Effective management of group A streptococcal (GAS) pharyngitis is hindered by impracticality of the gold standard diagnostic test: throat culture. Rapid antigen diagnostic tests (RADTs) are a promising alternative, although concerns about their sensitivity and specificity, and variation between test methodologies, have limited their clinical use. The objective of this study was to perform a systematic review with meta-analysis of the diagnostic accuracy of RADTs for GAS pharyngitis.
Medline and Embase from 1996 to 2013 were used as data sources. Of 159 identified studies, 48 studies of diagnostic accuracy of GAS RADTs using throat culture on blood agar as a reference standard were selected. Bivariate random-effects regression was used to estimate sensitivity and specificity with 95% confidence intervals (CIs). Additional meta-analyses were performed for pediatric data.
A total of 60 pairs of sensitivity and specificity from 48 studies were included. Overall summary estimates for sensitivity and specificity of RADTs were 0.86 (95% CI 0.83 to 0.88) and 0.96 (95% CI 0.94 to 0.97), respectively, and estimates for pediatric data were similar. Molecular-based RADTs had the best diagnostic accuracy. Considerable variability exists in methodology between studies. There were insufficient studies to allow meta-regression/subgroup analysis within each test type.
RADTs can be used for accurate diagnosis of GAS pharyngitis to streamline management of sore throat in primary care. RADTs may not require culture backup for negative tests in most low-incidence rheumatic fever settings. Newer molecular tests have the highest sensitivity, but are not true point-of-care tests.
Dear editor, The article of Lean and colleagues (1) refers to our article (2) but we did not mention the Australian guideline. Further, we cannot agree with the conclusion of the study of Lean and colleagues that rapid diagnostic tests for Group A streptococcal pharyngitis can be used for accurate diagnosis of GAS pharyngitis and to streamline management of sore throat in primary care. A highly sensitive (95% or more) and inexpensive rapid antigen detection test with a very rapid turnaround time could possibly make a contribution to control efforts in pharyngitis. However, no single test currently fulfills all 3 of these criteria.
To date, the current tests with sensitivity less than 86% - where we expect 95% or more for a mostly self-limiting condition in general practice- with heterogeneity across studies and insufficient numbers of studies within each test type, a cost of 5 to 10 American dollars, a turnaround time of 1 to 3 hours with the new molecular techniques, and a limited expiration date make it difficult to promote the antigen detection test. These are reasons why different European guidelines do not recommend the rapid diagnostic test to diagnose a strep throat. (2)
We are supported by the conclusion of another recent meta-analysis which states that RAST immunochromatographic methods do not appear to be very sensitive and highly specific to diagnose group A streptococcal pharyngitis in children. (3)
1. Lean WL, Arnup S, Danchin M, Steer AC. Rapid Diagnostic Tests for Group A Streptococcal Pharyngitis: A Meta-analysis. Pediatrics. 2014;134:771-781. Epub 2014.2.
2. Matthys J, De Meyere M, van Driel ML, De Sutter A. Differences among international pharyngitis guidelines: not just academic. Ann Fam Med. 2007;5:436-443.
3. Stewart EH, Davis B, Clemans-Taylor BL, Littenberg B, Estrada CA, Centor RM. Rapid antigen group a streptococcus test to diagnose pharyngitis: a systematic review and meta-analysis. PLoS One. 2014;9:e111727. doi: 10.1371/journal.pone.0111727.
Conflict of Interest:
None declared
I agree with the conclusions of Lean et. al. (1) in their excellent meta-analysis of group A streptococcal (GAS) rapid antigen detection tests (RADT) and would like to make some additional comments based upon a study I did in 1988, before their 1996 meta-analysis starting date.
We studied the Hybritech Icon Strep A RADT in an ambulatory clinic using a unique study design. (2) Two double-swabs (4 swabs total) were obtained on 264 pediatric patients with suspected streptococcal pharyngitis. All swabs were obtained by one of the two study investigators (SL, CW) using the same technique. One swab of each pair was tested with the RADT, and one underwent conventional culture (T/C) on 5% sheep blood agar in 5% CO2, confirmed by coagglutination. The first swab of each pair underwent immediate RADT testing and was used for patient care. The RADT on the second paired swab was performed at the end of the clinic session by one of the study investigators blinded to the results of the first RADT. The sensitivity and specificity of each of the RADTs was compared using each of the T/Cs as the "gold standard." We also compared the sensitivity and specificity of each of the T/C compared to the other T/C as the "gold standard."
The sensitivity of our RADT was 87%, similar to that reported by Lean. (1) Interestingly, the sensitivity of the T/C compared to the other T/C was also 87%. In our population, with a 21% prevalence of streptococcal pharyngitis, the negative predictive value of either a negative RADT or a negative T/C was 97%. Based on our results, the RADT was just as sensitive as the T/C and a negative RADT predicted a negative T/C just as well as the T/C.
Performing a T/C requires much more expertise than performing a RADT for the detection of GAS. Ferris and Fischer demonstrated that sixth and seventh grade students achieved a 95.9% sensitivity and 96.8% specificity on RADTs on unknown specimens using limited self-training. (3) The T/C is also an imperfect "gold standard" for comparison. The concordance rate between two T/C's in our study was 95%, which is consistent with results reported by others. (4,5) As Lean et al. noted in their discussion, "Methods of sample collection were not clearly reported in all studies and there is no way to control the quality of the swab samples." (1) We totally agree. It makes no difference how accurate the test is if the swabs are not properly obtained.
Given the current rarity of acute rheumatic fever in the United States, the increased costs associated with back-up throat cultures, the problems and delays performing the T/Cs on patients with negative RADTs, and the comparable sensitivity and negative predictive value of the RADT compared with the T/C, I believe the time has come to stop performing backup throat cultures. Instead, let's focus our attention on getting the best possible specimen for testing. You can't detect what isn't there!
References:
1. Lean WL, Arnup S, Danchin M, Steer AC. Rapid diagnostic tests for group A streptococcal pharyngitis: a meta-analysis. www.pediatrics.org/cgi/doi/10.1542/peds.2014-1094.
2. Lewey S, White CB, Lieberman MM, Morales E. Evaluation of the throat culture as a follow-up for an initially negative enzyme immunosorbent assay rapid streptococcal antigen detection test. Pediatr Infect Dis J. 1988;7:765-769.
3. Ferris, D. G., and P. M. Fischer. Elementary school students performance with two ELISA test systems. JAMA 1992;268:766-770.
4. Breese BB, Disney FA. The accuracy of diagnosis of beta streptococcal infections on clinical grounds. J Pediatr. 1954;44:670-673.
5. Kaplan EL, Top FH Jr, Dudding BA, Wannamaker LW. Diagnosis of streptococcal pharyngitis: differentiation of active infection from the carrier state in the symptomatic child. J Infect Dis. 1971;123:490-501.
Conflict of Interest:
None declared