Leptospirosis

Epidemiology

Demographics

  • Incidence: approximately 870k cases worldwide annually

Geography

  • Widespread
    • Incidence in Tropical Regions is 10x Higher than that in Temperate Regions
      • Tropical Cases are Seen Mainly in Areas with High Poverty
    • Highest Number of Annual Cases are Reported in Hawaii: possibly due to ongoing legally required reporting of cases
    • Peak Areas in Southern and Pacific Coastal States
    • Cases Have Been Reported in Florida

Risk Factors

Occupational

  • Abattoir Workers
  • Farming (Rice, etc)/Ranching
  • Laboratory Workers
  • Loggers
  • Military
  • Pet Traders
  • Sewer Workers
  • Trappers

Recreational

  • Canoeing/Kayaking
  • Freshwater Swimming
  • Trail Biking

Household

  • Pet Dogs
  • Domesticated Livestock
  • Rainwater Catchment Systems
  • Rodents

Other

  • Accidental Laboratory Exposure
  • Contact with Wild Rodents
  • Skin Lesions
  • Walking Barefoot Through Surface Water

Transmission/Microbiology

Transmission

  • Mammalian Vectors: infected animals may be asymptomatic or manifest clinical infection
    • Rodents: most important reservoir
      • Infection Usually Occurs Early in Life with Shedding or Organism Intermittently or Continuously Throughout Life (Typically with Contamination of Water Sources)
    • Cattle
    • Swine
    • Dogs
    • Horses
    • Sheep
    • Goats
    • Cats: rarely
  • Modes of Infection
    • Exposure to Animal Urine, Contaminated Water/Soil, or Infected Animal Tissue with Entry Via Wound (Cuts, Abraded Skin), Mucous Membranes, or Conjunctivae
      • It is Unclear as to Whether Leptospira Can Penetrate Intact Skin
    • Ingestion of Contaminated Food: rarely
    • Transplacental Infection: has been reported

Microbiology

  • Leptospira Species: 9 species are known to be pathogenic
    • Leptospira Interrogans
    • Leptospira kirschneri
    • Leptospira noguchii
    • Leptospira alexanderi
    • Leptospira weilii
    • Leptospira alstonii
    • Leptospira borgpetersenii
    • Leptospira santarosai
    • Leptospira kmetyi

Diagnosis

Serology

  • Most Commonly Used Diagnostic Methods
  • Techniques
    • Enzyme-Linked Immunosorbent Assay (ELISA)
    • Indirect Hemagglutination
    • Microscopic Agglutination Test (MAT)
      • Most Specific with Detection of a 4x-Increase Between Acute and Convalescent Serum Specimens
      • Single Titer of >1:800 is Reasonable Evidence of Current or Recent Leptospira Infection
    • Macroscopic Agglutination Test

Molecular Tests

  • Techniques
    • Real Time PCR
    • Loop-Mediated Isothermal Amplification (LAMP)

Culture

  • Technique
    • Blood Culture (see Blood Culture, [[Blood Culture]]): insensitive
    • Urine Culture (see Urine Culture, [[Urine Culture]]): become positive during the second week of illness and remain positive for 30 days after resolution of symptoms
    • Cerebrospinal Fluid Culture (see Lumbar Puncture, [[Lumbar Puncture]]): usually positive during the first 10 days of illness

Clinical Manifestations

General Comments

  • Clinical Course of Variable, Ranging from Subclinical Illness to Fata Illness
    • Most Cases are Mild and Self-Limited
  • Incubation Period: 2-26 days
  • Typical Presentation
    • Abrupt Onset of Fever, Rigors, Myalgias, and Headache: occurs in 75-100% of cases

Cardiovascular Manifestations

Dermatologic Manifestations

  • Rash

Gastrointestinal Manifestations

  • Abdominal Pain (see Abdominal Pain, [[Abdominal Pain]])
    • Epidemiology: less common
  • Acalculous Cholecystitis (see Acalculous Cholecystitis, [[Acalculous Cholecystitis]])
    • Epidemiology: reported in children
  • Acute Pancreatitis (see Acute Pancreatitis, [[Acute Pancreatitis]])
    • Epidemiology: reported in children
  • Diarrhea (see Diarrhea, [[Diarrhea]])
    • Epidemiology: occurs in 50% of cases
  • Elevated Liver Function Tests (LFT’s) (see Elevated Liver Function Tests, [[Elevated Liver Function Tests]])
    • Clinical
      • Mild-Moderate Transaminitis: occurs in 40% of cases
      • Hyperbilirubinemia/Jaundice (see Hyperbilirubinemia, [[Hyperbilirubinemia]]): may be severe in some cases
  • Hepatomegaly (see Hepatomegaly, [[Hepatomegaly]])
  • Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]])
    • Epidemiology: occurs in 50% of cases

Hematologic Manifestations

  • Hemorrhage
    • Epidemiology: odds ratio = 10.0 (J Nephrol, 2005) [MEDLINE]
  • Leukocytosis (see xxxx, [[xxxx]])
    • Clinical: usually <10k (range: 3-26k) with left shift in 66% of cases
  • Splenomegaly (see Splenomegaly, [[Splenomegaly]])
  • Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]])
    • Epidemiology
      • Occurs in Approximately 38% of Cases (Clin Infect Dis, 2008) [MEDLINE]
      • Odds Ratio = 4.8 (J Nephrol, 2005) [MEDLINE]
    • Prognosis: hospital length of stay correlated inversely with platelet nadir (J Nephrol, 2005) [MEDLINE]

Neurologic Manifestations

  • Aseptic Meningitis (see Meningitis, [[Meningitis]])
    • Epidemiology: occurs in 50-85% of cases (if cerebrospinal fluid is examined after 7 days of illness)
    • Diagnosis
      • Lumbar Puncture
        • Lymphocytic or Neutrophilic Pleocytosis
        • Minimal-Moderately Elevated Protein
        • Normal Glucose: low glucose occurs rarely
  • Headache (see Headache, [[Headache]])
  • Muscle Tenderness/Rigidity
  • Peripheral Neuropathy (see Peripheral Neuropathy, [[Peripheral Neuropathy]])

Ophthalmologic Manifestations

  • Conjunctival Suffusion
    • Epidemiology: occurs in 55% of cases
    • Clinical: this feature is unique to Leptospirosis (and is uncommon in other infectious illnesses)
  • Optic Neuritis (see xxxx, [[xxxx]])
  • Subconjunctival Hemorrhages
  • Uveitis (see xxxx, [[xxxx]])

Otolaryngologic Manifestations

Pulmonary Manifestations

  • Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])
    • Epidemiology: xxx
  • Cough (see Cough, [[Cough]])
    • Epidemiology: occurs in 25-35% of cases
    • Clinical: dry
  • Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]])
    • Epidemiology: xxx
  • Pneumonia/Lung Nodules (see Lung Nodule or Mass, [[Lung Nodule or Mass]])
    • Diagnosis (AJR Am J Roentgenol, 1989) [MEDLINE]
      • Small Nodular Infiltrates: 57% of cases
      • Diffuse Ill-Defined Ground-Glass Infiltrates: 27% of cases
      • Large Confluent Consolidations: 16% of cases

Renal Manifestations

  • Acute Interstitial Nephritis (see Acute Interstitial Nephritis, [[Acute Interstitial Nephritis]])
    • Epidemiology: xxxx
  • Acute Kidney Injury (AKI) (see Acute Kidney Injury, [[Acute Kidney Injury]])
    • Clinical: typically non-oliguric and associated with hypokalemia
    • Prognosis: hospital length of stay correlated with peak creatinine (J Nephrol, 2005) [MEDLINE]
  • Bilateral Renal Enlargement
    • Epidemiology: odds ratio = 7.5 (J Nephrol, 2005) [MEDLINE]
  • Hypokalemia (see Hypokalemia, [[Hypokalemia]])
    • Physiology: outer membrane protein of Leptospira inhibits the Na/K/Cl cotransporter in the thick ascending limb of Henle, causing hypokalemia and renal sodium wasting
  • Hyponatremia (see Hyponatremia, [[Hyponatremia]])
    • Epidemiology: common in severe Leptospirosis
    • Physiology: outer membrane protein of Leptospira inhibits the Na/K/Cl cotransporter in the thick ascending limb of Henle, causing hypokalemia and renal sodium wasting
  • Sterile Pyuria (see Urinalysis, [[Urinalysis]])
    • Clinical: proteinuria, pyuria, granular casts, and sometimes microscopic hematuria

Rheumatologic Manifestations

  • Arthralgias (see Arthralgias, [[Arthralgias]])
    • Epidemiology: less common
  • Bone Pain (see Bone Pain, [[Bone Pain]])
    • Epidemiology: less common
  • Muscle Tenderness/Rigidity
  • Myalgias (see Myalgias, [[Myalgias]])
    • Epidemiology: odds ratio = 8.0 (J Nephrol, 2005) [MEDLINE]
  • Rhabdomyolysis (see Rhabdomyolysis, [[Rhabdomyolysis]])
    • Epidemiology: elevated creatinine kinase occurs in 50% of cases (JAMA, 1975) [MEDLINE]

Other Manifestations

  • Fever (see Fever, [[Fever]])
  • Rigors (see Rigors, [[Rigors]])

Treatment

Respiratory Support

  • xxx

Renal Support

  • xxxx

Antibiotics

  • xxxxx

Prognosis

  • Mortality Rate in Hospitalized Patients: 4-52% (Natl Med J India, 2004) [MEDLINE] and (Emerg Infect Dis, 2012) [MEDLINE]

References

  • Serum creatine phosphokinase in leptospirosis. JAMA. 1975;233(9):981 [MEDLINE]
  • Leptospirosis of the lung: radiographic findings in 58 patients. AJR Am J Roentgenol. 1989;152(5):955 [MEDLINE]
  • Risk factors for mortality in patients with leptospirosis during an epidemic in northern Kerala. Natl Med J India. 2004;17(5):240 [MEDLINE]
  • Clinical distinction and evaluation of leptospirosis in Taiwan–a case-control study. J Nephrol. 2005;18(1):45 [MEDLINE]
  • Activation of the coagulation cascade in patients with leptospirosis. Clin Infect Dis. 2008;46(2):254 [MEDLINE]
  • Outbreak of leptospirosis after flood, the Philippines, 2009. Emerg Infect Dis. 2012;18(1):91 [MEDLINE]