Leptospira Species

Indications for Testing

Fever >3 days with severe myalgia, usually after contact with animals or contaminated water/soil, or in person with recent travel history

Laboratory Testing

Darkfield microscopic exam of peripheral blood smear during first few days may demonstrate leptospires but with low sensitivity (~40%) and specificity (~60%)
- May also use urine or CSF specimens
- 1x10⁴ leptospires/mL necessary to observe 1 cell/field
Antibody testing
- Leptospira antibody testing for IgM in acute phase
  - Low sensitivity in first week of illness
  - Methods include microscopic agglutination (MAT), ELISA, IHA
    - MAT has highest specificity
  - Titer >1:200 and compatible symptoms are suggestive of human infection
- Convalescent IgG – ≥2 weeks after IgM
  - Fourfold increase in titer when run in parallel with acute sample confirms human case
Molecular testing – PCR
- Sensitive and rapid but not widely available
- Useful only in first 7 days of illness
Culture – organism is fastidious and slow growing, occasionally requiring weeks to grow
- May be isolated from blood, CSF and peritoneal dialysate within first 10 days of illness; thereafter, urine preferable
- Gold standard, but not often used in diagnosis

Differential Diagnosis

Dengue fever virus
Infectious diarrhea (bacterial, viral, parasitic)
Hantavirus
Plasmodium species
Rickettsial disease

Human leptospirosis, an acute febrile illness that presents with many manifestations, is found worldwide.

Epidemiology

Incidence – ~100-200 cases annually in U.S. (approximately half in Hawaii)
Transmission
- Zoonotic disease caused by the spirochete Leptospira interrogans
  - Wild mammals (eg, rodents) serve as a primary natural reservoir, but domestic animals (dogs, cattle, swine, horses) serve as major sources of human infection
- ~50% of infections occur from July to October
- Transmission to humans – most often indirect by human contact with soil, food or water contaminated by urine from an infected animal
  - Common sources include contaminated well water, spring water, and food preparation surfaces
  - Transmission also occurs by swimming, rafting, or kayaking in water sources where livestock have been pastured
  - Certain occupational groups (agriculture, sewer, construction, veterinarians, and livestock/farm workers) are at higher risk for leptospirosis

Organism

Spirochete
- Member of the family Spirochaetaceae – also includes Treponema and Borrelia

Risk Factors

Contact with contaminated water (kayaking and rafting)
Poor sanitation
Livestock/farm work
Meat processing work

Clinical Presentation

Infection has variable clinical course; usually presents as one of the following
- Subclinical – only detectable by serologic means (~90% of infections)
- Influenza-like febrile illness with fever, chills, rigor, myalgia, abdominal pain, vomiting and diarrhea; coincides with leptospiremia following an 8-12 day incubation period (septicemic phase)
- Severe, life-threatening multi-organ failure; often follows influenza-like stage and transient reduction in severity of symptoms (immune phase)
Jaundice occurs infrequently in the U.S.
Leptospiral meningitis – occurs more frequently, accounting for 5-13% of sporadic lymphocytic meningitis cases
Kidneys are invariably involved – urine analysis demonstrates mild proteinuria, leukocytes, casts and variable hematuria
- Jaundice with nephritis – Weil disease
  - May also have pulmonary dysfunction, hemorrhagic disease
  - Mortality 5-40% in severe cases

Treatment

Treat with antimicrobials
Jarisch-Herxheimer reaction (fever, myalgias, headache, tachycardia, hypotension) may occur with initiation of treatment for all spirochetal diseases

Tests generally appear in the order most useful for common clinical situations

Test name: Leptospira Antibody, IgM by Dot Blot

ARUP #: 0055233

Methodology: Qualitative Dot Blot

Use: Detect the presence of serum IgM to Leptospira biflexa, serovar Patoc 1, which is genetically similar to disease-causing members of the genus Leptospira

Limitations:

Not sensitive in first week of illness

May require convalescent IgG to confirm human infection

Test name: Leptospira Antibody

ARUP #: 0050786

Methodology: Semi-Quantitative Indirect Hemagglutination

Use:

Detect Leptospira-specific IgG and IgM in serum or plasma samples in which Leptospira infection is suspected

Limitations:

Cannot be used to predict the point of IgM appearance or cessation in patients, nor can it be used to distinguish a current or recent leptospirosis infection from a past infection or reinfection with another serotype

Less sensitive than IgM by Dot Blot

Test name: Leptospira Culture

ARUP #: 0060158

Methodology: Standard reference procedures for Leptospira bacterial culture and exam

Use:

Gold standard for Leptospira identification

Limitations:

Time-sensitive test

Recommend obtaining acute serology testing concurrently because test takes up to 6 weeks for evaluation

CSF should be collected within first week of illness; after first week of illness, urine should be collected