CLINICAL MICROBIOLOGY REVIEWS, July 2002, p. 506–526 Vol. 15, No. 3 0893-8512/02/$04.00ϩ0 DOI: 10.1128/CMR.15.3.506–526.2002 Legionella and Legionnaires’ Disease: 25 Years of Investigation Barry S. Fields,* Robert F. Benson, and Richard E. Besser Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Disease, Centers for Disease Control and Prevention, Atlanta, Georgia 30333 INTRODUCTION .......................................................................................................................................................506 Clinical Presentation..............................................................................................................................................506 Microbial Ecology ...................................................................................................................................................507 Association with Amoebae .....................................................................................................................................507 Association with Biofilms.......................................................................................................................................507 Downloaded from PATHOGENESIS........................................................................................................................................................508 The Intracellular Cycle ..........................................................................................................................................508 Identification of Virulence Determinants by Molecular Techniques...............................................................510 DIAGNOSIS ................................................................................................................................................................510 Taxonomy.................................................................................................................................................................510 Culture of Legionella...............................................................................................................................................512 DFA Detection of Legionella ..................................................................................................................................512 Serologic Diagnosis.................................................................................................................................................513 Urine Antigen Detection ........................................................................................................................................514 http://cmr.asm.org/ Detection of Legionella Nucleic Acid ....................................................................................................................515 Subtyping of Legionella spp. ..................................................................................................................................516 EPIDEMIOLOGIC TRENDS....................................................................................................................................517 Incidence ..................................................................................................................................................................517 Treatment.................................................................................................................................................................517 Travel-Related Legionnaires’ Disease in the United States .............................................................................518 Community Outbreaks and Prevention ...............................................................................................................518 Nosocomial Outbreaks and Prevention ...............................................................................................................519 Potential Impact of Monochloramine ..................................................................................................................520 on April 16, 2016 by Richard Gilpin FUTURE DIRECTIONS AND CONCLUSIONS....................................................................................................520 ACKNOWLEDGMENT..............................................................................................................................................520 REFERENCES ............................................................................................................................................................520 INTRODUCTION to multiply within mammalian cells (91). These bacteria cause respiratory disease in humans when a susceptible host inhales Legionnaires’ disease has a false but enduring status as an aerosolized water containing the bacteria or aspirates water exotic plague. In reality, this disease is a common form of containing the bacteria. severe pneumonia, but these infections are infrequently diag- nosed. Failure to diagnose Legionnaires’ disease is largely due to a lack of clinical awareness. In addition, legionellae, the bacteria that cause this disease, are fastidious and not easily Clinical Presentation detected. Legionellosis classically presents as two distinct clinical en- Legionellae are gram-negative bacteria found in freshwater tities, Legionnaires’ disease, a severe multisystem disease in- environments. The first strains of Legionella were isolated in volving pneumonia (104), and Pontiac fever, a self-limited flu- guinea pigs by using procedures for the isolation of Rickettsia like illness (114). Additionally, many persons who seroconvert (203). The first was isolated in 1943 by Tatlock, with another to Legionella will be entirely asymptomatic (33). strain isolated in 1947 by Jackson et al. (268). In 1954, Drozan- It is not possible to clinically distinguish patients with Le- ski isolated a bacterium that infected free-living amoebae from gionnaires’ disease from patients with other types of pneumo- soil in Poland (68). This organism was classified as a species of nia (76). Features of Legionnaires’ disease include fever, non- Legionella in 1996 (143). The genus Legionella was established productive cough, headache, myalgias, rigors, dyspnea, in 1979 after a large outbreak of pneumonia among members diarrhea, and delirium (273). Although no chest X-ray pattern of the American Legion that had occurred 3 years earlier (38, can separate this infection from other types of pneumonia, 104) and was traced to a previously unrecognized bacterium, alveolar infiltrates are more common with Legionnaires’ dis- Legionella pneumophila (203). Legionellae are intracellular ease (188). The key to diagnosis is performing appropriate parasites of freshwater protozoa and use a similar mechanism microbiologic testing when a patient is in a high-risk category. There is some debate as to whether Legionnaires’ disease * Corresponding author. Mailing address: CDC, Mailstop GO3, presents as a clinical spectrum or whether the only manifesta- 1600 Clifton Road, Atlanta, GA 30333. Phone: (404) 639-3563. Fax: tion of disease is pneumonia. In a study of persons exposed to (404) 639-4215. E-mail: bfi[email protected]. L. pneumophila who did not develop pneumonia during a large 506 VOL. 15, 2002 LEGIONELLA: 25 YEARS 507 outbreak of Legionnaires’ disease in the Netherlands, there can shift the balance between protozoa and bacteria, resulting was no difference in the rate of respiratory symptoms between in rapid multiplication of legionellae, which can translate into those who were seropositive and those who were seronegative. human disease. Legionellosis is a disease that has emerged in This would suggest that patients either develop pneumonia or the last half of the 20th century because of human alteration of are asymptomatic (33). Outbreaks of legionellosis have oc- the environment. Left in their natural state, legionellae would curred in which some patients develop Legionnaires’ disease be an extremely rare cause of human disease, as natural fresh- and others Pontiac fever (21). water environments have not been implicated as reservoirs of One species of Legionella, L. pneumophila, causes approxi- outbreaks of legionellosis. Some outbreaks of legionellosis mately 90% of all reported cases of legionellosis in the United have been associated with construction, and it was originally States (199; R. E. Besser, unpublished data). This figure may believed that the bacteria could survive and be transmitted to be inflated because most diagnostic tests are specific for L. humans via soil. However, L. pneumophila does not survive in pneumophila. Currently, there are 48 species comprising 70 dry environments, and these outbreaks are more likely the distinct serogroups in the genus Legionella (5, 23, 184, 185). result of massive descalement of plumbing systems due to Although there are now 15 serogroups of L. pneumophila, 79% changes in water pressure during construction (159, 205). Downloaded from of all culture-confirmed or urine antigen-confirmed cases are caused by L. pneumophila serogroup 1 (199; A. L. Benin and Association with Amoebae R. E. Besser, Abstr. 41st Intersci. Conf. Antimicrob. Agents Chemother., abstr. 873, 2001). Approximately one-half of the The presence of the bacteria in an aquatic environment and 48 species of legionellae have been associated with human warm water temperature are two factors that can increase the disease. Since all legionellae are