223.1 🎓 醫孞生版

223.1.0.1 📌 䞀頁重點

223.1.0.1.1 Lassa Fever
  • Virus: ssRNA Arenaviridae, Mammarenavirus genus
  • Reservoir: Mastomys natalensis (multimammate rat) — West Africa
  • Geography: West Africa (Nigeria + Sierra Leone + Liberia + Guinea); 100,000-300,000 cases/yr, ~ 5,000 deaths
  • Transmission:
    • Rodent excreta (urine, feces) — direct or contaminated food
    • Direct person-to-person (blood, body fluids, sexual)
    • Aerosol (rodent activities — cooking with contaminated grain, sweeping)
    • Vertical
    • Healthcare (PPE breaches)
  • Clinical:
    • 80% mild / asymptomatic
    • 20% severe: prolonged fever + facial edema + pharyngitis + bleeding + organ failure
    • Mortality: 1% community, 15-20% hospitalized, 80%+ in 3rd trimester pregnancy
    • SNHL (sensorineural hearing loss) in 30% survivors (severe long-term)
  • Diagnosis:
    • PCR of blood (acute)
    • IgM (after day 6-10)
    • BSL-4
  • Treatment:
    • Ribavirin 30 mg/kg load → 16 mg/kg q6h × 4d → 8 mg/kg q8h × 6d
    • Start ASAP — better outcome if early (< 6 days)
    • Aggressive supportive care
  • Vaccines:
    • MVA-LASV (Janssen, FDA Breakthrough 2024) — Phase 3 ongoing
    • rVSV-Lassa (Public Health Vaccines) — Phase 1
    • CEPI accelerating
  • Prevention: rodent control + safe food storage + PPE
223.1.0.1.2 LCMV (Lymphocytic Choriomeningitis Virus)
  • Reservoir: house mouse (Mus musculus)
  • Worldwide where house mice live
  • Transmission:
    • Rodent excreta
    • Vertical (intrauterine — severe congenital disease)
    • Organ transplant (donor-recipient transmission causes severe disease)
    • Direct contact
  • Clinical:
    • Mild: febrile illness, aseptic meningitis
    • Severe: encephalitis (rare in healthy)
    • Congenital: severe (1st-2nd trimester maternal infection) — microcephaly + hydrocephalus + chorioretinitis + intracranial calcifications + intellectual disability (clinically similar to congenital CMV)
    • Transplant: severe + frequently fatal multi-organ disease
  • Diagnosis: PCR + serology (CSF, blood)
  • Treatment: supportive; ribavirin off-label transplant; reduce immunosuppression
223.1.0.1.3 S. American Hemorrhagic Fevers (Junin, Machupo, Guanarito, Sabia)
  • Junin (Argentine): rodent (Calomys musculinus) reservoir; rural Argentina
  • Machupo (Bolivian): rodent reservoir; Bolivia
  • Guanarito (Venezuelan): rodent; Venezuela
  • Sabia (Brazilian): rodent; Brazil
  • Clinical: similar to Lassa with hemorrhagic + neurological features
  • Mortality: 15-30%
  • Treatment: ribavirin + supportive
  • Vaccine: Candid #1 (Argentine Junin vaccine) — effective
223.1.0.1.4 Lujo
  • 2008 emergence (Zambia → South Africa)
  • Severe hemorrhagic fever
  • Rodent reservoir presumed
  • 5/5 cases died (initial outbreak)
  • Sporadic since

223.1.0.2 1⃣ Lassa Fever

223.1.0.2.1 Virology
  • ssRNA Arenaviridae, Mammarenavirus genus
  • “Arena” (sand) — appearance of host ribosomes inside virions on EM
  • Lineages: I, II, III, IV (different geographical + clinical)
223.1.0.2.2 Reservoir + Transmission
  • Mastomys natalensis (multimammate rat) — peridomestic, abundant in West Africa
  • Chronic shedding via urine + feces
  • 20-30% of rodents infected in endemic areas
  • Transmission:
    • Eating food contaminated with rodent excreta (most common)
    • Cooking rodents (delicacy in some areas)
    • Aerosol exposure during cleaning rodent-infested areas
    • Person-to-person (blood, body fluids, sexual, healthcare)
223.1.0.2.3 Epidemiology
  • West Africa endemic: Nigeria + Sierra Leone + Liberia + Guinea + Ghana + Benin
  • ~ 100,000-300,000 cases/yr (most mild + undiagnosed)
  • ~ 5,000 deaths/yr
  • Seasonal: dry season peak (rodents seek food indoors)
  • Healthcare workers significant risk
223.1.0.2.4 Clinical
223.1.0.2.4.1 Incubation 6-21 Days
223.1.0.2.4.2 Mild Disease (80%)
  • Asymptomatic or mild febrile
  • Often undiagnosed
223.1.0.2.4.3 Severe Disease (20%)
  • Phase 1 (Days 1-7): gradual onset fever, malaise, headache, sore throat (often pharyngitis with exudate)
  • Phase 2 (Days 7-14): progression — facial edema (characteristic), pleural + pericardial effusion, mucosal bleeding, neurological (encephalopathy, ataxia, tremor), hepatic involvement
  • Severe: shock + multi-organ failure
  • Sensorineural hearing loss (SNHL) in 30% of survivors (often permanent, bilateral)
  • Mortality:
    • Community: < 1%
    • Hospitalized severe: 15-20%
    • Pregnancy 3rd trimester: 80%+ maternal mortality
    • Fetal/neonatal mortality high
223.1.0.2.4.4 Late Sequelae
  • SNHL (30% — major)
  • Ataxia, tremor
  • Chronic fatigue
223.1.0.2.5 Diagnosis
  • PCR of blood — gold standard acute
  • IgM ELISA after day 6-10
  • BSL-4 lab required
  • Lassa-specific antigen
  • Cross-reactivity within Arenaviridae
223.1.0.2.6 Treatment
223.1.0.2.6.1 Ribavirin
  • 30 mg/kg IV loading dose → 16 mg/kg q6h × 4d → 8 mg/kg q8h × 6d
  • Start as early as possible (best if < 6 days from symptom onset)
  • Mechanism: nucleotide analog interfering with RNA replication
  • Toxicity: hemolytic anemia (reversible)
  • McCormick 1986 trial: reduced mortality 76% to 9% if given early
223.1.0.2.6.2 Supportive Care
  • IV fluid + electrolyte replacement
  • Hemodialysis if AKI
  • Mechanical ventilation if respiratory failure
  • Coagulation product replacement
  • ICU level care
  • Address obstetric complications
223.1.0.2.6.3 Pregnancy
  • Termination of pregnancy in severe Lassa improves maternal survival (historically supported; controversial)
  • Ribavirin (teratogenic — but life-saving in severe disease)
  • ICU obstetric
223.1.0.2.6.4 Healthcare Worker Exposure
  • Post-exposure ribavirin prophylaxis (oral)
  • Symptomatic monitoring
223.1.0.2.7 Vaccines (In Development)
223.1.0.2.7.1 MVA-LASV (Janssen)
  • Modified vaccinia Ankara backbone
  • 2-dose series
  • Phase 3 ongoing
  • FDA Breakthrough Therapy 2024
223.1.0.2.7.2 rVSV-Lassa (Public Health Vaccines + IAVI)
  • VSV backbone (similar to Ervebo Ebola)
  • Single dose
  • Phase 1-2
223.1.0.2.7.3 Other Candidates
  • mRNA vaccines
  • DNA vaccines
223.1.0.2.8 Prevention
223.1.0.2.8.1 Rodent Control
  • Food storage (rodent-proof containers)
  • Sealed homes
  • Limit rodent contact
223.1.0.2.8.2 Person-to-Person
  • PPE in healthcare
  • Isolation
  • Contact tracing
  • Sexual precautions for survivors (months)
223.1.0.2.8.3 Health Education
  • Avoid rodent-prepared foods
  • Hygiene
  • Healthcare worker training

223.1.0.3 2⃣ LCMV (Lymphocytic Choriomeningitis Virus)

223.1.0.3.1 Reservoir + Transmission
  • House mouse (Mus musculus) — worldwide
  • Pet rodent (hamsters, guinea pigs) — occasional source
  • 5-10% of house mice infected
  • Transmission:
    • Rodent excreta (urine, feces, saliva)
    • Vertical — major concern (in utero severe disease)
    • Organ transplant — donor-recipient transmission (very severe in recipient)
    • Direct contact with infected rodent (rare lab)
223.1.0.3.2 Clinical
223.1.0.3.2.1 Acquired (Postnatal)
  • 50% asymptomatic
  • 50% biphasic illness:
    • Phase 1: febrile, flu-like, GI
    • Brief defervescence
    • Phase 2: aseptic meningitis or encephalitis
  • CSF: lymphocytic pleocytosis (sometimes > 1000 cells), normal glucose, mildly elevated protein
  • Self-limited usually
  • Rare encephalitis with sequelae
223.1.0.3.2.2 Congenital LCMV
  • 1st-2nd trimester maternal infection
  • Clinically similar to congenital CMV:
    • Microcephaly
    • Hydrocephalus
    • Chorioretinitis (most common ocular finding)
    • Intracranial calcifications (periventricular)
    • Intellectual disability
    • Hearing loss less prominent than CMV
  • Important: don’t miss in CMV-negative congenital infection workup
223.1.0.3.2.3 Transplant LCMV
  • Donor LCMV+ → recipient infection within weeks
  • Multi-organ failure
  • High mortality
  • Surveillance + screening
223.1.0.3.3 Diagnosis
  • PCR of CSF + blood
  • Serology (paired sera or IgM)
  • Tissue PCR + IHC for congenital
223.1.0.3.4 Treatment
  • Supportive primarily
  • Ribavirin off-label for severe (transplant, immunocompromise)
  • Reduce immunosuppression in transplant
  • Anticonvulsants for seizures
  • Congenital: supportive + early intervention
223.1.0.3.5 Prevention
  • Rodent control
  • Pet rodent caution in pregnancy (limit handling, hygiene)
  • Donor screening for transplant (limited routine)

223.1.0.4 3⃣ S. American Hemorrhagic Fevers

223.1.0.4.1 Junin (Argentine Hemorrhagic Fever)
  • Junin mammarenavirus
  • Rodent: Calomys musculinus
  • Geography: Argentine pampas (rural)
  • Clinical: gradual febrile illness → bleeding + neurological + cardiovascular collapse; mortality 15-30%
  • Vaccine: Candid #1 (developed in Argentina) — effective; reduced incidence dramatically
  • Ribavirin + supportive
223.1.0.4.2 Machupo (Bolivian Hemorrhagic Fever)
  • Machupo mammarenavirus
  • Rodent reservoir (Calomys callosus)
  • Bolivia
  • Severe hemorrhagic fever
  • Mortality 30%+
  • Ribavirin treatment
223.1.0.4.3 Guanarito (Venezuelan Hemorrhagic Fever)
  • Guanarito mammarenavirus
  • Rodent reservoir
  • Venezuela
  • Similar to Machupo
  • Ribavirin
223.1.0.4.4 Sabia (Brazilian Hemorrhagic Fever)
  • Sabia mammarenavirus
  • Rodent reservoir
  • Brazil
  • Severe hemorrhagic
  • Ribavirin
223.1.0.4.5 Chapare (2003+, Bolivia)
  • Newer recognized arenavirus
  • Hemorrhagic fever
  • Bolivia
223.1.0.4.6 Lujo (2008)
  • Emerged Zambia → South Africa
  • Severe hemorrhagic fever
  • 5/5 cases initially died
  • Rodent reservoir suspected
  • Sporadic since