Legionellosis overview

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  Yazan Daaboul, M.D.; Serge Korjian M.D.

## Overview

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Legionellosis is an infectious disease caused by Legionella species, a pleomorphic, aerobic, catalase-positive, oxidase-positive, non-spore-forming, non-capsulated, motile, Gram-negative bacteria. The majority of cases of legionellosis are reported between the Summer and early Fall (between June and October). Approximately 8,000-18,000 individuals are hospitalized annually in the USA for Legionnaires' disease with a case fatality rate ranging between 10% to 35%. Legionellosis may be classified into three types based upon the affected organ systems and the clinical presentation: pulmonary infection (Legionnaires' disease), extrapulmonary infection, and Pontiac fever. Legionella is usually transmitted by aerosol droplets when individuals breathe in contaminated mist or vapor (e.g. whirlpool spa, river, cruise ships, cooling towers, air conditioners, water supply systems). L. pneumophila usually invades host cells and replicates intracellularly. In Legionnaires' disease, the majority of exposed patients do not develop any symptoms. Patients who develop clinical manifestations usually report pneumonia-like symptoms that worsen at 4 to 6 days following onset of symptoms and eventually resolve by day 5 to 10 of symptom-onset. Approximately 1% to 35% of individuals progress to develop Legionnaires'-related complications and death. Complications of Legionnaires' disease include empyema, lung failure, acute kidney injury, endocarditis, neurological disease, septic shock, and multi-organ failure. The prognosis is generally good for healthy patients, but patients with co-morbidities are at higher risk of developing complications and death. In contrast, Pontiac fever has a high attack rate but is associated with mild flu-like symptoms that resolve within 1 to 2 days and is almost always self-limited without any complications. The most important risk factor in the development of legionellosis is recent exposure to either aerosolized water or contaminated water. Other risk factors include old age, concomitant lung disease, active smoking status, and immunosuppression. Urine antigen testing in the first-line diagnostic method. Culture of the lower respiratory secretion is the gold standard for the detection of Legionella and diagnosis of Legionnaires' disease. Imaging may also be indicated among patients with Legionnaires' disease. Pharmacologic medical therapy is indicated in Legionnaires' disease, but not in Pontiac fever. The preferred regimens for both mild and moderate-to-severe Legionnaires' disease include either azithromycin or a fluoroquinolone. Patients who develop legionellosis-related complications may require other or additional pharmacologic agents. There is no vaccine against legionellosis, and antibiotic prophylaxis is not effective.

## Historical Perspective

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Legionnaires' disease acquired its name in 1976 when an outbreak of pneumonia occurred among people attending a convention of the American Legion in Philadelphia. On January 18, 1977 the causative agent was identified as a previously unknown bacterium, subsequently named Legionella.

## Classification

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Legionellosis may be classified into three types based upon the affected organ systems and the clinical presentation: pulmonary infection (Legionnaires' disease), extrapulmonary infection, and Pontiac fever. Legionellosis may also be classified based on the infectious species responsible for the disease.

## Pathophysiology

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Legionella is usually transmitted by aerosol droplets when individuals breathe in contaminated mist or vapor (e.g. whirlpool spa, river, cruise ships, cooling towers, air conditioners, water supply systems). L. pneumophila usually invades the host cells and replicates intracellularly. Legionella is internalized using pseudopods and protects itself in a membrane-bound vacuole that does not fuse with lysosomes.

## Causes

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L.pneumophila is a ubiquitous aquatic organism that thrives in warm environments (32°- 45°C). L. pneumophila is a pleomorphic, aerobic, catalase-positive, oxidase-positive, non-spore-forming, non-capsulated, motile, Gram-negative bacteria. Although Legionella is categorized as a Gram-negative bacterium, it stains poorly to Gram stain due to its unique lipopolysaccharide-content in the outer psuedospamodulating leaflet of the outer cell membrane.

## Differential Diagnosis

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Legionellosis must be differentiated from other causes of fever, dyspnea, cough, and sputum production, such as bacterial pneumonia, viral pneumonia, and other causes of atypical pneumonia.

## Epidemiology and Demographics

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The majority of cases of legionellosis are reported between the Summer and early Fall (between June and October). Approximately 8,000-18,000 individuals are hospitalized annually in the USA for Legionnaires' disease with a case fatality rate ranging between 10% to 35%. The median case-patient age is 61 years, and the male to female ratio is 1.8 to 1.

## Risk Factors

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The most important risk factor in the development of legionellosis is recent exposure to either aerosolized water or contaminated water. Other risk factors include old age, concomitant lung disease, active smoking status, and immunosuppression.

## Natural History, Complications and Prognosis

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In Legionnaires' disease, the majority of exposed patients do not develop any symptoms. Patients who develop clinical manifestations usually report pneumonia-like symptoms that worsen at 4 to 6 days following onset of symptoms and eventually resolve by day 5 to 10 of symptom-onset. Approximately 1% to 35% of individuals progress to develop Legionnaires'-related complications and death. Complications of Legionnaires' disease include empyema, lung failure, acute kidney injury, endocarditis, neurological disease, septic shock, and multi-organ failure. The prognosis is generally good for healthy patients, but patients with co-morbidities are at higher risk of developing complications and death. In contrast, Pontiac fever has a high attack rate but is associated with mild flu-like symptoms that resolve within 1 to 2 days and is almost always self-limited without any complications.

## Diagnosis

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### History and Symptoms

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Legionellosis may manifest with either Legionnaires' disease or Pontiac Fever. Legionnaires' disease is more severe and typically manifests with fatigue, malaise, symptoms of pneumonia (fever, dyspnea, chest pain, and cough) and occasionally diarrhea and nausea. In contrast, Pontiac fever is a milder form of respiratory flu-like disease (fever and cough) but does not result in pneumonia. Patients with legionellosis often report a recent history of travel, hospitalization, exposure to contaminated water, or exposure to healthcare settings.

### Physical Examination

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Physical examination may be remarkable for fever, as well as consolidation and crackles on pulmonary auscultation. Patients with advanced disease may develop neurological signs, including altered mental status, weakness, and ataxia.

### Laboratory Findings

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Laboratory abnormalities in Legionnaires' disease include leukocytosis with relative lymphopenia, hyponatremia, hypophosphatemia, and elevated levels of AST/ALT, CPK, ESR, CRP, LDH, and ferritin. Urine antigen testing in the first-line diagnostic method. Culture of the lower respiratory secretion is the gold standard for the detection of Legionella and diagnosis of Legionnaires' disease.

### Chest X ray

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Common chest x-ray findings in Legionnaires' disease include consolidation and pleural effusion. There are usually no chest x-ray findings in Pontiac fever.

### CT

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In Legionnaires' disease, chest CT findings may include bilateral, multiple affected segments and peripheral lung consolidation with ground glass opacity. There are usually no chest CT findings in Pontiac fever.

### Other Diagnostic Studies

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Additional studies are not required for the diagnosis of legionellosis.

## Treatment

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### Medical Therapy

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Pharmacologic medical therapy is indicated in Legionnaires' disease. The preferred regimens for both mild and moderate-to-severe pneumonia include either azithromycin or a fluoroquinolone. Patients who develop legionellosis-related complications may require other or additional pharmacologic agents. Pontiac fever is self-limited and may be treated with symptomatic therapy only.

### Prevention

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There is no vaccine against legionellosis, and antibiotic prophylaxis is not effective. Travelers at increased risk for infection, such as the elderly or those with immunocompromising conditions such as cancer or diabetes, may choose to avoid high-risk areas, such as whirlpool spas.

## References

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