PRESENCE OF LEGIONELLA PNEUMOPHILA IN TAP WATER AND ITS IMPORTANCE FOR PUBLIC HEALTH

Yıl 2024, Cilt: 15 Sayı: 2, 64 - 76, 31.08.2024

Ömer Çakmak , Tuba Aldemir , Erdi Ergene , Ulaş Acaröz , Damla Arslan-acaroz , Nuri Taş

https://doi.org/10.38137/vftd.1432171

Öz

Legionella pneumophila is one of the Legionella species that has been implicated in outbreaks of Legionnaires' disease in many countries, particularly in the United States of America (USA), which is caused by tap water, resulting in severe pneumonia and a mortality rate of 7 to 10%. The majority of outbreaks were linked to buildings with plumbing systems (healthcare facilities, hospitals, large buildings, etc.) and specially designed water systems (cooling towers, fountains, showers, etc.), which are optimal sources for the growth of Legionella spp. Infections caused by L. pneumophila are more likely to be caused by hot water in showers, while L. anisa appears to be more likely to cause infections from cold water in taps. Aging municipal water infrastructure, main line outages and leaks in the system are cited as reasons for the transmission of microorganisms, which are difficult to remove from plumbing systems. In addition, climatic changes such as temperature and precipitation are other factors that contribute to the spread of Legionella spp. in water systems and expose more people to the pathogen. In 2023, the outbreak of L. pneumophila in Poland, which resulted in the death of 14 people, brought the importance of Legionnaires' disease back to the agenda. In this review; the epidemiology, transmission routes and detection methods of L. pneumophila, the most important agent of the disease, were revealed in order to prevent and control Legionnaires' disease outbreaks by searching the current literature. Also included is the treatment of Legionnaires' disease.

Anahtar Kelimeler

Legionella pneumophila, Legionnaires disease, tap water, water pollution

ŞEBEKE SULARINDA LEGIONELLA PNEUMOPHILA VARLIĞI VE HALK SAĞLIĞI AÇISINDAN ÖNEMİ

Öz

Legionella pneumophila; başta Amerika Birleşik Devletleri (ABD) olmak üzere bir çok ülkede şebeke suyu kaynaklı olarak ortaya çıkan, ciddi zatürre ile seyreden ve %7 ila 10 ölüm oranına sahip Lejyoner hastalığı salgınlarına neden olan Legionella türlerinden biridir. Görülen salgınlarının çoğunluğu, Legionella spp.’nin gelişimi için en uygun kaynaklar olan sıhhi tesisat sistemleri (sağlık tesisleri, hastaneler, büyük binalar vb.) ve özel tasarlanmış su sistemlerine (soğutma kuleleri, çeşmeler, duşlar vb.) sahip binalarla ilişkilendirilmiştir. L. pneumophila’nın neden olduğu enfeksiyonlar daha çok duşlardaki sıcak su kaynaklı iken, L. anisa'nın musluklardaki soğuk sudan kaynaklanan enfeksiyon yapabilme riskinin daha yüksek olduğu görülmektedir. Eskiyen şebeke suyu altyapısı, ana hat kesintileri ve sistemdeki sızıntılar mikroorganizmaların bulaşmasına neden olarak gösterilmekte ve bulaşının tesisat sistemlerinden uzaklaştırılması oldukça zor olmaktadır. Bununla birlikte sıcaklık ve yağış gibi iklimsel değişiklikler de Legionella spp.’nin su sistemlerinde yayılmasına ve daha fazla kişinin etkene maruz kalmasına zemin hazırlayan diğer etkenlerdir. 2023 yılında Polonya’da yaşanan ve 14 kişinin ölümüyle sonuçlanan L. pneumophila kaynaklı salgının ortaya çıkması Lejyoner hastalığının önemini yeniden gündeme getirmiştir. Bu derlemede; güncel literatür taraması yapılarak Lejyoner hastalığı salgınlarının önlenmesi ve kontrol altına alınması amacıyla hastalığın en önemli etkeni L. pneumophila’nın epidemiyolojisi, bulaşma yolları ve tespit yöntemleri ortaya konulmuştur. Ayrıca Lejyoner hastalığının tedavisine de yer verilmiştir.

Anahtar Kelimeler

Legionella pneumophila, Lejyoner hastalığı, şebeke suyu, su kirliliği

Kaynakça

• Abbott, Z. D., Yakhnin, H., Babitzke, P. & Swanson, M. S. (2015). csrR, a paralog and direct target of CsrA, promotes Legionella pneumophila resilience in water. MBio, 6(3), e00595.
• Abdel-Nour, M., Duncan, C., Low, D. E. & Guyard, C. (2013). Biofilms: the stronghold of Legionella pneumophila. International Journal of Molecular Sciences, 14(11), 21660-21675.
• Abu Khweek, A. & Amer, A. O. (2018). Factors mediating environmental biofilm formation by Legionella pneumophila. Frontiers in Cellular and Infection Microbiology, 8, 38.
• Albalat, G. R., Broch, B. B. & Bono, M. J. (2014). Method modification of the Legipid® Legionella fast detection test kit. Journal of AOAC International, 97(5), 1403-1409.
• American Public Health Association (APHA) (2007). 9260J: detection of pathogenic bacteria: Legionella. Stand. Methods Exam. Water Wastewater, 22nd edn. American Public Health Association. 28–32.
• American Society of Heating Refrigeration and Air Conditioning Engineers (ASHRAE) (2015). Legionellosis: risk management for building water systems. ANSI/ASHRAE Standard 188–2015. Atlanta. ANSI/ASHRAE Addendum h to ANSI/ASHRAE Standard188-2015.
• Anonymous (2014). “Safety Code,” can be found under. Erişim Adresi: http://www.legisquebec.gouv.qc.ca/en/document/cr/B-1.1,%20r.%203/20140712#se:4172014.
• Anonymous (2020). National Academies of Sciences Engineering Medicine. Management of Legionella in Water Systems. Washington, DC: The National Academies Press, 290 p.
• Aurass, P., Gerlach, T., Becher, D., Voigt, B., Karste, S., Bernhardt, J., Riedel, K., Hecker, M. & Flieger, A. (2016). Life stage-specific proteomes of Legionella pneumophila reveal a highly differential abundance of virulence-associated Dot/Icm effectors. Molecular & Cellular Proteomics, 15(1), 177-200.
• Bai, L., Yang, W. & Li, Y. (2023). Clinical and Laboratory Diagnosis of Legionella Pneumonia. Diagnostics, 13(2), 280.
• Barskey, A. E., Derado, G. & Edens, C. (2022). Rising incidence of Legionnaires’ disease and associated epidemiologic patterns, United States, 1992–2018. Emerging Infectious Diseases, 28(3), 527-538.
• Beer, K. D., Gargano, J. W., Roberts, V. A., Hill, V. R., Garrison, L. E., Kutty, P. K., Hilborn, E. D., Wade, T. J., Fullerton, K. E. & Yoder, J. S. (2015). Surveillance for waterborne disease outbreaks associated with drinking water-United States, 2011-2012. Morbidity and Mortality Weekly Report, 64(31), 842.
• Benedict, K. M., Reses, H., Vigar, M., Roth, D. M., Roberts, V. A., Mattioli, M., Cooley, L. A., Hilborn, E. D., Wade, T. J., Fullerton, K. E., Yoder, J. S. & Hill, V. R. (2017). Surveillance for waterborne disease outbreaks associated with drinking water-United States, 2013–2014. Morbidity and Mortality Weekly Report, 66(44), 1216.
• Boamah, D. K., Zhou, G., Ensminger, A. W. & O'Connor, T. J. (2017). From many hosts, one accidental pathogen: the diverse protozoan hosts of Legionella. Frontiers in Cellular and Infection Microbiology, 7, 477.
• Bollin, G. E., Plouffe, J. F., Para, M. F. & Hackman, B. (1985). Aerosols containing Legionella pneumophila generated by shower heads and hot-water faucets. Applied and Environmental Microbiology, 50(5), 1128-1131.
• Burgos, R. M. & Rodvold, K. A. (2019). Omadacycline: a novel aminomethylcycline. Infection and Drug Resistance, 12, 1895-1915.
• Burstein, D., Amaro, F., Zusman, T., Lifshitz, Z., Cohen, O., Gilbert, J. A., Pupko, T., Shuman, H. A. & Segal, G. (2016). Genomic analysis of 38 Legionella species identifies large and diverse effector repertoires. Nature Genetics, 48(2), 167-175.
• Buse, H. Y., Ji, P., Gomez‐Alvarez, V., Pruden, A., Edwards, M. A. & Ashbolt, N. J. (2017). Effect of temperature and colonization of Legionella pneumophila and Vermamoeba vermiformis on bacterial community composition of copper drinking water biofilms. Microbial Biotechnology, 10(4), 773-788.
• Cassell, K., Davis, J. L. & Berkelman, R. (2021). Legionnaires’ disease in the time of COVID-19. Pneumonia, 13, 1-3.
• Centers for Disease Control and Prevention (2017). Developing a water management program to reduce Legionella growth and spread in buildings: A practical guide to implementing industry standard. Legionella Toolkit-Updated June 5, 2017 Version 1.1 (proasysinc.com).
• Chahin, A. & Opal, S. M. (2017). Severe pneumonia caused by Legionella pneumophila: differential diagnosis and therapeutic considerations. Infectious Disease Clinics, 31(1), 111-121.
• Collier, S. A., Stockman, L. J., Hicks, L. A., Garrison, L. E., Zhou, F. J. & Beach, M. J. (2012). Direct healthcare costs of selected diseases primarily or partially transmitted by water. Epidemiology & Infection, 140(11), 2003-2013.
• Collins, S., Jorgensen, F., Willis, C. & Walker, J. (2015). Real‐time PCR to supplement gold‐standard culture‐based detection of Legionella in environmental samples. Journal of Applied Microbiology, 119 (4), 1158-1169.
• Collins, S., Stevenson, D., Walker, J. & Bennett, A. (2017). Evaluation of Legionella real‐time PCR against traditional culture for routine and public health testing of water samples. Journal of Applied Microbiology, 122(6), 1692-1703.
• Craun, G. F. & Calderon, R. L. (2001). Waterborne disease outbreaks caused by distribution system deficiencies. Journal‐American Water Works Association, 93(9), 64-75.
• Cross, K. E., Mercante, J. W., Benitez, A. J., Brown, E. W., Diaz, M. H. & Winchell, J. M. (2016). Simultaneous detection of Legionella species and L. anisa, L. bozemanii, L. longbeachae and L. micdadei using conserved primers and multiple probes in a multiplex real-time PCR assay. Diagnostic Microbiology and Infectious Disease, 85(3), 295-301.
• Cunha, B. A., Burillo, A. & Bouza, E. (2016). Legionnaires' disease. The Lancet, 387(10016), 376-385.
• De Filippis, P., Mozzetti, C., Messina, A. & D'Alò, G. L. (2018). Prevalence of Legionella in retirement homes and group homes water distribution systems. Science of the Total Environment, 643, 715-724.
• Ditommaso, S., Giacomuzzi, M., Ricciardi, E. & Zotti, C. M. (2015). Viability-qPCR for detecting Legionella: Comparison of two assays based on different amplicon lengths. Molecular and Cellular Probes, 29(4), 237-243.
• Dooling, K. L., Toews, K. A., Hicks, L. A., Garrison, L. E., Bachaus, B., Zansky, S., Carpenter, L. R., Schaffner, B., Parker, E., Petit, S., Thomas, A., Thomas, S., Robert Mansmann, R., Morin, C., White, B. & Langley, G. E. (2015). Active bacterial core surveillance for legionellosis-United States, 2011-2013. Morbidity and Mortality Weekly Report, 64(42), 1190-1193.
• Dubois, J., Dubois, M. & Martel, J. F. (2020). In vitro and intracellular activities of omadacycline against Legionella pneumophila. Antimicrobial Agents and Chemotherapy, 64(5), e01972-19.
• Dybwad, M., Aarskaug, T., Fykse, E. M., Henie Madslien, E. & Blatny, J. M. (2016). Complete genome sequences of six Legionella pneumophila isolates from two collocated outbreaks of legionnaires' disease in 2005 and 2008 in Sarpsborg/Fredrikstad, Norway. Genome Announcements, 4(6), e01367-16.
• Ellington, A. D. & Szostak, J. W. (1990). In vitro selection of RNA molecules that bind specific ligands. Nature, 346(6287), 818-822.
• Environmental Protection Agency (EPA) (2002). National primary drinking water regulations: long term 1 enhanced surface water treatment rule. Final rule. Federal Register, 67(9), 1811-1844.
• Environmental Protection Agency (EPA) (2016). Technologies for Legionella Control in Premise Plumbing Systems: Scientific Literature Review. EPA 810-R-16-001. Technologies for Legionella Control in Premise Plumbing Systems: Scientific Literature Review (epa.gov)
• Erdogan, H. & Arslan, H. (2007). Colonization of Legionella species in hotel water systems in Turkey. Journal of Tavel Medicine, 14(6), 369-373.
• Erdoğan, H. & Arslan, H. (2013). Yeni Açılan Bir Otelde Ortaya Çıkan Legionella Salgınının İrdelenmesi. Mikrobiyoloji Bülteni, 47(2), 240-249.
• Erdogan, H., Turan, H., Hasimoğlu, R., OK Azap, O. K. & Arslan, H. (2009). Colonization of Legionella species in hospital water systems in Turkey. 7th International Conference Legionella, Paris, 2009, P184.
• Euronews (2023). Eleven people die from Legionnaires’ disease outbreak in Polish town of Rzeszow. Eleven people die from Legionnaires’ disease outbreak in Polish town of Rzeszow | Euronews.
• European Centre for Disease Prevention and Control (ECDC) (2018). Legionnaires’ disease: Annual Epidemiological Report for 2016. Stockholm: ECDC.
• European Centre for Disease Prevention and Control (ECDC) (2021). Legionnaires’ disease: Annual Epidemiological Report for 2019. Stockholm: ECDC.
• European Centre for Disease Prevention and Control (ECDC) (2022). Legionnaires’ disease: Annual Epidemiological Report for 2020. Stockholm: ECDC.
• Falkinham III, J. O. (2020). Living with Legionella and other waterborne pathogens. Microorganisms, 8(12), 2026.
• Fields, B. S. (1996). The molecular ecology of legionellae. Trends in microbiology, 4(7), 286-290.
• Fields, B. S., Benson, R. F. & Besser, R. E. (2002). Legionella and Legionnaires' disease: 25 years of investigation. Clinical Microbiology Reviews, 15(3), 506-526.
• Fisher, K. E., Wickenberg, L. P., Leonidas, L. F., Ranz, A. A., Habib, M. A., Buford, R. M. & McCoy, W. F. (2020). Next Day Legionella PCR: a highly reliable negative screen for Legionella in the built environment. Journal of Water and Health, 18(3), 345-357.
• Fisher-Hoch, S. P., Smith, M. G. & Colbourne, J. S. (1982). Legionella pneumophila in hospital hot water cylinders. The Lancet, 319(8280), 1073.
• Fitzhenry, R., Weiss, D., Cimini, D., Balter, S., Boyd, C., Alleyne, L., Stewart, R., McIntosh, N., Econome, A., Lin, Y., Rubinstein, I., Passaretti, T., Kidney, A., Lapierre, P., Kass, D. & Varma, J. K. (2017). Legionnaires’ disease outbreaks and cooling towers, New York city, New York, USA. Emerging Infectious Diseases, 23(11), 1769-1776.
• Fiume, L., Bucca Sabattini, M. A. & Poda, G. (2005). Detection of Legionella pneumophila in water samples by species‐specific real‐time and nested PCR assays. Letters in Applied Microbiology, 41(6), 470-475.
• Flemming, H. C. (1993). Biofilms and environmental protection. Water Science and Technology, 27(7-8), 1-10.
• Fliermans, C. B. (1996). Ecology of Legionella: from data to knowledge with a little wisdom. Microbial Ecology, 32, 203-228.
• 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. (1977). Legionnaires' disease: description of an epidemic of pneumonia. New England Journal of Medicine, 297(22), 1189-1197.
• Garcıa-Fulgueıras, A., Navarro, C., Fenoll, D., Garcıa, J., Gonzalez-Dıego, P., Jımenez-Bunuales, T., Rodrıguez, M., Lopez, R., Pacheco, F., Ruız, J., Segovıa, M., Baladron, B. & Pelaz, C. (2003). Legionnaires' disease outbreak in Murcia, Spain Emerging Infectious Diseases, 9(8), 915-921.
• Garrison, L. E., Kunz, J. M., Cooley, L. A., Moore, M. R., Lucas, C., Schrag, S., Sarisky, J. & Whitney, C. G. (2016). Vital signs: deficiencies in environmental control identified in outbreaks of Legionnaires’ disease-North America, 2000–2014. Morbidity and Mortality Weekly Report (MMWR), 65(22), 576-84.
• George, J. R., Pine, L., Reeves, M. W. & Harrell, W. K. (1980). Amino acid requirements of Legionella pneumophila. Journal of Clinical Microbiology, 11(3), 286-291.
• Graham, F. F. & Baker, M. G. (2023). Epidemiology and direct health care costs of hospitalised legionellosis in New Zealand, 2000–2020. Infection, Disease & Health, 28(1), 27-38.
• Hilbi, H., Hoffmann, C. & Harrison, C. F. (2011). Legionella spp. outdoors: colonization, communication and persistence. Environmental Microbiology Reports, 3(3), 286-296.
• Huang, S. W., Hsu, B. M., Chen, N. H., Huang, C. C., Huang, K. H., Chen, J. S. & Kao, P. M. (2011). Isolation and Identification of Legionella and Their Host Amoebae from Weak Alkaline Carbonate Spring Water Using a Culture Method Combined with PCR. Parasitology Research, 109(5),1233-1241.
• Hurley, M. A. & Roscoe, M. E. (1983). Automated statistical analysis of microbial enumeration by dilution series. Journal of Applied Microbiology, 55(1), 159-164.
• International Organization for Standardization (ISO) (2017). ISO 11731: 2017 Water Quality-Enumeration of Legionella. International Organization for Standardization: Geneva, Switzerland.
• Jinna, S. & Gaikwad, U. N. (2018). Environmental surveillance of Legionella pneumophila in distal water supplies of a hospital for early identification & prevention of hospital-acquired legionellosis. The Indian Journal of Medical Research, 147(6), 611-614.
• Joly, P., Falconnet, P. A., André, J., Weill, N., Reyrolle, M., Vandenesch, F., Maurin, M., Etienne, J. & Jarraud, S. (2006). Quantitative real-time Legionella PCR for environmental water samples: data interpretation. Applied and Environmental Microbiology, 72(4), 2801-2808.
• Kanarek, P., Bogiel, T. & Breza-Boruta, B. (2022). Legionellosis risk-an overview of Legionella spp. habitats in Europe. Environmental Science and Pollution Research, 29(51), 76532-76542.
• Koide, M., Haranaga, S., Higa, F., Tateyama, M., Yamane, N. & Fujita, J. (2007). Comparative evaluation of Duopath Legionella lateral flow assay against the conventional culture method using Legionella pneumophila and Legionella anisa strains. Japanese Journal of Infectious Diseases, 60(4), 214-216.
• Koide, M., Higa, F., Tateyama, M., Cash, H. L., Hokama, A. & Fujita, J. (2014). Role of Brevundimonas vesicularis in supporting the growth of Legionella in nutrient-poor environments. The New Microbiologica, 37(1), 33-39.
• Lanternier, F., Ader, F., Pilmis, B., Catherinot, E., Jarraud, S. & Lortholary, O. (2017). Legionnaire’s disease in compromised hosts. Infectious Disease Clinics, 31(1), 123-135.
• Lapierre, P., Nazarian, E., Zhu, Y., Wroblewski, D., Saylors, A., Passaretti, T., Hughes, S., Tran, A., Lin, Y., Kornblum, J., Morrison, S. S., Mercante, J. W., Fitzhenry, R., Weiss, D., Raphael, B. H., Varma, J. K., Zucker, H. A., Rakeman, J. L. &
• Musser, K. A. (2017). Legionnaires’ disease outbreak caused by endemic strain of Legionella pneumophila, New York, New York, USA, 2015. Emerging Infectious Diseases, 23(11), 1784-1791.
• Leoni, E. & Legnani, P. P. (2001). Comparison of selective procedures for isolation and enumeration of Legionella species from hot water systems. Journal of Applied Microbiology, 90(1), 27-33.
• McConnell, E. M., Cozma, I., Mou, Q., Brennan, J. D., Lu, Y. & Li, Y. (2021). Biosensing with dnazymes. Chemical Society Reviews, 50(16), 8954-8994.
• McDade, J. E., Brenner, D. J. & Bozeman, F. M. (1979). Legionnaires' disease bacterium isolated in 1947. Annals of Internal Medicine, 90(4), 659-661.
• Mondino, S., Schmidt, S., Rolando, M., Escoll, P., Gomez-Valero, L. & Buchrieser, C. (2020). Legionnaires’ disease: state of the art knowledge of pathogenesis mechanisms of Legionella. Annual Review of Pathology: Mechanisms of Disease, 15, 439-466.
• Monteiro, S. N., Robalo, A. M. & Santos, R. J. (2021). Evaluation of Legiolert™ for the Detection of Legionella pneumophila and Comparison with Spread-Plate Culture and qPCR Methods. Current Microbiology, 78(5), 1792-1797.
• Natas, O. B., Brekken, A. L., Bernhoff, E., Hetland, M. A. K., Löhr, I. H. & Lindemann, P. C. (2019). Susceptibility of Legionella pneumophila to antimicrobial agents and the presence of the efflux pump LpeAB. Journal of Antimicrobial Chemotherapy, 74(6), 1545-1550.
• Naumova, E. N., Liss, A., Jagai, J. S., Behlau, I. & Griffiths, J. K. (2016). Hospitalizations due to selected infections caused by opportunistic premise plumbing pathogens (OPPP) and reported drug resistance in the United States older adult population in 1991–2006. Journal of Public Health Policy, 37, 500-513.
• Neil, K. & Berkelman, R. (2008). Increasing incidence of legionellosis in the United States, 1990–2005: changing epidemiologic trends. Clinical Infectious Diseases, 47(5), 591-599.
• Oblinger, J. L. & Koburger, J. A. (1975). Understanding and teaching the most probable number technique. Journal of Milk and Food Technology, 38(9), 540-545.
• Ohno, A., Kato, N., Yamada, K. & Yamaguchi, K. (2003). Factors influencing survival of Legionella pneumophila serotype 1 in hot spring water and tap water. Applied and Environmental Microbiology, 69(5), 2540-2547.
• Perez Ortiz, A., Hahn, C., Schaible, T., Rafat, N. & Lange, B. (2021). Severe pneumonia in neonates associated with Legionella pneumophila: case report and review of the literature. Pathogens, 10(8), 1031.
• Phin, N., Parry-Ford, F., Harrison, T., Stagg, H. R., Zhang, N., Kumar, K., Lortholary, O., Zumla, A. & Abubakar, I. (2014). Epidemiology and clinical management of Legionnaires' disease. The Lancet Infectious Diseases, 14(10), 1011-1021.
• Qian, S., McConnell, E. M., Rothenbroker, M., Gu, J., Alungulesa, S., Godbout, L. & Li, Y. (2023). Detecting Legionella pneumophila in Cooling Tower Water Samples with a DNAzyme/Bead‐Based Fluorescence Assay. Analysis & Sensing, 3(6), e202300020.
• Rech, M. M., Swalla, B. M. & Dobranic, J. K. (2018). Evaluation of Legiolert for quantification of Legionella pneumophila from non-potable water. Current Microbiology, 75, 1282-1289.
• Ristroph, J. D., Hedlund, K. W. & Gowda, S. (1981). Chemically defined medium for Legionella pneumophila growth. Journal of Clinical Microbiology, 13(1), 115-119.
• Rothenbroker, M., McConnell, E. M., Gu, J., Urbanus, M. L., Samani, S. E., Ensminger, A. W., Filipe, C. D. M. & Li, Y. (2021). Selection and characterization of an RNA‐cleaving DNAzyme activated by Legionella pneumophila. Angewandte Chemie International Edition, 60(9), 4782-4788.
• Rucinski, S. L., Murphy, M. P., Kies, K. D., Cunningham, S. A., Schuetz, A. N. & Patel, R. (2018). Eight years of clinical Legionella PCR testing illustrates a seasonal pattern. The Journal of Infectious Diseases, 218(4), 669-670.
• Scaturro, M., Fontana, S., Dell’eva, I., Helfer, F., Marchio, M., Stefanetti, M. V., Cavallaro, M., Miglietta, M., Montagna, M. T., De Giglio, O. & Ricci, M. L. (2016). A multicenter study of viable PCR using propidium monoazide to detect Legionella in water samples. Diagnostic Microbiology and Infectious Disease, 85(3), 283-288.
• Sciuto, E. L., Laganà, P., Filice, S., Scalese, S., Libertino, S., Corso, D., Faro, G. & Coniglio, M. A. (2021). Environmental management of Legionella in domestic water systems: consolidated and innovative approaches for disinfection methods and risk assessment. Microorganisms, 9(3), 577.
• Selvakumar, A. & Tafuri, A. N. (2012). Rehabilitation of aging water infrastructure systems: key challenges and issues. Journal of Infrastructure Systems, 18(3), 202-209.
• Shadoud, L., Almahmoud, I., Jarraud, S., Etienne, J., Larrat, S., Schwebel, C., Timsit, J. F., Schneider, D. & Maurin, M. (2015). Hidden selection of bacterial resistance to fluoroquinolones in vivo: the case of Legionella pneumophila and humans. EBioMedicine, 2(9),1179-1185.
• Shah, P. P., Barskey, A. E., Binder, A. M., Edens, C., Lee, S., Smith, J. C., Schrag, S., Whitney, C. G. & Cooley, L. A. (2018). Legionnaires’ disease surveillance summary report, United States: 2014-1015.
• Shelton, B. G., Flanders, W. D. & Morris, G. K. (1994). Legionnaires' disease outbreaks and cooling towers with amplified Legionella concentrations. Current Microbiology, 28, 359-363.
• Söderberg, M. A., Dao, J., Starkenburg, S. R. & Cianciotto, N. P. (2008). Importance of type II secretion for survival of Legionella pneumophila in tap water and in amoebae at low temperatures. Applied and environmental microbiology, 74(17), 5583-5588.
• Sreenath, K., Dey, A. B., Kabra, S. K., Thakur, B., Guleria, R. & Chaudhry, R. (2021). Legionella pneumophila in Patients with Pneumonia at a Referral Hospital, New Delhi, India, 2015–2020. The American Journal of Tropical Medicine and Hygiene, 104(3), 854-860.
• Stahlmann, R. & Lode, H. (1999). Toxicity of quinolones. Drugs, 58, 37-42.
• T.C. Ministry of Health (2015). Lejyoner Hastalığı Kontrol Usul ve Esasları Hakkında Yönetmelik. Resmi Gazete: 13.05.2015 tarih ve 29354 sayılı. Erişim Adresi: https://www.mevzuat.gov.tr/mevzuat?MevzuatNo=20750&MevzuatTur=7&MevzuatTertip=5.
• Thacker, S. B., Bennett, J. V., Tsai, T. F., Fraser, D. W., McDade, J. E., Shepard, C. C., Williams, K. H., Jr., Stuart, W. H., Dull H. B. & Eickhoff, T. C. (1978). An outbreak in 1965 of severe respiratory illness caused by the Legionnaires' disease bacterium. Journal of Infectious Diseases, 138(4), 512-519.
• Tiemann, M. (2014). Safe drinking water act (SDWA): a summary of the act and its major requirements (pp. 7-5700). Washington, DC: Congressional Research Service.
• Tronel, H. & Hartemann, P. (2009). Overview of diagnostic and detection methods for legionellosis and Legionella spp. Letters in Applied Microbiology, 48(6), 653-656.
• Van Heijnsbergen, E., Schalk, J. A., Euser, S. M., Brandsema, P. S., den Boer, J. W. & de Roda Husman, A. M. (2015). Confirmed and potential sources of Legionella reviewed. Environmental Science & Technology, 49(8), 4797-4815.
• Vandewalle-Capo, M., Massip, C., Descours, G., Charavit, J., Chastang, J., Billy, P. A., Boisset, S., Lina, G., Gilbert, C., Maurin, M., Jarraud, S. & Ginevra, C. (2017). Minimum inhibitory concentration (MIC) distribution among wild-type strains of Legionella pneumophila identifies a subpopulation with reduced susceptibility to macrolides owing to efflux pump genes. International Journal of Antimicrobial Agents, 50(5), 684-689.
• Viasus, D., Di Yacovo, S., Garcia-Vidal, C., Verdaguer, R., Manresa, F., Dorca, J., Gudiol, F. & Carratala, J. (2013). Community-acquired Legionella pneumophila pneumonia: a single-center experience with 214 hospitalized sporadic cases over 15 years. Medicine, 92(1), 51-60.
• Viasus, D., Gaia, V., Manzur-Barbur, C. & Carratalà, J. (2022). Legionnaires’ disease: Update on diagnosis and treatment. Infectious Diseases and Therapy, 11, 973-986.
• Wang, H., Masters, S., Hong, Y., Stallings, J., Falkinham III, J. O., Edwards, M. A. & Pruden, A. (2012). Effect of disinfectant, water age, and pipe material on occurrence and persistence of Legionella, mycobacteria, Pseudomonas aeruginosa, and two amoebas. Environmental Science & Technology, 46(21), 11566-11574.
• Wang, Y., Yi, S. M., Huang, S. M., Xu, W. X., Wei, Y. W., Qu, Q. & Qu, J. (2024). Efficacy of omadacycline in the treatment of Legionella pneumonia: a case report. Frontiers in Cellular and Infection Microbiology, 14, 1380312.
• Whiley, H. & Taylor, M. (2016). Legionella detection by culture and qPCR: comparing apples and oranges. Critical Reviews in Microbiology, 42(1), 65-74.
• Woomer, P. L. (1994). Most probable number counts. Methods of Soil Analysis: Part 2 Microbiological and Biochemical Properties, 5, 59-79.
• Wullings, B. A. & Van Der Kooij, D. (2006). Occurrence and genetic diversity of uncultured Legionella spp. in drinking water treated at temperatures below 15 C. Applied and Environmental Microbiology, 72(1), 157-166.
• Zhang, C., Struewing, I., Mistry, J. H., Wahman, D. G., Pressman, J. & Lu, J. (2021). Legionella and other opportunistic pathogens in full-scale chloraminated municipal drinking water distribution systems. Water Research, 205, 117571.