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The article in the Canadian Medical Association Journal discusses a case of Legionnaires' disease in a 77-year-old man who presented with pneumonia symptoms after swimming in a lake in Iowa. Legionnaires' disease is caused by Legionella bacteria found in natural water sources and can lead to severe pneumonia. The article highlights the importance of considering Legionnaires' disease in patients with pneumonia who do not respond to broad-spectrum antibiotics, especially in those with risk factors like recent travel history or immunocompromised status. Diagnostic methods such as urinary antigen testing and bronchoalveolar lavage culture are crucial for accurate diagnosis and treatment. [Extracted from the article]

As cases of Legionnaires' disease increase worldwide, there is uncertainty on whether water management plans should focus on the measurement of Legionella species or specifically on L. pneumophila. This paper makes the case that for public water systems and buildings, the target organism should be L. pneumophila, as it is the overwhelming cause of illness, has simple methods for analysis, and remediation procedures avoid unnecessary costs that produce little public health benefit. A review of 930 outbreaks in the United States from 1973 through 2023 showed that there was no public health justification to require public water systems or public buildings (other than healthcare facilities) to monitor or manage for any other species of Legionella other than L. pneumophila. [ABSTRACT FROM AUTHOR]

Evolving technology and the development of new devices that can aerosolize water present a risk for new sources of Legionella bacteria growth and spread within industrial settings. We investigated a cluster of legionellosis among employees of a manufacturing facility in South Carolina, USA, and found 2 unique equipment sources of Legionella bacteria. The cluster of cases took place during August-November 2022; a total of 34 cases of legionellosis, including 15 hospitalizations and 2 deaths, were reported. Legionella pneumophila was isolated from 3 devices: 2 water jet cutters and 1 floor scrubber. L. pneumophila sequence type 36 was identified in environmental isolates and 1 patient specimen, indicating that those devices were the likely source of infection. Remediation was ultimately achieved through the development and implementation of a device-specific water management program. Manufacturing facilities that use aerosol-generating devices should consider maintaining updated Legionella water management programs to prevent Legionella bacterial infections. [ABSTRACT FROM AUTHOR]

Understanding the temporal relationship between key events in an individual's infection history is crucial for disease control. Delay data between events, such as infection and symptom onset times, is doubly censored because the exact time at which these key events occur is generally unknown. Current mathematical models for delay distributions are derived from heuristic justifications. Here, we derive a new model for delay distributions, specifically for incubation periods, motivated by bacterial-growth dynamics that lead to the Burr family of distributions being a valid modelling choice. We also incorporate methods within these models to account for the doubly censored data. Our approach provides biological justification in the derivation of our delay distribution model, the results of fitting to data highlighting the superiority of the Burr model compared to currently used models when the mode of the distribution is clearly defined or when the distribution tapers off. Under these conditions, our results indicate that the derived Burr distribution is a better-performing model for incubation-period data than currently used methods, with the derived Burr distribution being 13 times more likely to be a better-performing model than the gamma distribution for Legionnaires' disease based on data from a known outbreak. Author summary: In public health, it is important to know key temporal properties of diseases (such as how long someone is ill for or infectious for). Mathematical characterisation of properties requires information about patients' infection histories, such as the number of days between infection and symptom onset. These methods provide useful insights, such as how their infectiousness varies over time since they were infected. However, two key issues arise with these approaches. First, these methods do not have strong arguments for the validity of their usage. Second, the data typically used is provided as a rounded number of days between key events, as opposed to the exact period of time. We address both these issues by developing a new mathematical model to describe the important properties of the infection process of various diseases based on strong biological justification, and further incorporating methods within the mathematical model which consider infection and symptom onset to occur at any point within an interval, as opposed to an exact time. Under certain conditions, our approach provides more preferable results, based on AIC, than existing approaches, enhancing the understanding of properties of diseases such as Legionnaires' disease. [ABSTRACT FROM AUTHOR]

Background. Pulmonary superinfections increase the mortality risk among COVID-19 patients, highlighting the need for enhanced understanding to enable early and accurate diagnosis. Methods. We present the case of a patient, a 76-year-old man, hospitalized for a severe form of COVID-19, with a ground-glass pneumonia, involving 40–45% of lung surfaces. Results. In evolution, the clinical condition worsened, presenting leukocytosis with neutrophilia, imaging towards resorption, and computer tomography images showing the appearance of pulmonary condensations in the right lower lobe, the posterior portion of the left lower lobe and pleural collections. Carbapenemase-producing Klebsiella pneumoniae was isolated from the tracheal aspirate, and the real-time polymerase chain reaction test was positive for Klebsiella pneumoniae and Legionella pneumophila. The investigations that were carried out allowed us to establish the coinfections as a probable case of Legionnaire's disease and a ventilator-associated pneumonia with Klebsiella pneumoniae. Conclusions. The case analysis revealed that rare pneumonias may remain undiagnosed, and coinfections may be conditioned by pathophysiological factors or components of COVID-19 critical form treatment. Enhanced understanding of these aspects in clinical practice may contribute to reducing mortality risk in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: Legionella species are the causative agent of Legionnaires' disease and, as ubiquitous waterborne bacteria, are prone to antimicrobial resistance gene (ARG) acquisition and dissemination due to the antimicrobial contamination of natural environments. Given the potential health risks associated with ARGs, it is crucial to assess their presence in the Legionella population. Methods: The ARGs lpeAB and tet56 were detected in 348 samples, isolates, and DNA extracts using conventional PCR. In a subset of lpeAB-positive isolates, azithromycin (AZT) MIC values were obtained using the EUCAST protocol and LpeAB activity was evaluated through an efflux pump inhibition assay. Results: The lpeAB gene was found in 19% (66/348) of samples, with higher detection rates in the L. pneumophila and L. pneumophila sg1 subgroups, at 30% and 41%, respectively. A positive association between lpeAB and L. pneumophila sg1 was found. The MIC values of the lpeAB-positive isolates ranged from 0.064 to 2 mg/L. LpeAB inhibition resulted in 2- and 4-fold MIC reductions in 10 of the 13 isolates analyzed. One sample each of L. longbeacheae and L. bozemanae was found to possess the tet56 gene. Conclusions: The lpeAB gene is predominant in L. pneumophila sg1. A few isolates with the lpeAB gene exhibited MIC values below the EUCAST tentative highest MIC values for wild-type isolates. Expanding ARG monitoring in Legionella is essential to assess the public health risk of Legionnaires' disease. [ABSTRACT FROM AUTHOR]

Two sporadic cases of legionellosis occurring in consecutive years were confirmed by positive antigenuria to Legionella pneumophila serogroup 1 in individuals with limited mobility who were confined to their homes. Both cases had a history of using ultrasonic humidifiers and of low exposure to other possible sources of infection. This study was conducted through an expanded epidemiological survey and home inspection. Samples were collected from domestic hot water and humidifiers. Environmental isolates were characterised by immunoagglutination and immunofluorescence. The Dresden panel is employed for the determination of groups and subgroups of serogroup 1. The amoebae were isolated by water filtration and subsequent cultivation of the filters. Identification of the isolates was conducted through the sequencing of PCR products. In both cases, epidemiological studies identified the ultrasonic humidifiers as the probable source of infection. The presence of Legionella pneumophila was confirmed in the sanitary water installation and in the humidifiers, where high values of Legionella pneumophila serogroup 1 counts were also obtained. The isolates were characterised as Olda Oxford and Olda OLDA. Furthermore, in addition to the Legionella isolates, the presence of Vermamoeba vermiformis was also identified in samples obtained from domestic hot water and humidifiers in one of the residential addresses under investigation. It has been demonstrated that humidifiers can act as an amplification mechanism for pathogenic microorganisms when they are not cleaned and maintained correctly. This can pose a health danger, especially to people with previous respiratory pathologies, the immunosuppressed, and the elderly. Therefore, it is of the utmost importance that professionals who recommend the therapeutic use of this equipment should issue warnings regarding the importance of its correct use, cleaning, and disinfection. Finally, humidifiers should be considered in epidemiological surveys and in the study of sporadic cases. [ABSTRACT FROM AUTHOR]

Legionnaires disease is a serious pneumonia caused by Legionella bacteria. During November 2022-June 2024, CDC was notified of 12 cases of Legionnaires disease among travelers on two cruise ships; eight on cruise ship A and four on cruise ship B. CDC, in collaboration with the cruise lines, initiated investigations to ascertain the potential sources of on-board exposure after notification of the second potentially associated case for each ship. Epidemiologic data collected from patient interviews and environmental assessment and sampling results identified private hot tubs on selected cabin balconies as the most likely exposure source. To minimize Legionella growth, both cruise lines modified the operation and maintenance of these devices by removing the heating elements, draining water between uses, and increasing the frequency of hyperchlorination and cleaning. Hot tubs offer favorable conditions for Legionella growth and transmission when maintained and operated inadequately, regardless of location. Private hot tubs on cruise ships are not subject to the same maintenance requirements as are public hot tubs in common areas. Given the range of hot tub-type devices offered as amenities across the cruise industry, to reduce risk for Legionella growth and transmission, it is important for cruise ship water management program staff members to inventory and assess private balcony hot tubs and adapt public hot tub maintenance and operations protocols for use on private outdoor hot tubs. [ABSTRACT FROM AUTHOR]

Introduction: Legionnaires' disease is a severe pneumonia predominantly caused by Legionella pneumophila (Lp), whose major reservoirs are artificial water systems. As most human infections are caused by L. pneumophila serogroup 1 (Lp1), a reliable method for Lp distinction can be crucial for bacterial spread prevention. As the ability to withstand in environments and to cause the waterborne disease is strongly related to specific genes, the identification of virulent strains can be of great relevance to implement water environmental monitoring and to contain harmful outbreaks to public health. We aimed to test an assay for Lp identification among different Legionella species, and to determine the serogroups. Additionally, we investigated the carriage of virulence and antimicrobial resistance genes. Methods: A total of 90 Legionella spp. isolates identified by phenotypic tests were subjected to the designed quantitative PCR assay targeting specific mip for Lp, wzm for Lp1, pvcA and ahpD for biofilm production. Eleven serogroups were investigated in all our isolates tested positive for mip gene, subsequently analyzed for 12 virulence and 8 antimicrobial resistance genes. Results: Only the 70 Lp isolates were positive for mip. Out of 27 Lp isolates belonging to serogroup 1 based on agglutination test, 23 (85.2%) carried wzm. The presence of ahpD and pvcA was found in 94.3 and 98.6% of Lp isolates, respectively. By multiplex PCR, all 23 wzm-positive strains were confirmed as serogroup 1 that was the most predominant (33%). At least one virulence gene was detected in all Lp isolates. The most frequent gene was ispE (100%), followed by issD (96%), icmK and enhC (93%), cpxA (91%), rtxA2 (74%), lvhB8-B9 (61%), and prpA (54%). The other genes were less diffused in Lp strains (rtxA1, 44%; lvhB3-B4, 47%; pvcB, 27%; lvrE, 24%). Of the macrolide resistance genes, the ereA was found in 84% of Lp strains, while only 14 (20%) harbored the lpeAB among the efflux pump genes. Conclusion: The assays validated in this study enable the simultaneous Lp and Lp1 detection. The differentiation of Lp strains according to their virulence properties could be useful to predict the bacterial ability to survive and to cause the disease. [ABSTRACT FROM AUTHOR]

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Legionnaires' disease (LD) is a severe and potentially fatal form of bacterial pneumonia caused by Legionella spp. We evaluated the use of UV-light for detecting Legionella non- pneumophila in water samples according to the NEN-EN-ISO 11731:2017 methodology (reference method) in a collaborative effort involving 10 laboratories. First, a test panel was constructed of 298 strains: 157 Legionella strains and 141 non- Legionella strains were cultured on buffered charcoal yeast extract (BCYE)-medium and confirmed according to ISO 11731: 2017 (cultured on BCYE agar plates with and without l -cysteine), and by matrix-assisted laser desorption-ionization time of flight or next generation sequencing. All strains were additionally exposed to an UV-light to assess if they showed a bright blue fluorescence effect (UV-positive) or not (UV-negative). Second, in an interlaboratory study, 10 laboratories analyzed a blinded set of 16 Legionella strains and 8 non- Legionella strains using both methods. The test panel analyses showed 100% accordance between the UV-light and reference method. In addition, the interlaboratory study results showed full agreement between both methods. Our results support the implementation of UV-light detection to confirm Legionella presumptive colonies during analyses of water samples according to the NEN-EN-ISO 11731:2017 methodology. Implementation of UV-light confirmation could reduce workload, time-to-result and costs for the analyses of water samples for the presence of Legionella. [ABSTRACT FROM AUTHOR]

The bacterium of the genus Legionella were first detected during the American Legion convention held in Philadelphia in 1976, following a largeoutbreak of severe pneumonia (among residents of the Bellevue-Stratford Hotel) isolated by Dr. Joseph McDade. Legionella is an environmental Gram-negative bacterium that can cause spontaneously healing febrile illnesses (Pontiacfever) and fatal pneumonia (Legionnaires' disease) in humans. Legionella pneumophila is an important cause of community- and hospital-acquired pneumonia. It is phagocytosed within alveolar macrophages or epithelial cells by inhalation of aerosols contaminated with Legionella. Legionnaires' disease is caused by the bacilli engulfed in alveolar macrophages forming a vacuole containing Legionella by preventing phagolysosomal fusion, thanks to the Type 4 Secretion System encoded by the Dot/Icm genes, and its proliferation within this vacuole by escaping the host immune mechanisms. The most interesting aspect of the Legionella bacterium's genome is the motifs, most of which are of eukaryotic origin, that it acquired through gene transfer during its parasitism in amoebae. Thanks to the semotifs obtained by horizontal gene transfer, Legionella bacteria have an incredible number of virulence factors that will increase their resistance to environmental factors and host immunity, that is, "an army with a huge arsenal". Moreover, these eukaryotic motifs also apply to bacteria; Provides the capacity to develop exceptional adaptation strategies. Their survival in biofilms and amoebae protects them from intensive disinfection practices and increases their resistance to environmental factors. The twophase life cycle of Legionella includes the infectious phase and the non-infective replicative phase; It also reveals physiological, morphogenetic and metabolic change abilities. Amoebae and macrophages suggests that environmental amoebae act as an "educator" the similarity of the infection cycle between. It is aimed to review current information on the abilities of Legionella to infect amoebae and macrophages, virulence/survival strategies, infection mechanisms, host immunity and Legionella immunopathogenesis. [ABSTRACT FROM AUTHOR]

Background: The incidence of Legionnaires' disease (LD) is increasing steadily in Europe. Its early diagnosis by general practitioners (GPs) is crucial for better patient outcomes. Study objectives: This study assessed Belgian GPs' knowledge about LD and the accessibility of diagnostic tests in their practices. Methods: A specifically designed questionnaire was distributed to actively practicing GPs, including primary care trainees, between 31 January 2022 and 13 March 2022. This survey targeted approximately 4200 GPs with an estimated population catchment of 30% of the actively working Belgian GPs. Results: The response rate was estimated at 3%. Over 70% of the GPs correctly identified the LD occurrence peak, major risk factors, and clinical manifestations. While 62% of participants preferred the Legionella pneumophila urinary antigen test (UAT) as a primary diagnostic method, 75% were unsure about its availability within their laboratories and 82% had not prescribed it in the last year. Finally, 76% expressed a desire for additional information on this topic. Conclusions: Belgian GPs should evaluate the possibility of conducting UAT testing in their laboratories to enhance LD case management and improve their preparedness. Furthermore, initiatives should be implemented to improve communication between specialists and GPs and develop educational programs directed at Belgian GPs. [ABSTRACT FROM AUTHOR]

The study examines the impact of temperature on Legionella sp. bacteria in hot water systems in hospitals and social welfare homes in the Kielce Province, Poland, from 2014 to 2018. Results show that water temperature ≥ 55 ° C significantly reduces Legionella contamination. However, the majority of samples had temperatures below 55 ° C, indicating non-compliance with legal standards. Proper water temperature is crucial for health safety in such facilities, highlighting the importance of monitoring and maintaining correct water temperatures to prevent Legionella contamination. [Extracted from the article]

Legionella is an underdiagnosed and underreported etiology of pneumonia. Legionella pneumophila serogroup 1 (LpSG1) is thought to be the most common pathogenic subgroup. This assumption is based on the frequent use of a urinary antigen test (UAT), only capable of diagnosing LpSG1. We aimed to explore the frequency of Legionella infections in individuals diagnosed with pneumonia and the performance of diagnostic methods for detecting Legionella infections. We conducted a scoping review to answer the following questions: (1) "Does nucleic acid testing (NAT) increase the detection of non-pneumophila serogroup 1 Legionella compared to non-NAT?"; and (2) "Does being immunocompromised increase the frequency of pneumonia caused by non-pneumophila serogroup 1 Legionella compared to non-immunocompromised individuals with Legionnaires' disease (LD)?". Articles reporting various diagnostic methods (both NAT and non-NAT) for pneumonia were extracted from several databases. Of the 3449 articles obtained, 31 were included in our review. The most common species were found to be L. pneumophila, L. longbeachae, and unidentified Legionella species appearing in 1.4%, 0.9%, and 0.6% of pneumonia cases. Nearly 50% of cases were caused by unspecified species or serogroups not detected by the standard UAT. NAT-based techniques were more likely to detect Legionella than non-NAT-based techniques. The identification and detection of Legionella and serogroups other than serogroup 1 is hampered by a lack of application of broader pan-Legionella or pan-serogroup diagnostics. [ABSTRACT FROM AUTHOR]

Legionella contamination in public water systems poses significant health risks, particularly in schools where vulnerable populations, including children, regularly use these facilities. This study investigates the presence of Legionella in the hot water systems from 49 primary schools across two municipalities in the Danish capital region. Water samples were collected from taps in each school, and both first-flush and stabile temperature samples were analysed for Legionella contents. The findings revealed that 97% of schools in Municipality 1 and 100% in Municipality 2 had Legionella in their hot water systems. The content of Legionella colonies was significantly higher in schools in Municipality 1, which was probably because of overall lower water temperatures. At stabile temperatures, 76% and 50% of the schools in the two municipalities exceeded the European Union's recommended limit of 1000 CFU/L. Stabile peripheral water temperatures were achieved after 3 min. Tap water temperatures above 54 °C and central tank temperatures above 59 °C were associated with Legionella contents below 1000 CFU/L. This study highlights the need for more stringent Legionella control procedures in schools, including higher water temperatures and refining Legionella reducing interventions with the addition of regular flow and draining procedures. [ABSTRACT FROM AUTHOR]

A widespread strategy employed by pathogens to establish infection is to inhibit host-cell protein synthesis. Legionella pneumophila, an intracellular bacterial pathogen and the causative organism of Legionnaires' disease, secretes a subset of protein effectors into host cells that inhibit translation elongation. Mechanistic insights into how the bacterium targets translation elongation remain poorly defined. We report here that the Legionella effector SidI functions in an unprecedented way as a transfer-RNA mimic that directly binds to and glycosylates the ribosome. The 3.1 Å cryo-electron microscopy structure of SidI reveals an N-terminal domain with an 'inverted L' shape and surface-charge distribution characteristic of tRNA mimicry, and a C-terminal domain that adopts a glycosyl transferase fold that licenses SidI to utilize GDP-mannose as a sugar precursor. This coupling of tRNA mimicry and enzymatic action endows SidI with the ability to block protein synthesis with a potency comparable to ricin, one of the most powerful toxins known. In Legionella-infected cells, the translational pausing activated by SidI elicits a stress response signature mimicking the ribotoxic stress response, which is activated by elongation inhibitors that induce ribosome collisions. SidI-mediated effects on the ribosome activate the stress kinases ZAKα and p38, which in turn drive an accumulation of the protein activating transcription factor 3 (ATF3). Intriguingly, ATF3 escapes the translation block imposed by SidI, translocates to the nucleus and orchestrates the transcription of stress-inducible genes that promote cell death, revealing a major role for ATF3 in the response to collided ribosome stress. Together, our findings elucidate a novel mechanism by which a pathogenic bacterium employs tRNA mimicry to hijack a ribosome-to-nuclear signalling pathway that regulates cell fate.

BackgroundLegionnaires’ disease has a high clinical mortality rate, and early diagnosis and treatment are critical. Increasing evidence shows that metagenomic next-generation sequencing (mNGS) has excellent potential for the early identification of pathogens. To help clinicians better recognize Legionnaires’ disease in its early stage and to illustrate the diagnostic value of mNGS technology, we reviewed and summarized two cases of severe Legionnaires’ disease.Methods and analysisWe selected two patients with severe Legionnaires’ disease who were admitted to our department in recent years. We discuss experience with them and the shortcomings in their treatment by summarizing their medical history, disease evolution, tests, and diagnostic and therapeutic processes.ResultsIn both patients, the diagnosis of Legionnaires’ disease was confirmed through analysis of the bronchoalveolar lavage fluid (BALF). The middle-aged male patient was cured and discharged due to early detection and diagnosis. The elderly immunocompromised patient died due to a delay in diagnosis.ConclusionThis study highlights the importance of the early recognition and diagnosis of severe Legionnaires’ disease and the advantages of mNGS in identifying the pathogen.

Purpose/Aim of the Study: A case admitted with dysarthria and syncope and hyperintense lesion in the splenium of the corpus callosum, diagnosed as Legionnaires' disease by detecting Legionella antigen in the urine, and recovered only with antibiotic treatment is presented because it is rare in the literature. Materials and Methods: When a 64-year-old female patient was admitted to the emergency department with complaints of sudden loss of consciousness and fainting at home, she had speech impairment, and her pulse oxygen saturation in room air was 88%. In the neurological examination, there was no pathological finding except dysarthria in the patient with no motor deficit. The patient had no respiratory complaints and had a recent travel history. In laboratory examinations, hyponatremia was detected with increased C-reactive protein and liver enzymes. Consolidation was observed in the lower right zone on chest computed tomography. Ampicillin + sulbactam (4x1 gr, intravenous) and clarithromycin (2 × 500 mg orally) were initiated. On cranial magnetic resonance, a hyperintense lesion was observed in the splenium of the corpus callosum in the oval T2 sequence. Legionella pneumophila serogroup 1 antigen in urine was reported as positive. On the fourth day of her hospitalization, the patient, whose CRP and liver enzyme values regressed, her hyponatremia improved, her pulse oxygen saturation increased to 92% in room air, and her speech became comprehensible, was discharged after oral antibiotic treatment was arranged. On the 12th day, the speech ability of the patient completely returned to normal. Conclusion: Legionella infection should be suspected in the presence of pneumonia and corpus callosum splenium lesion. [ABSTRACT FROM AUTHOR]

Abstract The pandemic marked the beginning of an era of dynamic and rapid changes in the diagnosis of respiratory infections. Herein we describe Legionnaires’ disease trend in the years 2016–2023 in a large Italian hospital showing how improvements in diagnostic algorithms impact on its detection.

This study investigates the utility of Google Trends and Google Search data in retrospectively analyzing the Flint Water Crisis, a significant public health event. By examining keywords relevant to the crisis, such as "lead," "bottled water," "water filters," "pneumonia," and "Legionnaires' Disease," we aimed to uncover patterns in public awareness and response during a public crisis and explore how such awareness and responses could potentially aid in reducing the risk of similar crises in the future. Our analysis reveals a clear correlation between search frequencies and the crisis timeline, with spikes in search terms corresponding to key events. This suggests that such data can serve as a valuable tool for understanding public sentiment and behavior in the face of environmental disasters. The research underscores the potential of "Big Data," led by search engines and social media platforms, in shaping public policy and informed decision-making. However, it also addresses the limitations and challenges in using these data sources, including issues of data consistency, replicability, and the influence of sociocultural contexts on search behaviors. The study advocates for the combined use of Google Trends and Google Search data, complemented by other datasets, for a more comprehensive understanding of public engagement in environmental crises. This work contributes to the growing field of infodemiology, emphasizing the importance of big data analysis in environmental science and public health research. [ABSTRACT FROM AUTHOR]

Legionella infection, the causative agent of Legionnaires' disease, represents a significant threat to human health. The pathogenesis of this infection is intricately linked to the complex interactions between the bacterium and its host, resulting in profound metabolic perturbations. Central to these metabolic shifts is the bacterium's modulation of lipid metabolism, with changes in lipid synthesis and breakdown modifying membrane composition and function. These alterations can influence cellular signaling and immune responses, further contributing to disease progression. It also disrupts glucose utilization and lipid metabolism, altering cellular energy production and immune responses. Additionally, Legionella infection perturbs amino acid and protein metabolism, affecting protein synthesis and degradation, leading to changes in cellular functions and immune responses. This mini-review underscores the complexity of metabolic perturbations in Legionella infection and their significance in host-pathogen interactions. Understanding these metabolic shifts provides valuable insights into the pathogenesis of Legionnaires' disease and could lead to the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Legionella longbeachae and Legionella pneumophila are the most common causative agents of Legionnaires' disease. While the clinical manifestations caused by both species are similar, species-specific differences exist in environmental niches, disease epidemiology, and genomic content. One such difference is the presence of a genomic locus predicted to encode a capsule. Here, we show that L. longbeachae indeed expresses a capsule in post-exponential growth phase as evidenced by electron microscopy analyses, and that capsule expression is abrogated when deleting a capsule transporter gene. Capsule purification and its analysis via HLPC revealed the presence of a highly anionic polysaccharide that is absent in the capsule mutant. The capsule is important for replication and virulence in vivo in a mouse model of infection and in the natural host Acanthamoeba castellanii. It has anti-phagocytic function when encountering innate immune cells such as human macrophages and it is involved in the low cytokine responses in mice and in human monocyte derived macrophages, thus dampening the innate immune response. Thus, the here characterized L. longbeachae capsule is a novel virulence factor, unique among the known Legionella species, which may aid L. longbeachae to survive in its specific niches and which partly confers L. longbeachae its unique infection characteristics. Author summary: Legionella longbeachae can cause a severe pneumonia, known as Legionnaires' disease. In Australia and New Zealand, L. longbeachae is the predominant species causing up to 50% of all infections due to Legionella. However, L. longbeachae virulence factors are nearly unknown. Here, we show that L. longbeachae expresses a capsule that is a major virulence factor of this pathogen as it is important for virulence in vivo in mice and in the environment in its natural host Acanthamoeba castellanii. It dampens the innate immune response in mice and human cells. Our study sheds light on an understudied environmental pathogen and identifies a new virulence feature of Legionellae. [ABSTRACT FROM AUTHOR]

The accidental human pathogen Legionella pneumophila (Lp) is the etiological agent for a severe atypical pneumonia known as Legionnaires' disease. In human infections and animal models of disease alveolar macrophages are the primary cellular niche that supports bacterial replication within a unique intracellular membrane-bound organelle. The Dot/Icm apparatus—a type IV secretion system that translocates ~300 bacterial proteins within the cytosol of the infected cell—is a central virulence factor required for intracellular growth. Mutant strains lacking functional Dot/Icm apparatus are transported to and degraded within the lysosomes of infected macrophages. The early foundational work from Dr. Horwitz's group unequivocally established that Legionella does not replicate extracellularly during infection—a phenomenon well supported by experimental evidence for four decades. Our data challenges this paradigm by demonstrating that macrophages and monocytes provide the necessary nutrients and support robust Legionella extracellular replication. We show that the previously reported lack of Lp extracellular replication is not a bacteria intrinsic feature but rather a result of robust restriction by serum-derived nutritional immunity factors. Specifically, the host iron-sequestering protein Transferrin is identified here as a critical suppressor of Lp extracellular replication in an iron-dependent manner. In iron-overload conditions or in the absence of Transferrin, Lp bypasses growth restriction by IFNγ-primed macrophages though extracellular replication. It is well established that certain risk factors associated with development of Legionnaires' disease, such as smoking, produce a chronic pulmonary environment of iron-overload. Our work indicates that iron-overload could be an important determinant of severe infection by allowing Lp to overcome nutritional immunity and replicate extracellularly, which in turn would circumvent intracellular cell intrinsic host defenses. Thus, we provide evidence for nutritional immunity as a key underappreciated host defense mechanism in Legionella pathogenesis. In this work, authors indicate a cooperation between nutritional immunity and interferon limits Legionella replication during infection and compromised nutritional immunity may increase severity by allowing the bacteria to replicate outside of host cells. [ABSTRACT FROM AUTHOR]

Legionella longbeachae is the leading cause of Legionnaires' disease (LD) in Australasia and has been linked to exposure to compost and potting soils. Adding antimicrobial metal ions such as copper (Cu2+), zinc (Zn2+), and manganese (Mn2+) to potting soils may reduce the load of L. longbeachae bacteria and infection risk. Baseline concentrations of metal ions in leachate from peat, bark dust, bagging base, and an all-purpose potting soil were: iron 0.40–0.99 µg/ml, Cu of 0.003–0.03 µg/ml, Zn 0.01–0.06 µg/ml and Mn 0.11–0.29 µg/ml. Addition of Cu2+ ions to leachate reduced L. longbeachae viability in a concentration dependent manner. A similar effect was seen in potting soil with Zn2+ and Mn2+ but 10-fold higher concentrations were needed. These metal ions have potential to reduce the load of L. longbeachae in potting soils but toxicity in plants needs to be determined. [ABSTRACT FROM AUTHOR]

We retrospectively reviewed 64 cases of cancer with pulmonary legionellosis (Legionella pneumophila in 73%). Nearly all patients received Legionella -active antibiotics, yet 30-day mortality was 23%. Independent predictors of 30-day mortality were hyponatremia, bilateral lung involvement, and Sequential Organ Failure Assessment score ≥5. Lung coinfections were common (31%) but did not significantly increase mortality. [ABSTRACT FROM AUTHOR]

The pandemic marked the beginning of an era of dynamic and rapid changes in the diagnosis of respiratory infections. Herein we describe Legionnaires' disease trend in the years 2016–2023 in a large Italian hospital showing how improvements in diagnostic algorithms impact on its detection. [ABSTRACT FROM AUTHOR]

Legionella pneumophila, the bacteria responsible for Legionnaires' disease, is able to evade the host's defense mechanisms by modifying the ubiquitin landscape on the Legionella-containing vacuole (LCV). Two recent studies published in Nature Communications have revealed the cooperative action between two Legionella effectors, Sdc and Sde, in decorating the LCV with mixed ubiquitin chains. These modifications prevent the recognition of the LCV by autophagy receptors, allowing Legionella to establish a replicative niche within host cells. The findings highlight the sophisticated strategies employed by Legionella to manipulate the host ubiquitin system and evade autophagic clearance. Further research is needed to understand the temporal and spatial regulation of these effectors and their interplay with other bacterial effectors. The discovery of this mechanism opens up new avenues for studying host-pathogen interactions and developing therapeutic strategies against infections. [Extracted from the article]

Legionella pneumophila is ubiquitous and sporadically infects humans causing Legionnaire's disease (LD). Globally, reported cases of LD have risen fourfold from 2000 to 2014. In 2016, Sydney, Australia was the epicenter of an outbreak caused by L. pneumophila serogroup 1 (Lpsg1). Whole-genome sequencing was instrumental in identifying the causal clone which was found in multiple locations across the city. This study examined the epidemiology of Lpsg1 in an urban environment, assessed typing schemes to classify resident clones, and investigated the association between local climate variables and LD outbreaks. Of 223 local Lpsg1 isolates, we identified dominant clones with one clone isolated from patients in high frequency during outbreak investigations. The core genome multi-locus sequence typing scheme was the most reliable in identifying this Lpsg1 clone. While an increase in humidity and rainfall was found to coincide with a rise in LD cases, the incidence of the major L. pneumophila outbreak clone did not link to weather phenomena. These findings demonstrated the role of high-resolution typing and weather context assessment in determining source attribution for LD outbreaks in urban settings, particularly when clinical isolates remain scarce. [ABSTRACT FROM AUTHOR]

Legionella is the pathogen that causes Legionnaires' disease, an increasingly prevalent and sometimes fatal disease worldwide. In 2021, 97% of cases in Europe were caused by Legionella pneumophila. We present a mathematical model that can be used by public health officials to assess the effectiveness and efficiency of different Legionella monitoring and control strategies to inform government requirements to prevent community-acquired Legionnaires' disease in non-hospital buildings. This simulation model was built using comprehensive data from multiple scientific and field-based sources. It is a tool for estimating the relative economic and human costs of monitoring and control efforts targeting either L. pneumophila or Legionella species and was designed to analyze the potential application of each approach to specific building classes across Italy. The model results consistently showed that targeting L. pneumophila is not only sufficient but preferable in optimizing total cost (direct and economic) for similar human health benefits, even when stress-tested with extreme inputs. This cost–benefit analytical tool allows the user to run different real-life scenarios with a broad range of epidemiological and prevalence assumptions across different geographies in Italy. With appropriate modifications, this tool can be localized and applied to other countries, states, or provinces. [ABSTRACT FROM AUTHOR]

Background: Legionella pneumophila is a Gram-negative intracellular bacillus and is the causative agent of a severe form of pneumonia called Legionnaires' disease which accounts for 2-9% of cases of community acquired pneumonia. It produces an extremely large protein belonging to the RTX (Repeats in ToXin) family, called RtxA, and we previously reported that RtxA is transported by a dedicated type 1 secretion system (T1SS) to the cell surface. RTX proteins have been shown to participate in the virulence or biofilm formation of various bacteria, the most studied models being the pore forming hemolysin A (HlyA) of Escherichia coli and the biofilm associated protein LapA of P. fluorescens. LapA localization depends on the enzymatic release by LapD/LapG complex activity. This study aimed to elucidate the dual localization (cell surface associated or released state) of L. pneumophila RTX protein (RtxA) and whether this released versus sequestered state of RtxA plays a role in L. pneumophila virulence. Results: The hereby work reveals that, in vitro, LapG periplasmic protease cleaves RtxA N-terminus in the middle of a di-alanine motif (position 108–109). Consistently, a strain lacking LapG protease maintains RtxA on the cell surface, whereas a strain lacking the c-di-GMP receptor LapD does not exhibit cell surface RtxA because of its continuous cleavage and release, as in the LapA-D-G model of Pseudomonas fluorescens. Interestingly, our data point out a key role of RtxA in enhancing the infection process of amoeba cells, regardless of its location (embedded or released); therefore, this may be the result of a secondary role of this surface protein. Conclusions: This is the first experimental identification of the cleavage site within the RTX protein family. The primary role of RtxA in Legionella is still questionable as in many other bacterial species, hence it sounds reasonable to propose a major function in biofilm formation, promoting cell aggregation when RtxA is embedded in the outer membrane and facilitating biofilm dispersion in case of RtxA release. The role of RtxA in enhancing the infection process may be a result of its action on host cells (i.e., PDI interaction or pore-formation), and independently of its status (embedded or released). [ABSTRACT FROM AUTHOR]

Given the recent global surge in Legionnaires' disease cases, the monitoring of Legionella pneumophila becomes increasingly crucial. Epidemiological cases often stem from local outbreaks rather than widespread dissemination, emphasizing the need to study the characteristics of this pathogen at a local level. This study focuses on isolates of L. pneumophila in the Italian region of Friuli Venezia Giulia to assess specific genotype and phenotype distribution over time and space. To this end, a total of 127 L. pneumophila strains isolated between 2005 and 2017 within national surveillance programs were analysed. Rep-PCR, RAPD, and Sau-PCR were used for genotypic characterization, while phenotypic characterization was conducted through fatty acids analysis. RAPD and Sau-PCR effectively assessed genetic characteristics, identifying different profiles for the isolates and excluding the presence of clones. Although Sau-PCR is rarely used to analyse this pathogen, it emerged as the most discriminatory technique. Phenotypically, hierarchical cluster analysis categorized strains into three groups based on varying membrane fatty acid percentages. However, both phenotypic and genotypic analyses revealed a ubiquitous profile distribution at a regional level. These results suggest an absence of correlations between strain profiles, geographical location, and isolation time, indicating instead high variability and strain dissemination within this region. [ABSTRACT FROM AUTHOR]

Backgroud: Although not fully investigated, studies show that Legionella pneumophila can develop antibiotic resistance. As there is limited data available for Portugal, we determined the antibiotic susceptibility profile of Portuguese L. pneumophila serogroup 1 (LpnSg1) isolates against antibiotics used in the clinical practice in Portugal. Methods: Minimum inhibitory concentrations (MICs) were determined for LpnSg1 clinical (n = 100) and related environmental (n = 7) isolates, collected between 2006–2022 in the context of the National Legionnaire´s Disease Surveillance Programme, against azithromycin, clarithromycin, erythromycin, levofloxacin, ciprofloxacin, moxifloxacin, rifampicin, doxycycline, tigecycline, and amoxicillin/clavulanic acid, using three different assays. Isolates were also PCR-screened for the presence of the lpeAB gene. Results: Twelve isolates had azithromycin MICs above the EUCAST tentative highest WT MIC, 9 of which were lpeAB negative; for erythromycin and clarithromycin, all isolates tested within the susceptible range. The number of isolates with MICs above the tentative highest WT MIC for the remaining antibiotics was: ciprofloxacin: 7; levofloxacin: 17; moxifloxacin: 8; rifampicin: 11; doxycycline: 82; tigecycline: 4. EUCAST breakpoints are not available for amoxicillin/clavulanic acid. We estimated the ECOFFs and one isolate had a MIC eightfold higher than the E-test ECOFF. Additionally, a clinical isolate generated three colonies growing on the E-test inhibition zone that resulted in MICs fourfold higher than for the parental isolate. Conclusions: We report, for the first time, elevated MICs against first-line and other antibiotics (including azithromycin, fluoroquinolones and amoxicillin/clavulanic acid commonly used to treat pneumonia patients in Portugal) in Portuguese L. pneumophila strains. Results point towards decreased susceptibility in circulating strains, justifying further investigation. [ABSTRACT FROM AUTHOR]

Wastewater treatment plants (WWTPs) are suspected reservoirs of Legionella pneumophila (Lp). The required aeration and mixing steps lead to the emission and dispersion of bioaerosols potentially harboring Lp. The aim of the project is to evaluate municipal WWTPs as a possible source of legionellosis through the statistical analysis of case clusters. A space–time scanning statistical method was implemented in SaTScan software to identify and analyze WWTPs located within and close to spatiotemporal clusters of legionellosis detected in Quebec between 2016 and 2020. In parallel, WWTPs were ranked according to their pollutant load, flow rate and treatment type. These parameters were used to evaluate the WWTP susceptibility to generate and disperse bioaerosols. Results show that 37 of the 874 WWTPs are located inside a legionellosis cluster study zone, including six of the 40 WWTPs ranked most susceptible. In addition, two susceptible WWTPs located within an extended area of 2.5 km from the study zone (2.5-km buffer) were included, for a total of 39 WWTPs. The selected 39 WWTPs were further studied to document proximity of population, dominant wind direction, and surrounding water quality. Samples collected from the influent and the effluent of six selected WWTPs revealed the presence of Legionella spp. in 92.3% of the samples. Lp and Lp serogroupg 1 (Lp sg1) were detected below the limit of quantification in 69% and 46% of the samples, respectively. The presence of Legionella in wastewater and the novel statistical approach presented here provides information to the public health authorities regarding the investigation of WWTPs as a possible source of Legionella exposure, sporadic cases, and clusters of legionellosis. [ABSTRACT FROM AUTHOR]

This article discusses the use of rifampin in clinical drug-drug interaction (DDI) studies. Rifampin is an antibiotic that is commonly used as an inducer of drug-metabolizing enzymes and transporters. However, recent reports of a nitrosamine impurity called 1-methyl-4-nitrosopiperazine (MNP) in rifampin products have raised concerns. The FDA has set a limit for MNP in rifampin products, and this has led to the search for alternative inducers for DDI studies. The authors argue that rifampin should continue to be used in these studies due to its well-established induction effects, pleiotropic effects, and safety profile compared to alternative inducers like carbamazepine and phenytoin. [Extracted from the article]

Legionella pneumophila is the waterborne pathogen primarily responsible for causing both Pontiac Fever and Legionnaire's Disease in humans. L. pneumophila is transmitted via aerosolized water droplets. The purpose of this study was to design and test primers to allow for rapid polymerase chain reaction (PCR) melt detection and identification of this infectious agent in cases of clinical or emergency response detection. New PCR primers were designed for this species of bacteria; the primer set was purchased from IDT and the target bacterial DNA was purchased from ATCC. The L. pneumophila primers targeted the macrophage infectivity potentiator gene (mip), which inhibits macrophage phagocytosis. The primers were tested for specificity, repeatability, and sensitivity using PCR–high-resolution melt (HRM) assays. The primer set was found to be specific to the designated bacteria and did not amplify the other twenty-one species from the panel. The L. pneumophila assay was able to be multiplexed. The duplex assay consists of primers for L. pneumophila and Vibrio parahaemolyticus, which are both waterborne pathogens. The triplex assay consists of primers for L. pneumophila, V. parahaemolyticus, and Campylobacter jejuni. The unique melting temperature for the L. pneumophila primer assay is 82.84 ± 0.19 °C, the C. jejuni assay is 78.10 ± 0.58 °C, and the V. parahaemolyticus assay is 86.74 ± 0.65 °C. [ABSTRACT FROM AUTHOR]

Although cases of Legionnaires' disease are notifiable, data on the phenotypic and genotypic characterisation of clinical isolates are limited. This retrospective study aims to report the results of the characterisation of Legionella clinical isolates in Spain from 2012 to 2022. Monoclonal antibodies from the Dresden panel were used for phenotypic identification of Legionella pneumophila. Genotypic characterisation and sequence type assignment were performed using the Sequence-Based Typing scheme. Of the 1184 samples, 569 were identified as Legionella by culture. Of these, 561 were identified as L. pneumophila, of which 521 were serogroup 1. The most common subgroups were Philadelphia (n = 107) and Knoxville (n = 106). The SBT analysis revealed 130 different STs, with the most common genotypes being ST1 (n = 87), ST23 (n = 57), ST20 (n = 30), and ST42 (n = 29). Knoxville has the highest variability with 32 different STs. ST23 is mainly found in Allentown/France (n = 46) and ST42 in Benidorm (n = 18), whereas ST1 is widely distributed. The results demonstrate that clinical isolates show high genetic diversity, although only a few sequence types (STs) are responsible for most cases. However, outbreaks can also occur with rare genotypes. More data on LD and associated epidemiological studies are needed to establish the risk of an isolate causing outbreak in the future. [ABSTRACT FROM AUTHOR]

ABSTRACT Legionella pneumophila serogroup 1 sequence types (ST) 213 and 222, a single-locus variant of ST213, were first detected in the early 1990s in the Midwest United States (U.S.) and the late 1990s in the Northeast U.S. and Canada. Since 1992, these STs have increasingly been implicated in community-acquired sporadic and outbreak-associated Legionnaires’ disease (LD) cases. We were interested in understanding the change in LD frequency due to these STs and identifying genetic features that differentiate these STs from one another. For the geographic area examined here (Mountain West to Northeast) and over the study period (1992–2020), ST213/222-associated LD cases identified by the Centers for Disease Control and Prevention increased by 0.15 cases per year, with ST213/222-associated LD cases concentrated in four states: Michigan (26%), New York (18%), Minnesota (16%), and Ohio (10%). Additionally, between 2002 and 2021, ST222 caused at least five LD outbreaks in the U.S.; no known outbreaks due to ST213 occurred in the U.S. during this time. We compared the genomes of 230 ST213/222 isolates and found that the mean of the average nucleotide identity (ANI) within each ST was high (99.92% for ST222 and 99.92% for ST213), with a minimum between ST ANI of 99.50% and a maximum of 99.87%, indicating low genetic diversity within and between these STs. While genomic features were identified (e.g., plasmids and CRISPR-Cas systems), no association explained the increasing geographic distribution and prevalence of ST213 and ST222. Yet, we provide evidence of the expanded geographical distribution of ST213 and ST222 in the U.S.IMPORTANCESince the 1990s, cases of Legionnaires’ disease (LD) attributed to a pair of closely related Legionella pneumophila variants, ST213 and ST222, have increased in the U.S. Furthermore, between 2002 and 2021, ST222 caused at least five outbreaks of LD in the U.S., while ST213 has not been linked to any U.S. outbreak. We wanted to understand how the rate of LD cases attributed to these variants has changed over time and compare the genetic features of the two variants. Between 1992 and 2020, we determined an increase of 0.15 LD cases ascribed to ST213/222 per year in the geographic region studied. Our research shows that these STs are spreading within the U.S., yet most of the cases occurred in four states: Michigan, New York, Minnesota, and Ohio. Additionally, we found little genetic diversity within and between these STs nor could specific genetic features explain their geographic spread.

IntroductionLegionnaires’ disease is a severe pneumonia predominantly caused by Legionella pneumophila (Lp), whose major reservoirs are artificial water systems. As most human infections are caused by L. pneumophila serogroup 1 (Lp1), a reliable method for Lp distinction can be crucial for bacterial spread prevention. As the ability to withstand in environments and to cause the waterborne disease is strongly related to specific genes, the identification of virulent strains can be of great relevance to implement water environmental monitoring and to contain harmful outbreaks to public health. We aimed to test an assay for Lp identification among different Legionella species, and to determine the serogroups. Additionally, we investigated the carriage of virulence and antimicrobial resistance genes.MethodsA total of 90 Legionella spp. isolates identified by phenotypic tests were subjected to the designed quantitative PCR assay targeting specific mip for Lp, wzm for Lp1, pvcA and ahpD for biofilm production. Eleven serogroups were investigated in all our isolates tested positive for mip gene, subsequently analyzed for 12 virulence and 8 antimicrobial resistance genes.ResultsOnly the 70 Lp isolates were positive for mip. Out of 27 Lp isolates belonging to serogroup 1 based on agglutination test, 23 (85.2%) carried wzm. The presence of ahpD and pvcA was found in 94.3 and 98.6% of Lp isolates, respectively. By multiplex PCR, all 23 wzm-positive strains were confirmed as serogroup 1 that was the most predominant (33%). At least one virulence gene was detected in all Lp isolates. The most frequent gene was ispE (100%), followed by issD (96%), icmK and enhC (93%), cpxA (91%), rtxA2 (74%), lvhB8-B9 (61%), and prpA (54%). The other genes were less diffused in Lp strains (rtxA1, 44%; lvhB3-B4, 47%; pvcB, 27%; lvrE, 24%). Of the macrolide resistance genes, the ereA was found in 84% of Lp strains, while only 14 (20%) harbored the lpeAB among the efflux pump genes.ConclusionThe assays validated in this study enable the simultaneous Lp and Lp1 detection. The differentiation of Lp strains according to their virulence properties could be useful to predict the bacterial ability to survive and to cause the disease.

Legionnaires' disease (LD) is a serious type of pneumonia, typically contracted by susceptible people through the inhalation of aerosols contaminated with Legionella pneumophila (Lp). In this report, the first case of coinfection with Lp–Bordetella bronchiseptica (Bb) is described. A possible source of the Lp infection may be the hotel in Paris (France) where the patient had stayed before developing the symptoms. The Bb infection may have been transmitted by the dog with which he had constant contact, although this has not been proven.

We report a case of Legionnaires’ disease caused by Legionella bozemanae, which is the first time that L. bozemanae has been isolated from a bronchoalveolar lavage fluid sample from an immunocompromised patient in China. The findings highlight the susceptibility of immunocompromised patients to infections caused by the rare but highly pathogenic L. bozemanae.

Abstract 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. Graphical Abstract

The article discusses two cases of patients diagnosed with VEXAS syndrome, a rare autoinflammatory disorder caused by somatic mutations in the UBA1 gene, who also presented with autoimmune blistering diseases (AIBDs). Patient 1 had pemphigus vulgaris (PV) and experienced various symptoms, including recurrent fever, cytopenia, and pulmonary inflammation. Patient 2 had dermatitis herpetiformis (DH) and exhibited cutaneous symptoms alongside constitutional issues. The co-occurrence of VEXAS syndrome and AIBDs is uncommon, and further research is needed to understand the underlying mechanisms. [Extracted from the article]

Cutaneous Legionella infection is rare and primarily seen in immunosuppressed patients. Herein, we present a case of cutaneous and pulmonary legionellosis presenting with fever and erythematous subcutaneous nodules in a neonate with severe combined immunodeficiency. This case underscores the importance of considering this diagnosis and highlights the use of modern testing modalities to promptly diagnose and treat infections in immunocompromised patients. [ABSTRACT FROM AUTHOR]