Clinical Diagnosis and Treatment of Leptospirosis
Immediate Clinical Action
Start antibiotic treatment immediately upon clinical suspicion of leptospirosis without waiting for laboratory confirmation, as each hour of delay increases mortality. 1, 2
Clinical Diagnosis
Key Historical Features to Elicit
- Exposure history within 2-20 days including contact with flood water, contaminated fresh water, or animals (rats, cattle, pigs, dogs) 1, 2, 3
- Occupational exposure in agricultural workers, especially those working in flooded rice fields 2, 3
- Recreational water activities in fresh water sources 1, 3
Characteristic Clinical Presentation
- Biphasic course with initial bacteremic phase lasting 4-7 days 1
- High fever (usually ≥39°C) with chills 1
- Severe myalgias, especially in the calves 1
- Headache 1
- Conjunctival suffusion - a highly suggestive physical finding 1, 2
Signs of Severe Disease (Weil's Disease)
- Jaundice 1, 2
- Hemorrhagic manifestations 1, 2
- Hepatomegaly 2
- Respiratory distress or hypoxemia 2
- Renal failure 1
Laboratory Findings
- Proteinuria and hematuria on urinalysis 1
- Leukocytosis with polymorphonuclear predominance 1
- Elevated bilirubin with mild transaminase elevation 1
- Elevated creatinine indicating renal dysfunction 1
- Anemia if significant hemorrhage present 1
Diagnostic Confirmation
Immediate Testing (Do Not Delay Treatment)
- Blood cultures - obtain within first 5 days before antibiotics if this causes no significant delay (<45 minutes) 1, 2
- Complete blood count, comprehensive metabolic panel, urinalysis 2
Serological Testing
- IgM ELISA: Titers >1:320 are diagnostic; titers 1:80-1:160 suggest early infection 1, 2
- Convalescent serology (MAT) should be repeated >10 days after symptom onset for confirmation 1, 2
- Important caveat: Serology is often negative in the first week - do not wait for results before starting antibiotics 2
Treatment Algorithm
Mild to Moderate Disease (Outpatient or Hospitalized Without Organ Failure)
Doxycycline 100 mg orally twice daily for 7 days 1, 2, 4
- This is the treatment of choice for mild-to-moderate disease 2
- Reduces duration of illness by 2 days and favorably affects fever, malaise, headache, and myalgias 4
- Prevents leptospiruria 4
Alternative regimens:
- Penicillin - acceptable alternative though doxycycline is preferred 1, 5
- Azithromycin - appears promising for less severe disease 6
Severe Disease (Weil's Disease with Jaundice, Hemorrhage, or Organ Failure)
Start antibiotics within 1 hour of recognition 1, 2
First-line treatment:
Alternative regimen:
- Penicillin G 1.5 million units IV every 6 hours for 7 days 2
Treatment duration:
Special Populations
Children <8 years:
- Avoid doxycycline due to risk of permanent tooth discoloration 2
- Use penicillin or ceftriaxone instead 2
Pregnant women:
Supportive Care for Severe Disease
Fluid Resuscitation
- Target systolic blood pressure >90 mmHg in adults 1
- Monitor for fluid overload with development of crepitations indicating impaired cardiac function 1
- Continuous observation - septic patients should never be left alone 1
ICU Admission Criteria
- Persistent or worsening tissue hypoperfusion despite initial fluid resuscitation 1
- Respiratory complications 1
- Severe organ dysfunction 1
Respiratory Complications
- Methylprednisolone 0.5-1.0 mg/kg IV daily for 1-2 weeks may be used for respiratory complications 2
Post-Flood Prophylaxis
Doxycycline 200 mg single dose orally provides 76.8% protection for post-flood exposure prophylaxis 2
- Should be reserved for high-risk settings 2
Critical Pitfalls to Avoid
- Do not wait for serological confirmation before starting antibiotics - serology is often negative in the first week 2
- Do not mistake leptospirosis for viral hepatitis in patients with fever and jaundice 1, 2
- Do not discontinue antibiotics early despite clinical improvement - complete the full 7-day course 1
- Do not use urine for culture - it is not suitable for leptospira isolation 2
- Do not delay treatment beyond 4 days of symptoms - early treatment is critical for effectiveness 1
Evidence Quality Note
While antibiotics (particularly penicillin and doxycycline) are widely used and recommended by major health organizations including the WHO 1, a 2024 Cochrane review found very low-certainty evidence regarding their effectiveness 7. However, given the potential severity of leptospirosis, the biological plausibility, and consistent guideline recommendations from WHO, CDC, and IDSA 1, 2, antibiotic treatment remains the standard of care and should be initiated promptly upon clinical suspicion.