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 consists of 200 serovars.
• It is a spirochete, Gram-negative bacteria (GNB), and motile.
• Leptospira interrogans is obligate aerobic and slow-growing, lives in water, soils, and moist organic matter, also present in infected urine and parturition tissue.
• It survives weeks to months in the environment.

Pathogenesis

• Transmission occurs through cuts, abraded or soft skin, mucous membranes, and conjunctiva.
• It can also occur through inhalation or ingestion.
• Following transmission, it enters bloodstream, lymphatics, and organs.
• Systemic vasculitis and hemorrhage can result.
• Further complications include renal failure (ischemia), jaundice (hepatic cell dysfunction), myalgias (necrosis of myofibrils, hemorrhage), and intrauterine infections.

Clinical Manifestations

• The incubation period for Leptospirosis is 5-30 days.
• There are two phases of Leptospirosis: anicteric and icteric.
• Icteric leptospirosis is also known as Weil's syndrome.

Septicemic Phase-Anicteric (90%)

• High fever (38-40ºC) may be present.
• Other symptoms include headache, chills, rigors, meningeal irritation, abdominal pain, anorexia, myalgias, conjunctival suffusion, nausea, vomiting, diarrhea, cough, pharyngitis, hemoptysis, and maculopapular rash.

Weil's Syndrome – Icteric (10%)

• Hepatic and renal dysfunction can occur.
• Other symptoms include hemorrhagic pneumonitis, ARDS, cardiac arrhythmia, circulatory collapse, and jaundice (occurring after the 7th day).
• Other complications: adrenal hemorrhage (sudden death), hepatosplenomegaly (25%), hypoprothrombinemia, elevated CPK, thrombocytopenia, interstitial nephritis, congestive heart failure, and myocarditis.

Diagnosis

• Confirmatory tests include MAT microscopy (using acute and convalescent serum samples), PCR, and urine antigen (testing begins one week after symptoms).
• Pathology diagnostic tests include using Formalin fixed samples and running them through the CDC.
• Supportive tests available: IgM

Diagnostic Tests for Leptospirosis

• Microscopy with Gram stain: Organisms cannot be seen
• Microscopy with Darkfield: Intensive, nonspecific
• Microscopy with Direct Fluorescent Antibody: Insensitive, generally unavailable
• Blood Culture: Positive during first week
• CSF Culture: Positive during final or second week
• Urine Serology: Begins positive after first week.
• Urine Microscopy Agglutination: Sensitive, specific, tests become positive after the second week with a peaks after 5 to 6 weeks, and may persist for months

Laboratories

• Laboratory findings include proteinuria, pyuria, hematuria, increased creatinine, increased liver enzymes, increased bilirubin (< 20mg/dl), and increased prothrombin time (PT).
• Other possible findings include increased WBCs, decreased hemoglobin (Hgb), and decreased platelets (plat).
• CSF analysis may show pleocytosis, normal glucose, and mild elevation of protein

Prevention

• Ways to prevent infection include reducing contact with infected animals, contaminated water, soil, and mud.
• Animal vaccines may be available.
• Chemoprophylaxis (95%) can be done

Agents Recommended for Chemoprophylaxis and Treatment

• Chemoprophylaxis: Doxycycline 200mg once a week
• Treatment of mild leptospirosis: Doxycycline 100mg 10 bid, Ampicillin 500-750mg q6h, or Amoxicillin 500mg q6h.
• Treatment of moderate to severe leptospirosis: Penicillin G 1.5 million UIV q6h or Ampicillin 0.5-1g IV q6h.