1. Group A Streptococcal Pharyngitis (GRASP) Study Egypt Cairo University Pediatric Department & Johns Hopkins University, Pediatric and International health Departments, WHO By Hala Hamza Professor of Pediatrics Cairo University

2. Group A Streptococcal Pharyngitis (GRASP) Study Introduction :  Pharyngitis or 'sore throat' is a common ailment the world over, and is especially common in children.  There are a number of different agents, both viral and bacterial that can cause pharyngitis.  About 10.0 – 30.0% of acute pharyngitis in children is caused by GABHS; viral infection accounts for the majority of the others.

3. Group A Streptococcal Pharyngitis (GRASP) Study  Pharyngitis due to group A beta hemolytic streptococcus (GABHS) assumes a special significance because of the risk of subsequent rheumatic fever (RF) and chronic rheumatic heart disease (RHD) in the infected child.  About 0.3 – 3.0% of patients of untreated GABHS pharyngitis go on to develop RF.  Carditis occurs in about 70.0% of children with RF and about a fourth of these go on to develop chronic RHD.  The incidence of RF in low and middle-income countries is approximately 5 per 100,000 per year.

4. Rheumatic fever and Rheumatic heart disease  The prevalence of RHD ranges from 1.0 to 10 per 1000 and the incidence from 10 to 100 per 100,000 per year. The estimated excess mortality rate due to RHD in these countries is 1.0 to 2.0 % per year. Thus about 12 million people are affected by RHD/RF, resulting in about 40,000 deaths annually

5. GABHS pharyngitis and non-GABHS pharyngitis  Signs and symptoms overlap broadly.  A laboratory test should be performed to determine whether group A streptococci are present in the throat.  In low and middle income countries, because bacteriological culture facilities are not readily available and cost can be prohibitive to patients, physicians often make a clinical diagnosis and offer presumptive treatment.

6. Rationale Of GRASP  In these settings, clinical prediction instruments that allow physicians to make rationale decisions on diagnosis and treatment course would be very useful.  Individual signs and symptoms have not been found to be accurate enough to make a diagnosis alone, therefore, clinical prediction rules have been developed that use several key elements of patient history and physical examination to predict the probability of GABHS pharyngitis.

7. Table (1): Selected Clinical Prediction Rules for GABHS Pharyngitis in Children

8. Clinical Prediction Rule for Streptococcal Pharyngitis  provides the clinician with a rational basis for assigning a patient to a low risk category, which requires neither testing nor treatment; a high risk category in which empiric treatment may be indicated; or in some cases, a moderate risk category which may require further diagnostic testing, if available.  The World Health Organization Acute Respiratory Infections (ARI) treatment program suggests that, in the absence of laboratory diagnosis for children under five years of age, acute streptococcal pharyngitis should be suspected and presumptively treated when pharyngeal exudate plus enlarged and tender cervical lymph nodes are found.

9. WHO Recommendations  When Steinhoff et al. evaluated these recommendations in a prospective study; the guidelines were shown to be highly specific, but with low sensitivity.  451 children 2- 13 years of age in an urban pediatric clinic in Egypt were studied. The clinical features most highly associated with positive throat culture were pharyngeal exudate and enlarged anterior cervical lymph nodes. Presence of one or both of these signs had a high sensitivity of 0.84 but a low specificity of 0.40

10. Aim Of The Study  Since it is not desirable to treat all pharyngitis cases with antibiotics and laboratory facilities for culture and serology are not generally available in low and middle income country settings, it would be useful to have guidelines that are created specifically for clinical identification of GABHS pharyngitis in these regions.  We therefore undertook this study to formulate a new clinical prediction rule that would have improved sensitivity yet retain adequate specificity and applicability in multiple country settings.

11. Methods Of The Study Study Population  From August 2001 until April 2003, 1638 children presenting with respiratory symptoms of cough, cold, red or sore throat were enrolled at the outpatient clinic of Cairo University Pediatric Hospital in Egypt.  Exclusion criteria: - oral antibiotic use within the 3 days prior or intramuscularly administered antibiotics within the 28 days prior to the clinic visit - history of previous rheumatic fever or rheumatic heart disease. - presence of another illness requiring hospitalization..

12. Methods Of The Study  After enrollment, demographic information was recorded and a physical examination was performed. Data was collected on specific signs and symptoms associated with pharyngitis using standard definitions.  We used a simple to use commercial rapid antigen test for diagnosis of GABHS pharyngitis (Strep Max OIA Test; Biostar, Denver CO). The rapid antigen test was performed by the physician conducting the physical examination for each child and results were recorded in a standard format.

13. Statistical Methods  Children participating in the study were categorized as having acute GAHBS pharyngitis or nonspecific pharyngitis based on rapid antigen test results  The sensitivity, specificity and positive predictive value of each sign and symptom in predicting a diagnosis of GAHBS pharyngitis were calculated.  In addition, a χ 2 statistic was calculated to assess whether or not signs and symptoms were significantly associated with GABHS pharyngitis

14. Statistical Methods  Variables that were statistically significantly associated with GABHS pharyngitis were chosen for the next stage of analysis. Logistic regression was used to model the probability of GAHBS pharyngitis in terms of these variables.  Each selected sign or symptom was defined in such a way that it was a positive predictor of GAHBS pharyngitis (i.e. absence of cough instead of cough) and therefore had a positive coefficient in the regression model.  Next, backwards and forward stepwise regression techniques were used to create a subset of signs and symptoms that were independent predictors of GABHS pharyngitis (P < 0.05).  A score for GAHBS pharyngitis was then calculated from this subset using a simple count of signs and symptoms present for each child..

15. Results Table (2): Patient Characteristics for Egypt

16. Table (3): Patient Characteristics and Association with GABHS Pharyngitis

17. Table (4): Clinical Presentation of Pharyngitis (Signs and Symptoms) Egypt.

19. Table (5): The performance of Individual Predictors for a Positive Diagnosis of GABHS Pharyngitis in Egypt

20. Table (6): Clinical Prediction Model Egypt

21. Table (7): Predictive Value of clinical prediction Rules at Varying Treatment Cut off Score

22. List of Participants in the Study Cairo University - Dr. Hadeer Mahmoud - Dr.Sanaa El Awady - Dr. Naglaa Abdel Rahman - Dr.Hend EL Sherbiny - Dr. Nivin El Menawy - Dr.Mona El Lawendy - Dr. Hussam Galal Johns Hopkins University - Dr. Soha Emam - Dr. Mark Steinhoff - Dr Sanaa Youssef - Mrs. Ann Rimoin - Dr. Inas El Eleimy WHO - Dr. Aya Ahmed -Dr.Shamim Qazi - Dr. Hala Hamza

23. Center for Social and Preventive Medicine, Cairo University

27. Thank you