Leptospirosis: Etiology and Pathogenesis

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

Etiology

• It is caused by Leptospira interrogans, which has 200 serovars
• Leptospira is a spirochete, Gram-negative bacteria (GNB), and motile.
• Leptospira are obligate aerobes and slow-growing.
• Leptospira are found in water, soils, and moist organic matter.
• They can also be found in infected urine and parturition tissue.
• Leptospira can survive for weeks to months in the environment.

Pathogenesis

• Leptospirosis enters the body through cuts, abraded skin, or soft skin.
• It can also enter through mucous membranes or the conjunctivae.
• Other routes of entry are inhalation and ingestion.
• Once in the body, it enters the bloodstream, lymphatics, and organs.
• Pathogenesis leads to systemic vasculitis and hemorrhage.
• Renal failure can occur due to ischemia.
• Jaundice results from hepatic cell dysfunction.
• Myalgias occur due to necrosis of myofibrils and hemorrhage.
• Intrauterine infections may also occur.

Clinical Manifestations

• The incubation period for Leptospirosis is 5-30 days.
• Clinical manifestations include anicteric leptospirosis and icteric leptospirosis, otherwise know as Weil's syndrome.

Septicemic Phase (Anicteric)

• Septicemic phase (anicteric) accounts for approximately 90% of cases
• High fever (38-40ºC)
• Other symptoms include headache, chills, rigors, and meningeal irritation.
• Patients may experience abdominal pain, anorexia, myalgias, and conjunctival suffusion.
• Nausea, vomiting, diarrhea, cough, pharyngitis, hemoptysis, and a maculopapular rash can occur.

Weil's Syndrome (Icteric)

• Weil's syndrome (icteric) accounts for 10% of cases
• Symptoms include hepatic and renal dysfunction, hemorrhagic pneumonitis, and ARDS.
• Other symptoms include cardiac arrhythmia and circulatory collapse.
• Jaundice can occur after the 7th day.
• Features also include adrenal hemorrhage, sudden death, and hepatosplenomegaly (25%).
• Hypoprothrombinemia, increased CPK, thrombocytopenia, interstitial nephritis, congestive heart failure, and myocarditis can be seen.

Diagnosis

• Confirmatory tests include MAT microscopic agglutination, test-acute, convalescence nt serum samples, PCR, urine antigen one week after symptoms, and pathology (CDC) formalin fixed.
• Supportive tests include measuring IgM levels.

Diagnostic Tests for Leptospirosis

• Microscopy using Gram stain results in organisms unable to be seen
• Microscopy with darkfield staining is intensive and nonspecific.
• Direct fluorescent antibody testing is insensitive and generally unavailable.
• Blood culture results are positive during the first week.
• CSF culture results are positive during the final or second week.
• Serology is positive after the first week.
• Urine analysis using microscopic agglutination is sensitive, specific, and positive after the second week, with peaks after 5 to 6 weeks and may persist for months.

Laboratories

• Laboratory abnormalities include proteinuria, pyuria, and hematuria.
• Increased creatinine and liver enzymes
• Increased bilirubin (less than 20mg/dl) and prothrombin time (PT)
• Increased WBC's, decreased hemoglobin (Hgb) and platelets
• CSF findings include pleocytosis, normal glucose, and mild increases in protein.

Prevention

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

Agents Recommended for Chemoprophylaxis and Treatment

• For chemoprophylaxis, the recommended drug is Doxycycline (200mg once a week).
• For mild leptospirosis, treatments include Doxycycline (100mg 10 bid), Ampicillin (500-750mg qóh), or Amoxicillin (500mg q6h).
• For moderate to severe leptospirosis, treatments include Penicillin G (1.5 million UIV q6h) or Ampicillin (0.5-1g IV q6h).