WHAT IS IT

What Is Legionnaires' Disease?

Legionnaires' disease is a pneumonia caused by Legionella bacteria. An outbreak of this disease among persons attending a state convention of the American Legion in Philadelphia in 1976 led to its name. It is not a new disease; the earliest documented case was in 1947. Although cases occur all year long, both single cases and outbreaks occur more frequently in the summer and fall.

People with Legionnaires' disease often have flu-like symptoms with muscle aches, headache, loss of appetite, and dry cough. Fevers are often between 102o - 105o and some people have stomach cramps and diarrhea. Chest X-ray usually shows pneumonia. Symptoms usually begin 2 to 10 days after a person is infected with the bacteria. Another illness caused by Legionella bacteria is called Pontiac Fever. It consists of fever, headache, weakness and muscle ache, usually lasts for 2 to 5 days, and there is no pneumonia.

The bacteria are found normally in many places in the environment. A common source is water. Outbreaks have been related to contaminated air-conditioning cooling towers, NOT window air conditoners. The bacteria also have been found in hot and cold water taps, showers, whirlpool baths, creeks, ponds and wet soil.

People get Legionnaires' disease by breathing in the Legionella bacteria, usually carried by a mist. It is NOT spread from one person to another.

Because Legionnaires' disease can cause symptoms similar to the "flu" and other kinds of pneumonia, it can take longer to diagnose. A number of different laboratory tests to identify Legionella can be done on blood, urine, respiratory secretions (sputum) and lung tissue. Your doctor can order these tests.

Anyone can get Legionnaires' disease but it is more common among the elderly and those with impaired immune systems or underlying diseases. People who smoke cigarettes or drink heavily are also at increased risk of getting Legionnaires' disease.

It can be for people over 50 years of age or smokers, or those who have impaired immune systems due to underlying diseases (e.g., cancer, kidney failure, diabetes, HIV infection, chronic lung disease or heart failure) or medications (e.g., steroids, chemotherapy). Some studies have shown that 5-15% of people diagnosed with Legionnaires' disease die.

Legionnaires' disease is usually treated with an antibiotic called erythromycin. Other drugs may also be used.

Measures can be taken to reduce the likelihood of exposure. For example, large air conditioning systems with cooling towers and evaporative condensers should be operated and maintained according to manufacturers' recommendations. Because Legionella bacteria are found throughout the environment, testing potential sources is not recommended when individual cases occur.

A form of lung infection named after an epidemic that affected 234 people attending an American Legion convention in 1976.

General ill feeling. Headache. Chills and fever up to 105F (40.6C). Muscle aches. Cough without sputum that progresses to one with gray or blood-streaked sputum. Nausea, vomiting, diarrhea. Disorientation.

Infection from bacteria (Legionella pneumophilia) that is not contagious between persons. The germ is transmitted through the air, and the incubation period after exposure is 2 to 10 days. In the 1976 epidemic, the germ was transmitted through the cooling and evaporating elements of a large, central air-conditioning system. The bacteria are also found in excavation sites and newly plowed soil.

Chronic, debilitating illness including diabetes mellitus, chronic kidney failure or emphysema. Smoking. This increases the risk 3 to 4 times. Excess alcohol consumption. Use of immunosuppressive drugs, including cortisone and anticancer drugs.

Don't drink more than 1 or 2 alcoholic drinks--if any--a day.

What To Expect

Your own observation of symptoms. Medical history and physical exam by a doctor. Laboratory blood studies and culture of sputum, bronchoscopy (see Surgery section).

Doctor's treatment. Hospitalization for intensive care and oxygen (severe cases). Self-care for mild cases or during convalescence after hospitalization.

Use a cool-mist ultrasonic humidifier to increase air moisture and thin lung secretions so they can be coughed up more easily. Clean humidifier daily. Use warm compresses or a heating pad on the chest to relieve chest pain. Practice deep-breathing exercises as often as your strength allows. Avoid loud talking, laughing or singing. They may trigger excessive coughing. Keep warm. If you become chilled, the infection can become more severe.

Your doctor may prescribe antibiotics. Be sure to finish all prescribed medication. If the cough is painful and doesn't produce sputum, you may use non-prescription medicine to suppress it. If the cough produces sputum, don't suppress it. You may take aspirin or acetaminophen to reduce fever.

You have symptoms of Legionnaires' disease. The following occurs during or after treatment: Temperature spike to 102F (38.9C). Severe chest pain, despite treatment. Increased shortness of breath. Dark or bluish nails, lips or skin. Blood in the sputum. New, unexplained symptoms develop. Drugs used in treatment may produce side effects.

Both cases that were presented first need to have a laboratory-confirmed diagnosis of Legionnaires' disease before issues of nosocomial acquisition can be entertained. Legionnaires' disease can be confirmed by:

1. culture of respiratory secretions using media specific for the growth of Legionella,

2. detection of Legionella pneumophila serogroup 1 antigens in urine by radioimmunoassay or enzyme immunoassay,

3. a fourfold rise in Legionella antibody titers to a level greater than or equal to 1:128 in paired acute- and convalescent-phase serum specimens by indirect fluorescent antibody assay,

4. direct fluorescent antibody testing of respiratory secretions or tissue,

5. polymerase chain reaction testing of respiratory secretions or tissue (not yet commercially available).

The most rapid of the above listed tests is the urine antigen test. The test has high sensitivity and specificity and can be ordered through most commercial reference laboratories. A diagnosis of Legionnaires' disease can be made in 24-48 hours in many instances. Direct fluorescent antibody testing is also rapid but does not have the specificity of urine testing for Legionella pneumophila serogroup 1. Single elevated titers of Legionella antibodies obtained during acute illness should not be used alone to diagnose Legionnaires' disease (see references below).

The incubation period for Legionnaires' disease is generally 2-10 days, thus for epidemiologic purposes, the Hospital Infection Control Practices Advisory Committee (HICPAC) has defined "definite" nosocomial Legionnaires' disease as "laboratory-confirmed legionellosis that occurs in a patient who has spent greater than or equal to 10 days continuously in the hospital prior to onset of illness. Laboratory-confirmed infection that occurs 2-9 days after hospitalization is considered "possible" nosocomial infection."

These definitions and a detailed explanation of prevention and control measures can be found in the reference:

The bacterium Legionella pneumophilia belongs to the gram negative class of bacteria. The cell wall of Gram-negative bacteria is a thinner structure, than that of the gram positive, and contains distinct layers. An outer layer which is more like a cytoplasmic membrane in its composition with the typical trilaminar structure.

The main component of the Gram-negative cell wall is lipopolysaccharide. The lipopolysaccharide consists of a core region to which are attached repeating units of polysaccharide moieties.
A component of the cell wall of most Gram-negative bacteria is associated with endotoxic activity, with which are associated the pyrogenic effects of Gram-negative infections.
On the side-chains are carried the bases for the somatic antigen specifity of these organisms.
The chemical composition of these side chains both with respect to components as well as arrangement of the different sugars determines the nature of the somatic or O antigen determinants, which are such important means of serologically classifying many Gram-negative species. In many cases it has been shown that the reason for certain organisms belonging to quite different species, giving strong serological cross-reactivity is due their having chemically similar carbohydrate moieties as part of their lipopolysaccharide side chains, which generally have about 30 repeating units.
These side chains have as part of their structure frequently quite common hexoses, but in many cases there are also present some unusual hexoses, such as 6-deoxyhexoses and 3,6-dideoxyhexoses. Also O -methyl sugars may be part of these side chain structures.
There is a great deal of variation among these side chains, however, the composition of the core region is much more conserved among many Gram-negative groups of bacteria. Characteristic of the core region of many of the Enterobacteriaceae is phophorylated 2-keto-3-deoxyoctonoate, phosphorylated L-glycero-D-mannoheptose, D-galactose, D-glucose and N -acetyl-glucosamine. The first two are by far the most widespread components of the core region of many species.
The lipid component of the lipopolysaccharide, known as lipid A is predominantly associated with the endotoxic activity. It is the most conserved part of the Gram-negative cell wall and the basis of its structure is a beta-1,6-linked D-glucosamine disaccharide. In some Pseudomonas and Rhodopseudomonas strains this is replaced by 2,3-diamino-2,3-dideoxy-D-glucose.
This has phosphate residues in positions 1 and 4. To both the amino and hydroxyl groups of the glucosamine moieties are linked long-chain fatty acids. Among the enterobacterial lipopolysaccharides the N -acyl residues are frequently fatty acids like beta-hydroxymyristic acid or similar 3-hydroxyalkanoic acids. Some Gram-negative bacteria lack phosphate in their lipid A and some types contain other carbohydrates 2,3-diamino-2,3-dideoxy-D-glucose. Legionella pneumophilia belongs to the class: LEGIONELLACEAE

These are Gram-negative, non-sporing non-acid fast rods, 1-2µm long by 0.5µm wide. They are fastidious bacteria requiring iron and cysteine for primary isolation. They are generally motile with one to three polar flagellae.
They are chemoorganotrophs and lack the ability to ferment any sugars. They do not have a glucose transport system. Some amino acids act as primary carbon and energy sources and are metabolised through the tricarboxylic acid cycle, while carbohydrate synthesis occurs along the Embden-Meyerhof pathway. Most strains produce catalase and liquify gelatin and many produce beta-lactamase and oxidase. A number of species are pigmented and some show autofluorescence.
The optimum temperature for growth of human isolates is around 35°C. Legionella : This is the only accepted genus and comprises over 30 species.
Two other genera have been proposed, Tatlockia and Fluoribacter , for the species T. micdadei , F. bozemanii , F. dumoffii and F. gormanii , but generally theses species are accepted as members of the genus Legionella. The traditional methods of classification cannot be used because of their general inertness.
They have a unique cell wall among Gram-negative bacteria, containing large amounts of branched chain fatty acids. They are also subdivided on the basis of their unusual isoprenoid quinones in their respiratory chain. The GC content of the DNA is 38-52 mol%.

Legionella pneumophila They are Gram-negative non-acid fast non-capsulated rods 0.3-0.9 µm x 2-20µm. They are aerobic and do not hydrolyse gelatin or produce urease. They are non-fermentative. L. pneumophila is neither pigmented nor does it autofluoresce. It is oxidase and catalase positive, produces beta-lactamase. It is a strict aerobe. It hydrolyses hippurate and liquifies gelatin but does not ferment any carbohydrates.
It requires specialised media for growth. There is up 67% relatedness between the species on the basis of DNA hybridization studies. DNA probes specific for rRNA sequences of Legionella have been produced, as have ones for other specific genes. Plasmids have been demonstrated in many species and plasmid profile analysis has been used to characterise relationships between strains. At least 14 different serovars of L. pneumophila have been described as well as several other species being subdivided into a number of serovars. Sera have been used both for slide agglutination studies as well as for direct detection of bacteria in tissues using fluorescent-labelled antibody.
Specific antibody in patients can be determined by the indirect fluorescent antibody test. ELISA and microagglutination tests have also been successfully applied. L. pneumophila is an intracellar pathogen. The internalisation of the bacteria is enhanced by the presence of antibody and complement. A pseudopod coils around the bacterium in this unique form of phagocytosis.
Once Internalised, the bacteria surround themselves by a membrane-bound phagolysosome. This becomes a vescicle, within which the bacteria multiply. They produce a 39kDa metalloprotease into culture fluids, which is cytotoxic for some cultured tissue culture cells.
This may be a virulence factor. A novel cytotoxin consisting of small peptides, which are acid and heat resistant has also been described. L. pneumophila may also have a unique iron scavanging system. Apart from carriers Legionallae do not form part of the normal flora of humans or animals. Intestinal Infections:
These may only occur as part of respiratory infections, where gastrointestinal symptoms have on occasion been described. Extraintestinal Infections: L. pneumophila is specifically considered as a pathogen of the respiratory tract, where it is a cause of atypical pneumonia, also known as Legionnaires' disease. Other infections have also been reported, including haemodialysis fistulae, pericarditis and wound and skin infections.
Bacteraemia is often associated with Legionnaires' disease. Animal Infections: None specifically recorded. Infections of Protozoa: Protozoa such as Harmanella vermiformis and related protozoa have been shown to be able to support the growth of L. pneumophila in tap water.
Also Acanthamoeba , Naegleria and Tetrahymena can be infected by L. pneumophila . It is considered that this may be how these fastidious organisms survive in the environment.

Definition:
An acute respiratory infection caused by the bacteria Legionella pneumophilia, which causes a serious pneumonia.

Causes
incidence, and risk factors: The bacteria has been found in water delivery systems and can survive in the warm, moist, air conditioning systems of large buildings including hospitals. The infection is transmitted through the respiratory route.
Person to person spread has not been proven.

From the onset of symptoms, a worsening of the condition is typical during the first 4 to 6 days, with improvement starting in another 4 to 5 days. Most infection occurs in middle-aged or older people, although it has been reported in children. Typically, the disease is LESS severe in children.

Risk factors include cigarette smoking; underlying diseases such as renal failure, cancer, diabetes or chronic obstructive pulmonary disease; people with suppressed immune systems from chemotherapy, steroid medications or diseases such as cancer and leukemia; alcoholism; being middle-aged or elderly, and in chronically ventilated patients.

Prevention: Active surveillance of infections that were acquired within a hospital can lead to the treatment of contaminated water delivery systems. Detection and treatment of sources outside hospitals usually occurs during or after an epidemic has happened.

Symptoms:

muscle aches and stiffness joint pain loss of energy general discomfort, uneasiness, or ill feeling (malaise) headache fever shaking chills nonproductive cough coughing of blood shortness of breath chest pain rales diarrhea ataxia (lack of coordination)

Signs and tests: Listening to the chest with a stethoscope (auscultation) reveals fine crackles.

Sputum DFA (direct fluorescent antibody) staining shows Legionella. Chest X-ray shows pneumonia. Arterial blood gas analysis may show low concentrations of oxygen. CBC shows an increased white blood cell count. Erythrocyte sedimentation rate is increased. Liver function tests may show moderate elevation. The causative organism can be cultured from the airway, also.

Treatment: The goal of treatment is to eliminate the infection with antibiotics. Treatment is started as soon as Legionnaires' disease is suspected, without waiting for confirmation by culture results. Erythromycin is the drug of choice. Rifampin may be added to improve results.

Supportive treatment includes hospitalization for fluid and electrolyte replacement and oxygen administration by mask or by mechanical ventilation, if the respiratory system becomes severely compromised by the infection.

Expectations (prognosis): The overall death rate for those with pneumonia is about 15%, and the death rate increases in those with underlying diseases.

Complications:

respiratory failure requiring mechanical ventilation (use of a respirator)

Legionella is a gram negative bacterium which is commonly found in fresh water. Prior to l976 the organism had not been identified until an outbreak of acute febrile respiratory illness occurred among members of the American Legion who were attending an American Legion conference at a hotel in Philadelphia.

Retrospective documentation indicates that the organism caused human disease at least as early as 1947, and in all probability much earlier than that considering the ubiquitous nature of the bacterium. Legionella pneumophila is the particular strain of Legionella which caused the outbreak in Philadelphia in 1976, and which causes the illness which has come to be known as Legionnaires' Disease. L. pneumophila has been isolated from environmental water sources such as lakes and creeks, as well as from man-made water systems such as cooling towers, evaporative condensers, shower heads, hot water tanks, spas, and ultrasonic nebulizers. System conditions such as warm temperatures and high nutrient levels typically cause proliferation of the organism once the bacterium has "seeded" a particular water system.

Hospital cast off Legionnaires' Disease, known as nosocomial Legionella, infections, are often associated with the potable water system. Disease causing exposures have been documented from aerosols generated by running water taps and shower heads and rinsing ventilation equipment in non-sterile tap water. Further-more, fatal, extra-pulmonary infections from cleansing post-cardiovascular surgery wounds with non-sterile tap water have also been documented.

Whereas sporadic cases of Legionnaires' Disease are not uncommon, and are probably under-reported, outbreaks of Legionnaires' Disease are typically associated with buildings such as hotels and particularly hospitals. The organism is an opportunistic pathogen so that exposure presents clinical symptoms almost exclusively in immuno-compromised individuals. In the wild the bacterium replicates by invading waterborne protozoa and commandeering intra-cellular macromolecules to accomplish intracellular multiplication. Following the intracellular replication phase, the organisms lyse the host cell (the protozoa) and re-invade new hosts. In immuno-compromised humans the organism is usually inhaled as an aerosol and after penetrating to the lower lung reproduces intracellularly in the alveolar macrophages finally resulting in pneumonia. Legionella pneumophila caused pneumonias can usually be effectively treated with erythromycin.

While it is probably impossible to permanently eradicate Legionella from water systems, maintenance and administrative interventions will decrease the likelihood of exposure and subsequent disease. Cooling towers must be maintained in a manner that will minimize accumulation of bio-film with its associated nutrients. While cooling towers are commonplace in Hong Kong, there are no cooling towers at HKUST.

Routine and systematic treatment of cooling tower water with biocides is recommended (chlorine being the treatment method with the best track record to date). Plastic, and particularly rubber type components within the potable water system, particularly hot or tepid systems, seem to allow multiplication of the numbers of the organism. Replacement of these components with non-plastic parts is preferred where possible. New materials which resist microbial growth are becoming available on the market.

Maintaining hot water storage temperatures at or above 1310F, and 1250F or more at the tap is recommended. Contact between hot and cold water pipes should be prevented by separation or insulation. If Legionella have colonized a potable water system and disease has been documented from exposure to this water then continuous feed chlorine injection seems to be the chemical treatment of choice. If this approach is chosen care must be given to maintain the optimum pH range for the water and ensure chlorine levels are not excessive which can damage water system components. Generally speaking, a thorough and systematic preventive maintenance program for all water systems will control Legionella populations optimally.

All servicing or maintenance of the heating, ventilating, and air-conditioning equipment (HVAC) including inspections, water testing and applications of biocide treatments must be documented. Furthermore, it is recommended to drain and mechanically clean the interior of cooling towers at least once annually. If cooling tower units are only used during the summer they should be cleaned and treated prior to the first summer start-up. For others cleaning and treatment should at least be in accordance with the manufacturers recommendations. Some success in maintaining trouble-free cooling towers has been claimed from routinely alternating types of biocides used to treat the tower water. At a minimum, cooling towers should be drained and cleaned before restarting whenever they have been out of operation for any extended period of time L> 1 0 days). Monthly total plate count sampling for heterotrophic bacteria is recommended as an indicator of water cleanliness for all cooling towers as part of the preventive maintenance program.

As far as the tap water is concerned, even though Legionella bozemanii has not been implicated as a disease causing strain of the organism efforts should be made to prevent respiratory exposure of immuno-compromised to the aerosol, since it is not clear whether or not any strains of the organism can be categorically described as non-pathogenic. It may be that the location of the tap in relation to the patient bed would preclude such an exposure. Nursing staff should never use tap water for rinsing or cleaning any respiratory therapy equipment, or for cleaning wounds, but should use sterile water for all such applications. Since the organism that caused a fatal post surgery infection was detected in the recovery room tap water it is likely that it was present throughout the system even though it was not detected in any other tap water samples. The organism was detected at a low concentration in the recovery room tap water sample so that the concentration in the whole system was probably low. The recovery room was vacant and the tap may have been unused for some time thus allowing the organism to proliferate to a detectable concentration. A remedial intervention in such a case would be to raise the temperature of the hot water system. However, if the hot water pipes are un-insulated and the cold water pipes are close enough, the cold water pipes may be heated to a point where the organism will proliferate in the cold water lines. A second option would be to install a chlorine injection system for the building water (although this can shorten the lifespan of the pipes).

(This selection has been taken from January, 1994 issue of SafetyWise)

LEGIONNAIRES' DISEASE

1.Epidemiology Legionnaires' disease is a multisystem illness, with pneumonia, caused by Legionella sp.

Since the etiologic agent of Legionnaires' disease was identified, numerous nosocomial outbreaks of the disease have been reported, thus enabling researchers to study the epidemiology of epidemic legionellosis. In contrast, the epidemiology of sporadic (i.e., nonoutbreak-related) nosocomial Legionnaires' disease has not been well defined. However, when one case is identified, the presence of additional cases should be suspected. Of 196 cases of nosocomial Legionnaires' disease reported in England and Wales during 1980-1992, 69% occurred during 22 nosocomial outbreaks (defined as two or more cases occurring at a hospital during a 6-month period).

Nine percent of cases occurred greater than 6 months before or after a hospital outbreak, and another 13% occurred in hospitals in which other sporadic cases, but no outbreaks, were identified. Only 9% occurred at institutions in which no outbreaks or additional sporadic cases were identified. In North America, the overall proportion of nosocomial pneumonias caused by Legionella sp. has not been determined, although the reported proportions from individual hospitals have ranged from zero to 14%. Because diagnostic tests for Legionella sp. infection are not performed routinely on all patients who have hospital-acquired pneumonia in most U.S. hospitals, this range probably underestimates the incidence of Legionnaires' disease.

Legionella sp. are commonly found in various natural and man-made aquatic environments and may enter hospital water systems in low or undetectable numbers . Cooling towers, evaporative condensers, heated potable-water-distribution systems within hospitals, and locally produced distilled water can provide a suitable environment for legionellae to multiply.

Factors known to enhance colonization and amplification of legionellae in man-made water environments include temperatures of 25-42 C , stagnation , scale and sediment, and the presence of certain free-living aquatic amoebae that are capable of supporting intracellular growth of legionellae .

A person's risk for acquiring legionellosis after exposure to contaminated water depends on a number of factors, including the type and intensity of exposure and the person's health status . Persons who are severely munosuppressed or who have chronic underlyingillnesses, such as hematologic malignancy or end-stage renal disease, are at a markedly increased risk for legionellosis.

Persons in the later stages of acquired immunodeficiency syndrome (AIDS) also are probably at increased risk for legionellosis, but data are limited because of infrequent testing of patients .

Persons who have diabetes mellitus, chronic lung disease, or nonhematologic malignancy; those who smoke cigarettes; and the elderly are at moderately increased risk . Nosocomial Legionnaires' disease also has been reported among patients in pediatric hospitals .

Underlying disease and advanced age are risk factors not only for acquiring Legionnaires' disease but also for dying as a result of the illness. In a multivariate analysis of 3,524 cases reported to CDC from 1980 through 1989, immunosuppression, advanced age, end-stage renal disease, cancer, and nosocomial acquisition of disease were each independently associated with a fatal outcome.

The mortality rate was 40% among 803 persons who had nosocomially acquired cases, compared with 20% among 2,721 persons who had community-acquired cases ; this difference probably reflected the increased severity of underlying disease in hospitalized patients.

2.Diagnosis The clinical spectrum of disease caused by Legionella sp. is broad and ranges from asymptomatic infection to rapidly progressive pneumonia. Legionnaires disease cannot be distinguished clinically or radiographically from pneumonia caused by other agents , and evidence of infection with other respiratory pathogens does not exclude the possibility of concomitant Legionella sp. infection .

The diagnosis of legionellosis may be confirmed by any one of the following: culture isolation of Legionella from respiratory secretions or tissues, microscopic visualization of the bacterium in respiratory secretions or tissue by immunofluorescent microscopy, or, for legionellosis caused by Legionella pneumophila serogroup 1, detection of L. pneumophila serogroup-1 antigens in urine by radioimmunoassay, or observation of a four-fold rise in L. pneumophila serogroup-1 antibody titer to greater than or equal to 1:128 in paired acute and convalescent serum specimens by use of an indirect immunofluorescent antibody (IFA) test .

A single elevated antibody titer does not confirm a case of Legionnaires' disease because IFA titers greater than or equal to 1:256 are found in 1%-16% of healthy adults . Because the above tests complement each other, performing each test when Legionnaires' disease is suspected increases the probability of confirming the diagnosis .

However, because none of the laboratory tests is 100% sensitive, the diagnosis of legionellosis is not excluded even if one or more of the tests are negative . Of the available tests, the most specific is culture isolation of Legionella sp. from any respiratory tract specimen (419,420).

3.Modes of Transmission Inhalation of aerosols of water contaminated with Legionella sp. might be the primary mechanism by which these organisms enter a patient's respiratory tract . In several hospital outbreaks, patients were considered to be infected through exposure to contaminated aerosols generated by cooling towers, showers, faucets, respiratory therapy equipment, and room-air humidifiers, . In other studies, aspiration of contaminated potable water or pharyngeal colonizers was proposed as the mode of transmission to certain patients . However, person-to-person transmission has not been observed.

4.Definition of Nosocomial Legionnaires Disease' The incubation period for Legionnaires disease is usually 2-10 days ; thus, for the purposes of this document and the accompanying HICPAC recommendations, laboratory-confirmed legionellosis that occurs in a patient who has been hospitalized continuously for greater than or equal to 10 days before the onset of illness is considered a definite case of nosocomial Legionnaires' disease, and laboratory-confirmed infection that occurs 2-9 days after hospital admission is a possible case of the disease.
 

5.Prevention and Control Measures 1.Prevention of Legionnaires' Disease in Hospitals with No Identified Cases (Primary Prevention) Prevention strategies in health-care facilities in which no cases of nosocomial legionellosis have been identified have differed depending on the immunologic status of the patients, the design and construction of the facility, the resources available for implementing prevention strategies, and state and local regulations.

At least two strategies are practiced with regard to the most appropriate and cost-effective means of preventing nosocomial legionellosis, especially in hospitals in which no cases or only sporadic cases of the illness have been detected. However, a study comparing the cost-benefit ratios of these strategies has not been conducted. The first approach is based on periodic, routine culturing of water samples from the hospital's potable water system for the purpose of detecting Legionella sp.

When greater than or equal to 30% of the samples obtained are culture-positive for Legionella sp., the hospital's potable water system is decontaminated , and diagnostic laboratory tests for legionellosis are made available to clinicians in the hospital's microbiology department so that active surveillance for cases can be implemented .

This approach is based on the premise that no cases of nosocomial legionellosis can occur if Legionella sp. is not present in the potable water system, and, conversely, if Legionella sp. are cultured from the water, cases of nosocomial legionellosis could occur . Proponents of this strategy indicate that when physicians are informed that the potable water system of the hospital is culture-positive for Legionella sp., they are more inclined to conduct the necessary tests for legionellosis .

A potential advantage of using this approach in hospitals in which no cases of nosocomial legionellosis have occurred is that routinely culturing a limited number of water samples is less costly than routinely performing laboratory diagnostic testing for all patients who have nosocomial pneumonia.

The main argument against this approach is that, in the absence of cases, the relationship between the results of water cultures and the risk for legionellosis remains undefined. The bacterium has been frequently present in water systems of buildings , often without being associated with known cases of disease .

In a study of 84 hospitals in Quebec, 68% of the water systems were found to be colonized with Legionella sp., and 26% were colonized at greater than 30% of sites sampled; however, cases of Legionnaires' disease were reported rarely from these hospitals . Similarly, at one hospital in which active surveillance for legionellosis and environmental culturing for Legionella sp. were done, no cases of legionellosis occurred in a urology ward during a 3.5-month period when 70% of water samples from the ward were culture-positive for L. pneumophila serogroup 1 .

Interpretation of the results of routinely culturing the water might be confounded by differing results among the sites sampled within a single water system and by fluctuations in the concentration of Legionella sp. at the same site . In addition, the risk for illness after exposure to a given source might be influenced by a number of factors other than the presence or concentration of organisms; these factors include the degree to which contaminated water is aerosolized into respirable droplets, the proximity of the infectious aerosol to the potential host, the susceptibility of the host, and the virulence properties of the contaminating strain .

Thus, data are insufficient to assign a level of risk for disease even on the basis of the number of colony-forming units detected in samples from the hospital environment. By routinely culturing water samples, many hospital administrators will have to initiate water- contamination programs if Legionella sp. are identified.

Because of this problem, routine monitoring of water from the hospital's potable water system and from aerosol-producing devices is not widely recommended .
The second approach to preventing and controlling nosocomial legionellosis involves
a) maintaining a high index of suspicion for legionellosis and appropriately using diagnostic tests for legionellosis in patients who have nosocomial pneumonia and who are at high risk for developing the disease and dying from the infection ,

b) initiating an investigation for a hospital source of Legionella sp. upon identification of one case of definite or two cases of possible nosocomial Legionnaires disease, and c) routinely maintaining cooling towers and using only sterile water for the filling and terminal rinsing of nebulization devices. Measures used in hospitals in which cases of nosocomial legionellosis have been identified include either

a) routine maintenance of potable water at greater than or equal to 50 C or less than 20 C at the tap or b) chlorination of heated water to achieve 1-2 mg/L of free residual chlorine at the tap, especially in areas where immunosuppressed and other high-risk patients are located .
However, the cost-benefit ratio of such measures in hospitals in which no cases of legionellosis have been identified needs additional evaluation.
 

2.Prevention of Legionnaires' Disease in Hospitals with Identified Cases (Secondary Prevention) The indications for a full-scale environmental investigation to search for and subsequently decontaminate identified sources of Legionella sp. in hospital environments have not been clarified, and these indications probably differ depending on the hospital.

In hospitals in which as few as one to three nosocomial cases are identified during a period of several months, intensified surveillance for Legionnaires' disease has frequently identified numerous additional cases .

This finding suggests the need for a low threshold for initiating an investigation after laboratory confirmation of cases of nosocomial legionellosis. However, when developing a strategy for responding to such an identification, infection-control personnel should consider the level of risk for nosocomial acquisition of, and mortality from, Legionella sp. infection at their particular hospital. An epidemiologic investigation conducted to determine the source of Legionella sp. involves several important steps.

First, microbiologic and medical records should be reviewed.
Second, active surveillance should be initiated to identify all recent or ongoing cases of legionellosis.

Third, potential risk factors for infection (including environmental exposures such as showering or use of respiratory-therapy equipment) should be identified by creating a line listing of cases, analyzing the collected information (by time, place, and person), and comparing case-patients with appropriate controls.

Fourth, water samples should be collected from environmental sources implicated by the epidemiologic investigation and from other potential sources of aerosolized water. Fifth, subtype-matching between legionellae isolated from patients and environmental samples should be conducted .

This last step can be crucial in supporting epidemiologic evidence of a link between human illness and a specific source .

In some hospitals in which the heated-water system was identified as the source of the organism, the system was decontaminated by pulse (one-time) thermal disinfection or superheating (i.e., flushing each distal outlet of the hot-water system for at least 5 minutes with water at greater than or equal to 65 C) and hyperchlorination (flushing all outlets of the hot-water system with water containing greater than or equal to 10 mg/L of free residual chlorine) .

After either of these procedures, most hospitals either a) maintain heated water at greater than or equal to 50 C or less than 20 C at the tap or b) chlorinate heated water to achieve 1-2 mg/L of free residual chlorine at the tap .

Additional measures (e.g., physical cleaning or replacement of hot-water storage tanks, water-heaters, faucets, and showerheads) may be required because scale and sediment might accumulate in this equipment and protect organisms from the biocidal effects of heat and chlorine .

Alternative methods for controlling and eradicating legionellae in water systems (e.g., treating water with ozone, ultraviolet light, or heavy metal ions) have limited the growth of legionellae under laboratory and/or operating conditions. However, additional data are needed regarding the efficacy of these methods before they can be considered standard precautions.

Measures for decontaminating hospital cooling towers have been published previously .

Additional preventive measures have been used to protect severely immunocompromised patients.

At one hospital, immunosuppressed patients were restricted from taking showers, and, for these patients, only sterile water was used for drinking or flushing nasogastric tubes . In another hospital, a combined approach consisting of continuous heating, particulate filtration, ultraviolet treatment, and monthly pulse hyperchlorination of the water supply to the bone-marrow transplant unit was used to decrease the incidence of Legionnaires' disease.

The decision to search for hospital environmental sources of Legionella sp. and the choice of procedures to use to eradicate such contamination should take into account the type of patient population served by the hospital.

Furthermore, decision makers should consider a) the high cost of an environmental investigation and of instituting control measures to eradicate Legionella sp. from sources in the hospital and b) the differential risk, based on host factors, for acquiring nosocomial legionellosis and of having severe and fatal infection with the microorganism.

Extracts from CDC Guidelines 1994

Clinical Description: An illness with acute onset commonly characterized by fever, cough, and pneumonia that is confirmed by chest radiograph. Encephalopathy and diarrhea may also be included.

Laboratory Criteria for Diagnosis: Isolation of Legionella from lung tissue, respiratory secretions, pleural fluid, blood, or other normally sterile sites, OR Demonstration of a fourfold or greater rise in the reciprocal IF (immunofluorescence) antibody titer to > 128 against Legionella pneumophila serogroup 1, OR Demonstration of L. pneumophila serogroup 1 in lung tissue, respiratory secretions, or pleural fluid by direct fluorescence antibody testing, OR Demonstration of L. Pneumophila serogroup 1 antigens in urine by radioimmunoassay.

Case Classification: Confirmed: A case that is laboratory-confirmed.

Probable: A clinically compatible illness with demonstration of a reciprocal antibody titer >256 from single convalescent-phase serum specimen.

The Legionellaceae are a family of fastidious, slow growing, aerobic, gram-negative bacteria of which Legionella pneumophila is the member most commonly found as a cause of human disease . It occurs naturally in aqueous habitats. For disease to occur, a susceptible person must inhale an infected aerosol of sufficiently small particle size to penetrate to alveolar level. Outbreaks of legionnaires' disease have been caused by contamination of cooling water systems used in industrial premises or in air conditioning plant, of hot water systems in large buildings such as hotels and hospitals, of recreational pools and of respiratory therapy equipment. Sporadic cases are most common in the late summer and autumn. The frequency of legionnaires' disease as a cause of community-acquired pneumonia varies between 2% and 15% in different studies.

Legionnaires' disease affects men more than women, and is most common in the 40-70 year age group. It is rarely found in children. The disease is more severe in smokers, alcoholics, diabetics and in immunosuppressed patients. Serological surveys show that some infections are subclinical, and that some give rise to a `flu-like' illness known as Pontiac fever, in which pneumonia does not occur. The reasons for these different manifestations of the same infection are unknown.

The clinical features of legionnaires' disease overlap with those of other acute pneumonias and it is not possible to make a certain diagnosis on the strength of the clinical observations alone. However, there is a relatively high incidence of confusion and other neurological findings, diarrhoea and liver and renal dysfunction. These features, in a patient seriously ill with pneumonia and, particularly, with recent exposure to possible sources of legionella infection, make a diagnosis of legionnaires' disease much more likely.

Specific investigation of the cause of legionnaires' disease depends on direct identification of the organism by culture or immunofluorescent staining, or on the demonstration of a rising titre of antibody in the serum. In some cases the organism can be isolated from blood or expectorated sputum, but a higher yield of positive results has been reported from lung secretions obtained by transtracheal aspiration or bronchoalveolar lavage .

A retrospective diagnosis may be made by serological testing using the indirect fluorescent antibody test. The rate at which specific antibody appears in patients with legionnaires' disease varies from less than a week to more than a month. It is therefore necessary to examine specimens taken not only during the acute and early convalescent stages but also in late convalescence (about 6 weeks) to ensure a maximum diagnostic yield.

Other laboratory investigations are likely to show moderate neutrophilia of the peripheral blood and, in about half of the cases, hyponatraemia. Proteinuria and evidence of hepatocellular disturbance are also seen. The chest x-ray appearance is somewhat variable, with segmental, lobar and nodular shadows all being reported. These may be restricted to one part of the lung, but in about one-third of cases more than one lung zone is affected . Rapid deterioration of the chest x-ray appearance over the first few days seems to be particularly common in legionnaires' disease. Pleural effusions occasionally develop but are small. Radiographic recovery may be slow and there are reports of permanent lobar collapse and fibrosis in survivors of severe attacks.

Erythromycin has been used most widely for the treatment of legionnaires' disease. In severe cases it should be given intravenously and consideration should be given to the addition of another agent such as rifampicin. If erythromycin cannot be used, doxycycline is the recommended alternative. The reported mortality in cases admitted to hospital is 5-15% in previously healthy patients and 70% in the immunosuppressed. illustrates the autopsy appearance of extensive pulmonary consolidation in a case of legionnaires' disease.

Legionnaires' Disease

Germs sometimes impersonate other germs, causing symptoms that lead you to believe you're suffering from a mild illness instead of a severe one.

Legionnaires' Disease is a case in point. It's a bacterial infection of the lungs that may begin with flu-like symptoms such as headache, fever, chills, and muscle aches. But it can progress rapidly to pneumonia and result in mental confusion, shock, kidney and liver damage, and congestive heart failure. Death occurs in about 15 percent of the cases.

Although outbreaks of Legionnaires' Disease probably occurred in the distant past, scientists did not identify the affliction until a well-publicized 1976 outbreak at an American Legion convention in Philadelphia. More than 224 persons came down with the disease, and 29 died. Medical sleuths traced the cause to a bacteria populating the air-conditioning system at the convention hotel.
They named it Legionella pneumophilia and found that it not only inhabits moldy air-conditioning systems but also reservoir water and moist soil. The germ enters the body through contaminated water vapor that people breathe. Apparently the infection is not contagious.

How do you know if you have Legionnaires' disease? Can you protect yourself from the germ that causes it?

First, there's no way that you or any other lay person can tell you have the illness without the help of a physician. But you should suspect it as a possible cause if you experience the aforementioned flu-like symptoms, as well as diarrhea, abdominal pain, vomiting, or a dry cough that sometimes produces bloody sputum. You should be especially wary if you experience those symptoms and you have one or more of the following risk factors:

1.You are elderly.
2.You smoke cigarettes.
3.You drink alcohol to excess.
4.You take drugs that lower your susceptibility to illness.

If you think there is the slightest chance you could have Legionnaires' disease, see your physician for a physical exam and blood tests. If the results show that you do have the illness, the physician can begin treatment with an antibiotic, probably erythromycin. The earlier the treatment begins, the better will be your chances of a complete recovery.

No vaccine exists to protect you against Legionnaires' disease. But you can take the following measures to minimize your risk of getting the disease:

1.If you smoke, quit.
2.If you drink to excess, cut down or quit.
3.If you are elderly or take immune-suppressing drugs, lead a healthful lifestyle and eat a nutritious diet.
4.Have air-conditioning systems cleaned and inspected regularly

Evaporation. Evaporative units have a fan inside them that blows air through a wet pad, and this moisture-laden air then continues on into the room. ("Wicking" humidifiers do the same thing, only the air is blown through a moisturized filter instead of a pad.) Evaporative units don't produce a spray and are therefore less likely to spread germs than are units that throw a cool mist into the air. The wet pads, however, can become a breeding ground for bacteria if not cleaned regularly.

Legionella Pneumonia

Legionnaires’ diseases derives its name from an outbreak of pneumonia at the 1976 American Legion Convention in Philadelphia. Thirty-four of the 221 individuals who developed pneumonia eventually died.
The microorganism Legionella pneumophila, was isolated 6 months after the epidemic. Since then, this pneumonia has been documented throughout the world, and over 30 species are now classified in the new family Legionellaceae.

L. pneumophila is small, weakly staining gram-negative rod and is associated with fresh water supplies, such as air-conditioner condensers and cooling towers. It is estimated to account for between 1% and 5% of all pneumonias. Unlike other gram-negative pneumonias, symptoms may resemble viral or mycoplasmal infection early on the course. The infection is often accompanied by relative bradycardia, fevers, elevated white blood cell count, proteinuria, and a "patchy" alveolar infiltrate that frequently progress to lobar consolidation. A dry, irritanting cough and pleural effusions are also common.

The diagnosis of Legionnaires’ disease is usually based on a "positive" serology with a consistent clinical picture. A single-complement fixation titer of 128 or greater or a documental fourfold increase in the titer is consideraded diagnostic of an acute infection. Culturing Legionella is difficult since 3-4 days is required for growth, and special medias are needed. Sensitivity of sputum culture approaches 70% when dye-containing selective media are used in combination with the buffered yeast extract agar following acid pretreatment for contamination species. Direct fluorescent antibody stain of respiratory tract secretions or a tissue sample is a mores rapid means of diagnosis Legionella infecction, but there are false-negatives with this test.

Dr. João B. Bonnassis Jr. bonna@netlan.com.br

 

Legionnaires' disease (Legionella pneumonia)  Description: atypical community acquired pneumonia, for general information see pneumonia in general (community-acquired pneumonia)  Organs Involved: lung; GI tract, kidney, liver, CNS Who Is Most Affected: males > 55 Incidence: most predominant atypical pneumonia (in adults), 5-10% community acquired pneumonia Etiology: Causes: L. pneumophila or L. micdadei, 22 other species Pathogenesis: ubiquitous (water source), aerosol spread, not person-to-person necrotizing bronchopneumonia protected from antibiotics that don't penetrate macrophages  Increased Risks/Associated Conditions/Complications  Increased Risks: warm moist environments (air conditioning, nebulizer), alcoholic, smoker, dialysis, COPD, heart disease, lung disease, renal disease, diabetes Associated Conditions: Pontiac fever Complications: bacterial superinfection, DIC, SIADH History: asymptomatic infection, subacute non-productive cough + dyspnea, abrupt high fever, shaking chills, cough, nausea, vomiting, diarrhea, sudden headache, slight hemoptysis; occasionally scant mucoid sputum, myalgia, arthralgia, malaise, abdominal pain; rarely pleuritic pain in elderly - fever less common, altered mental status HPI: may be insidious or virulent presentation Physical: General: Faget sign (high fever with normal heart rate, relative bradycardia) Lungs: normal lungs Neuro: occasionally neurologic + MSE findings (confusion) Diagnostic: diagnosis can not be made on clinical grounds alone usually diagnosed by serology (titer > 1:256 or 4x rise in indirect FAb to titer > 1:128) Rule out: typical pneumonia, Mycoplasma pneumonia, Chlamydia pneumonia, psittacosis, Q fever Blood tests: WBC < 15,000, serology, hyponatremia, abnormal liver function tests, azotemia Urine studies: hematuria, microhematuria, proteinuria Imaging studies: CXR patchy + interstitial or lobar takes 2-6 mos for complete CXR clearing, >65% worsening at 2-3 days despite defervescence (Clin Chest Med 1987;8;529) Other: sputum staining or staining of other secretions (e.g. brocho-alveolar lavage) gram stains shows many PMNs, no bugs DFA (direct FAb) of sputum - rapid diagnosis other methods - Dieterle silver impregnation stain, nucleic acid hybridization culture 90% positive by transtracheal aspiration, 50-70% by sputum culture use charcoal-enriched yeast extract agar with increased iron + cysteine see gram-negative pleomorphic rods (which stain poorly) Prognosis: 18% mortality (due to comorbidity), most self-limited 7-10 days Treatment: General: treat at least 2 wks Medications: frequently produces ß-lactamase macrolide (erythromycin, azithromycin, clarithromycin) e.g. erythromycin 1 g IV q6h doxycycline or tetracycline (if erythromycin not tolerated) alternatives - Bactrim, ofloxacin (also empiric), ciprofloxacin add rifampin 600 mg PO bid for seriously ill patients Prevention: heat + hyperchlorinate water Screening: urinary Ag

Legionella spp:
Legionnaires' Disease and Pontiac Fever

Organism:

1. Several species capable of causing disease

2. L. pneumophila is best-studied species

a. accounts for about 85% of Legionella infections

b. motile gram-negative aerobic rod with complex nutritional requirements

3. L. micdadei causes febrile illness called Pontiac fever

a. unlike legionnaires' disease, Pontiac fever is self-limiting, little or no tissue damage

Disease:

1. First recognized as a cause of pneumonia in 1976 (L. pneumophila)

2. Incidence increased dramatically with installation of central air conditioning in large buildings

3. Legionella sp. are ubiquitous in soil and water, grow well in air-conditioning cooling towers

a. aerosols from air-conditioning machinery are inhaled

b. devices for inhalation therapy can become contaminated, introduce bacteria

c. dust, liquid aerosols from construction sites also sources of Legionella

4. Healthy not very susceptible, but underlying conditions that impair respiratory defenses (heavy alcohol use, smoking, old age) increase susceptibility

a. first outbreak of note was in elderly men at American Legion convention in Philadelphia

b. hospital patients with underlying immune defects also susceptible

5. Characterized by fever, disorientation, lethargy, considerable lung damage

a. appears on X-ray films as patchy regions of fluid accumulation

b. most invading bacteria found inside phagocytes, growing inside phagosomes

c. extensive lysis of phagocytes

Virulence Factors:

1. Environmental survival

a. free living

b. parasitism of amoebae (Acanthamoeba sp.and Naegleria sp)

1. more resistant than free-living bacteria to biocides

c. biofilms

1. more resistant to disinfectants (very slow growth rate in the biofilm)

2. Activation of complement

a. activation of both pathways

b. LPS activates alternative pathway, but C3b preferentially binds to outer membrane porin

3. Interaction with phagocytes

a. opsonization enhances uptake but can enter macrophages without opsonization

1. attaches to macrophages

2. provokes coiling phagocytosis

3. long thin pseudopod engulfs bacterium in coiled vesicle

4. vesicle does not acidify, phagolysosome fusion inhibited

5. bacteria divide within vesicle

6. vesicle studded with ribosomes

7. significance uncertain (not demonstrated in vivo)

b. eventually kill macrophage, mechanism unknown

c. outer membrane protein designated Mip (macrophage invasion protein)

1. may promote invasion in absence of opsonization

2. mip mutants

a. reduced invasion of human macrophages in vitro

b. increased LD50 for guinea pigs

c. no effect on growth of internalized bacteria

d. phospholipase C (hydrolyzes phosphatidylcholine)

1. injure phagocytes and lung tissue

2. could act on phagosome membrane, allow escape to cytoplasm of phagocyte

e. protein kinases

1. phosphorylate specific tyrosine, serine, or threonine residues involved in activation/deactivation of eucaryotic signaling proteins

2. Two protein kinases from L. micdadei

Damage to the lung:

1. Phagocytes and T cells attracted to lung release cytokines, other toxic products, do not kill bacteria

2. Proteases

a. 40-kDa zinc metalloprotease from L. pneumophila

b. intranasal, intratracheal challenge of guinea pigs produces compatible lesions

c. amino acid sequence suggests similarity to Pseudomonas aeruginosa elastase

d. enzymatically inactivates IL-2, CD4 receptors on T cells, could inhibit T cell activation

e. antibodies are protective

Treatment and prevention:

1. Drug of choice is erythromycin.

2. Prevention requires disinfection of water systems.

The bacterium Legionella pneumophilia belongs to the gram negative class of bacteria. The cell wall of Gram-negative bacteria is a thinner structure, than that of the gram positive, and contains distinct layers. An outer layer which is more like a cytoplasmic membrane in its composition with the typical trilaminar structure.

The main component of the Gram-negative cell wall is lipopolysaccharide. The lipopolysaccharide consists of a core region to which are attached repeating units of polysaccharide moieties. A component of the cell wall of most Gram-negative bacteria is associated with endotoxic activity, with which are associated the pyrogenic effects of Gram-negative infections. On the side-chains are carried the bases for the somatic antigen specifity of these organisms. The chemical composition of these side chains both with respect to components as well as arrangement of the different sugars determines the nature of the somatic or O antigen determinants, which are such important means of serologically classifying many Gram-negative species. In many cases it has been shown that the reason for certain organisms belonging to quite different species, giving strong serological cross-reactivity is due their having chemically similar carbohydrate moieties as part of their lipopolysaccharide side chains, which generally have about 30 repeating units. These side chains have as part of their structure frequently quite common hexoses, but in many cases there are also present some unusual hexoses, such as 6-deoxyhexoses and 3,6-dideoxyhexoses. Also O -methyl sugars may be part of these side chain structures. There is a great deal of variation among these side chains, however, the composition of the core region is much more conserved among many Gram-negative groups of bacteria. Characteristic of the core region of many of the Enterobacteriaceae is phophorylated 2-keto-3-deoxyoctonoate, phosphorylated L-glycero-D-mannoheptose, D-galactose, D-glucose and N -acetyl-glucosamine. The first two are by far the most widespread components of the core region of many species. The lipid component of the lipopolysaccharide, known as lipid A is predominantly associated with the endotoxic activity. It is the most conserved part of the Gram-negative cell wall and the basis of its structure is a beta-1,6-linked D-glucosamine disaccharide. In some Pseudomonas and Rhodopseudomonas strains this is replaced by 2,3-diamino-2,3-dideoxy-D-glucose. This has phosphate residues in positions 1 and 4. To both the amino and hydroxyl groups of the glucosamine moieties are linked long-chain fatty acids. Among the enterobacterial lipopolysaccharides the N -acyl residues are frequently fatty acids like beta-hydroxymyristic acid or similar 3-hydroxyalkanoic acids. Some Gram-negative bacteria lack phosphate in their lipid A and some types contain other carbohydrates 2,3-diamino-2,3-dideoxy-D-glucose. Legionella pneumophilia belongs to the class: LEGIONELLACEAE

These are Gram-negative, non-sporing non-acid fast rods, 1-2µm long by 0.5µm wide. They are fastidious bacteria requiring iron and cysteine for primary isolation. They are generally motile with one to three polar flagellae. They are chemoorganotrophs and lack the ability to ferment any sugars. They do not have a glucose transport system. Some amino acids act as primary carbon and energy sources and are metabolised through the tricarboxylic acid cycle, while carbohydrate synthesis occurs along the Embden-Meyerhof pathway. Most strains produce catalase and liquify gelatin and many produce beta-lactamase and oxidase. A number of species are pigmented and some show autofluorescence. The optimum temperature for growth of human isolates is around 35°C. Legionella : This is the only accepted genus and comprises over 30 species. Two other genera have been proposed, Tatlockia and Fluoribacter , for the species T. micdadei , F. bozemanii , F. dumoffii and F. gormanii , but generally theses species are accepted as members of the genus Legionella. The traditional methods of classification cannot be used because of their general inertness. They have a unique cell wall among Gram-negative bacteria, containing large amounts of branched chain fatty acids. They are also subdivided on the basis of their unusual isoprenoid quinones in their respiratory chain. The GC content of the DNA is 38-52 mol%.

Legionella pneumophila They are Gram-negative non-acid fast non-capsulated rods 0.3-0.9 µm x 2-20µm. They are aerobic and do not hydrolyse gelatin or produce urease. They are non-fermentative. L. pneumophila is neither pigmented nor does it autofluoresce. It is oxidase and catalase positive, produces beta-lactamase. It is a strict aerobe. It hydrolyses hippurate and liquifies gelatin but does not ferment any carbohydrates. It requires specialised media for growth. There is up 67% relatedness between the species on the basis of DNA hybridization studies. DNA probes specific for rRNA sequences of Legionella have been produced, as have ones for other specific genes. Plasmids have been demonstrated in many species and plasmid profile analysis has been used to characterise relationships between strains. At least 14 different serovars of L. pneumophila have been described as well as several other species being subdivided into a number of serovars. Sera have been used both for slide agglutination studies as well as for direct detection of bacteria in tissues using fluorescent-labelled antibody. Specific antibody in patients can be determined by the indirect fluorescent antibody test. ELISA and microagglutination tests have also been successfully applied. L. pneumophila is an intracellar pathogen. The internalisation of the bacteria is enhanced by the presence of antibody and complement. A pseudopod coils around the bacterium in this unique form of phagocytosis. Once Internalised, the bacteria surround themselves by a membrane-bound phagolysosome. This becomes a vescicle, within which the bacteria multiply. They produce a 39kDa metalloprotease into culture fluids, which is cytotoxic for some cultured tissue culture cells. This may be a virulence factor. A novel cytotoxin consisting of small peptides, which are acid and heat resistant has also been described. L. pneumophila may also have a unique iron scavanging system. Apart from carriers Legionallae do not form part of the normal flora of humans or animals. Intestinal Infections: These may only occur as part of respiratory infections, where gastrointestinal symptoms have on occasion been described. Extraintestinal Infections: L. pneumophila is specifically considered as a pathogen of the respiratory tract, where it is a cause of atypical pneumonia, also known as Legionnaires' disease. Other infections have also been reported, including haemodialysis fistulae, pericarditis and wound and skin infections. Bacteraemia is often associated with Legionnaires' disease. Animal Infections: None specifically recorded. Infections of Protozoa: Protozoa such as Harmanella vermiformis and related protozoa have been shown to be able to support the growth of L. pneumophila in tap water. Also Acanthamoeba , Naegleria and Tetrahymena can be infected by L. pneumophila . It is considered that this may be how these fastidious organisms survive in the environment.

From Mosby's Infectious Diseases, 1995

Legionnaires' Disease The Legionellaceae are a family of fastidious, slow growing, aerobic, gram-negative bacteria of which Legionella pneumophila is the member most commonly found as a cause of human disease . It occurs naturally in aqueous habitats. For disease to occur, a susceptible person must inhale an infected aerosol of sufficiently small particle size to penetrate to alveolar level. Outbreaks of legionnaires' disease have been caused by contamination of cooling water systems used in industrial premises or in air conditioning plant, of hot water systems in large buildings such as hotels and hospitals, of recreational pools and of respiratory therapy equipment. Sporadic cases are most common in the late summer and autumn. The frequency of legionnaires' disease as a cause of community-acquired pneumonia varies between 2% and 15% in different studies.

Legionnaires' disease affects men more than women, and is most common in the 40-70 year age group. It is rarely found in children. The disease is more severe in smokers, alcoholics, diabetics and in immunosuppressed patients. Serological surveys show that some infections are subclinical, and that some give rise to a `flu-like' illness known as Pontiac fever, in which pneumonia does not occur. The reasons for these different manifestations of the same infection are unknown.

The clinical features of legionnaires' disease overlap with those of other acute pneumonias and it is not possible to make a certain diagnosis on the strength of the clinical observations alone. However, there is a relatively high incidence of confusion and other neurological findings, diarrhoea and liver and renal dysfunction. These features, in a patient seriously ill with pneumonia and, particularly, with recent exposure to possible sources of legionella infection, make a diagnosis of legionnaires' disease much more likely.

Specific investigation of the cause of legionnaires' disease depends on direct identification of the organism by culture or immunofluorescent staining, or on the demonstration of a rising titre of antibody in the serum. In some cases the organism can be isolated from blood or expectorated sputum, but a higher yield of positive results has been reported from lung secretions obtained by transtracheal aspiration or bronchoalveolar lavage (Fig 2.28).

A retrospective diagnosis may be made by serological testing using the indirect fluorescent antibody test. The rate at which specific antibody appears in patients with legionnaires' disease varies from less than a week to more than a month. It is therefore necessary to examine specimens taken not only during the acute and early convalescent stages but also in late convalescence (about 6 weeks) to ensure a maximum diagnostic yield.

Other laboratory investigations are likely to show moderate neutrophilia of the peripheral blood and, in about half of the cases, hyponatraemia. Proteinuria and evidence of hepatocellular disturbance are also seen. The chest x-ray appearance is somewhat variable, with segmental, lobar and nodular shadows all being reported. These may be restricted to one part of the lung, but in about one-third of cases more than one lung zone is affected (Fig 2.29). Rapid deterioration of the chest x-ray appearance over the first few days seems to be particularly common in legionnaires' disease. Pleural effusions occasionally develop but are small. Radiographic recovery may be slow and there are reports of permanent lobar collapse and fibrosis in survivors of severe attacks.

Erythromycin has been used most widely for the treatment of legionnaires' disease. In severe cases it should be given intravenously and consideration should be given to the addition of another agent such as rifampicin. If erythromycin cannot be used, doxycycline is the recommended alternative. The reported mortality in cases admitted to hospital is 5-15% in previously healthy patients and 70% in the immunosuppressed.

LEGIONNAIRES' DISEASE

Scott Robertson, MD

December 5, 1996

During the summer of 1976, the American Legion held a convention at the Bellevue-Stratford Hotel in Philadelphia. Within days of the event, one after another of the veterans in attendance became deathly ill. Ultimately 221 patients were stricken with a syndrome characterized by high unremitting fevers, rigors, general prostration, frequently with rapidly progressive pulmonary infiltrates unresponsive to antibiotic therapy. Thirty-four patient eventually died of the syndrome, usually from rapidly progressive pneumonia or related complications. Epidemiologists from state and federal divisions began intense investigation of the hotel, which seemed to be the only common thread uniting the patients affected by this unknown illness; meanwhile, basic scientists and microbiologists began the search for a pathogen in tissues and fluids from survivors and fatalities.

Initially, this was epidemic was feared to be the beginning of an influenza pandemic, as the "Swine Flu" had begun to affect populations in Asia during this year. Eventually this possibility was excluded, and, for the next several months, imaginations ran wild with multiple proposed etiologies from scientists, physicians, media personnel, and the general public. Theories would ebb and flow with time, including the likes of nickel carbonyl intoxication, viral pneumonia, and communist or pharmaceutical company conspiracies against the American veterans. The only real consensus to develop among scientists was that this was NOT a bacterial disease! With no progress toward proving an of these theories, CDC officials broadened the search for a cause.

Joseph McDade, a "rickettsiologist" at the CDC for less than 8 months, was asked to rule-out Q-fever as a cause of this syndrome. In his search, he used techniques which were commonly employed to isolate rickettsial pathogens. He inoculated guinea pigs with material from victims of the illness, and the animals all died of a febrile illness. On microscopy of spleen preparations, McDade saw several cocci and several small bacilli, but, initially doubted the significance of this finding. He then inoculated embryonated eggs with suspensions of the guinea pig spleen tissue and added a small amount of antibiotic to inhibit the growth of contaminating bacteria, but still allow rickettsial growth. The eggs grew nothing, and he felt rickettsiae had been effectively eliminated as a possibility. Several weeks later, however, McDade returned to his slides, troubled by the fact that the rods seen initially did not grow in the eggs. This time he found a cluster of bacilli being engulfed by a white cell, and re-innoculated the eggs, without antibiotics added to the preparation. The bacilli grew and reacted with sera from victims of the illness, and antibody titers were found to rise between early and late stages of the illness. Later, this bacteria would be named Legionella pneumophila in tribute to the people affected and in reference to the major pathologic process the organism causes. Later, samples of serum from a similar unexplained episode eight years earlier in Pontiac, Michigan, tested positive for antibody to the same organism.

ETIOLOGY

Legionella pneumophila is an aerobic, gram negative rod. There are at least 34 different species of Legionella and 52 serogroups. Around half of the species can cause disease in humans. Legionella pneumophila serogroup 1 is responsible for more than 80% of all Legionella infections in humans with serogroups 4 and 6 responsible for the remainder. Variable virulence between strains may account for distinct clinical syndromes. The organisms are fastidious and require special techniques for isolation. Specimens must be cultured immediately and yields are increased with acidification. Additionally, special plating is required, with the standard being a buffered charcoal yeast extract agar.

Water reservoirs are the natural habitat of L. pneumophila. Warm water frequently supports algae growth, which, in turn, can provide nutrients necessary to Legionella proliferation. Additionally, amoebae may also proliferate in warm waters and provide Legionella shelter from unfavorable environmental factors. Initially, air conditioning cooling towers were implicated as the most common source of infections; however, these studies suffered from detection bias. After decontaminating the towers, infections rates did not drop until potable water supplies were also sterilized. Currently it is recognized that contaminated supplies of potable water are likely the most common source of spread to patients. Patient-to-patient spread has never been documented.

Epidemiology

Legionellosis is a world-wide problem. Cases appear in sporadic, endemic, and epidemic fashions. Epidemics usually result from exposure to aerosolized bacteria in the nosocomial setting or in the workplace. The incidence in community acquired pneumonia varies from 1-27% in various studies, but is most consistently found in about 6% of adult pneumonias. The frequency increases, however, in "severe" community acquired pneumonias, and in some ICU studies, actually surpasses pneumococcus as a pathogen. In the nosocomial setting, legionella causes between 1-40% of pneumonias acquired after admission. Attack rates are higher in patients with underlying debilitating illnesses (such as COPD and diabetes), tobacco abuse, advancing age, and in those with immunodeficiencies (especially organ transplant recipients).

The organisms are intracellular pathogens, and thus, cell mediated immunity, especially at the alveolar macrophage level, plays the most important role in host defense. Serum antibodies enhance opsonization, but are of minor importance in host defense strategies; infections have occurred in hosts with preexisting antibody levels. Infection typically occurs after exposure to aerosolized droplets of water contaminated with legionella. Direct infection of surgical wounds as well as infections of the gastrointestinal tract have occurred after bathing or drinking contaminated water. Based on low infection rates in low-aspiration-risk head and neck surgeries versus high infection rates in those with high aspiration risk, it has been theorized that aspiration of contaminated water may also play a role in pulmonary infection.

CLINICAL FEATURES

Pontiac Fever is a non-pneumonic, acute, self-limited febrile illness which is characterized by flu-like (apologies to Dr. Hayden) symptoms of malaise, myalgias, fever, chills, and headaches. Non-productive cough has been reported, but chest x-rays remain clear and complete recovery within one week is the rule, with only symptomatic treatment necessary. The attack rate is over 90% in those who are exposed, and symptoms develop within 24-48 hours of exposure. The limited nature of this syndrome is felt to be due to a lower virulence strains of L. pneumophila.

Legionnaires' Disease is an illness with a vast spectrum of clinical symptoms ranging from mild cough and fever to widespread pulmonary infiltrates and multisystem organ failure. The syndrome was originally felt to fit a category of "atypical pneumonia", which was characterized by nonproductive cough, relative bradycardia, abnormal liver function tests, diarrhea, myalgias, confusion, rigors, hyponatremia, and hypophosphatemia. Several prospective studies have not found statistically significant differences in many of these areas.

From Roig, J., et. al., Chest, 2/91, V. 99, 344-350.

Fang et. al. prospectively examined 359 cases of community acquired pneumonia in three Pittsburgh, PA hospitals between July 1, 1986 and June 30, 1987. 58.5% had an identifiable definitive or presumptive etiology. Of all cases, Legionella accounted for 6% and ranked third behind S. pneumoniae (15.3%) and H. influenzae (10.9%). Compared to all other etiologies, Legionella showed statistically significant differences in only a few areas: fever > 40 C, diarrhea, and ICU admission. There was no increased incidence of hyponatremia, renal failure, or LFT abnormalities seen in this study. The details are found in the table below:

In summary, although there is clearly too much overlap to allow for distinctions between various syndromes on a clinical basis, several features are suggestive of Legionella infection: fevers over 40C, significant hyponatremia, failure to respond to -lactam antibiotics, and occurrence in a hospital or environment known to have potable water supplies contaminated by L. pneumophila. Radiographs will reveal an infiltrate in over 90% of cases, and, although there are no pathognomonic features, a patchy or segmental alveolar unilobar infiltrate is the most common early finding. Without specific treatment, these infiltrates can expand rapidly. Even with treatment, infiltrates in the immunocompromised patients will not infrequently cavitate. Pleural effusions are seen in up to 30% of patients.

EXTRAPULMONARY MANIFESTATIONS

The majority of extrapulmonary disease will develop in patients with either immunocompromise or overwhelming pneumonia. Occasionally, symptoms and signs of extra-pulmonary disease will be present without obvious pneumonia. Autopsy studies of fatal cases have identified organisms in the spleen, liver, and kidneys in 50% of cases. Other studies have found L. pneumophila in myocardium, bone marrow, and intrathoracic lymph nodes, suggesting both a hematogenous and lymphatic spread of organisms. Lowry and Tompkins summarize 22 patients reported in the literature to have extrapulmonary infections. Fifteen of the 22 patients had no underlying illnesses and only 5 were on immunosuppressive agents. 3 of the patients had sternal wound infections due to post-operative sponge baths given with non-sterile water.

With Pneumonia Without Pneumonia Blood Pericardium Blood Endocardium Brain Bone marrow Surgical wounds Peritoneum Bowel Skin and fascia Bowel Pericardium Kidney Rectum Respiratory sinus Skin and fascia Liver Myocardium Spleen Peripheral lymph nodes Hemodialysis shunt Thyroid Peritoneum Pancreas Prostate Testes

DIAGNOSIS

With the difficulty in defining the syndrome clinically or with basic laboratories, sophisticated testing has been developed to aid in diagnosis. Culture is possible from a wide variety of specimens, and the organism has been isolated from sputum, transtracheal aspirates, endotracheal suction specimens, blood, lung biopsy tissue, pleural fluid, BAL fluid, peritoneal fluid, and sinus aspirates. It may take up to 10 days before colonies grow and selective techniques and agars are necessary. Sensitivity is increased with samples more representative of the lower respiratory tract, but positive results are seen even with inadequate sputa by classical criteria, and colonization/false positives are not seen in non-infected individuals. Serologic testing takes 6-8 weeks to show a rise in the convalescent period and is of little use in the acute setting. Most labs use an indirect fluorescent assay (IFA). 75% of immunologically normal individuals with culture proven infection will have a 4-fold increase in titers by week 8. 30% of healthy volunteers have titers to serogroup 1 of 1:128 or greater, thus only a four-fold rise maintains specificity. Cross-reactions have been reported (tularemia, melioidosis, plague, leptospirosis, Pseudomonas, and B. fragilis bacteremia) and specificity is estimated at 90%. Direct fluorescent antibody (DFA) testing is rapid and can be used on secretions as well as tissue and fluids. There are cross-reactions with Bordatella pertussis, Bacteroides fragilis, Pseudomonas spp., Xanthomonas, and other gram negative organisms have been reported, and occasionally to Staph. Aureus, B. cereus, and Lactobacillus brevis. Yields are decreased with antibiotic treatment, but this test can be used to help identify the etiologies of sterile abscesses in immunocompromised patients. Urinary antigen detection by RIA or ELISA is sensitive and specific, but only for serogroup 1 at present; however, this organism accounts for over 80% of infections. The test will remain positive for several days even after initiation of treatment. DNA probes are not currently commercially available, but may enhance diagnostic certainty in the future. Usually, a combination of methods should be employed if the diagnosis is suspected to enhance the sensitivity of testing.

Selective media required, current antibiotic use may decrease sensitivity, saline for BAL inhibits growth Serologic study (IFA) Serum 75

Optimal sensitivity requires acute and convalescent sera; highest specificity is for L. pneumophila serogroup 1 DFA Sputum, BAL

Detects serogroup 1; not sensitive for other Legionella species; may cross react with other

From Shelhamer, JH, moderatory, "NIH Conference: The laboratory eval. Of opportunistic pulmonary infections", Ann Int Med, V.124, N.6, p. 591.

TREATMENT

There is a paucity of prospective comparative studies of treatments for Legionnaires' disease. Retrospective studies have identified effective regimens. In vitro studies often cannot be extrapolated to in vivo results due to the intracellular location of the pathogen; however, animal model and cellular infection studies have shown higher activities for the bactericidal fluoroquinolones. In these studies, azithromycin was shown to kill intracellular L. pneumophila whereas clarithromycin was static. Because of its history, only erythromycin is FDA approved for the treatment of this disease. Several alternative regimens are listed below:

1.Erythromycin (+/- rifampin) 4 gm per day optimal treatment (failures seen with lower doses) Often continued for 3 weeks to prevent recrudescence Side effects include local pain and phlebitis at infusion site and transitory neural hearing loss Cylcosporine levels must be monitored and doses reduced accordingly 2.Rifampin (as added agent only) 600 mg every 12 hours added to erythromycin Resistant mutants which develop on treatment preclude use of this agent alone Animal studies show decreased lung damage with rifampin added to erythromycin, but survival is not improved 3.Doxycycline (+/- rifampin) 200 mg IV every 12 hours for two doses then 200 mg IV per day Limited data make this a second line agent with, 4.Ciprofloxacin 400 mg IV every 12 hours or 500 mg PO every 12 hours Limited data, but fluoroquinolones are bactericidal in animal studies 5.TMP/Sulfamethoxazole 320/1,600 mg every 8-12 hours, sometimes combined with erythromycin and rifampin Some L. micdadei infections which failed erythromycin have responded to IV treatment with TMP/Sulfa Decreased frequency of Legionnaires' disease found in HIV patient taking prophylactic TMP/Sulfa for PCP 6.Clarithromycin 250 mg PO every 12 hours 7.Azithromycin 500 mg PO on day 1 and then 250 mg PO daily for 4 days

PREVENTION

Home water heaters and hospital water supplies are major reservoirs for infection. Hyperchlorination is marginally successful in decreasing colony counts, but heating to higher temperatures (140-180 F) is the most important deterrent to colony proliferation.
This must be balanced against an increased risk of scalding injuries. Substituting sterile water for tap water in drinking supply for immunocompromised patients has been attempted. Sterile water or post-washing sterilization is recommended for all respiratory equipment.

REFERENCES

Blatt, SP, et. al., "Legionnaires' Disease in HIV-Infected Patients: Eight Cases and Review", Clinical Infectious Diseases, Feb. 18, 1994, Vol. 18, pp. 227-232.

Edelstein, Paul H., "Legionnaires' Disease", Clinical Infectious Diseases, June 16, 1993, Vol. 16, pp. 741-749.

Fang, Guo-Dong, et. al., "New and Emerging Etiologies for Community-Acquired Pneumonia with Implications for Therapy: A Prospective Multicenter Study of 359 Cases", Medicine, 1990, vol. 69, No. 5, pp. 307-316.

Fraser, DW, et. al., "Legionnaires' Disease: Description of an Epidemic of Pneumonia", The New England Journal of Medicine, December 1, 1977, Vol 297, No.22, pp. 1189-1196.

Lowry, PW, Tompkins, LS, "Nosocomial legionellosis: A review of pulmonary and extrapulmonary syndromes", American Journal of Infection Control, 1993, Vol. 21, pp. 21-27.

McDade, JE, et. al., " Legionnaire's Disease: Isolation of a Bacterium and Demonstration of Its Role in Other Respiratory Diseases", The New England Journal of Medicine, December 1, 1977, Vol 297, No.22, pp. 1197-1203.

Miller, Leonard D., " The ill-fated Tripartite Meeting of 1976", Surgery, February, 1989, Vol. 105, No. 2, Part 2, pp. 303-308.

Roig, Jorge, et. al., "Legionnaires' Disease", Chest, June 6, 1994, Volume 105, pp. 1817-1825.

Shelhamer, JH, moderator, "NIH Conference: The laboratory evaluation of Opportunistic Pulmonary Infections", Annals of Internal Medicine, March 15, 1996, Vol. 124, No. 6, pp. 585-599.

Weisse, Allen B., "A Plague in Philadelphia: The Story of Legionnaires' Disease", Hospital Practice, June 15, 1992, pp.151-180.

Yu, Victor L., "Legionella Pneumophila", In: Mandell, GL, et.al., Principles and Practice of Infectious Diseases, 3rd ed., New York, Churchill Livingstone, 1990, pp. 1764-74.

Legionellosis: Legionnaires' disease and Pontiac fever

Legionellosis is an infection caused by the bacterium Legionella pneumophila. The disease has two distinct forms: Legionnaires' disease, the more severe form of infection which includes pneumonia, and Pontiac fever, a milder illness. Legionnaires' disease acquired its name in 1976 when an outbreak of pneumonia occurred among persons attending a convention of the American Legion in Philadelphia. Later, the bacterium causing the illness was named Legionella.

How common is legionellosis in the United States?

An estimated 10,000 to 15,000 persons get Legionnaires' disease in the United States each year. An additional unknown number are infected with the Legionella bacterium and have mild symptoms or no illness at all.

Outbreaks of Legionnaires' disease have received the most media attention; however, most often the disease occurs as single, isolated cases not associated with any recognized outbreak. Outbreaks are usually recognized in the summer and early fall, but cases may occur year-round. About 5% to 15% of known cases of Legionnaires' disease have been fatal.

What are the usual symptoms of legionellosis?

Patients with Legionnaires' disease usually have fever, chills, and a cough, which may be dry or may produce sputum. Some patients also have muscle aches, headache, tiredness, loss of appetite, and, occasionally, diarrhea. Laboratory tests may show decreased function of the kidneys. Chest X-rays often show pneumonia. It is difficult to distinguish Legionnaires' disease from other types of pneumonia by symptoms alone; other tests are required for diagnosis.

Persons with Pontiac fever experience fever and muscle aches and do not have pneumonia. They generally recover in 2 to 5 days without treatment.

The time between exposure and onset of illness for Legionnaires' disease is 2 to 10 days; for Pontiac fever, it is shorter, generally a few hours to 2 days.

How is legionellosis diagnosed?

The diagnosis of legionellosis requires special tests not routinely performed on persons with fever or pneumonia. Therefore, a physician must consider the possibility of legionellosis in order to obtain appropriate tests.

Several types of tests are available. The most useful are detecting the bacteria in sputum, finding Legionella antigens in a urine sample, and comparing antibody levels to Legionella in two blood samples obtained 3 to 6 weeks apart.

Who gets legionellosis?

People of any age may get Legionnaires' diasease, but the illness most often affects middle-aged and older persons, particularly those who smoke cigarettes or have chronic lung disease. Also at increased risk are persons whose immune system is suppressed by diseases such as cancer, kidney failure requiring dialysis, diabetes, or AIDS. Those that take drugs that suppress the immune system are also at higher risk.

Pontiac fever most commonly occurs in persons who are otherwise healthy.

What is the treatment for legionellosis?

Erythromycin is the antibiotic currently recommended for treating persons with Legionnaires' disease. In severe cases, a second drug, rifampin, may be used in addition. Other drugs are available for patients unable to tolerate erythromycin.

Pontiac fever requires no specific treatment.

How is legionellosis spread?

Outbreaks of legionellosis have occurred after persons have inhaled aerosols that come from a water source (e.g., air conditioning cooling towers, whirlpool spas, showers) contaminated with Legionella bacteria. Persons may be exposed to these aerosols in homes, workplaces, hospitals, or public places. Infection cannot be acquired from another person with legionellosis, and there is no evidence of persons becoming infected from auto air conditioners or household window air-conditioning units.

Where is the Legionella bacterium found?

Legionella organisms can be found in many types of water systems. However, the bacteria reproduce to high numbers in warm, stagnant water (95-115oF), such as that found in certain plumbing systems and hot water tanks, cooling towers and evaporative condensers of large air-conditioning systems, and whirlpool spas. Cases of legionellosis have been identified throughout the United States and in several foreign countries. The disease likely occurs worldwide.

What is being done to prevent legionellosis?

Improved design and maintenance of cooling towers and plumbing systems to limit the growth and aerosolization of Legionella organisms are the foundations of legionellosis prevention.

During outbreaks, CDC and health department investigators seek to identify the source of disease transmission and recommend appropriate prevention and control measures, such as decontamination of the water source. Current research will likely identify additional prevention strategies.

Further information on legionellosis is available from:

Division of Bacterial and Mycotic Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta, Georgia 30333, USA

National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta, GA

Legionnaires' disease (Legionella pneumonia)

Description:

a typical community acquired pneumonia,

Organs Involved:

lung; GI tract, kidney, liver, CNS

Who Is Most Affected:

males > 55

Incidence:

Most predominant atypical pneumonia (in adults), 5-10% community acquired pneumonia

Etiology:

Causes:

L. pneumophila or L. micdadei, 22 other species

Pathogenesis:

ubiquitous (water source), aerosol spread, not person-to-person

necrotizing bronchopneumonia

protected from antibiotics that don't penetrate macrophages

Increased Risks/Associated Conditions/Complications

Increased Risks:

warm moist environments (air conditioning, nebulizer), alcoholic, smoker, dialysis, COPD, heart disease, lung disease, renal disease, diabetes

Associated Conditions:

Pontiac fever

Complications:

bacterial superinfection, DIC, SIADH

History:

CC:

a symptomatic infection, subacute non-productive cough + dyspnea, abrupt high fever, shaking chills, cough, nausea, vomiting, diarrhea, sudden headache, slight hemoptysis; occasionally scant mucoid sputum, myalgia, arthralgia, malaise, abdominal pain; rarely pleuritic pain

in elderly - fever less common, altered mental status

HPI:

may be insidious or virulent presentation

Physical:

General:

Faget sign (high fever with normal heart rate, relative bradycardia)

Lungs:

normal lungs

Neuro:

occasionally neurologic + MSE findings (confusion)

Diagnostic:

diagnosis can not be made on clinical grounds alone

usually diagnosed by serology (titer > 1:256 or 4x rise in indirect FAb to titer > 1:128)

Rule out:

typical pneumonia, Mycoplasma pneumonia, Chlamydia pneumonia, psittacosis, Q fever

Blood tests:

WBC < 15,000, serology, hyponatremia, abnormal liver function tests, azotemia

Urine studies:

hematuria, microhematuria, proteinuria

Imaging studies:

CXR patchy + interstitial or lobar takes 2-6 mos for complete CXR clearing, >65% worsening at 2-3 days despite defervescence (Clin Chest Med 1987;8;529)

Other:

sputum staining or staining of other secretions (e.g. brocho-alveolar lavage)gram stains shows many PMNs, no bugs
DFA (direct FAb) of sputum - rapid diagnosis
other methods - Dieterle silver impregnation stain, nucleic acid hybridization

culture
90% positive by transtracheal aspiration, 50-70% by sputum culture
use charcoal-enriched yeast extract agar with increased iron + cysteine
see gram-negative pleomorphic rods (which stain poorly)

Prognosis:

18% mortality (due to comorbidity), most self-limited 7-10 days

Treatment:

General:

treat at least 2 wks

Medications:

frequently produces ß-lactamase

macrolide (erythromycin, azithromycin, clarithromycin) e.g. erythromycin 1 g IV q6h

doxycycline or tetracycline (if erythromycin not tolerated)

alternatives - Bactrim, ofloxacin (also empiric), ciprofloxacin

add rifampin 600 mg PO bid for seriously ill patients

Prevention:

heat + hyperchlorinate water

Screening:

urinary Ag

The term "Legionnaires' disease" was coined in 1976 after a dramatic outbreak of serious respiratory disease at a convention of the American Legion led to the discovery of a new disease entity and, eventually, to the identification of the responsible bacteria, Legionella pneumophila.

L. pneumophila, one of more than twenty currently recognised species of the genus Legionella, is the species most commonly implicated in cases reported both in Australia and overseas. Illnesses caused by any species of Legionella are called Legionellosis. "Legionnaires' disease" is the term used for the disease caused by L. pneumophila. However, "Legionnaires' disease" has become the familiar term used to refer to any severe form of pneumonia which is caused by a species of Legionella.

This form of pneumonia may be accompanied by involvement of other organs such as the brain, causing confusion; the bowel, causing diarrhoea; and the kidneys, causing kidney failure.
Symptoms include rapid onset of high fever, non-productive cough, chills, headache and general 'aches and pains'. Positive identification can be achieved by isolating and identifying the L. pneumophila from the patient's respiratory secretions or blood. The incubation period, that is the time between infection and signs and symptoms appearing, is usually 2-10 days. Less than 5 per cent of the exposed persons are likely to become ill, but up to 30 per cent of these may die.

Pontiac fever, also caused by a species of Legionella, is an influenza-like illness with symptoms including fever, chills and headache.
The incubation period ranges from 4 hours to 3 days. Up to 95 per cent of the exposed persons become ill.
Pneumonia does not occur and full recovery can be expected.

Many infections by L. pneumophila do not result in recognisable signs and symptoms. Antibodies have been found in up to 25% of adults tested. This suggests that up to I in 4 adults have been infected at some time in their life but have not necessarily developed any symptoms.

Humidifier fever is not caused by Legionella, yet it is often considered, incorrectly, as a form of Legionnaires' disease. This influenza-like fever may result from the inhalation of micro-organisms that cause allergic reactions. The potential source is often the humidifier of an air conditioning system. Humidifier fever belongs to a group of illnesses known collectively as hypersensitivity pneumonitis. Sensitisation to these microbial contaminan