BRIEF REPORT
Legionnaires’ Disease Outbreak in an Automobile Engine Manufacturing Plant Alicia M. Fry,1,2 Miai Rutman,1 Terry Allan,3 Heidi Scaife,3 Ellen Salehi,4 Robert Benson,1 Barry Fields,1 Scott Nowicki,4 Mary Kay Parrish,4 Joseph Carpenter,1 Ellen Brown,1 Claressa Lucas,1 Timothy Horgan,3 Elizabeth Koch,4 and Richard E. Besser1 1
Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, and 2Epidemic Intelligence Service and Epidemiology Program Office, Centers for Disease Control and Prevention, Atlanta, Georgia; 3Cuyahoga County Board of Health and 4Ohio Department of Health, Cleveland, Ohio
We investigated 4 cases of legionnaires’ disease (LD) reported among workers at an Ohio automotive plant in March 2001. A “confirmed” case of LD was defined as x-ray–confirmed pneumonia and a confirmatory laboratory test. A “possible” case of LD was defined as elevated titers of antibody and respiratory symptoms. Legionella pneumophila serogroup 1 (LP1) was isolated from 1 case patient. Legionella was isolated from 18 (9%) of 197 environmental samples; 3 isolates were LP1 but did not match the case isolate. We conducted a casecontrol study; 17 case patients with confirmed or possible LD and 86 control subjects (workers with low antibody titers and without symptoms) were enrolled. Visiting a specific cleaning line (odds ratio, [OR], 7.29; 95% confidence interval [CI], 2.31–23.00) and working in the cleaning region of the plant (OR, 3.22; 95% CI, 1.11–9.38) were associated with LD. LD can be transmitted in industrial settings in which aerosols are produced. Clinicians should consider LD when treating persons from these settings for pneumonia. Legionella species are estimated to account for 8000–18,000 cases of pneumonia legionnaires’ disease (LD) in the United States each year; most are sporadic, isolated cases that often have an undefined source [1]. We know little about what proportions of LD cases are acquired in the home, in the workplace, or in other
Received 3 July 2002; accepted 4 December 2002; electronically published 27 February 2003. Informed consent was obtained from each participant. Reprints or correspondence: Dr. Richard Besser, 1600 Clifton Rd., MSC-23, Atlanta, GA 30333 (
[email protected]). The Journal of Infectious Diseases 2003; 187:1015–8 2003 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2003/18706-0017$15.00
settings in the community. Although outbreaks of legionellosis are uncommon, investigations of outbreaks help identify sources of Legionella exposure and risk factors for LD, as well as facilitate appropriate prevention strategies. Several industrial settings have been implicated in outbreaks of LD among workers, including factories that use water to cool molded plastics [2] and wastewater treatment facilities [3]. In addition, an automobile plant coolant system was implicated in an outbreak of Pontiac fever due to L. feeleii among plant workers [4]. In each setting, an aerosol-producing device was implicated in the transmission of Legionella to susceptible workers. We describe 4 cases of LD among workers at the same automotive engine manufacturing plant that were reported to the Cuyahoga County Board of Health (Cleveland) from 2–15 March 2001. We investigated the plant as the possible source for Legionella exposure. Materials and methods. We defined a “confirmed” case of LD as x-ray–confirmed pneumonia and laboratory evidence of Legionella infection (a positive Legionella urine antigen test result, isolation of Legionella from respiratory secretions or lung tissue, or a 4-fold increase in anti–Legionella antibody titer). We established active surveillance for LD in all hospitals in the greater Cleveland area and collected specimens from each of the 4 previously identified workers for the isolation of Legionella. The plant manufactures cast-iron engine components, is operated by a workforce of ∼2500 employees, and covers 11.6 million square feet of floor space (figure 1). We conducted an environmental investigation to sample aerosol-producing water sources that were potential sources for Legionella transmission, including cooling towers, cooling units, water hoses, and water heaters. We conducted a case-control study to determine risk factors for exposure to Legionella among plant workers using the above definition for a confirmed case of legionellosis. We defined a “possible” case of LD as one in a worker with an elevated titer of anti–Legionella antibody and ⭓2 of the following symptoms: cough, shortness of breath, fever, headache, myalgia, or fatigue. An elevated titer was either a combined titer for anti–Legionella IgG, IgA, and IgM (IgGAM) ⭓1:1024 or an anti–Legionella IgM fluorescence ⭓3 (on a scale of 1–4) at a 1:16 dilution. We defined a control subject as a worker with an IgGAM titer ⭐1: 64, IgM fluorescence ⭐1, and !2 symptoms (cough, shortness of breath, fever, headache, myalgia, or fatigue). To assure adequate numbers of case patients and control subjects (whose status could not be determined until laboratory testing was performed at the conclusion of the study), we used BRIEF REPORT • JID 2003:187 (15 March) • 1015
Figure 1. Schematic layout of the automobile engine manufacturing plant. The plant was a large, open building with 4 main areas, including the core, molding, melting, and cleaning areas. Engines moved along production lines from core to molding, to melting, and, finally, to the cleaning area as the engine mold was completed, the melted iron was poured into the mold, and excess metal was removed from each engine base. Water was used throughout the plant to cool the equipment and engine parts. Workers were not soaked but occasionally were sprayed with water. Lines in the figure depict production lines within each area. Striped stars represent normal work areas of the 4 workers with confirmed legionnaires’ disease. The circles with slashes represent 2 of the 3 sites with positive environmental cultures for Legionella pneumophilia serogroup 1 (LP1). The third site positive for LP1 was a cooling tower in the roof above the molding area (not shown).
a 2-tiered system to select workers with and without symptoms. We distributed a short, self-administered questionnaire asking about symptoms experienced from February 14 to March 23 and randomly selected workers from those who reported ⭓2 symptoms. We also contacted all workers who were hospitalized or on medical leave from February 14 to March 23. We identified workers without symptoms by randomly selecting workers from a master list of plant employees and screening them for symptoms with a brief interview. All study participants were asked detailed questions about where they spent their time inside and outside of the plant. Because nonspecific symptoms were part of our case definition, we also asked workers about illness among family members. We used illness among family members as a marker for personto-person spread to differentiate viral illness symptoms from legionellosis symptoms. We also collected a blood sample from each participant to determine the titer of anti–Legionella antibody. We calculated 2-tailed P values with the x2 test for dichotomous variables or the Wilcoxon signed-rank test for continuous variables. We also stratified outcomes by potential confounding variables and calculated the Mantel-Haenszel odds ratio (ORMH) to compare with the crude OR. Differences were considered to be statistically significant at P ⭐ .05. All environmental samples were processed as described elsewhere [5]. Legionella isolates were identified to species and serogroup by slide agglutination using absorbed rabbit antiserum. Lung tissue specimens were tested for Legionella by both the direct fluorescent antibody (DFA) assay with L. pneumophila serogroup 1 (LP1) conjugate and by immunohistochemical stain1016 • JID 2003:187 (15 March) • BRIEF REPORT
ing by use of procedures described elsewhere [6]. Serum specimens from workers participating in the case-control study were tested for the presence of anti–Legionella antibodies IgGAM and IgM by use of the indirect fluorescent antibody assay [6]. The level of IgM antibodies was determined by measuring the fluorescence intensity at a dilution of 1:16 and was recorded on a scale of 1–4 fluorescence. Results. All 4 confirmed case patients had onset of illness during 2–4 March 2001; 3 worked in the cleaning area (figure 1). Two of the case patients died. The results of testing for Legionella antigen in urine were positive in all 4 case patients. Case patient specimens included 2 lung tissue specimens (1 obtained after embalming), 2 bronchoalveolar lavage (BAL) fluid specimens, and 2 sputum specimens. The BAL fluid and sputum specimens were collected 11 week before our specimen collection began. LP1 was isolated from 1 specimen, the sputum specimen from case patient 4. Lung tissue specimens from both deceased patients were negative for Legionella by DFA test. However, LP1 was identified in the lung tissue specimen of 1 patient by immunohistochemical staining, using antiserum to LP1. No additional cases of LD due to LP1 were identified among workers in the plant. Only 1 case of LD in an immunocompromised person who was not associated with the plant was reported during this period. Environmental samples were taken from ∼43 sites in the core area, 10 in the molding area, 19 in the melting area, and 48 in the cleaning area, as well as from cooling towers, the powerhouse, the locker rooms, and the cafeteria. Legionella were isolated from 18 (9%) of 197 environmental samples; 3 of the
isolates were LP1 (figure 1). None of the environmental LP1 isolates matched the patient isolate by monoclonal subtyping. Overall, 5 different species of Legionella was present. We found no Legionella species in 8 additional samples obtained from the cleaning area after decontamination. Of the 436 workers who reported ⭓2 symptoms on the selfadministered survey and the 65 workers who were hospitalized or on medical leave from February 14 to March 23, we asked 287 to participate in the case-control study; 148 (52%) agreed to participate. To identify workers without symptoms, we asked 568 workers to participate; 285 (50%) agreed, and 190 (67%) workers had !2 symptoms. Overall, 84% of participants agreed to give blood. After receiving the serologic analysis results, we determined that 13 workers met the definition for a possible case of legionellosis (8 workers with IgM fluorescence ⭓3 and 5 with IgGAM ⭓1:1024) and 4 workers had confirmed cases of legionellosis; 86 (66%) of 130 workers who had !2 symptoms and agreed to give blood met the definition for control subjects. There was no significant difference between the median age of case patients and control subjects (48 years; range, 5–66 years] vs. 52 years [range, 19–75 years], respectively; P p .27). Case patients were more likely to be current smokers (75% vs. 40%; OR, 4.43; 95% confidence interval [CI], 2.12–21.89) and to have reported a history of pneumonia (50% vs. 12%; OR, 7.60; 95% CI, 2.33–24.76) or bronchitis (50% vs. 13%; OR, 6.82; 95% CI, 2.12–21.89) than control workers. Workers with possible or confirmed legionellosis were more likely to work in the cleaning area of the plant (table 1). Of Table 1.
the case patients, 12% worked on cleaning line 0, 24% worked on the cleaning line 2, and 6% worked on each of the other cleaning lines (1, 3, 5, and 10). Although working on a particular cleaning line was not significantly associated with legionellosis, visiting cleaning line 0, 1, or 2 during work hours was significantly associated with disease. Visiting cleaning line 0 posed the highest risk. Risk for legionellosis was less for workers visiting the other cleaning lines and decreased with the lines’ distance from the cleaning line 0. Workers in the core area, the area farthest from cleaning, were least likely to have legionellosis. The association between visiting cleaning line 0 and having legionellosis was not confounded by history of family illness (workers with family members with symptoms [OR, 7.50; 95% CI, 0.65–87.19]; workers without family members with symptoms [OR, 8.15; 95% CI, 2.12–31.29; ORMH, 8.01; 95% CI, 2.46–26.05). Discussion. The tightly clustered dates for the onset of illness, the lack of epidemiological associations among the 4 workers with confirmed LD other than working in the plant, and the paucity of cases in the community that were not associated with the plant implicate the plant as the likely source of Legionella in this outbreak. The narrow period for onset of illness among the 4 workers with confirmed LD and the lack of new cases among plant workers suggest that exposure to the infecting strain of Legionella was short-lived. We did not find an environmental sample that matched the clinical isolate, perhaps because the exposure to the infecting strain of Legionella
Areas inside the automobile engine manufacturing plant, as risk factors for legionellosis. Case patients (n p17)
Control subjects (n p 86)
OR (95% CI)
9 (53)
22 (26)
3.22 (1.11–9.38)*
Core
3 (18)
41 (47)
0.23 (0.06–0.88)*
Molding
5 (29)
25 (29)
1.02 (0.32–3.19)
Melting
2 (12)
17 (20)
0.54 (0.11–2.60)
Area Work location Cleaning
Cleaning line 0
10 (63)
16 (19)
7.29 (2.31–23.00)*
Worked in cleaning area/visited line 0
7 (78)
2 (22)
2.92 (0.49–17.32)
Worked in other area/visited line 0
3 (42)
3 (5)
15.00 (2.26–99.64)*
1
8 (50)
18 (21)
3.67 (1.21–11.13)*
2
8 (50)
20 (23)
3.25 (1.08–9.77)*
3
3 (19)
17 (20)
0.91 (0.23–3.56)
5
4 (27)
9 (11)
3.03 (0.79–11.54)
10
4 (27)
13 (15)
1.99 (0.55–7.20)
NOTE. Data are no. (%) of case patients or control subjects. Working the evening shift (3–11 P.M.) was associated with legionellosis (case patients, 65%; control subjects 36%; odds ratio [OR], 3.19; 95% confidence interval [CI], 1.07–9.48), especially if working the evening shift was stratified by working in the cleaning area (case patients, 47%; control patients, 1%; OR, 8.80; 95% CI, 0.93–83.35). The following factors were not associated with legionellosis: using tools that emit steam or use a compressed air (pneumatic) source, visiting the power house or cooling tower, showering at work, or using respirators as protective equipment. *P ! .05.
BRIEF REPORT • JID 2003:187 (15 March) • 1017
was transient. Despite the lack of an environmental sample to help identify the source within the plant, our case-control study implicated the cleaning area of the plant, especially the area around the cleaning line 0, as the likely source of exposure. Although visiting other cleaning lines also was a risk for legionellosis, the risk decreased with each line’s distance from the cleaning line 0. The proximity of several of the affected workers to that area supports the conclusion that the area around the cleaning line 0 was the likely source of Legionella. We were unable to identify specific exposure sources or causes, such as recent construction, plumbing activities, or repaired machinery, that might explain a transient exposure in the area of cleaning line 0. It is possible that the delay between environmental sampling and detection of LD among workers reduced our ability to identify specific sources and to implement specific prevention strategies. Improved surveillance for LD, including early diagnostic tests for LD for industrial workers being treated for pneumonia, will improve our ability to identify sources of Legionella in the community and to prevent new outbreaks. The 4 workers with confirmed LD were probably exposed to Legionella during the last 2 weeks of February, and our investigation began mid-March. Therefore, we were unable to obtain acute and chronic serum samples from participants in the case-control study and to definitively prove acute exposure to Legionella. Some of the workers with elevated antibody titers may have been exposed before the event that exposed the 4 confirmed case patients or may have been exposed to a different source. Several studies have reported single-titer prevalence of anti–Legionella antibody ranging from 5% to 30% [7], although most of these prevalence surveys used IgG titers of 1:128 or 1: 256 as evidence of infection. To decrease misclassification, we used very high titers of IgGAM and IgM plus ⭓2 symptoms consistent with legionellosis. A recent outbreak investigation suggested that higher titers of anti–Legionella antibody from a single serum sample were associated with recent exposure [8]. Therefore, it seems unlikely that misclassification of workers with elevated antibody titers due to previous exposure significantly biased our results. Our identification of L. pneumophila in multiple environmental samples from the plant demonstrates that legionellae can survive in this work environment. Similarly, many industrial settings have water sources that meet the nutritional and
1018 • JID 2003:187 (15 March) • BRIEF REPORT
temperature requirements for Legionella growth and propagation, and workers often use equipment that allows transmission of Legionella-contaminated water droplets. This outbreak, another example of industrial exposure to Legionella that can result in serious illness among high-risk workers, provides further evidence that LD should be considered in the differential diagnosis of persons who work in industrial settings and present with an acute febrile respiratory illness with systemic symptoms, especially those with chronic diseases and a smoking habit.
Acknowledgments
We would like to acknowledge the help of Jeff Nemhauser (National Institute for Occupational Safety and Health), Centers for Disease Control and Prevention [CDC], Atlanta) and Melanie Gamble (National Center for Infectious Diseases, CDC); the staff at the Cuyahoga County Board of Health (Cleveland); Mary DiOrio and Daryl Koop (Ohio Department of Health, Cleveland); Terry Rhetta and Reilly Coch (Case Western Reserve University, Cleveland); the physicians and infection control practitioners in the greater Cleveland metropolitan region; and the plant employees and management who assisted with or participated in our investigation.
References 1. Marston BJ, Plouffe JF, File TM Jr, et al. Incidence of communityacquired pneumonia requiring hospitalization: results of a populationbased active surveillance. Arch Intern Med 1997; 157:1709–18. 2. Muraca PW, Stout JE, Yu VL, Yee YC. Legionnaires’ disease in the work environment: implications for environmental health. Am Ind Hyg Assoc J 1988; 49:584–90. 3. Gregersen P, Grunnet K, Uldum SA, Andersen BH, Madsen H. Pontiac fever at a sewage treatment plant in the food industry. Scand J Work Environ Health 1999; 25:291–5. 4. Herwaldt LA, Gorman GW, McGrath T, et al. A new Legionella species, Legionella feeleii species nova, causes Pontiac fever in an automobile plant. Ann Intern Med 1984; 100:333–8. 5. Centers for Disease Control and Prevention. Procedures for the recovery of Legionella from the environment. Atlanta: US Department of Health and Human Services, 1994. 6. Wilkinson HW. Hospital-laboratory diagnosis of Legionella infections. Atlanta: Centers for Disease Control and Prevention, 1988. 7. Fields BS, Benson RF, Besser RE. Legionella and legionnaires’ disease: 25 years of investigation. Clin Microbiol Rev 2002; 15:506–26. 8. Boshuizen HC, Neppelenbroek SE, van Vliet H, et al. Subclinical Legionella infection in workers near the source of a large outbreak of legionnaires’ disease. J Infect Dis 2001; 184:515–8.
