eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Legionella Infection

Author: Mobeen H Rathore, MD, CPE, FAAP, FIDSA, Chief of Division of Pediatric Infectious Diseases/Immunology, Associate Chairman of Department of Pediatrics, University of Florida College of Medicine at Jacksonville; Hospital Epidemiologist and Section Chief of Infectious Disease and Immunology, Wolfson Children's Hospital; Director of University of Florida Center for HIV/AIDS Research, Education and Service (UF CARES)
Coauthor(s): Ana Alvarez, MD, Assistant Professor of Pediatrics, Pediatric Infectious Diseases Fellowship Director, Departments of Pediatrics, University of Florida Health Science Center at Jacksonville
Contributor Information and Disclosures

Updated: Feb 5, 2009

Introduction

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

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.² Optimal growth temperature is 28-40°C; organisms are dormant below 20°C and are killed at temperatures above 60°C.  

Although 64 Legionella serogroups have been identified among 42 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.³

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 spas⁴
• Evaporative condensers
• Potable water distribution systems (eg, showers, faucets)^1,5

Most nosocomial infections and hospital outbreaks have been linked to contaminated hot water supply. However, contamination of cold-water supply has also been reported.⁶ Nosocomial Legionnaires disease associated with water birth is reported in a few neonates, but the risk appears to be low.^7,8 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.⁹

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.¹⁰

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.³

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.¹¹

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 1.¹²

Serologic studies suggest that children are frequently exposed to Legionella species. However, this organism is not a common cause of acute respiratory disease in children.¹³  The estimated frequency of Legionella pneumonia cases that require hospitalization is approximately 1-5%.^3,14 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 immunocompromised³ (including those with prolonged courses of corticosteroids¹⁵ ), and children with underlying respiratory disease.¹⁶

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:

• Age (especially those younger than 1 y 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

Sex

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

Age

Middle-aged and older adults have a higher risk of developing Legionnaires disease than do young adults and children. Among children, more than one third of reported cases have occurred in infants younger than 1 year.

Clinical

History

• Pneumonia is the predominant clinical manifestation of Legionnaires disease (LD).
  • After an incubation period of 2-10 days, patients typically develop the following nonspecific symptoms:
    • Fever
    • Weakness
    • Fatigue
    • Malaise
    • Myalgia
    • Chills
  • Respiratory symptoms may not be present initially but develop as the disease progresses. Almost all patients develop a cough, which is initially dry and nonproductive, but may become productive, with purulent sputum and, (in rare cases) hemoptysis. Patients may experience chest pain.
  • Neurologic and GI symptoms are usually prominent. Neurologic complaints may include the following:
    • Headache
    • Lethargy
    • Confusion
    • Cerebellar ataxia
    • Agitation
    • Stupor
  • Common GI symptoms include diarrhea (watery and nonbloody), nausea, vomiting, and abdominal pain.¹⁷
  • In neonates, Legionnaires disease can manifest as septicemia and/or pneumonia with a fulminant course, often diagnosed at autopsy.
  • Extrapulmonary legionellosis is rare; the most common site of extrapulmonary infection in adults is the heart. In children, extrapulmonary sites may include the liver, spleen, brain, and lymph nodes.¹⁸ Manifestations of extrapulmonary legionellosis may include the following:
    • Sinusitis
    • Cellulitis
    • Peritonitis
    • Pyelonephritis
    • Pancreatitis
    • Wound infection
    • Lymphadenopathy
    • Prosthetic valve endocarditis
    • Myocarditis
    • Pericarditis
    • Postcardiotomy syndrome
• Pontiac fever is an influenzalike illness, typically with an abrupt onset. The incubation period is 24-48 hours. Prominent symptoms include fever, malaise, myalgia, cough, and headache. Pontiac fever tends to occur in outbreaks, and the infection rate is greater than 90%. The disease is self-limiting, persisting for approximately 1 week.

Physical

The severity of illness at presentation varies from mild nonspecific findings to profound respiratory and/or multiorgan failure.

• Fever is typically present (98%). Temperatures exceeding 40°C occur in 20-60% of patients. The occurrence of bradycardia relative to fever has been overemphasized, but it may occur in patients with advanced pneumonia.¹⁷
• Hypotension has been reported in 17% of patients with community-acquired pneumonia(CAP).
• Lung examination reveals rales and signs of consolidation late in the disease course.
• In patients with extrapulmonary legionellosis, physical findings relate to the involved organs.
• Manifestations in children who are immunocompromised appear similar to manifestations in adults. However, in neonates, signs of sepsis with multisystemic involvement appear to be more prominent. Progression to respiratory failure is very rapid, and the disease is likely to be fatal.¹⁹

Causes

• In adults, recognized risk factors for legionellosis include the following:
  • Cigarette smoking
  • Chronic lung 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:³
  • 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)
• Rare cases of legionellosis are reported in children who are immunocompetent and who lack predisposing conditions.

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