1. INTRODUCTION Upper respiratory tract infections, including acute pharyngitis, are common in general practice. Although the most common cause of pharyngitis is viral, approximately 10% of incidences are bacterial, and are mostly accountable by group A β-haemolytic streptococci (GABHS). Unlike other forms of pharyngitis, GABHS pharyngitis requires treatment with antibiotics. Antibiotics prevent serious complications (e.g. rheumatic fever), reduce duration of symptoms and spread of disease. GABHS can be diagnosed with a throat swab, however, this test is relatively expensive and the results can take days to come back, leading to withholding of treatment or the prescription of unnecessary antibiotics. A number of clinical prediction rules have been developed to distinguish streptococcal pharyngitis from other types of pharyngitis using signs and symptoms. The most widely recognised of these is the Centor score 1. The signs and symptoms included in the Centor Score can be found in Table 1a. One point is assigned for the presence of each sign or symptom and the probability of GABHS is based on the patients score (Table 1b). The Centor rule is recommended in a number of guidelines from north America; including the ‘American College of Physicians-American Society of Internal Medicine’ guidelines and the ‘Centres for Disease Control and Prevention’ (CDC) guidelines. Table 1. a) The Centor score, b) probability of GABHS based on score, from Centor et al 1981 1 *indicates average probabilities AIM The aim of this systematic review was twofold; to establish the discriminatory power of individual signs and symptoms for ruling in or out a diagnosis of GABHS pharyngitis in adults, and secondly to establish the validity of the Centor score. METHOD We searched PubMed (1966 to October 2008), EMBASE (1988 to October 2008), Cochrane Library, Google Scholar and MEDION using a combination of terms and filters. We included studies that assessed the diagnostic accuracy of signs and symptoms and/or validated the Centor score using a throat swab as the gold standard reference test. Only patients over the age of 15 years were included. For the diagnostic accuracy of signs and symptoms, 2x2 tables were constructed and sensitivities, specificities and SROC curves were calculated. To examine the validity of the Centor score, the number of predicted GABHS patients (based on Centor’s derivation study) was compared with the number of observed patients with GABHS in each study. The quality of each study was assessed independently by two researchers using a modified version of the QUADAS tool. Review Manager 5 (Cochran collaboration) and a bivariate random effects model were used for analysis. RESULTS Search strategy identified 340 potentially relevant articles. After reading title, abstract or full text, 34 of these articles fitted our inclusion criteria. 17 of the articles included only adults. The authors of articles without the necessary data and those who also included children were contacted. Data on the diagnostic test accuracy of signs and symptoms was available in 18 studies. 13 studies also had data on the Centor score. The majority of the studies were undertaken in a primary care/family practice setting, two were carried out in an emergency department. There was a good deal of variability in the prevalence of GABHS between studies, ranging from 4.7% to 37.6%. Diagnostic test accuracy of signs and symptoms The signs and symptoms of ‘fever’ and ‘any exudate’ had a higher specificity than sensitivity (Table 2), suggesting that they are more useful at ruling in a diagnosis of GABHS when present. ‘Tender anterior cervical adenopathy’ and ‘absence of cough’, on the other hand, have a higher sensitivity than specificity and are therefore more useful at ruling out a diagnosis of GABHS when they are absent. It should be noted that between study heterogeneity was high, however the bivariate random effects model used in the analysis accounts for this. CONCLUSIONS No sign or symptom on its own was powerful enough to rule in or rule out the diagnosis of GABHS pharyngitis. However, our analysis suggests that the Centor score is a useful tool for predicting the risk of GABHS pharyngitis and should be recommended in UK & Irish guidelines, as it is in the US and Canada, so as to reduce unnecessary prescribing of antibiotics. A systematic review of the diagnostic accuracy of signs and symptoms and the validation of the Centor score in predicting group A β-haemolytic streptococcal pharyngitis in adults in Primary Care J Aalbers 1,2, KK O’Brien 1, WS Chan 1, BD Dimitrov 1, G Falk 1 C Teljeur 1 & T Fahey 1 HRB Centre for Primary Care Research, RCSI 1 & Radboud University, Nijmegen Medical Centre 2 REFERENCES 1 Centor, R.M., et al., The diagnosis of strep throat in adults in the emergency room. Med Decis Making, 1981. 1(3): p. 239-46. Validation of the Centor Score Figure 2 & Table 3 show the results from validation studies of the Centor score. There is no significant difference between predicted and observed values in any of the Centor score categories, suggesting that overall the Centor score correctly predicts the risk of GABHS pharyngitis. There is a tendency towards underprediction in studies with a high prevalence of GABHS pharyngitis and overprediction in studies with a low prevalence of GABHS pharyngitis. a b Table 2. Pooled sensitivities and specificities, positive LR and negative LR calculated using a bivariate random effects model Figure 2. Forest plots showing validation studies of the Centor score Centor Score 0-1 Centor Score 2-3 Centor Score 4 Table 3. Validation of the Centor Score for predicting GABHS pharyngitis Figure 1. Summary ROC Curves for signs and symptoms. AUC =0.670 AUC =0.674 AUC =0.673 AUC =0.734 Figure 1 shows ROC-curves for each sign and symptom. The curves are close together, suggesting the ability of any individual sign or symptom to discriminate GABHS from non GABHS patients is similar. ‘Any exudates’ has the highest accuracy. The symbols around the ROC-curves indicate individual studies and visually demonstrates the high level of heterogeneity. No sign or symptom on its own was powerful enough to rule in or out a diagnosis of GABHS.