Leptospirosis

Leptospirosis is a zoonotic disease caused by gram-negative Leptospira bacteria. Direct transmission to humans occurs when broken skin and mucous membranes come into contact with the urine of infected animals such as rodents. The early phase of the disease is mild and characterized by nonspecific symptoms (e.g., fever, headache, and myalgia). In most cases, symptoms resolve spontaneously after a week. However, in 10% of cases, the disease progresses rapidly to a severe form (icterohemorrhagic leptospirosis, or Weil disease), which typically presents with a triad of jaundice, bleeding manifestations, and acute kidney injury. Diagnosis is based on patient history, clinical findings, and laboratory tests. Treatment consists of antibiotics and supportive care.

• Leptospirosis is the most common zoonotic disease worldwide and is most common in the tropics
• Low incidence in the US (100–200 cases per year): Half of these cases are reported in Hawaii.

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: Leptospira (especially L. interrogans); , a genus of gram-negative spirochete with hook-shaped ends
• Route of infection
  • Contact with soil, food, and/or water contaminated with the urine of infected animals (most commonly rodents; ) → entry of Leptospira through skin/mucous membrane lesions
  • Occupational groups at risk
    • Farmers, sewer workers
    • Water sports enthusiasts (e.g., surfers) may also be affected

The incubation time is 2–30 days. The disease has a mild form, which is characterized by nonspecific symptoms that generally resolve spontaneously after a week. In 10% of cases, the disease progresses rapidly to a severe form (icterohemorrhagic leptospirosis, or Weil disease). ^[1][2]

Mild (anicteric) leptospirosis ^[3]

Clinical manifestations during the early phase are due to bacteremia.

• High fever, headache
• Diarrhea, vomiting
• Conjunctival suffusion: bilateral diffuse reddening of the conjunctivae without exudates
• Photophobia
• Rash
• Myalgias; (especially in the calves and lower back)
• Possibly aseptic meningitis → worsening headache and photophobia

Most cases of mild leptospirosis resolve spontaneously. Only 10% of patients with mild leptospirosis progress to the severe form (Weil disease).

Severe leptospirosis (Weil disease, icterohemorrhagic leptospirosis) ^[3]

Clinical features are due to systemic spread and multiorgan involvement.

• Fever
• Hepatitis; → hepatomegaly, jaundice, acute liver failure
• Acute kidney injury (interstitial nephritis, acute tubular necrosis) → oliguria, hematuria
• Anemia, azotemia
• Hemorrhagic diathesis
  • Purpura
  • Pulmonary hemorrhage → hemoptysis
• Cardiac abnormalities (e.g. myocarditis, pericarditis, arrhythmia, conductivity impairment)

Severe leptospirosis is associated with a high mortality rate.

• Dark-field microscopy of urine or blood; samples (the thin Leptospira spirochetes cannot be visualized by light microscopy)
• Serological tests
  • Four-fold rise in the level of IgM titers within one month of the onset of symptoms
  • Microscopic agglutination test (MAT)
    • Patient serum is incubated with Leptospira serovars, and titers are obtained for serovars that react with patient serum.
    • Positive one week after the onset of symptoms.
• PCR: detect leptospiral DNA in bodily fluids
• Culture
• Complete blood count
  • Leukocytosis (neutrophilic)
  • Can show thrombocytopenia and anemia in Weil disease
• Kidney function tests: elevated BUN in Weil disease
• Liver function tests: ↑ AST/ALT

• For mild leptospirosis: doxycycline, azithromycin, or aminopenicillins (ampicillin, amoxicillin)
• For severe leptospirosis
  • IV penicillin G, doxycycline, or 3^rd generation cephalosporins (e.g., ceftriaxone) ^[4]
  • Supportive therapy for multiorgan failure

If leptospirosis is suspected based on a patient's clinical features and history, empiric therapy should be started right away.

Antibiotic treatment may induce a Jarisch-Herxheimer reaction.

• Leptospirosis is a notifiable disease. ^[3]
• Prophylaxis against leptospirosis: doxycycline
• Disease control: implement appropriate pest control, vaccination of livestock and pets