Pulmonary legionellosis, also known as Legionella pneumonia (LP), is an infectious disease caused by Legionella pneumophila, mainly manifested by pneumonia but also extrapulmonary involvement or involvement of multiple organs, and can easily progress to severe pneumonia. The overall mortality of legionellosis is 5% - 10%. In individuals with low immunity, the mortality can reach 30%, and if not treated promptly and properly, the mortality can reach 40% - 80%.
Etiology and pathogenesis
Legionella is a Gram-negative bacterium, mainly parasitic in prokaryotes in water and soil, and has 52 species and 70 serotypes. Legionella pneumophila is most closely related to human diseases, causing about 90% of legionellosis. Legionella pneumophila can cause community-acquired and hospital-acquired pneumonia and should be considered as one of the pathogens of atypical pneumonia. Epidemiological studies show that cooling water and shower water are the main sources of Legionella. Legionellosis can be sporadic or epidemic, mostly sporadic.
Epidemiology
Risk factors include contaminated air conditioners or air conditioning cooling towers, drinking water, hot spring water; engaging in gardening, pipe repair work; rain exposure; a history of travels to areas with legionellosis; and direct inhalation of contaminated water (water birth for infants). Individuals with low immunity are more likely to be infected, while older adults, immunosuppressed individuals, smokers, patients with multiple underlying diseases, and delayed diagnosis and treatment are closely related to its high mortality. The main route of infection is inhalation of aerosols produced from contaminated water sources, especially in susceptible hospitalized patients.
Clinical manifestations
The clinical manifestations vary greatly, usually occur 2 - 14 days after infection, and mainly include non-specific respiratory symptoms such as rigors, fever, dry cough, and dyspnea, as well as extrapulmonary organ involvement symptoms such as headache, myalgia, dyspnea, diarrhea, and delirium. There are also pulmonary manifestations, such as fever over 38.8°C, rigor, cough, thoracodynia, hemoptysis, and dyspnea, and extrapulmonary manifestations, such as diarrhea, nausea, emesis, mental disorders, myalgia or arthralgia, and headache.
Laboratory and other examinations
Positive Legionella culture is the gold standard for diagnosis of Legionella infection. Legionella colonies can be cultured usually in 3 - 5 days, and some rarely isolated Legionella species may require 14 days. Culture plates should be inspected on days 1 - 5 and day 14 of culture.
It is diagnostically valuable when the serum specimens in the acute and convalescent phases show a 4-fold or more increase. Most patients with Legionella infection produce antibodies 3 weeks after infection, and immunosuppressed patients may never produce antibodies.
Legionella urinary antigen detection is the most used diagnostic method. The result is not affected by previous anti-infective treatment. It enables rapid bedside detection within 15 minutes, with high sensitivity and specificity, and can be used for rapid diagnosis in the acute phase. However, it can only detect the infection of Legionella pneumophila serotype 1, and has poor sensitivity to positive strains of non-Legionella pneumophila serotypes. Complete dependence on this detection technology may cause missed diagnoses, and the positive detection rate in patients with Legionella pneumonia of different severities fluctuates greatly. Although Legionella antigen detection in lower respiratory tract specimens is rapid and simple, and can conduct identification of species and differentiation of subtypes, its sensitivity and specificity are very poor.
Nucleic acid amplification tests (NAAT) can distinguish Legionella pneumophila serotype 1 from other serotypes. Both conventional PCR and real-time PCR can be used to detect Legionella. Next-generation sequencing (NGS) has high sensitivity and can detect multiple pathogens, but it is expensive and has not yet been used as a routine clinical detection method.
19kD peptidoglycan associated lipoprotein (PAL) is a soluble antigen excreted through urine. Some studies have suggested that the detection of PAL in concentrated urine can assist in the diagnosis of Legionella pneumonia. Research on ribosomal proteins L7/L12 and interleukin-17A (IL-17A) as emerging markers for Legionella detection is ongoing.
Diagnosis and differential diagnosis
Diagnostic requirements include:
- Clinical manifestations including fever, rigors, cough, and thoracodynia
- Chest x-ray showing infiltrative opacities with or without pleural effusion
Diagnostic considerations include:
- Respiratory secretions, sputum, blood, or pleural effusion culture showing Legionella growth on the buffered charcoal yeast extract agar (BCYE) or other specialized media
- Respiratory secretions positive for Lp on fluorescent antibody examination
- Blood indirect fluorescence examines showing a 4-fold increase of IgG antibody or IgG antibody titer remains ≥ 1∶128 in 2 species collected with an interval of 2 - 4 weeks
- Positive urinary antigen test
- Positive nucleic acid test
If there are all diagnostic requirements and at least one of diagnostic considerations, Legionella pneumonia can be diagnosed.
In non-severe CAP patients with specific risk factors or epidemiological exposure, as well as severe CAP patients requiring hospitalization, Legionella pneumonia testing is recommended.
Treatment
Currently, common drugs available for the treatment of Legionella infection include quinolones, macrolides, and doxycycline. Additionally, tigecycline, compound sulfamethoxazole, and rifampicin have also been proven effective against Legionella infection. In recent years, there have been occasional reports of failed single-drug treatment for Legionella pneumonia, which may result from multiple bacterial infections in patients with Legionella pneumonia, pulmonary fibrosis caused by Legionella, and Legionella resistance.