In the summer of 1976, a mysterious epidemic of fatal respiratory disease in Philadelphia launched an intensive investigation that resulted in the definition of a new family of pathogenic bacteria, the Legionellaceae. In retrospect, members of the family had been isolated from clinical specimens as early as 1943. Unsolved epidemics of acute respiratory disease dating to the 1950s were subsequently attributed to the newly described pathogens. In the intervening years, the Legionellaceae have been firmly established as important causes of sporadic and epidemic respiratory disease. The sources of the infecting bacteria are environmental, and geographic variation in the frequency of infection has been documented. Airborne dissemination of bacteria from cooling towers and evaporative condensers has been responsible for some epidemics, but potable water systems are perhaps more important sources. The mode of transmission from drinking water is unclear. The Legionellaceae are gram-negative, facultative, intracellular pathogens. The resident alveolar macrophage, usually an effective antibacterial defense, is the primary site of growth. Cell-mediated immunity appears to be the most important immunological defense; the role of humoral immunity is less clear. Erythromycin remains the antibiotic of choice for therapy of infected patients, but identification and eradication of environmental sources are also essential for the control of infection.

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The purposes of this study were to determine whether antigen is excreted by patients with Legionnaires disease early enough after the onset of symptoms to be useful for making therapeutic decisions and whether antigen excretion ends when successful treatment is concluded. Specific antigen was detected in the urine of 14 (88%) of 16 patients with Legionnaires disease during days 1 to 3 of symptoms, 33 (80%) of 41 patients during days 4 to 7, 25 (89%) of 28 patients during days 8 to 14, and 11 of 11 patients after day 14, by solid-phase immunoassays for serogroup 1 Legionella pneumophila antigen. Antigen excretion persisted for 42 days or longer after the onset of treatment in at least 15 patients. The longest documented duration of excretion was 326 days. We conclude that antigen can be detected approximately as often early after symptoms begin as later, allowing meaningful therapeutic decisions to be made, but that prolonged antigen excretion may negate the diagnostic value of urinary antigen detection for relapsing or recurrent L. pneumophila pneumonia.

Legionella pneumophila multiplied rapidly in guinea pig and rat alveolar macrophages but failed to grow when phagocytic activity was inhibited by pretreatment with 0.5 or 1.0 ,ug of cytochalasin D per ml. Attachment was not inhibited by cytochalasin D. No extracellular multiplication occurred when L. pneumophila were in close proximity to viable functional macrophages or even when the bacteria were attached to plasma membranes of the macrophages. Nonopsonized L. pneumophila were avidly phagocytized by alveolar macrophages. When bacteria were centrifuged onto a cell pellet, more than 85% of the phagocytes contained one or more bacteria within 15 min. In contrast, under the same conditions only approximately 15% of the macrophages contained nonopsonized Escherichia coi or Staphylococcus aureus. Phagocytosis of L. pneumophila by untreated guinea pig macrophages occurred by extension of pseudopodia around the bacteria in a classical manner. The failure of the bacteria to actively penetrate the phagocyte suggests that their intracellular survival must not depend on avoidance of a phagosome but rather on an inhibition of or resistance to subsequent microbicidal functions of the macrophage.Legionella pneumophila is a ubiquitous gram-negative bacterium which is an important cause of endemic and epidemic pneumonia (24,38). As a facultative intracellular parasite, the bacterium has a close relationship to macrophages in vivo.

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