Background
Legionella pneumophila is an important cause of both nosocomial and community-acquired pneumonia (CAP) and must be considered a possible causative pathogen in any patient who presents with pneumonia.
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. A bacterium that would later be named L pneumophila was isolated from different organ tissues of guinea pigs inoculated with lung tissue samples from 4 individuals who died. Although this pathogen was not identified until 1976, retrospective analysis suggests that L pneumophila may have been responsible for previous pneumonia epidemics in Philadelphia; Washington, DC; and Minnesota. L pneumophila was identified in a clinical specimen dating to 1943.
Legionellosis is the term that collectively describes infections caused by members of the Legionellaceae family. Legionnaires disease (LD) is the pneumonia caused by L 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.
Pathophysiology
The Legionella bacterium is a small, aerobic, waterborne, gram-negative, unencapsulated bacillus that is nonmotile, catalase-positive, and weakly oxidase-positive. Legionella 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.
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 Legionella micdadei (otherwise known as the Pittsburgh pneumonia agent), Legionella bozemanii, Legionella dumoffii, and Legionella 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.
Legionella species are obligate or facultative intracellular parasites. Water is the major environmental reservoir for Legionella. The bacterium can infect and replicate within protozoa such as Acanthamoeba and Hartmannella species, which are free-living amoebae found in both natural and manufactured water systems. The Legionella species within the amebic cells can avoid the endosomal-lysosomal pathway and can replicate within the phagosome. Legionella can survive and grow in the amebic cells, thereby enabling the organism to persist in nature.
Legionella species infect human macrophages and monocytes, and intracellular replication of the bacterium is observed within these cells in the alveoli. The intracellular infections of protozoa and macrophages have many similarities.
Transmission is thought to occur via inhalation of aerosolized mist from water sources (eg, whirlpools, showers, cooling towers, ice machines/potting soil/compost/roadside puddles[1] ) contaminated with either the bacterium. Direct inhalation is the most likely method of transmission, with aerosol-generating systems playing a crucial role.[2] Legionnaires' disease may be travel associated from exposure in aircraft or hotel facilities. Person-to-person transmission has not been documented. The highest incidence occurs during the warmer months, when air-conditioning systems are used more frequently. Nosocomial acquisition likely occurs via aspiration, respiratory therapy equipment[2] , 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 man-made water environments: (1) temperature of 25-42°C, (2) stagnation, (3) scale and sediment, and (4) presence of certain free-living aquatic amoebae capable of supporting intracellular growth of legionellae. Legionellae can resist low levels of chlorine used in water distribution systems.
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.
Epidemiology
Frequency
United States
LD has a reported incidence of 8000-18,000 cases per year. In certain geographic areas, community-acquired LD is more common.
LD is reportable in all 50 states. Only 5-10% of cases are estimated to be reported. While most cases of LD are sporadic, 10-20% are linked to outbreaks. 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). LD ranks second, after pneumococcal pneumonia, as the etiology of pneumonia severe enough to require ICU admission.
Some LD cases are acquired in the hospital; they usually occur as outbreaks. Legionellae in the hospital setting is usually due to its presence 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.[3, 4]
International
LD is thought to occur worldwide and to be the cause of 2-15% of all CAP cases that require hospitalization.
Mortality/Morbidity
The mortality rate may approach 100% in patients with underlying disease. In untreated patients, the mortality rate may be as high as 80%. According to the US Centers for Disease Control and Prevention, the incidence of Legionnaires disease is increasing.[5]
Sex
Men have a greater risk of acquiring L pneumophila infection.
Age
Elderly persons have a greater risk of acquiring infection with Legionella species.
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| Clinical Features | Qualifying Conditions | Point Score |
| Temperature >103°F* | With relative bradycardia | +5 |
| Headache | Acute onset | +2 |
| Mental confusion/lethargy* | Not drug induced | +4 |
| Ear pain | Acute onset | -3 |
| Nonexudative pharyngitis | Acute onset | -3 |
| Hoarseness | Acute, not chronic | -3 |
| Sputum (purulent) | Excluding chronic bronchitis | -3 |
| Hemoptysis* | Mild/moderate | -3 |
| Chest pain (pleuritic) | Rapidly progressive asymmetrical infiltrates* (excluding severe influenza/severe acute respiratory syndrome) | -3 |
| Loose stools/watery diarrhea* | Not drug induced | +3 |
| Abdominal pain* | With or without diarrhea | +5 |
| Renal failure* | Acute, not chronic | +3 |
| Shock/hypotension* | Not 2° to acute cardiac | -5 |
| /pulmonary causes | +5 | |
| Splenomegaly | Excluding non-CAP causes | -5 |
| Lack of response to beta lactams | After 72 h (excluding viral pneumonias) | +5 |
| Laboratory Features | ||
| Chest radiograph | Rapidly progressive asymmetrical infiltrates* (excluding severe influenza/SARS) | +3 |
| ↓ PO2 with ↑ A-a gradient (>35)* | (Excluding severe influenza/SARS) | -5 |
| ↓ Na+ | Acute onset | +1 |
| ↓ PO4 =* | Acute onset | +5 |
| ↑ SGOT/SGPT (early mild/transient)* | Acute onset | +4 |
| ↑ Total bilirubin | Otherwise unexplained | +1 |
| ↑ LDH (>400 U/L)* | Excluding HIV/PCP | -5 |
| ↑ CPK/aldolase | Otherwise unexplained | +4 |
| ↑ CRP (>30 mg/L) | Acute onset | +5 |
| ↑ Cold agglutinins (≥ 1:64) | Acute onset | -5 |
| ↑ Creatinine | Acute onset | +2 |
| Microscopic hematuria* | Excluding trauma, BPH, Foley catheter, bladder/renal neoplasms | +2 |
| Likelihood of Legionella infection | ||
| Total points | >15 Legionella infection very likely | |
| 5-15 Legionella infection likely | ||
| < 5 Legionella infection unlikely | ||
| *Otherwise unexplained (acute and associated with pneumonia) | ||
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