Legionella pneumophila

Diagnosis

Indications for Testing

Laboratory Testing

  • Legionellosis resources (CDC)
  • Perform routine microbiology testing only for pathogens that would alter empirical decisions (recommendation from Infectious Diseases Society of America and American Thoracic Society)
  • Nonspecific testing
    • Serum sodium – hyponatremia
    • Serum phosphate – hypophosphatemia
    • Urine analysis – hematuria
    • CBC – thrombocytopenia common
    • Liver function studies – elevated transaminases
  • Consider testing for other common agents of community-acquired pneumonia – Streptococcus pneumoniae, Chlamydophila pneumoniae, Mycoplasma pneumoniae
  • Rapid testing may aid in early initiation of treatment
    • Point of care testing – available for urine specimens (sensitivity 70-80%; specificity 97-100%)
    • Urine antigen testing (EIA)  
      • Urine antigen testing more sensitive than DFA and highly specific for serogroup 1  
      • Detects only serogroup 1 (most common serogroup causing disease)
      • Antigens or antibodies may be detected as early as 1 day after symptom onset; positivity of test may persist >60 days
    • DFA of respiratory specimen
      • Highly insensitive compared to PCR and culture
      • Can detect various serogroups
      • Technically demanding; requires large respiratory specimen
      • Urine antigen detects serogroup 1; DFA detects various serogroups
    • PCR testing of respiratory secretions – good sensitivity; rate of false positives is 5-10%
  • Culture – considered gold standard in diagnosis
    • Best yield from sputum, which may be difficult to obtain with legionellosis
    • May be used to confirm PCR results
    • Takes at least 48 hours 
    • Genotyping isolates may help identify source of outbreak
  • Serological testing may be used for retrospective diagnosis
    • Seroconversion may take several weeks

Imaging Studies

  • Chest x-ray
    • Rapidly progressive asymmetrical infiltrates are common
    • Infiltrates may initially enlarge concurrent with clinical improvement while on appropriate antimicrobial therapy

Differential Diagnosis

Clinical Background

Legionellosis refers to two clinical syndromes caused by bacteria of the genus Legionella – Legionnaires’ disease and Pontiac fever. Legionnaires’ disease is considered an atypical pneumonia.

Epidemiology

  • Incidence – >10,000 annually in U.S.
  • Age – usually 45-64 years; rare cause of pneumonia in children
  • Sex – M>F; 2-3:1
  • Transmission
    • Mostly sporadic cases
    • More common in summer months – outbreaks of pneumonia have occurred after inhalation of contaminated water droplets from water sources such as evaporative coolers, hot tubs, heating systems
    • Person-to-person transmission has not been shown
    • Nosocomial cases are not uncommon
      • Sources of infection are often hospital showers, drinking fountains, and respiratory-therapy equipment

Organism

  • Legionella is a fastidious gram-negative coccobacillus
    • Widespread in nature but live mainly in freshwater bodies
    • Parasitizes freshwater amoeba in the environment and pulmonary macrophages in humans
  • >50 species compose at least 70 different serogroups of Legionellae
  • L. pneumophila is major pathogen and most commonly encountered member of group
    • Serogroup 1 is most common infecting type

Risk Factors

  • Adults
    • Older age (average ~55 years)
    • Cigarette smoking
    • Underlying chronic disease (eg, chronic obstructive pulmonary disease, diabetes, renal failure)
    • Compromised immune system (immunosuppressive therapy or T-cell dysfunction, including cancer)
    • Recent surgery
    • Alcoholism
    • Long-term use of breathing machines (ventilators)
  • Children – prematurity, immunocompromised, bronchopulmonary dysplasia

Clinical Presentation

  • Legionnaires' disease
    • Incubation period of 2-15 days
      • Prodromal phase of headache and myalgia progressing to fever with chills
      • Productive cough, possibly with hemoptysis 
      • Chest pain 
      • Shortness of breath
    • Symptoms may suggest pneumococcal pneumonia
    • Frequently includes gastrointestinal symptoms – primarily loose stools, diarrhea and/or abdominal pain
    • Frequently associated systemic involvement – kidney, liver and central nervous system dysfunction
      • Central nervous system – headache, lethargy, confusion, ataxia, encephalopathy 
    • Case fatality rate – 5-30%
      • Greater risk of death exists for elderly and immunocompromised  
  • Pontiac fever
    • Self-limiting, febrile illness with non-pneumonic, influenza-like illness characterized by myalgia, malaise and fever
      • Usually affects healthy individuals

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Legionella pneumophila Antigen, Urine 0070322
Method: Qualitative Enzyme-Linked Immunosorbent Assay

Rapid diagnostic test with good sensitivity and high specificity

Sensitivity – 70%  

Specificity – 100%

Only detects antigens to L. pneumophila serogroup 1; however, this serogroup causes >70% of the Legionnaires’ disease cases  
Legionella Species by Qualitative PCR 2010125
Method: Qualitative Polymerase Chain Reaction

Rapid diagnostic test

Aid in diagnosing etiology of pneumonia when Legionella is suspected

Detects and speciates L. pneumophila; nucleic acid from other Legionella species will be detected by this test but cannot be differentiated

Increases chances for discovery of organism in patient partially treated with empirical antibiotics

Sensitivity – 80%

Specificity – 100%

Only for respiratory secretions

Negative result does not rule out the presence of PCR inhibitors in patient specimen or test-specific nucleic acid in concentrations below the level of detection by this test

 
Legionella Species, Culture 0060113
Method: Culture/Identification

Gold standard test

Detects different species

Sensitivity – 20-95%

Specificity – 100%

Requires 3-5 days

Most sensitive in severe disease

Isolates may be useful in determining source of outbreaks

Legionella pneumophila DFA 2004598
Method: Direct Fluorescent Antibody Stain

Not a first-line test for diagnosis of Legionella infection

Recommend culture or PCR testing

Sensitivity – 25-75%

   Negative test does not rule out Legionella infection
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Sodium, Plasma or Serum 0020001
Method: Quantitative Ion-Selective Electrode

Nonspecific testing

Phosphorus, Inorganic, Plasma or Serum 0020028
Method: Quantitative Spectrophotometry

Nonspecific testing

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Nonspecific testing

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Nonspecific testing

May be useful in distinguishing bacterial from viral etiologies

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Nonspecific testing

Legionella pneumophila Antibody (Type 1), IgM by IFA 0050273
Method: Semi-Quantitative Indirect Fluorescent Antibody

Epidemiologic purposes only

Sensitivity – 40-60%  

Specificity – 96-99%

Legionella pneumophila Antibody (Types 1-6), IgM by IFA 0050274
Method: Semi-Quantitative Indirect Fluorescent Antibody

Epidemiologic purposes only

Sensitivity – 40-60%  

Specificity – 96-99%

Legionella pneumophila Antibody (Types 1-6), IgG by IFA 0050365
Method: Semi-Quantitative Indirect Fluorescent Antibody

Epidemiologic purposes only

Sensitivity – 40-60%  

Specificity – 96-99%

Legionella pneumophila Antibody (Type 1), IgG by IFA 0050376
Method: Semi-Quantitative Indirect Fluorescent Antibody

Epidemiologic purposes only

Sensitivity – 40-60%  

Specificity – 96-99%

Chlamydia pneumoniae by PCR 0060715
Method: Qualitative Polymerase Chain Reaction
Mycoplasma pneumoniae by PCR 0060256
Method: Qualitative Polymerase Chain Reaction
Streptococcus pneumoniae Antigen, Urine 0060228
Method: Qualitative Immunochromatography