222.1 🎓 醫孞生版

222.1.0.1 📌 䞀頁重點

222.1.0.1.1 Ebola Virus
  • Family: Filoviridae; ssRNA filamentous virus
  • 6 species: Zaire ebolavirus (most deadly, 50-90% mortality); Sudan ebolavirus; Bundibugyo; Tai Forest; Reston (non-pathogenic to humans, infects monkeys); Bombali (recent discovery)
  • Reservoir: bats (Rousettus aegyptiacus + others); non-human primates intermediate hosts
  • Outbreaks:
    • 2014-2016 W Africa epidemic (Liberia, Sierra Leone, Guinea, Mali): 28,000+ cases, 11,000+ deaths
    • 2018-2020 DRC outbreak (2nd largest, 3500+ cases)
    • 2022 Uganda Sudan Ebola outbreak
    • 2023-2025 ongoing African outbreaks
  • Transmission:
    • Direct contact with body fluids (blood, vomit, diarrhea, urine, saliva, semen, sweat)
    • Mucous membranes + broken skin
    • Contaminated objects
    • Sexual transmission (semen carries virus weeks-months post-recovery)
    • Vertical
    • Healthcare-associated (PPE failures)
  • Clinical:
    • 8-21 days incubation
    • Phase 1: fever + malaise + headache + myalgia
    • Phase 2: GI symptoms — severe vomiting + diarrhea + abdominal pain (dehydration risk)
    • Phase 3: hemorrhagic manifestations (~ 50%) — bleeding gums + GI + skin + IV sites
    • Phase 4: shock + multi-organ failure
    • Mortality: 50-90% Zaire; 25-50% Sudan
  • Diagnosis:
    • RT-PCR of blood (gold standard)
    • BSL-4 for handling
    • Antigen detection (Ebola NP, GP)
  • Treatment:
    • Aggressive supportive care (IV fluids, electrolyte replacement, organ support)
    • Monoclonal antibodies:
      • Inmazeb (atoltivimab-maftivimab-odesivimab, REGN-EB3) — FDA 2020 — cocktail of 3 mAbs
      • Ebanga (ansuvimab, mAb114) — FDA 2020 — single mAb
    • Remdesivir — used in 2018-2020 outbreak; less effective than mAbs (per PALM trial)
    • Convalescent plasma — historical, replaced by mAbs
  • Vaccines:
    • Ervebo (rVSV-ZEBOV-GP, Merck, FDA 2019) — single dose live recombinant vaccine; ring vaccination strategy revolutionized response
    • Zabdeno + Mvabea (Janssen, 2-dose heterologous prime-boost) — preventive
  • Survivors: post-Ebola syndrome (uveitis, arthralgia, neurologic; viral persistence in immune-privileged sites — eye, brain, testis; sexual transmission risk)
222.1.0.1.2 Marburg Virus
  • Filoviridae family
  • Similar to Ebola but distinct (Marburgvirus genus)
  • Outbreaks:
    • 1967 Marburg, Germany (lab outbreak from monkeys)
    • 2004-2005 Angola (252 cases, 90% mortality)
    • 2017 Uganda
    • 2023 Equatorial Guinea + Tanzania
    • 2025 Rwanda outbreak ongoing
  • Reservoir: bats (Rousettus aegyptiacus)
  • Transmission: similar to Ebola (direct contact body fluids)
  • Clinical: very similar to Ebola; mortality 23-90% (variable)
  • Diagnosis: PCR
  • Treatment:
    • Supportive
    • Marburg-specific mAbs in development (MBP091 etc.)
    • Remdesivir investigational
  • Vaccine:
    • No licensed Marburg vaccine yet
    • Candidates in development (cAd3-Marburg, rVSV-MARV)
    • 2025 emergency rollout in Rwanda (Phase 2 trials)

222.1.0.2 1⃣ Ebola Virus

222.1.0.2.1 Virology
  • ssRNA filamentous, ~ 19 kb
  • 7 genes (NP, VP35, VP40, GP, VP30, VP24, L)
  • GP (glycoprotein) major antigen + target
  • 6 species (different mortality + epidemiology)
222.1.0.2.2 Reservoir
  • Fruit bats primary natural reservoir (Rousettus aegyptiacus, others)
  • Non-human primates (monkeys, gorillas, chimpanzees) intermediate
  • Hunting/butchering bushmeat → spillover
222.1.0.2.3 Transmission
222.1.0.2.3.1 Direct Body Fluid Contact
  • Blood, vomit, diarrhea, urine, saliva, sweat, semen, breast milk
  • Mucous membrane + broken skin entry
222.1.0.2.3.2 Sexual Transmission
  • Semen carries Ebola for weeks-months post-recovery
  • Documented late sexual transmission events
  • Survivors counseled
  • WHO recommends abstinence or condom use up to 12 months for male survivors
222.1.0.2.3.3 Vertical
  • Mother → infant (in utero + breastfeeding)
222.1.0.2.3.4 Healthcare-Associated
  • PPE breaches
  • 2014-2016 epidemic: ~ 7% healthcare worker (HCW) cases
  • 511 HCW deaths in epidemic
222.1.0.2.3.5 Postmortem
  • Deceased remain infectious; safe burial practices critical (changed African mourning practices controversially)
222.1.0.2.4 Clinical
222.1.0.2.4.1 Phase 1: Febrile (Days 1-5)
  • Sudden fever (39-40°C)
  • Headache, myalgia, fatigue
  • Indistinguishable from many febrile illnesses
222.1.0.2.4.2 Phase 2: GI (Days 5-10)
  • Severe vomiting
  • Severe diarrhea (often bloody)
  • Abdominal pain
  • Severe dehydration
  • Electrolyte derangement
222.1.0.2.4.3 Phase 3: Hemorrhagic (Days 7-14)
  • Bleeding gums, nose, GI, skin (petechiae)
  • IV site bleeding
  • Conjunctival hemorrhage
  • ~ 50% of severe cases
222.1.0.2.4.4 Phase 4: Shock + Multi-Organ Failure
  • Hypovolemic + septic shock
  • AKI
  • ARDS
  • DIC
  • Encephalopathy
  • Death typically days 8-14
222.1.0.2.4.5 Recovery (Survivors)
  • 1-2 wk for symptoms to resolve
  • Post-Ebola syndrome:
    • Uveitis (eye sequelae)
    • Arthralgia, myalgia
    • Headache, neurologic
    • Hearing loss
    • Sexual dysfunction
    • Hair loss
    • Persistent inflammation
222.1.0.2.5 Diagnosis
222.1.0.2.5.1 RT-PCR
  • Gold standard for confirmation
  • BSL-4 lab required
  • Multiple specimens: blood, saliva, semen, breast milk
  • Quantitative PCR for monitoring
222.1.0.2.5.2 Antigen Tests
  • Rapid tests (POC) for outbreak surveillance
  • Less sensitive than PCR
  • Lateral flow GP antigen
  • ReEBOV (Corgenix)
222.1.0.2.5.3 Serology
  • IgM + IgG (mostly for retrospective)
  • Cross-reactivity within Filovirus family
222.1.0.2.6 Treatment
222.1.0.2.6.1 Supportive Care (Foundation)
  • Aggressive IV fluid + electrolyte replacement
  • Antiemetics
  • Antimotility (cautious)
  • Analgesia
  • Hemodialysis if AKI
  • Mechanical ventilation if respiratory failure
  • Coagulation product replacement
  • Blood transfusion
  • ICU for severe
222.1.0.2.6.2 Monoclonal Antibodies (Game Changer)
222.1.0.2.6.3 Inmazeb (REGN-EB3, FDA 2020)
  • Cocktail of 3 mAbs: atoltivimab + maftivimab + odesivimab
  • IV single infusion
  • PALM trial 2019: significantly reduced mortality (35.1% mAb vs 51% ZMapp)
  • Stockpile for outbreak response
222.1.0.2.6.4 Ebanga (mAb114 / Ansuvimab, FDA 2020)
  • Single mAb derived from 1995 Kikwit survivor
  • IV single infusion
  • PALM trial: similar efficacy to REGN-EB3 (33.5% mortality)
222.1.0.2.6.5 Remdesivir
  • Used in 2018-2020 DRC outbreak
  • PALM trial: less effective than mAbs (53% mortality)
  • Now adjunct, not first-line
222.1.0.2.6.6 Convalescent Plasma
  • Historical use
  • Replaced by purified mAbs
  • Some Ebola-specific Ig preparations under development
222.1.0.2.7 Vaccines
222.1.0.2.7.1 Ervebo (rVSV-ZEBOV-GP, Merck, FDA 2019)
  • Single dose live recombinant vaccine
  • VSV (vesicular stomatitis virus) backbone expressing Ebola GP
  • Ring vaccination strategy revolutionized outbreak response
  • 100% efficacy in Guinea ring vaccination trial 2015-2016
  • Approved for Zaire ebolavirus only (not Sudan or others)
  • 2018-2020 DRC outbreak: > 300,000 vaccinated
  • WHO stockpile for emergency deployment
222.1.0.2.7.2 Zabdeno + Mvabea (Janssen, 2-dose)
  • Heterologous prime-boost
  • Zabdeno (Ad26.ZEBOV) prime + Mvabea (MVA-BN-Filo) boost
  • 2-dose schedule 8 weeks apart
  • Preventive (longer-term)
  • Approved EMA 2020
222.1.0.2.7.3 Future Vaccines
  • Pan-filovirus vaccines (Ebola + Marburg combination)
  • Sudan-specific vaccines
  • mRNA candidates
222.1.0.2.8 Prevention + Infection Control
  • PPE (gown, gloves, mask, eye protection, boots)
  • Strict + monitored donning + doffing
  • Patient isolation in designated treatment units
  • Safe burial practices
  • Contact tracing + monitoring
  • Ring vaccination of contacts + contacts of contacts
  • HCW vaccination
  • Border + travel surveillance
222.1.0.2.9 Outbreak Response
  • WHO emergency response
  • Mobile labs (BSL-4)
  • Treatment centers
  • Community engagement (critical)
  • Ring vaccination
  • Safe burial teams

222.1.0.3 2⃣ Marburg Virus

222.1.0.3.1 Background
  • 1967 Marburg, Germany — first identified (lab workers handling green monkeys from Uganda)
  • Distinct genus (Marburgvirus) within Filoviridae
  • Single species (Marburg marburgvirus)
  • 2 main lineages: Marburg + Ravn
222.1.0.3.2 Reservoir
  • Rousettus aegyptiacus (Egyptian fruit bat)
  • Cave-dwelling
  • Aerosolized bat urine + feces in caves
  • Mining/exploration outbreaks
222.1.0.3.3 Outbreaks
  • 1967 Germany (32 cases, 7 deaths) — index lab outbreak
  • 2004-2005 Angola (252 cases, 90% mortality)
  • 2007 Uganda
  • 2012 Uganda
  • 2014 Uganda
  • 2017 Uganda (3 cases)
  • 2021 Guinea (1 case)
  • 2023 Equatorial Guinea + Tanzania
  • 2024 Rwanda ongoing (largest)
  • 2024-2025 ongoing concerns
222.1.0.3.4 Transmission
  • Same as Ebola: direct body fluid contact
  • Sexual transmission documented
  • Healthcare-associated
222.1.0.3.5 Clinical
  • Very similar to Ebola
  • 5-10 d incubation
  • Phases: febrile → GI → hemorrhagic → shock/MOF
  • Mortality 23-90% (varied; 2024 Rwanda outbreak ~ 30%)
222.1.0.3.6 Diagnosis
  • RT-PCR
  • BSL-4
222.1.0.3.7 Treatment
  • Supportive care (foundation)
  • Marburg-specific mAbs in development:
    • MBP091 (Mapp Biopharmaceutical) — Phase 2/3
    • Other candidates
  • Remdesivir investigational
222.1.0.3.8 Vaccine
  • No licensed Marburg vaccine yet
  • 2025 emergency rollout in Rwanda outbreak: cAd3-Marburg (Sabin) + rVSV-MARV (Public Health Vaccines + IAVI)
  • Phase 2 trials in outbreak setting
  • Stockpiling + accelerated development priority
222.1.0.3.9 Outbreak Response
  • Same as Ebola: PPE + isolation + contact tracing + safe burial + community engagement
  • Mobile BSL-4 labs
  • Vaccine deployment in emergency

222.1.0.4 3⃣ Filovirus Outbreak Considerations

222.1.0.4.1 When to Suspect
  • Returning traveler from endemic country
  • Fever within 21 days
  • Compatible clinical features
  • Healthcare workers, family contacts
222.1.0.4.2 Isolation + Testing
  • Strict isolation immediately
  • BSL-4 lab for testing
  • CDC + WHO notification
  • Standard hospital usually cannot test on-site
222.1.0.4.3 Differentiation
  • Filovirus PCR panel
  • Differentiate from malaria, severe leptospirosis, typhoid, hemorrhagic fever viruses (Lassa, others)
  • Other tropical infections