Potential for Molecular Testing for Group A Streptococcus to Improve Diagnosis and Management in a High-Risk Population: A Prospective Study

Abstract

Background: In high-burden settings, guidelines recommend antibiotic treatment for all suspected group A Streptococcus (GAS) infections to prevent rheumatic fever and poststreptococcal glomerulonephritis. Highly sensitive rapid GAS tests could reduce unnecessary antibiotic use in these settings.

Methods: This was a prospective study of the Xpert Xpress Strep A (Cepheid) molecular test compared with culture of throat swab samples collected at a referral hospital in northern Australia. Demographic and clinical data and results of streptococcal serology and culture were collected.

Results: Of 164 throat swab samples, 145 (88%) were eligible for inclusion; 49 (34%) were molecular test positive and 24 (17%) were culture positive for GAS. The sensitivity, specificity, and positive and negative predictive values for the molecular test versus culture were 100.0%, 79.3%, 48.8%, and 100.0%, respectively. Among 25 samples testing positive with the molecular test and negative with culture, group C or G streptococci were cultured in 2, and a plausible clinical explanation, such as pharyngotonsillitis, or rheumatic fever with positive results of streptococcal serology, was apparent in 19 instances. In 25 patients with rheumatic fever or poststreptococcal glomerulonephritis diagnoses, molecular testing nearly trebled the detection of GAS in throat swab samples, from 3 (12%) detected with culture to 8 (32%) detected with molecular testing. Reasons for "false-positive" molecular test results could include the presence of GAS below the threshold of culture detection or persistence of nonviable organisms after infection.

Conclusion: Implementation of molecular testing could improve antibiotic use in this high-burden setting. The incremental yield in poststreptococcal syndromes, by which time cultures are negative, has high potential in the diagnostic workup of autoimmune poststreptococcal syndromes and warrants further investigation.

Keywords: Group A Streptococcus; molecular test; pharyngotonsillitis; point-of-care test; rheumatic fever.

Figure 1.

Study flow chart.

Figure 2.

Indications for throat swab samples, according to ethnicity (A) and age (B). Abbreviations: APSGN, acute poststreptococcal glomerulonephritis; ARF, acute rheumatic fever; URTI, upper respiratory tract infection.

Figure 3.

Cycle threshold for molecular test by sample type (A) and by grade of group A Streptococcus (GAS) (B). Culture results were obtained from the hospital laboratory; “culture negative” indicates to no growth of β-hemolytic streptococci. Abbreviations: GCS, group C Streptococcus; GGS, group G Streptococcus.

Figure 4.

Streptococcal serology results according to molecular testing (A, B) and culture (C, D) Cultures were classified as positive if any β-hemolytic Streptococcus (group A, C, or G) was identified. Abbreviations: ASO, antistreptolysin O; ADB, anti-DNase B.