Chest
Volume 136, Issue 6, December 2009, Pages 1576-1585
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Original Research
Respiratory Infections
Systematic Review and Metaanalysis: Urinary Antigen Tests for Legionellosis

https://doi.org/10.1378/chest.08-2602Get rights and content

Background

Urinary antigen assays offer simplicity and rapidity in diagnosing Legionnaires' disease, though studies report a range of sensitivities. We conducted a systematic review to assess the test characteristics of Legionella urinary antigen.

Methods

We searched Medline, Excerpta Medica Database, and bibliographies of retrieved articles. English-language studies were used and included if the absolute number of true-positive, false-negative, true-negative, and false-positive observations were available, and the “gold standards” were described clearly. Two investigators independently reviewed articles and extracted data. Quality was assessed with the Quality Assessment for Diagnostic Accuracy Studies (QUADAS). Sensitivities and specificities were pooled using a random-effects model weighted with the inverse of the SE calculated through the Wald method.

Results

Fifty articles were retrieved for detailed evaluation, and 30 met the inclusion criteria. All but two studies focused on serotype 1 Legionella. Forty assays were reported using six different methodologies, whereas 26 assays used commercial tests, and 14 assays used in-house tests. Study quality was generally low, with average QUADAS scores of 4.4 of a total of 14 points (range, 1 to 9 points). The pooled sensitivity was 0.74 (95% CI, 0.68 to 0.81), and the specificity was 0.991 (95% CI, 0.984 to 0.997). Higher quality studies had lower sensitivity, and there was evidence of publication bias.

Conclusions

Legionella urinary antigen for serotype 1 appears to have excellent specificity, though modest sensitivity. However, the poor quality of the included studies and the presence of publication bias suggest an overestimation of test performance. High-quality studies are needed.

Section snippets

Search Strategy

We searched Medline from 1966 to August 2008 using Medical Subject Headings and a free-text search strategy, using the terms “urinary antigens”; “antigen, urine”; “antigens, bacterial”; “Legionellosis”; “Legionella”; and “Legionnaire.” In addition, we searched Excerpta Medica Database from 1968 to August 2008, using the search strategy (“Legionnaires disease” OR “Legionella” OR “Legionellosis”) AND (“urinary antigens” OR “bacterial antigens” OR Legionella urinary antigen“). Both searches were

Studies Identified

In the first stage, we identified 68 possibly relevant articles from the Medline search. Fifty full articles among these were selected for detailed analysis on the basis of title or abstract; 30 articles met the inclusion criteria. Retrieval and inclusion flow is shown in Figure 1, and the study characteristics of the 30 included studies15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44 are outlined in Table 1. Patient

Discussion

Our pooled analysis found that Legionella urinary antigen has very good specificity but low sensitivity for L pneumophila serogroup 1; thus, it is better for ruling in than ruling out disease. One of our most interesting findings is the 26% false-negative rate for Legionella urinary antigen. Practically speaking, this finding suggests that stopping therapy with anti-Legionella antibiotics in patients with a clinical suspicion for L pneumophila after a negative urinary antigen test result,

Acknowledgments

Author contributions: Drs. Shimada and Noguchi contributed to the conception and design of the study. Drs. Shimada, Jackson, and Miyashita contributed to acquisition, analysis, and interpretation of the data. Drs. Shimada, Noguchi, and Jackson drafted the article. Drs. Noguchi, Jackson, Hayashino, Kamiya, and Yamazaki critically revised the article for important intellectual content. Drs. Shimada, Jackson, and Fukuhara contributed to the final approval of the article. Dr. Jackson provided

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Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).

Funding/Support: This study was supported by a grant (No. H18-001) from the Ministry of Health, Labor and Welfare in Japan, “Development of Clinical Research Fellowship” (Principal Investigator, Shunichi Fukuhara)

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