183.1 🎓 醫學生版

183.1.0.1 📌 一頁重點

• 菌: Leptospira interrogans (pathogenic) + non-pathogenic L. biflexa — spirochete with hooked ends, 動 sharply (corkscrew)
• Reservoir: 動物 renal tubules (rats, cattle, dogs, pigs); shed in urine into water/soil
• Transmission: 皮膚 / 黏膜 / 結膜 / 食 / 喝水 contact with contaminated water/soil
• Risk: 農業 (rice/sugarcane farmers), abattoir, sewer workers, military, 颱風 / 洪水 outbreaks, 戶外運動 (triathletes), 水上活動 (kayaking, swimming)
• 2 phase 臨床:
  • Phase 1 (Leptospiremic, 1-7d): 急 fever, 頭痛, myalgia (calf!), conjunctival suffusion, nausea, abdominal pain
  • Brief defervescence 1-3d
  • Phase 2 (Immune, 4-30d): meningitis (aseptic), uveitis, severe forms
• Severe (10% — “Weil’s disease”):
  • Jaundice (cholestatic) + AKI + 出血 (pulmonary hemorrhage)
  • Pulmonary hemorrhage syndrome (SPHS) — Taiwan/Asia variant
  • Myocarditis, arrhythmia
  • Mortality 5-15%
• Dx:
  • MAT (microscopic agglutination test) — gold standard, paired serology
  • PCR of blood (early), urine (later)
  • IgM ELISA rapid
  • Dark-field microscopy — historical
• Treatment:
  • Mild: doxycycline 100 PO bid × 7d OR azithromycin
  • Severe: ceftriaxone 1-2 g IV qd × 7d OR PCN G 1.5 M U IV q6h × 7d
  • Supportive: ICU, dialysis, ventilator, transfusion
• Prevention: Doxycycline 200 mg PO weekly for high-risk exposure (military, agricultural, flood relief workers); avoid contaminated water

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183.1.0.2 1️⃣ 細菌學

• Leptospira — spirochete with hooked / question-mark shape
• Motile (axial filaments)
• Aerobic, dark-field visible (rare in routine)
• 250+ serovars in 25+ serogroups; pathogenic in L. interrogans
• Common serovars:
  • Icterohaemorrhagiae — Weil’s classic
  • Canicola — dogs
  • Hardjo — cattle
  • Pomona — pigs
  • Australis, Autumnalis — varied
• Reservoir hosts: rodents (rat #1), domestic livestock, dogs (canicola), wild animals
• Animal asymptomatic carriers — chronic shed urine
• Survival in warm fresh water weeks-months — explains outbreak after floods

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183.1.0.3 2️⃣ 流行病學

• Global ~ 1 million severe cases/yr, 60,000 deaths
• Tropical / subtropical: SE Asia, India, Caribbean, Pacific
• Outbreaks after: 颱風, 洪水, 海嘯, hurricane
• Taiwan: 颱風後 surge (Morakot 2009, etc.)
• USA: Hawaii dominant, also continental sporadic
• 2024: ongoing 颱風 / climate change increasing risk
• High-risk occupations: rice farmer, abattoir worker, sewer worker, military deployment, veterinarian, water sports
• 2010s emerging issue: urban outbreaks in 紐約 / Baltimore from rat-contaminated water

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183.1.0.4 3️⃣ 臨床表現 (Biphasic Classic)

183.1.0.4.1 Phase 1: Leptospiremic / Septicemic (Days 1-7)

• 急性 onset, 高燒, severe headache, myalgia (especially calves + back) — classic
• Conjunctival suffusion (redness without exudate — diagnostic clue)
• Nausea, vomiting, abdominal pain
• Pharyngitis, cough
• Lymphadenopathy
• Self-limited if mild

183.1.0.4.2 Brief Defervescence (Days 5-7)

• 1-3 day improvement
• Many recover here without further illness

183.1.0.4.3 Phase 2: Immune (Days 7-30+)

• Recurrence of fever (lower grade)
• Aseptic meningitis (mononuclear CSF)
• Uveitis (anterior, posterior, panuveitis)
• Hepatitis (icteric)
• Renal involvement
• Hemorrhage

183.1.0.4.4 Severe Disease (“Weil’s Disease”)

• 5-10% of all cases
• Triad: jaundice (cholestatic hyperbilirubinemia) + AKI + bleeding
• Severe hepatic involvement (bilirubin > 20 mg/dL, modest ALT/AST)
• AKI: ATN + interstitial nephritis, hypokalemia (early, distal tubular dysfunction)
• Bleeding: skin petechiae, GI bleed, alveolar hemorrhage, retinal
• Severe Pulmonary Hemorrhage Syndrome (SPHS) — Taiwan + Asia variant; alveolar hemorrhage + ARDS + high mortality 50%+
• Myocarditis (T-wave changes, AVB)
• Mortality 5-15% overall, higher with SPHS

183.1.0.4.5 Special Forms

• Aseptic meningitis as predominant presentation
• Pulmonary hemorrhage as predominant (Asia)
• Uveitis late post-infection (weeks to months) — distinct, treatable
• Cardiac involvement (myocarditis)

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183.1.0.5 4️⃣ 診斷

183.1.0.5.1 A. Serology

• MAT (Microscopic Agglutination Test) — gold standard, paired sera (acute + convalescent)
  • 4-fold rise or single high titer (1:800+)
  • Slow (specialty labs)
• IgM ELISA — rapid, 確診 days 5-10 onwards
• Rapid tests (LFA / lateral flow) — point of care, sensitivity varies

183.1.0.5.2 B. Molecular

• PCR of blood — high yield first 7-10 days (leptospiremic phase)
• PCR of urine — days 10-30 (immune phase shed urine)
• PCR CSF — meningitis form

183.1.0.5.3 C. Dark-Field Microscopy

• Blood (early), CSF, urine (late) — sensitivity low, lab capability rare
• Historical method

183.1.0.5.4 D. Culture

• Blood, CSF, urine
• Specialized media (EMJH, Fletcher’s)
• Slow (4-6 wk) — not for clinical decision

183.1.0.5.5 E. Lab Findings

• WBC ↑ or normal, neutrophilic
• Thrombocytopenia
• ↑ CK (myalgia)
• ↑ AST/ALT (modest, often < 200)
• ↑ Bilirubin (severe, often disproportional to LFT)
• BUN/Cr ↑
• Hypokalemia (distal tubular)
• CSF: lymphocytic pleocytosis, normal glucose, mild protein ↑

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183.1.0.6 5️⃣ 治療

183.1.0.6.1 Mild Disease (Outpatient)

• Doxycycline 100 mg PO bid × 7d
• Alt: azithromycin 500 mg day 1 → 250 qd × 4d
• Amoxicillin (less data)

183.1.0.6.2 Severe Disease (ICU)

• Ceftriaxone 1-2 g IV qd × 7d
• OR PCN G 1.5 M U IV q6h × 7d
• OR Doxycycline 100 mg IV q12h × 7d (alt)
• OR Cefotaxime 1 g IV q6h × 7d
• 同 antibiotic efficacy (PCN, doxy, ceftriaxone same outcome in multiple RCTs)
• Add steroid for SPHS — controversial; some RCTs show benefit in pulmonary hemorrhage

183.1.0.6.3 Supportive

• ICU monitoring
• Dialysis if AKI
• Mechanical ventilation if SPHS / ARDS
• Transfusion for bleeding
• Vasopressor for shock
• Plasma exchange — some advocate severe SPHS

183.1.0.6.4 Jarisch-Herxheimer Reaction

• Can occur after PCN dose
• Less common than syphilis

183.1.0.6.5 Pregnancy

• Doxycycline contraindicated
• PCN G or ceftriaxone preferred

183.1.0.6.6 Pediatric

• Ceftriaxone or PCN
• Doxycycline avoided < 8 yr (or short course OK)

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183.1.0.7 6️⃣ Prevention

183.1.0.7.1 Personal

• Avoid contaminated water (especially after flood)
• Protective gear (boots, gloves) for high-risk work
• Wound care after exposure
• Boil / treat water

183.1.0.7.2 Doxy-PEP Chemoprophylaxis

• Doxycycline 200 mg PO weekly during high-risk exposure period
• Military, flood relief workers, athletes in endemic
• Pre-exposure or post-exposure (within 48 hr)

183.1.0.7.3 Vaccination

• Animals: routine in dogs (4 serovars), livestock
• Human: limited (some countries use serovar-specific killed vaccine — China, Japan, France for high-risk workers)
• Not US-available

183.1.0.7.4 Public Health

• Rodent control
• Sanitation
• Flood response messaging
• 通報 (notifiable in most countries)

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