202.1 🎓 醫孞生版

202.1.0.1 📌 䞀頁重點

  • Poxviridae: largest viruses (200-400 nm, visible by light microscopy); brick-shaped; cytoplasmic replication (unique for DNA viruses)
  • Orthopoxvirus genus (human-relevant):
    • Variola (smallpox) — eradicated 1980
    • Vaccinia — vaccine strain
    • Mpox (monkeypox) — Clade I (Africa) + Clade II (W Africa + 2022 global)
    • Cowpox — sporadic Europe
  • Parapoxvirus: orf, milker’s nodule, paravaccinia (occupational)
  • Molluscipoxvirus: molluscum contagiosum — common pediatric + STI
202.1.0.1.1 Smallpox (Variola)
  • Eradicated 1980 (last natural case Somalia 1977)
  • Last lab death: Birmingham UK 1978
  • Stockpiles: USA CDC + Russia VECTOR (declared)
  • Bioterror Category A
  • Clinical: high fever → rash starting on face/extremities → synchronous progression of all lesions (unlike chickenpox successive crops)
  • Mortality 30%+ for variola major
  • Vaccine: ACAM2000 (live vaccinia, traditional); JYNNEOS (non-replicating vaccinia, safer in immunocompromise)
202.1.0.1.2 Mpox (Monkeypox)
  • 2022-2024 global outbreak:
    • Clade IIb (W African origin) — primarily MSM sexual transmission, mild-moderate, USA + EU + worldwide
    • Peak 2022; resurgence 2024-2025 in some regions
  • 2023-2024 Clade Ib — DRC + neighboring African countries; more severe, household transmission + heterosexual + pediatric
  • Reservoir: rodents (not actually monkeys despite name)
  • Transmission: contact with skin lesions, body fluids, respiratory droplets (prolonged); sexual (Clade IIb)
202.1.0.1.2.1 Clinical
  • 7-14 d incubation
  • Prodrome: fever, malaise, LAP (distinguishes from smallpox — LAP prominent in Mpox)
  • Rash: starts face/extremities → lesions all same stage (synchronous like smallpox)
  • Vesicles → pustules → crusts
  • 2022 outbreak: many cases with limited / anogenital-only lesions (sexual transmission predominant)
  • Complications: bacterial superinfection, encephalitis, severe in immunocompromise (especially HIV uncontrolled)
  • Mortality: Clade IIb ~ 0.1-1%, Clade I 1-10% historic
202.1.0.1.2.2 Diagnosis
  • PCR of lesion swab (most sensitive)
  • Specialty labs / public health
202.1.0.1.2.3 Treatment
  • Tecovirimat (TPOXX): FDA-approved smallpox; expanded access for Mpox
  • 2024 STOMP trial NEGATIVE for Clade I Mpox treatment efficacy in adults
  • May still use for severe disease / immunocompromise compassionate / pediatric
  • VIG (vaccinia immune globulin) — vaccine complications
  • Brincidofovir, cidofovir — limited data
  • Supportive: skin care, pain management, prevent secondary infection
202.1.0.1.2.4 Vaccination
  • JYNNEOS (modified vaccinia Ankara, MVA-BN, non-replicating) — preferred
    • 2 doses 4 weeks apart
    • Pre-exposure prophylaxis (PEP) for high-risk (MSM with multiple partners)
    • Post-exposure prophylaxis < 4-14 days of exposure
    • Safe in immunocompromise
  • ACAM2000 (live vaccinia) — traditional, contraindicated in immunocompromise
202.1.0.1.3 Molluscum Contagiosum
  • Common pediatric + adult
  • Pearly papules with central umbilication
  • Sexual transmission in adults (anogenital)
  • HIV + → extensive
  • Treatment: usually self-limited; cryotherapy, curettage, cantharidin, podophyllin
202.1.0.1.4 Orf + Milker’s Nodule (Parapoxvirus)
  • Occupational (sheep, cow workers)
  • Single nodule on finger/hand
  • Self-limited
  • Cosmetic / surgical removal if needed

202.1.0.2 1⃣ Poxvirus Biology

  • Brick-shaped, 200-400 nm (largest virus)
  • dsDNA genome, ~ 200 kb
  • Cytoplasmic replication (unique for DNA viruses — most DNA viruses replicate in nucleus)
  • Encode own DNA polymerase + transcription machinery
  • Highly antigenic
202.1.0.2.1 Pathogenesis
  • Infection via skin / mucous membrane / respiratory
  • Local replication → primary lesion + viremia
  • Dissemination
  • Lifelong immunity after primary infection (or vaccination)

202.1.0.3 2⃣ Smallpox (Variola)

202.1.0.3.1 Eradication
  • WHO global campaign 1959-1980
  • Last natural case Somalia 1977
  • Last laboratory accident death Birmingham UK 1978
  • Eradication declared 1980 (WHO)
  • 仍 stockpiles: CDC (USA) + VECTOR (Russia)
  • 仍 bioterror concern + lab accident risk
202.1.0.3.2 Clinical (Historical + Bioterror Awareness)
  • 7-14 d incubation
  • Severe prodrome: fever 39-40°C, severe headache, backache, prostration
  • Rash starts oral mucosa → face → extremities centrifugally
  • Papules → vesicles → pustules → crusts
  • All lesions synchronous progression (different stages distinguish from chickenpox)
  • Especially dense on face / extremities (centrifugal)
  • Severe pain
  • Mortality 30%+ for variola major; less for variola minor (1-2%)
202.1.0.3.3 Bioterror Awareness
  • Single case = international emergency
  • Notify CDC + WHO immediately
  • Isolate + contact trace
  • Vaccinia immune globulin + tecovirimat / brincidofovir
  • ACAM2000 / JYNNEOS vaccine for ring vaccination
202.1.0.3.4 Vaccine
  • ACAM2000 (live vaccinia, traditional)
    • Vaccinia not smallpox virus — gives cross-protection
    • Stockpiled
    • Adverse events: progressive vaccinia (immunocompromise), eczema vaccinatum, myocarditis, encephalitis
  • JYNNEOS (MVA-BN, non-replicating)
    • Safer alternative
    • Approved smallpox + Mpox
    • Pre-exposure prophylaxis for high-risk personnel

202.1.0.4 3⃣ Mpox (Monkeypox)

202.1.0.4.1 Reservoir + Geography
  • Not actually monkeys (misnomer from 1958 lab outbreak in monkeys)
  • True reservoir: rodents (squirrels, dormice, Gambian giant rats) in W + C Africa
  • Endemic in DRC + W African countries
  • 2022-2024 global outbreak: Clade IIb (W African) — primarily MSM sexual transmission, hundreds of countries
  • 2023-2024 Clade Ib: DRC + neighboring; more severe; mixed transmission
202.1.0.4.2 Clades
Clade Origin 2022-2024 Activity Severity
Clade I (Congo Basin) DRC, Central Africa 2023-2024 outbreak (Ib) More severe
Clade Ib DRC variant 2024 outbreak, household + heterosexual + pediatric More severe
Clade IIb (West African) Nigeria, W Africa 2022 global outbreak, mostly MSM sexual Milder
202.1.0.4.3 Transmission
  • Contact with skin lesions
  • Body fluids
  • Respiratory (prolonged close contact)
  • Fomites
  • Sexual transmission predominated 2022 (MSM)
  • Vertical
  • Animal bite / contact
202.1.0.4.4 Clinical
202.1.0.4.4.1 Classic Course
  • 7-14 d incubation
  • Prodrome: fever, malaise, headache, LAP (prominent, distinguishes from smallpox), fatigue
  • Rash: starts face → extremities (centrifugal) → trunk
  • Lesions synchronous progression (like smallpox)
  • Vesicles → pustules → crusts
202.1.0.4.4.2 2022 Outbreak Variants
  • Many cases with limited or anogenital-only lesions
  • Skip prodrome in some
  • Less centrifugal distribution
  • Proctitis common in MSM
  • Sexually transmitted classic appearance
202.1.0.4.4.3 Complications
  • Bacterial superinfection
  • Encephalitis (rare)
  • Myocarditis
  • Severe in immunocompromise (especially uncontrolled HIV with CD4 < 200)
  • Scarring
  • Eye involvement (keratitis)
202.1.0.4.4.4 Mortality
  • Clade IIb ~ 0.1-1% in HIV+ uncontrolled higher
  • Clade I 1-10% historic
  • 2024 Clade Ib outbreak: mortality higher in pediatric + immunocompromised
202.1.0.4.5 Diagnosis
  • Lesion swab PCR
  • Two swabs per lesion (capsule + base)
  • Specialty labs / public health
  • Differential: VZV, HSV, syphilis (LGV proctitis MSM), molluscum
202.1.0.4.6 Treatment
202.1.0.4.6.1 Tecovirimat (TPOXX)
  • FDA-approved smallpox 2018
  • Expanded access for Mpox
  • 2024 STOMP trial NEGATIVE for Clade I Mpox adult treatment efficacy
  • 14-day oral course
  • Severe / immunocompromise / pediatric / pregnancy may still consider compassionate
202.1.0.4.6.2 Brincidofovir + Cidofovir
  • Limited data
  • Severe nephrotoxicity (cidofovir) — brincidofovir less
202.1.0.4.6.3 VIG (Vaccinia Immune Globulin)
  • For vaccine complications
  • Not routine Mpox treatment
202.1.0.4.6.4 Supportive
  • Skin care, pain management
  • Antihistamine for itch
  • Bacterial superinfection coverage if signs
  • Hospitalization for severe / complicated
202.1.0.4.7 Vaccination
  • JYNNEOS (MVA-BN) preferred for general
  • 2 doses 4 weeks apart
  • PrEP: MSM multi-partner, occupational exposure, lab worker
  • PEP: < 4 days = highly protective; 4-14 days may reduce severity
  • Subcutaneous (preferred) or intradermal (dose-sparing)
  • Safe in immunocompromise (non-replicating)
  • Public Health distribution prioritization
202.1.0.4.8 2024 Global Status
  • Clade IIb cases declined post-2022 peak but persistent transmission in MSM networks
  • Clade Ib outbreak in DRC + Burundi + Uganda + Rwanda — declared PHEIC by WHO Aug 2024
  • Vaccine distribution to Africa critical
  • Surveillance + early detection

202.1.0.5 4⃣ Other Poxviruses

202.1.0.5.1 Molluscum Contagiosum
  • Molluscum contagiosum virus (Molluscipoxvirus)
  • Pearly papules with central umbilication
  • Skin-skin contact, fomites, sexual
  • Children: face, trunk, extremities (sports, swimming)
  • Adults: anogenital (sexual)
  • HIV +: extensive, atypical
  • Self-limited in healthy (months-years)
  • Treatment options:
    • Observation
    • Cryotherapy (liquid N2)
    • Curettage
    • Cantharidin topical
    • Imiquimod (controversial — discouraged in CDC 2024)
    • Tretinoin
  • Sexual partner notification + STI screen if anogenital
202.1.0.5.2 Orf (Parapoxvirus)
  • Sheep / goat workers (also wool processing)
  • Single nodule on finger / hand
  • 3-6 wk self-limited
  • Cosmetic if persistent
202.1.0.5.3 Milker’s Nodule
  • Cattle worker
  • Similar to orf
  • Self-limited
202.1.0.5.4 Cowpox
  • Sporadic Europe
  • Cat / rodent reservoir
  • Mild lesions
  • Self-limited
202.1.0.5.5 Tanapox
  • E Africa
  • Self-limited