Leptospirosis

A 32-year-old male farmer presents with a 5-day history of high-grade fever, chills, severe myalgia, headache, and vomiting. He complains of intense pain in both calves and lower back. He also reports redness of both eyes without discharge and decreased urine output for the past 2 days. One week before symptom onset, he had been working barefoot in stagnant floodwater after heavy monsoon rains. On examination, he is febrile, tachycardic, mildly hypotensive, and dehydrated. Bilateral conjunctival suffusion and mild scleral icterus are noted. Laboratory investigations reveal thrombocytopenia, elevated bilirubin, mild to moderate transaminitis with AST predominance, serum creatinine 2.1 mg/dL, hyponatremia, hypokalemia, and elevated creatine phosphokinase (CPK). Diagnosis?

Diagnosis is Leptospirosis (severe icteric form, Weil’s disease).

1. Definition

1. Leptospirosis is a zoonotic bacterial infection caused by pathogenic Leptospira species.
2. It ranges from a mild self-limited febrile illness to severe multiorgan disease.
3. Severe disease (Weil’s disease) is characterized by:
1. Jaundice
2. Acute kidney injury (AKI)
3. Hemorrhage and/or pulmonary involvement

2. Etiology / Epidemiology

1. Caused by pathogenic Leptospira interrogans and related serovars
2. Reservoirs:
1. Rats (most important)
2. Dogs
3. Cattle
4. Pigs
3. Organisms are shed in animal urine contaminating:
1. Water
2. Soil
3. Mud
4. Transmission occurs via:
1. Skin abrasions
2. Mucosal surfaces
3. Conjunctiva
5. Risk factors:
1. Farmers
2. Sewage workers
3. Veterinarians
4. Flood exposure
5. Freshwater swimming
6. Common in tropical and subtropical regions, especially during monsoon seasons

3. Pathophysiology

1. Organisms enter through abraded skin or mucosa
2. Initial leptospiremic phase:
1. Hematogenous dissemination
2. Involvement of liver, kidneys, lungs, CNS, and heart
3. Immune phase occurs after antibody formation.
4. Vasculitis and endothelial injury cause:
1. Capillary leak
2. Hemorrhage
3. Organ dysfunction
5. Renal involvement commonly causes:
1. Non-oliguric AKI (classically)
2. Hypokalemia
6. Pulmonary hemorrhage and ARDS are major causes of mortality
7. Pulmonary involvement may occur even without jaundice

4. Clinical Features

4.1 General Features

1. Abrupt onset fever
2. Chills
3. Severe myalgia
4. Headache
5. Fatigue

4.2 Characteristic Features

1. Severe calf muscle tenderness
2. Conjunctival suffusion (conjunctival injection without purulent discharge)
3. Back and thigh pain

4.3 Gastrointestinal / Hepatic Features

1. Nausea
2. Vomiting
3. Abdominal pain
4. Jaundice
5. Hepatomegaly (occasionally)

4.4 Renal Features

1. Acute kidney injury
2. Non-oliguric AKI is classically seen, although oliguria may occur in severe disease
3. Electrolyte abnormalities:
1. Hypokalemia
2. Hyponatremia

4.5 Pulmonary Features

1. Cough
2. Hemoptysis
3. Pulmonary hemorrhage
4. ARDS

4.6 Neurological Features

1. Aseptic meningitis
2. Altered mental status
3. Encephalopathy

4.7 Cardiac Features

1. Myocarditis
2. Arrhythmias
3. Hypotension

5. Diagnosis

5.1 Clinical Suspicion

1. Acute febrile illness with:
1. Severe myalgia
2. Conjunctival suffusion
3. Floodwater or animal exposure
2. High suspicion in endemic tropical regions during monsoon season

5.2 Laboratory Findings

1. Leukocytosis
2. Thrombocytopenia
3. Elevated bilirubin
4. Mild to moderate transaminitis, often with AST predominance
5. Elevated creatinine
6. Hyponatremia and hypokalemia
7. Elevated CPK
8. Proteinuria or hematuria

5.3 Confirmatory Tests

1. IgM ELISA
2. Microscopic agglutination test (MAT)
3. PCR:
1. Blood in early disease
2. Urine later in disease
4. Culture (rarely used clinically)

5.4 Severity Indicators

1. Jaundice
2. AKI
3. Pulmonary hemorrhage
4. Hypotension
5. Altered sensorium
6. Respiratory failure

6. Differential Diagnosis

1. Dengue fever
2. Malaria
3. Scrub typhus
4. Typhoid fever
5. Viral hepatitis
6. Hantavirus infection
7. Rickettsial infections
8. Sepsis

7. Management

7.1 Mild Disease

1. Doxycycline 100 mg orally twice daily for 7 days
2. Alternatives:
1. Azithromycin
2. Amoxicillin
3. Antibiotics are most effective when started early in the leptospiremic phase

7.2 Severe Disease

1. Hospital admission
2. Ceftriaxone 1 to 2 g IV daily
3. Alternatives:
1. IV Penicillin G
2. Cefotaxime

7.3 Supportive Care

1. Intravenous fluids
2. Electrolyte correction
3. Dialysis for severe AKI
4. Oxygen or ventilatory support
5. Vasopressors if shock develops
6. Blood product transfusion if hemorrhage occurs

7.4 Special Considerations

1. Avoid doxycycline in pregnancy and young children
2. Jarisch Herxheimer reaction is uncommon but may occur after antibiotic initiation
3. Early antibiotic therapy reduces complications

8. Monitoring

1. Vital signs
2. Urine output
3. Renal function
4. Electrolytes
5. Platelet count
6. Liver function tests
7. Respiratory status

9. Complications

1. Acute kidney injury
2. Pulmonary hemorrhage
3. ARDS
4. Shock
5. Myocarditis
6. Arrhythmias
7. Meningitis
8. Disseminated intravascular coagulation (DIC)
9. Multiorgan failure

10. Prognosis

1. Mild disease usually resolves completely
2. Severe disease carries significant mortality
3. Mortality is highest in patients with pulmonary hemorrhage, ARDS, shock, or multiorgan failure
4. Early diagnosis and treatment improve outcomes

11. Prevention

1. Avoid contaminated water exposure
2. Use protective clothing and boots
3. Rodent control measures
4. Safe drinking water
5. Weekly doxycycline prophylaxis may be considered for short-term high-risk exposure, although evidence is limited

12. Key Clinical Insight

1. Fever + severe calf muscle pain + conjunctival suffusion + floodwater exposure strongly suggests leptospirosis

13. Key Exam Points

1. Conjunctival suffusion is a classic clue
2. Severe calf tenderness is highly characteristic
3. Weil’s disease = jaundice + AKI + hemorrhage
4. Pulmonary hemorrhage is the leading cause of death
5. Hypokalemia with AKI is a classic laboratory clue
6. IgM ELISA is commonly used for diagnosis
7. Do not delay empiric antibiotics if suspicion is high
8. Early treatment reduces complications and mortality