Streptococcus pyogenes is the most common cause of bacterial pharyngitis. Pharyngitis testing and diagnosis can be improved by utilizing existing molecular testing capacity.
By Tyler Radke, MLS(ASCP)
Streptococcus pyogenes, more commonly known as Group A Streptococcus (GAS), is frequently the cause of bacterial pharyngitis. If misdiagnosed or left untreated, GAS pharyngitis can progress to more severe diseases such as glomerulonephritis or scarlet fever. Even more concerning is that cases of invasive infections from GAS, those being found in the bloodstream of children and adults, appear on the rise1. It is therefore prudent to consider the current pharyngitis testing landscape as diagnosis of bacterial pharyngitis can be improved by utilizing current molecular testing capacity.
Pathogenicity of Streptococcus pyogenes
Group A Streptococcus is known clinically for manifesting as bacterial pharyngitis (Strep Throat). Beyond pharyngitis, GAS can cause other diseases and complications including:
- Rheumatic fever
- Cellulitis, impetigo, or pyoderma
- Necrotizing fasciitis
- Toxic shock-like syndrome
GAS is capable of inflicting severe morbidity and/or death if undiagnosed and untreated. The pathogenesis of this organism comes from its many virulent factors. GAS contains lipoteichoic acid and an M protein in the cell wall, allowing for epithelium adhesion and white cell evasion respectively. The M protein is believed to be responsible for acute rheumatic fever after the development of antibodies against this protein. Antibodies to cell wall M protein can cross-react with myocardial tissue. Other virulence is found in the battery of enzymes GAS can produce, further contributing to disease manifestation. Finally, some strains of GAS possess superantigens causing an overreacting immune response. These superantigens are associated with the development of necrotizing fasciitis and toxic shock-like syndrome.
Treatment of Streptococcus pyogenes is predictable as there have been no documented cases of resistance to penicillin. Susceptibility testing of Streptococcus pyogenes is unnecessary except in cases of a penicillin allergy. Still, some institutions may choose to test susceptibility of those strains present in a sterile body fluid like blood or CSF.
By contrast, treatment of pharyngitis caused by viral etiologies may encompass an antiviral, supportive fluids, and/or an anti-inflammatory.
Seasonal Complications of Pharyngitis
Pharyngitis has a predilection for the winter season, with most cases occurring in children and adolescents. This is further complicated as pharyngitis is a symptom overlapping both bacterial and viral upper respiratory tract infections. Smoldering cases of COVID-19 and the return of an influenza season amongst high activity of RSV, rhinovirus, and other coronaviruses make diagnosis especially complex.
Additionally, the presence of influenza, COVID-19, or RSV does not preclude co-infection with GAS. The opportunity for co-infections with overlapping symptoms necessitates the use of sound diagnostics as treatment strategies greatly differ.
Pharyngitis Testing Methods
Rapid Antigen Diagnostic Test
Like influenza and COVID-19, testing of pharyngitis is available in antigen and nucleic acid amplification (NAA) format. Antigen testing for GAS has been around for decades and can be seen as paving the way for the pandemic testing response in the form of widespread use of COVID-19 antigen tests. Distinct advantages of the rapid antigen diagnostic test (RADT) include speed, low complexity, and low cost. RADTs take only minutes to result and are easy enough for any trained person to perform. However, RADTs ability to detect Streptococcus pyogenes from a throat swab is widely variable, necessitating culture confirmation on negative findings. Sensitivity for RADTs is widely variable, ranging from 55% – 94% sensitive2. Studies have pointed to different performance being notable when comparing laboratory personnel with that of nursing personnel3.
Amongst three commonly used vendors, a meta-analysis4 determined overall sensitivity of RADTs for Group A Streptococcus to be 86%. The review notes several factors influencing variability in performance such as disease duration, specimen adequacy, and test operator.
Standard of care has traditionally been throat culture for official diagnosis of GAS pharyngitis. Sensitivity of throat culture for detection of Streptococcus pyogenes is in the range of 90%-95%. Throat culture requires specialized laboratory personnel and equipment, limiting its adoption to larger and/or specialty laboratories. Throat culture is notoriously slow with a time to result of one to two days from day of setup. As culture cannot be completed near the patient, throat swabs are sent to a centrally located laboratory, adding another one to two days to total test time.
Nucleic Acid Amplification Test
Nucleic acid amplification tests (NAAT) for GAS perform exceptionally well with a sensitivity of >95%. This performance is notable as the test method is subject to the same factors influencing test performance (adequacy, disease duration, operator, etc.) as a RADT and culture. Besides sensitivity, one of the primary improvements that NAATs offer is their speed and simplicity. Though generally slower than a RADT, NAATs allow for same-day testing in the performing laboratory. This is exceptionally faster than traditional culture methods and several NAATs do not require highly specialized personnel typically required for microbiology. The simplicity of some GAS NAATs allows for testing to be completed near the patient by general laboratory staff familiar with the principles and practices relevant to molecular testing methods.
Molecular Testing Capacity
Laboratory response to the COVID-19 pandemic was either finding a referral laboratory to handle COVID-19 testing or expanding in-house testing capabilities. Many laboratories expanded internal testing capabilities through the addition of new or more molecular instrumentation. As COVID-19 continues to move into an endemic seasonal virus, laboratories that expanded molecular testing in response to COVID-19, now find themselves with excess molecular testing capacity. Of the vendors who provided those COVID-19 molecular tests, many also offer a molecular test for Group A Streptococcus5.
Why Upgrade Now?
The advent of the RADT was borne out of the need to expedite GAS pharyngitis findings, but real-world experience has shown limited ability to detect cases. The performance limitation of RADT necessitates the continued need for throat culture confirmation with specialized laboratories, leading to care delays of two to four days. Waiting two to four days for definitive detection of GAS which is responsible for causing 15%-30% of pharyngitis cases6 is simply too long.
In a heightened era of antimicrobial stewardship and thoughtful prescribing practices, providers may withhold antibiotics on negative results of an RADT. With culture pending, patients may be symptomatic without appropriate treatment for multiple days. Streptococcus pyogenes has demonstrated virulence capable of causing significant morbidity if left unchecked. Thankfully, Streptococcus pyogenes is universally susceptible to penicillin with patients responding well when treated appropriately. It is therefore prudent to start treatment promptly when Streptococcus pyogenes is detected.
Complexity & Capacity
As labor shortages persist, laboratories are looking for ways to capitalize on efficient practices. That opportunity exists in the form of near patient NAA testing for GAS on molecular instruments. Many vendors offer simplicity in operation, allowing for pharyngitis testing by general laboratory personnel. As many laboratories have excess molecular capacity available, the testing burden can be distributed amongst a larger pool of qualified personnel.
Laboratories continue to seek efficiency gains during a time of labor shortages and inflationary pressures. Conversion to a NAA test for pharyngitis achieves a multi-factorial benefit of reducing needs for specialized labor, faster and more reliable results, and capitation of available capacity. Early detection and treatment of GAS pharyngitis is essential to the prevention of downstream sequalae. With CDC voicing concern about an increase in invasive GAS infection, now is an opportune time for laboratories to upgrade their pharyngitis testing.
ABOUT THE AUTHOR
Tyler Radke, MLS(ASCP) has been both a generalist and technical lead of microbiology. Since 2017, he has been the laboratory manager at Bellin Memorial Hospital and Bellin Health Oconto Hospital in Wisconsin. He is also a member of the laboratory technical advisory group (LabTAG) for the Wisconsin Clinical Laboratories Network (WCLN). He is a regular contributor to CLP.
- “Increase in Invasive Group A Strep Infections, 2022–2023.” Centers for Disease Control and Prevention. Feb. 2, 2023. www.cdc.gov/groupastrep/igas-infections-investigation.html
- Banerjee S, Ford C. Rapid Tests for the Diagnosis of Group A Streptococcal Infection: A Review of Diagnostic Test Accuracy, Clinical Utility, Safety, and Cost-Effectiveness [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 May 31. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532707/
- Dithi Banerjee, PhD, and Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA. The Evolution of Group A Streptococcus Pharyngitis Testing. Clinical Laboratory News. Sept 1, 2018. www.aacc.org/cln/articles/2018/september/the-evolution-of-group-a-streptococcus-pharyngitis-testing
- Lean WL, Arnup S, Danchin M, Steer AC. Rapid diagnostic tests for group A streptococcal pharyngitis: a meta-analysis. Pediatrics. 2014 Oct;134(4):771-81. doi: 10.1542/peds.2014-1094. Epub 2014 Sep 8. PMID: 25201792.
- “Comparison of Molecular Assays for Group A Streptococcus.” AACC.org. Undated. https://www.aacc.org/-/media/Files/CLN/2018/Comparison-of-Molecular-Assays-for-Group-A-Streptococcus-T3.pdf?la=en&hash=9EA712D503E2D2CECB8C1D20373AB82F0F6C484F
- “Pharyngitis (Strep Throat).” Centers for Disease Control and Prevention. June 27, 2022. https://www.cdc.gov/groupastrep/diseases-hcp/strep-throat.html