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We describe 2 cases of healthcare-associated Legionnaires' disease in patients in France hospitalized 5 months apart in the same room. Whole-genome sequencing analyses showed that clinical isolates from the patients and isolates from the room's toilet clustered together. Toilet contamination by Legionella pneumophila could lead to a risk for exposure through flushing.

The aim of this review was to describe the current knowledge of Legionnaires' disease (LD) illustrated by the epidemiological situation in France in 2013. LD is a severe pneumonia commonly caused by Legionella pneumophila serogroup 1. The diagnosis is usually based on the urinary antigen test. This rapid method reduces the delay between clinical suspicion and initiation of an appropriate treatment. However, the availability of a clinical strain is important to improve knowledge of circulating bacteria, to document case clusters, and to identify the sources of contamination. The source of contamination is unknown in most cases. The main contamination sources generating aerosols are water network systems and cooling towers. Thanks to the strengthening of clinical and environmental monitoring and to several guidelines, no epidemic has been reported in France since 2006. Despite these efforts, the number of LD cases has not decreased in recent years. It is essential that applied research continue to better understand the spatial and temporal dynamics of the disease and its characteristics (impact of environmental factors, sources of exposure, strains, host, etc.). Fundamental knowledge has been greatly improved (pathogenesis, immune mechanisms, etc.). The results of this research should help define new strategies for the diagnosis, prevention, and control to decrease the number of LD cases diagnosed every year., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

The notification rate of Legionnaires' disease (LD) in France was 2.4/100 000 population in 2010, varying across regions with an increasing rate from west to east. Two sources [mandatory notifications (MN) and a survey of hospital laboratories] were used in a capture-recapture study to estimate the number of LD cases and the sensitivity of the MN system at national and regional levels in 2010. The number of missed cases was estimated using Chapman's method. The estimated sensitivity of MN was 88.5% (95% CI 88.0-89.0) and ranged from 70% to 100% by region. The estimated incidence was 2.7/100 000 population. Sensitivity of the MN system improved since the previous capture-recapture estimates (10% in 1995, 33% in 1998). This study confirmed that the observed west-east gradient is not related to regional notification disparities. Ecological studies should be conducted to better understand the observed spatial variations in LD incidence.

Objective: Our objective was to describe the incidence and risk factors of legionellosis associated with tumor necrosis factor (TNF)-α antagonist use., Methods: From February 1, 2004, to January 31, 2007, we prospectively collected all cases of legionellosis among French patients receiving TNF-α antagonists in the Research Axed on Tolerance of Biotherapies (RATIO) national registry. We conducted an incidence study with the French population as a reference and a case-control analysis with four control subjects receiving TNF-α antagonists per case of legionellosis., Results: Twenty-seven cases of legionellosis were reported. The overall annual incidence rate of legionellosis for patients receiving TNF-α antagonists, adjusted for age and sex, was 46.7 (95% CI, 0.0-125.7) per 100,000 patient-years. The overall standardized incidence ratio (SIR) was 13.1 (95% CI, 9.0-19.1; P < .0001) and was higher for patients receiving infliximab (SIR, 15.3 [95% CI, 8.5-27.6; P < .0001]) or adalimumab (SIR, 37.7 [95% CI, 21.9-64.9; P < .0001]) than etanercept (SIR, 3.0 [95% CI, 1.00-9.2; P = .06]). In the case-control analysis, exposure to adalimumab (OR, 8.7 [95% CI, 2.1-35.1]) or infliximab (OR, 9.2 [95% CI, 1.9-45.4]) vs etanercept was an independent risk factor for legionellosis., Conclusions: The incidence rate of legionellosis for patients receiving TNF-α antagonists is high, and the risk is higher for patients receiving anti-TNF-α monoclonal antibodies than soluble TNF-receptor therapy. In case of pneumonia occurring during TNF-α antagonist therapy, specific urine antigen detection should be performed and antibiotic therapy should cover legionellosis., Trial Registry: ClinicalTrials.gov; No.: NCT00224562; URL: www.clinicaltrials.gov.

Endemic strains of Legionella pneumophila sequence type 1 (ST1), in particular the ST1/Paris pulsotype, are dispersed worldwide and represent about 10% of culture-proven clinical cases of Legionnaires' disease in France. The high rate of isolation of this strain from both clinical and environmental samples makes identification of the source of infection difficult during epidemiological investigations. The full-length genome sequence of this strain was recently determined, and it revealed the presence of a CRISPR/cas complex. The aim of this study was to develop and evaluate a spoligotyping tool based on the diversity of this CRISPR locus that would allow the accurate subtyping of the L. pneumophila serogroup 1 ST1/Paris pulsotype. The CRISPR loci of 28 L. pneumophila ST1/Paris pulsotype isolates were sequenced, and 42 different spacers regions were characterized. A membrane-based spoligotyping method was developed and used to determine the subtypes of 406 L. pneumophila isolates, including 233 with the ST1/Paris pulsotype profile that were collected in France from 2000 to 2011. A total of 46 different spoligotypes were detected, and 41 of these were specifically identified in the ST1/Paris pulsotype isolates. In 27 of 33 epidemiological investigations, the environmental source of contamination was confirmed by comparing spoligotypes of clinical isolates with those of environmental isolates. With an index of discrimination of 79.72% (95% confidence interval, 75.82 to 83.63), spoligotyping of the L. pneumophila ST1/Paris pulsotype has the potential to be a useful complementary genotyping tool for discriminating isolates with undistinguishable pulsed-field gel electrophoresis (PFGE) and ST genotypes, which could help to identify environmental sources of infection.

Since 1997, both the prevention of legionellosis and the control of Legionella in water networks and cooling towers have greatly improved in France. The epidemiological surveillance of Legionnaires' disease showed an increase, which was followed by a decrease in the incidence after a maximum was reached in 2005 (incidence rate of 2.5 per 10(5)). A steady decrease in the incidence rate has been observed since 2006, mainly due to the efficacy of control measures both for cooling towers and hospital water networks. In hospitals, a proactive approach was proposed in 1998 and quantitative limit values with systematic survey were put into force in 2002. The percentage of nosocomial cases has decreased dramatically and is now around 6-7% of all cases recorded in France. No nosocomial outbreak has been reported in recent years. However, this is not the case for community cases linked to diverse exposure sources, including cooling towers.

Background: In France, the notification of Legionnaires' disease (LD) has been mandatory since 1987. Following a study showing an important under-reporting of the disease, the surveillance system was strengthened in 1997: the urinary antigen detection test was introduced as a new diagnostic tool and guidelines for prevention and control of the disease were implemented. After these measures, the incidence of LD increased gradually, reaching 2.5 per 100,000 in 2005, and then slightly decreased (2.0 per 100,000 in 2008)., Methods: Data from the mandatory notification system and from the national reference centre for Legionella were analysed. Analysis covered the 1998-2008 period., Results: During the period 1998-2008 a total of 11147 cases of LD were reported in France through the mandatory system. The majority of cases were diagnosed by urinary antigen test. The median age of cases was 61 years, the male to female ratio was 2.9, and the case fatality rate was 13%. Exposure during travel was documented for 17% of cases. A hospital-acquired infection was suspected for 9% of cases, and this percentage decreased from 21% in 1998 to 7% in 2008. Over this period, 14 community outbreaks were identified involving 380 cases, and cooling towers were the most probable source of infection for 13. No outbreak was reported in 2008. Registration at the regional level of all cooling towers became mandatory at the end of 2004, and the 1997 prevention and control guidelines were updated in 2005. In recent years, several regulations have also been implemented in the hospital setting and care homes for the elderly., Conclusion: All these measures have contributed to strengthen the French surveillance system and improve our ability to better prevent, detect, and control LD., (Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

In May 2010, a cluster of three cases of Legionnaires' disease was identified in France. The results of the epidemiological, environmental and microbiological investigations allowed the rapid identification of a public whirlpool spa as the most probable source of contamination and the implementation of appropriate control measures. This investigation has stressed the need for good cooperation between partners and the importance of the molecular analysis of Legionella strains.

Unlabelled: We performed urinary antigen tests for pneumococcus and Legionella for patients with community-acquired pneumonia (CAP), to prescribe a documented antibiotic therapy. We report the efficiency of low-spectrum antibiotic treatment, illustrating the inappropriateness of bacteriological respiratory sampling., Patients and Methods: Patients with CAP were enrolled from three different units; the pneumonia severity index was used to assess the disease. Respiratory samples were also listed. Low-spectrum antibiotic therapy was amoxicillin for pneumococcal infection, and macrolides or non-anti-pneumococcal fluoroquinolone for legionellosis., Results: Six hundred and seventy-five CAP were diagnosed during the study period,, 150 with positive urinary antigen tests (23%), among which 108 pneumococcal infections (73%), 40 legionellosis (26%), and two mixed infections. The pneumonia severity index was 106+/-38. Amoxicillin was prescribed in 108 cases, fluoroquinolone in 24 cases, macrolide in 18 cases. The outcome was favourable for 138 patients (92%). Eighty three respiratory samples allowed identification of a bacterium for 58 patients (39%), among which 24 strains were not in the antibiotic spectrum: Haemophilus influenzae and Pseudmomonas aeruginosa in six cases, Staphylococcus aureus in five cases, Klebsiella pneumoniae in two cases, and another Gram negative bacillus in five cases. These strains were resistant in vitro to the prescribed treatment in 19/24 cases (79%). One out of 12 patients who died had a respiratory sample positive for Enterobacter spp strain resistant to the ongoing antibiotic treatment., Conclusion: The low-spectrum antibiotic therapy based on urinary antigen tests is efficient, and demonstrates respiratory tract colonisation with bacteriological strains usually considered as pathogenic.

To reduce the Legionella-linked risk in the several sites of Sud-Francilien Hospital, following a hospital-acquired legionellosis case, a multidisciplinary working group performed an action plan monitored through Legionella pneumophila counts in hot water supply. From 2003 to the first half year 2009, positive points for Legionella pneumophila in the main sites of the hospital decreased from 85.71 to 28.00%, representing a significant reduction of 67.33%. Similar results were observed for three of the four establishments, whereas the last did not describe a pronounced reduction of Legionella pneumophila counts and showed constantly serogroup 1 strains. During this period, investigations of additional cases of legionellosis demonstrated a nosocomial transmission in one case in this last site. Multidisciplinary mobilization in management of Legionella-linked risk contributed to these results., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Background: In France, Legionnaires disease is mainly caused by Legionella pneumophila. Here, we investigated possible host factors associated with susceptibility to community-acquired Legionnaires disease caused by the endemic Paris and Lorraine strains., Methods: We conducted a double-nested exploratory case-control study with use of data from the French national surveillance network of incident Legionnaires disease cases notified from 1998 through 2007. Patients with community-acquired Legionnaires disease and an L. pneumophila serogroup 1 isolate were eligible. Case patients were patients infected by the Paris or Lorraine strain, and control patients were those infected by sporadic strains. Epidemiological and clinical factors associated with infection with the Paris and Lorraine strains were assessed by calculating adjusted odds ratios (aOR) in multivariate logistic regression models., Results: We studied 1090 patients infected by sporadic strains (n = 920), the Paris strain (n = 80), or the Lorraine strain (n = 90). Infection with the Paris strain was significantly associated with female sex (aOR, 1.98; 95% confidence interval [CI], 1.19-3.28), steroid therapy (aOR, 3.16; 95% CI, 1.76-5.68), and a history of cancer or hematologic malignancies (aOR, 2.08; 95% CI, 1.15-3.76). In addition, the mortality rate was higher among patients infected with the Paris strain than in the control group (38% vs. 25.5%). The Lorraine strain was associated with smoking (aOR, 1.82; 95% CI, 1.14-2.91) and reduced mortality (9.9%). ., Conclusion: Several host characteristics were associated with the risk of infection by endemic strains of L. pneumophila serogroup 1. These findings may help to guide preventive measures. Factors predisposing patients to infection by specific strains need to be explored further.

Legionnaires' disease (LD) is an aetiology of community-acquired bacterial pneumonia in adults, with a high case-fatality ratio (CFR). We conducted a matched case-control study to identify risk factors for sporadic, community-acquired LD. Cases of sporadic, community-acquired and biologically confirmed LD, in metropolitan France from 1 September 2002 to 31 September 2004, were matched with a control subject according to age, sex, underlying illness and location of residence within 5 km. We performed a conditional logistic regression on various host-related factors and exposures. Analysis was done on 546 matched pairs. The CFR was 3.5%. Age ranged from 18-93 years (mean 57 years), with a 3.6 male:female sex ratio. Cases were more likely to have smoked with the documentation of a dose-effect relation, to have travelled with a stay in a hotel (OR 6.1, 95% CI 2.6-14.2), or to have used a wash-hand basin for personal hygiene (OR 3.5, 95% CI 1.6-7.7) than controls. Tobacco and travel have been previously described as risk factors for LD, but this is the first time that such a dose-effect for tobacco has been documented among sporadic cases. These findings will provide helpful knowledge about LD and help practitioners in identifying patients at high risk.

Legionnaire's disease is a recently described infection and surveillance in France was implemented in 1987. In 2005, 1,527 cases were notified corresponding to a population incidence rate of 2.5 per 100,000. The median age of cases was 61 years [5-100] and the male to female sex ratio was 3.0. The case fatality rate was 11%. One or more risk factors were identified for 1,084 (71%) cases. The majority of cases (91%) was diagnosed by urinary antigen detection and a strain was identified in 276 cases (18%). Legionella pneumophila serogroup 1 infection was confirmed in 95% of cases. A specific exposure during the incubation period was reported for 39% of cases. Travel exposure was reported for 17% and hospital exposure for 7%. Multiple clusters and outbreaks were investigated. The largest one reported was identified in the north Lyon with 34 cases. Since 1997 the incidence of LD has steadily increased. This probably suggests a better detection of cases and an improvement in the surveillance system. In recent years, several new measures concerning prevention and control were implemented. However these efforts must continue particularly in the research domain to improve knowledge of the disease, in order to limit its impact on exposed populations.

For several years, over 50% of the cases of travel-associated Legionnaires' disease (TALD) reported to the European Working Group for Legionella Infections (EWGLINET) have been among travellers to France, Italy, and Spain. We describe clusters of TALD cases reported in these countries during a four-year period. We analysed data from EWGLINET and from the individual countries. In all three countries, upon notification of a cluster, local health authorities are alerted by the national collaborator and immediately begin an environmental investigation at the accommodation site, which includes risk assessments and analysis of water samples. From July 1, 2002 to June 30, 2006, 2,101 accommodation sites were associated with TALD cases and reported by EWGLINET to Italian, Spanish and French collaborators. Of these, 252 sites (12%) were associated with clusters: 13.8% (96/697) in Italy, 13.2% (81/615) in Spain and 9.5% (75/789) in France. Overall, 641 cases were reported. Hotels, camping sites and ships and other sites represented respectively 83%, 10% and 7% of the total accommodation sites, with similar proportions in the three countries. In 99% of the sites, samples were collected; 62% of them were found to be positive for Legionella. The findings of this study highlight that disinfection and long-term preventive measures were correctly implemented by the large majority of sites. However, additional efforts must be made to further reduce the percentage of re-offending sites so as to reduce the number of accommodations that are contaminated by Legionella.

Unlabelled: Risk factors for Legionnaires' disease are well known (older age, smoking, or immunosuppression), however, the factors associated with mortality are less documented. A retrospective analysis based on cases notified between 2002 and 2004 was conducted in France to identify these factors., Method: Cases were identified through mandatory notifications sent to the Institut de veille sanitaire, France. Factors associated with mortality were identified using a logistic regression analysis., Results: Three thousand two hundred sixty-seven cases of Legionnaire's disease were notified during the study period and the evolution was documented for 85% of the cases (2.791). Three hundred seventy-seven deaths (13.5%) were notified. 72.5% of the patients were men and the median age was 61. The multivariate analysis applied to patients under 60 years revealed that cancer or hemopathy (OR=6.4 CI95% 3.6-11.2), underlying renal disease (OR=3.2 CI95% 1.0-9.9), or alcohol abuse (OR=2.2 CI95% 1.1-4.4) were associated with mortality. For older patients (>60 years) factors linked to mortality were: cancer/hemopathy (OR=1.8 CI95% 1.2-2.6), underlying renal disease (OR=3 CI95% 1.4-6.4), underlying cardiac disease (OR=2.4 CI95% 1.4-4), alcohol abuse (OR=2.4 CI95% 1.2-5.2), immunosuppression (OR=1.7 CI95% 1.1-2.6), nosocomial acquisition of the disease (OR=2.0 CI95% 1.3-3), or infection acquired in nursing home residents (OR=2.4 IC 95% 1.6-3.6)., Conclusion: These preliminary results further describe Legionnaires' disease and its mortality. However, they should be confirmed by carefully conducted prospective analysis. The description of LD patients at high risk of death will contribute to better prevention measures.

Much data has been gathered by the EWGLINET scheme on the distribution of cases of travel-associated Legionnaires' disease (TALD) by country of infection, but less analysis has been carried out on the distribution of these cases within countries. Travel-associated cases with onset in 2002 linked to France, Italy, Spain and Turkey were mapped. Rates of Legionnaires' disease per 100,000 tourists were calculated for internal and foreign visitors for the regions of each country, and mapped. Rates of 1.5 cases/100,000 and 2 cases/100,000 tourists were classified as 'high' and 'very high' respectively. Cases of TALD were concentrated in certain regions, but when rates were calculated using tourist data, the results were relatively constant throughout each country. Rates were higher among foreign visitors than internal visitors; three of the countries had at least one region with 'high' rates, whilst Turkey additionally had three regions with 'very high' rates.

A community-wide outbreak of legionnaires disease occurred in Pas-de-Calais, France, in November 2003-January 2004. Eighteen (21%) of 86 laboratory-confirmed cases were fatal. A case-control study identified smoking, silicosis, and spending >100 min outdoors daily as risk factors for acquiring the disease. Legionella pneumophila strain Lens was isolated from cooling towers, wastewater, and air samples from plant A. This unique strain matched all 23 clinical isolates, as assessed by pulsed-field gel electrophoresis subtyping. Modeling of atmospheric dispersion of aerosols emitted from plant A cooling towers showed good coverage of the communes where patients lived and showed that the dispersion extended over a distance of at least 6 km from plant A. No other aerosol-producing installation was identified as a plausible source, and no common source of indoor exposure was found. These findings implicate plant A as the most likely outbreak source and suggest that the distance of airborne transmission of L. pneumophila may be greater than previously reported.

Legionella pneumophila is a microorganism present in water and able to develop pneumoniae through inhalation of contaminated aerosols. Legionnaires'disease is rare (1000 cases per year in France) concerning particularly people with risk factors, but potentially with severe prognosis (lethality 15-20%). The diagnosis was recently facilitated by the introduction of urinary antigen test. Hospital is the most frequent place where L. pneumophila were acquired; however the proportion of nosocomial cases is decreasing since 2001. The associated mortality is higher for hospital acquired cases than for community acquired cases. Several official guidelines were written about prevention of legionnaires' disease. Primary prevention is essentially based on control and maintaining of water-distribution system. Secondary prevention should be a prompt response to identification of a case in order to find the source of Legionella and to protect immunocompromised persons.

Patients and Method: To describe epidemiological, clinical, biological, radiological data and therapeutic features of legionnaire's disease during an outbreak occurring in Meurthe-et-Moselle between July-August 2004., Results: 12 cases were recorded including 11 men, 6 smokers, 4 alcoholo-nicotinic, 3 diabetics, 3 with hemopathy, 1 with corticotherapy; in one case no risks factors were found; mean age was 68.5 years [minimum=48; maximum=96]. Nine cases had sudden symptoms. Nine cases had a fever up to 40 degrees C, 9 with dyspnoea, 7 with cough, 7 with a relative bradycardia, 3 with diarrhoea, 3 felt faint, 3 with confusion. Radiology: unilateral unilobe localisation in 10 cases. Biological data: cytolysis in 8 cases, CRP >300 mg/l in 8. The diagnosis confirmed with urinary antigen of Legionella pneumophila serogroup 1 (UrAgLp1) in 12 cases. In 2 cases, UrAgLp1 appeared negative between 3rd and 10th day after the beginning of a treatment although UrAgLp1 was positive before the treatment. In all cases, the first serology realised during first days following occurrence the first symptoms remained negative. Two serology of control in four were positive. One search of L. pneumophila serogroup 1 in sputum was positive in 7. Bitherapy was used in 7 cases with preferential association: fluoroquinolone+rifampicin. Two patients died. Origin of the contamination remains unknown., Conclusion: Culture of Legionella is essential, in epidemic context, to compare clinical and environmental Legionella and to locate the origin of contamination.

Since 1987, in France, Legionella infection is a notifiable disease. Notification should be transmitted by the clinician to the referent public health physician in the Direction départementale des Affaires sanitaires et sociales. Criteria for certain and probable cases have been defined. From this level, nationwide information is centralised in the institut de veille sanitaire. The public health physician is responsible for the inquiry in the health care facility or community setting and for action taking as appropriate. After isolation, Legionella strains are further studied in the Centre national de référence in Lyon. This center is also responsible for typing of environmental strains. In 2002, the incidence of notified legionellosis was 1,7 per 100,000 inhabitants and the mortality rate of 13%. Median age was 61 years and the sex-ratio M/F of 2.9. Only 39 cases were nosocomial. Very few cases have been observed in children, almost all in immunocompromised patients. Legionellosis is of exceptional occurrence in neonates, but the lethality is high. Treatment guidelines have been published in France only for adult patients.

Clusters of travel associated legionnaires' disease warrant urgent attention, and are detected by the French national surveillance system and the European network EWGLINET. Between September 2001 and August 2003, 37 clusters were identified in French tourist accommodation: 27 hotels and 10 campsites. The number of clinical cases per cluster was as follows: 30 clusters of 2 cases (81%), 6 clusters of 3 cases (16%) and one cluster of 4 cases (3%), a total of 82 cases. The local health authorities performed environmental investigations for 36 of the 37 clusters. Among the 36 clusters investigated, water samples were collected for 35. At 16 (46%) sites, Legionella pneumophila was found at a level of more than 103 cfu/litre. In all of the accommodation where risk assessment was found to be inadequate- control measures were implemented immediately. Six hotels were closed immediately following cluster alerts. Comparison of clinical and environmental isolates by pulsed field gel electrophoresis (PFGE) was possible in 3 clusters and identical genomic profiles of the isolates were found in all. During this two year period of surveillance, we found that on many sites there has been a risk of exposure to Legionella. This reinforces the importance of the European surveillance network and the timely notifications of all the cases to EWGLINET.

Pulsed-field gel electrophoresis (PFGE) was used to type Legionella pneumophila isolates collected from the water systems of Besançon University Hospital and other hospitals in Franche-Comté region between January 2001 and December 2002 and compare them with patient isolates to identify hospital-acquired pneumonia. Genomic DNA was digested with SfiI and subjected to PFGE in a clamped, homogeneous electric field apparatus. Two of 11 Legionella infections were hospital-acquired. Both were with the same type, also present in the ward water. An environmental strain isolated from the water system of Vesoul Hospital, exhibited DNA pattern 6, also found in three patients with community-acquired pneumonia, who had never been in Vesoul hospital and lived in different towns located >60 km away. Patient 11, who lived in Besançon, was infected with a DNA pattern 12 strain. This patient had never been to the Besançon swimming pool, from which a similar strain was collected. Subtype matching of patient and environmental isolates should be interpreted with caution, and it is important to combine a molecular typing method with sound epidemiological data to ensure that the most stringent criteria are used to determine whether a hospital-reservoir is responsible for nosocomial pneumonia.

We evaluated improvements made to the mandatory notification surveillance system for Legionnaires' disease in France by estimating its sensitivity in 1995 and 1998 using a repeat capture-recapture method. A case of Legionnaires' disease was defined as a person treated for pneumonia in whom legionella had been detected. Patient details were collected from (1) mandatory notifications; (2) the National Reference Centre for Legionella; (3) a postal survey of all hospital laboratories. The three sources were cross-matched and 715 individual cases were identified. A log-linear model, which included an interaction term between mandatory notifications and both the National Reference Centre and Laboratory sources, provided an estimated total of 1124 cases (95% CI 973-1275) in 1998, a twofold increase compared with 1995. The sensitivity of the surveillance system improved from 10% in 1995 to 33% (95% CI 29-38%) in 1998. Capture-recapture methods are important tools in the evaluation of surveillance systems.

An analysis of 691 French clinical Legionella isolates showed that the endemic L. pneumophila serogroup 1 strain Paris was responsible for 12.2% of all cases of legionellosis and had a specific pulsed-field gel electrophoresis pattern. We also demonstrated the presence of this endemic clone throughout Europe.

Study Objective: To explore the relation between incidence of sporadic and community acquired legionnaires' disease and exposure to potentially contaminated industrial aerosols., Design: Geographical ecological approach using the postcode as the statistical unit. A multivariate Poisson regression model was used to model the relation between exposure to industrial aerosols and legionnaires' disease., Setting: Metropolitan France., Main Results: More than 1000 sources of industrial exposure (aerosol and plume of smoke) were identified in 42 French departments. After adjusting for confounding factors, there was a statistically increased incidence of legionnaires' disease in postcodes with plume of smoke in comparison with postcodes without (RR=1.45, 95% CI=1.12 to 1.87), and in postcodes with more than one aerosol in comparison with postcodes without (RR=1.37, 95% CI=1.04 to 1.79)., Conclusion: These findings highlight that any industrial systems generating water aerosols should be regarded as potential sources of contamination for legionnaires' disease.

The European Surveillance Scheme for Travel Associated Legionnaires' Disease (EWGLINET) was notified of 360 cases in 2000 and 481 cases in 2001, the highest number reported since 1987. This increase reflects enhanced surveillance activities, especially in the Netherlands, France and Italy, mainly through urinary antigen detection test (78% of cases in 2001). The median delay in reporting to the scheme fell to under 30 days, at the cost of some loss of information on the outcomes of illness. In 2000, 28 clusters were detected compared to 72 in 2001, most of this rise resulting from a change in the definition of clusters. In 2000 and 2001, 55 and 140 environmental investigations were reported respectively.

In 2001, 807 cases of Legionnaires' disease were reported to the Institut de veille sanitaire (French national public health centre). The incidence of the disease was 1.35 cases per 100,000 inhabitants, compared to a mean European incidence of 0,6 per 100,000. The median age was 59 years [16-97], the group aged more than 80 being the most affected. The sex ratio M/W was 3.1. The outcome of the disease was known in 69% of all cases, the case fatality ratio rating 19.9%. Among the contributing factors found in 558 cases, 11% had a cancer or blood disease, 12% received an immunosuppressant treatment, 10% were diabetic and 40% were smokers. In 2001, 13% (105/807) cases stayed in a hospital or a clinic during the incubation period, compared to 20% in 2000, and 11% were travel-associated.

Legionelosis is an environment-related disease with particular pulmonary tropism. Reporting is mandatory in France. Legionellosis may result from nosocomial or community-acquired infection. In both cases, humans are contaminated from a humid environmental reservoir that must be identified. Cellular immunity is the main mechanism of defense and transplant recipients, particularly those on an immunosuppressor regimen, are at risk. There is no clinical, biological or radiographic sign specific of nosocomial legionellosis. Culture provides the diagnosis. Treatment is based on prevention and curative antibiotic treatment using compounds with an intracellular activity. Preventive measures have been reinforced by legislation regulating the steps required in case of nosocomial legionellosis.

Two cases of Legionnaire's disease caused by Legionella oakridgensis were diagnosed at the university hospital in Nantes, France. The two patients' isolates were identified by means of phenotyping and genotyping methods. Epidemiological investigations concluded that the first case was hospital acquired while the second case was considered community acquired.

Arbitrarily primed PCR with three primers and pulsed-field gel electrophoresis were used to characterize a set of 75 clinical Legionella pneumophila serogroup 1 isolates, with no apparent epidemiological link, obtained from 24 hospitals in Paris, France, from 1987 to 1997. Unexpectedly, 25 clinical isolates from 15 hospitals had an identical profile (termed type A) by both methods. The same profile was subsequently found in 16 of 64 randomly selected environmental L. pneumophila serogroup 1 isolates from 15 different sites in the Paris area. There was no evidence of geographic clustering or a peak incidence of type A isolation. Type A has not been found in France outside the Paris area, suggesting that a particular type of L. pneumophila serogroup 1 is specifically present in the Paris water distribution network.

The outbreak of pneumonia involving delegates to the 1976 American Legion convention at a Philadelphia hotel was the first example of travel-associated legionnaires' disease. Travel is now well known as a common risk factor for legionnaires' disease. This travel-associated disease is a preoccupation among European countries because of morbidity among citizens of the European Union. The definition of the case of legionellosis is a patient who presents an acute lower respiratory tract infection with focal signs of pneumonia and/or radiological features, and microbiological evidence of Legionella infection. A case is considered to be travel associated if the patient has spent one or more nights away from home during the ten days before becoming ill. An European Surveillance Scheme for Travel-Associated Legionnaires' Disease was established in 1987 to identify clusters and outbreaks of cases of the disease. This group centralizes the case reports of twenty-nine collaborating centres in twenty-five countries. Outbreaks of legionnaires' disease were described in hotels, camps or cruise ships. In 1996, the number of travel-associated cases of legionnaires' disease represented 16% of the total number cases. The increase of the number of reported cases may reflect improved surveillance and increased ascertainment. In Europe in 1996, the diagnosis of legionellosis was confirmed by detection of Legionella pneumophila sero-group 1 antigen in urine (36%), seroconversion (fourfold rise in antibody titre, 33%) and culture of the organism (16%). Fifteen per cent of legionellosis was diagnosed by the identification of a single high antibody titre. In France a coordination between Public Health Institutions (Réseau National de Santé Public and DDASS), clinicians, laboratories and National Reference Center was established to improve prevention and control of legionnaires' disease outbreaks. Legislation obliges to report each case. When more two cases in the same area are notified an epidemiological investigation must be done. The knowing of the source of the contamination and its eradication allows to prevent new cases and outbreaks. Outbreaks of Legionnaires' disease are even now mediatic and this fact leads to maintain attention for the quality of diagnosis and epidemiology investigation due to touristic and economic consequences for the implicated countries.

Legionella disease is among the leading causes of acute pulmonary infections. Nevertheless, the precise frequency remains difficult to assess because of its clinical aspects, the empirical treatment and the diagnostic requirements. According to the existing literature, the frequency of Legionella infections varies from 1 to 15% of documented pulmonary infections. In a survey carried out in 1990 in the Lyon area, the precise incidence of infections due to Legionella in daily medical practice has been estimated according to various types of practice. In general practice, only one case of Legionella infection was proved among 88 pulmonary infections. This weak incidence is also found in hospital practice: 10 cases among 398 hospitalized pulmonary infections in pneumology; none of 158 cases of severe pulmonary infections hospitalized in intensive care units. On the other hand, of 162 cases of hospitalized AIDS patients in a unit specialized in infections, two cases of Legionella infections were diagnosed. In a multidisciplinary 876 bed hospital, 16 cases of pulmonary infections due to Legionella were seen in 1990 by comparison with 32 cases in 1989 (chlorination of water since 1988). The data of Centre national de référence (Fleurette) report figures of 400 cases per year since 1985, without any change from one year to the other. These data are nevertheless underestimated. Global mortality is of 10%. No acquired resistance during the treatment is observed and infections caused by Legionella are consistently sensitive to macrolides, rifampicin and fluoroquinolones.(ABSTRACT TRUNCATED AT 250 WORDS)

The prevalence of antibodies to 13 Legionella antigens was compared in three populations: 583 blood donors, 140 tuberculosis patients and 66 patients with acute non-legionellosis pneumonia. Antibody levels were determined by indirect immunofluorescence (IFA) using formalin-fixed antigens prepared from bacteria developed in embryonated hen yolk sac. The very weak prevalence of anti-L. pneumophila antibodies in a healthy population [almost 0 for serogroups (SG) 2, 3, 4 and 5; 1.5% for SG 6 and a maximum of 2.5% for SG 1 at a titer of 1: 16] confirms the criteria that have been recommended by the Centers for Disease control, USA. For the other legionellae studied, these criteria cannot be applied due to a higher prevalence in healthy populations (14.5% with levels of 1: 16-32 and 1% with levels of 1: 64-128 for L. bozemanii and progressively decreasing by as much as 2% for the other species: L. micdadei, L. longbeachae, L. gormanii, L. dumoffii and L. jordanis), in tuberculosis patients (12.1% with a level at 1: 64-128 for L. bozemanii, and for the same titer, 9.2% for L. gormanii, 5.7% for L. micdadei, 5% for L. longbeachae 2), and also in acute pneumonia (2 to 3.3% with levels of 1: 64-128 for L. longbeachae 1 and 2, L. jordanis, L. dumoffii, L. micdadei and L. bozemanii). Although the significance of these prevalences remains to be discussed, with formalin-fixed antigens, it seems reasonable for these species to assign a threshold of 1: 256 for the presumptive serodiagnosis following seroconversion.

Following the occurrence of five cases of Legionnaires' disease among patients and therapists at a French hot spring spa, a series of cleansing procedures and an epidemiological study were undertaken. During a 3-month period, the spring water was repeatedly sampled. Serum samples were taken from 689 randomly selected patients, 230 therapists, 134 administrative staff and a control group of 904 blood donors. Legionellaceae were present in the spring water at concentrations of 10(3)-10(5) colony forming units/l. Fifteen different species or serogroups were isolated with Legionella pneumophila serogroups 3 and 1 predominating. No clinical cases of Legionnaires disease were observed during the study. However, 11% of the therapists and 5% of the patients either had a high titre of antibody (greater than or equal to 256) to at least one species or serogroup or seroconverted during the study. Mean antibody titres in the three study groups were significantly higher than those in the blood donors against 11 of the 32 legionella antigens tested. Nine of these 11 antigens corresponded to species or serogroups isolated from the spring water. The highest mean antibody titres in all three study groups were against L. pneumophila serogroup 3, the most common legionella in the spring water. These findings have important implications for the maintenance of adequate standards of hygiene, bacteriological sampling and clinical surveillance in this and similar establishments.

To asses the efficacy and the safety of ofloxacin as therapy of pneumonia caused by intracellular pathogens, 35 patients were studied (26 male, 9 female, mean age: 52.5 +/- 16.6 years). Causative pathogens were Chlamydia psittaci (n = 13), Legionella pneumophila (n = 10), Mycoplasma pneumoniae (n = 7) and Coxiella burnetii (n = 5). Ofloxacin was administered orally in 32 cases (200 mg b.i.d. in 80% of cases) and by I.V. route in 3 cases. All patients were cured without any side effects. In conclusion, ofloxacin appears, in our study, as an efficient therapy for these pneumonias. It could be considered as a valuable alternative to other antimicrobial agents with intra-cellular activity.

A new case of fatal systemic legionnaires' disease is reported in an infant. This 8 month-old boy was given a protracted treatment with adrenocorticotropic hormones for infantile spasms. Legionella pneumophila type I was found in tracheal secretions and there was multivisceral involvement at autopsy. The mode of contamination and the severity of the disease are discussed in the light of the immunosuppressive properties of the glucocorticoids administered over a period of 4 weeks.

Several cases of Legionnaires' disease occurred in a French hospital in 1982. Thirteen strains of a legionella-like organism with several unusual characteristics were subsequently isolated from the hospital hot water system. The various features of these strains show that they are identical to the new species 'Legionella anisa' described by the Centers for Disease Control. The possible pathogenicity of these strains to man and their relationship with the recently described Legionella bozemanii serogroup 2 are discussed.