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|2012 || [[Calp]], [[Spain]] || AR Diamante Beach Hotel || ||{{sort|018|18}} ||{{sort|003|3}} || 17% || Origin unknown at present. Large hotel with solar water heating system for spa and domestic hot water.<ref>{{cite news |title=Three British pensioners die after Legionnaires' Disease outbreak 'at Spanish beach hotel' |url=http://www.dailymail.co.uk/news/article-2095709/Legionnaires-outbreak-3-British-pensioners-die-disease-AR-Diamante-Beach-Hotel-Spain.html |newspaper=[[The Daily Mail]] |date= February 04, 2012 |accessdate=2012-02-05 }}</ref>
|2012 || [[Calp]], [[Spain]] || AR Diamante Beach Hotel || ||{{sort|018|18}} ||{{sort|003|3}} || 17% || Origin unknown at present. Large hotel with solar water heating system for spa and domestic hot water.<ref>{{cite news |title=Three British pensioners die after Legionnaires' Disease outbreak 'at Spanish beach hotel' |url=http://www.dailymail.co.uk/news/article-2095709/Legionnaires-outbreak-3-British-pensioners-die-disease-AR-Diamante-Beach-Hotel-Spain.html |newspaper=[[The Daily Mail]] |date= February 04, 2012 |accessdate=2012-02-05 }}</ref>
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|2012|| [[Québec City]], [[Canada]] || Lower Québec City || Possibly [[cooling towers]] ||{{sort|165|165}} ||{{sort|010|10}} || 6%|| 165 confirmed cases as of September 1, 2012, probably due to contaminated water in industrial cooling towers.<ref>{{cite news |url=http://www.dspq.qc.ca/legionellose.html |date= September 1, 2012 |accessdate=2012-09-01 }}</ref>
|2012|| [[Québec City]], [[Canada]] || Lower Québec City || Possibly [[cooling towers]] ||{{sort|165|165}} ||{{sort|011|11}} || 6%|| 165 confirmed cases as of September 1, 2012, probably due to contaminated water in industrial cooling towers.<ref>{{cite news |url=http://www.dspq.qc.ca/legionellose.html |date= September 1, 2012 |accessdate=2012-09-01 }}</ref>
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|2012|| [[Chicago]], [[Illinois]] || JW Marriott Hotel || [[Decorative Lobby Fountain]] ||{{sort|8|8}} || {{sort|003|3}} || 25% || 8 confirmed cases with people who stayed at the JW Marriott Chicago during July-August 2012. <ref>{{cite news|title=3 dead in Legionnaires' outbreak tied to downtown hotel|url=http://www.chicagotribune.com/news/local/breaking/chi-4-more-legionnaires-cases-tied-to-downtown-hotel-20120827,0,921365.story |newspaper=[Chicago Tribune] |date= August 27, 2012 |accessdate=2012-08-27 }}</ref>
|2012|| [[Chicago]], [[Illinois]] || JW Marriott Hotel || [[Decorative Lobby Fountain]] ||{{sort|8|8}} || {{sort|003|3}} || 25% || 8 confirmed cases with people who stayed at the JW Marriott Chicago during July-August 2012. <ref>{{cite news|title=3 dead in Legionnaires' outbreak tied to downtown hotel|url=http://www.chicagotribune.com/news/local/breaking/chi-4-more-legionnaires-cases-tied-to-downtown-hotel-20120827,0,921365.story |newspaper=[Chicago Tribune] |date= August 27, 2012 |accessdate=2012-08-27 }}</ref>

Revision as of 20:00, 2 September 2012

Legionnaires' disease
SpecialtyInfectious diseases, pulmonology Edit this on Wikidata

Legionellosis is a potentially fatal infectious disease caused by gram negative, aerobic bacteria belonging to the genus Legionella.[1][2] Over 90% of legionellosis cases are caused by Legionella pneumophila, a ubiquitous aquatic organism that thrives in temperatures between 25 and 45 °C (77 and 113 °F), with an optimum temperature of 35 °C (95 °F).[3]

Legionellosis takes two distinct forms:

  • Legionnaires' disease, also known as "legion fever",[4] is the more severe form of the infection and produces high fever and pneumonia.[5][6]
  • Pontiac fever is caused by the same bacteria but produces a milder respiratory illness without pneumonia that resembles acute influenza.[5] Pontiac fever also has a spontaneous resolution.

Legionnaires' disease acquired its name in July 1976 when an outbreak of pneumonia occurred among people attending a convention of the American Legion at the Bellevue-Stratford Hotel in Philadelphia. On January 18, 1977 the causative agent was identified as a previously unknown strain of bacteria, subsequently named Legionella. Some people can be infected with the Legionella bacteria and have only mild symptoms or no illness at all.

Outbreaks of Legionnaires' disease receive significant media attention. However, this disease usually occurs as single, isolated cases not associated with any recognized outbreak. When outbreaks do occur, they are usually in the summer and early autumn, though cases may occur at any time of year. Most infections occur in those who are middle-age or older.[7]

Signs and symptoms

Patients with Legionnaires' disease usually have fever, chills, and a cough, which may be dry or may produce sputum. Some patients also have muscle aches, headache, tiredness, loss of appetite, loss of coordination (ataxia), and occasionally diarrhea and vomiting. Confusion and impaired cognition may also occur [8], as can a so-called 'relative bradycardia', i.e. low or low normal heart rate despite the presence of a fever. [9] Laboratory tests may show that patients’ renal functions, liver functions and electrolytes are deranged, including hyponatremia. Chest X-rays often show pneumonia with bi-basal consolidation. It is difficult to distinguish Legionnaires' disease from other types of pneumonia by symptoms or radiologic findings alone; other tests are required for diagnosis.

Persons with Pontiac fever experience fever and muscle aches without pneumonia. They generally recover in 2 to 5 days without treatment.

The time between the patient's exposure to the bacterium and the onset of illness for Legionnaires' disease is 2 to 10 days; for Pontiac fever, it is shorter, generally a few hours to 2 days.

Cause

Colorized scanning electron micrograph (SEM) with moderately-high magnification of 8000X depicting a large grouping of Gram-negative Legionella pneumophila bacteria
This micrograph depicted details seen in a lung tissue specimen from a Knoxville patient with fatal pneumonia due to Legionnaires’ disease. The tissue was stained using hematoxylin-eosin (H&E) stain. Legionella pneumophila are Gram-negative bacteria. Using H&E stain, these organisms, if present in the specimen, would stain a pink or red color. Note how the alveolar spaces are so congested with a leukocytic infiltrate in response to the infection.

L. pneumophila is specifically considered as a pathogen of the respiratory tract. Surface organelles are made up from at least forty various protein components reconcile motile bacteria.[10][clarification needed] Other infections have also been reported, including haemodialysis fistulae, pericarditis, and wound and skin infections. Bacteraemia is often associated with Legionnaires' disease. Intestinal infections may only occur as part of respiratory infections, and where gastrointestinal symptoms have on occasion been described.

One interesting feature in transmissive Legionella pneumophila is how monopolar flagellum is made up of the flagellin subunit FlaA. The function of the flagellum involves the development of Legionella pneumophila for "human macrophage-like cell lines and cytotoxicity to macrophages". Recent studies have shown flagellin noticed by mouse macrophages brings about cell death by the activation of cytosolic Naip5 (Birc1e) receptor.[10]

According to the Centers for Disease Control and Prevention laboratory, antisera produced in rabbits have been prepared against all species and serogroups of Legionella and have been used in the CDC laboratory to distinguish the most Legionella strains in slide agglutination tests. Although, the development of an antigen that can diagnose infections with all species and serogroups of Legionella has not yet been discovered. [11]

Infections of protozoa such as Hartmannella vermiformis and related protozoa have been shown to be able to support the growth of L. pneumophila in tap water. Also Acanthamoeba, Naegleria and Tetrahymena can be infected by L. pneumophila. This pathway may be how these organisms survive in the environment.[citation needed]

Transmission

Infection normally occurs after inhaling an aerosol (fine airborne particles) containing Legionella bacteria. Such particles could originate from any infected water source. When mechanical action breaks the surface of the water, small water droplets are formed, which evaporate very quickly. If these droplets contain bacteria, the bacteria cells remain suspended in the air, invisible to the naked eye and small enough to be inhaled into the lungs.[12] This often occurs in poorly ventilated areas such as prisons where a condensating air conditioner can spread it throughout the entire room, infecting anyone not immune to the strain of bacteria.

Potential sources of such contaminated water include cooling towers (some 40% to 60% of ones tested[13]) used in industrial cooling water systems as well as in large central air conditioning systems, evaporative coolers, nebulizers, humidifiers, whirlpool spas, hot water systems, showers, windshield washers[14], architectural fountains, room-air humidifiers, ice making machines, misting equipment, and similar disseminators that draw upon a public water supply.

The disease may also be transmitted from contaminated aerosols generated in hot tubs if the disinfection and maintenance program is not done rigorously.[15] Freshwater ponds, creeks, and ornamental fountains are potential sources of Legionella.[16] The disease is particularly associated with hotels, fountains, cruise ships and hospitals with complex potable water systems and cooling systems.

The development of bacterial infections may cause Legionnaires’ disease. Respiratory care devices such as humidifiers and nebulizers used with contaminated tap water may contain Legionella. Using sterile water is very important, especially when using respiratory care devices. [17]

Prevention

A recent research study provided evidence that Legionella pneumophila, the causative agent of Legionnaires' disease, can travel airborne at least 6 km from its source. In 2000, ASHRAE issued guidelines to maintain water systems and to decrease the chances of Legionnaires’ disease transmission. The guidelines were not valued because legionella multiply in such temperatures. On the other hand, a lot of states had regulations that limited temperatures in health care facilities in order to reduce scalding injuries.[11] It was previously believed that transmission of the bacterium was restricted to much shorter distances. A team of French scientists reviewed the details of an epidemic of Legionnaires' disease that took place in Pas-de-Calais in northern France in 2003–2004. There were 86 confirmed cases during the outbreak, of whom 18 died. The source of infection was identified as a cooling tower in a petrochemical plant, and an analysis of those affected in the outbreak revealed that some infected people lived as far as 6–7 km from the plant.[18]

A study of Legionnaires' disease cases in May 2005 in Sarpsborg, Norway concluded that: "The high velocity, large drift, and high humidity in the air scrubber may have contributed to the wide spread of Legionella species, probably for >10 km. "...[19]

In 2010 a study by the UK Health Protection Agency reported that 20% of cases may be caused by infected windscreen washer systems filled with pure water. The finding came after researchers spotted that professional drivers are five times more likely to contract the disease. No cases of infected systems were found whenever a suitable washer fluid was used.[20]

Temperature affects the survival of Legionella as follows:[21]

  • 70 to 80 °C (158 to 176 °F): Disinfection range
  • At 66 °C (151 °F): Legionellae die within 2 minutes
  • At 60 °C (140 °F): They die within 32 minutes
  • At 55 °C (131 °F): They die within 5 to 6 hours
  • Above 50 °C (122 °F): They can survive but do not multiply
  • 35 to 46 °C (95 to 115 °F): Ideal growth range
  • 20 to 50 °C (68 to 122 °F): Growth range
  • Below 20 °C (68 °F): They can survive but are dormant

Removing slime, which can carry legionellae when airborne, may be an effective control process.[22][23]

Action levels

The European Working Group for Legionella Infections (EWGLI)[24] was established in 1986 within the European Union framework to share knowledge and experience about potential sources of Legionella and their control. This group has published guidelines[25] about the actions to be taken to limit the number of colony forming units (i.e., the "aerobic count") of micro-organisms per mL at 30 °C (minimum 48 hours incubation):

Aerobic count Legionella Action required
10,000 or less 1,000 or less System under control.
more than 10,000
up to 100,000		 more than 1,000
up to 10,000		 Review program operation. The count should be confirmed by immediate re-sampling. If a similar count is found again, a review of the control measures and risk assessment should be carried out to identify any remedial actions.
more than 100,000 more than 10,000 Implement corrective action. The system should immediately be re-sampled. It should then be ‘shot dosed’ with an appropriate biocide, as a precaution. The risk assessment and control measures should be reviewed to identify remedial actions.

Almost all natural water sources contain Legionella and their presence should not be taken as an indication of a problem. The tabled figures are for total aerobic plate count, cfu/ml at 30 °C (minimum 48 hours incubation) with colony count determined by the pour plate method according to ISO 6222(21) or spread plate method on yeast extract agar. Legionella isolation can be conducted using the method developed by the US Center for Disease Control using buffered charcoal yeast extract agar with antibiotics.

Many other governmental agencies, cooling tower manufacturers, and industrial trade organizations have developed design and maintenance guidelines for preventing or controlling the growth of Legionella in cooling towers. However, in the US, there are no regulations requiring testing or maintaining any specified levels in these facilities.

Breeding ground

The bacteria grow best in warm water, like the kind found in hot tubs, cooling towers, hot water tanks, large plumbing systems, or parts of the air-conditioning systems of large buildings. Indoor ornamental fountains have been confirmed as a cause of Legionnaires' disease outbreaks, in which submerged lighting as a heat source was attributed to the outbreak in all documented cases.[citation needed] Controlling the growth of Legionella in ornamental fountains is touched on in many of the listed guidelines. However, specific guidelines for solar water heating systems http://www.wras.co.uk/PDF_Files/Preheated_Water_Report.pdfornamental fountains have also been published.[26]

Adding an antibacterial agent to the automobiles' windshield system's reservoir is also recommended.[17] Legionellae have been discovered in up to 40% of freshwater environments and have been in up to 80% of freshwater sites by PCR hybridization assay. [11]

Regulations and ordinances

The guidance issued by the UK government's Health and Safety Executive (HSE) now recommends that microbiological monitoring for wet cooling systems, using a dipslide, should be performed weekly. The guidance now also recommends that routine testing for legionella bacteria in wet cooling systems be carried out at least quarterly, and more frequently when a system is being commissioned, or if the bacteria have been identified on a previous occasion.[27]

Further non-statutory UK guidance from the Water Regulations Advisory Scheme now exists for pre-heating of water in applications such as solar water heating systems. http://www.wras.co.uk/PDF_Files/Preheated_Water_Report.pdf

The City of Garland, Texas requires yearly testing for legionella bacteria at cooling towers at apartment buildings.[28]

Malta requires twice yearly testing for Legionella bacteria at cooling towers and water fountains. Malta prohibits the installation of new cooling towers and evaporative condensers at health care facilities and schools.[29]

The Texas Department of State Health Services has provided guidelines for hospitals to detect and prevent the spread of nosocomial infection due to legionella.[30]

Limiting growth

Legionella bacteria themselves can be inactivated by UV light. However, Legionella bacteria that grow and reproduce in amoebae or that are sheltered in corrosion particles cannot be killed by UV light alone. An innovative way is the combination of ultrasonics and UVC light. This uses a two-stage process, where ultrasonic cavitation disrupts the amoebae or corrosion particles and leaves the Legionella bacteria exposed for UV radiation. Such combined system are used for example in hot water systems in sensitive areas, such as hospitals, where the inhabitants are more vulnerable than in normal environments.[31]Legionellae thrives in moist soil and environments as “intracellular parasites of free-living protozoa”. Molds, protozoa and mammalian cells are all various hosts that Legionellae can still infect. [11][10]

Legionella will grow in water at temperatures from 20 to 50 °C (68 to 122 °F). However, the bacteria reproduce at the greatest rate in stagnant water at temperatures of 35 to 46 °C (95 to 115 °F).

Copper-Silver ionization is an effective industrial control and prevention process to eradicate Legionella in potable water distribution systems and cooling towers found in health facilities, hotels, nursing homes and most large buildings. In 2003, ionization became the first such hospital disinfection process to have fulfilled a proposed four-step modality evaluation; by then it had been adopted by over 100 hospitals.[32] Additional studies indicate ionization is superior to thermal eradication.[33]

A 2011 study by Lin, Stout and Yu [34][3] found Copper-Silver ionization to be the only Legionella control technology which has been validated through a 4 step scientific approach.

Diagnosis

People of any age may suffer from Legionnaires' disease, but the illness most often affects middle-age and older persons, particularly those who smoke cigarettes or have chronic lung disease. Immunocompromised patients are also at elevated risk. Pontiac fever most commonly occurs in persons who are otherwise healthy.

The most useful diagnostic tests detect the bacteria in sputum, find Legionella antigens in urine samples (due to renal fibrosis), or the comparison of Legionella antibody levels in two blood samples taken 3 to 6 weeks apart. A urine antigen test which is simple, quick, and very reliable will only detect Legionella pneumophila serogroup 1, which accounts for 70% of disease cause by L. pneumophila. This test was developed by Richard Kohler and described in the Journal of Infectious disease in 1982 while Dr. Kohler was a junior faculty member at the Indiana University School of Medicine.[35] In addition the urine antigen test will not identify the specific subtypes; so it cannot be used to match the patient with the environmental source of infection. Legionella can be isolated on a CYE agar as well.

Legionella stains poorly with gram stain, stains positive with silver, and is cultured on charcoal yeast extract with iron and cysteine.

There is a significant under-reporting problem with Legionellosis. Even in countries with effective health services and readily available diagnostic testing, about 90% of cases of Legionnaires’ disease are missed. This is partly due to Legionnaire’s disease being a relatively rare form of pneumonia, which many clinicians will not have encountered before and therefore may mis-diagnose. A further issue is that patients with Legionellosis can present with a wide range of symptoms some of which (such as diarrhea) may distract clinicians from making a correct diagnosis.[36]

Treatment

Current treatments of choice are the respiratory tract quinolones (levofloxacin, moxifloxacin, gemifloxacin) or newer macrolides (azithromycin, clarithromycin, roxithromycin). The antibiotics used most frequently have been levofloxacin and azithromycin. Macrolides are used in all age groups while tetracyclines are prescribed for children above the age of 12 and quinolones above the age of 18. Rifampicin can be used in combination with a quinolone or macrolide. It is uncertain whether rifampicin is an effective antibiotic to take for treatment.The Infectious Diseases Society of America does not recommend the usage of rifampicin with added regimens.[11] Tetracyclines and erythromycin led to improved outcomes compared to other antibiotics in the original American Legion outbreak. These antibiotics are effective because they have excellent intracellular penetration and Legionella infected cells.

The mortality at the original American Legion convention in 1976 was high (34 deaths in 180 infected individuals) because the antibiotics used (including penicillins, cephalosporins, and aminoglycosides) had poor intracellular penetration. Mortality has plunged to less than 5% if therapy is started quickly. Delay in giving the appropriate antibiotic leads to higher mortality.

Prognosis

The fatality rate of Legionnaires' disease has ranged from 5% to 30% during various outbreaks and approaches 50% for nosocomial infections, especially when treatment with antibiotics is delayed.[37]According to the journal Infection Control and Hospital Epidemiology, hospital-acquired Legionella pneumonia has a fatality rate of 28%, and the principal source of infection in such cases is the drinking-water distribution system.[38]

Epidemiology

There are about 8,000 to 18,000 cases of Legionnaires’ disease each year in the United States, according to the Bureau of Communicable Disease Control.[39] Much has been learned about the epidemiology of Legionnaires' disease since the organism was first identified in 1976. National surveillance systems and research studies were established early, and in recent years improved ascertainment and changes in clinical methods of diagnosis have contributed to an upsurge in reported cases in many countries. Environmental studies continue to identify novel sources of infection, leading to regular revisions of guidelines and regulations. Between 1995 and 2005 over 32,000 cases of Legionnaires' disease and more than 600 outbreaks were reported to the European Working Group for Legionella Infections (EWGLI). In the future, there may be an increase in cases as the population becomes more elderly.[2] There is a shortage of data on Legionella in developing countries and it is likely that Legionella-related illness is underdiagnosed worldwide.[40] Improvements in diagnosis and surveillance in developing countries would be expected to reveal far higher levels of morbidity and mortality than are currently recognised. Similarly, improved diagnosis of human illness related to legionella species and serogroups other than Legionella pneumophila would improve knowledge about their incidence and spread.[11]

Outbreaks

Year City Venue Source Cases Deaths Fatality rate Notes
1976 Philadelphia, Pennsylvania 1976 Philadelphia legionellosis outbreak air conditioning 221 34 15.4% This was the eponymous outbreak and probably the deadliest recorded outbreak as of yet.[41]
1999 Bovenkarspel, Netherlands 1999 Bovenkarspel legionellosis outbreak hot tub 318 32 10.0% In March 1999, an outbreak in the Netherlands occurred during the Westfriese Flora flower exhibition in Bovenkarspel. 318 people became ill and at least 32 people died. There is a possibility that more people died from it (which might make it the deadliest recorded outbreak), but these people were buried before the Legionella infection was recognized. The source of the bacteria was a hot tub in the exhibition area.[42][43]
1985 Stafford, England, United Kingdom Stafford District Hospital air conditioning 175 28 16.0% In April 1985, 175 patients were admitted to the District or Kingsmead Stafford Hospitals with chest infection or pneumonia. A total of 28 people died. Medical diagnosis showed that Legionnaires' disease was responsible and the immediate epidemiological investigation traced the source of the infection to the air-conditioning cooling tower on the roof of Stafford District Hospital. A Government Inquiry was convened to investigate how the infection occurred and why it became Britain's largest epidemic of Legionnaires' disease. The infection was linked to one small zone in the hospital: the outpatients department. The initial investigation searched for engineering reasons to explain why this particular zone was the risk area. More detailed and wider epidemiological surveys subsequently showed that staff working in the whole area supplied with fresh air taken adjacent to the tower, had antibodies to the disease. The outpatients department was unique in having a very large transient population of susceptible individuals either receiving treatment or accompanying friends.[41]
2005 Toronto, Canada Seven Oaks Home for the Aged cooling tower 127 21 16.5% [44]
2005 Fredrikstad, Norway factory air scrubber 56 10 17.8% 56 people became ill and ten died from Legionnaires' disease caused by bacteria growing in an air scrubber of a nearby factory.
2002 Barrow-in-Furness, UK 2002 Barrow-in-Furness legionellosis outbreak air conditioning 172 7 4.1% In 2002, Barrow-in-Furness in the U.K. suffered an outbreak of Legionnaires' disease. Six women and one man died as a result of the illness; another 172 people also contracted the disease. The cause was found to be a contaminated cooling tower at the town’s Forum 28 arts centre.[45] Barrow Borough Council later became the first public body in the UK to be charged with corporate manslaughter but were cleared. They were, however, along with architect Gillian Beckingham, fined for breaches of Health and Safety regulations in a trial that ended in 2006.
2001 Murcia, Spain hospital 800 6 0.8% The world’s largest outbreak of Legionnaires' disease happened in July 2001 with patients appearing at the hospital on July 7, in Murcia, Spain. More than 800 suspected cases were recorded by the time the last case was treated on July 22; 636–696 of these cases were estimated and 449 confirmed (so, at least 16,000 people were exposed to the bacterium) and 6 died . A case-fatality rate of approximately 1%.
2000 Melbourne, Australia Melbourne Aquarium cooling tower 125 4 4.2% In April 2000, an outbreak of Legionella pnemophila serogroup 1 occurred in Melbourne, Australia. The outbreak resulted in 125 confirmed cases of Legionnaire's disease, with 95 (76%) hospitalised. It is reported that 4 died from the outbreak. The investigation traced the source of the infection to the cooling tower at the newly opened aquarium.[46] Since this outbreak, legionella infection statistics are required to be reported by the state government as a notifiable disease.[47] Stringent Regulations were introduced by the State to control legionella in 2001.[48]
2008 New Brunswick, New Jersey Saint Peter's University Hospital Drinking water 6 2 33.3% Chlorination in the water system had dropped below effective levels.[49]
2010 Wales, United Kingdom South Wales Valleys Likely cooling towers 22 2 9% Thought to be cooling towers in local industry.[50]
2012 Edinburgh, Scotland, UK South west of Edinburgh Possibly cooling towers 99 3 3% 50 confirmed cases, with 49 additional suspected cases. Three people are known to have died from the outbreak.[51]
2012 Auckland, New Zealand Unknown Water Source and/or Air Conditioning 11 1 9% The number of people affected in a major outbreak of Legionnaires' disease in Auckland, which has claimed one life, has risen to 11.[52]
2012 Stoke-on-Trent, England Warehouse, Fenton Hot Tub 19 1 5.2% Seventeen of the confirmed cases visited the warehouse a couple of weeks before becoming ill. [53]
2012 Calp, Spain AR Diamante Beach Hotel 18 3 17% Origin unknown at present. Large hotel with solar water heating system for spa and domestic hot water.[54]
2012 Québec City, Canada Lower Québec City Possibly cooling towers 165 11 6% 165 confirmed cases as of September 1, 2012, probably due to contaminated water in industrial cooling towers.[55]
2012 Chicago, Illinois JW Marriott Hotel Decorative Lobby Fountain 8 3 25% 8 confirmed cases with people who stayed at the JW Marriott Chicago during July-August 2012. [56]

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  35. ^ Kohler R, Wheat LJ (1982). "Rapid diagnosis of pneumonia due to Legionella pneumophila serogroup 1". J. Infect. Dis. 146 (3): 444. PMID 7050258. {{cite journal}}: Unknown parameter |month= ignored (help)
  36. ^ Makin, Dr T (2008). "Legionella bacteria and solar pre-heating of water for domestic purposes" (PDF). UK Water Regulations Advisory Scheme Report: 4. {{cite journal}}: Unknown parameter |month= ignored (help); Unknown parameter |para= ignored (help)
  37. ^ MedlinePlus Encyclopedia: Legionnaire's disease
  38. ^ Stout JE, Muder RR, Mietzner S; et al. (2007). "Role of environmental surveillance in determining the risk of hospital-acquired legionellosis: a national surveillance study with clinical correlations". Infect Control Hosp Epidemiol. 28 (7): 818–24. doi:10.1086/518754. PMID 17564984. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) as PDF
  39. ^ "Legionellosis". Massachusetts Department of Public Health. Bureau of Communicable Disease Control. Nov. 2011. Retrieved 2012-11-12. {{cite web}}: Check date values in: |date= (help)
  40. ^ World Health Organization 2007. Legionella and the prevention of legionellosis. Geneva, Switzerland: WHO. Available at http://www.who.int/water_sanitation_health/emerging/legionella.pdf
  41. ^ a b "Legionnaires' Disease History". Archived from the original on 2008-02-25. Retrieved 2008-10-19.
  42. ^ "The Westfriese Flora flower exhibition and fair". Q-net.net.au. Retrieved 2010-09-11.
  43. ^ Template:Nl "25 februari 1999: Legionellabesmetting Westfriese Flora, Bovenkarspel". Zwaailichten disaster website. 2005. Retrieved December 02, 2011. {{cite web}}: Check date values in: |accessdate= (help)
  44. ^ "Legionnaires' Disease". Toronto Public Health.
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  46. ^ Greig JE, Carnie JA, Tallis GF; et al. (2004). "An outbreak of Legionnaires' disease at the Melbourne Aquarium, April 2000: investigation and case-control studies". Med. J. Aust. 180 (11): 566–72. PMID 15174987. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  47. ^ http://www.health.vic.gov.au/environment/downloads/cts_ehindicators.pdf
  48. ^ "Download Menu". Austlii.edu.au. Retrieved 2010-09-11.
  49. ^ "Second patient with Legionnaires' disease dies at New Brunswick hospital". The Star-Ledger. September 24, 2008. Retrieved 2011-10-08.
  50. ^ "South Wales legionnaires' disease outbreak declared over". NHS Wales. 12 October, 2010. Retrieved 6 June 2012. {{cite web}}: Check date values in: |date= (help)
  51. ^ "Legionnaires' Disease outbreak: Third death reported". bbc.co.uk. 3 July 2012. Retrieved 3 July 2012.
  52. ^ "Legionnaires' cases rise to 11". [The Press]. April 06, 2012. Retrieved 2012-06-04. {{cite news}}: Check date values in: |date= (help)
  53. ^ "Stoke-on-Trent Legionnaires' source 'could be hot tub'". [The Press]. July 31, 2012. Retrieved 2012-08-02.
  54. ^ "Three British pensioners die after Legionnaires' Disease outbreak 'at Spanish beach hotel'". The Daily Mail. February 04, 2012. Retrieved 2012-02-05. {{cite news}}: Check date values in: |date= (help)
  55. ^ . September 1, 2012 http://www.dspq.qc.ca/legionellose.html. Retrieved 2012-09-01. {{cite news}}: Missing or empty |title= (help)
  56. ^ "3 dead in Legionnaires' outbreak tied to downtown hotel". [Chicago Tribune]. August 27, 2012. Retrieved 2012-08-27.
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