What are the guidelines for managing leptospirosis (Leptospirosis Clinical Practice Guidelines, CPG) in the Philippines?

Leptospirosis Clinical Practice Guidelines for the Philippines

Classification and Clinical Presentation

Leptospirosis should be classified into two main clinical forms: mild-to-moderate disease (flu-like illness) and severe disease (Weil's disease) characterized by hemorrhage, jaundice, and hepato-renal failure. 1

Mild-to-Moderate Disease

• The septicemic phase lasts 4-7 days and presents with high fever (≥39°C), diffuse myalgias (especially in the calves), headache, and conjunctival suffusion 1
• Conjunctival suffusion is a highly suggestive clinical sign that should raise immediate suspicion 1, 2
• This is the most common presentation of leptospirosis 1

Severe Disease (Weil's Disease)

• Occurs in approximately 5-10% of infected individuals 1
• Characterized by the triad of jaundice, hepatorenal syndrome, and hemorrhagic manifestations due to capillary fragility 2
• May present with a biphasic illness pattern: initial bacteremic phase followed by an immune phase with potential organ failure 2

Diagnostic Approach

Clinical Suspicion Criteria

Suspect leptospirosis in any patient presenting with sudden onset fever, severe general malaise, muscular pain, and conjunctival suffusion, especially with relevant exposure history. 2

Key Exposure History to Elicit

• Recreational water sports in fresh water 1
• Occupational exposure to animals or contaminated water 1
• Recent flooding with water contact 1
• Contact with rats, dogs, cattle, or other domestic/wild animals 1

Laboratory Findings

• Urinalysis: Proteinuria and hematuria 1, 2
• Complete blood count: Leukocytosis with polymorphonuclear predominance 1, 2
• Liver function tests: Elevated bilirubin with mild transaminase elevation (do not underestimate severity based on modest transaminase elevations) 1, 2
• Renal function: Alterations in renal function tests 1
• Anemia: May occur if significant hemorrhage present 1

Confirmatory Testing

• Serology (most common method): IgM titers >1:320 are suggestive; titers of 1:80-1:160 consistent with early infection 1
• Convalescent serology: Obtained >10 days after symptom onset can confirm diagnosis 1
• Blood cultures: Most useful if obtained within first 5 days before antibiotics; three or more cultures should be taken at least 1 hour apart 1, 3
• Molecular testing (NAAT): Turnaround time typically 1-2 hours 1

Critical Pitfall: Serology may not be positive until 6-10 days after symptom onset; do not delay treatment while awaiting laboratory confirmation 2

Treatment Algorithm

Immediate Management Decision Tree

Start antibiotics immediately upon clinical suspicion without waiting for laboratory confirmation, as each hour of delay increases mortality. 1, 2

Step 1: Assess Disease Severity

Mild-to-Moderate Disease (Outpatient or Hospitalization Based on Clinical Judgment):

• No jaundice, renal failure, hemorrhage, or respiratory compromise 4
• Hospitalization recommended if systemic signs of infection present, even without severe disease criteria 1

Treatment:

• Doxycycline 100 mg orally twice daily for 7 days (preferred) 1, 3
• Alternative: Penicillin orally for 7 days (effective during bacteremic phase) 4, 3
• Alternative: Azithromycin (appears promising for less severe disease) 3

For children <8 years: Use penicillin or amoxicillin instead of doxycycline due to effects on bone and teeth development 4

Step 2: Severe Disease (Weil's Disease) - Requires Immediate ICU Consideration

Criteria for Severe Disease:

• Jaundice 4
• Renal insufficiency 4
• Hemorrhage 4
• Respiratory compromise 4
• Persistent tissue hypoperfusion despite initial fluid resuscitation 1

Treatment Protocol:

• Start antibiotics within 1 hour of recognition (Grade 1B for septic shock, Grade 1C for severe sepsis without shock) 1
• Penicillin IV (preferred) or ceftriaxone or cefotaxime for 7 days 1, 3
• May extend to 10 days in patients with slow clinical response 1
• Reassess antimicrobial regimen daily for potential de-escalation (Grade 1B) 1

Critical Consideration: Treatment initiated after 4 days of symptoms may be less effective; early initiation is crucial 1

Supportive Care for Severe Disease

Fluid Resuscitation

• Target systolic blood pressure >90 mmHg in adults and normal heart rate/blood pressure in children 1
• Monitor for crepitations indicating fluid overload or impaired cardiac function during resuscitation 1
• Continuous observation required; septic patients should never be left alone 1

Source Control

• Consider source control measures within 12 hours if applicable (Grade 1C) 1

Organ Support

• Patients may require renal or liver support despite antibiotic therapy 4, 2
• The severe phase is immunologically mediated, so antibiotic benefit may be limited in this stage 4

Special Considerations and Pitfalls

Critical Pitfalls to Avoid

• Never delay treatment while awaiting laboratory confirmation - this increases mortality 1, 2
• Do not underestimate disease severity based on modest transaminase elevations - patients can become critically ill despite this 2
• Do not discontinue antibiotics too early - complete the full 7-day course even with clinical improvement 1
• Do not misdiagnose as viral hepatitis - always consider leptospirosis in patients with fever and jaundice in endemic areas 1

Pregnancy Considerations

• Avoid tetracyclines (doxycycline) in pregnant women 4
• Use penicillin or amoxicillin as alternatives 4

Antibiotic Sensitivity

• Leptospires are sensitive to penicillins, cephalosporins, aminoglycosides, tetracyclines, and macrolides 5, 3
• Streptomycin shows the best bactericidal action but requires short-term treatment 5, 6
• Penicillins, cephalosporins, tetracyclines, and macrolides may require longer therapy with larger doses from early disease stage until antibody appearance 5, 6

Monitoring During Treatment

• Obtain blood cultures before antibiotics if this causes no significant delay (<45 minutes) 1
• Monitor for development of complications including myocarditis, pericarditis (independently predictive of severe disease), and aseptic meningitis (occurs in ~19% of cases) 1

Prevention Counseling

• Avoid contact with urine from infected animals 1
• Avoid contact with water contaminated with urine 1
• Take precautions during water recreational activities, occupational exposure, and during floods 1