Legionnaires Disease

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Legionnaires disease (LD) is the pneumonia caused by Legionella pneumophila. LD also refers to a more benign, self-limited, acute febrile illness known as Pontiac fever, which has been linked serologically to L pneumophila, although it presents without pneumonia. (See Pathophysiology and Etiology.)

L pneumophila is an important cause of nosocomial and community-acquired pneumonia (CAP) and must be considered a possible causative pathogen in any patient who presents with atypical pneumonia. (See Clinical Presentation and Workup.)

The Legionella bacterium was first identified in the summer of 1976 during the 58th annual convention of the American Legion, which was held at the Bellevue-Stratford Hotel in Philadelphia. Infection was presumed to be spread by contamination of the water in the hotel’s air conditioning system. The presentation ranged from mild flulike symptoms to multisystem organ failure. Of the 182 people infected, 29 died.

Although Legionella was not identified until 1976, L pneumophila was subsequently found in a clinical specimen dating to 1943 and, according to retrospective analysis, may have been responsible for pre-1976 pneumonia epidemics in Philadelphia; Washington, DC; and Minnesota.

Legionnaires disease is the term that collectively describes infections caused by members of the Legionellaceae family.

The Legionella bacterium is a small, aerobic, waterborne, gram-negative, unencapsulated bacillus that is nonmotile, catalase-positive, and weakly oxidase-positive. It is a fastidious organism and does not grow anaerobically or on standard media. Buffered charcoal yeast extract (CYE) agar is the primary medium used for isolation of the bacterium. (See Workup.)

The Legionellaceae family consists of more than 42 species, constituting 64 serogroups. L pneumophila is the most common species, causing up to 90% of the cases of legionellosis, followed by L micdadei (otherwise known as the Pittsburgh pneumonia agent), L bozemanii, L dumoffii, and L longbeachae. Fifteen serogroups of L pneumophila have been identified, with serogroups 1, 4, and 6 being the primary causes of human disease. Serogroup 1 is thought to be responsible for 80% of the reported cases of legionellosis caused by L pneumophila. ^[1]

For patient education information, see Bronchoscopy.

Legionella species are obligate or facultative intracellular parasites. Water is the major environmental reservoir for Legionella; the bacteria can infect and replicate within protozoa such as Acanthamoeba and Hartmannella, which are free-living amoebae found in natural and manufactured water systems. (Legionellae can resist low levels of chlorine used in water distribution systems.)

Within the amebic cells, Legionella species can avoid the endosomal-lysosomal pathway and can replicate within the phagosome. Surviving and growing in amebic cells allows Legionella to persist in nature. (See the image below.)

Legionella species infect human macrophages and monocytes; intracellular replication of the bacterium is observed within these cells in the alveoli. The intracellular infections of protozoa and macrophages have many similarities.

Activated T cells produce lymphokines that stimulate increased antimicrobial activity of macrophages. This cell-mediated activation is key to halting the intracellular growth of legionellae. The significant role of cellular immunity explains why legionellae are observed more frequently in immunocompromised patients. Humoral immunity is thought to play a secondary role in the host response to legionellae infection.

Legionella transmission is thought to occur via inhalation of aerosolized mist from water sources, such as the following, that have been contaminated with the bacterium ^{[2, 3]} :

Cooling systems

Showers

Decorative fountains

Humidifiers

Respiratory therapy equipment

Whirlpool spas

Ice machines

Potting soil

Compost

Roadside puddles

Tubs used for water births ^[4]

Legionnaires disease may be travel associated from exposure in aircraft or hotel facilities. Person-to-person transmission, however, has not been documented.

The highest incidence of Legionnaires disease occurs during late spring and early fall, when air-conditioning systems are used more frequently. ^{[5, 6]} Nosocomial acquisition likely occurs via aspiration, respiratory therapy equipment, ^[3] or contaminated water. In addition, transmission has been linked to the use of humidifiers, nebulizers, and items that were rinsed with contaminated tap water.

The following features increase the likelihood of colonization and amplification of legionellae in human-made water environments:

Temperature of 25-42°C

Stagnation

Scale and sediment

Presence of certain free-living aquatic amoebae capable of supporting intracellular growth of legionellae

The risk of infection increases with the type and intensity of the exposure, as well as the health status of the exposed individual. Numerous factors increase the risk of acquiring legionellae infections, including the following:

Advanced age

Smoking

Chronic heart or lung disease

Immunocompromised hosts with impaired cell-mediated immunity (eg, acquired immunodeficiency syndrome [AIDS]) or immunosuppressive medication use (especially corticosteroids)

Diabetes

Hematologic malignancies

End-stage renal disease

Alcohol abuse

LD has a reported incidence of 8000-18,000 cases per year. In certain geographic areas, community-acquired LD is more common. Although LD is reportable in all 50 states, it is estimated that only 5-10% of cases are reported. While most cases of the disease are sporadic, 10-20% of them are linked to outbreaks. LD is more common in the summer, especially in August, and is slightly more prevalent in the northern US.

Prevalence reports for Legionella have increased with time, likely due to the availability of more effective testing modalities. However, it is also possible that Legionella infections are increasing in frequency for environmental, population-based, or behavioral reasons.

LD is among the top 3-4 microbial causes of CAP, constituting approximately 1-9% of patients with CAP who require hospitalization. LD is an even more common cause of severe pneumonia in patients who require admission to an intensive care unit (ICU), ranking second, after pneumococcal pneumonia, in such cases. In addition, it has become recognized as the most common cause of atypical pneumonia in hospitalized patients.

LD cases acquired in the hospital usually occur as outbreaks and most often result from the presence of legionellae in water sources and on surfaces (eg, pipes, rubber, plastics). The organism is also found in water sediment, which may explain its ability to persist despite flushing of hospital water systems. ^{[7, 8]}

LD is thought to occur worldwide and to be the cause of 2-15% of all CAP cases that require hospitalization. Outbreaks have been recognized throughout North America, Africa, Australia, Europe, and South America.

Men have a greater risk of acquiring L pneumophila infection. Older age is another risk factor; the weighted mean age for patients with LD is 52.7 years, with increasing incidence until age 79 years. Mortality rates are also higher in older patients. The incidence of LD in persons younger than 35 years is less than 0.1 cases per 100,000 people.

Recovery is variable in LD; some patients experience rapid improvement, while others have a much more protracted course despite treatment. The mortality rate approaches 50% with nosocomial infections.

Progressive respiratory failure is the most common cause of death in patients with Legionella pneumonia. However, the mortality rate depends on the comorbid conditions of the patient, as well as on the choice and timeliness of antibiotics administration. The site of acquisition (eg, nosocomial, community-acquired) may also affect the outcome.

See the list below:

Decreased pulmonary function

Fulminant respiratory failure

Dehydration, septic shock

Hyponatremia due to syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

Respiratory insufficiency, hypoxic respiratory failure

Endocarditis

Neurologic symptoms: Including lethargy, headache, altered mental status, and nonfocal neurologic examination findings

Gastrointestinal symptoms: Diarrhea, vomiting

Renal failure

Rhabdomyolysis

Multiple organ failure

Coma

Bacteremia or abscess formation (in the lungs or at extrapulmonary sites) in immunocompromised patients

Death: In 10% of treated nonimmunocompromised patients and in as many as 80% of untreated immunocompromised patients

A study by van Loenhout et al that included 190 patients with LD found that a year after the disease’s onset, many patients were still suffering from 1 or more adverse health effects, particularly fatigue and reduced general quality of life. ^[9]

Kozak-Muiznieks NA, Lucas CE, Brown E, Pondo T, Taylor TH Jr, Frace M, et al. Prevalence of sequence types among clinical and environmental isolates of Legionella pneumophila serogroup 1 in the United States from 1982 to 2012. J Clin Microbiol. 2014 Jan. 52(1):201-11. [Medline]. [Full Text].

Nguyen TM, Ilef D, Jarraud S, Rouil L, Campese C, Che D. A community-wide outbreak of legionnaires disease linked to industrial cooling towers–how far can contaminated aerosols spread?. J Infect Dis. 2006 Jan 1. 193(1):102-11. [Medline].

Woo AH, Goetz A, Yu VL. Transmission of Legionella by respiratory equipment and aerosol generating devices. Chest. 1992 Nov. 102(5):1586-90. [Medline].

Granseth G, Bhattarai R, Sylvester T, Prasai S, Livar E. Notes from the Field: Two Cases of Legionnaires’ Disease in Newborns After Water Births – Arizona, 2016. MMWR Morb Mortal Wkly Rep. 2017 Jun 9. 66 (22):590-591. [Medline].

Brandsema PS, Euser SM, Karagiannis I, DEN Boer JW, VAN DER Hoek W. Summer increase of Legionnaires’ disease 2010 in The Netherlands associated with weather conditions and implications for source finding. Epidemiol Infect. 2014 Jan 24. 1-12. [Medline].

Halsby KD, Joseph CA, Lee JV, Wilkinson P. The relationship between meteorological variables and sporadic cases of Legionnaires’ disease in residents of England and Wales. Epidemiol Infect. 2014 Jan 9. 1-8. [Medline].

Cristino S, Legnani PP, Leoni E. Plan for the control of Legionella infections in long-term care facilities: Role of environmental monitoring. Int J Hyg Environ Health. 2011 Sep 16. [Medline].

Lin YE, Stout JE, Yu VL. Controlling Legionella in hospital drinking water: an evidence-based review of disinfection methods. Infect Control Hosp Epidemiol. 2011 Feb. 32(2):166-73. [Medline].

van Loenhout JA, van Tiel HH, van den Heuvel J, Vercoulen JH, Bor H, van der Velden K, et al. Serious long-term health consequences of Q-fever and Legionnaires’ disease. J Infect. 2014 Jan 25. [Medline].

Cunha BA. Hypophosphatemia: diagnostic significance in Legionnaires’ disease. Am J Med. 2006 Jul. 119(7):e5-6. [Medline].

Kashuba AD, Ballow CH. Legionella urinary antigen testing: potential impact on diagnosis and antibiotic therapy. Diagn Microbiol Infect Dis. 1996 Mar. 24(3):129-39. [Medline].

Tan MJ, Tan JS, Hamor RH, File TM Jr, Breiman RF. The radiologic manifestations of Legionnaire’s disease. The Ohio Community-Based Pneumonia Incidence Study Group. Chest. 2000 Feb. 117(2):398-403. [Medline].

Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1. 44 Suppl 2:S27-72. [Medline].

[Guideline] Arizona Department of Health Services. Guidelines for water immersion and water birth. ADHS. Available at http://www.azdhs.gov/documents/licensing/special/midwives/training/guidelines-for-water-immersion-water-birth.pdf. November 2016; Accessed: June 9, 2017.

Cunha BA. Legionnaires’ disease: clinical differentiation from typical and other atypical pneumonias. Infect Dis Clin North Am. 2010 Mar. 24 (1):73-105. [Medline].

Cunha BA, Strollo S, Schoch P. Extremely elevated erythrocyte sedimentation rates (ESRs) in Legionnaires’ disease. Eur J Clin Microbiol Infect Dis. 2010 Dec. 29 (12):1567-9. [Medline].

Cunha BA. Highly elevated serum ferritin levels as a diagnostic marker for Legionella pneumonia. Clin Infect Dis. 2008 Jun 1. 46 (11):1789-91. [Medline].

Diagnostic Predictors

Diagnostic Eliminators

Clinical Predictors

Clinical Eliminators

Laboratory Predictors ^b

Laboratory Eliminators

Legionnaire disease very likely if >3 predictors present

Legionnaires disease very unlikely if < 3 predictors or >3 diagnostic eliminators present

Abbreviations: CPK = creatinine phosphokinase test; CRP = C-reactive protein; ESR = erythrosedimentation rate.

^a Pulmonary symptoms: shortness of breath, cough, and so forth with fever and a new focal/segmental infiltrate on chest radiograph.

^b Otherwise unexplained. If finding is due to an existing disorder, it should not be used as a clinical predictor.

Burke A Cunha, MD Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Frank C Smeeks, III, MD Specialty Medical Director of Emergency Medicine, Applied Medico Legal Solutions

Frank C Smeeks, III, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Association for Physician Leadership, American Medical Association, North Carolina Medical Society

Disclosure: Nothing to disclose.

Joseph F John Jr, MD, FACP, FIDSA, FSHEA Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina College of Medicine; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Eric M Kardon, MD, FACEP Attending Emergency Physician, Georgia Emergency Medicine Specialists; Physician, Division of Emergency Medicine, Athens Regional Medical Center

Eric M Kardon, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Fred A Lopez, MD Associate Professor and Vice Chair, Department of Medicine, Assistant Dean for Student Affairs, Louisiana State University School of Medicine

Fred A Lopez, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, Infectious Diseases Society of America, and Louisiana State Medical Society

Disclosure: Nothing to disclose.

Scott Savage, DO Associate Clinical Faculty, Department of Emergency Medicine, Wright State University, Boonshoft School of Medicine

Disclosure: Nothing to disclose.

Lynn E Sullivan, MD Assistant Professor of Medicine, Yale University School of Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Jeter (Jay) Pritchard Taylor III, MD Compliance Officer, Attending Physician, Emergency Medicine Residency, Department of Emergency Medicine, Palmetto Health Richland, University of South Carolina School of Medicine; Medical Director, Department of Emergency Medicine, Palmetto Health Baptist

Jeter (Jay) Pritchard Taylor III, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Legionnaires Disease

Research & References of Legionnaires Disease|A&C Accounting And Tax Services
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