BACKGROUND: Legionnaires\' disease (LD) is a common but under-diagnosed cause of community-acquired pneumonia (CAP), although rapid detection of urine antigen testing (UAT) and advances in molecular testing have improved the diagnosis. LD entails intensive care unit (ICU) admission in almost one-third of cases, and the mortality rate ranges from 4% to 40%. This review aims to discuss recent advances in the study of this condition and to provide an update on the diagnosis, pathogenesis and management of severe LD.
RESULTS: The overall incidence of LD has increased worldwide in recent years due to the higher number of patients with risk factors, especially immunosuppression, and to improvements in diagnostic methods. Although LD is responsible for only around 5% of all-cause CAP, it is one of the three most common causes of CAP requiring ICU admission. Mortality in ICU patients, immunocompromised patients or patients with a nosocomial source of LD can reach 40% despite appropriate antimicrobial therapy. Regarding pathogenesis, no Legionella-specific virulence factors have been associated with severity; however, recent reports have found high pulmonary Legionella DNA loads, and impairments in immune response and lung microbiome in the most severe cases. The clinical picture includes severe lung injury requiring respiratory and/or hemodynamic support, extrapulmonary symptoms and non-specific laboratory findings. LD diagnostic methods have improved due to the broad use of UAT and the development of molecular methods allowing the detection of all Lp serogroups. Therapy is currently based on macrolides, quinolones, or a combination of the two, with prolonged treatment in severe cases.
CONCLUSIONS: Numerous factors influence the mortality rate of LD, such as ICU admission, the underlying immune status, and the nosocomial source of the infection. The host immune response (hyperinflammation and/or immunoparalysis) may also be associated with increased severity. Given that the incidence of LD is rising, studies on specific biomarkers of severity may be of great interest. Further assessments comparing different regimens and/or evaluating host-directed therapies are nowadays needed.

We determined whether the incidence rates of travel-associated Legionnaires\' disease (TALD) in hotels in Germany increased after a previous occurrence and whether control measures required by the European Legionnaires\' Disease Surveillance Network after a cluster (>2 cases within 2 years) restored the rate to baseline. We analyzed TALD surveillance data from Germany during 2015-2019; a total of 307 TALD cases (163 domestic, 144 nondomestic) in hotels were reported. The incidence rate ratio was 5.5 (95% CI 3.6-7.9) for a second case and 25 (95% CI 11-50) for a third case after a cluster had occurred, suggesting that control measures initiated after the occurrence of TALD clusters might be inadequate to restore the incidence rate to baseline. Our findings indicate that substantial LD preventive measures should be explored by hotels or other accommodations after the first TALD case occurs to reduce the risk for future infections.

BACKGROUND: Legionnaires\' Disease (LD) rarely evolves into pulmonary abscesses. The current systematic review has been designed to explore therapeutical strategies in pulmonary cavitary LD.
METHODS: A research strategy was developed and applied to the databases Embase, Pubmed, and Web of Science from the 1st of January 2000 to the 1st of November 2022. Original articles, case series, case reports, and guidelines written in English, French, German, Italian, and Dutch were considered. Furthermore, medical records of patients treated at the University Hospital UZ Brussel for LD cavitary pneumonia, between the 1st of January 2016 to the 1st of January 2022, were reviewed.
RESULTS: Two patients were found by the UZ Brussel\'s medical records investigation. Through the literature review, 23 reports describing 29 patients, and seven guidelines were identified. The overall evidence level was low.
UNASSIGNED: The median age was 48 years and 65% were male. A polymicrobial infection was detected in 11 patients (44%) with other aerobic bacteria being the most commonly found. At diagnosis, 52% of patients received combination therapy, and fluoroquinolones were the preferred antimicrobial class. Anaerobic coverage was neglected in 33% of patients.
UNASSIGNED: Three guidelines favor monotherapy with fluoroquinolones or macrolides, while one suggested an antimicrobial combination in case of severe LD. Four guidelines recommended anaerobic coverage in case of lung abscesses.
CONCLUSIONS: To date, the evidence supporting cavitary LD treatment is low. Monotherapy lowers toxicity and might be as effective as combination therapy. Finally, anaerobes should not be neglected.

Severe Legionnaires\' disease (LD) can lead to multi-organ failure or death in 10%-30% of patients. Although hyper-inflammation and immunoparalysis are well described in sepsis and are associated with high disease severity, little is known about the immune response in LD. This study aimed to evaluate the immune status of patients with LD and its association with disease severity.
A total of 92 hospitalized LD patients were included; 19 plasmatic cytokines and pulmonary Legionella DNA load were measured in 84 patients on the day of inclusion (day 0, D0). Immune functional assays (IFAs) were performed from whole blood samples collected at D2 and stimulated with concanavalin A [conA, n = 19 patients and n = 21 healthy volunteers (HV)] or lipopolysaccharide (LPS, n = 14 patients and n = 9 HV). A total of 19 cytokines (conA stimulation) and TNF-α (LPS stimulation) were quantified from the supernatants. The Sequential Organ Failure Assessment (SOFA) severity score was recorded at D0 and the mechanical ventilation (MV) status was recorded at D0 and D8.
Among the 84 patients, a higher secretion of plasmatic MCP-1, MIP1-β, IL-6, IL-8, IFN-γ, TNF-α, and IL-17 was observed in the patients with D0 and D8 MV. Multiparametric analysis showed that these seven cytokines were positively associated with the SOFA score. Upon conA stimulation, LD patients had a lower secretion capacity for 16 of the 19 quantified cytokines and a higher release of IL-18 and MCP-1 compared to HV. IL-18 secretion was higher in D0 and D8 MV patients. TNF-α secretion, measured after ex vivo LPS stimulation, was significantly reduced in LD patients and was associated with D8 MV status.
The present findings describe a hyper-inflammatory phase at the initial phase of Legionella pneumonia that is more pronounced in patients with severe LD. These patients also present an immunoparalysis for a large number of cytokines, except IL-18 whose secretion is increased. An assessment of the immune response may be relevant to identify patients eligible for future innovative host-directed therapies.

Legionella, the bacterium that causes Legionnaires\' disease, can grow and spread in building water systems and devices. The COVID-19 pandemic impacted building water systems through reductions in water usage. Legionella growth risk factors can be mitigated through control measures, such as flushing, to address stagnation, as part of a water management program (WMP). A national lodging organization (NLO) provided WMP data, including Legionella environmental testing results for periods before and during the pandemic. The statistical analysis revealed an increased risk of water samples testing positive for Legionella during the pandemic, with the greatest increase in risk observed at the building\'s cold-water entry test point. Sample positivity did not vary by season, highlighting the importance of year-round Legionella control activities. The NLO\'s flushing requirements may have prevented an increased risk of Legionella growth during the pandemic. However, additional control measures may be needed for some facilities that experience Legionella detections. This analysis provides needed evidence for the use of flushing to mitigate the impacts of building water stagnation, as well as the value of routine Legionella testing for WMP validation. Furthermore, this report reinforces the idea that WMPs remain the optimal tool to reduce the risk of Legionella growth and spread in building water systems.

Legionella pneumophila is the primary causative agent of Legionnaires\' disease. The mutant-type strain interrupted in the ORF7 gene region responsible for the lipopolysaccharide biosynthesis of the L. pneumophila strain Heysham-1, lacking the O-acetyl groups attached to the rhamnose of the core part, showed a higher surface polarity compared with the wild-type strain. The measurement of excitation energy transfer between fluorophores located on the surface of bacteria and eukaryotic cells showed that, at an early stage of interaction with host cells, the mutant exhibited weaker interactions with Acanthamoeba castellanii cells and THP-1-derived macrophages. The mutant displayed reduced adherence to macrophages but enhanced adherence to A. castellanii, suggesting that the O-acetyl group of the LPS core region plays a crucial role in facilitating interaction with macrophages. The lack of core rhamnose O-acetyl groups made it easier for the bacteria to multiply in amoebae and macrophages. The mutant induced TNF-α production more strongly compared with the wild-type strain. The mutant synthesized twice as many ceramides Cer(t34:0) and Cer(t38:0) than the wild-type strain. The study showed that the internal sugars of the LPS core region of L. pneumophila sg 1 can interact with eukaryotic cell surface receptors and mediate in contacting and attaching bacteria to host cells as well as modulating the immune response to infection.

Legionella pneumophila is an opportunistic intracellular pathogen that inhabits artificial water systems and can be transmitted to human hosts by contaminated aerosols. Upon inhalation, it colonizes and grows inside the alveolar macrophages and causes Legionnaires\' disease. To effectively control and manage Legionnaires\' disease, a deep understanding of the host-pathogen interaction is crucial. Bacterial extracellular vesicles, particularly outer membrane vesicles (OMVs) have emerged as mediators of intercellular communication between bacteria and host cells. These OMVs carry a diverse cargo, including proteins, toxins, virulence factors, and nucleic acids. OMVs play a pivotal role in disease pathogenesis by helping bacteria in colonization, delivering virulence factors into host cells, and modulating host immune responses. This review highlights the role of OMVs in the context of host-pathogen interaction shedding light on the pathogenesis of L. pneumophila. Understanding the functions of OMVs and their cargo provides valuable insights into potential therapeutic targets and interventions for combating Legionnaires\' disease.

BACKGROUND: The number of reported cases of Legionnaires\' disease (LD) in the Republic of Korea surged nationally in 2016; however, in 2022, this number was higher in Jeju Province than the previous national peak. A descriptive epidemiological study was conducted to analyze trends in the incidence of reported LD cases in Jeju Island from 2015 to 2022.
METHODS: The data for this study were obtained from case reports submitted to the Korea Disease Control and Prevention Agency through its Disease and Health Integrated Management System. The selection criteria were cases or suspected cases of LD reported among Jeju residents between 2015 and 2022. The 95% confidence interval of the crude incidence rate was calculated using the Poisson distribution.
RESULTS: Since 2020, the incidence rate of LD in Jeju has risen sharply, showing a statistically significant difference from the national incidence rate. A particular medical institution in Jeju reported a significant number of LD cases. Screening with the urine antigen test (UAT) also increased significantly.
CONCLUSIONS: Our findings indicate that the rapid increase in cases of LD in Jeju Province since 2020 was due to the characteristics of medical-care use among Jeju residents, which were focused on a specific medical institution. According to their clinical practice guidelines, this medical institution conducted UATs to screen patients suspected of pneumonia.

Legionnaire\'s disease can cause rare and severe complications such as rhabdomyolysis and acute kidney injury. This case report details a 45-year-old male patient who presented with features of Legionnaire\'s disease. Laboratory results showed a significantly elevated serum creatinine kinase level and an increased creatinine level. Imaging showed right lower lobe consolidation, and a positive urine antigen test confirmed Legionnaire\'s disease. The patient was administered azithromycin and underwent fluid repletion to manage the rhabdomyolysis and acute kidney injury, resulting in improved creatinine kinase levels and kidney function. He was discharged and continued on azithromycin for 10 days. His outpatient follow-up showed that creatinine kinase levels had further decreased. This case report emphasises the importance of early recognition and management of Legionnaire\'s disease and its rare but severe complications.
CONCLUSIONS: Legionnaire\'s disease is a severe form of pneumonia caused by Legionella bacteria that can lead to rare complications such as rhabdomyolysis and acute kidney injury, which have high morbidity and mortality rates.The treatment for Legionnaire\'s disease complicated with rhabdomyolysis and acute kidney injury involves early fluid repletion, antibiotics and close monitoring of creatinine kinase levels, electrolytes and kidney function.For patients with creatinine kinase levels over 5000 U/l without hypocalcaemia or alkalaemia, urinary alkalinisation with bicarbonate therapy may be considered as a treatment option.

Legionellosis is a respiratory disease of bacterial and environmental origin that usually presents two distinct clinical entities, \"Legionnaires\' disease\" (LD) and \"Pontiac fever\". LD is an important cause of hospital-acquired pneumonia (HAP). The objective of this study is to describe the epidemiology of legionellosis-associated hospitalization (L-AH) in Spain from 2002 to 2021 and the burden of hospitalization due to legionellosis. Discharge reports from the Minimum Basic Data Set (MBDS) were used to retrospectively analyze hospital discharge data with a diagnosis of legionellosis, based on the ICD-9-CM and ICD-10-CM diagnosis codes, from 2002 to 2021. 21,300 L-AH occurred throughout the year during 2002-2021. The incidence of hospitalization associated per 100,000 inhabitants by month showed a similar trend for the 2002-2011, 2012-2021, and 2002-2021 periods. In Spain, during 2002-2021, the hospitalization rate (HR) in the autonomous communities ranged from 4.57 (2002-2011) to 0.24 (2012-2021) cases per 100,000 inhabitants. The HR of legionellosis in Spain has substantially increased across the 2002-2021 period, and the estimate is consistent with available European data. It is considered that in-depth epidemiological surveillance studies of legionellosis and improvements in the prevention and control of the disease are required in Spain.