
  • ICU
  • Steroid + IVIG (limited evidence)
  • Treat neurogenic pulmonary edema (vasopressor, ventilator, fluid management)
  • ECMO
211.1.0.7.4 Chronic Enteroviral Meningoencephalitis (X-linked Agammaglobulinemia)
  • Persistent CNS infection in B-cell-deficient
  • IVIG + pleconaril investigational
  • Mortality high