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Legionella pneumophila is a facultative intracellular gram-negative rod that causes pneumonia in humans. Free-living amoebas are thought to serve as a reservoir for Legionella infections. Signature-tagged mutagenesis was employed to identify Legionella pneumophila genes necessary for survival in the amoeba Acanthamoeba castellanii. Six mutant strains were defective in assays of invasion and intracellular growth. Four mutants also exhibited invasion and replication defects in Hartmannella vermiformis, an amoeba linked to hospital outbreaks of Legionella pneumonia. The six mutants also were tested in macrophages derived from peripheral blood mononuclear cells. Two mutants had intracellular replication defects, and two different strains entered cells less efficiently. Two transposon insertions were in known L. pneumophila genes, lspK and aroB. The other four were in novel genes. One gene has similarity to a cytochrome c-type biogenesis protein of Pseudomonas fluorescens. Another has similarity to a transcriptional activator regulating flagellar biosynthesis in Vibrio cholera. The third is similar to traA of Rhizobium sp. strain NGR234, which is involved in conjugal transfer of DNA. The fourth has no homology. By using survival in amoeba as a selection, we have isolated mutant strains with a range of phenotypes; and we have potentially identified new L. pneumophila virulence genes.

An epidemic of isoniazid (INH)- and streptomycin (SM)-resistant tuberculosis began among Boston's homeless population in 1984. Individuals with skin test conversions who agreed to preventive therapy received either INH, rifampin, or a combination of INH and rifampin. A total of 204 individuals with documented tuberculin skin test conversions who did not have active tuberculosis at the time of the clinical evaluation for their positive skin test were eligible for preventive therapy. Data on type and length of preventive therapy were obtained from the Tuberculosis Clinic and the Boston Tuberculosis Registry records at Boston City Hospital. The individuals were followed for development of active tuberculosis. Six of 71 (8.6%) individuals who received no therapy, 3 of 38 (7.9%) in the INH group, and none in the rifampin or rifampin plus INH groups (49 and 37 persons, respectively) developed active tuberculosis. Patients in the rifampin group were significantly less likely to develop tuberculosis than patients in the no therapy group (p = 0.04; odds ratio [OR] = 0.00, 95% confidence interval [CI] = 0.00-0.91). Treatment with any rifampin-containing preventive therapy (rifampin or rifampin plus INH) was effective (p < 0.01 ) in preventing development of active disease. The three INH failures were with organisms that were resistant to INH.

We reviewed 106 patients referred to our institution for treatment of peripheral tuberculous adenitis to establish the epidemiologic, clinical, and pathologic manifestations of this disease. Tuberculous lymphadenitis occurred predominantly in young, foreign-born women a mean of 5 years after arrival in the United States. Tuberculin skin tests were positive in 94% of cases. Lymphadenopathy occurred most frequently in the neck (57%) or supraclavicular area (26%) and involved 1-3 nodes. Forty (38%) patients had an abnormal chest radiograph consistent with granulomatous infection. Culture-positive pulmonary tuberculosis was diagnosed in 41% of those patients with abnormal chest radiographs. Fine needle aspiration was an essential step in the evaluation and diagnosis of tuberculous lymphadenitis. Granulomas were seen in 61% of fine needle aspirates and 88% of surgical biopsies. Positive cultures for Mycobacterium tuberculosis were obtained from 62% of fine needle aspirate samples and 71% of excisional biopsies. The presence of necrosis and/or neutrophilic inflammation in tissue samples correlated with culture positivity. Given the high yield of positive cultures from fine needle aspirates, surgery was rarely indicated as an initial step in immunocompetent adults. In this cohort, 101 patients received a final diagnosis of peripheral tuberculous lymphadenitis. Eighty-two percent received their entire therapy under direct observation, and response to antituberculous therapy was uniformly successful. Paradoxical expansion of adenopathy was seen in 20% of all patients and was more commonly noted in human immunodeficiency virus-seropositive patients. We present a diagnostic algorithm based on our experience.