leptospirosis

Introduction

Zoonosis.

Etiology

• infection with spirochetes of the genus Leptospira
• direct contact with urine, blood or tissue from an infected animal or exposure to a contaminated water

Epidemiology

• occurs most commonly in tropics
• 40-120 cases reported in US annually
• occupational groups at risk: veterinarians, agricultural workers, sewage workers, slaughterhouse employees, workers in the fishing industry
• recreational water & domestic animal contact use increase risk
• outbreaks occur with heavy rains & flooding

Pathology

• organisms may enter host through abrasions in the skin or through intact mucous membranes
• multiplication in blood & in tissues
• vasculitis most important manifestation of disease
• kidney: interstitial nephritis & tubular necrosis
• liver: centrilobular necrosis with proliferation of Kupffer cells
• pulmonary involvement may result in pneumonia, hemoptysis, or ARDS
• skeletal muscle: vacuolization of myofibrils & focal necrosis
• antibodies eliminate organism from host except in eye, proximal renal tubules & brain where organism may persist for weeks or months
• Leptospires in aqueous humor may result in recurrent uveitis
  • conjunctival suffusion
• Leptospires in CSF appear not to cause damage to brain
• antibodies may also produce symptomatic inflammatory response
• Weil syndrome (severe, icteric leptospirosis)
  • hepatic necrosis, nephropathy, pulmonary disease

Clinical manifestations

• may be asymptomatic
• symptoms vary from mild to serious, even fatal
• 90% of patients have mild disease
• incubation period 2-26 days, generally 1-2 weeks
• may present as an acute flu-like syndrome
  • fever/chills
  • severe headache (aseptic meningitis)
  • nausea/vomiting
  • myalgia (especially calves, back, abdomen)
  • cough, dyspnea
  • nonbloody diarrhea
• sore throat & rash (maculopapular) less common
  • generalized rash is rare
• conjunctivitis; scleral hemorrhage in some cases
• most patients become asymptomatic within 1 week
• illness may recur after an interval of 1-3 days
  • referred to as immune phase
  • coincides with development of antibodies
  • aseptic meningitis may develop during immune phase
    • symptoms generally disappear after a few days
    • symptoms may persist for years
• Weil syndrome (severe, icteric leptospirosis)- jaundice

Laboratory

• urinalysis: proteinuria, leukocytes, erythrocytes, hyaline or granular casts
• urine culture (after 1 week)
• erythrocyte sedimentation rate (ESR) generally elevated
• complete blood count (CBC):
  • leukocytosis with a left shift
  • mild thrombocytopenia (associated with renal failure)
• blood culture (1st 4-10 days)
• liver function tests (LFTs)
  • elevated serum bilirubin
  • elevated alkaline phosphatase
  • mild increases (to 200 U/L) of serum transaminases
• prothrombin time may be prolonged in Weil's syndrome (may be corrected with vitamin K)
• serum lipase markedly elevated (case report)
• serum creatine kinase increased (50%)
• cerebrospinal fluid (CSF):
  • neutrophils predominate initially
  • increases in lymphocytes occur later
  • protein may be increased
  • glucose normal
  • Leptospira culture (1st 4-10 days)
• Leptospira serology
  • microscopic agglutination test (MAT) & ELISA (CDC)
  • antibody titer > 1:100 is diagnostic
• Leptospira antigen
• Leptospira DNA
• Leptospira culture
• isolation of organisms
  • from blood or CSF during 1st 4-10 days of illness
  • from urine after 1 to several weeks
  • culture media
    • Ellinghausen-McCullough-Johnson-Harris (EMJH)
    • Fletcher
    • Korthoff
  • Leptospira remain viable in uncoagulated blood for up to 11 days
  • isolation is the only means of identifying serotype (called serovar)
• Leptospira identified in specimen
  • darkfield examination frequently results in misdiagnosis
• see ARUP consult

Radiology

• chest X-ray
  • abnormalities develop after 3-9 days
  • most commonly patch alveolar pattern that corresponds to patchy alveolar hemorrhage
  • abnormalities most often affects lower lobes & periphery of lung fields

Complications

• Jarisch-Herxheimer reaction
• renal failure requiring dialysis
• Weil's syndrome
• iritis, iridocyclitis & chorioretinitis are late complications that may persist for years
• severe pulmonary hemorrhagic syndrome infrequent, but high mortality
• death (most patients recover)
  • mortality highest among elderly
  • high fetal mortality when associated with pregnancy

Differential diagnosis

• malaria
• enteric fever
• viral hepatitis
• dengue
• Hantavirus infection
• Rocky Mountain spotted fever

Management

• general
  • treatment should be begun as soon as possible
  • treatment begun after 4 days is still effective
• pharmaceutical agents
  • mild disease
    • doxycycline 100 mg PO BID for 7 days
    • ampicillin 500-750 mg PO QID for 7 days
    • amoxicillin 500 mg PO QID for 7 days
  • moderate to severe disease
    • penicillin G 1.5 million units IV QID for 7 days
    • ampicillin 1 g IV QID for 7 days
    • erythromycin 1 g IV QID for 7 days
  • prophylaxis: doxycycline 200 mg PO once a week

More general terms

• spirochete infection

More specific terms

• Weil's syndrome

Additional terms

• Leptospira