Original Contributions
The relationship between the clinical features of pharyngitis and the sensitivity of a rapid antigen test: Evidence of spectrum bias*,**,*,**

https://doi.org/10.1067/mem.2001.119850Get rights and content

Abstract

Study Objective: We evaluate the test characteristics and test for spectrum bias of a rapid antigen test for group A β-hemolytic streptococcal (GABHS) pharyngitis among adults. Methods: Medical record and laboratory results of consecutive adult patients receiving a rapid antigen test for GABHS in the emergency department or urgent care clinic of an urban teaching hospital between August 1999 and December 1999 were analyzed. Patients were stratified according to the number of clinical features present using the following modified Centor criteria: history of fever, absence of cough, presence of pharyngeal exudate, and cervical lymphadenopathy. The sensitivity of the rapid antigen test was defined as the number of patients with positive rapid antigen test results divided by the number of patients with either positive rapid antigen test results or negative rapid antigen test results and positive throat culture results. Results: In the study sample of 498 patient visits, the prevalence of GABHS pharyngitis was 28% (95% confidence interval [CI] 24% to 32%). The prevalence of GABHS pharyngitis increased as modified Centor scores increased: 0 or 1=14%, 2=20%, 3=43%, and 4=52%. An increased number of modified Centor criteria (0 or 1, 2, 3, 4) was associated with increased rapid antigen test sensitivity (61%, 76%, 90%, and 97%, respectively) (Mantel-Haenszel trend test; P =.001). Conclusion: The sensitivity of the rapid antigen test for GABHS is not a fixed value but varies with the spectrum of disease. Among adults with 3 or 4 clinical criteria for GABHS pharyngitis, further study may reveal that culture confirmation of negative rapid antigen test results are not necessary. [DiMatteo LA, Lowenstein SR, Brimhall B, Reiquam W, Gonzales R. The relationship between the clinical features of pharyngitis and the sensitivity of a rapid antigen test: evidence of spectrum bias. Ann Emerg Med. December 2001;38:648-652.]

Introduction

Group A β-hemolytic streptococcal (GABHS) pharyngitis is a common upper respiratory tract infection with important clinical implications. The prevalence of GABHS recovery from adults with acute pharyngitis has been reported to range from 5% to 15%.1, 2 Antimicrobial treatment of GABHS pharyngitis has been demonstrated to reduce the incidence of acute rheumatic fever as long as antibiotics are initiated within 7 to 10 days of illness onset.3, 4 More rapid diagnosis and treatment of GABHS pharyngitis, usually within 48 hours of illness onset, provide additional symptomatic benefit.5, 6 Rapid diagnosis and treatment are also more convenient for patients and clinicians and may be more cost-effective.

Recovery of GABHS from a throat swab culture has been regarded as the criterion standard for the diagnosis of GABHS pharyngitis, even though this technique does not distinguish between colonization and acute infection with GABHS. Because results from throat swab culture are not available for 24 to 48 hours, more rapid methods for diagnosis of GABHS pharyngitis are desirable. Rapid antigen diagnostic tests can be processed during an office or emergency department visit and have become a popular alternative to throat swab cultures.

The Infectious Disease Society of America, the American Heart Association, and the American Academy of Pediatrics recommend antibiotic treatment of pharyngitis for only those patients with positive GABHS identification test results.7, 8, 9 Among patients with negative rapid antigen test results, confirmation with a throat swab culture is recommended. This recommendation is based on reported sensitivity rates of rapid antigen testing that range from 80% to 90%. However, these are aggregated estimates of sensitivity based on all patients with sore throat, regardless of disease severity. In fact, the sensitivity of rapid antigen tests may vary across the clinical spectrum of disease, a property known as “spectrum bias.”10 For example, spectrum bias has been demonstrated with rapid urine dipstick tests for urinary tract infection.11 In a study from The Netherlands, the sensitivity of the rapid antigen test for detecting positive throat swab culture results was 75% when the likelihood for GABHS was high, compared with 48% when the likelihood for GABHS was intermediate or low.12

Whether this finding can be duplicated in the United States, where rapid antigen tests with higher reported sensitivities are used, is not known. The present study was conducted to determine the sensitivity of the rapid antigen test across the full spectrum of clinical manifestations of streptococcal pharyngitis.

Section snippets

Materials and methods

This is a chart review–based study of consecutive adults (age ≥18 years) who had a rapid antigen test performed between August 1999 and December 1999 at the urgent care clinic or ED of an urban teaching hospital. This study was approved by the Colorado Multiple Institution Review Board.

A modification of the Centor criteria was used in this study to define the clinical spectrum of pharyngitis.13 The original Centor criteria, which were developed to estimate the probability of acute GABHS

Results

During the study period, 598 patients had a rapid antigen test performed. Seventy-three patients were excluded for the following reasons: 22 (4%) because the patient identifier in the laboratory database and medical record were not consistent, 2 (0.3%) because the rapid antigen test results in the laboratory database were indeterminate, and 49 (8%) because the rapid antigen test date and the medical record visit date were inconsistent (most differed by only 1 or 2 days). Of the 525 patients

Discussion

This study provides evidence that spectrum bias affects the sensitivity of the rapid antigen test for GABHS in adults with acute pharyngitis. The sensitivity of the rapid antigen test was only 61% when applied to patients with few clinical features and a low probability of GABHS pharyngitis (modified Centor scores of 0 or 1). As the probability for GABHS pharyngitis increased, based on modified Centor scores, so did the sensitivity of the rapid antigen test. Dagnelie et al12 reported a rapid

Acknowledgements

Author contributions: LAD, SRL, and RG conceived of the study design. LAD, SRL, BB, WR, and RG supervised the conduct of the data collection and analysis. SRL and RG provided statistical advise and RG conducted statistical computations. LAD drafted the manuscript, and all authors contributed substantially to its revision. RG takes responsibility for the paper as a whole.

We thank Jan Monahan, ASCP, supervisor of the Microbiology Laboratory, Clinical Laboratory, University of Colorado Health

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*

Dr. Gonzales is a Robert Wood Johnson Minority Medical Faculty Development Fellow.

**

Author contributions are provided at the end of this article.

*

This project was sponsored in part by grant No. DK07496 (T35) from the National Institutes of Health Short-Term Training Students in Health Professional Schools program (Ms. DiMatteo).

**

Address for reprints: Ralph Gonzales, MD, MSPH, Division of General Internal Medicine, UCSF School of Medicine, 3333 California Street, Suite 430, Box 1211, San Francisco, CA 94118; 415-514-0569, fax 415-476-9531; E-mail [email protected].

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