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Infection Oct 2023Switzerland has one of the highest annual Legionnaires' disease (LD) notification rates in Europe (7.8 cases/100,000 population in 2021). The main sources of infection...
Switzerland has one of the highest annual Legionnaires' disease (LD) notification rates in Europe (7.8 cases/100,000 population in 2021). The main sources of infection and the cause for this high rate remain largely unknown. This hampers the implementation of targeted Legionella spp. control efforts. The SwissLEGIO national case-control and molecular source attribution study investigates risk factors and infection sources for community-acquired LD in Switzerland. Over the duration of one year, the study is recruiting 205 newly diagnosed LD patients through a network of 20 university and cantonal hospitals. Healthy controls matched for age, sex, and residence at district level are recruited from the general population. Risk factors for LD are assessed in questionnaire-based interviews. Clinical and environmental Legionella spp. isolates are compared using whole genome sequencing (WGS). Direct comparison of sero- and sequence types (ST), core genome multilocus sequencing types (cgMLST), and single nucleotide polymorphisms (SNPs) between clinical and environmental isolates are used to investigate the infection sources and the prevalence and virulence of different Legionella spp. strains detected across Switzerland. The SwissLEGIO study innovates in combining case-control and molecular typing approaches for source attribution on a national level outside an outbreak setting. The study provides a unique platform for national Legionellosis and Legionella research and is conducted in an inter- and transdisciplinary, co-production approach involving various national governmental and national research stakeholders.
Topics: Humans; Legionnaires' Disease; Legionella pneumophila; Switzerland; Prospective Studies; Disease Outbreaks; Case-Control Studies
PubMed: 36905400
DOI: 10.1007/s15010-023-02014-x -
Tropical Medicine and Infectious Disease Jul 2023In Italy, Legionnaires' Disease (LD) causes >1000 hospital admissions per year, with a lethality rate of 5 to 10%. Occupational exposures could reasonably explain a...
In Italy, Legionnaires' Disease (LD) causes >1000 hospital admissions per year, with a lethality rate of 5 to 10%. Occupational exposures could reasonably explain a substantial share of total cases, but the role of Occupational Physicians (OPs) in management and prevention of LD has been scarcely investigated. The present survey therefore evaluates the knowledge, attitudes and practices (KAP) regarding LD from a convenience sample of Italian OPs, focusing on their participation in preventive interventions. A total of 165 OPs were recruited through a training event (Parma, Northeastern Italy, 2019), and completed a specifically designed structured questionnaire. The association between reported participation in preventive interventions and individual factors was analyzed using a binary logistic regression model, calculating corresponding multivariable Odds Ratio (aOR). Overall, participants exhibited satisfactory knowledge of the clinical and diagnostic aspects of LD, while substantial uncertainties were associated epidemiological factors (i.e., notification rate and lethality). Although the majority of participating OPs reportedly assisted at least one hospital (26.7%) and/or a nursing home (42.4%) and/or a wastewater treatment plant, only 41.8% reportedly contributed to the risk assessment for LD and 18.8% promoted specifically designed preventive measures. Working as OPs in nursing homes (aOR 8.732; 95% Confidence Intervals [95%CI] 2.991 to 25.487) and wastewater treatment plants (aOR 8.710; 95%CI 2.844 to 26.668) was associated with participation in the risk assessment for LD, while the promotion of preventive practice was associated with working as an OP in hospitals (aOR 6.792; 95%CI 2.026 to 22.764) and wastewater treatment plants (aOR 4.464, 95%CI 1.363 to 14.619). In other words, the effective participation of the OP in the implementation of preventive measures appears uncommon and is limited to certain occupational settings. Collectively, these results highlight the importance of tailoring specifically designed information campaigns aimed to raise the involvement of OPs in the prevention of LD in occupational settings other than healthcare.
PubMed: 37505660
DOI: 10.3390/tropicalmed8070364 -
Emerging Infectious Diseases Aug 2023In the United States, tropical cyclones cause destructive flooding that can lead to adverse health outcomes. Storm-driven flooding contaminates environmental,...
In the United States, tropical cyclones cause destructive flooding that can lead to adverse health outcomes. Storm-driven flooding contaminates environmental, recreational, and drinking water sources, but few studies have examined effects on specific infections over time. We used 23 years of exposure and case data to assess the effects of tropical cyclones on 6 waterborne diseases in a conditional quasi-Poisson model. We separately defined storm exposure for windspeed, rainfall, and proximity to the storm track. Exposure to storm-related rainfall was associated with a 48% (95% CI 27%-69%) increase in Shiga toxin-producing Escherichia coli infections 1 week after storms and a 42% (95% CI 22%-62%) in increase Legionnaires' disease 2 weeks after storms. Cryptosporidiosis cases increased 52% (95% CI 42%-62%) during storm weeks but declined over ensuing weeks. Cyclones are a risk to public health that will likely become more serious with climate change and aging water infrastructure systems.
Topics: Humans; United States; Cyclonic Storms; Waterborne Diseases; Cryptosporidiosis; Legionnaires' Disease; Communicable Diseases
PubMed: 37486189
DOI: 10.3201/eid2908.221906 -
Cureus Jul 2023Legionellosis among welders and other metalworkers is a rare but potentially underappreciated occupational hazard. The same mechanisms that predispose welders to severe...
Legionellosis among welders and other metalworkers is a rare but potentially underappreciated occupational hazard. The same mechanisms that predispose welders to severe pneumonia from and may similarly predispose them to infection. We present a case of a previously healthy, immunocompetent 31-year-old male welder presenting with three days of shortness of breath, hypoxia, high-grade fever, and blood-tinged sputum. Chest computed tomography (CT) revealed a lobar consolidation of the right middle and lower lobes. Laboratory evaluation showed borderline hyponatremia, hypophosphatemia, and elevated liver enzymes. The patient was ultimately intubated and started on broad-spectrum antibiotics. Multiple respiratory cultures were negative and urine antigen testing was also negative. Eventually, bronchial culture was positive for and a blood next-generation sequencing test also confirmed the diagnosis. He was extubated six days following admission and subsequently discharged.
PubMed: 37605706
DOI: 10.7759/cureus.42250 -
Environmental Research Sep 2023The number of reported cases of Legionnaires' disease (LD) has risen markedly in Switzerland (6.5/100,000 inhabitants in 2021) and abroad over the last decade....
BACKGROUND
The number of reported cases of Legionnaires' disease (LD) has risen markedly in Switzerland (6.5/100,000 inhabitants in 2021) and abroad over the last decade. Legionella, the causative agent of LD, are ubiquitous in the environment. Therefore, environmental changes can affect the incidence of LD, for example by increasing bacterial concentrations in the environment or by facilitating transmission.
OBJECTIVES
The aim of this study is to understand the environmental determinants, in particular weather conditions, for the regional and seasonal distribution of LD in Switzerland.
METHODS
We conducted a series of analyses based on the Swiss LD notification data from 2017 to 2021. First, we used a descriptive and hotspot analysis to map LD cases and identify regional clusters. Second, we applied an ecological model to identify environmental determinants on case frequency at the district level. Third, we applied a case-crossover design using distributed lag non-linear models to identify short-term associations between seven weather variables and LD occurrence. Lastly, we performed a sensitivity analysis for the case-crossover design including NO levels available for the year 2019.
RESULTS
Canton Ticino in southern Switzerland was identified as a hotspot in the cluster analysis, with a standardised notification rate of 14.3 cases/100,000 inhabitants (CI: 12.6, 16.0). The strongest association with LD frequency in the ecological model was found for large-scale factors such as weather and air pollution. The case-crossover study confirmed the strong association of elevated daily mean temperature (OR 2.83; CI: 1.70, 4.70) and mean daily vapour pressure (OR: 1.52, CI: 1.15, 2.01) 6-14 days before LD occurrence.
DISCUSSION
Our analyses showed an influence of weather with a specific temporal pattern before the onset of LD, which may provide insights into the effect mechanism. The relationship between air pollution and LD and the interplay with weather should be further investigated.
Topics: Humans; Legionnaires' Disease; Cross-Over Studies; Switzerland; Weather; Air Pollution
PubMed: 37354934
DOI: 10.1016/j.envres.2023.116327 -
BMJ (Clinical Research Ed.) Aug 2023
Topics: Humans; Refugees; Legionnaires' Disease; Ships; Stress Disorders, Post-Traumatic
PubMed: 37580068
DOI: 10.1136/bmj.p1876 -
BioRxiv : the Preprint Server For... Nov 2023is an accidental human bacterial pathogen that infects and replicates within alveolar macrophages causing a severe atypical pneumonia known as Legionnaires' disease. As...
is an accidental human bacterial pathogen that infects and replicates within alveolar macrophages causing a severe atypical pneumonia known as Legionnaires' disease. As a prototypical vacuolar pathogen establishes a unique endoplasmic reticulum (ER)-derived organelle within which bacterial replication takes place. Bacteria-derived proteins are deposited in the host cytosol and in the lumen of the pathogen-occupied vacuole via a type IVb (T4bSS) and a type II (T2SS) secretion system respectively. These secretion system effector proteins manipulate multiple host functions to facilitate intracellular survival of the bacteria. Subversion of host membrane glycerophospholipids (GPLs) by the internalized bacteria via distinct mechanisms feature prominently in trafficking and biogenesis of the -containing vacuole (LCV). Conventional GPLs composed of a glycerol backbone linked to a polar headgroup and esterified with two fatty acids constitute the bulk of membrane lipids in eukaryotic cells. The acyl chain composition of GPLs dictates phase separation of the lipid bilayer and therefore determines the physiochemical properties of biological membranes - such as membrane disorder, fluidity and permeability. In mammalian cells, fatty acids esterified in membrane GPLs are sourced endogenously from synthesis or via internalization from the exogenous pool of lipids present in serum and other interstitial fluids. Here, we exploited the preferential utilization of exogenous fatty acids for GPL synthesis by macrophages to reprogram the acyl chain composition of host membranes and investigated its impact on LCV homeostasis and intracellular replication. Using saturated fatty acids as well as - and - isomers of monounsaturated fatty acids we discovered that under conditions promoting lipid packing and membrane rigidification intracellular replication was significantly reduced. Palmitoleic acid - a C16:1 monounsaturated fatty acid - that promotes membrane disorder when enriched in GPLs significantly increased bacterial replication within human and murine macrophages but not in axenic growth assays. Lipidome analysis of infected macrophages showed that treatment with exogenous palmitoleic acid resulted in membrane acyl chain reprogramming in a manner that promotes membrane disorder and live-cell imaging revealed that the consequences of increasing membrane disorder impinge on several LCV homeostasis parameters. Collectively, we provide experimental evidence that replication within its intracellular niche is a function of the lipid bilayer disorder and hydrophobic thickness.
PubMed: 38045297
DOI: 10.1101/2023.11.19.567753 -
Virulence Dec 2024() is a prevalent pathogenic bacterium responsible for significant global health concerns. Nonetheless, the precise pathogenic mechanisms of have still remained...
() is a prevalent pathogenic bacterium responsible for significant global health concerns. Nonetheless, the precise pathogenic mechanisms of have still remained elusive. Autophagy, a direct cellular response to infection and other pathogens, involves the recognition and degradation of these invaders in lysosomes. Histone deacetylase 6 (HDAC6), a distinctive member of the histone deacetylase family, plays a multifaceted role in autophagy regulation. This study aimed to investigate the role of HDAC6 in macrophage autophagy via the autophagolysosomal pathway, leading to alleviate -induced pneumonia. The results revealed a substantial upregulation of HDAC6 expression level in murine lung tissues infected by . Notably, mice lacking HDAC6 exhibited a protective response against -induced pulmonary tissue inflammation, which was characterized by the reduced bacterial load and diminished release of pro-inflammatory cytokines. Transcriptomic analysis has shed light on the regulatory role of HDAC6 in infection in mice, particularly through the autophagy pathway of macrophages. Validation using -induced macrophages from mice with HDAC6 gene knockout demonstrated a decrease in cellular bacterial load, activation of the autophagolysosomal pathway, and enhancement of cellular autophagic flux. In summary, the findings indicated that HDAC6 knockout could lead to the upregulation of p-ULK1 expression level, promoting the autophagy-lysosomal pathway, increasing autophagic flux, and ultimately strengthening the bactericidal capacity of macrophages. This contributes to the alleviation of -induced pneumonia.
Topics: Animals; Mice; Autophagy; Histone Deacetylase 6; Legionella; Legionella pneumophila; Legionnaires' Disease; Macrophages; Pneumonia
PubMed: 38466143
DOI: 10.1080/21505594.2024.2327096 -
Tropical Medicine and Infectious Disease Oct 2023A bacterium is ubiquitous in water distribution systems, including dental unit waterlines (DUWLs). Legionellosis is atypical pneumonia, including Legionnaires' disease...
A bacterium is ubiquitous in water distribution systems, including dental unit waterlines (DUWLs). Legionellosis is atypical pneumonia, including Legionnaires' disease (LD) and the less acute form of Pontiac fever. Legionellosis occurs as a result of inhalation/aspiration of aerosolized -contaminated water by susceptible patients, health workers, and dentists. In this study, we undertook to determine the prevalence of in water and biofilm samples from Tap and DUWLs collected from five sites of dental clinics and faculties across the West Bank. Water samples were tested for physical and chemical parameters. The study samples included 185 samples, 89 (48%) water samples, and 96 (52%) biofilm swabs, which were analyzed by cultivation-dependent analysis (CDA) and by the cultivation-independent technique (CIA). Also, partial sequencing of the 16S rRNA gene for fifteen isolates was performed for quality assurance and identification. was isolated from 28 (15%) of 185 samples using CDA and was detected in 142 (77%) of 185 samples using CIA. The abundance of culturable was low in DUWL of the sampling sites (range: 27-115 CFU/Liter). PCR was 5× more sensitive than the culture technique. Sg 1 was detected in (75%) of the isolates, while (25%) isolates were Sg 2-14. All fifteen sequenced isolates were identified as ≥ 94.5%. The analysis of phylogenetic tree showed that branch clearly identified and distinguished from other branches. These results show that DUWLs of the examined dental clinics and faculties are contaminated with . This finding reveals a serious potential health risk for infection of immunocompromised patients and dentists' post-exposure.
PubMed: 37999609
DOI: 10.3390/tropicalmed8110490 -
Annals of Clinical Microbiology and... Nov 2023Legionnaires' Disease (LD) rarely evolves into pulmonary abscesses. The current systematic review has been designed to explore therapeutical strategies in pulmonary... (Review)
Review
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.
RESULT OF SYNTHESIS (CASE REPORTS)
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.
RESULT OF SYNTHESIS (GUIDELINES)
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.
CONCLUSION
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.
Topics: Humans; Male; Middle Aged; Female; Legionnaires' Disease; Pneumonia; Anti-Bacterial Agents; Fluoroquinolones; Macrolides
PubMed: 38031167
DOI: 10.1186/s12941-023-00652-5