Legionella pneumonia (LP), also known as Legionnaires' disease or Legionellosis, is an infectious disease caused by Legionella pneumophila. It primarily presents as pneumonia but may also involve extrapulmonary manifestations or multi-organ damage. It is a clinical subtype of Legionnaires' disease (LD). According to WHO data, the overall mortality rate for Legionnaires' disease is 5%-10%. Among immunocompromised individuals, the mortality rate can reach 30%, and without timely and appropriate treatment, the mortality rate may rise to 40%-80%.
Etiology and Pathogenesis
Legionella is a Gram-negative bacterium that primarily resides in aquatic and soil-based prokaryotic organisms. There are 52 species and 70 serogroups of Legionella. The species most closely associated with human disease is Legionella pneumophila (Lp), which accounts for approximately 90% of Legionnaires' disease cases. Legionella pneumophila can cause both community-acquired and hospital-acquired pneumonia and should be considered a potential pathogen in atypical pneumonia. Epidemiological studies have shown that cooling water and shower water are the main sources of Legionella contamination. Legionnaires' disease can occur sporadically or in outbreaks, with most cases being sporadic.
Epidemiology
Infection can occur through exposure to contaminated air conditioning systems, cooling towers, drinking water, hot springs, or while engaging in gardening or plumbing work. Other risk factors include rain exposure, travel to areas with known Legionella sources, or direct inhalation of contaminated water aerosols (e.g., during water births). Immunocompromised individuals are more susceptible to infection. Advanced age, immunosuppression, smoking, multiple underlying diseases, and delayed diagnosis and treatment are closely associated with the high mortality rate of this disease. The primary route of infection is inhalation of aerosols generated from contaminated water sources, particularly in hospitalized patients who are vulnerable.
Clinical Manifestations
The clinical presentation of Legionella pneumonia varies widely and typically appears 2-14 days after infection. Common symptoms include rigors, fever, dry cough, and dyspnea, as well as extrapulmonary symptoms such as headache, myalgia, diarrhea, and delirium. Pulmonary symptoms include fever (often exceeding 38.8°C), rigors, cough, chest pain, hemoptysis, and dyspnea. Extrapulmonary manifestations can include diarrhea, nausea or emesis, mental status changes, muscle or joint pain, and headache.
Laboratory and Other Examinations
Culture
A positive Legionella culture is the gold standard for diagnosis. Colonies typically appear after 3-5 days of culture, but some rare Legionella species may require up to 14 days. Culture plates should be inspected on days 1-5 and again on day 14.
Serology
Detection of Legionella antibodies in paired acute and convalescent serum samples showing a fourfold or greater rise is diagnostic. However, most Legionella infections do not produce detectable antibodies until around the third week after infection, and immunosuppressed patients may never produce antibodies.
Urinary Antigen Test
This is the most commonly used diagnostic method. It is unaffected by prior antimicrobial treatment and can provide rapid bedside results within 15 minutes. It has high sensitivity and specificity and is useful for acute-phase diagnosis. However, it only detects Legionella pneumophila serogroup 1 and has limited sensitivity for other serogroups. Sole reliance on this test may lead to missed diagnoses, and its positivity rate varies among patients with different severities of Legionella pneumonia.
Antigen Detection in Lower Respiratory Tract Specimens
This method is rapid, simple, and capable of identifying species and distinguishing subtypes. However, its sensitivity and specificity are relatively low.
Nucleic Acid Amplification Tests (NAAT)
These tests, including conventional PCR and real-time PCR, can differentiate Legionella pneumophila serogroup 1 from other serogroups. High-throughput genomic sequencing has high sensitivity and can detect multiple pathogens simultaneously, but it is expensive and not yet widely used in routine clinical practice.
Emerging Biomarkers
Research is ongoing into new diagnostic markers for Legionella pneumonia, such as the detection of the 19kD oligoglycoside-associated lipoprotein (PAL) in concentrated urine, ribosomal protein L7/L12, and interleukin-17A (IL-17A).
Diagnosis and Differential Diagnosis
A diagnosis of Legionella pneumonia can be made if criteria 1 and 2 are met, along with any one of criteria 3-7:
- Clinical symptoms: Fever, chills, cough, chest pain, etc.
- Chest imaging: Infiltrative opacities on chest X-ray or pleural effusion.
- Culture: Growth of Legionella from respiratory secretions, sputum, blood, or pleural effusion on buffered charcoal yeast extract (BCYE) or other specialized media.
- Fluorescent antibody test: Positive detection of Legionella pneumophila in respiratory secretions.
- Serology: A fourfold rise in IgG antibody titer in paired samples taken 2-4 weeks apart, or a persistent IgG titer ≥1:128 (though this method is rarely used now).
- Urinary antigen test: Positive result.
- Nucleic acid test: Positive result.
Testing for Legionella pneumonia is recommended for non-severe CAP patients with specific risk factors or epidemiological exposure, as well as for severe or hospitalized CAP patients.
Treatment
Commonly used antibiotics for treating Legionella infections include fluoroquinolones, macrolides, and doxycycline. Tigecycline, trimethoprim-sulfamethoxazole, and rifampin have also been shown to be effective. In recent years, treatment failures with monotherapy have been reported, which may be due to:
- Co-infection with multiple pathogens in patients with Legionella pneumonia.
- Lung fibrosis caused by Legionella.
- Development of Legionella antibiotic resistance.