Leptospirosis

Fig. 298-1 - Leptospira interrogans: helical morphology and characteristic hooked end (Goldman-Cecil Medicine)

Definition

• Goldman-Cecil Medicine, Ch. 298

The Pathogen

• Leptospira comes from the Greek "leptos" (thin) + "speira" (coil)
• Tightly coiled, highly motile spirochetes: 0.1 µm diameter, 6-20 µm length
• The trailing end is hooked when moving through liquid, giving it a question-mark shape - hence Leptospira interrogans
• Over 64 species described; pathogenic species include >25 serogroups and 250 serovars
• L. interrogans serovar Icterohaemorrhagiae (via rats) is the most common cause of Weil disease
• L. interrogans serovar autumnalis is associated with pretibial (Fort Bragg) fever
• Survives days to weeks in water at pH >7.0; killed rapidly by acidic conditions, drying, and common disinfectants
• Periplasmic flagella drive motility and enable tissue burrowing
• Sherris & Ryan's Medical Microbiology, 8th Ed.

Epidemiology

• Goldman-Cecil Medicine, Ch. 298

Pathogenesis

• Leptospiral proteins bind LPS and peptidoglycan, shielding them from innate immune detection
• Surface proteins bind complement regulators, resisting complement-mediated killing
• Disruption of endothelial cell junctions facilitates multi-organ invasion

• Kidney: Renal tubular colonization → interstitial nephritis → impaired Na/water reabsorption → potassium wasting and fluid loss (proximal tubular dysfunction)
• Liver: Hepatic sinusoidal invasion → hepatocellular disruption → bile leakage → jaundice
• Lungs: Impaired hemostasis + thrombocytopenia → pulmonary hemorrhage
• Hemostasis: Thrombocytopenia and coagulopathy → bleeding at multiple sites

1. Leptospiremic phase - bacteremia, organism in blood, CSF, urine
2. Immune phase - agglutinating antibodies appear, bacteremia clears, but immune activation can produce a sepsis-like syndrome. Antibiotics are less effective in this phase.

Fig. 298-2 - Interstitial nephritis in severe leptospirosis (Goldman-Cecil Medicine)

Clinical Manifestations

Phase 1 - Leptospiremic (Septicemic) Phase (days 1-7)

• High fever and chills
• Severe bitemporal/frontal throbbing headache with retro-orbital pain and photophobia
• Myalgia - characteristically involving calves and lower back (calf tenderness is a key clinical clue)
• Conjunctival suffusion - pathognomonic injection without exudate
• Subconjunctival hemorrhages
• Nonproductive cough (~50% of cases)
• Nausea, vomiting, diarrhea, abdominal pain
• Maculopapular erythematous skin rash (especially pretibial in Fort Bragg fever)

Fig. 298-4 - Conjunctival suffusion and scleral icterus in a patient with Weil disease (Goldman-Cecil Medicine)

Phase 2 - Immune Phase (days 7-14+)

• Fever may transiently resolve then return
• Aseptic meningitis - headache, neck stiffness, CSF lymphocytosis (Leptospira rarely recovered from CSF at this stage)
• Uveitis, iritis (can be a late complication, weeks to months after acute illness)

Weil Disease (Severe Leptospirosis, ~10% of cases)

1. Jaundice (direct hyperbilirubinemia from hepatocellular + cholestatic injury)
2. Acute renal failure (non-oliguric early → oliguric late; hypokalemia)
3. Hemorrhage - petechiae, ecchymoses, GI bleed, pulmonary hemorrhage (most feared complication - diffuse alveolar hemorrhage with hemoptysis; high mortality)

• Acute hemolytic anemia (especially in G6PD deficiency)
• Multiorgan failure (liver, kidney, lung, brain)
• Cardiac arrhythmias, myocarditis
• Pancreatitis

Case Definitions (WHO/PAHO)

Diagnosis

Laboratory Tests

• Leukocytosis (>80% neutrophils) with thrombocytopenia
• Elevated INR, aPTT, D-dimer
• Elevated creatinine, BUN, direct bilirubin
• Moderate transaminase elevation (AST/ALT usually <200 IU/L - lower than viral hepatitis)
• Pyuria, hematuria, proteinuria
• Elevated procalcitonin and CRP (helps distinguish from viral illness like dengue)
• CSF: aseptic meningitis pattern (lymphocytes, raised protein, normal glucose)
• CT chest: ground-glass opacities/airspace nodules in pulmonary hemorrhage

Differential Diagnosis

• Dengue fever (most common mimic in tropics)
• Malaria
• Typhoid fever
• Viral hepatitis
• Hantavirus
• Melioidosis
• Rickettsial disease
• Influenza

Treatment

Antibiotic Therapy

• Antibiotics are most effective when started early (leptospiremic phase)
• IV penicillin remains first-line for severe/Weil disease; ceftriaxone is equally effective and more convenient

Supportive Care

• Hypokalemia + non-oliguric renal failure (early): Aggressive IV fluids and potassium supplementation
• Oliguric renal failure: Early initiation of hemodialysis or peritoneal dialysis
• Pulmonary hemorrhage: Mechanical ventilation, consider corticosteroids (limited evidence)
• Monitor for arrhythmias, bleeding, and multiorgan failure

2024 Cochrane Evidence

Chemoprophylaxis

Prevention

• Rodent control - particularly in urban/peri-urban settings
• Avoid swimming/wading in potentially contaminated floodwaters
• Use protective clothing and boots in occupational settings
• Drain contaminated water sources
• Vaccination of livestock and pets (reduces human exposure)
• Human vaccines available in some countries (Cuba, China, France) - not widely used elsewhere
• Avoid ingestion or skin contact with animal urine

Key Points Summary