Leptospirosis: Etiology and Pathogenesis

• Leptospirosis is a spirochetal infection
• It is acquired by animals and humans through direct or indirect contact of skin or mucous membranes with contaminated urine

Etiology

• Leptospira interrogans is the causative agent, with 200 serovars
• This spirochete is Gram-negative bacillus (GNB), motile, obligate aerobic, and slow growing
• It lives in water, soils, and moist organic matter
• It is found in infected urine and parturition tissue
• It may survive weeks to months outside a host

Pathogenesis

• Leptospirosis enters the body through cuts, abraded or soft skin, mucous membranes, and conjunctiva
• It can also be transmitted through inhalation or ingestion
• The infection spreads through the blood stream, lymphatics, and organs
• It causes systemic vasculitis and hemorrhage
• Renal failure can occur due to ischemia
• Jaundice can occur due to hepatic cell dysfunction
• Myalgias can occur due to necrosis of myofibrils and hemorrhage
• Intrauterine infections are also possible

Clinical Manifestations

• The incubation period is 5-30 days
• Anicteric leptospirosis is a manifestation
• Icteric leptospirosis is a manifestation, also known as Weil's syndrome

Septicemic Phase-Anicteric (90%)

• High fever (38-40ºC) is a symptom
• Headache, chills, and rigors are symptoms
• Meningeal irritation is a symptom
• Abdominal pain and anorexia are symptoms
• Myalgias and conjunctival suffusion are symptoms
• Nausea, vomiting, and diarrhea are symptoms
• Cough, pharyngitis, and hemoptysis are symptoms
• Maculopapular rash is a symptom

Weil's Syndrome - Icteric (10%)

• Hepatic and renal dysfunction occur
• Hemorrhagic pneumonitis and ARDS occur
• Cardiac arrhythmia and circulatory collapse occur
• Jaundice occurs after the 7th day
• Adrenal hemorrhage, possibly leading to sudden death, occurs
• Hepatosplenomegaly occurs in 25% of cases
• Hypoprothrombinemia occurs
• CPK increases
• Thrombocytopenia occurs
• Interstitial nephritis, congestive heart failure, and myocarditis occur

Diagnosis

• Confirmatory tests include MAT microscopic agglutination, PCR, urine antigen testing one week after symptoms, and pathology with formalin-fixed samples
• Supportive tests include IgM testing

Diagnostic Tests

• Microscopy using Gram stain is insensitive
• Microscopy using Darkfield is intensive and nonspecific
• Direct fluorescent antibody microscopy is generally unavailable
• Blood cultures are positive during the first week
• CSF cultures are positive during the final or second week
• Urine serology is positive after the first week
• Microscopic agglutination is sensitive, specific, and positive after the second week, peaking after 5 to 6 weeks and potentially persisting for months

Laboratories

• Proteinuria, pyuria, and hematuria are found
• Creatinine and liver enzymes increase
• Bilirubin increases to less than 20mg/dl
• PT increases
• WBC increases, and Hgb and platelets decrease
• CSF shows pleocytosis, normal glucose, and mild increase in protein

Prevention

• Avoid contact with infected animals and contaminated water, soil, and mud
• Animal vaccines may be available
• Chemoprophylaxis can be 95% effective

Agents Recommended for Chemoprophylaxis and Treatment

• Doxycycline is used for chemoprophylaxis at a dosage of 200mg once a week
• Doxycycline is used for treatment of mild leptospirosis at a dosage of 100mg 10 bid
• Ampicillin or amoxicillin are used for treatment of mild leptospirosis at dosages of 500-750mg q6h or 500mg q6h respectively
• Penicillin G or ampicillin are used for treatment of moderate to severe leptospirosis at dosages of 1.5 million UIV g6h or 0.5-1g IV q6h respectively