Leptospirosis

Definition & Causative Organism

Epidemiology

• Global burden: ~1 million severe cases/year; mean case-fatality rate nearly 10%.
• Distribution: Worldwide, but most common in tropics and subtropics (climate favors survival). Peak incidence in summer/fall (temperate zones) and rainy season (tropics).
• Reservoir hosts: Rodents (especially rats) are the most important. Other wild mammals and domestic/farm animals also harbor the organism. Leptospires persist in the urogenital tract of reservoir hosts for years.
• Serovar-host associations:

• Transmission: Contact with urine, blood, or tissue of infected animals, or more commonly exposure to contaminated water/soil (leptospires survive in humid environments for months). Outbreaks occur after flooding.
• High-risk occupations: Veterinarians, agricultural workers, sewage workers, slaughterhouse employees, fishery workers.
• Recreational risks: Swimming, canoeing, waterskiing, mud-runs, jungle trekking, caving. Also a traveler's disease (Southeast Asia predominant - especially Thailand).

Pathogenesis

1. Leptospiremic phase (Days 1-7): Organisms proliferate, cross tissue barriers, and disseminate hematogenously to all organs. Leptospires evade complement-mediated killing and phagocytosis. An exaggerated proinflammatory immune response is linked to mortality.
2. Immune phase (Week 2+): Antibody appearance coincides with disappearance of leptospires from blood. Bacteria persist in liver, lung, kidney, heart, and brain.

• Kidney: Acute tubular damage + interstitial nephritis → tubular necrosis. Impaired sodium absorption, tubular potassium wasting, polyuria due to transporter deregulation.
• Liver: Focal necrosis, inflammation, bile canalicular plugging, hepatocyte apoptosis. Leptospira infiltrate Disse space and migrate between hepatocytes.
• Lungs: Pulmonary hemorrhage is a major cause of death.
• Muscle: Rhabdomyolysis with myoglobinuria.

Clinical Manifestations

Phase 1: Anicteric Leptospirosis (mild; ~90% of cases)

• Abrupt-onset high fever, severe headache, myalgia (especially calf muscles), conjunctival suffusion (non-purulent redness - pathognomonic clue)
• Pharyngeal injection, lymphadenopathy, rash, meningismus, hepatomegaly, splenomegaly

• Symptoms may briefly resolve then recur (biphasic pattern)
• Aseptic meningitis in ~15% of all cases
• Uveitis (may be delayed by weeks to months)

Phase 2: Icteric Leptospirosis - Weil's Disease (~5-10% of cases)

• Jaundice (elevated bilirubin - more conjugated; liver failure is rare)
• Acute kidney injury (interstitial nephritis, tubular necrosis)
• Pulmonary hemorrhage - ARDS-like presentation, often fatal
• Thrombocytopenia and bleeding
• Myocarditis/arrhythmias
• Uveitis

Diagnosis

• Serology (MAT titre ≥1:100 with compatible illness, or seroconversion) is confirmatory.
• PCR on blood is most useful in the first week before antibodies develop.

• Elevated creatinine, bilirubin, transaminases (moderate)
• Thrombocytopenia
• CK elevated (myositis)
• Urinalysis: proteinuria, hematuria, casts

Treatment

Mild-Moderate Disease

• Doxycycline 100 mg oral twice daily for 7 days (drug of choice)
• Amoxicillin or ampicillin are alternatives

Severe Disease (hospitalized)

• Penicillin G 1.5 million units IV q6h for 7 days - traditional first-line
• Ceftriaxone 1 g IV once daily - at least as effective as penicillin; now preferred by many
• Cefotaxime is an alternative

Supportive Care

• Aggressive fluid management for AKI
• Renal replacement therapy (dialysis) for severe AKI - dramatically reduces mortality
• Mechanical ventilation for ARDS/pulmonary hemorrhage
• Manage electrolyte abnormalities (hypokalemia common)

Prophylaxis

• Doxycycline 200 mg orally once weekly for high-risk occupational/recreational exposure
• Post-exposure: doxycycline 200 mg single dose within 1-2 days
• Vaccines exist for animals; human vaccines used in some endemic countries (Cuba, China, France) but not widely available

Prognosis

• Elderly patients
• Pulmonary hemorrhage syndrome (up to 50% mortality)
• Weil's disease (5-15% mortality with treatment)

Differential Diagnosis

• Dengue fever, malaria, typhoid fever, viral hepatitis
• Influenza, rickettsiosis, hantavirus
• Viral meningitis, bacterial sepsis
• ARDS from other causes

Recent evidence note: A 2025 meta-analysis (PMID 39856559) examined dengue-leptospirosis coinfection, which carries elevated mortality compared to either infection alone - an important diagnostic consideration in tropical regions where both are endemic.