Legionella Infection

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:

• Cooling towers

• Humidifiers

• Respiratory therapy equipment

• Whirlpool spas ^[5]

• Evaporative condensers

• Potable water distribution systems (eg, showers, faucets) ^{[1, 6]}

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 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]

In adults, recognized risk factors for legionellosis include the following:

• Cigarette smoking

• Alcoholism

• Chronic lung disease

• Chronic heart disease

• Immunosuppression (eg, malignancies, immunosuppressive therapy such as corticosteroids, human immunodeficiency virus [HIV], acquired immunodeficiency syndrome [AIDS])

• End-stage renal disease

• Diabetes mellitus

• Advanced age

Surgery, especially for head and neck malignancies and for solid organ transplantations, predisposes patients to nosocomial infections.

Risk factors for children are less well defined than they are in adults. Apparent predisposing factors, from reported cases, include the following: ^{[4, 8]}

• Immunodeficiency (primary or secondary) - Malignancies, severe combined immunodeficiency, chronic granulomatous disease, organ transplantation, and treatment with corticosteroids

• Preexisting respiratory disease - Acute or chronic lung disease, asthma, tracheal stenosis, and tracheobronchomalacia

• Young age (especially neonates)

• Water births

Rare cases of legionellosis are reported in children who are immunocompetent and who lack predisposing conditions.

United States statistics

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 Centers for Disease Control and Prevention (CDC) reported 2809 cases of Legionnaires disease in 2015, of which 3% were confirmed to be associated with a healthcare facility and 17% were possibly associated. Among the definite healthcare-associated cases, 88% occurred in those 60 years of age and older. The fatality rate was 25% in definite healthcare-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 1449 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 6141 of Legionella cases were reported, a 4.5-fold increase since 2000. ^{[24, 25]}

International statistics

Legionnaires disease is believed to have worldwide distribution and to cause 2-15% of all CAP cases requiring hospitalization.

A review of 45 cases of legionellosis in neonates from Europe, North America, and Asia found that 32 (71%) were nosocomial infections. An underlying condition, such as prematurity, immunodeficiency, congenital heart disease, and transesophageal fistula, was reported in 13 patients (29%). ^[26]

A study that used data from the European Surveillance System reported that about 68% of cases of healthcare-associated Legionnaires disease were hospital-acquired and nearly 32% were associated with other healthcare facilities. The risk of healthcare-associated disease was higher for women, children, adolescents, and older adults. ^[27]

Sex- and age-related demographics

Males are more than twice as likely as females to develop Legionnaires disease.

Middle-aged and older adults have a high risk of developing Legionnaires disease, whereas 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.

With early initiation of appropriate therapy, most patients experience defervescence and symptomatic improvement within 3-5 days. Factors that predict a poor outcome include advanced age, underlying disease (including prematurity), delayed therapy, and respiratory failure. Subsequent episodes are rare.

Morbidity/mortality

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:

• Age (especially those younger than 1 year and elderly patients)

• Predisposing underlying conditions, such as chronic lung disease, immunodeficiency, malignancies, end-stage renal disease, and diabetes mellitus

• Nosocomial acquisition

• Delayed initiation of specific antimicrobial therapy

Complications

The following complications may persist for weeks to months after disease onset:

• Empyema

• Pulmonary cavitation

• Bullous emphysema

• Renal failure

• Memory loss

• Fatigue

• Neurologic disorders

• Multiorgan failure

Legionnaires disease can be fatal.