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
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
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
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
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
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
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
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
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.