How should leptospirosis be treated in mild versus severe disease, and what prophylaxis is recommended for high‑risk exposures?

Management of Leptospirosis

Treatment Based on Disease Severity

For mild to moderate leptospirosis, start doxycycline 100 mg orally twice daily for 7 days immediately upon clinical suspicion; for severe disease (Weil's disease), initiate ceftriaxone 2g IV daily for 7 days or penicillin G 1.5 million units IV every 6 hours within the first hour of recognition. 1, 2

Mild to Moderate Disease

Oral antibiotic therapy should be initiated as soon as leptospirosis is clinically suspected, without waiting for laboratory confirmation, as each hour of delay increases mortality. 1, 2

• First-line treatment: Doxycycline 100 mg orally twice daily for 7 days 1, 2
• Alternative oral options: Amoxicillin or tetracycline if doxycycline is unavailable 2
• Treatment duration: Complete the full 7-day course even if clinical improvement occurs earlier; extending to 10 days may be necessary in patients with slow clinical response 1
• Expected response: Clinical improvement should occur within 3 days of antibiotic initiation 2

Severe Disease (Weil's Disease)

Severe leptospirosis requires immediate IV antibiotic therapy plus aggressive supportive care, ideally within 1 hour of recognition. 1, 2

• First-line IV treatment: Ceftriaxone 2g IV daily for 7 days 2
• Alternative IV treatment: Penicillin G 1.5 million units IV every 6 hours for 7 days 2
• Supportive care essentials:
  • Aggressive IV fluid resuscitation with crystalloid solutions, up to 60 mL/kg as three boluses of 20 mL/kg, reassessing after each bolus 2, 3
  • Monitor continuously for pulmonary complications (crepitations/crackles); stop fluids immediately if these develop 3
  • Target urine output >0.5 mL/kg/hour and systolic blood pressure >90 mmHg 1, 3
  • Early ICU consultation if repeated fluid boluses are needed or circulatory failure develops 2
• Adjunctive therapy: Methylprednisolone 0.5-1.0 mg/kg IV daily for 1-2 weeks may be used for respiratory complications 2

Recognizing Severe Disease

Severe leptospirosis (Weil's disease) is characterized by jaundice, hemorrhage, and hepato-renal failure, occurring in approximately 5-10% of infected individuals. 1

Key indicators of severe disease include:

• Jaundice with hepatorenal syndrome pattern: Marked hyperbilirubinemia with only modest transaminase elevations 2, 4
• Acute kidney injury: Occurs in ~30% of severe cases, sometimes requiring dialysis 2, 4
• Cardiac involvement: Myocarditis or pericarditis independently predicts severe disease 2, 4
• Pulmonary hemorrhage: Can progress to ARDS 4
• Thrombocytopenia: Platelets <140 G/L in 65.5% of cases 4

Prophylaxis for High-Risk Exposures

Doxycycline 200 mg as a single oral dose provides 76.8% protection for post-flood exposure prophylaxis, but should be reserved only for high-risk settings where attack rates exceed 10 cases per 100 person-years. 2, 5

When to Use Prophylaxis

• Mass outbreak situations with documented high attack rates in endemic areas 3
• Military personnel or workers training/working in endemic areas with high exposure risk 5
• Not recommended for routine use after casual water exposure or in low-risk settings 2, 3

Prophylaxis Regimen

• Adults: Doxycycline 200 mg single oral dose weekly during exposure period 5
• Children <8 years: Doxycycline is contraindicated due to permanent tooth discoloration and enamel hypoplasia; no alternative prophylaxis is established 2, 3
• Adverse effects: 3% experience side effects versus 0.2% with placebo (Number needed-to-harm: 39) 5

Special Populations

Pediatric Patients

• Avoid doxycycline in children <8 years due to permanent tooth discoloration 2
• Use instead: Penicillin or ceftriaxone for both mild and severe disease 2

Pregnant Women

• Avoid tetracyclines and azoles in pregnancy 2
• Use instead: Penicillin or ceftriaxone for treatment 2

Clinical Recognition and Diagnosis

The characteristic biphasic illness pattern includes an initial bacteremic phase (days 1-7) with sudden high fever (≥39°C), severe myalgias (especially calves), frontal headache, and conjunctival suffusion—a highly distinctive non-purulent conjunctival redness that should immediately raise suspicion. 1, 2, 3

Key Diagnostic Features

• Exposure history: Contact with flood water, contaminated fresh water, or animals (rats, dogs, cattle) within 2-20 days 2, 3
• Conjunctival suffusion: Highly suggestive physical finding, present in a minority but pathognomonic when present 1, 2, 4
• Laboratory findings: Proteinuria, hematuria, leukocytosis, elevated bilirubin with mild transaminase elevation 1

Diagnostic Testing

• Serology (IgM ELISA): Titer >1:320 is diagnostic; titers 1:80-1:160 suggest early infection 1
• Convalescent serology: Fourfold increase in titer between acute and convalescent specimens confirms diagnosis 1
• Blood cultures: Only useful if obtained within first 5 days before antibiotics 1, 3
• PCR: Can provide results in 1-2 hours but availability is limited 1

Critical pitfall: Serology is often negative in the first week, so treatment must begin on clinical suspicion alone without waiting for laboratory confirmation. 2, 3

Common Pitfalls to Avoid

• Do not delay treatment while awaiting laboratory confirmation—each hour increases mortality 1, 2
• Do not mistake leptospirosis for viral hepatitis in patients with fever and jaundice 1
• Do not discontinue antibiotics early despite clinical improvement; complete the full 7-day course 1
• Do not use doxycycline prophylaxis in children <8 years—it causes permanent dental damage 2, 3
• Do not add potassium to initial IV fluids despite expected hypokalemia; wait for laboratory confirmation and renal function assessment 3
• Stop fluid resuscitation immediately if crepitations develop, indicating fluid overload or pulmonary hemorrhage 3

Monitoring and Follow-up

• Seriously ill patients: Follow-up 2 days after initial visit to assess treatment response 2
• All patients: Return if symptoms persist longer than 3 weeks 2
• Severe disease: Continuous monitoring in ICU setting with frequent reassessment of perfusion, respiratory status, and renal function 1, 3