CIRCULAR DGS No. 97/311 of April 24, 1997

GUIDE INVESTIGATION OF ONE OR MORE CASE OF LEGIONELLOSIS

Authors

Recall on the disease

Infectious agent
Diagnosis
Epidemiology

Monitoring of the Legionellosis in France

Obligatory declaration (DO)
National Center of Reference (CNR)
Committees of Fight against the Infections Nosocomiales (CLIN)
European Network of monitoring of the Legionellosis acquired at the time of voyages

Definitions of case

Case of Legionellosis
Cases grouped of Legionellosis
Legionellosis nosocomiale

Investigation of a case isolated from Legionellosis

Confirmation Identification of the exposures at the risk Legionellosis nosocomiale " Community " Legionellosis particular Case of the Legionellosis acquired at the time of the voyages

Epidemiologic investigation of group cases

Descriptive study
analytical Study

Environmental investigation

Appraise potential sources of contamination
Recherche of Legionella in environment
Conclusions

Comparisons of the clinical and environmental stocks

Measurements of fight and prevention

Medical networks hot water supply
systems of air-conditioning and aero-cooling towers
Baths with movement, basins with jets medical
Devices of respiratory treatment

Epidemiologic and environmental monitoring

Epidemiologic monitoring
Environmental Monitoring

Useful addresses

References

Appendix

GUIDE INVESTIGATION OF ONE OR MORE CASE OF LEGIONELLOSIS

Rapporteurs: B Hubert, A. Infuso, Mr. Ledrans (National Network of Public health)
Working group: General direction of Health: I Capek, J Carm2es, C Gobet
Laboratory of Hygiene of the Town of Paris: S. Dubrou
National Network of Public health: J.C. Desenclos
CNR of Legionella: J Etienne the Higher Council of Public health of France: E Grooving plane, J Lesne
Document approved by the Section of Water and the Section Disease prevention of the Transmissible Diseases of the Higher Council of Public health of France.

This practical guide has as an aim to give a progress report on current knowledge (in 1996) on the Legionellosis and to specify the action to be taken around each case of Legionellosis to improve the prevention of this disease. It is intended to the doctors inspectors of public health, to the engineers of the medical genious and for the committees of fight against the infections nosocomiales (CLIN).

Infectious agent

The Legionellosis are infections caused by bacteria of the Legionella kind (including/understanding 39 species and more than 50 serogroupes). Legionella is a Gram bacillus negative, cultivable on specific medium BYEa. Legionella pneumophila serogroupe 1 (Lp1) most frequently is found in human pathology (more than 80%), followed serogroupe 6. Other species (L. micdadei, L bozemanii, L longbeachae, etc.) were insulated, mainly at immunodeprimees people.

Diagnosis

Clinical diagnosis One distinguishes two distinct clinical pictures: the disease of the Legionnaries and the fever of Pontiac. These two affections are initially characterized by an asthenia, a high fever (40°C), myalgias and cephalgias. Disease of the Legionnaries: one observes usually a nonproductive initial cough, then bringing back a expectoration mucoide, sometimes hemoptoic. The clinical examination, poor, contrast with the pulmonary radiography which shows badly limited infiltrates, heterogeneous, extending gradually in the two pulmonary fields. This clinical picture is not observed in a systematic way. The infection can involve a respiratory insufficiency. Lethality can reach 40% among in-patients, and more at immunodeprimes. Fever of Pontiac: it has a pace of syndrome grippal, is not accompanied by pneumonia and does not put the vital forecast concerned. The cure is usually spontaneous into 2 to 5 days. Because of the benign character of the fever of Pontiac and the scarcity of its diagnosis, in the continuation of this document, the term " Legionellosis " will correspond to the disease of the Legionnaries.

Biological diagnosis

Insofar as the results of the diagnoses of laboratory are an essential element of the definition of a case of Legionellosis for the monitoring, it is important to know the various methods and their value diagnoses (tabl. 1): - search for Legionella by culture of bronchial secretions on specific medium BYEa. It is the examination of reference which should be carried out in a systematic way. The result is available in 3 days. The hemoculture, Si it sub-is cultivated on medium BCYE, can identify of Legionella in 10 to 30% of the cases. - direct immunofluorescence (specific of L pneumophila 1) in bronchial secretions (bronchoalveolar washing, brushing) or on pulmonary parenchyma after biopsy. - soluble antigen detection of L pneumophila in the urines (by a method RIA or currently specific EIA for the s3erogroupe 1). This fast method (realization in less than 24 hours) allows a diagnosis early from the very start of the signs and late (up to 2 months) even after an adapted antibiotic treatment. It has a better sensitivity than the IFD and serology and especially a good specificity. It should not replace the culture but represents a good alternative to serology by improving the predictive values of the results and by reducing the times of confirmation. - serology: significant increase (x4) in the titles of antibodies measured by indirect immunofluorescence in two serums (2 to 5 ml on dry tube) taken, the first as of the first days of the disease, the second after 3 to 6 weeks of evolution. Only the serology of Lp1 is recognized at the international level. The specificity of an insulated high title is poor, involving in practice current a very bad positive predictive value which improves only when the incidence increases (epidemic situations). - detection by genomic amplification (PCR): this method of fast detection is still at the stage of development and is not currently used in routine.

Table 1: Sensitivity and specificity of the diagnostic methods of the Legionellosis (according to Edelstein 1993)

Epidemiology

Frequency - the proportion of the Legionellosis among Community pneumopathies varies from 0,5 to 5%. - the prevalence of the antibodies against L pneumophila serogroupe 1 (title > 256) varies from 1 to 16% in the adult population in good health, according to estimates' carried out.

- the number of cases diagnosed in France in 1995 was evaluated with 530 cases, that is to say an incidence of 0,9/100 000. The real number of cases of Legionellosis is estimated at 2 000 to 3 000 annual cases. - the rate of attack (a number of patients / a number of exposed people) is weaker in the epidemics of disease of the Legionaries (0,1 to 5%) that of fever of Pontiac (95%).

Tank the tank is mainly hydrous (bacterium found in a natural state in the lakes, rivers...). Legionella can have an intracellular development in the protozoa, and can be conveyed by free cysts of amoebas. The sources of contamination accused in the epidemics are generally installations causing a multiplication of Legionella in water (optimal temperature: 37°C) and a aerosolisation: - systems distribution of domestic hot water feeding from the showers. - systems of air-conditioning and aero-cooling towers. - basins used for the relaxation, the balneotherapy or the hydrotherapy in which water is hot (> 30°) and agitated (baths with movement, baths with jet... - medical equipment for respiratory treatments by aerosols. - thermal springs. - decorative fountains. Among all these sources, the domestic hot water circuits represent the most frequent cause of infection.

Transmission
- air Transmission by inhalation of contaminated water diffused in aerosol (showers, vapor... - No transmission interhumaine brought back. - other modes of transmission are possible (ingestion) but were not proven.

Incubation the duration of incubation varies according to the clinical form of the disease:
- disease of the Legionnaries: 2 to 10 days (usually 5 to 6 days). - fever of Pontiac: 5 hours at 3 days (usually 24 to 48 hours).

Individual factors of risk the factors of risk to develop a Legionellosis are the following: - increasing Age. - male Sex (sex-ratio M/F = 2,5). - Nicotinism, alcoholism. - Immuno-depression, cancer, diabetes, corticotherapie. - chronic respiratory Affections.

The monitoring of the Legionellosis in France rests on several complementary systems represented on the following diagram:

Obligatory declaration (C)
the obligatory declaration, instituted in 1987, aims to follow the evolution of the incidence, to detect the grouped cases and to direct measurements of prevention. The declaration is made to the doctors inspectors Public health of the DDASS. Since the beginning of the year 1996, this system is coordinated at the national level by the National Network of Public health. The performance of this system is very poor, so much on the level of the rate of declaration (estimated at 10% in 1995) that quality of information collected. Measures of improvement of this system were taken in 1997 (new definition of case, news card-indexes declaration, improvement of the description of the cases, diversification of the sources of information).

Center National Reference (CNR)

The CNR of Legionella named by the minister in charge of Health, has missions of biological expertise, maintenance of a bacterial collection and a serotheque, of antigen supply of reference and contribution to the epidemiologic monitoring. For this reason, it receives stocks and serums accompanied by information on the cases having had a diagnosis of laboratory. CNR also ensures an expertise for the stocks insulated in the environment. Thus, within the framework of investigation of grouped cases, CNR can compare, by methods of molecular typing, the stocks insulated among patients and in the environment.

Committees of Fight against the Infections Nosocomiales (CLIN)

These committees are in charge in each hospital of the monitoring and the prevention with the infections nosocomiales. During the investigation of epidemic phenomena, the CLIN can require the methodological assistance of the interregional centers of coordination (CCLIN).

European network of monitoring of the Legionellosis acquired at the time of the voyages

With these systems, a European network of monitoring of the Legionellosis acquired at the time of the voyages is added (European Working Group for Legionella Infections, EWGLI). France takes part in this network and, for this reason, provides and receives information on the cases of Legionellosis acquired at the time of voyages in France or abroad.

Case of Legionellosis

Clinical and/or radiological signs of pneumopathy accompanied by the one of the following biological signs:

Confirmed case - identification of Legionella by culture or direct immunofluorescence in a clinical taking away; - presence of soluble antigens of Legionella in the urines; - increase in the titles of antibody of 4 times (that is to say 2 dilutions) with a second minimum title of 128. Possible case Titrates single high > 256, whatever the species.

Grouped cases of Legionellosis

Grouped cases: at least 2 cases, which have occurred in an interval of time lower than 6 months, at people having attended the same place. At least one of these cases must be confirmed. If the interval of time between the cases is higher than 6 months, one will speak about dependent cases which have an epidemiologic importance less than the grouped cases.

Legionellosis nosocomiale

- the origin nosocomiale can be regarded as certain if the patient remained in an establishment during the 10 days preceding the beginning by the clinical signs.
- the origin nosocomiale can be regarded as probable if the patient remained in an establishment during at least 1 day in the 10 days preceding the beginning by the clinical signs.

The objectives of this investigation are to confirm the diagnosis, to identify the places attended by the patient which constitute a potential source of infection (places " at the risk "), to seek other cases in the entourage and to take systematic measures of prevention (figure 1). Apart from the particular case of the Legionellosis of origin nosocomiale or occurred at the time of a cure at a watering-place, the investigation around an isolated case should not give place to systematic environmental taking away, because of the poor cost-effectiveness ratio of this step.

Figure 1: Step of investigation of a case isolated from Legionellosis

Confirmation of the diagnosis

The first stage must check the confirmation of the diagnosis of Legionellosis (cf. §"cas definition of Legionellosis "). For the cases considered as possible (c.a.d. not having a significant increase in the antibodies), it is necessary to make sure that the interval between the two blood taking away is at least equal to 3 weeks (optimum: 6 weeks). If this interval is shorter, it is desirable to obtain a new serology to increase the chances to highlight a seroconversion. For recent cases, a fast confirmation can be obtained by the urinary search for antigen.

Identification of the exposures at the risk

It is necessary to obtain a precise description of the places and dates of stay of the patient during the 10 days preceding the beginning by the clinical signs. This stage must make it possible to determine if the Legionellosis is of origin nosocomiale or Community (cf definitions of case § " Legionellosisnosocomiale " higher). In this last case, it is important to seek the frequentation of places " at the risk " (another establishment of care, thermal spa, hotel, swimming pool, baths with movement... and the concept of a recent voyage in France or abroad.

Legionellosis nosocomiale

The Legionellosis of origin nosocomiale must be the subject of an investigation by the Committee of Fight against the Infections Nosocomiales (CLIN), if need be in connection with the center regional coordinator (CCLIN). As previously, one will seek other confirmed or possible cases of Legionellosis. Even if the case is isolated, an environmental study is essential:
- To seek an exposure to care " at the risk " (humidifiers of oxygen treatment, aerosols...
- To check the maintenance of the medical networks water supply hot and possible a3ero-cooling towers with the hospital engineer.
- To supervise the microbiological contamination of the circuit of domestic hot water serving the service concerned.
- To compare the stocks insulated at the patient and in the environment (with techniques of typing available to CNR).

A report/ratio of the investigation will have to be addressed to the DDASS to supplement the data of obligatory declaration.

" Community " Legionellosis

Seeks other cases of Legionellosis confirmed or possible among the people having attended the same place within the communities identified higher. According to the exposure " at the risk ", and thus of the community concerned, this research will be more or less easy. The identification of other cases involves a thorough investigation (cf § " epidemiologic Investigation of grouped cases "). Occurred of a case isolated from Legionellosis, even if it cannot be allotted with precision to a source of contamination, should be the subject of systematic recommendations of prevention. It is thus necessary for each case to count the potential exposures. According to the context, the answer will be adapted: - cure at a watering-place: the environmental investigation must be systematic with a reinforcement of the analytical control of thermal springs of the attended station. It is also necessary to make sure that the source of infection is not external with the establishment (hotel for example). - work environment: checking of the maintenance of the possible aero-cooling towers and the systems of air-conditioning. Inquire into the use of the medical hot water supply network (showers) and checking of the maintenance of the installations. - hotels, camp-sites: cf § (" particular case of the Legionellosis acquired at the time of the voyages ")

Particular Case of the Legionellosis acquired at the time of the voyages

The cases which have occurred following voyage accounted for approximately 10% of the French cases declared between 1987 and 1995. The description by EWGLI of the cases which have occurred among foreigners following a stay in France increases the frequency of this situation.
L is frequent to note that the cases attended several hotels during their voyage, which multiplies the potential sources of infection; it is thus important to be limited to the establishments attended in the 2 to 10 days preceding the beginning by the clinical signs. In these establishments, one will take care of the application of the " good practices of maintenance of a medical hot water supply network " (appendix III) and of the checking of the maintenance of possible the a3ero-cooling towers, baths with movement, decorative fountains. It is not desirable to seek of Legionella in the environment.

This investigation is the logical continuation of the preceding stage when two or several cases were identified. Its objective is to identify a common source of infection to adapt measurements of prevention. The epidemiologic study of the grouped cases of Legionellosis is usually enough complex for several reasons: cases relatively very few and frequently spaced in time, often incomplete confirmation of the diagnosis, multiplicity of the exposures, difficulties of measuring the intensity and the duration of these exposures.

Descriptive study

• to define and identify the cases:
it is preferable to be limited to the confirmed or possible cases. When the epidemic is recent, the possible cases (c.a.d. having only one insulated high title) should be the subject of a urinary search for antigen. • In certain circumstances, the identification of case of Legionellosis can be associated with an increase in case of pneumopathy. In Community medium, a significant increase can be defined by an incidence higher than 2/1000 people over one 6 months period; in hospital medium, by a proportion of pneumopathies nosocomiales higher than 1% of the admissions. In this case, it is necessary of: - To eliminate another etiology (influenza for example). - To carry out a search for soluble antigen urinary at the recent cases (less than 2 months) - To identify the people having had a taking away of serum (whatever is the reason) to the acute phase of the disease.

To obtain the serum corresponding (preserved normally during a year by the laboratories). To obtain a new blood taking away at the time of the investigation (more than 3 weeks after the first taking away). To analyze the two serums in the same laboratory.

• to seek denominators of population in the community in order to be able to calculate incidence rates, in particular by age and sex.
• to graphically represent the distributions of the cases in time and space (cf figures)

• to formulate assumptions: in order to examine what the patients can have in common, all their activities during the 10 days preceding their disease must meticuleusement be raised (standard of care if cure at a watering-place, no. of room in the hotels... These assumptions on the sources of infection can be very difficult to formulate, in particular at the time of contamination in the open air by aero-cooling towers.

Analytical study

It is not enough to frequently observe a factor of exposure among patients, still is necessary it that it is less frequently observed at the people not infected to be able to blame this factor. One is thus brought to compare the cases to witnesses. This stage can require a methodological help available, according to the context, in the following structures: CCLIN, interregional Cells of epidemiology (WAX), RNSP. • selection of witnesses: the witnesses must have had the possibility of being exposed to the source of contamination and must not have had clinical signs of pneumopathy. • assumptions tested - questionnaire: the questionnaire is identical for the patients and the witnesses; it must detail all the assumptions formulated and to be sufficiently precise over the dates and exposure times. • the comparison of the exposures between the cases and the witnesses calls upon the calculation of odds ratios and statistical tests. The power of these tests is likely to be very limited when the number of cases is weak.

It must include/understand a thorough visit of the establishment during which research of Legionella can be carried out. A complete groundwork for the realization of such an investigation is presented in appendix I and can be adapted according to the size of the establishment.

Appraise potential sources of contamination

The elements minimum to collect to carry out a diagnosis of the environmental context are the following:
• Description of the establishment and its vicinity
• Description of the medical hot water supply network
- plan of the networks
- type of production: instantaneous or with accumulation
- associated treatment: softening, filtration, film forming.
- distribution system: looping...
- quality of materials
- statement of the temperature of water in the balloons and at the points of water supply use
• cold Network: to check that water is not heated at the time of the passage of the drains in the overheated buildings
• Description of the installations of air conditioning
- Site of the new air intakes (to seek the proximity of source of contamination)
- Central of treatment of air Systemes of humidification: with water streaming, pulverization by ultrasounds, vapor cold Batteries:
-to check the absence of stagnant water and the correct operation of the siphons
- Air-flues: to locate the risks of condensation
• Turns aeror Refrigerantes of the building and the vicinity Device by evaporation with open circuit: establishment
• Various - Baths movement
- cooling Fountains and machines with ice
- medical Equipment: to note the origin of the supply water
- Device of humidification
- decorative Fountain

This makes it possible to carry out a diagnosis environmental context and an analysis of the critical points (significant points being able to constitute a risk of multiplication or diffusion of Legionella). In the particular case of hydrotherapy, the recommendations good medical practices in the hydropathic establishments can be used as reference.

Search for Legionella in the environment

Places of taking away: Legionella are very frequently insulated in the artificial hydrous environment; moreover, the analyses of samples in the environment are expensive. It is thus important to direct these taking away according to the epidemiologic arguments, of the structure of the water supply networks and the identification of the critical points.

The places of taking away to privilege are the following:
- medical hot water supply Network
-points of domestic hot water drawing up left low the balloons of storage
- cold water supply Network: if the temperature is abnormally high > 25°C
- Installations of air conditioning
-condensates of cold batteries
-fluid of humidification
-water of the siphons
- aero-cooling Towers:
-surface water

Various: any site likely to contain heated water or wet deposits.

Methods of taking away:
A taking away consists in collecting one liter of water in a sterile bottle. When taken water is treated by a biocide oxidizing, the bottles must contain sodium thiosulfate with 0,50% in order to block the germ-destroying action in the bottle. The conditions of taking away in terms of localization, on buckling of the peripheral elements, enrichment by stagnation or cleaning depend on the finality of the search and the enumeration for Legionella. Several techniques of taking away can be carried out at the points of use:
* if the contamination at the point of use under standard conditions of use is sought, the taking away will be made without buckling and by taking the first jet of water at temperature of use. If the most unfavourable situation in term of contamination is sought, a taking away can be made after one night stagnation.
* if the contamination of the network to the upstream of the point of use is sought, the intake points must be flamed and the taking away carried out after prolonged flow.
* incorporation with the taking away of the products of cleaning can be interesting to study the ecology of the intake point and is to be recommended in the framework of the monitoring of the installation and the evaluation of measurements of fight and prevention. The flue brush must be introduced most deeply possible inside the tap or of the pommel of the shower and the taking away must be carried out by a circular epic repeated (approximately 4 times). The flue brush is then broken in the corresponding taking away of water.
- Whatever the adopted technique, it is important to seek of it reproducibility for the taking away intended to compare contaminations in space or time. This is why it is important to draw up protocols detailed for the people in charge of the taking away and to very carefully fill the card with taking away for each sample. On the cards of taking away must be indicated: the nature of analyzed water (domestic hot water, condensates..) and operations undergone (treatments, mixture..); identification of the intake point; the date and the hour and conditions of the taking away.

Methods of transport:

the taken samples must be transported out of refrigerator. The taking away are conveyed at the laboratory in less than 48 hours, with a packing cooled in period of summer. In the event of waiting, to preserve at +4°C before the sending, especially not to freeze. ]

Analysis laboratories:

Among the laboratories able to identify the Legionellosis ones, the laboratories approved in the accordance with the control of natural mineral water were the subject of a intercalibration on the detection of the Legionellosis ones.

The research and the numeration of Legionella in water are carried out according to standard AFNOR NT90-431 (November 1993).
This standardized method allows obtaining homogeneous results with a sensitivity (50 UFC/litre, UFC = units forming colony) sufficient to the glance of the medical risk. For the determination of the density of Legionellosis, the analytical standard requires that the filtrate be recovered in 5 ml. The characteristics of certain water (turbides...) make sometimes necessary a filtration in several stages. Recovery can then be done only in 10 ml and this operation modifies the threshold of detection which passes to 100 UFC/litre. The complete results of research and enumeration are in general available into 8 to 10 days. Acceptable thresholds (thermal springs, domestic hot water... - For the distribution networks of domestic hot water there is not any lawful text fixing an acceptable maximum density of Legionella. It is recognized that below a density of 103 UFC/litre, the risk of appearance of case of l3egionellose is very weak. However, this risk varies according to the immunizing state of the exposed people and the density and exposure time to the contaminated aerosols. - For thermal springs, circular DGS/SD1D/92 n° 513 of July 20, 1992 relating to the quality of mineral water in the hydropathic establishments proposed to take 10² UFC/litre as nonimperative value of reference beyond which an attentive follow-up of the situation must be carried out. From 103 UFC/litre, measures of fight and prevention must be taken for the uses and care causing the production of aerosols. - being given that these thresholds were fixed according to the medical risk, it is preferable that the techniques of taking away can translate the contamination at the point of use under normal or unfavourable conditions of use.

The interpretation of the results will have to be done by taking account of the preliminary expertise on the network. These results will also be used as reference to evaluate the effectiveness of measurements taken.

Conclusions

The environmental investigation will have to always be the subject of a written report/ratio indicating the principal results of the investigation and measurements under consideration of reduction of the risk (closing, restrictions of activities or use of water, outage of buildings or equipment, cleaning, disinfection, protocols of maintenance and monitoring). Taking into account the times of analysis for the research of Legionella, it will be often preferable not to await the results of analysis to make the first recommendations of fight and prevention if the elements provided by the investigations epidemiologic and environmental are enough to define them.

The comparison of the stocks insulated among patients with stocks insulated in the environment by techniques from molecular typing can be used to confirm the source of contamination. However, taken separately without epidemiologic argument, the identity of the stocks is not sufficient to establish a causal relation.

Immediate measurements are measurements of massive disinfection aiming at making disappear the contamination from the medium by Legionella. However, these specific measurements are not sufficient for they allow only one provisional eradication followed by a rapid recolonisation. They must thus be supplemented by measurements of prevention to the long course allowing a durable reduction of the flora.

Medical networks water supply hot

The disinfection of the distribution networks of water requires first of all, an expertise on the state of the drains and structure of the network in order to determine its tolerance with the operations of disinfection. Measurements of disinfection are described in appendix II.

Systems of air-conditioning and aero-cooling towers

Measurements of fight and prevention depend on the type of system blamed at the time of the environmental investigation. The first measurements of fight consist primarily of a draining of the circuits or zones of recovery of the condensates, with the cleaning and the disinfection of the installations. Appendix IV more precisely described the measures which can be recommended according to the type of equipment.

Baths with movement, jet basins

Measurements of fight and prevention depend on the type of basin in question in the contamination. The appendix V more precisely describes the measures which can be recommended.

Medical devices of respiratory treatment

- Use of material of single use or, cleaning, disinfection, then sterilization between each use.
- In the equipment of treatment respiratory, use only of water sterile at the same time for the rinsing and the filling.
- To proscribe the handing-over on level of liquid in the tanks of atomizers. Epidemiologic and environmental monitoring.

Epidemiologic monitoring

It includes/understands coordinated information of the persons in charge, users (committees of hygiene and safety) and medical profession. The doctors will have to be sensitized with the examinations to practise in front of a pneumopathy.

Environmental monitoring

The proof of the resolution of the problem is generally brought only if analytical control shows that the results are satisfactory and that a permanent and recognized technical solution as suitable is brought. In the contrary case, the maintenance of a reinforced monitoring will be necessary. With regard to the hydropathic establishments, one will be able to refer to the recommendations of good medical practices. For the other communities, a program of monitoring is set up by the medical authority (DDASS, SCHS) according to the characteristics and of the critical points of the establishment. For example, in the case of a seasonal operation, a medical control including of the analyses can be programmed at the time of the opening (after the operations of maintenance and reconditioning).

• General Direction of Health, office VS2 and VS4
1, place Fontenoy 75350 PARIS 07 SP
Telephone: 01 40 56 40 35 Telecopie: 01 40 56 50 56
email : lepoutre@b3e.jussieu.fr

• National Network of Public health
14, street of the Valley of Osne 94415 SAINT MAURICE Cedex
Telephone: 01 43 96 66 20 Telefax: 01 43 96 65 02
email : umi@b3e.jussieu.fr

• National Centre of Reference of Legionella
pr. J Etienne Laboratoire Central of Microbiology
Hospital Edouard Herriot
Places of Arsonval 69437 LYON Cedex 03
Telephone: 04 72 11 07 62 T3el3ecopie: 04 72 11 07 64
email : hehbac@laennec.univ-lyon1.fr

• the list of the laboratories approved by the ministry for Health, in the accordance with the control of natural mineral water, is available to office VS4 of the General Management of Health.

Diagnosis - Epidemiology

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3. Plouffe JF, File TM, Breiman RF et al.. Reevaluation of the definition of Legionnaires' disease: use of the urinary antigen assay. Covering joint. Repugnant. Say. 1995;20:1286-91.
4. National network of Public health and CNR of Legionella. Legionellosis in France in 1995: microbiological diagnosis and epidemiologic monitoring. Rnsp, Holy Maurice, France, December 1996.