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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2010, Vol. 4 Issue (2) : 166-176     DOI: 10.1007/s11684-010-0036-3
Research articles |
Research advances of Legionella and Legionnaires’ disease
Xiao-Yong ZHAN MD,Chao-Hui HU PhD,Qing-Yi ZHU MD,
Guangzhou Kingmed Center for Clinical Laboratory, Guangzhou 510330, China;
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Abstract  Legionella is a causative agent of legionellosis or Legionnaires’ disease. Infection with Legionella spp. is an important cause of community and hospital-acquired pneumonia. Moreover, infection with Legionella is one of the most common causes of severe pneumonia in community settings, and Legionella is isolated in 40% of hospital-acquired pneumonia cases. The clinical features of legionellosis or Legionnaires’ disease are not unique, which makes the diagnosis challenging. Macrolides and fluoroquinolones are the most widely used drugs in treatment. Early recognition, treatment and effective measures for prevention and control of the disease are important and required. Although there have been a lot of methods for diagnosis of Legionella infection, they were often time-consuming or complex, not suitable for clinical purposes. This review summarizes available information regarding the microbiology, taxonomy, epidemiology, pathogenesis and diagnosis of Legionnaires’ disease, with an emphasis on the laboratory diagnosis of infection with Legionella spp.
Keywords Legionella      Legionella pneumophila      diagnosis      Legionnaires&#8217      disease      
Issue Date: 05 June 2010
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Thornsberry C, Balows A, Feeley J C, Jakubowski W. Proceedings of the Second International Symposium on Legionella. Washington D.C.: American Societyfor Microbiology, 1984, 277–280
Tatlock H. A Rickettsia-like organism recovered from guinea pigs. Proc Soc Exp Biol Med, 1944, 57(4): 95–99
Drozanski W. Fatal bacterial infection in soil amoebae. Acta Microbiol Pol, 1956, 5(3―4): 315–317
Hookey J V, Saunders N A, Fry N K, Birtles R J, Harrison T G. Phylogeny of legionellaceae based on small-subunit ribosomal DNA sequences and proposal of Legionella lytica comb. nov. for Legionella-like amoebal pathogens. Int J Syst Bacteriol, 1996, 46(2): 526–531

doi: 10.1099/00207713-46-2-526
Fraser D W, Tsai T R, Orenstein W, Parkin W E, Beecham H J, Sharrar R G, Harris J, Mallison G F, Martin S M, McDade J E, Shepard C C, Brachman P S. Legionnaires’ disease: description of an epidemicof pneumonia. N Engl J Med, 1977, 297(22): 1189–1197
McDade J E, Shepard C C, Fraser D W, Tsai T R, Redus M A, Dowdle W R. Legionnaires’ disease: isolationof a bacterium and demonstration of its role in other respiratorydisease. N Engl J Med, 1977, 297(22): 1197–1203
Garrity G M, Brown A, Vickers R M. Tatlockia and Fluorib-acter: two newgenera of organisms resembling Legionella pneumophila. Int J Syst Bacteriol, 1980, 30(4): 609–614

doi: 10.1099/00207713-30-4-609
Benson R F, Fields B S. Classification of the genus Legionella. Semin Respir Infect, 1998, 13(2): 90–99
Anonymous. Outbreak of Legionnaires’ disease associated withan aquarium in Australia. CDR Wkly, 2000, 10(18): 161
Pine L, George J R, Reeves M W, Harrell W K. Development of a chemically defined liquid mediumfor growth of Legionella pneumophila. J Clin Microbiol, 1979, 9(5): 615–626
Riffard S, Presti F L, Vandenesch F, Forey F, Reyrolle M, Etienne J. Comparative analysis of infrequent-restriction-sitePCR and pulsed-field gel electrophoresis for epidemiologicaltyping of Legionella pneumophila serogroup 1 strains. J Clin Microbiol, 1998, 36(1): 161–167
Harrison T G, Taylor A G. A laboratory manual for Legionella. New York: Wiley, 1988, 57–68
Vesey G, Dennis P J, Lee J V, West A A. Further development of simple tests to differentiatethe legionellas. J Appl Bacteriol, 1988, 65(4): 339–345
Ratcliff R M, Lanser J A, Manning P A, Heuzenroeder M W. Sequence-based classification schemefor the genus Legionella targeting the mip gene. J Clin Microbiol, 1998, 36(6): 1560–1567
Marston B J, Plouffe J F, File T M Jr, Hackman B A, Salstrom S J, Lipman H B, Kolczak M S, Breiman R F. Incidence of community-acquired pneumonia requiring hospitalization—resultsof a population-based active surveillance study in Ohio. Arch Intern Med, 1997, 157(15): 1709–1718

doi: 10.1001/archinte.157.15.1709
Fields B S, Benson R F, Besser R E. Legionella and Legionnaires’disease: 25 years of investigation. J Clin Microbiol, 2002, 15(3): 506–526

doi: 10.1128/CMR.15.3.506-526.2002
Barbaree J M, Fields B S, Feeley J C, Gorman G W, Martin W T. Isolation of protozoa from water associated with a legionellosisoutbreak and demonstration of intracellular multiplication of Legionellapneumophila. Appl Environ Microbiol, 1986, 51(2): 422–424
Heath C H, Grove D I, Looke D F. Delay in appropriate therapy of Legionella-pneumoniaassociated with increased mortality. Eur J Clin Microbiol Infect Dis, 1996, 15(4): 286–290

doi: 10.1007/BF01695659
Edelstein P H. Antimicrobial chemotherapy for Legionnaires’ disease:time for a change. Ann Intern Med, 1998, 129(4): 328–330
Stout J E, Yu V L. Legionellosis. N Engl J Med, 1997(9), 337: 682–687

doi: 10.1056/NEJM199709043371006
Horwitz M A, Maxfield F R. Legionella pneumophila inhibits acidification of its phagosomein human monocytes. J Cell Biol, 1984, 99(6): 1936–1943

doi: 10.1083/jcb.99.6.1936
Rowbotham T J. Current views on the relationships between amoebae, legionellaeand man. Isr J Med Sci, 1986, 22(6): 678–689
Fields B S. The molecular ecology of legionellae. Trends Microbiol, 1996, 4(7): 286–290

doi: 10.1016/0966-842X(96)10041-X
Hägele S, Köhler R, Merkert H, Schleicher M, Hacker J, Steinert M. Dictyostelium discoideum:a new host model system for intracellular pathogens of the genus Legionella. Cell Microbiol, 2000, 2(2): 165–171

doi: 10.1046/j.1462-5822.2000.00044.x
Solomon J M, Rupper A, Cardelli J A, Isberg R R. Intracellular growth of Legionella pneumophila in Dictyosteliumdiscoideum, a system for genetic analysis of host-pathogen interactions. Infect Immun, 2000, 68(5): 2939–2947

doi: 10.1128/IAI.68.5.2939-2947.2000
Muder R R, Yu V L, Woo A H. Mode of transmission of Legionella pneumophila. Arch Intern Med, 1986, 146(8): 1607–1612

doi: 10.1001/archinte.146.8.1607
Zusman T, Yerushalmi G, Segal G. Functional Similarities betweenthe icm/dot Pathogenesis Systems of Coxiella burnetii and Legionellapneumophila. Infect Immun, 2003, 71(7): 3714–3723

doi: 10.1128/IAI.71.7.3714-3723.2003
Pan X, Lührmann A, Satoh A, Laskowski-Arce M A, Roy C R. Ankyrin repeat proteins comprise a diverse family of bacterial typeIV effectors. Science, 2008, 320(5883): 1651–1654

doi: 10.1126/science.1158160
Cazalet C, Rusniok C, Brüggemann H, Zidane N, Magnier A, Ma L, Tichit M, Jarraud S, Bouchier C, Vandenesch F, Kunst F, Etienne J, Glaser P, Buchrieser C. Evidence in the Legionellapnuemophila genome for exploitation of host cell functions and highgenome plasticity. Nat Genet, 2004, 36(10): 1165–1173

doi: 10.1038/ng1447
Marra A, Blander S J, Horwitz M A, Shuman H A. Identification of a Legionella pneumophila locus requiredfor intracellular multiplication in human macrophages. Proc Natl Acad Sci USA, 1992, 89(20): 9607–9611

doi: 10.1073/pnas.89.20.9607
Berk S G, Faulkner G, Garduño E, Joy M C, Ortiz-Jimenez M A, Garduño R A. Packaging of Live Legionella pneumophila into Pellets Expelled by Tetrahymena spp.does not require bacterial replication and depends on a Dot/Icm-mediatedsurvival mechanism. Appl Environ Microbiol, 2008, 74(7): 2187–2199

doi: 10.1128/AEM.01214-07
Segal G, Feldman M, Zusman T. The Icm/Dot type-IV secretionsystems of Legionella pneumophila and Coxiella burnetii. FEMS Microbiol Rev, 2005, 29(1): 65–81

doi: 10.1016/j.femsre.2004.07.001
Cianciotto N P. Pathogenicity of Legionella pneumophila. Int J Med Microbiol, 2001, 291(5): 331–343

doi: 10.1078/1438-4221-00139
Ricketts K D, Joseph C A; European Working Group for Legionella Infections. Legionnaires diseasein Europe: 2005―2006. Euro Surveill, 2007, 12(12): E7–8
Huang B, Yuan Z, Heron B A, Gray B R, Eglezos S, Bates J R, Savill J. Distribution of 19 major virulence genes in Legionella pneumophila serogroup 1isolates from patients and water in Queensland, Australia. J Med Microbiol, 2006, 55(8): 993–997

doi: 10.1099/jmm.0.46310-0
Zhu Q Y, Hu Z H, Liang Y M. Genotyping identification of pathogenicityisland locus for Legionella pneumophila. Chin J Med Lab Technol, 2007, 3(1): 5–12
Cirillo J D, Cirillo S L, Yan L, Bermudez L E, Falkow S, Tompkins L S. Intracellular growth in Acanthamoebacastellanii affects monocyte entry mechanisms and enhances virulenceof Legionella pneumophila. Infect Immun, 1999, 67(9): 4427–4434
Feeley J C, Gorman G W, Weaver R E, Mackel D C, Smith H W. Primary isolationmedia for Legionnaires’ disease bacterium. J Clin Microbiol, 1978, 8(3): 320–325
Edelstein P H. Antimicrobial chemotherapy for Legionnaires’ disease:time for a change. Ann Intern Med, 1998, 129(4): 328–330
Edelstein P H. Improved semiselective medium for isolation of Legionellapneumophila from contaminated clinical and environmental specimens. J Clin Microbiol, 1981, 14(3): 298–303
Pasculle A W, Feeley J C, Gibson R J, Cordes L G, Myerowitz R L, Patton C M, Gorman G W, Carmack C L, Ezzell J W, Dowling J N. Pittsburgh pneumonia agent: direct isolation from humanlung tissue. J Infect Dis, 1980, 141(6): 727–732
Vickers R M, Brown A, Garrity G M. Dye-containing buffered charcoal-yeastextract medium for differentiation of members of the family Legionellaceae. J Clin Microbiol, 1981, 13(2): 380–382
Morrill W E, Barbaree J M, Fields B S, Sanden G N, Martin W T. Increased recovery of Legionella micdadei and Legionella bozemaniion buffered charcoal yeast extract agar supplemented with albumin. J Clin Microbiol, 1990, 28(3): 616–618
Edelstein P H. The laboratory diagnosis of Legionnaires’ disease. Semin Respir Infect, 1987, 2(4): 235–241
Maiwald M, Helbig J H, Luck P C. Laboratory methods for thediagnosis of Legionella infections. J Microbiol Methods, 1998, 33(1): 59–79

doi: 10.1016/S0167-7012(98)00041-4
Edelstein P H. Legionnaires’ disease. Clin Infect Dis, 1993, 16(2): 741–749
Ingram J G, Plouffe J F. Danger of sputum purulence screens in culture of Legionella species. J Clin Microbiol, 1994, 32(1): 209–210
Roig J, Domingo C, Morera J. Legionnaires’ disease. Chest, 1994, 105(6): 1817–1825

doi: 10.1378/chest.105.6.1817
Rowbotham T J. Isolation of Legionella pneumophila serogroup 1 fromhuman feces with use of amebic cocultures. Clin Infect Dis, 1998, 26(2): 502–503

doi: 10.1086/517095
Buesching W J, Brust R A, Ayers W. Enhanced primary isolation of Legionellapneumophila from clinical specimens by low-pH treatment. J Clin Microbiol, 1983, 17(6): 1153–1155
Edelstein P H, Snitzer J B, Bridge J A. Enhancement of recovery ofLegionella pneumophila from contaminated respiratory tract specimensby heat. J Clin Microbiol, 1982, 16(6): 1061–1065
Farshy C E, Cruce D D, Klein G C, Wilkinson H W, Feeley J C. Immunoglobulin specificityof the microagglutination test for the Legionnaires’ diseasebacterium. Ann Intern Med, 1979, 90(4): 690
Klein G C, Jones W L, Feeley J C. Upper limit of normal titer for detectionof antibodies to Legionella pneumophila by the microaggluti- nationtest. J Clin Microbiol, 1979, 10(5): 754–755
Holliday M. Counterimmunoelectrophoresis in the serodiagnosis ofLegionnaires’ disease. J Clin Pathol, 1983, 36(4): 466–470

doi: 10.1136/jcp.36.4.466
Holliday M G. Use of latex agglutination technique for detecting Legionellapneumophila (serogroup 1) antibodies. J Clin Pathol, 1990, 43(10): 860–862

doi: 10.1136/jcp.43.10.860
Harrison T G, Taylor A G. A laboratory manual for Legionella, Chichester: John Wiley and Sons, Ltd., 1988, 1: 113–135
Boswell T C. Serological cross reaction between Legionella and Campylobacterin the rapid microagglutination test. J Clin Pathol, 1996, 49(7): 584–586

doi: 10.1136/jcp.49.7.584
Bangsborg J M, Shand G H, Hansen K, Wright J B. Performance of four different indirect enzyme-linked immunosorbentassays (ELISAs) to detect specific IgG, IgA, and IgM in Legionnaires’disease. APMIS, 1994, 102(7): 501–508

doi: 10.1111/j.1699-0463.1994.tb05197.x
Wilkinson H W, Reingold A L, Brake B J, McGiboney D L, Gorman G W, Broome C V. Reactivity of serum frompatients with suspected legionellosis against 29 antigens of legionellaceaeand Legionella like organisms by indirect immunofluorescenceassay. J Infect Dis, 1983, 147(1): 23–31
Taylor A G, Harrison T G. Serological tests for Legionella pneumophila serogroup 1 infections. Zentralbl Bakteriol Mikrobiol Hyg A, 1983, 255(1): 20–26
Bangsborg J M, Shand G, Pearlman E, Hoiby N. Cross-reactive Legionella antigens and the antibody response during infection. APMIS, 1991, 99(9): 854–865

doi: 10.1111/j.1699-0463.1991.tb01271.x
Neumeister B, Susa M, Nowak B, Straube E, Ruckdeschel G, Hacker J, Marre R. Enzyme immunoassayfor detection of antibodies against isolated flagella of Legionellapneumophila. Eur J Clin Microbiol InfectDis, 1995, 14(9): 764–767

doi: 10.1007/BF01690990
Wilkinson H W, Farshy C E, Fikes B J, Cruce D D, Yealy L P. Measure of immunoglobulin G-, M-, and A-specific titers against Legionellapneumophila and inhibition of titers against nonspecific, gram-negativebacterial antigens in the indirect immunofluorescence test forlegionellosis. J Clin Microbiol, 1979, 10(5): 685–689
Edelstein P H. Manual of clinical laboratory immunology, Washington, D.C.: American Society for Microbiology, 1997, 502–509
De Ory F, Echevarria J M, Pelaz C, Téllez A, Mateo M A, López J. Detection of specificIgM antibody in the investigation of an outbreak of pneumonia dueto Legionella pneumophila serogroup 1. Clin Microbiol Infect, 2000, 6(2): 64–69

doi: 10.1046/j.1469-0691.2000.00050.x
Starnbach M N, Falkow S, Tompkins L S. Species-specific detectionof Legionella pneumophila in water by DNA amplification and hybridization. J Clin Microbiol, 1989, 27(6): 1257–1261
Mahbubani M H, Bej A K, Miller R, Haff L, DiCesare J, Atlas R M. Detection of Legionella with polymerase chain reactionand gene probe methods. Mol Cell Probes, 1990, 4(3): 175–187

doi: 10.1016/0890-8508(90)90051-Z
Jonas D, Rosenbaum A, Weyrich S, Bhakdi S. Enzyme-linked immunoassay for detection of PCR-amplifiedDNA of legionellae in bronchoalveolar fluid. J Clin Microbiol, 1995, 33(5): 1247–1252
Miyamoto H, Yamamoto H, Arima K, Fujii J, Maruta K, Izu K, Shiomori T, Yoshida S. Development of a new seminested PCR method for detection of Legionella speciesand its application to surveillance of legionellae in hospital coolingtower water. Appl Environ Microbiol, 1997, 63(7): 2489–2494
Matsiota-Bernard P, Pitsouni E, Legakis N, Nauciel C. Evaluation of commercial amplification kit for detectionof Legionella pneumophila in clinical specimens. J Clin Microbiol, 1994, 32(6): 1503–1505
Helbig J H, Engelstädter T, Maiwald M, Uldum S A, Witzleb W, Lück P C. Diagnostic relevance of thedetection of Legionella DNA in urine samples by the polymerase chainreaction. Eur J Clin Microbiol Infect Dis, 1999, 18(10): 716–722

doi: 10.1007/s100960050384
Matsiota-Bernard P, Waser S, Vrioni G. Detection of Legionella pneumophilaDNA in urine and serum samples from patients with pneumonia. Clin Microbiol Infect, 2000, 6(4): 223–225

doi: 10.1046/j.1469-0691.2000.00041-2.x
Murdoch D R, Chambers S T. Detection of Legionella DNA in peripheral leukocytes, serum, andurine from a patient with pneumonia caused by Legionella dumoffii. Clin Infect Dis, 2000, 30(2): 382–383

doi: 10.1086/313656
Socan M, Kese D, Marinic-Fisher N. Polymerase chain reactionfor detection of Legionellae DNA in urine samples from patients withcommunity-acquired pneumonia. Folia Microbiol, 2000, 45(5): 469–472

doi: 10.1007/BF02817623
Cloud J L, Carroll K C, Pixton P, Erali M, Hillyard D R. Detection of Legionella species in respiratory specimens using PCRwith sequencing confirmation. J Clin Microbiol, 2000, 38(5): 1709–1712
Ballard A L, Fry N K, Chan L, Surman S B, Lee J V, Harrison T G, Towner K J. Detection of Legionella pneumophila using a real-time PCR hybridizationassay. J Clin Microbiol, 2000, 38(11): 4215–4218
Hayden R T, Uhl J R, Qian X, Hopkins M K, Aubry M C, Limper A H, Lloyd R V, Cockerill F R. Direct detection of Legionellaspecies from bronchoalveolar lavage and open lung biopsy specimens:comparisonof LightCycler PCR, in situ hybridization, direct fluorescenceantigen detection and culture. J Clin Microbiol, 2001, 39(7): 2618–2626

doi: 10.1128/JCM.39.7.2618-2626.2001
Zhan X Y, Li L Q, Hu C H, Zhu Q Y. Two-step scheme for rapid identification and differentiationof Legionella pneumophila and non-Legionella pneumophila species. J Clin Microbiol, 2010, 48(2): 433–439

doi: 10.1128/JCM.01778-09
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