Background
Legionnaires disease (LD) was recognized in 1976 after an outbreak of pneumonia at an American Legion convention in Philadelphia. Soon after, the etiologic agent was identified as a fastidious gram-negative bacillus and named Legionella pneumophila. Although several other species of the genus Legionella were subsequently identified, L pneumophila is the most frequent cause of human legionellosis and a relatively common cause of community-acquired and nosocomial pneumonia in adults. In children, L pneumophila is also an important, although relatively uncommon, cause of pneumonia.
Legionellosis refers to 2 distinct clinical syndromes: Legionnaires disease, which most often manifests as severe pneumonia accompanied by multisystemic disease, and Pontiac fever, which is an acute, febrile, self-limited, viral-like illness. [1, 2]
Pathophysiology
Legionella organisms are aerobic, motile, and nutritionally fastidious pleomorphic gram-negative rods. The growth of the organisms depends on the presence of L-cysteine and iron in special media. The organism has been isolated in natural aquatic habitats (freshwater streams and lakes, water reservoirs) and artificial sources (cooling towers, potable water distribution systems). Freshwater amoebae appear to be the natural reservoir for the organisms. [3] Optimal growth temperature is 28-40°C; organisms are dormant below 20°C and are killed at temperatures above 60°C.
Although more than 70 Legionella serogroups have been identified among 50 species, L pneumophila causes most legionellosis. L pneumophila serogroup 1 alone is responsible for 70-90% of cases in adults. In a pediatric series, L pneumophila serogroup 1 accounted for only 48% of cases, serogroup 6 accounted for 33%, and the remaining cases involved other serotypes and species. Legionella micdadei and L dumoffii are the second and third most common species to cause Legionnaires disease in children, respectively. [4]
Transmission occurs by means of aerosolization or aspiration of water contaminated with Legionella organisms. Wounds may become infected after contact with contaminated water. The following systems are linked to transmission of Legionella organisms:
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Cooling towers
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Humidifiers
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Respiratory therapy equipment
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Whirlpool spas [5]
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Evaporative condensers
Most nosocomial infections and hospital outbreaks have been linked to contaminated hot water supply. However, contamination of cold-water supply has also been reported. [7] Nosocomial Legionnaires disease associated with water birth is reported in a few neonates, but the risk appears to be low. [8, 9] Person-to-person transmission has not been demonstrated.
Mucociliary action clears Legionella organisms are cleared from the upper respiratory tract. Any process that compromises mucociliary clearance (eg, smoking tobacco) increases risk of infection. Virulence varies between strains of L pneumophila. For example, some strains can adhere to the respiratory epithelial cells via pili, whereas strains with a mutated gene that encodes for the pili show reduced adherence in vitro. [10]
Organisms that reach the alveoli undergo phagocytosis by the alveolar macrophages but are not actively killed. Macrophages may actually support the growth of Legionella organisms. The bacteria multiply intracellularly until the cell ruptures. Liberated bacteria then infect other macrophages. Additional virulence factors include genes that potentiate infection of macrophages and inhibit phagosomal fusion, allowing intracellular growth. [11]
Cell-mediated immunity appears to be the primary host defense mechanism against Legionella infection. Activation of macrophages produces cytokines that regulate antimicrobial activity against Legionella organisms. Individuals with certain deficiencies in cell-mediated immunity are at increased risk for legionellosis. [4] Complicated cases have been reported in children treated with steroids. [12, 13]
The role of neutrophils in host defense against Legionella infection is unclear; neutropenia does not appear to predispose patients to legionellosis. Humoral immunity may play a secondary role.
Once infection is established, Legionella organisms cause an acute fibrinopurulent pneumonia with alveolitis and bronchiolitis. In addition to the lungs, Legionella organisms may infect the lymph nodes, brain, kidney, liver, spleen, bone marrow, and myocardium. [14]
Epidemiology
Frequency
United States
An estimated 8000-18,000 cases of Legionnaires disease are reported in the United States each year. Most cases are not reported. More than 80% of cases are sporadic throughout the year, and the rest occur in outbreaks during the summer and early fall.
In adults, legionellosis causes 2-15% of all cases of community-acquired pneumonia (CAP) requiring hospitalization. Legionellosis is the second most frequent cause of severe pneumonia requiring ICU admission. Estimates for the proportion of nosocomial pneumonias caused by Legionella species widely vary, but the numbers probably represent an underestimation because most hospitals only test for serogroup 1. [15]
Serologic studies suggest that children are frequently exposed to Legionella species. However, this organism is a rare cause of acute respiratory disease in the pediatric population, with only scattered case reports available to determine its natural history in this age group. Moreover, it is not commonly seen in immunocompromised pediatric patients. [16]
The estimated frequency of Legionella pneumonia cases that require hospitalization is approximately 1-5%. [4, 17] The reported annual incidence of both CAPs and nosocomial pneumonias caused by Legionella species has increased. Most reported cases have involved neonates, children who are immunocompromised [4] (including those with prolonged courses of corticosteroids [12, 13] ), and children with underlying respiratory disease. [18]
The CDC reported 2,809 cases of Legionnaires’ disease in 2015, of which 3% were confirmed to be associated with a health-care facility and 17% were possibly associated. Among the definite health care-associated cases, 88% occurred in those 60 years of age and older. The fatality rate was 25% in definite health care- associated cases and 10% for the possibly associated cases. [19]
A study reviewed case records to determine the epidemiology of and risk factors for the 1,449 cases reported to the New York City Department of Health and Mental Hygiene from 2002–2011. Incidence of Legionnaires’ disease in the city of New York increased 230% from 2002 to 2009 and followed a socioeconomic gradient, with highest incidence occurring in the highest poverty areas. The study also added that further studies are required to clarify whether neighborhood-level poverty and work in some occupations represent risk factors for this disease. [20, 21]
According to the CDC, passive surveillance for legionellosis in the United States showed a 249% increase in crude incidence during 2000-2011. In 2011, the Active Bacterial Core (ABC) surveillance system was instituted, Overall rates were similar to the passive system however, ABC’s data showed that during 2011-2013, 44% of patients with legionellosis required intensive care, and 9% died. [22, 23]
In 2016, a total of 6,141 of Legionella cases were reported, a 4.5-fold increase since 2000. [40, 41]
International
Legionnaires disease is believed to have worldwide distribution and to cause 2-15% of all CAP cases requiring hospitalization.
Mortality/Morbidity
The mortality rate in patients with Legionnaires disease is 5-80%, depending on certain risk factors. The factors associated with high mortality rates include the following:
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Age (especially those younger than 1 y and elderly patients)
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Predisposing underlying conditions, such as chronic lung disease, immunodeficiency, malignancies, end-stage renal disease, and diabetes mellitus
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Nosocomial acquisition
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Delayed initiation of specific antimicrobial therapy
Sex
Males are more than twice as likely as females to develop Legionnaires disease.
Age
Middle-aged and older adults have a high risk of developing Legionnaires disease while it is rare in young adults and children. Among children, more than one third of reported cases have occurred in infants younger than 1 year.
