Leptospirosis

Introduction

• Leptospirosis: Infectious disorder of animals and humans, most common zoonotic infection globally.
• Transmission: Through infected animal urine, contaminated soil, or water.
• Disease Severity: Ranges from a self-limiting flu-like illness to Weil’s disease, which can cause multiorgan failure and death.
• Occupational Risk: Sewage workers, agricultural workers.
• Recreational Risk: Water sports enthusiasts.

Etiology

• Causative Agent: Spirochete bacterium Leptospira.
• Transmission:
  • Direct contact with urine of infected animals.
  • Contact with contaminated soil or water.

High-Risk Groups

• Common Animal Vectors: Cattle, pigs, horses, raccoons, porcupines, domesticated dogs.
• Animal Carriers: Over 160 species can carry the disease without symptoms and act as vectors for months.

Leptospirosis in Australia

Sources of Infection:

• Occupational Exposure:
  • Livestock and dairy farmers.
  • Abattoir and meat workers.
  • Banana workers (exposure to rodents).
• Recreational Exposure:
  • Activities like white water rafting, kayaking, ecotourism, and other outdoor activities.
• International Travel:
  • Travel to tropical, developing countries increases risk for both occupational and recreational exposure.

Environmental and Climatic Factors:

• Tropical Climates:
  • Ideal conditions for Leptospira survival.
  • Transmission exacerbated by high rainfall and flooding.
• Poor Sanitation and Drainage:
  • Increases exposure, especially in urban slums with an abundance of rodents.
• Notable Post-Flooding Outbreaks:
  • Densely populated developing countries such as Brazil, India, and the Philippines.

Pathophysiology, Clinical Features, and Complications

• Incubation Period: Typically 5 to 14 days, but can range from 2 to 30 days.
• Entry: Through nonintact skin, mucous membranes, or inhalation of contaminated water.
• Environmental Survival:
  • Freshwater: up to 16 days.
  • Soil: up to 24 days.
• Transmission During Pregnancy: Can lead to miscarriage or stillbirth.
• Spread in Body: Through lymphatics and bloodstream, settling in liver and kidneys.

Biphasic Illness:

• Acute/Bacteraemic Phase:
  • Duration: 7 to 10 days from symptom onset.
  • Symptoms: Sudden onset of fever, myalgia, headache, calf tenderness, conjunctival suffusion.
  • Non-specific symptoms: Anorexia, nausea, vomiting, abdominal pain, dizziness, lethargy, arthralgia, eye pain, photophobia, rashes.
• Late/Immune Phase:
  • Onset: >7 days from symptom onset.
  • Symptoms: Immunologically mediated organ damage.
  • Severe Complications: Acute renal failure, pulmonary haemorrhage, myocarditis, arrhythmias, shock, liver failure, coagulopathy, neurological complications.
  • Weil’s Disease:
    • Classic triad of
      • jaundice
      • renal failure
      • haemorrhage
    • not always occurring together
    • High mortality if untreated.
    • Complications: Disseminated intravascular coagulation, haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura.

Neurological Complications:

• Aseptic meningitis, encephalitis, convulsions.
• Guillain–Barré syndrome, transverse myelitis, other neurological syndromes.

Ocular Manifestations:

• Acute or chronic optic complications.
• Subconjunctival and retinal haemorrhages.
• Optic neuritis, chronic uveitis.

Differential Diagnosis

• Viral upper respiratory infections
• Dengue fever
• Malaria
• Hantavirus
• Hemorrhagic fevers
• Typhoid fever
• Cholecystitis
• Mononucleosis
• Primary HIV
• Measles, rubella

Laboratory Diagnosis of Leptospirosis

• Acute/Bacteraemic Phase:
  • Tests to order:
    • PCR (Polymerase Chain Reaction):
      • Collect blood in a serum-separating tube before starting antibiotics.
      • High sensitivity in the early phase, useful for immediate clinical management.
    • IgM ELISA (Immunoglobulin M Enzyme-Linked Immunosorbent Assay):
      • Lower sensitivity compared to PCR in the early phase but helpful in determining illness phase.
    • Blood Cultures:
      • Use specific culture medium (Ellinghausen–McCullough–Johnson–Harris medium) if available.
      • Cultures examined for six weeks by dark-field microscopy.
• Late/Immune Phase:
  • Tests to order:
    • IgM ELISA:
      • Reactive results sent to reference laboratories for confirmation by MAT.
    • MAT (Microscopic Agglutination Test):
      • Convalescent sample collected 14 days later to confirm rising titres.
      • Includes a panel of serovars from different serogroups.
• Case Definition of Leptospirosis (NNDSS):
  • Confirmed Case:
    • Isolation of pathogenic Leptospira species.
    • Fourfold or greater rise in Leptospira MAT titre between acute and convalescent-phase sera.
    • Single Leptospira MAT titre ≥400, supported by a positive ELISA IgM result.
  • Probable Case:
    • Positive IgM ELISA or positive PCR alone.

Additional Investigations Based on Clinical Presentation

• Full Blood Count:
  • Findings: Leucocytosis, neutrophilia with left shift, lymphopenia, normochromic anaemia, thrombocytopenia.
• Urea, Electrolytes, Creatinine:
  • Findings: Raised urea and creatinine if renal impairment, low sodium, normal or low potassium (high potassium indicates poor outcomes).
• Liver Function Tests:
  • Findings: Raised bilirubin (mainly direct), normal or raised liver enzymes, AST and ALT typically three to five times above normal.
• Urinalysis:
  • Findings: Proteinuria, microscopic haematuria, pyuria, granular casts.
• Creatine Phosphokinase:
  • Findings: Raised in patients with myalgia.
• Coagulation:
  • Findings: Raised prothrombin time, partial thromboplastin time, and INR due to impaired liver function.
• Arterial Blood Gases:
  • Findings: Low PaO2, SaO2, PaO2/FiO2 ratio, metabolic acidosis.
• Electrocardiograph:
  • Findings: Atrial fibrillation, extrasystoles, AV block, other arrhythmias.
• Chest X-ray:
  • Findings: Alveolar infiltrates, nodular densities, consolidation, which could represent alveolar haemorrhage, ARDS, pulmonary edema.
• Lumbar Puncture:
  • Findings: Neutrophilic or lymphocytic pleocytosis, mild protein elevation, normal glucose.

Clinical Management

• Empirical Antibiotics:
  • Mild Disease:
    • Preferred: Doxycycline (100 mg twice daily).
    • Alternatives: Amoxicillin, erythromycin.
  • Severe Infection:
    • IV Benzylpenicillin (1.2 g six-hourly) or ceftriaxone (1 g daily).
• Jarish–Herxheimer Reaction:
  • Features: Sudden onset of shivers or rigors, fever, hypotension.
  • Cause: Acute inflammatory response from rapid death of Leptospira.
• Life-threatening Complications:
  • Referral to hospital for further management.
  • Possible interventions: IV fluids, inotropes, ventilation, haemodialysis, treatment of arrhythmias and coagulopathies.
• Corticosteroids:
  • Currently not recommended due to conflicting evidence and risk of nosocomial infections in severe cases.

Surveillance, Prevention, and Control of Leptospirosis

Surveillance:

• Leptospirosis is a notifiable disease, mandatory reporting to NNDSS.
• Public health units investigate cases, explore risk factors, and potential infection sources.

Infection Risk Reduction:

• Avoid Direct Contact:
  • Contaminated soil or water, particularly floodwaters.
  • Animals or animal products.
• Occupational Risk:
  • Target groups: farmers, abattoir and meat workers, banana workers, military personnel.
  • Educational materials about preventive measures.
  • Use of protective gear (boots, goggles, aprons, gloves).
  • Clean and cover open wounds.
  • Thorough washing after exposure.
• Travelers:
  • Avoid floodwaters, swimming in rivers, and waterfalls after heavy rainfall in tropical developing countries.
  • Seek medical care promptly if a febrile illness develops.

Environmental Control Measures:

• Livestock vaccination.
• Segregating infected animals.
• Rodent control.
• Flood mitigation.
• Reducing garbage to prevent rodent attraction and drain blockage.
• Managing identified sources of infection from case investigations.
• Issuing public health warnings and alerts during high-risk periods (e.g., post-flooding).

Prophylaxis:

• Doxycycline:
  • Regular use (200 mg weekly) associated with nausea and vomiting, no clear benefit for reducing risk.
  • Not recommended routinely.
  • Considered for short-term intense exposures (e.g., soldiers, outbreak response personnel, recreational exposure) or after high-risk exposures (e.g., floodwaters).
  • Provides protection against other infectious diseases (e.g., malaria, rickettsia).
  • For travelers to malaria-endemic areas, consider doxycycline for malaria prophylaxis if at risk of leptospirosis.

Human Vaccines:

• Rarely used due to limited effectiveness, adverse reactions, and short duration of protection.
• No vaccines available in Australia.