Review: Diagnostic Potential for Collaborative Pharyngitis Biomarkers.

Pharyngitis is an inflammatory condition of the pharynx and/or tonsils commonly seen in both children and adults. Viruses and bacteria represent the most common encountered etiologic agents-yeast/fungi and parasites are infrequently implicated. Some of these are predominantly observed in unique populations (eg, immunocompromised or unvaccinated individuals). This manuscript (part 3 of 3) summarizes the current state of biomarker diagnostic testing and highlights the expanding role they will likely play in the expedited diagnosis and management of patients with acute pharyngitis. Biomarkers, in conjunction with rapid antigen and/or nucleic acid amplification testing, will likely become the standard of care to accurately diagnose the etiologic agent(s) of pharyngitis. This novel testing paradigm has the potential to guide appropriate patient management and antibiotic stewardship by accurately determining if the cause of pharyngitis is due to a viral or bacterial etiology.

Review: Current Laboratory and Point-of-Care Pharyngitis Diagnostic Testing and Knowledge Gaps.

Pharyngitis is an inflammatory condition of the pharynx and/or tonsils commonly seen in both children and adults. Viruses and bacteria represent the most common encountered etiologic agents-yeast/fungi and parasites are infrequently implicated. Some of these are predominantly observed in unique populations (eg, immunocompromised or unvaccinated individuals). This manuscript (part 2 of 3) summarizes the current state of laboratory and point-of-care diagnostic testing and highlights the expanding role of nucleic acid amplification in the expedited diagnosis and management of patients with acute pharyngitis. It discusses preanalytical, analytical, and postanalytical variables that impact the performance of culture, rapid antigen, and nucleic acid amplification testing. Finally, it sets the stage for part 3, which discusses the emerging role of biomarkers in the management of individuals with acute pharyngitis.

Carrier rates of group A streptococci in Australian wet tropics and their impact on the clinical usefulness of throat swabs.

BACKGROUND AND OBJECTIVES: Rapid point-of-care tests (POCT) are likely to assist with the detection of group A streptococci (GAS), but their usefulness is determined by the presence of carriers of GAS. This is insufficiently explored in the wet tropics. METHOD: This study included 77 patients attending primary care in the wet tropics complaining of a sore throat, and 49 healthy controls. Carrier rates of GAS and the positive and negative etiological predictive values (P-EPV and N-EPV, respectively) of a POCT were calculated. RESULTS: The carrier rates were 8.3% among healthy children and 2.7% for adults. The P-EPV for children was 71% (95% confidence interval [CI]: 0.0-100%) and for adults it was 85% (95% CI: 0.0-100%). The corresponding N-EPV was 99% (95% CI: 95-100%) for children and 99% (95% CI: 98-100%) for adults. DISCUSSION: N-EPV, ruling out GAS, was sufficiently high with narrow CIs to allow for defining a stopping rule to avoid unnecessary antibiotic prescribing.

A Hypothesis-Driven, Near-Peer Physical Diagnosis Module on Streptococcal Pharyngitis Within the Pediatrics Clerkship.

Introduction: In busy clinical settings, there is limited time to teach physical examination (PE) and procedural skills, particularly when the traditional head-to-toe PE approach is time-consuming. Near-peer teaching of a more efficient approach, the hypothesis-driven PE (HDPE), increases students' learning opportunities. We developed a near-peer HDPE module to improve medical student confidence, knowledge, and skills for diagnosing and managing streptococcal pharyngitis. Methods: During this 1-hour module, residents taught the diagnostic approach for a patient with sore throat and facilitated small groups for practicing PE and throat swab skills. We assessed students using pre- and postmodule surveys including Likert-scale confidence scores (1 = not at all confident, 5= extremely confident), multiple-choice knowledge questions, and a skills rubric. A control group was surveyed at clerkship conclusion. Results: Of the 71 pediatric clerkship students who participated, 69 (97%) completed premodule surveys and 65 (91%) completed skills assessments. Twenty-eight (39%) completed postmodule surveys and skill assessments. After participation, students' survey responses and rubrics indicated significant increase in confidence (Mdn pre = 2 [IQR = 1,2], Mdn post = 4 [IQR = 4,5]; p < .001), knowledge (M pre = 40%, M post = 77%; p < .001), and skills (M pre = 5.3, M post = 7.5; p < .01). Participating students also had significantly higher confidence (p < .005) and knowledge (p < 0.01) compared to the control group. Discussion: This near-peer HDPE module improved students' knowledge, confidence, and skills related to streptococcal pharyngitis diagnosis and management and achieved compliance for a required clerkship skill.

[Clinical diagnosis of group A streptococcal pharyngitis and progress in the application of scoring systems]. / A族链球菌咽炎的临床诊断及评分制的应用进展.

Pharyngitis can be caused by various pathogens, including viruses and bacteria. Group A streptococcus (GAS) is the most common bacterial cause of pharyngitis. However, distinguishing GAS pharyngitis from other types of upper respiratory tract infections is challenging in clinical settings. This often leads to empirical treatments and, consequently, the overuse of antimicrobial drugs. With the advancement of antimicrobial drug management and healthcare payment reform initiatives in China, reducing unnecessary testing and prescriptions of antimicrobial drugs is imperative. To promote standardized diagnosis and treatment of GAS pharyngitis, this article reviews various international guidelines on the clinical diagnosis and differential diagnosis of GAS pharyngitis, particularly focusing on clinical scoring systems guiding laboratory testing and antimicrobial treatment decisions for GAS pharyngitis and their application recommendations, providing a reference for domestic researchers and clinical practitioners.

The impact of national guidelines on the diagnostics of sore throat in children.

BACKGROUND: The Finnish treatment guidelines for sore throat were updated in June 2020. The aim of this study was to determine how the publication of these guidelines affected the treatment of pediatric patients, particularly through the use of the Centor criteria, C-reactive protein tests, and microbiological testing in the diagnosis of Group A ß-hemolytic streptococci tonsillitis. METHODS: We conducted a retrospective single-center before-and-after cohort study in Finland from 2019 to 2022. We included all patients who visited the pediatric emergency department and were diagnosed with tonsillitis or pharyngitis. RESULTS: We included 246 patients who were admitted before the guidelines were updated and 219 patients after. Only two patients in the after group had a Centor score reported in their patient records. Rapid antigen tests were administered to 231 patients (93.9%) before the update and 202 patients (92.2%) after (proportion difference of 1.7%, CI -3.0-6.6%). C-reactive protein was taken from 193 patients (78.5%) before the update and 189 patients (86.3%) after (proportion difference of 7.8%, CI 0.1-14.7%). CONCLUSIONS: Centor scores were not used as recommended in the guidelines and did not impact the use of microbiological or C-reactive protein testing. More education and examining the preconceptions of health care personnel is required to implement the updated treatment guidelines in clinical practice.

Diagnosis and Treatment of Group A Streptococcal Pharyngitis in Children.

The purpose of this review is to summarize the current evidence regarding the management of streptococcal pharyngitis in children. This article aims to provide a valid support to discriminate streptococcal pharyngitis from viral cases and treat it appropriately to avoid the development of complications. Differential diagnosis based only on clinical features is not always easy. For this reason, different clinical scores were created to provide an accurate diagnosis. Microbiological tests are valuable tools as well, but their use is not recommended unanimously. Concerning treatment, all guidelines agree on the drug to be used. However, doubts remain about the optimal duration of antibiotic therapy, especially in this specific historical moment as we are experiencing a peak in streptococcal infections. [Pediatr Ann. 2024;53(6):e234-e238.].

Perioperative care of the patient with a periodic fever syndrome.

Periodic fever syndromes are autoinflammatory disorders associated with recurrent fevers unrelated to infection. Little is known about the perioperative management of patients with these syndromes, and existing literature consists primarily of case reports and occasional case series. This narrative review discusses background information and diagnostic criteria for the three most common periodic fever syndromes: periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA), familial Mediterranean fever (FMF), and TNF receptor-associated periodic syndrome (TRAPS), and describes perioperative considerations for anesthesia providers when caring for the patient with a periodic fever syndrome. We include a systems-based framework in which to organize these considerations.

Is Streptococcus pyogenes a pathogen or passenger in uncomplicated acute sore throat? A systematic review and meta-analysis.

OBJECTIVES: The objective was to estimate the probability that finding a Streptococcus pyogenes (Group A Streptococcus) in a throat swab in a patient with a sore throat reflects the aetiology. We also investigated to what extent this is influenced by age, carrier rates of S. pyogenes and climate zone. METHODS: We conducted a comprehensive search of Medline and Scopus up until October 2023 for case-control studies reporting the prevalence of S. pyogenes in patients with a sore throat and healthy controls. We only included studies with separate data for children and adults. We used the positive and negative etiologic predictive values (P-EPV and N-EPV) to estimate the probability of a link between a sore throat and a finding of S. pyogenes. RESULTS: We included 15 studies in our meta-analysis. The overall P-EPV for children and adults were 63% (49-74%) and 92% (87-95%), respectively. The P-EPV rose to 83% (64-93%) for children and 94% (90-97%) for adults when only patients with 3-4 Centor criteria were included. The overall N-EPV was 97% (96-98%) for children and 96% (95-97%) for adults. CONCLUSION: Detecting S. pyogenes in adult patients with an uncomplicated acute sore throat is useful to rule in S. pyogenes as the likely aetiologic agent. The P-EPV significantly increased for children when those with 3-4 Centor criteria were selected. A negative throat swab is always useful for both children and adults to rule out S. pyogenes as the cause of sore throat.

What Is Strep Throat?

This JAMA Patient Page describes strep throat, its signs and symptoms, diagnosis, treatment, and potential complications.

Machine Learning for Clinical Decision Support of Acute Streptococcal Pharyngitis: A Pilot Study.

BACKGROUND: Group A Streptococcus (GAS) is the predominant bacterial pathogen of pharyngitis in children. However, distinguishing GAS from viral pharyngitis is sometimes difficult. Unnecessary antibiotic use contributes to unwanted side effects, such as allergic reactions and diarrhea. It also may increase antibiotic resistance. OBJECTIVES: To evaluate the effect of a machine learning algorithm on the clinical evaluation of bacterial pharyngitis in children. METHODS: We assessed 54 children aged 2-17 years who presented to a primary healthcare clinic with a sore throat and fever over 38°C from 1 November 2021 to 30 April 2022. All children were tested with a streptococcal rapid antigen detection test (RADT). If negative, a throat culture was performed. Children with a positive RADT or throat culture were considered GAS-positive and treated antibiotically for 10 days, as per guidelines. Children with negative RADT tests throat cultures were considered positive for viral pharyngitis. The children were allocated into two groups: Group A streptococcal pharyngitis (GAS-P) (n=36) and viral pharyngitis (n=18). All patients underwent a McIsaac score evaluation. A linear support vector machine algorithm was used for classification. RESULTS: The machine learning algorithm resulted in a positive predictive value of 80.6 % (27 of 36) for GAS-P infection. The false discovery rates for GAS-P infection were 19.4 % (7 of 36). CONCLUSIONS: Applying the machine-learning strategy resulted in a high positive predictive value for the detection of streptococcal pharyngitis and can contribute as a medical decision aid in the diagnosis and treatment of GAS-P.

Unravelling the clinical heterogeneity of undefined recurrent fever over time in the European registries on Autoinflammation.

BACKGROUND: Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries. METHODS: Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients. RESULTS: Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria. CONCLUSIONS: Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.

A highly sensitive 3base™ assay for detecting Streptococcus pyogenes in saliva during controlled human pharyngitis.

Streptococcus pyogenes (Group A Streptococcus; GAS) is a Gram-positive bacterium responsible for substantial human mortality and morbidity. Conventional diagnosis of GAS pharyngitis relies on throat swab culture, a low-throughput, slow, and relatively invasive 'gold standard'. While molecular approaches are becoming increasingly utilized, the potential of saliva as a diagnostic fluid for GAS infection remains largely unexplored. Here, we present a novel, high-throughput, sensitive, and robust speB qPCR assay that reliably detects GAS in saliva using innovative 3base™ technology (Genetic Signatures Limited, Sydney, Australia). The assay has been validated on baseline, acute, and convalescent saliva samples generated from the Controlled Human Infection for Vaccination Against Streptococcus (CHIVAS-M75) trial, in which healthy adult participants were challenged with emm75 GAS. In these well-defined samples, our high-throughput assay outperforms throat culture and conventional qPCR in saliva respectively, affirming the utility of the 3base™ platform, demonstrating the feasibility of saliva as a diagnostic biofluid, and paving the way for the development of novel non-invasive approaches for the detection of GAS and other oropharyngeal pathogens.

Disease phenotypes in adult patients with suspected undifferentiated autoinflammatory diseases and PFAPA syndrome: Clinical and therapeutic implications.

BACKGROUND: Undifferentiated autoinflammatory diseases are characterized by recurrent or persistent fever, usually combined with other inflammatory manifestations, and negative or inconclusive genetic studies for monogenic autoinflammatory disorders. AIMS: To define and characterize disease phenotypes in adult patients diagnosed in an adult reference center with undifferentiated autoinflammatory diseases, and to analyze the efficacy of the drugs used in order to provide practical diagnostic and therapeutic recommendations. METHODS: Retrospective study (2015-2022) of patients with undifferentiated autoinflammatory diseases among all patients visited in our reference center. Demographic, clinical, laboratory features and detailed therapeutic information was collected. RESULTS: Of the 334 patients with a suspected autoinflammatory disease, 134 (40%) patients (61% women) were initially diagnosed with undifferentiated autoinflammatory diseases. Mean age at disease onset and at diagnosis was 28.7 and 37.7 years, respectively. In 90 (67.2%) patients, symptoms started during adulthood. Forty-four (32.8%) patients met diagnostic/classification criteria for adult periodic fever with aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome. In the remaining patients, four additional phenotypes were differentiated according to the predominant manifestations: a) Predominantly fever phenotype (n = 18; 13.4%); b) Predominantly abdominal/pleuritic pain phenotype (n = 9; 6.7%); c) Predominantly pericarditis phenotype (n = 18; 13.4%), and d) Complex syndrome phenotype (n = 45; 33.6%). Prednisone (mainly on demand), colchicine and anakinra were the drugs commonly used. Overall, complete responses were achieved with prednisone in 41.3%, colchicine in 40.2%, and anakinra in 58.3% of patients in whom they were used. By phenotypes, prednisone on demand was more effective in adult PFAPA syndrome and colchicine in patients with the abdominal/pleuritic pain pattern and PFAPA syndrome. Patients with complex syndrome achieved complete responses with prednisone (21.9%), colchicine (25.7%) and anakinra (44.4%), and were the group more often requiring additional immunosuppressive drugs. CONCLUSIONS: The analysis of the largest single-center series of adult patients with undifferentiated autoinflammatory diseases identified and characterized different disease phenotypes and their therapeutic approaches. This study is expected to contribute to increase the awareness of physicians for an early identification of these conditions, and to provide the best known therapeutic options.

Streptococcal Pharyngitis: Rapid Evidence Review.

Group A beta-hemolytic streptococcal pharyngitis is a common infection responsible for more than 6 million office visits in the United States annually. Only 10% of adults seeking care for a sore throat have group A beta-hemolytic streptococcal pharyngitis; however, 60% or more are prescribed antibiotics. Guidelines recommend using clinical decision rules to assess the risk of group A beta-hemolytic streptococcal infection, followed by rapid antigen testing if a diagnosis is unclear, before prescribing antibiotics. Fever, tonsillar exudate, cervical lymphadenitis, and patient ages of 3 to 15 years increase clinical suspicion. A cough is more suggestive of a viral etiology. The limited history used in these decision rules is amenable to virtual visits. After a negative rapid antigen test result, a throat culture is recommended in children and adolescents. Penicillin and amoxicillin are first-line antibiotics, with a recommended course of 10 days; first-generation cephalosporins are recommended for patients with nonanaphylactic allergies to penicillin. There is significant resistance to azithromycin and clarithromycin in some parts of the United States. Steroids are not recommended for symptomatic treatment. Patients with worsening symptoms after appropriate antibiotic initiation or with symptoms lasting 5 days after the start of treatment should be reevaluated. Tonsillectomy is rarely recommended as a preventive measure: seven episodes of streptococcal pharyngitis in 1 year, five episodes in each of the past 2 years, or three episodes in each of the past 3 years are commonly used thresholds for considering surgery.

Symptoms predictive of Fusobacterium necrophorum pharyngotonsillitis - an observational study of cases presenting to hospitals in Southern Sweden.

OBJECTIVES: Fusobacterium necrophorum is a common cause of pharyngotonsillitis. However, no guidelines exist on when to diagnose or treat it. We aimed to investigate associations between clinical criteria and F. necrophorum-positivity in pharyngotonsillitis and assess the predictive potential of a simple scoring system. METHODS: Pharyngotonsillitis patients who were tested for F. necrophorum (PCR) and presented to hospitals in the Skåne Region, Sweden, between 2013-2020 were eligible. Data were retrieved from electronic chart reviews and registries. By logistic regression we investigated associations between F. necrophorum-positivity and pre-specified criteria: age 13-30 years, symptom duration ≤ 3 days, absence of viral symptoms (e.g. cough, coryza), fever, tonsillar swelling/exudate, lymphadenopathy and CRP ≥ 50 mg/L. In secondary analyses, associated variables were weighted by strength of association into a score and its predictive accuracy of F. necrophorum was assessed. RESULTS: Among 561 cases included, 184 (33%) had F. necrophorum, which was associated with the following criteria: age 13-30, symptom duration ≤ 3 days, absence of viral symptoms, tonsillar swelling/exudate and CRP ≥ 50 mg/L. Age 13-30 had the strongest association (OR5.7 95%CI 3.7-8.8). After weighting, these five variables had a sensitivity and specificity of 68% and 71% respectively to predict F. necrophorum-positivity at the proposed cut-off. CONCLUSION: Our results suggest that F. necrophorum cases presenting to hospitals might be better distinguished from other pharyngotonsillitis cases by a simple scoring system presented, with age 13-30 being the strongest predictor for F. necrophorum. Prospective studies, involving primary care settings, are needed to evaluate generalisability of findings beyond cases presenting to hospitals.

Fifteen-minute consultation: Group A streptococcal pharyngitis, diagnosis and treatment in children.

Group A streptococcus (GAS) is the most common bacterial cause of pharyngitis in children. GAS causes significant suppurative and non-suppurative complications including invasive GAS disease and acute rheumatic fever. This article describes the current epidemiology and clinical presentation of GAS pharyngitis and explores how diagnostic and treatment decisions differ globally. Several key decision support tools are discussed including international guidelines, clinical decision scores and laboratory tests along with the evidence for treatment choice and duration. With recent international reports describing an increase in GAS infections, clinicians should be familiar with their local GAS pharyngitis guidelines and the rationale for diagnosis and treatment of this common childhood illness.

Group A Streptococcus pharyngitis in Children: New Perspectives on Rapid Diagnostic Testing and Antimicrobial Stewardship.

The most common cause of bacterial pharyngitis is Group A Streptococcus (GAS). Accurate diagnosis of GAS pharyngitis is crucial to identify children who would benefit from antibiotic treatment. Rapid diagnosis has the potential to reduce antibiotic overuse. Current national guidelines differ in their recommendations for GAS testing. While rapid antigen detection tests (RADTs) are widely used, their sensitivity is considered too low for stand-alone testing by several expert bodies. Newer molecular tests using nucleic acid amplification show higher accuracy and fast results, but their cost, complexity, and very high sensitivity may limit widespread adoption. This review provides up-to-date evidence regarding rapid diagnostic testing and antimicrobial stewardship in children with sore throat. We discuss discrepancies across GAS testing guidelines at the international level, patient selection for testing for GAS, rapid test accuracy, and the potential role of rapid GAS tests to promote antibiotic stewardship, with emphasis on emerging rapid molecular tests.