210.1 🎓 醫孞生版

210.1.0.1 📌 䞀頁重點

210.1.0.1.1 Adenovirus
  • dsDNA virus, Adenoviridae family, > 100 serotypes (7 species A-G)
  • Diverse tropism — respiratory, conjunctival, GI, GU
  • Clinical Forms:
    • Pediatric URI: pharyngitis, fever, otitis (community + military outbreaks)
    • Pharyngoconjunctival fever (children, swimming pools): pharyngitis + conjunctivitis + fever
    • Epidemic keratoconjunctivitis (EKC): highly contagious; serotypes 8, 19, 37; “pink eye”
    • Pneumonia: pediatric + immunocompromise; serotypes 3, 4, 7 military
    • Gastroenteritis: F species (40, 41) — pediatric watery diarrhea
    • Hemorrhagic cystitis: 11, 21, 35 (pediatric + HSCT)
    • Encephalitis, meningitis (rare, immunocompromise)
    • Disseminated in HSCT, AIDS — multi-organ severe
  • Diagnosis: PCR, multiplex panels, viral culture
  • Treatment:
    • Supportive (most cases)
    • Cidofovir or brincidofovir for severe disseminated immunocompromise
    • Adoptive T cell therapy emerging
    • No FDA-approved antiviral
  • Vaccine: live oral types 4 + 7 — US military only
210.1.0.1.2 BK Polyomavirus
  • dsDNA polyomavirus
  • Universal childhood infection (asymptomatic)
  • Latent in renal tubular epithelium + lymphocytes
  • Clinical:
    • BK Virus-Associated Nephropathy (BKVAN) — renal transplant; 1-10% of recipients; loss of allograft if untreated
    • Hemorrhagic Cystitis (HC) in HSCT — hematuria, dysuria, urinary frequency post-transplant
    • Rare: ureteral stenosis, encephalitis, pneumonia
  • Diagnosis: urine PCR + blood PCR (quantitative); decoy cells in urine cytology; renal biopsy with SV40 staining (BKVAN)
  • Treatment:
    • Reduce immunosuppression = primary management (BKVAN)
    • Cidofovir / brincidofovir off-label
    • Leflunomide off-label
    • IVIG adjunct
    • Mesna + hydration for HC
210.1.0.1.3 JC Polyomavirus
  • Latent in kidney + B cells + brain (in immunocompromise)
  • Clinical:
    • Progressive Multifocal Leukoencephalopathy (PML) — fatal demyelinating disease
    • Immune suppression: HIV (AIDS), natalizumab (multiple sclerosis), rituximab, transplant
    • Brain MRI: multifocal demyelinating lesions in white matter (no enhancement, mass effect)
    • Mortality high without immune reconstitution
  • Diagnosis: CSF JC virus PCR + MRI + clinical
  • Treatment:
    • Immune reconstitution (ART for HIV; stop offending drug; plasmapheresis for natalizumab to remove drug rapidly)
    • Pembrolizumab (PD-1 inhibitor) — emerging therapy, case reports + small series
    • No specific antiviral
    • Mirtazapine, mefloquine — limited evidence
210.1.0.1.4 Merkel Cell Polyomavirus (MCV)
  • Discovered 2008
  • Associated with Merkel cell carcinoma (aggressive skin cancer)
  • 80%+ of Merkel cell carcinoma cases MCV-positive
  • Sun-exposed skin, elderly, immunocompromise
  • Treatment: surgery + radiation + pembrolizumab / avelumab (anti-PD-1/L1) — significant response rates

210.1.0.2 1⃣ Adenovirus

210.1.0.2.1 Virology
  • dsDNA, ~ 35 kb
  • Non-enveloped (alcohol-resistant, environmental stability)

  • 100 serotypes (numbered by date of discovery)

  • 7 species: A, B, C, D, E, F, G
  • Different serotypes → different clinical syndromes
210.1.0.2.2 Receptors + Tropism
  • CAR (coxsackie-adenovirus receptor) — most serotypes
  • CD46 — some species B
  • Diverse cellular tropism (respiratory, GI, GU, conjunctival epithelia)
210.1.0.2.3 Clinical Forms
210.1.0.2.3.1 Pediatric URI
  • Pharyngitis + fever + otitis
  • Common
  • Self-limited
  • Outbreaks in childcare, schools
210.1.0.2.3.2 Pharyngoconjunctival Fever
  • Pharyngitis + conjunctivitis + fever
  • Children
  • Swimming pool / fomite outbreaks
  • Serotypes 3, 7 mostly
210.1.0.2.3.3 Epidemic Keratoconjunctivitis (EKC)
  • “Pink eye” pandemic
  • Serotypes 8, 19, 37 — distinct from typical adenovirus conjunctivitis
  • Highly contagious (eye doctor’s office outbreaks)
  • Corneal involvement (subepithelial infiltrates can persist months)
  • Painful, photophobia, foreign body sensation
  • Self-limited 2-3 wk
  • Cold compress, supportive
  • No topical antiviral standard
  • Strict hand hygiene + isolation
210.1.0.2.3.4 Pneumonia
  • Pediatric primary or secondary
  • Serotypes 3, 4, 7 military outbreaks (recruits)
  • Severe pneumonia rare in healthy
  • HSCT + AIDS: severe + high mortality
210.1.0.2.3.5 Gastroenteritis
  • F species (40, 41) main cause
  • Watery diarrhea + fever in young children
  • Up to 10-15% of pediatric viral gastroenteritis
  • Self-limited 7-10d
  • Supportive (ORS)
210.1.0.2.3.6 Hemorrhagic Cystitis
  • Serotypes 11, 21, 35 main
  • Hematuria, dysuria, urinary frequency
  • Pediatric + HSCT post-transplant
  • Can be severe — blood loss, clot retention
  • Supportive: hydration, transfusion, irrigation
  • BK virus is more common cause in HSCT (Ch 200 + here)
210.1.0.2.3.7 Hepatitis
  • Adenovirus 41 + 2 implicated in 2021-2022 pediatric severe hepatitis cluster (UK, USA, Europe) — controversial cause
  • Rare in adults
210.1.0.2.3.8 CNS Disease
  • Encephalitis, meningitis (rare)
  • Immunocompromise
210.1.0.2.3.9 Disseminated Disease
  • HSCT + AIDS
  • Multi-organ failure
  • Pneumonia + hepatitis + colitis + cardiac + CNS
  • High mortality without treatment
210.1.0.2.4 Diagnosis
  • Respiratory PCR (multiplex) for URI/LRTI
  • Stool PCR for gastroenteritis
  • Urine PCR for HC
  • Tissue + IHC for invasive disease
  • Blood quantitative PCR in HSCT monitoring
210.1.0.2.5 Treatment
  • Supportive (most cases)
  • Cidofovir 5 mg/kg IV weekly with probenecid + IV hydration — for severe disseminated immunocompromise
  • Brincidofovir (oral) — less nephrotoxic alternative; in development / expanded access
  • Adoptive T cell therapy — donor-derived adenovirus-specific T cells for HSCT
  • Reduce immunosuppression in transplant context
210.1.0.2.6 Vaccine
  • Live oral types 4 + 7 — US military only (recruits); 96% efficacy
  • Civilian use limited (concern about pediatric immunization)
  • No general-population adenovirus vaccine

210.1.0.3 2⃣ BK Polyomavirus

210.1.0.3.1 Virology
  • dsDNA polyomavirus
  • Discovered 1971 from patient initials “B.K.”
  • Latent in kidney + uroepithelium + lymphocytes after primary childhood infection
  • ~ 90% adults seropositive
210.1.0.3.2 BK Virus-Associated Nephropathy (BKVAN)
  • 1-10% of renal transplant recipients
  • Occurs 3-12 months post-transplant typically
  • Risk factors:
    • Heavy immunosuppression
    • Ureteral stenting
    • HLA mismatch
    • Older donor / recipient age
  • Clinical: progressive renal allograft dysfunction
  • Diagnosis:
    • Urine BK PCR — surveillance (most centers q3 mo first year)
    • Plasma BK PCR > 10,000 copies/mL = suggestive
    • Renal biopsy + SV40 large T antigen IHC = definitive
    • Decoy cells in urine cytology — viral inclusions in epithelial cells
  • Treatment:
    • Reduce immunosuppression (primary intervention)
    • Cidofovir / brincidofovir off-label
    • Leflunomide off-label
    • IVIG adjunct
    • Outcome: allograft loss if untreated; recovery if early intervention + tolerable immunosuppression
210.1.0.3.3 Hemorrhagic Cystitis in HSCT
  • 5-25% of allogeneic HSCT recipients
  • Late-onset (1-3 months post-transplant)
  • BK > Adenovirus > CMV
  • Clinical: severe hematuria, dysuria, urinary frequency, suprapubic pain
  • Severe: clot retention, transfusion-dependent
  • Diagnosis: urine BK PCR + cystoscopy if severe
  • Treatment:
    • Bladder irrigation + hydration
    • Mesna to bind acrolein (cyclophosphamide metabolite — also cystitis trigger)
    • Hyperbaric oxygen for severe / refractory
    • Cidofovir intravesical or IV
    • Reduce immunosuppression as feasible
210.1.0.3.4 Encephalitis (Rare)
  • Rare; immunocompromise
  • CSF BK PCR
  • Outcome variable
210.1.0.3.5 Diagnosis Tools
  • Urine BK PCR (high sensitivity, screening)
  • Plasma BK PCR (clinical disease marker)
  • Decoy cells urine cytology
  • Renal biopsy + SV40 IHC for BKVAN definitive

210.1.0.4 3⃣ JC Polyomavirus

210.1.0.4.1 Virology
  • dsDNA polyomavirus
  • Discovered 1971 from patient initials “J.C.”
  • Latent in kidney + B cells + brain (in immunocompromise)
  • ~ 70% adults seropositive
210.1.0.4.2 Progressive Multifocal Leukoencephalopathy (PML)
210.1.0.4.2.1 Setting
  • Severe T cell immunodeficiency required (rarely B cell)
  • HIV / AIDS (CD4 < 100) historic main
  • Natalizumab (Tysabri) for multiple sclerosis — well-established risk
  • Rituximab, ocrelizumab (anti-CD20)
  • Transplant (HSCT, SOT)
  • Hematologic malignancy (CLL)
  • Chemotherapy
  • Rare without identifiable immunosuppression
210.1.0.4.2.2 Clinical
  • Subacute neurologic decline
  • Visual deficits (cortical, optic radiation), motor (hemiparesis), cognitive, ataxia
  • Multifocal — different deficits over time
  • Seizures uncommon
  • Progressive to death in months-2 years without immune reconstitution
210.1.0.4.2.3 Diagnosis
  • MRI: multifocal demyelinating white matter lesions
    • Hyperintense on T2/FLAIR
    • No enhancement (vs tumor, abscess)
    • No mass effect (vs tumor, edema)
    • Parieto-occipital + subcortical U-fibers
  • CSF JC virus PCR = gold standard (sens 70-90%)
  • Brain biopsy if PCR negative + high suspicion
  • PML-IRIS with immune reconstitution: paradoxical worsening + enhancement
210.1.0.4.2.4 Treatment
  • Immune reconstitution = primary intervention
    • HIV: ART
    • Natalizumab PML: plasmapheresis to remove drug rapidly; switch to other MS drug
    • Rituximab / ocrelizumab: stop, switch agents (slow recovery)
    • Transplant: reduce immunosuppression
    • Chemo: stop / switch
  • Pembrolizumab (anti-PD-1) — emerging therapy
    • Case reports + small series with response
    • Immune checkpoint inhibitor concept: restore T cell immunity
  • Mirtazapine, mefloquine — limited evidence (don’t routinely use)
  • No specific antiviral
210.1.0.4.2.5 Outcome
  • Mortality 30-80% varying by underlying immunosuppression
  • HIV-PML with ART: 50%+ survival with neurological sequelae
  • Natalizumab-PML with plasmapheresis: 70%+ survival (better than HIV PML in modern era)
210.1.0.4.2.6 PML-IRIS
  • Paradoxical worsening after immune reconstitution
  • Especially HIV-PML with ART or natalizumab-PML with plasmapheresis
  • MRI: enhancement, edema, mass effect (new)
  • Treatment: continue immune reconstitution + steroid for IRIS

210.1.0.5 4⃣ Merkel Cell Polyomavirus (MCV)

210.1.0.5.1 Discovery
  • 2008 — Chang + Moore (subtractive PCR)
  • 80%+ Merkel cell carcinoma cases MCV-positive
210.1.0.5.2 Merkel Cell Carcinoma
  • Aggressive neuroendocrine skin carcinoma
  • Sun-exposed skin (head, neck, extremities)
  • Elderly, immunocompromise (HIV, transplant, CLL)
  • Painless red-purple nodule, rapid growth
  • High mortality without treatment
  • Treatment:
    • Wide local excision + sentinel LN biopsy
    • Radiation
    • Pembrolizumab / Avelumab (anti-PD-1/L1) — significant response rates (40-50%+)
    • Chemotherapy for advanced
    • Carboplatin + etoposide historic

210.1.0.6 5⃣ Other Polyomaviruses

  • WU + KI polyomaviruses — respiratory
  • MWPyV (MW polyomavirus) — gastroenteritis
  • Most low / unclear pathogenicity