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Legionnaires' disease outbreak in Murcia, Spain. (Research).

An explosive outbreak of Legionnaires' disease Legionnaires' disease

A type of pneumonia usually caused by infection with the bacterium Legionella pneumophila, but occasionally with a related species (such as L. micdadei or L. dumoffii).
 occurred in Murcia, Spain, in July 2001. More than 800 suspected cases were reported; 449 of these cases were confirmed, which made this the world's largest outbreak of the disease reported to date. Dates of onset for confirmed cases ranged from June 26 to July 19, with a case-fatality rate of 1%. The epidemic curve and geographic pattern geographic pattern A general descriptor for lesions in which large areas of one color, histologic pattern, or radiologic density with variably scalloped borders sharply interface with another color, pattern or density, fancifully likened to national boundaries  from the 600 completed epidemiologic questionnaires indicated an outdoor point-source exposure in the northern part of the city. A case-control study case-control study,
n an investigation employing an epidemiologic approach in which previously existing incidents of a medical condition are used in lieu of gathering new information from a randomized population.
 matching 85 patients living outside the city of Murcia with two controls each was undertaken to identify the outbreak source; the epidemiologic investigation implicated im·pli·cate  
tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates
1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot.

 the cooling towers at a city hospital. An environmental isolate from these towers with an identical molecular pattern as the clinical isolates was subsequently identified and supported that epidemiologic conclusion.


Legionnaires' disease (LD) has been an emergent emergent /emer·gent/ (e-mer´jent)
1. coming out from a cavity or other part.

2. pertaining to an emergency.


1. coming out from a cavity or other part.

2. coming on suddenly.
 disease since the 1970s. In the last few years, the Years, The

the seven decades of Eleanor Pargiter’s life. [Br. Lit.: Benét, 1109]

See : Time
 increased use of a simple test for detecting urinary antigen Legionella pneumophila Legionella pneumophila is a thin, pleomorphic, flagellated Gram-negative bacterium of the genus Legionella.[1] L. pneumophila is the primary human pathogen in this group and is the causative agent of legionellosis or Legionnaires' disease.  serogroup 1 in patients with pneumonia has facilitated diagnosis (1). Transmission by aerosols has been extensively reported, and evidence of Legionella Legionella /Le·gion·el·la/ (le?jah-nel´ah) a genus of gram-negative, aerobic, rod-shaped bacteria (family Legionellaceae), normal inhabitants of lakes, streams, and moist soil; they have often been isolated from cooling-tower water,  in aerosols derived from cooling towers has been provided (2-5). Although a considerable body of epidemiologic evidence exists for the association of LD outbreaks with aerosols produced by cooling towers, some controversy exists about the role that cooling towers play in LD (6-13).

We describe an explosive outbreak of LD that occurred in July 2001 in Murcia, a municipality MUNICIPALITY. The body of officers, taken collectively, belonging to a city, who are appointed to manage its affairs and defend its interests.  with 360,000 inhabitants
:This article is about the video game. For Inhabitants of housing, see Residency
Inhabitants is an independently developed commercial puzzle game created by S+F Software. Details
The game is based loosely on the concepts from SameGame.
 in southeastern Spain. We also report results of a case-control study performed to identify the source of this outbreak, which turned out to be a cooling tower. The outbreak of pneumonia was first detected on July 7. At the end of the first day of active surveillance, July 8, approximately 100 cumulative suspected cases were reported. More than 800 suspected cases were recorded by July 22, when the last case was treated, 2 weeks after the onset of the investigation. The epidemiologic investigation using a case-control study emphasizes a combination of strategies to measure and analyze an outbreak of LD that occurs in an area with many large potential sources of environmental contamination.


Case Detection

An active surveillance system to detect patients with any form of pneumonia was established on July 8 at all hospitals in the region of Murcia. Any reported case of pneumonia was considered a suspected case of LD if this diagnosis could not be ruled out. A confirmed case of LD was defined as a case of pneumonia with laboratory evidence of acute infection with Legionella including a) isolation of any species or serogroup of Legionella from respiratory secretions, lung tissue, or blood, b) a fourfold fourfold

1. having four times as many or as much

2. composed of four parts


by four times as many or as much

Adj. 1.
 or higher rise in antibody titers antibody titer The amount of a specific antibody present in the serum, usually as a result of an acquired infection; titers for IgM usually rise abruptly at the time of infection–acute phase and fall slowly; during the 'convalescent' phase, IgG ↑ and is  from 1:128 against L. pneumophila SG1 by immunofluorescence Immunofluorescence

A technique that uses a fluorochrome to indicate the occurrence of a specific antigen-antibody reaction. The fluorochrome labels either an antigen or an antibody.
 or microaglutination in paired acute- and convalescent-phase serum specimens, or c) detection of L. pneumophila antigen in urine.

An epidemiologic questionnaire to elicit information on clinical aspects, predisposing factors, risk factors, place of residence, and recent urban mobility within the city of Murcia was administered to 662 persons with suspected cases, most within 24 to 48 hours after the case was reported. A computerized database was set up as well as maps showing geographically referenced cases and a spatial analysis (Data West Research Agency definition: see GIS glossary.) Analytical techniques to determine the spatial distribution of a variable, the relationship between the spatial distribution of variables, and the association of the variables of an area.  by census division The term Census division or Census Division is officially used for the Census divisions of Canada and the Census divisions of the United States.

 that used a geographic information system geographic information system (GIS)

Computerized system that relates and displays data collected from a geographic entity in the form of a map. The ability of GIS to overlay existing data with new information and display it in colour on a computer screen is used primarily to

Case-Control Study

Inclusion in the study was restricted to patients who had confirmed LD, were residents outside the city of Murcia, and had been reported July 8-20 as case-patients. Each case-patient was matched to two controls according to according to
1. As stated or indicated by; on the authority of: according to historians.

2. In keeping with: according to instructions.

 place of residence, sex, and age. Controls were randomly selected from the population of the same area of residence and health district as the matched patient.

A standardized questionnaire to interview patients and controls was designed. It focused on urban mobility and exposure to outside air within the northern part of Murcia 2 weeks before the patient's onset of illness. Patients and controls were interviewed in person at home between July 25 and August 8. Itineraries of all participants, including information about means of transport See: mode of transport.  and frequency of trips, were outlined on a map of Murcia. In addition, any travel into or visit to 30 specific zones of the city in which putative sources of contaminated contaminated,
v 1. made radioactive by the addition of small quantities of radioactive material.
2. made contaminated by adding infective or radiographic materials.
3. an infective surface or object.
 aerosols were located was recorded. The questionnaire also requested information about place of residence and work, occupation, education level, employment status, smoking habit, alcohol intake, chronic lung disease lung disease Pulmonary disease Pulmonology Any condition causing or indicating impaired lung function Types of LD Obstructive lung disease–↓ in air flow caused by a narrowing or blockage of airways–eg, asthma, emphysema, chronic bronchitis; , diabetes, renal or heart disease, malignancy malignancy: see cancer. , immunocompromising disease, organ transplant organ transplant: see transplantation, medical. , therapy with corticosteroids Corticosteroids Definition

Corticosteroids are group of natural and synthetic analogues of the hormones secreted by the hypothalamic-anterior pituitary-adrenocortical (HPA) axis, more commonly referred to as the pituitary gland.
, and other risk factors for LD within 2 weeks before illness.

A multivariate analysis multivariate analysis,
n a statistical approach used to evaluate multiple variables.

multivariate analysis,
n a set of techniques used when variation in several variables has to be studied simultaneously.
 that used conditional logistic regression In statistics, logistic regression is a regression model for binomially distributed response/dependent variables. It is useful for modeling the probability of an event occurring as a function of other factors.  was conducted to calculate odds ratios (OR) with 95% confidence intervals confidence interval,
n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%.
 (CI) as estimates of the relative risk for LD associated with a person's travel through each zone; we controlled for the confounding confounding

when the effects of two, or more, processes on results cannot be separated, the results are said to be confounded, a cause of bias in disease studies.

confounding factor
 effects of traveling through other zones. Any zone of exposure that was significant in univariate analysis or showed biologic plausibility as a source was entered into the multiple analysis. The frequency with which participants visited Murcia city was also introduced into the multivariate analysis. Statistical analysis was conducted with STATA software (15).

Strategies of Analysis

Exposure zones were analyzed in two ways after codification The collection and systematic arrangement, usually by subject, of the laws of a state or country, or the statutory provisions, rules, and regulations that govern a specific area or subject of law or practice.  of the information obtained from each patient or control as he or she traveled or did not travel through a) the area defined by the block around a building with a cooling tower or the block around an ornamental fountain (in this way, 30 zones of the northern part of the city were coded), and b) the area delineated de·lin·e·ate  
tr.v. de·lin·e·at·ed, de·lin·e·at·ing, de·lin·e·ates
1. To draw or trace the outline of; sketch out.

2. To represent pictorially; depict.

 by a circle of 200 m radius around a cooling tower or a large ornamental fountain. Therefore, eight high-risk zones were studied.

In all cases, for each area of exposure, how the patient or control traveled through the area (i.e., walking [a category that also included bicycling or motorbiking] or driving [a car, bus, or truck]) was specified. This information was analyzed for the following: a) walking versus not passing through a zone or b) walking versus not passing through an area or traveling through it by car. Finally, for all possibilities, data were analyzed in two further ways: a) complete, which took into account all persons in the study, or b) restricted, which took into account only the trios of case-patients and their two paired controls in which all three persons stated that they had visited Murcia in the study period.

Environmental Investigation

Possible sources of aerosols were inspected, and water samples were collected from the water supply network and from 339 installations (e.g., cooling towers, storage tanks, and decorative fountains). Cooling towers were identified by aerial inspection because no census of these installations was available. Attack rates by residence were used to determine in which locations inspections and environmental samplings could be conducted.

Microbiologic Study

Environmental samples were processed according to ISO (1) See ISO speed.

(2) (International Organization for Standardization, Geneva, Switzerland, An organization that sets international standards, founded in 1946. The U.S. member body is ANSI.
 11731/1998. Environmental and clinical L. pneumophila serogroup 1 isolates were typed by monoclonal antibody monoclonal antibody, an antibody that is mass produced in the laboratory from a single clone and that recognizes only one antigen. Monoclonal antibodies are typically made by fusing a normally short-lived, antibody-producing B cell (see immunity) to a fast-growing  (MAb) with International and Dresden MAb panels (16,17) and compared by three molecular methods, amplified fragment length polymorphism Amplified fragment length polymorphism PCR, or "AFLP-PCR" (often AFLP), is a tool used in the study of genetics and in the practice of genetic engineering.

Amplified Fragment Length Polymorphism (AFLP
 (AFLP), pulsed-field gel electrophoresis gel electrophoresis
Electrophoresis performed in a gel composed of agarose, polyacrylamide, or starch.
 (PFGE PFGE Pulsed-Field Gel Electrophoresis )-SfiI, and arbitrarily primed-polymerase chain reaction (AP-PCR) (18-20).


Descriptive Epidemiology descriptive epidemiology

see descriptive epidemiology.

The outbreak of pneumonia was detected on the evening of July 7, when the Regional Department was notified that an increase in pneumonia cases had occurred in three hospitals in Murcia. Legionella antigen was detected in some patients' urine. Approximately 800 suspected cases were reported July 8-22; confirmed cases numbered 449. We estimate that 636-696 persons were affected. These estimates took into account the sensitivity of the antigen test in urine of 70% (4) and the background number of pneumonia cases estimated from the median of patients admitted with pneumonia in the region's hospitals during the summers from 1996 through 2000.

Onset of illness of the first confirmed case-patient was June 26. Until July 1, only a small number of cases occurred. After this date, the outbreak became explosive, with most cases occurring in <10 days (83% of confirmed cases had onset from July 2 through July 9). The last case-patient became ill on July 19 (Figure 1). The outbreak was considered compatible with massive exposure to a common source of contamination. When LD's incubation period incubation period
1. See latent period.

2. See incubative stage.

Incubation period 
 was taken into account, the maximum emission was estimated to have occurred June 29-July 1 and to have ended completely July 9-17.


Hospital admission was necessary for 64% of all reported case-patients and 74% of confirmed case-patients. Six deaths from LD were confirmed to be directly related to this outbreak, five confirmed cases and one suspected. Therefore, the case-fatality rate was 1.1% for confirmed cases only and 0.9% for total estimated cases. For all confirmed case-patients, 74% were men and 26% women. The age range was from 19 to 91 years; 70% were [greater than or equal to] 50, and 29% were [greater than or equal to] 70. The incidence rate increased with age in both sexes and was higher in men in all age groups (Figure 2).


Of the confirmed case-patients, 68% lived in Murcia city proper, 16% in the satellite districts within the municipality of Murcia, and 16% in other municipalities of the region. To evaluate the risk by quarters within the city of Murcia, the Standardized Incidence Ratio (SIR) was used. Three neighborhoods located in the northern part of the city had the highest incidence rate (4.9-6.7 per 1,000 population), significantly higher than the average for the city of Murcia (Table 1, Figure 3). According to epidemiologic interviews, 95% of the confirmed case-patients lived, worked, or visited in the northern districts in the 10 days before the outbreak began.


L. pneumophila serogroup 1 was recovered from clinical samples of 19 patients; 18 samples were characterized. All were Pontiac (MAb 2+) Philadelphia MAb type and shared an identical molecular pattern by AFLP, PFGE-SfiI, and AP-PCR.

Case-Control Study

The descriptive study showed no common indoor source of exposure and determined that the outbreak was provoked by a common source located in the northern part of the city. The study hypothesis was that the outbreak had its origin in environmental contamination from cooling towers or other installations capable of producing and dispersing large quantities of aerosols potentially contaminated by legionellae.

A total of 85 cases and 170 controls were included in a case-control study. Participation in the case-control study was classified as recently proposed by Olsen et al. (21). The response rate among eligible cases was 89% (85/96) and 96% (85/89) among those eligible who were contacted. The response rate among persons selected as eligible controls was 51% (170/334) and 61% (170/279) among those eligible who were contacted. The distribution of cases and controls according to sex, age, and residence was identical. No significant differences were found between cases and controls in any of the variables considered as a risk for or predisposing factor to the disease, as shown in Table 2. No differences were found with respect to education level or employment situation (Table 3). A strong association between visiting the city of Murcia and being ill with LD was found (OR 14.1, 95% CI 4.2 to 45.9).

The zone of exposure, defined either by the block surrounding hospital H or by a circle of 200 m in radius around hospital H, was significantly associated with illness in all eight models of multivariate analysis (Table 4). This zone of exposure also showed a much higher OR in every model. Thus, LD was 4.8-11.4 times more likely to develop in persons who passed through the zone around hospital H during the risk period than in persons who did not travel through this zone, independent of their having passed through the other zones. These results were also independent of the number of times the patient had visited the city.

An association between the illness and walking through the zone was observed in the multivariate analysis for another three zones of exposure. However, none of these zones appeared in more than two of the eight models, and each had an OR that was lower or much lower than that for the zone around hospital H in the corresponding model.

Nosocomial nosocomial /noso·co·mi·al/ (nos?o-ko´me-il) pertaining to or originating in a hospital.

1. Of or relating to a hospital.

 Outbreak at Hospital H

During the epidemiologic study epidemiologic study A study that compares 2 groups of people who are alike except for one factor, such as exposure to a chemical or the presence of a health effect; the investigators try to determine if any factor is associated with the health effect  of this community outbreak of LD, a nosocomial outbreak of LD at hospital H was discovered. In all 11 definite or probable nosocomial cases, some portion of the previous 1 O-day period of hospitalization hospitalization /hos·pi·tal·iza·tion/ (hos?pi-t'l-i-za´shun)
1. the placing of a patient in a hospital for treatment.

2. the term of confinement in a hospital.
 coincided with the period when the cooling towers could have been active.

Environmental Inspection and Microbiologic Study of Environmental Samples

L. pneumophila was not recovered from water samples from the drinking water drinking water

supply of water available to animals for drinking supplied via nipples, in troughs, dams, ponds and larger natural water sources; an insufficient supply leads to dehydration; it can be the source of infection, e.g. leptospirosis, salmonellosis, or of poisoning, e.g.
 supply network in the city of Murcia. L. pneumophila serogroup 1 Pontiac (MAb 2+) was recovered from 22 installations (cooling towers of 11 buildings in the city and water storage tanks from 3 buildings). Ten of 11 cooling towers contained a Philadelphia MAb-type strain, but only two colonies, recovered in October from a cooling tower of hospital H, were indistinguishable from the patient strains by AFLP (Figure 4). Identical results were obtained when PFGE-SfiI and AP-PCR were applied.


Weather Conditions

Data provided by the Weather Centre of Murcia showed that during the last days of June and early July some atmospheric thermal inversion occurred every day, except one. Winds were predominantly from the northeast quadrant with a very low average speed (9 kph) and very high temperatures (33.5[degrees]C-35[degrees]C).


This LD outbreak is the largest to date in the world, with 449 confirmed cases and an estimated total number of cases of 650. The reported case-fatality rate (1%) is much lower than those observed in other community outbreaks (22,23). This rate can be attributed, at least partially, to the quick detection of the outbreak, early diagnosis of the disease, and appropriate treatment of patients. The explosive quality of the outbreak not only led patients to seek quick assistance at hospital emergency units but also helped clinicians to perform an accurate diagnosis and to immediately initiate adequate treatment, factors reported as linked to low case fatality In epidemiology, case fatality (CF) refers the rate of death among people who already have a condition. It is usually defined with a period of time, such as a 28-day CF or a 24-hour CF. It is usually measured as a decimal or as a percent.  (24,25). This explosive appearance could also be related to a lower presence of predisposing factors in case-patients in comparison with other community outbreaks (7,9,13), which could also partially explain the low case-fatality rate.

The initial investigation encountered obstacles, such as a large number of potential sources of environmental contamination located in the northern part of the city and the absence of environmental Legionella isolates identical to those of patients. The case-control study showed a significant association, with a high consistency between the analyzed models and with a high magnitude of association, between passing through the zone around hospital H and being ill with LD. Results were similar even when the area radius was expanded to 400 m. However, large overlap of areas was observed within this radius, and multicollinearity among zones was a common finding.

The case-control study was designed to select patients residing outside the city of Murcia. We decided on this approach for two reasons. First, the incidence of LD was almost 1% in some neighborhoods, a rate within the 0.1% to 5% attack rate described for this disease (26) Therefore, all the persons living in these quarters could possibly have been exposed to Legionella, as has been described in outbreaks of other transmissible transmissible /trans·mis·si·ble/ (trans-mis´i-b'l) capable of being transmitted.

Capable of being conveyed from one person to another.
 diseases (27). If everyone had been exposed, finding incidence differences between persons exposed and those not exposed would have been almost impossible. Second, persons residing outside the city would probably have a more accurate memory of the itineraries they followed in Murcia some weeks previously and would probably have a lesser number of routes than persons living within the city. Conducting 255 personal interviews with questions about itineraries within 2 weeks from the last case and 4 weeks from the outbreak onset may also have been important to our findings.

One concern in case-control studies is that participation rate is not reported consistently (21). Indeed, this information is usually omitted in case-control studies of outbreaks, especially when controls are selected from a population database, as was our situation. A further complication was that the study had to be conducted in July, when many people go on holiday. In spite of achieving the participation of one in two controls whom we initially selected, we evaluated possible selection bias. We determined that it was unlikely to have occurred since neither socioeconomic status socioeconomic status,
n the position of an individual on a socio-economic scale that measures such factors as education, income, type of occupation, place of residence, and in some populations, ethnicity and religion.
 nor predisposing risk factors for LD differed significantly among cases and controls. Information bias overestimating this outcome was ruled out since news media did not mention hospital H among the probable sources of the outbreak.

Meteorologic me·te·or·ol·o·gy  
The science that deals with the phenomena of the atmosphere, especially weather and weather conditions.

[French météorologie, from Greek
 conditions were favorable for the emission of aerosols to be dispersed in a horizontal manner. Low wind speed together with atmospheric thermal inversion between June 29 and July 1 would have facilitated the presence of the aerosols in the environment (9).

The result of the epidemiologic study was subsequently confirmed by the isolation of a strain retrieved on October 30 from a sample from one of the cooling towers of the same hospital; that strain is identical to the strain isolated from the patients. The difficulties found previously in the isolation of this strain were not unexpected. The day after the outbreak was detected, when the first sample was taken, the cooling towers of hospital H were highly chlorinated chlorinated /chlo·ri·nat·ed/ (klor´i-nat?ed) treated or charged with chlorine.


charged with chlorine.

chlorinated acids
some, e.g.
, which could explain why these first samples gave negative results. Later samples retrieved on four different dates between July 28 and September 13 showed positive results to L. pneumophila but were characterized as different strains from those from patients. This strain was only isolated upon the restarting of one tower after it was shut down for more than 1 month, a condition that favors the reappearance Re`ap`pear´ance   

n. 1. A second or new appearance; the act or state of appearing again.

Noun 1. reappearance - the event of something appearing again; "the reappearance of Halley's comet"
 of Legionella (8,12,13). The fact that the same clone of Legionella can be found in an installation for long periods is also documented (28,29). The possible contamination of the tower by new Legionella from the water supply was ruled out since the strain linked to the outbreak was not found in samples collected from many other installations during the same period, including July to November.

The coincidence of a nosocomial LD outbreak in hospital H reinforces the previous hypothesis. A nosocomial outbreak of LD as part of a wider community outbreak of the disease has been described (12,30), although in other outbreaks originating in the cooling towers of a hospital no cases of nosocomial LD were identified (7). The use of double HEPA HEPA  
1. high-efficiency particulate air

2. high-efficiency particulate arresting
 filters on air-intake vents in some hospitals could justify, at least in part, these contradictory observations.

Our research indicates that the cooling towers of a hospital located in the northeastern part of the city of Murcia were the origin of this community outbreak. This study underlines important risk factors that must be taken into account to prevent a new LD outbreak. First, cooling towers had to be identified by aerial and direct inspection in the absence of any census of such installations. Second, the size, location, and state of maintenance of cooling towers are very important. In contrast with epidemics associated with relatively small systems (8), this outbreak was related to a large refrigeration refrigeration, process for drawing heat from substances to lower their temperature, often for purposes of preservation. Refrigeration in its modern, portable form also depends on insulating materials that are thin yet effective.  system that seems to have infected patients up to 1.3 km downwind down·wind  
In the direction in which the wind blows.

 to the west from the cooling tower; this finding suggests that airborne infection with L. pneumophila may extend over a large distance from the dissemination source, as has been reported elsewhere (9,10). Although most of the installations in the area showed inadequate maintenance, the cooling towers from hospital H were poorly maintained and had a high-risk size and location. Once the outbreak was identified, urgent measures were undertaken to clean, disinfect To remove the virus code that has attached itself to a legitimate file. Sometimes, the antivirus program cannot untangle the code, and the infected file has to be deleted. See quarantine. , or close possibly contaminated sources. The cooling tower that was the source of the outbreak was subsequently replaced by an air-cooled system.

Before June 2001, no specific national legislation existed in Spain concerning LD, although a recommendation guide and legislation existed in several Spanish autonomous regions that had had community LD outbreaks (31). As an immediate consequence of this outbreak, a national law about prevention and control of LD was enacted in Spain 20 days after the outbreak began (32). The extent of this outbreak is useful to assess the relative role of cooling towers as a source of LD and highlights the importance of prioritizing control measures related to cooling towers among strategies to prevent LD in the community. Compliance with these measures would help to reduce not only community outbreaks but also, perhaps, sporadic cases that could be due to infected cooling towers (33).
Table 1. Confirmed cases of Legionnaires' disease within Murcia
city, Murcia, Spain

                                                         Incidence per
Neighborhood           Confirmed cases   Inhabitants         1,000

Sta. M (a) de Gracia         90            13,410              6.7
Vistalegre                   62            12,677              4.9
San Anton                    48             9,373              5.1
San Miguel                   28             9,511              2.9
San Basilio                  17             5,509              3.1
Santiago Z                    8             3,215              2.5
San Pio X                     4               824              4.8

Neighborhood           SIR (a) (95% CI)

Sta. M (a) de Gracia   6.3 (5.1 to 7.8)
Vistalegre             4.8 (3.7 to 6.1)
San Anton              5.2 (3.8 to 6.9)
San Miguel             2.5 (1.5 to 3.3)
San Basilio            3.0 (1.8 to 4.8)
Santiago Z             2.5 (1.1 to 4.9)
San Pio X              4.2 (1.1 to 10.8)

(a) SIR, standardized incidence ratio by neighborhood within
Murcia city. Only results of neighborhoods with SIR > 1 are
represented; CI, confidence intervals.

Table 2. Risk factors for Legionnaires' disease patients and
controls, Murcia, Spain

Predisposing factors           Cases n=85   Controls n=170

Smoking (%)                        43.5           40.6
Alcohol intake (cc/week)          134            106
Chronic illness or immuno-
suppressive therapy (%)            16.5           14.7
Previous hospitalization (%)        1.2            1.8
Previous travel (%)                11.8           13.5

Table 3. Educational level and employment status for
Legionnaires' disease cases and controls, Murcia, Spain

Education and employment   Cases (n=85)   Controls (n=170)

Educational level (%)
  Primary                      52.9             51.5
  Secondary                    38.8             37.3
  University                    8.2             11.2
Employment status (%)
  Employed                     65.5             63.5
  Unemployed                    5.9              3.6
  Retired                      19.1             21.1
  Housewife/husband             8.3              8.4
  Student                       1.2              3.0

Table 4. Association between Legionnaires' disease and a patient's
traveling through specific areas of the northern part of the city of
Murcia, Spain (a)

                    Block-area study

                    Complete analysis

                     OR              OR
                  (95% CI)        (95% CI)

                                 Walking vs.
                                 not passing
                 Walking vs.     through or
                 not passing     passing by
Area of city       through         driving

Hospital H          10.2             9.7
                (3.6 to 28.8)   (3.9 to 23.6)
Garden P             5.2             4.6
                (1.0 to 25.8)   (1.2 to 17.0)
Car-park X

                     Block-area study

                    Restricted analysis

                     OR              OR
                  (95% CI)        (95% CI)

                                 Walking vs.
                                 not passing
                 Walking vs.     through or
                 not passing     passing by
Area of city       through         driving

Hospital H          10.7             6.0
                (2.5 to 45.5)   (1.9 to 18.4)
Garden P
Car-park X

                     Circle area study

                     Complete analysis

                     OR              OR
                  (95% CI)        (95% CI)

                                 Walking vs.
                                 not passing
                 Walking vs.     through or
                 not passing     passing by
Area of city       through         driving

Hospital H           6.9             6.4
                (1.8 to 26.0)   (2.5 to 15.7)
Garden P
Car-park X           5.1             3.6
                (1.7 to 14.9)   (1.4 to 9.2)
Commercial                           2.9
building                        (1.1 to 7.4)

                     Circle area study

                    Restricted analysis

                     OR              OR
                  (95% CI)        (95% CI)

                                 Walking vs.
                                 not passing
                 Walking vs.     through or
                 not passing     passing by
Area of city       through         driving

Hospital H          11.4             4.8
                (3.2 to 40.1)   (1.5 to 5.2)
Garden P
Car-park X

(a) Areas associated to the disease in a multivariate analysis
of data from eight different models. OR, odds ratio; CI, confidence


We thank E. Gomez, C. Gutierrez, B. Marsilla, A. Sanchez, M.A. Castano, M.J. Lorente, M.D. Chirlaque, J. Almansa, L. Cirera, M. Brotons, F. Belmonte, E. Gonzalez, J.L. Garcia, J.R. Soria, C. Carpe, J.A. Vera, F. Bailon, E. Salcedo, J.C. Casado, and A. Garrido for their participation and support in the outbreak investigation; the personnel of the Epidemiology Service and Public Health Service at the Consejeria de Sanidad and Ayuntamiento de Murcia for their technical assistance; A. Tobias for statistical advice and our public health colleagues C. Pons, H. Vanaclocha, P. Hernando, J.M. Ordonez, and X. Hervada for their help; J.L. Kool, C. Joseph, and J.V. Lee for their expert advice; P. Aparicio, F. Bolumar, F. Martinez Navarro, A. Plasencia, M. Sabria, and O. Tello for their valuable comments; J.H. Helbig for monoclonal antibody panels; and the staff of all the hospitals in Murcia Region for their collaboration in data collection.


(1.) Breiman RF. Impact of technology on the emergence of infectious diseases infectious diseases: see communicable diseases. . Epidemiol Rev 1996; 18:4-9.

(2.) Fields BS, Benson RF, Besser RE. Legionella and legionnaires' disease: 25 years of investigation. Clin Microbiol Rev 2002; 15:506-26.

(3.) Shelton BG. Review of legionnaires' disease. American Industrial Hygiene Association The American Industrial Hygiene Association (AIHA) is a professional membership organization of industrial hygienists, and occupational health and safety, and environmental health professionals.  Journal 2000;61:738-42.

(4.) Stout JE, Yu VL. Legionellosis. N Engl J Med 1997;337:682-7.

(5.) Ishimatsu S, Hiroshi M, Hori H, Tanaka Y, Yoshida SI. Sampling and detection of Legionella pneumophila aerosols generated from an industrial cooling tower. Ann Occup Hyg 2001 ;45:421-7.

(6.) Yu VL. Legionellapneumophila (Legionnaires' disease). In: Mandell GL, Benett JE, Dolin R, editors. Mandell, Douglas and Bennet's principles and practice of infectious diseases. Fifth ed. Philadelphia: Churchill Livingstone Imprint of a medical publishing company owned by Elsevier Ltd, but previously owned by Harcourt and Pearsons. Originally formed from Livingstone, Edinburgh, Scotland, and J & A Churchill, London, UK, and subsequently with an office in New York, but now integrated with the rest of ; 2000. p. 2424-35.

(7.) Brown CM, Nuorty PJ, Breiman RF, Lathcock AL, Fields BS, Lipman HB, et al. A community outbreak of Legionnaires' disease linked to hospital cooling towers: an epidemiological method to calculate dose of exposure. Int J Epidemiol 1999;28:353-9.

(8.) Bentham RH, Broadbent CR. A model for autumn outbreaks of Legionnaires' disease associated with cooling towers, linked to system operation and size. Epidemiol Infect 1993;111:287-95.

(9.) Addiss DG, Davis JP, LaVenture M, Wand P J, Hutchinson A, McKinney RM, et al. Community-acquired Legionnaires' disease associated with a cooling tower: evidence for longer distance transport of Legionella pneumophila. Am J Epidemiol 1989; 130:557-68.

(10.) Report of an ad-hoc committee. Outbreak of legionellosis in a community. Lancet 1986;2:380-3.

(11.) Garbe PL, Davis B J, Weisfeld JS, Markowitz L, Miner P, Garrity F, et al. Nosocomial legionnaires' disease. Epidemiological demonstration of cooling tower as a source. JAMA JAMA
Journal of the American Medical Association

(12.) Dondero TJ, Rendtorff RC, Mallison GF, Weeks RM, Levy JS, Wong EW, et al. An outbreak of Legionnaires' disease associated with a contaminated air-conditioning cooling tower. N Engl J Med 1980;302:365-70.

(13.) Keller DW, Hajjeh R, DeMaria A, Fields BS, Pruckler JM, Benson RS, et al. Community outbreak of Legionnaires' disease: an investigation confirming the potential for cooling towers to transmit Legionella species. Clin Infect Dis 1996;22:257-61.

(14.) Intergraph Corporation. Geomedia professional. Release 3.0. Huntsville (AL): Intergraph Corporation; 1999.

(15.) Stata Corporation. Stata statistical software: Release 7.0. College Station (TX): The Corporation; 2001.

(16.) Joly JR, McKinney RM, Tobin JO, Bibb bibb  
1. Nautical A bracket on the mast of a ship to support the trestletrees.

2. A bibcock.

[Alteration of bib.]
 WF, Watkins ID, Ramsay D. Development of a standardized subgrouping scheme for Legionella pneumophila serogroup 1 using monoclonal antibodies This is a list of monoclonal antibodies, antibodies which are clones of a single parent cell. When used as medications, the generic names end in -mab (see "Nomenclature of monoclonal antibodies"). . J Clin Microbiol 1986;23:768-71.

(17.) Helbig JH, Bernander S, Castellani Pastoris M, Etienne J, Gaia V, Lauwers S, et al. Pan-European study on culture-proven Legionnaires' disease: distribution of Legionella pneumophila serogroups and monoclonal subgroups. Eur J Clin Microbiol Infect Dis 2002;21:710-6.

(18.) Fry NK, Bansborg JM, Bernander S, Etienne J, Forsblom B, Gaia V, et al. Assessment of intercentre reproducibility and epidemiological concordance concordance /con·cor·dance/ (-kord´ins) in genetics, the occurrence of a given trait in both members of a twin pair.concor´dant

 of Legionella pneumophila serogroup 1 genotyping Genotyping refers to the process of determining the genotype of an individual with a biological assay. Current methods of doing this include PCR, DNA sequencing, and hybridization to DNA microarrays or beads.  by amplified fragment length polymorphism analysis. Eur J Clin Microbiol Infect Dis 2000; 19:773-80.

(19.) Luck PC, Helbig H, Gunter U, Assmann M, Blau R, Koch H, et al. Epidemiologic investigation by macrorestriction analysis and by using monoclonal antibodies of nosocomial pneumonia nosocomial pneumonia An infection of lungs–bronchoalveolar unit–in a Pt who has been hospitalized ≥ 48 hrs, and directly attributable to pathogens acquired during the hospital visit Etiology Pseudomonas spp, S aureus, Legionella  caused by Legionella pneumophila serogroup 10. J Clin Microbiol 1994;32:2692-7.

(20.) Gomez Lus P, Fields BS, Benson RF, Martin WT, O'Connor SP, Black CM. Comparison of arbitrarily primed polymerase chain reaction polymerase chain reaction (pŏl`ĭmərās') (PCR), laboratory process in which a particular DNA segment from a mixture of DNA chains is rapidly replicated, producing a large, readily analyzed sample of a piece of DNA; the process is , ribotyping, and monoclonal antibody analysis for subtyping Legionella pneumophila serogroup 1. J Clin Microbiol 1993 ;31:1940-2.

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(23.) De Schrijver K, Van Bouwel E, Mortelmans L, Van Rossom P, De Beukelaer T, Vael C, et al. An outbreak of Legionnaire's disease Legionnaire's disease (lē'jənârz`), infectious, sometimes fatal, disease characterized by high fever, dry cough, lung congestion, and subsequent pneumonia. Major organs, such as the heart, may be damaged as the disease progresses.  among visitors to a fair in Belgium, 1999. Eurosurveillance Monthly 2000;5:115-9.

(24.) Heath CH, Grove DI, Looke DFM DFM Design for Manufacturing (newsletter)
DFM Design for Manufacturability
DFM Dubai Financial Market
DFM Delphi Form (computer filename extension)
DFM Distinguished Flying Medal
DFM Diesel Fuel Marine
. Delay in appropriate therapy of Legionella pneumonia associated with increased mortality. Eur J Clin Microbiol Infect Dis 1996; 15:286-90.

(25.) Bening AL, Benson RF, Besser RE. Trends in Legionnaires Legionnaires may refer to:
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  • French Foreign Legion
  • Legionnaires' Movement in Romania, see: Iron Guard
  • Legionnaires' disease
  • Legion of Christ
  • Charlemagne's Legionnaires
  • Legion of Super-Heroes
  • Legionnaire of Christ
 disease, 1980-1998: declining mortality and new patterns of diagnosis. Clin Infect Dis 2002;35:1039-46.

(26.) Chin J, editor. Control of communicable diseases communicable diseases, illnesses caused by microorganisms and transmitted from an infected person or animal to another person or animal. Some diseases are passed on by direct or indirect contact with infected persons or with their excretions. . An official report of the American Public Health Association The American Public Health Association (APHA) is Washington, D.C.-based professional organization for public health professionals in the United States. Founded in 1872 by Dr. Stephen Smith, APHA has more than 30,000 members worldwide. . 17th edition. Washington: American Public Health Association; 2000.

(27.) Goma Epidemiology Group. Public health impact of Rwandan refugee crisis: what happened in Goma, Zaire, in July, 19947 Lancet 1995 ;345:339-44.

(28.) Sabria M, Garcia-Nunez M, Pedro-Botet MI, Sopena N, Gimeno JM, Reynaga E, et al. Presence and chromosomal subtyping of Legionella species in potable potable /pot·a·ble/ (po´tah-b'l) fit to drink.

Fit to drink; drinkable.


fit to drink.
 water systems in 20 hospitals of Catalonia, Spain. Infect Control Hosp Epidemiol 2001 ;22:673-6.

(29.) Rangel-Frausto MS, Rhomberg P, Hollis RJ, Pfaller MA, Wenzel RP, Helms ChM, et al. Persistence of Legionella pneumophila in a hospital's water system: a 13-year survey. Infect Control Hosp Epidemiol 1999;20:793-7.

(30.) Darelid J, Hallander H, Lofgren S, Malmvall BE, Olinder-Nielsen AM. Community spread of Legionella pneumophila serogroup 1 in temporal relation Noun 1. temporal relation - a relation involving time
relation - an abstraction belonging to or characteristic of two entities or parts together

antecedent, forerunner - anything that precedes something similar in time; "phrenology was an antecedent of
 to a nosocomial outbreak. Scand J Infect Dis 2001:33:194-9.

(31.) Ordonez JM. La nueva normativa estatal frente a la legionelosis: entre la ambicion y la realidad. Gac Sanit 2002; 16:105-8.

(32.) Real Decreto del Ministerio de Sanidad y Consumo, por el que se establecen los criterios higienico-sanitarios para la prevencion y control de la legionelosis. Real Decreto 909/2001. Boletin Oficial del Estado. July 28, 2001.

(33.) Bhopal R. Source of infection for sporadic Legionnaires' disease: a review. J Infect 1995;30:9-12.

Ana Garcia-Fulgueiras, * Carmen Carmen

throws over lover for another. [Fr. Lit.: Carmen; Fr. Opera: Bizet, Carmen, Westerman, 189–190]

See : Faithlessness


the cards repeatedly spell her death. [Fr.
 Navarro, * Daniel Fenoll, ([dagger]) Jose Garcia Jose Garcia / José García is a common name that can refer to:
  • Jose Garcia (Franciscans, OSM), Franciscans, OSM
  • Jose Garcia (game designer), Shadowfist game designer
  • José Andreu García (b. 1937), Puerto Rican jurist, chief justice.
, * Paulino Gonzalez-Diego, * Teresa Jimenez-Bunuales, * Miguel Rodriguez Miguel Rodriguez can be one of three persons who share the same name:

1. Miguel Rodriguez a Puerto Rican who is the Chief of the Integration Office of the Cape Canaveral Spaceport Management Office..

2. Miguel Rodríguez a Mexican race walker.

, * Rosa Lopez, * Francisco Pacheco For Singer of the same name, see .
Francisco Pacheco (bap. November 3, 1564-November 27, 1644) was a Spanish painter, best known as the teacher of Diego Velázquez and Alonso Cano, and for his textbook on painting that is an important source for the study of 17th-century practice
, * Joaquin Ruiz, ([double dagger double dagger
A reference mark () used in printing and writing. Also called diesis.

Noun 1.
]) Manuel Segovia, ([section]) Beatriz Baladron, ([paragraph]) and Carmen Pelaz ([paragraph])

* Regional Health Council of Murcia, Murcia, Spain; ([dagger]) Council of Murcia, Murcia, Spain; ([double dagger]) Virgen de la Arrixaca Hospital, Murcia, Spain; ([section]) Morales Meseguer Hospital, Murcia, Spain; and ([paragraph]) Health Institute of Carlos III Carlos III may refer to:
  • Charles III of Spain, King of Spain from 1716 to 1788.
  • Universidad Carlos III de Madrid, a Spanish university bearing his name.
, Madrid, Spain.

Dr. Garcia-Fulgueiras is an epidemiologist at the Murcia Regional Health Council in southeast Spain. She coordinates the regional epidemiologic surveillance epidemiologic surveillance The ongoing, systematic collection, analysis, and interpretation of health data essential to planning, implementing, and evaluating public health practice, closely integrated with the timely dissemination of these data to those who need to know  network. Her primary research interests include the epidemiology of infectious diseases and outbreaks.

Address for correspondence: A. Garcia-Fulgueiras, Servicio de Epidemiologia, Consejeria de Sanidad, Ronda de Levante 11, 30008 Murcia, Spain; fax: +34 968366656; email:
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Author:Pelaz, Carmen
Publication:Emerging Infectious Diseases
Geographic Code:4EUSP
Date:Aug 1, 2003
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