Leptospirrosis

- zoonotic disease - Very thin spirochetes (0.1 µm in diameter) - they are Gram-negative by cell wall structure, they do not retain the stain well due to their thinness.

• obligate aerobes that can survive for several weeks in the environment.

Pathobiology

• Leptospires enter the body through cuts and abrasions, mucous membranes
• Leptospire tissue penetration may be mediated by a burrowing motion and secreted enzymes including collagenase and sphingomyelinase.
• Leptospiral lipopolysaccharides and lipopeptides have low endotoxic potency but can activate innate immune response through toll-like receptor (TLR)-2 signaling and are thought to generate a cytokine response. Circulating immune complexes may contribute to renal damage and endothelial dysfunction.
• Leptospires may also directly activate plasminogen to plasmin, the main enzyme of the fibrinolytic system, which could promote hemorrhage.

Risk group

• The major groups at risk are sanitaion workers,slum dwellers, farmers, and animal workers, owing to exposure to rodent, domestic, and wild animal reservoirs.
• during travel, extreme outdoor sports activities, and military operations.
• Humans are considered accidental hosts
• rare human-to-human transmission by transplacental infection and breast-feeding has been reported.

Incubation

• the mean incubation period is 10 days, ranging from 5 to 14 days;

Manifestations

• initial septicemic stage

  • high fever and myalgia [calves and lumbar musculature]
  • Cough, nausea and vomiting, diarrhea, headache[ frontal or retroorbital region ], photophobia, and rash may be seen.

  • Conjunctival suffusion is a characteristic finding but only in 1/3 pt at end of septic phase

  • acute phase lasts from 5 to 7 days.

  • CBC indicate bacterial infection

• Temporary decline in fever

• Resolution of symptoms for 1-3days coincides with the presence of agglutinating immunoglobulin (IgM) antibodies and reduction in leptospiremia.

Disease

• Anicteric leptospirosis:mild and self-limiting - milder cases do not always include the second phase

spontaneous resolution within 7–10 days,

• Icteric leptospirosis (Weil's syndrome):severe with life-threatening manifestations including massive pulmonary hemorrhage and Weil’s disease (the triad of jaundice, acute renal failure, and bleeding)

• Immune phase - damage by host immune system after IgM development

• immune phase of illness generally lasts from 4 to 30 days

  • immune phase may be characterized by any or all of the following signs and symptoms:

    • Jaundice

      • Renal failure
      • Cardiac arrhythmias
      • Pulmonary symptoms

      • Aseptic meningitis characteristic of the immune phase of illness 80% of cases

      • Photophobia

      • Eye pain
      • Muscle tenderness
      • Adenopathy
      • Hepatosplenomegaly

  Kidney Presenstation

• hypokalemic, Hyponatremia{ impaired tubular sodium reabsorption.},hypomagnesium

• urinalysis finidings are proteinuria, white blood cells, hematuria, and hyaline and granular casts.

Cardiac

• Cardiac conduction abnormalities can be seen in mild disease.
• First-degree AV and features of pericarditis are the most common findings in severe disease.
• Arrhythmias including ventricular fibrillation may also occur.

Lung manifestation

• cough, dyspnea, and hemoptysis. Leptospirosis-associated pulmonary hemorrhage and acute respiratory distress syndrome is now recognized as a common clinical presentation.
• Xray chest patchy alveolar infiltrate to large areas of consolidation due to hemorrhage

Severe immune phase aka Weils diease (impaired hepatic and renal function.)

• 10-50% mortaility

• Altered mental status has been found to be the strongest predictor of death.

• Other poor prognostic signs include acute renal failure (oliguria, hyperkalemia, serum creatinine >3 mg/ respiratory insufcfiiency (dyspnea, pulmonary rales, chest radiograph infiltrates), hypotension, and arrhythmias.

Post Leptospira sequela

• fatigue, myalgia, malaise, and headache and may persist for years.
• Autoimmune-associated uveitis

Lab Presentation

• Oliguria
• Elevated bilirubin and aminotransferases
• elevated creatinine (greater than 1.5 mg/dL) (132.6 mcmol/L)
• Serum creatine kinase is usually elevated in persons with leptospirosis and normal in persons with hepatitis.

Diagnosis

• (EMJH) or Fletcher media, with often more than 4 weeks needed, with observation under darkfield microscopy.
• Best microbioal source at 1-4th day of illness
• urine leptospira positive for 10days
• Gold Standard microagglutination test (MAT)
• IgM enzyme-linked immunosorbent assay (ELISA) and indirect hemagglutination assays are also available.

• A + B ≥ 26 → Presumptive diagnosis
• A + C ≥ 25 → Confirmed/probable diagnosis

Mng

Mild Leptospirosis – Treatment Options

1. Doxycycline

2. 100 mg PO twice daily (BID)

3. Amoxicillin

4. 500 mg PO every 8 hours (q8h)

5. Ampicillin

6. 500 mg PO every 6 hours (q6h)

7. Azithromycin

8. 1 g single dose, followed by 500 mg once daily for 2 days

Severe Leptospirosis – Treatment Options

1. Intravenous (IV) Penicillin

2. 1.5 million units IV every 6 hours (q6h)

3. Ceftriaxone

4. 1 g IV daily

5. Cefotaxime

6. 1 g IV every 6 hours (q6h)

7. Doxycycline

8. 100 mg IV every 12 hours (q12h)

Treatment duration: Typically 7 days

Prevention

• Proper sanitation to prevent population exposure
• Vaccination for Dogs and cats