Summary
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 manifests with a triad of liver failure, acute kidney injury, and bleeding diathesis. Diagnosis is based on patient history, clinical findings, and laboratory tests. Treatment consists of antibiotics and supportive care.
Epidemiology
- Most commonly found in tropical climates [1]
- Worldwide incidence of ∼ 1 million cases resulting in ∼ 59,000 deaths annually [1]
- Most cases in the US and its territories occur in Hawaii or Puerto Rico or are associated with international travel. [1]
Epidemiological data refers to the US, unless otherwise specified.
Etiology
- Pathogen: Leptospira (especially L. interrogans sensu lato); , a genus of gram-negative spirochete with hook-shaped ends [2]
-
Transmission [3]
- Sources
- Urine, blood, or tissue of an infected animal (most commonly rats)
- Environmental contamination (e.g., water contaminated with urine of infected animals)
- Entry points: broken skin or exposed mucous membranes (e.g., conjunctiva, oral mucosa)
-
Risk factors
- Occupations that involve direct or indirect contact with animals (e.g., agricultural or sewage workers)
- Freshwater recreational activities (e.g., canoeing, swimming, windsurfing)
- Sources
Clinical features
Most infections are asymptomatic. Patients with symptoms generally present 1–2 weeks after exposure with a self-limited flu-like illness that progresses to multiple organ failure in 5–10% of patients. [1]
Mild leptospirosis (anicteric leptospirosis) [1][3][4]
- Symptoms
-
Signs
- Conjunctival suffusion: bilateral diffuse reddening of the conjunctivae without exudates
- Mild jaundice
- Lymphadenopathy
- Hepatosplenomegaly
- Meningeal signs
- Rash
Severe leptospirosis (icteric leptospirosis) [1][4]
In addition to the signs and symptoms of mild leptospirosis, severe leptospirosis manifests with rapidly progressive multiple organ failure and may include the following:
-
Classic triad of Weil disease
- Signs of acute kidney injury (e.g., oliguria, anuria)
- Signs of liver failure (e.g., jaundice)
- Hemorrhagic diathesis (e.g., hemoptysis, purpura, melena)
- Clinical features of shock (e.g., hypotension)
- Clinical features of cardiac inflammation: e.g., myocarditis, pericarditis, arrhythmia
Severe leptospirosis has a high mortality rate. [4]
Diagnosis
The initial diagnosis of leptospirosis requires a high index of suspicion because the clinical features are nonspecific. Do not delay treatment to obtain confirmatory studies.
Laboratory studies [3][4][5]
Laboratory findings are nonspecific but may help assess for end-organ damage.
- CBC: leukocytosis with left shift, thrombocytopenia, anemia
- Electrolytes: hyponatremia, hypokalemia, hypomagnesemia
- Renal function tests: ↑ creatinine, ↑ BUN
- ↑ ESR and ↑ CRP
- Liver function tests: increased bilirubin, AST, ALT, and ALP
- ↑ CPK
- Urinalysis: proteinuria, pyuria, microscopic hematuria, hyaline casts, granular casts
- CSF: may show pleocytosis; protein and glucose levels are usually normal
Confirmatory studies [1][4][5]
A definitive diagnosis may be made based on direct detection or serology. [3]
- Direct detection from blood, urine, and/or CSF samples
-
Serology
- Cannot be used for early diagnostic or treatment decisions [3]
-
Microscopic agglutination test (MAT): gold standard [1][5]
- Patient serum is incubated with Leptospira serovars and titers are obtained for positive reactions. [6]
- Can only be performed at specific laboratories (e.g., CDC laboratories)
The thin Leptospira spirochetes cannot be visualized by light microscopy.
Leptospirosis is a notifiable disease in the US; report confirmed cases to the CDC. [1]
Differential diagnoses
- Influenza
- Dengue
- Chikungunya fever
- Acute HIV infection
- Rickettsial infections (e.g., Rocky Mountain spotted fever, murine typhus)
- Viral hemorrhagic fever (e.g., hantavirus infection, Lassa fever)
- Malaria
- Typhoid fever
- Acute viral hepatitis (e.g., hepatitis A)
The differential diagnoses listed here are not exhaustive.
Treatment
Antibiotics [3][7]
Start antibiotics immediately if leptospirosis is suspected; do not wait for confirmatory testing. [1]
-
Options for mild leptospirosis
- Doxycycline (off-label) [7]
- Amoxicillin (off-label) [7]
- Ampicillin (off-label) [7]
- Azithromycin (off-label) [7]
-
Options for severe leptospirosis
- Penicillin G (off-label) [7]
- Ceftriaxone (off-label) [7]
- Doxycycline (off-label) [7]
Doxycycline or azithromycin are preferred in regions where rickettsial infections are coendemic. [3]
Initiation of antibiotic therapy may cause a Jarisch-Herxheimer reaction. [1]
Supportive care [3]
-
Renal dysfunction
- IV fluid therapy
- Electrolyte repletion
- Dialysis in patients with oliguric renal failure
- Respiratory failure: mechanical ventilation using lung protective ventilation strategies
Disposition [4][7]
- Severe leptospirosis: Admit to the ICU.
- Moderate leptospirosis: Admit to a monitored bed.
- Mild leptospirosis: Discharge with close follow-up and strict return precautions if symptoms of end-organ damage occur (e.g., oliguria, jaundice).
Prevention
- Avoid exposure to urine, blood, and tissue of infected animals by wearing appropriate personal protective equipment (e.g., eyewear, footwear).
- Implement appropriate pest control strategies.
- Vaccinate livestock and pets.
- Consider antibiotic prophylaxis for high-risk, short-term exposures.
- Agents
- Doxycycline (off-label) [1]
- OR azithromycin (off-label) [3]
- Duration: Initiate 1–2 days before anticipated exposure and continue throughout the period of exposure.
- Agents
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