Epidemiology

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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

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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

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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

• Myocarditis (see Myocarditis, [[Myocarditis]])

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

• Pharyngitis (see Pharyngitis, [[Pharyngitis]])

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]])

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Treatment

Respiratory Support

• xxx

Renal Support

• xxxx

Antibiotics

• xxxxx

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Prognosis

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

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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]