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General Questions about Legionnaires' Disease

What is Legionnaires' disease?

Legionnaires' disease is a lung infection (pneumonia) caused by a bacterium named Legionella pneumophila. The name Legionella pneumophila was derived from the original outbreak at the 1976 American Legion Convention in Philadelphia. Pneumophila means lung-loving in Greek.

What organism causes Legionnaires’ disease?

Legionnaires’ disease is caused by bacteria that belong to the family Legionellaceae. This family now includes 48 species and over 70 serogroups. Approximately half of these species have been implicated in human disease. Legionella pneumophila is responsible for approximately 90% of infections. Most cases are caused by L. pneumophila, serogroup 1. Legionella species are small (0.3 to 0.9 µm in width and approximately 2 µm in length) faintly staining Gram-negative rods with polar flagella (except L. oakridgensis). They generally appear as small coccobacilli in infected tissue or secretions. They are distinguished from other saccharolytic bacteria by their requirement for L-cysteine and iron salts for primary isolation on solid media and by their unique cellular fatty acids and ubiquinones.

What is the natural habitat of Legionella bacteria?

Legionella organisms are readily found in natural aquatic bodies and some species have been recovered from soil. The organisms can survive in a wide range of conditions, including temperatures of 0 to 63o C, pH of 5.0 to 8.5, and dissolved oxygen concentrations of 0.2 to 15 ppm in water. Temperature is a critical determinant for Legionella proliferation. Colonization of hot water tanks is more likely if tank temperatures are between 40 and 50oC (104 to 122o F). Legionella and other microorganisms become attached to surfaces in an aquatic environment forming a biofilm. Legionella has been shown to attach to and colonize various materials found in water systems including plastics, rubber, and wood. Organic sediments, scale, and inorganic precipitates provide Legionella with a surface for attachment and a protective barrier. Interestingly, the growth of other environmental organisms is stimulated by organic sediment, which in turn leads to the formation of by-products that stimulate the growth of Legionella.

What are the symptoms of Legionnaires' disease?

The incubation period of Legionnaires' disease is from two to ten days; this is the time it takes before symptoms of the illness appear after being exposed to the bacteria. For several days, the patient may feel tired and weak. Most patients who are admitted to the hospital develop high fever often greater than 39.5°C (103°F). Cough can be the first sign of a lung infection. The cough may be sufficiently severe to cause sputum production (coughed up mucous). Gastrointestinal stomach symptoms are common with diarrhea being the most distinctive symptom. Many patients have nausea, vomiting, and stomach discomfort. Other common symptoms include headaches, muscle aches, chest pain, and shortness of breath.

Is Legionnaires' disease contagious?

Legionnaires' disease is not contagious. No special precautions are necessary. The disease is transmitted via drinking water, not by infected persons. (So it differs from SARS and influenza where masks must be worn). Likewise, women who are pregnant and their fetuses have nothing to fear from patients with Legionnaires' disease.

What is the prognosis and outcome for patients who have contracted Legionnaires' disease?

If the patient is treated with appropriate antibiotics near the onset of pneumonia, the outcome is excellent, especially if the patient has no underlying illness that compromises his/her immune system. For patients whose immune systems are compromised, including transplant recipients, delay of appropriate therapy can result in prolonged hospitalization, complications, and death.

For those patients who are discharged from the hospital, we have found that many will experience fatigue, loss of energy, and difficulty concentrating for several months after discharge from the hospital. In a long-term study of 122 survivors of Legionnaires’ disease in the Netherlands, symptoms of fatigue (75%), neurologic symptoms (such as concentration problems and malaise) (75%), and neuromuscular symptoms (such as joint pain or muscle weakness) (79%) had persisted 17 months later (Lettinga KD, Clin Infect Dis, July 1, 2002). Respiratory tract symptoms were also present, but in lower frequency including cough (48%) and shortness of breath on exertion (38%). It could not be determined whether or not the persistence of these symptoms were due to specifically for Legionnaires’ disease or for severe pneumonia, in general.

Serious sequelae, fortunately, are rare. In our experience, most patients will recover completely within one year. If the patients are cigarette smokers, the patients should discontinue smoking.

If I have contracted Legionnaires' disease, what are the chances that I will have a recurrence?

Contracting Legionnaires' disease a second time is extremely rare. We have never encountered such a case. Thus, it seems likely that there is some immunity after the patient experiences the first infection. The most common risk factor is cigarette smoking. So, any patient who has contracted Legionnaires' disease (or any other type of pneumonia) should immediately quit smoking.

How is Legionnaires' disease diagnosed?

Specialized laboratory tests are necessary and, unfortunately, may not be available in many hospitals. These include culture on specialized Legionella media. Culture media furnish nutrients for the bacterium. When sputum from the patients are placed onto the culture media, the bacterium grows on the medium and can be identified. Other tests include direct fluorescent antibody (DFA) in which the bacterium can be stained and becomes visible under a fluorescent microscope. Antibody testing is a blood test in which antibodies that are reactive against Legionella are present in the human body showing that the patient has come into contact with the bacterium previously. Urinary antigen is a test that detects Legionella in the urine.

What are the common risk factors for Legionnaires' disease?

The most common risk factor is heavy cigarette smoking. However, chronic lung disease is also common. The most intense risk factor is organ transplantation; the medicines used to protect the new organ also compromise the patient' defense system against infection. Patients who take corticosteroid medicines are also at high risk.

How is Legionnaires' disease treated?

Many antibiotics are highly effective against Legionella bacteria. The two most potent classes of antibiotic are the macrolides (azithromycin), and the quinolones (ciprofloxacin, levofloxacin, moxifloxacin, gemifloxacin, trovofloxacin). Other agents that have been shown to be effective include tetracycline, doxycycline, minocycline, trimethoprim- sulfamethoxazole. Erythromycin, the former antibiotic of choice, has been replaced by more potent and less toxic antibiotics.

Where do Legionella bacteria come from?

Legionella are natural inhabitants of water and can be detected in rivers, lakes, and streams. One type of Legionella species (L. longbeachae) has been found in potting soil.

How do people contract Legionella?

The most popular theory is that the organism is aerosolized in water and people inhale the droplets containing Legionella. However, new evidence suggests that another way of contracting Legionella is more common. "Aspiration" is the most common way that bacteria enter into the lungs to cause pneumonia. Aspiration means choking such that secretions in the mouth get past the choking reflexes and instead of going into the esophagus and stomach, mistakenly, enter the lung. The protective mechanisms to prevent aspiration is defective in patients who smoke or have lung disease. Aspiration now appears to be the most common mode of transmission.

How does Legionella escape the host defense of the patient and cause disease?

Legionella enters the lung via aspiration (choking) when foreign particles including bacteria escape the gag reflex and fall directly into the respiratory tract (windpipe and lung). It can also enter by inhalation of aerosols, although we believe that this mode of transmission is overemphasized.

Once the Legionella enters the mouth, for example, by drinking water contaminated by Legionella, the organism is prevented from going into the lung by cilia on the cells of the respiratory tract. Cilia are hair-like structures which sweep back and forth and keep the respiratory tract clear of particles including bacteria. In patients who smoke cigarettes or in ill patients, this process is impaired and it is easier for bacteria to bypass the gag reflex and the ciliary process and fall into the respiratory tract (aspiration). Legionella can also stick (adhere) onto the cells of the respiratory tract, and then enter and multiply within cells of the respiratory tract.

Once the Legionella enters into the lung, white blood cells (neutrophils, macrophages) will migrate to the Legionella in an attempt to engulf (phagocytose) and kill them. The alveolar (air sac) macrophage is the most important cell. The alveolar macrophages engulf Legionella, but the Legionella can escape the killing mechanisms of the alveolar macrophage and multiply within the macrophage. The organism multiplies until the cell ruptures, and the liberated bacteria are released into the lung only to be engulfed by other cells, and the cycle of phagocytoses, multiplication, and release begins anew. Other white blood cells are recruited from the blood. However, the Legionella can escape the killing effects of these other cells by hiding in the respiratory tract cells or alveolar macrophages. That is why Legionella is called an intracellular pathogen.

In a simplified explanation, the human body has two major components of the immune system: 1) humoral immunity in which antibodies produced by the human body attach to the Legionella and facilitate killing of Legionella by white blood cells, and 2) cell-mediated immunity in which white blood cells attack, engulf, and kill the organism. The major host defense against Legionella is considered to be cell-mediated immunity, but Legionella can often escape the effects of this host defense.

The intracellular location of Legionella is also important in therapy. Many antibiotics effective against pneumonia are ineffective against Legionella because they do not penetrate the respiratory tract cells or alveolar macrophages. The newer antibiotics called the macrolides (azithromycin) or quinolones (ciprofloxcin, leveofloxacin, gemifloxacin and moxifloxacin) do penetrate cells and can then effectively kill Legionella.

What have been the water sources for Legionnaires' disease?

The major source is water distribution systems of large buildings including hotels and hospitals. Cooling towers have long been thought to be a major source for Legionella, but new data suggest that this is an overemphasized mode of transmission. Other sources include mist machines, humidifiers, whirlpool spas, and hot springs. Air conditioners are not a source for Legionnaires' disease. They were suspected to be the source in the original American Legion outbreak in a Philadelphia hotel, but new data now suggests that the water in the hotel was the actual culprit.

Why it Took so Long to Find the Bacillus

The Legionnaires' Disease bacillus, later named Legionella pneumophila, was no ordinary microbe. It could not be grown under typical conditions, being dependent upon ridiculous demands: high levels of the amino acid cysteine and inorganic iron supplements, low sodium concentrations, as well as activated charcoal to absorb free radicals. In addition, it preferred elevated temperatures, which was highly abnormal among pathogens, who preferred near-body temperatures. It did not help that the team of CDC researchers had been using the wrong animal model at the start, and had only gotten results when they switched from mice to guinea pigs4.

Once the etiological agent had been determined, however, another question popped up: where exactly was this bacteria from, and how did it come to infect the World War II veterans?

Dr Carl Fliermans solved the first part of the puzzle when he discovered that L pneumophila lipids resembled those of the thermophilic bacteria he'd found in the thermal regions of the Yellowstone National Park, and that this bacteria tended to live as biofilm (scum) associated with certain species of algae. Subsequently, Fliermans began poking around aquatic habitats and found - guess what? - this bacteria residing in thermal waters discharged from a nuclear reactor at Savannah River Laboratory. This bacteria was later found to be living in natural hot springs all over the United States and, most importantly, in air-conditioning cooling towers.

The Mystery Solved

One very important clue pertaining to the nature of the cause of Legionnaires' Disease, one that would have pointed researchers in the right direction, had earlier been overlooked. The clue was this: of the 221 people who became sick, 72 were people who were not involved in the American Legion convention - people who had either been inside the Bellevue Stratford Hotel, or had walked past it. Later when it was discovered that the organism resided in the water of cooling towers, the pieces fell into place. The Legionnaires' Disease bacillus was actually being spread by the air-conditioning system itself, in aerosolised water droplets. People who inhaled the aerosols inevitably inhaled the micro-organisms, which were subsequently brought into the respiratory tract. Here, they multiplied in patrolling macrophages, safe from other hostile mechanisms of the human immune system, causing flu-like symptoms and, where untreated, pneumonia that resulted in death.

Once this fact had been discovered, it struck scientists that this Legionnaires' Disease bacteria, that bred unchecked both in natural freshwater sources and in that of manmade containers, could not possibly be a new organism5. Scientists scrambled to dig through the medical archives in pursuit of evidence that this bacteria had wreaked havoc before. Sure enough, they discovered that a number of previously unresolved outbreaks, including the one in 1968 where 95 out of 100 people working in a building in Pontiac, Michigan contracted respiratory disease, had been actually caused by Legionella pneumophila. They would later find that although L pneumophila was responsible for 90% of sporadic outbreaks, other (later discovered) species were also fully capable of assaulting the immune system. Other outbreaks and epidemics occurring throughout the world since then would eventually show them that occurrence of Legionella in manmade environments was not restricted to cooling towers alone - that wherever on earth there was a machine that could produce mist, there was Legionella and Legionnaires' Disease.

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