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.].

Streptococcus pyogenes carriage and infection within households in The Gambia: a longitudinal cohort study.

BACKGROUND: Streptococcus pyogenes causes more than 500 000 deaths per year globally, which occur disproportionately in low-income and middle-income countries. The roles of S pyogenes skin and pharyngeal carriage in transmission are unclear. We aimed to investigate the clinical epidemiology and household transmission dynamics of both S pyogenes asymptomatic carriage and infection in a high-burden setting. METHODS: We did a 1-year prospective, longitudinal, household cohort study, recruiting healthy participants from households in Sukuta, The Gambia. Households were eligible if they comprised at least three members, including one child younger than 18 years, and were excluded if more than half of household members declined to participate. Households were identified by random GPS coordinates derived from census data. At monthly visits, pharyngeal and normal skin swabs were collected for S pyogenes culture, and sociodemographic data were recorded by interview. Incident pharyngitis and pyoderma infections were captured. Cultured isolates underwent emm genotyping. The primary outcome measures were incidence of S pyogenes carriage and disease. Additional outcomes were prevalence of S pyogenes skin and pharyngeal carriage, S pyogenes skin and pharyngeal clearance time, S pyogenes emm type, risk factors for carriage and disease events, household secondary attack rate, and emm-linked household transmission events. The study is registered on ClinicalTrials.gov, NCT05117528. FINDINGS: Between July 27, 2021, and Sept 28, 2022, 442 participants were enrolled from 44 households. The median age was 15 years (IQR 6-28) and 233 (53%) were female. We identified 17 pharyngitis and 99 pyoderma events and 49 pharyngeal and 39 skin S pyogenes carriage acquisition events. Mean monthly prevalence was 1·4% (95% CI 1·1-1·9) for S pyogenes pharyngeal carriage and 1·2% (0·9-1·6) for S pyogenes skin carriage. Incidence was 120 per 1000 person-years (95% CI 87-166) for S pyogenes pharyngeal carriage, 124 per 1000 person-years (90-170) for S pyogenes skin carriage, 51 per 1000 person-years (31-84) for S pyogenes pharyngitis, and 263 per 1000 person-years (212-327) for S pyogenes pyoderma. Pharyngeal carriage risk was higher during the rainy season (HR 5·67, 95% CI 2·19-14·69) and in larger households (per additional person: 1·03, 1·00-1·05), as was pharyngitis risk (rainy season: 3·00, 1·10-8·22; household size: 1·04, 1·02-1·07). Skin carriage risk was not affected by season or household size, but was lower in female than in male participants (0·45, 0·22-0·92) and highest in children younger than 5 years compared with adults (22·69, 3·08-167·21), with similar findings for pyoderma (female sex: 0·34, 0·19-0·61; age <5 years: 7·00, 2·78-17·64). Median clearance time after carriage acquisition was 4·0 days for both skin (IQR 3·5-7·0) and pharynx (3·5-7·3). The mean household secondary attack rate was 4·9 (95% CI 3·5-6·3) for epidemiologically linked S pyogenes events and 0·74 (0·3-1·2) for emm-linked S pyogenes events. Of the 204 carriage and disease events, emm types were available for 179 (88%). Only 18 emm-linked between-visit household transmission events were identified. Pyoderma was the most common source of S pyogenes household transmissions in 11 (61%) of 18 emm-linked transmissions. Both pharynx to skin and skin to pharynx transmission events were observed. INTERPRETATION: S pyogenes carriage and infection are common in The Gambia, particularly in children. Most events are non-household acquisitions, but skin carriage and pyoderma have an important role in S pyogenes household transmission and bidirectional transmission between skin and pharynx occurs. FUNDING: Wellcome Trust, Chadwick Trust, Fonds National de la Recherche Scientifique (Belgium), European Society for Paediatric Infectious Diseases, and Medical Research Council (UK).

[The use of autologous platelet-rich plasma in the treatment of chronic pharyngitis]. / Primenenie obogashchennoi trombotsitami autoplazmy v terapii khronicheskogo faringita.

The results of a prospective open cohort study of the use of platelet-rich plasma (platelet-rich plasma - PRP) in patients with chronic pharyngitis during the exacerbation of the disease are presented. OBJECTIVE: To evaluate the clinical efficacy of autologous PRP in the treatment of chronic pharyngitis. MATERIAL AND METHODS: Autologous PRP was injected into the posterior pharyngeal wall as a course of endopharyngeal blockages as part of the complex therapy of chronic pharyngitis. Patients in the control group received standard therapy, without the use of autologous PRP. The effectiveness of the studied technique was evaluated by statistical analysis of the intensity of symptoms of the disease, determined by patients throughout the entire period of treatment in the patient's diary, as well as by analyzing data from mass spectrometry of microbial markers and bacteriological examination of the pharyngeal mucosa, collected at the beginning of the study and 14 days after completion of the course of therapy. CONCLUSION: The use of a course of endopharyngeal blockades with autologous platelet-rich plasma as part of the complex therapy of chronic pharyngitis, according to our estimates, provides a significant effect in the form of higher rates of reduction in the severity of symptoms of the disease, a significant reduction in the number of microorganisms deviating from the reference values (by 2 times or more), a decrease in the duration of the disease compared with the control group.

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.

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.

[Antibacterial therapy for acute streptococcal tonsillopharyngitis: results of a randomized comparative clinical trial with amoxicillin + clavulanic acid EXPRESS].

BACKGROUND: Acute tonsillopharyngitis is one of the most common types of respiratory tract infections. In case of bacterial etiologies of the disease, penicillin antibiotics are prescribed, in particular amoxicillin + clavulanic acid. Dispersible forms of antibiotics have a number of advantages over film-coated tablets and are characterized by better pharmacokinetic parameters that increase the effectiveness and safety of treatment, as well as patient compliance. AIM: To compare the effectiveness and safety of Amoxicillin + Clavulanic acid EXPRESS in the form of dispersible tablets and amoxicillin with clavulanic acid in film-coated tablets in the treatment of acute streptococcal tonsillopharyngitis. MATERIALS AND METHODS: A randomized comparative clinical study involved 60 adult patients diagnosed with acute streptococcal tonsillopharyngitis. Group 1 (n=30) received the Amoxicillin + Clavulanic acid EXPRESS, dispersible tablets, 875+125 mg 2 times a day at the beginning of meals. Group 2 (n=30) received Amoxiclav, film-coated tablets, 875+125 mg 2 times a day at the beginning of meals. The duration of the treatment was 10 days. The following procedures were performed to all participants: general clinical and otorhinolaryngological examinations, an express test to detect group A streptococcal antigens in a smear from the posterior pharyngeal wall (streptatest), assessment of symptoms of acute tonsillopharyngitis on the McIsaac scale, severity of sore throat, difficulty swallowing, swelling of the throat, measurement of body temperature, assessment of the clinical global impression of the therapy, adherence to treatment, frequency of the adverse reactions before treatment, 3 days after the beginning of therapy and after the course completion (day 10). RESULTS: Recovery occurred in 96.6% of patients in group 1 according to examination on the 10th day of treatment and in 93.3% of patients in group 2. The rate of fever regression was higher in group 1 - on the 3rd day of treatment, normalization of temperature was observed in 36.6% and 30% of patients in the comparison group. Pain syndrome, symptoms of throat swelling and difficulty swallowing significantly (p<0.01) regressed by the 10th day in patients of both treatment groups. The incidence of adverse reactions on the 10th day of treatment in group 1 was 10%, in group 2 - 33.3% (p=0.03). CONCLUSION: Amoxicillin + Clavulanic acid EXPRESS has high therapeutic efficacy in the treatment of acute streptococcal tonsillopharyngitis, comparable to the Amoxiclav in film-coated tablets. At the same time, dispersible tablets of Amoxicillin + Clavulanic acid EXPRESS demonstrated a significantly higher safety profile compared to the simple tablet form.

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.

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.

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.

Recombinational exchange of M-fibril and T-pilus genes generates extensive cell surface diversity in the global group A Streptococcus population.

Among genes present in all group A streptococci (GAS), those encoding M-fibril and T-pilus proteins display the highest levels of sequence diversity, giving rise to the two primary serological typing schemes historically used to define strain. A new genotyping scheme for the pilin adhesin and backbone genes is developed and, when combined with emm typing, provides an account of the global GAS strain population. Cluster analysis based on nucleotide sequence similarity assigns most T-serotypes to discrete pilin backbone sequence clusters, yet the established T-types correspond to only half the clusters. The major pilin adhesin and backbone sequence clusters yield 98 unique combinations, defined as "pilin types." Numerous horizontal transfer events that involve pilin or emm genes generate extensive antigenic and functional diversity on the bacterial cell surface and lead to the emergence of new strains. Inferred pilin genotypes applied to a meta-analysis of global population-based collections of pharyngitis and impetigo isolates reveal highly significant associations between pilin genotypes and GAS infection at distinct ecological niches, consistent with a role for pilin gene products in adaptive evolution. Integration of emm and pilin typing into open-access online tools (pubmlst.org) ensures broad utility for end-users wanting to determine the architecture of M-fibril and T-pilus genes from genome assemblies.IMPORTANCEPrecision in defining the variant forms of infectious agents is critical to understanding their population biology and the epidemiology of associated diseases. Group A Streptococcus (GAS) is a global pathogen that causes a wide range of diseases and displays a highly diverse cell surface due to the antigenic heterogeneity of M-fibril and T-pilus proteins which also act as virulence factors of varied functions. emm genotyping is well-established and highly utilized, but there is no counterpart for pilin genes. A global GAS collection provides the basis for a comprehensive pilin typing scheme, and online tools for determining emm and pilin genotypes are developed. Application of these tools reveals the expansion of structural-functional diversity among GAS via horizontal gene transfer, as evidenced by unique combinations of surface protein genes. Pilin and emm genotype correlations with superficial throat vs skin infection provide new insights on the molecular determinants underlying key ecological and epidemiological trends.

Group A Streptococcus pyogenes in wastewater: Applicability of wastewater-based epidemiology for monitoring the prevalence of GAS pharyngitis during the late COVID-19 pandemic phase.

Streptococcus pyogenes, Group A Streptococcus (GAS), is a human pathogen that causes a spectrum of diseases from mild to severe, including GAS pharyngitis, a common acute respiratory disease in developed countries. Although wastewater-based epidemiology (WBE) has been extensively used to monitor viral pathogens such as severe acute respiratory syndrome coronavirus 2, its applicability to S. pyogenes remains unexplored. This study was conducted to investigate the feasibility of detecting and quantifying S. pyogenes in wastewater by quantitative polymerase chain reaction (qPCR) and evaluate the applicability of WBE for monitoring the prevalence of GAS pharyngitis. A total of 52 grab influent samples were collected from a wastewater treatment plant in Japan once a week between March 2023 and February 2024. The samples were centrifuged, followed by nucleic acid extraction and qPCR for the S. pyogenes-specific genes speB and spy1258. Of the 52 samples, 90 % and 81 % were positive for speB and spy1258 genes, respectively, indicating the feasibility of S. pyogenes for wastewater surveillance. However, the percentage of quantifiable samples for speB gene was significantly higher in winter than in spring and summer. Similarly, the concentrations of both genes in wastewater samples were significantly higher in winter (speB, 4.1 ± 0.27 log10 copies/L; spy1258, 4.1 ± 0.28 log10 copies/L; One-way ANOVA, p < 0.01) than in spring and summer. Higher concentrations and detection ratios of S. pyogenes genes were observed during increased GAS pharyngitis cases in the catchment. Significant moderate correlations were observed between target gene concentrations and reported GAS pharyngitis cases. This study enhances the understanding role of WBE in monitoring and managing infectious diseases within communities.

"Give Me Five": The Case for 5 Days of Antibiotics as the Default Duration for Acute Respiratory Tract Infections.

Acute respiratory tract infections (ARTIs) account for most antibiotic prescriptions in pediatrics. Although US guidelines continue to recommend ≥10 days antibiotics for common ARTIs, evidence suggests that 5-day courses can be safe and effective. Academic imprinting seems to play a major role in the continued use of prolonged antibiotic durations. In this report, we discuss the evidence supporting short antibiotic courses for group A streptococcal pharyngitis, acute otitis media, and acute bacterial rhinosinusitis. We discuss the basis for prolonged antibiotic course recommendations and recent literature investigating shorter courses. Prescribers in the United States should overcome academic imprinting and follow international trends to reduce antibiotic durations for common ARTIs, where 5 days is a safe and efficacious course when antibiotics are prescribed.

Burden of antimicrobial prescribing in primary care attributable to sore throat: a retrospective cohort study of patient record data.

BACKGROUND: Reducing antibiotic use in Australia, and the subsequent impact on antimicrobial resistance, requires multiple, sustained approaches with appropriate resources and support. Additional strategies to reduce antibiotic prescribing include effective vaccines, against pathogens such as Streptococcus pyogenes, the most common bacterial cause of sore throat. As part of efforts towards assessing the benefits of introducing new strategies to reduce antimicrobial prescribing, we aimed to determine the burden of antimicrobial prescribing for sore throat in general practice. METHODS: General practice activity data from 2013 - 2017 derived from the first 8 practices participating in the 'Primary Care Audit, Teaching and Research Open Network' (Patron) program were analysed according to reason for visit (upper respiratory tract infection, URTI, or sore throat) and antibiotic prescription. The main outcome measures were percentage of sore throat or URTI presentations with antibiotic prescription by age. RESULTS: A total of 722,339 visits to general practice were made by 65,449 patients; 5.7% of visits were for URTI with 0.8% meeting the more specific criteria for sore throat. 66.1% of sore throat visits and 36.2% of URTI visits resulted in antibiotic prescription. Penicillin, the recommended antibiotic for sore throat when indicated, was the antibiotic of choice in only 52.9% of sore throat cases prescribed antibiotics. Broader spectrum antibiotics were prescribed more frequently in older age groups. CONCLUSIONS: Frequency of antibiotic prescribing for sore throat is high and broad, despite Australian Therapeutic guideline recommendations. Multiple, sustained interventions to reduce prescribing, including availability of effective S. pyogenes vaccines that could reduce the incidence of streptococcal pharyngitis, could obviate the need to prescribe antibiotics and support ongoing efforts to promote antimicrobial stewardship.

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.

Spatiotemporal Trends in Group A Streptococcal Pharyngitis in the United States.

BACKGROUND: Group A Streptococcus (GAS) causes an estimated 5.2 million outpatient visits for pharyngitis annually in the United States, with incidence peaking in winter, but the annual spatiotemporal pattern of GAS pharyngitis across the United States is poorly characterized. METHODS: We used outpatient claims data from individuals with private medical insurance between 2010 and 2018 to quantify GAS pharyngitis visit rates across U.S. census regions, subregions, and states. We evaluated seasonal and age-based patterns of geographic spread and the association between school start dates and the summertime upward inflection in GAS visits. RESULTS: The South had the most visits per person (yearly average, 39.11 visits per 1000 people; 95% confidence interval, 36.21-42.01) and the West had the fewest (yearly average, 17.63 visits per 1000 people; 95% confidence interval, 16.76-18.49). Visits increased earliest in the South and in school-age children. Differences in visits between the South and other regions were most pronounced in the late summer through early winter. Visits peaked earliest in central southern states, in December to January, and latest on the coasts, in March. The onset of the rise in GAS pharyngitis visits correlated with, but preceded, average school start times. CONCLUSIONS: The burden and timing of GAS pharyngitis varied across the continental United States, with the South experiencing the highest overall rates and earliest onset and peak in outpatient visits. Understanding the drivers of these regional differences in GAS pharyngitis will help in identifying and targeting prevention measures.

Systematic review and meta-analysis of the accuracy of McIsaac and Centor score in patients presenting to secondary care with pharyngitis.

BACKGROUND: Centor and McIsaac scores are clinical prediction rules for diagnosing group A streptococcus (GAS) infection in patients with pharyngitis. Their recommended thresholds vary between guidelines. OBJECTIVES: To estimate the sensitivity and specificity of the McIsaac and Centor scores to diagnose GAS pharyngitis and evaluate their impact on antibiotic prescribing at each threshold in patients presenting to secondary care. DATA SOURCES: MEDLINE, Embase, and Web of Science were searched from inception to September 2022. STUDY ELIGIBILITY CRITERIA: Studies of patients presenting with acute pharyngitis to emergency or outpatient clinics that estimated the accuracy of McIsaac or Centor scores against throat cultures and/or rapid antigen detection tests (RADT) as reference standards. TESTS: Centor or McIsaac score. REFERENCE STANDARD: Throat cultures and/or RADT. ASSESSMENT OF RISK OF BIAS: Quality Assessment of Diagnostic Accuracy Studies. METHODS OF DATA SYNTHESIS: The sensitivities and specificities of the McIsaac and Centor scores were pooled at each threshold using bivariate random effects meta-analysis. RESULTS: Fourteen studies were included (eight McIsaac and six Centor scores). Eight studies had unclear and six had a high risk of bias. The McIsaac score had higher estimated sensitivity and lower specificity relative to Centor scores at equivalent thresholds but with wide and overlapping confidence regions. Using either score as a triage to RADT to decide antibiotic treatment would reduce antibiotic prescription to patients with non-GAS pharyngitis relative to RADT test for everyone, but also reduce antibiotic prescription to patients with GAS. DISCUSSION: Centor and McIsaac scores are equally ineffective at triaging patients who need antibiotics presenting with pharyngitis at hospitals. At high thresholds, too many true positive cases are missed, whereas at low thresholds, too many false positives are treated, leading to the over prescription of antibiotics. The former may be compensated by adequate safety netting by clinicians, ensuring that patients can seek help if symptoms worsen.

Use of saliva-based qPCR diagnostics for the accurate, rapid, and inexpensive detection of strep throat.

OBJECTIVES: Outpatient health care facilities are essential for quickly diagnosing common infectious diseases such as bacterial and viral pharyngitis. The only form of pharyngitis requiring antibiotics is strep throat (ST); however, antibiotic prescription rates are much higher than ST prevalence, suggesting antibiotics are being inappropriately prescribed. Current rapid ST diagnostics may be contributing to this problem due to the low sensitivity and variable specificity of these tests. It is best practice to verify a negative ST diagnosis with a group A Streptococcus (GAS) culture, but many clinics do not perform this test due to the additional cost and 24-72 h required to obtain results. This indicates there is great need for more accurate rapid diagnostic tools in outpatient facilities. We hypothesized that next generation qPCR technology could be adapted to detect GAS DNA from saliva samples (instead of the traditional throat swab) by creating a simple, fast, and inexpensive protocol. METHODS: Saliva specimens collected from patients at James Madison University Health Center were used to test the effectiveness of our Chelex 100-based rapid DNA extraction method, followed by a fast protocol developed for the Open qPCR machine to accurately detect ST. RESULTS: Our final saliva processing and qPCR protocol required no specialized training to perform and was able to detect ST with 100 % sensitivity and 100 % specificity (n=102) in 22-26 min, costing only $1.12 per sample. CONCLUSIONS: Saliva can be rapidly analyzed via qPCR for the accurate and inexpensive detection of ST.