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Evaluation of possible legionellosis (Legionnaires disease, Pontiac fever, extrapulmonary legionella infection caused by Legionella pneumophila)
Legionella pneumophila may cause pulmonary disease in both normal and immunocompetent hosts. The disease may occur sporadically in the form of community acquired pneumonia and in epidemics. Pneumonia (often referred to as Legionnaires disease) occurs more frequently in severely immunosuppressed individuals; a milder form of the illness, referred to as Pontiac fever, is more prevalent in normal hosts. Extrapulmonary infection with Legionella pneumophila is rare. Legionnaire's disease, Pontiac fever, and extrapulmonary infection have been collectively referred to as legionellosis.
Approximately 85% of the documented cases of legionellosis have been caused by Legionella pneumophila. Serogroups 1 and 6 of Legionella pneumophila, by themselves, account for up to 75% of cases of legionellosis.
The definitive diagnosis of Legionella pneumophila is made by isolation of the organism on specialized culture medium (buffered charcoal yeast extract agar). Pulmonary secretions can be directly examined using a direct fluorescent antibody procedure, but the sensitivity of this method is low (25%-70%). Often it is difficult for the patient to produce pulmonary secretion (sputum) for examination, the pneumonia is frequently interstitial and sputum is scant. In the absence of invasive procedures (eg, bronchial alveolar lavage), urine evaluation for Legionella pneumophila antigen or indirect serological (antibody) methods may be useful.
A negative result indicates that IgG/A/M antibody to Legionella pneumophila serogroups 1-6 is not detected. Negative results do not exclude Legionella infection. It may require 4 to 8 weeks to develop a detectable antibody response; serum specimens taken early in the course of infection may not yet have significant antibody titers. Furthermore, antibody levels can fall to undetectable levels within a month of infection, early antibiotic therapy may suppress antibody response, and some individuals may not develop antibodies above detectable limits.
Some culture-positive cases of Legionella do not develop Legionella antibody.
Positive results are suggestive of Legionella infection; however, a single positive result only indicates immunologic exposure at some time. It does not distinguish between previous or current infection. The level of antibody response may not be used to determine active infection. Other laboratory procedures or additional clinical information are necessary to establish a diagnosis.
Specimens with equivocal results are retested prior to reporting. Repeat testing on a second specimen should be considered in patients with equivocal results, if clinically indicated.
A diagnosis should not be made on the basis of positive Legionella antibody results alone. Test results for Legionella antibodies should be interpreted in conjunction with the clinical evaluation and the results of other diagnostic procedures.
A positive result suggests infection with 1 or more of the groups 1-6 species; however, one will not be able to distinguish between species with the results of this enzyme-linked immunosorbent assay (ELISA) test alone.
Use of serogroups 1-6 for assessing antibody responses to different Legionella species and serogroups has not been established.
Cross-reactivity may occur in sera with infections due to other Legionella species.
Positive results may be due to cross-reactivity with antibody generated as a result of non-Legionella infection. Serologic cross-reactions have been reported with Pseudomonas aeruginosa, several Rickettsia species, Coxiella burnetii, enteric gram-negative rods, Bacteroides species, Haemophilus species, Citrobacter freundii, and Campylobacter jejuni. Additionally, some reports indicate that a number of apparently healthy individuals may carry antibodies to legionellae; however, a positive result, along with clinical signs and symptoms may indicate possible Legionella infection. Additional serologic testing, such as paired sera analysis by immunofluorescence assay (IFA), or other clinical testing such as direct fluorescent antibody (DFA) and culturing, may be necessary to establish diagnosis.
The assay performance characteristics have not been established for matrices other than sera.
Although the conjugate is designed to detect human IgG, IgM, and/or IgA, one will not be able to determine which antibody is present with this assay.
The affinity and/or avidity of the anti-IgG/IgM/IgA conjugate has not been determined.
The use of hemolytic, lipemic, bacterially contaminated, or heat-inactivated specimens should be avoided. Erroneous results may occur.
1. Color Atlas and Textbook of Diagnostic Microbiology. Fifth edition Lippincott. Edited by EW Koneman, SD Allen, WM Janda, et al: Philadelphia, Lippincott-Raven Publishers 1997
2. Principals and Practice of Infectious Diseases. Third edition. Edited by GL Mandell, RG Douglas, JE Bennett. Churchill Livingston, 1990