In the last few decades, Legionnaire’s disease has emerged as an important cause of human morbidity and mortality and has been implicated in a wide spectrum of human disease. Although it is not spread by human transmission, it is ubiquitous in the environment and aerosol exposure to contaminated water has been responsible for outbreaks both in the community and hospitals. As the body relies on cell-mediated immunity to help fight the disease, the most susceptible people are the elderly, hospitalized patients, and the immune suppressed. If treated with appropriate antibiotics the mortality is low, but the clinical syndrome is vague and diagnosis relies on specialized laboratory tests. Control is possible through careful monitoring of water sources along with appropriate decontamination.
In summer 1976, participants of an American Legions conference in Philadelphia began to fall ill with a mysterious pneumonia. The illness, dubbed Legionnaire’s disease, led to 34 deaths among the 221 people affected. Ultimately, Legionella pneumophilia, a novel gram-negative bacterium, was isolated from harvested lung tissue of the epidemic’s victims.
Over the last three decades, over 40 species and 64 serotypes of Legionella have been identified. Most have been isolated from the environment and nearly half have been implicated with human disease. L. pneumophilia remains the most clinically significant species accounting for over 80 percent of Legionellosis cases in the United States and is being increasingly recognized as a fairly common cause of pneumonia in adults. Legionella infections may be sporadic or epidemic, community or hospital acquired.
Epidemiologically, there are three main requirements for a Legionella infection to occur: a contaminated source, a means of dissemination, and host susceptibility.
Water is the only documented source of Legionella species, particularly the surface waters of rivers, lakes, and reservoirs, and drinking water. Man-made sources include cooling towers and potable water distributions systems. Freshwater amoebas serve as a reservoir and have been found to facilitate the growth of the bacteria. Another factor that supports the survival of Legionella in natural or treated water is its relative resistance to heat and chlorination, which is why it can thrive in normally inhospitable environments such as hot-water tanks.
Transmission occurs through inhalation of aerosols or aspiration of contaminated water. Documented sources of dissemination include cooling towers, humidifiers, respiratory therapy equipment, whirlpool spas, evaporative condensers, hot-water supplies, and potable water distributors (e.g., showers, faucets). Because numerous activities, including taking a shower and flushing a toilet, can produce aerosols in the environment, it is often difficult to identify the source of infection. Direct infection of wounds after contact with contaminated water has also been documented. No human-to-human transmission has ever been documented.
Host susceptibility to Legionella depends on both specific and nonspecific defenses. Processes that compromise the mucociliary action of the upper respiratory tract, such as smoking, can leave a person more vulnerable to infection. Other significant risk factors include chronic lung disease, end-stage renal disease, diabetes mellitus, and advanced age. Immunosuppression (e.g., malignancy, corticosteroid therapy, human immunodeficiency virus) has been shown to be the most important factor in the development and severity of infection. Surgery (especially head/neck, transplant procedures) has also been shown to predispose a patient to hospital-acquired infections. Infections are more common in the summer months, presumably because there is an increased use of aerosol-generating cooling systems and improved growth conditions for the organism.
Legionella infections begin in the lower respiratory tract. Once the bacteria reach the alveoli, they undergo phagocytosis by alveolar macrophages. Unfortunately, Legionella is a facultative intracellular parasite with the ability to block the normal killing action of the macrophage. Thus, instead of killing the microorganism, the macrophage becomes a reservoir for the bacteria to proliferate intracellularly until the cell ruptures releasing more bacteria to go on and infect other cells.
The body’s primary immune response to Legionella infections rests on cell-mediated immunity. Immunologically activated monocytes and macrophages restrict intracellular bacterial growth through cytokines which regulate the body’s antimicrobial activity against the bacteria. Also lymphocytes have been shown to be extremely active during an infection.
There are two distinct clinical syndromes associated with Legionella. The first and most common is an acute pneumonia referred to as Legionnaire’s diseases. The second, and much less common form, is a viral-like syndrome known as Pontiac fever named after the city in Michigan where the first-known epidemic occurred.
Legionnaire’s disease can vary in severity from a mild illness (walking pneumonia) to a fatal multilobular pneumonia. The incubation period is two to ten days. Typical symptoms are nonspecific and include headache, confusion, weakness, muscle aches, malaise, fatigue, fever, and chills. Prominent gastrointestinal disturbances often occur and may include diarrhea (watery, nonbloody), nausea, vomiting, and abdominal pain. In neonates, Legionnaire’s disease can be manifest as fulminant sepsis and/or pneumonia which progresses rapidly to respiratory failure and death.
The classic patient presentation is a chronically ill, middle-aged smoker with a high, unremitting fever, nonproductive cough, diarrhea, confusion, low sodium, and abnormal liver function tests. As the disease progresses, the cough can turn productive with purulent sputum. Chest pain is common and progressive shortness of breath is the rule. Legionella may also infect lymph tissue, brain, kidneys, liver, bone marrow, and heart, although extrapulmonary infection is rare.
Pontiac fever is an acute flu-like illness that begins with an abrupt onset. The incubation period is 24 to 48 hours. Symptoms include fever, headache, weakness, and severe muscle aches. Neurological disturbances such as dizziness, ataxia, confusion, irritability, nightmares, and neck pain or stiffness are common. Patients may or may not have a cough and sore throat. The disease is self-limiting with symptoms lasting approximately one week with full recovery taking weeks. Pontiac fever tends to occur in outbreaks and has an infection rate greater than 90 percent.
Legionella can be suspected clinically but can only be confirmed through laboratory testing. Some general nonspecific laboratory examinations may show low blood sodium and other chemical abnormalities. Protein and blood in the urine are often seen on urinalysis. The gold standard for diagnosis is culture from respiratory secretions or other specimens on special media. A rapid urinary antigen test is available to help in diagnosis, although it only detects L. pneumophilia serotype 1, the most common cause of Legionnaire’s disease. Other tests such as direct fluorescent antibody testing, polymerase chain reaction, and serologic tests are available but are not as widely used.
Response to antibiotic therapy is generally quick, although convalescence may last many weeks to months. Fluoroquinolones, macrolides, tetracycline, and rifampin have been shown to be effective in the treatment of Legionella infections. The antibiotic treatment of choice is azithromycin. Rifampin has been shown to be beneficial when added to treatment regimens in severe cases. With appropriate therapy, the mortality of Legionnaire’s disease varies from around 5 percent in healthy persons to 25 percent in immunocompromised patients. Pontiac fever should be treated symptomatically and does not require antibiotic therapy.
Decontamination of environmental source is of primary importance for preventing infections. Water systems can be treated through superheating or shock chlorination. Facilities with high-risk populations such as transplant centers should regularly monitor and culture water supplies for Legionella. Potable water should be maintained at temperatures not suitable for growth of Legionella species. Cooling towers must receive regular routine maintenance and be filled with sterile water. Immunization has been effective in experimental animals but has not been attempted in humans.
Gerontology; Infectious Diseases (General); Pneumonia.
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