The Legionella bacterium is present worldwide and is found in natural water bodies and water distribution systems; the infection it can cause is a major public health problem whose notification rates are still low. Most cases are sporadic and community-acquired (more than 70 percent) followed by those associated with travel (more than 20 percent) or healthcare-related (about 10 percent). Over the past decade, incidence rates of legionellosis have increased in the United States, Canada, Europe, Israel, and Japan.
Despite this increase over the past decade, globally, legionella cases are grossly underdiagnosed and underestimated because different countries differ in level of awareness, diagnostic methods, and investigation efforts. Despite this, available information on this disease has increased significantly over the past two decades due to more frequent diagnostics and increased case reporting. In the United States, there was a general increase in Legionnaires' disease cases in the 2000s to an incidence of 200 percent. Contributing causes to this increase were a real increase in the number of cases, increased use of diagnostic tests, and increased reporting. In the recent European report, Legionellosis showed marked seasonality and geographic variation in cases. 74 percent of these cases occurred in five countries-France, Germany, Italy, Portugal, and Spain. In Eastern European countries, on the other hand, the number of reported cases is very low and probably does not reflect the true number of infections. The European report shows that Legionella pneumophila and its serogroup 1 are responsible for 95 percent of all cases and 85 percent of culture-confirmed cases. Other species reported are L. longbeachae (2%), L. micdadei (1%), L. bozemanae (<1%), L. maceachernii (<1%) and L. sainthelensi (<1%).
Legionella can manifest with two clinical pictures: with a flu-like form that resolves within 4 to 5 days (called Pontiac disease) or with a significantly severe pulmonary infection, usually with multiple parenchymal foci.
The incubation period varies from 2 to 10 days (average 7 days).
Laboratory tests for Legionella detection may include respiratory culture, urinary antigen testing, serum antibody testing, and other molecular methods (e.g., Polymerase Chain Reaction, the PCR). Respiratory culture is the standard for a diagnosis of legionellosis and allows species identification. Although urinary antigen detection is increasingly used among physicians, this method can only diagnose serogroup Lp1. PCR is increasingly used in several countries and is currently the only valid approach for rapid diagnosis of Legionellosis.
Risk factors for Legionella infection include:
- Male individuals;
- Age over 40 years;
- smoking;
- alcohol abuse;
- Presence of chronic disease (e.g., diabetes, chronic heart/lung disease, chronic renal failure);
- immunocompromised individuals (e.g., corticosteroids, chemotherapy, transplant recipients), with hematologic malignancies, iron overload, and/or a history of recent travel.
Guidelines on the management of community-acquired pneumonia (CAP) in adults recommend urinary antigen testing in patients:
- Who do not respond to outpatient antibiotic treatment;
- with severe pneumonia, especially if they require intensive care;
- immunocompromised;
- Who actively abuse alcohol;
- Who have traveled in the past two weeks;
- with pleural effusion;
- with pneumonia in the context of a Legionella outbreak.
Molecular techniques can improve a diagnosis of LD because they detect different serogroups and species. These techniques also have higher sensitivity (about 30 percent) than culture methods. Serologic methods are not sufficiently effective. High antibody titers detected in acute-phase serum samples are not diagnosed because antibodies from previous subclinical Legionella infection or cross-reacting antibodies from heterologous bacterial infections may be present. Moreover, in most patients with culture-confirmed Legionella, serum-conversion is not detectable until three weeks after infection.
Fluoroquinolones and macrolides are suitable for targeted therapy in Legionella pneumonia. Most cohort study data are available for levofloxacin, azithromycin, and clarithromycin. In a meta-analysis of 12 cohort studies with 879 patients in 2014, significantly shorter hospital stays and a nonsignificant trend in reduced mortality were shown among fluoroquinolones (predominantly levofloxacin) compared with macrolides (predominantly clarithromycin or erythromycin). In summary, the data show a potential superiority of fluoroquinolone therapy over erythromycin and clarithromycin at least in severe legionellosis, while levofloxacin was not detected in comparison to azithromycin. Therefore, levofloxacin should be considered the drug of choice in severe legionellosis in an appropriate dose (750-1000 mg/d). Alternatives are azithromycin or moxifloxacin. There are also anecdotal reports of successful short-term therapy lasting 5 days. Therefore, in patients without evidence of abscess formation, a 7-day duration of therapy is generally considered sufficient. Azithromycin, doxycycline or levofloxacin may be considered within clinical experience as first-line therapy. For severe or life-threatening legionellosis, the British Thoracic Society recommends the use of a fluoroquinolone. Parenteral therapy is administered until there is clinical response, although outpatients with mild disease achieve good results with oral therapy. The recommended duration of treatment is 5-10 days for levofloxacin130 and 3-5 days for azithromycin. An extended course is recommended for patients with immunosuppression, those with severe disease, extrapulmonary infection, and those on inappropriate initial therapy. Early appropriate therapy is a major factor in reducing mortality. There are only a few studies on antibiotic resistance. Resistance to therapeutics from the group of fluoroquinolones, macrolides, tetracyclines, or rifampin has been found only in isolated clinical cases.
The main tool to prevent the circulation of the virus and the most severe cases of the disease is vaccination. Developed in an unprecedented global effort, four specific, highly effective and safe vaccines are used in Italy: Comirnaty (Pfizer-BioNTech), Spikevax (Moderna), Vaxzevria (AstraZeneca) and Janssen (Johnson&Johnson). In addition to the vaccine, practices are recommended to reduce the possibility of exposure to the virus, such as wearing masks, distancing oneself from other people, and using disinfectants to remove viruses on hands and surfaces, to which isolation and quarantine have been added at peak times.A graphic detail of the physical composition of the virus, can be found on the University Vita - Salute San Raffaele website, at this link dedicated to the structure of Sars-Cov-2,