Legionnaires' disease

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Legionellosis
Classification and external resources
Legionella pneumophila 01.jpg
TEM image of L. pneumophila, responsible for over 90% of Legionnaires' Disease cases
ICD-10 A48.1, A48.2
ICD-9 482.84
DiseasesDB 7366
MedlinePlus 000616
eMedicine med/1273
MeSH D007876

Legionnaires' disease (also legionellosis or Legion fever) is a form of pneumonia caused by any species of Gram-negative aerobic bacteria belonging to the genus Legionella.[1] Over 90% of cases of Legionnaires' disease are caused by Legionella pneumophila.

Other causative species include L. longbeachae, L. feeleii, L. micdadei and L. anisa. These species cause a less severe infection known as Pontiac fever, which resembles acute influenza. These species can be water-borne or present in soil, whereas L. pneumophila has only been found in aquatic systems, where it is symbiotically present in aquatic-borne amoebae.[2] It thrives in temperatures between 25 and 45°C (77 and 113°F), with an optimum temperature of 35°C (95°F). During infection, the bacterium invades macrophages and lung epithelial cells and replicates intracellularly.[3][4]

Transmission[edit]

Legionnaires' disease is transmitted by inhalation of aerosolized water and/or soil contaminated with the bacteria. It is not airborne and it is not transmitted from person-to-person. Sources where temperatures allow the bacteria to thrive include hot-water tanks, cooling towers, and evaporative condensers of large air-conditioning systems, such as those commonly found in hotels and large office buildings. Though the first known outbreak was in Philadelphia, Pennsylvania, cases of legionellosis have occurred throughout the world.[5]

Epidemiology[edit]

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. Of the 182 reported cases, mostly men, 29 died.[6] On January 18, 1977, the causative agent was identified as a previously unknown strain of bacteria, subsequently named Legionella, and the species that caused the outbreak was named Legionella pneumophila.[7][8]

Outbreaks of Legionnaires' disease receive significant media attention. However, this disease usually occurs in 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-aged or older.[9] Legionella pneumophila 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. About 8,000 to 18,000 cases of Legionnaires' disease occur each year in the United States, according to the Bureau of Communicable Disease Control.[10]

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 The data on Legionella are limited in developing countries and Legionella-related illnesses likely are underdiagnosed worldwide.[11] 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.

A 2011 study successfully used modeling to predict the likely number of cases during Legionnaires’ outbreaks based on symptom onset dates from past outbreaks. In this way, the eventual likely size of an outbreak can be predicted, enabling efficient and effective use of public health resources in managing an outbreak.[12]

Reservoirs[edit]

L. pneumophila thrives in aquatic systems where it is established within amoeba in a symbiotic relationship. In the built environment, central air conditioning systems in office buildings, hotels, and hospitals are sources of contaminated water.[13] Other places it can dwell include cooling towers used in industrial cooling systems, evaporative coolers, nebulizers, humidifiers, whirlpool spas, water heating systems, showers, windshield washers, fountains, room-air humidifiers, ice-making machines, and misting systems typically found in grocery-store produce sections.[14][15]

The disease may also be transmitted from contaminated aerosols generated in hot tubs if the disinfection and maintenance program is not done rigorously.[16] Freshwater ponds, creeks, and ornamental fountains are potential sources of Legionella.[17] The disease is particularly associated with hotels, fountains, cruise ships and hospitals with complex potable water systems and cooling systems.

Respiratory care devices such as humidifiers and nebulizers used with contaminated tap water may contain Legionella species, so using sterile water is very important.[18] Other sources include exposure to potting mix and compost and misting systems in produce sections of grocery stores.[19]

Signs and symptoms[edit]

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,[20] as can a so-called 'relative bradycardia', i.e. low or low normal heart rate despite the presence of a fever.[21] 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.

Diagnosis[edit]

Various stages of the disease: Chest radiograph (A) and high-resolution computed tomography (B) at hospital admission, repeat high-resolution computerized tomography of the chest a week after hospital admission (C,D), shown in a 42-year-old male with severe pneumonia caused by L. pneumophila serogroup 11a

People of any age may suffer from Legionnaires' disease, but the illness most often affects middle-aged 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.[22] 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 species can be isolated on 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.

A significant under-reporting problem occurs 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 may not have encountered before, so may misdiagnose. 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.[23]

Treatment[edit]

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 use of rifampicin with added regimens. 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 in Legionella-infected cells.

The mortality at the original American Legion convention in 1976 was high (34 deaths in 180 infected individuals[citation needed]) 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[edit]

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.[9] 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.[24]

History[edit]

The first recognized cases of Legionnaires' disease occurred in 1976 in Philadelphia, Pennsylvania. Among attendees of a Legionnaires' convention held at the Bellevue-Stratford Hotel, 221 attendees contracted the disease and 34 of them died.[25]

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.

In March 1999, a large outbreak in the Netherlands occurred during the Westfriese Flora flower exhibition in Bovenkarspel; 318 people became ill and at least 32 people died. This was the second-deadliest outbreak since the 1976 outbreak and possibly the deadliest as several people were buried before Legionnaires' disease had been diagnosed.

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 six died, a case-fatality rate around 1%.

In late September, 2005, 127 residents of a nursing home became ill with L. pneumophila. Within a week, 21 of the residents had died. Culture results at first were negative, which is not unusual, as L. pneumophila is a fastidious bacterium, meaning it leaves virtually no trace of itself. The source of the outbreak was traced to the air-conditioning cooling towers on the nursing home's roof.[26][27]

References[edit]

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  2. ^ Winiecka-Krusnell, J.; Linder, E. (1999). "Free-living amoebae protecting Legionella in water: The tip of an iceberg?". Scandinavian journal of infectious diseases 31 (4): 383–385. doi:10.1080/00365549950163833. PMID 10528878.  edit
  3. ^ Takamatsu, R.; Teruya, H.; Takeshima, E.; Ishikawa, C.; Matsumoto, K.; Mukaida, N.; Li, J. D.; Heuner, K.; Higa, F.; Fujita, J.; Mori, N. (2010). "Molecular characterization of Legionella pneumophila-induced interleukin-8 expression in T cells". BMC Microbiology 10: 1. doi:10.1186/1471-2180-10-1. PMC 2824691. PMID 20051107.  edit
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  16. ^ Silivanch v. Celebrity Cruises, Inc., 171 F.Supp.2d 241 (S.D.N.Y. 2001) (plaintiff successfully sued cruise line and manufacturer of filter after catching disease on cruise)
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