Transcript Group A Streptococcal Pharyngitis (GRASP) Study

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
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.
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.
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
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.
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.
Table (1): Selected Clinical Prediction Rules for
GABHS Pharyngitis in Children
% Culture
Positive
670 54.0
>26
>30
>32
Sen*
(%)
98.0
83.0
68.0
Spec**
(%)
40.0
72.0
85.0
PPV
(%)
66.0
78.0
84.0
NPV
(%)
94.0
78.0
69.0
2+
97.0
12.0
38.0
87.0
3+
4+
3+
4+
5+
6+
84.0
63.0
98.0
92.0
64.0
22.0
38.0
67.0
7.0
28.0
65.0
93.0
43.0
51.0
51.0
55.0
64.0
75.0
81.0
76.0
76.0
77.0
65.0
55.0
Author
Country N
Score
Breese
USA
McIsaac et
Canada 90
al.
36.0
Wald et al.
USA
365 48.0
Steinhoff
et al.
Egypt
451 24.0
rule
84.0
40.0
30.0
89.0
94.0
38.0
95.0
15.0
77.0
297 29.0
WHO 12.0
high
low
Attia et al.
USA
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.
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
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.
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..
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.
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 χ2 statistic was calculated to assess whether
or not signs and symptoms were significantly associated
with GABHS pharyngitis
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..
Results
Table (2): Patient Characteristics for Egypt
Site Characteristic
Number of children (N)
Sex (% Male)
Age above 5 years *
Mean Age (years)*
GABHS Rapid Test (%+)*
Egypt
1638
57.7%
45.8%
4.8
24.7%
Table (3): Patient Characteristics and Association with
GABHS Pharyngitis
Site Characteristic
Egypt (n = 1638 )
GABHS - GABHS + P-value Ratio
Sex (Male)
73.9%
26.1%
0.750
Sex (Female)
73.2%
26.8%
Age Above 5 years* 43.3%
52.7%
0.001
Mean Age (years)* 4.7
5.2
0.000
Table (4): Clinical Presentation of Pharyngitis (Signs
and Symptoms) Egypt.
Egypt
Symptom
Fever
Chills *
No rung Nose *
Nasal congestion
Sore throat
Difficulty / pain swallowing*
No cough*
Vomiting
Earache
Abdominal Pain
Activity below normal *
Disturbed sleep
Hoarseness
% with
symptom
GABHS
– ve
(n = 1205)
GABHS
+ ve
(n = 432)
Pvalue
OR
83.0
34.1
46.9
33.5
85.1
78.3
82.6
32.7
43.6
33.2
84.1
76.8
84.0
38.2
56.3
34.3
88.0
82.4
0.490
0.039
0.000
0.688
0.05
0.02
1.1
1.3
1.4
1.1
1.4
1.4
33.0
22.5
9.5
36.2
48.1
35.7
24.0
30.2
22.2
9.6
36.2
46.1
34.8
22.4
40.7
23.4
9.0
36.1
53.7
38.2
24.8
0.000
0.627
0.715
0.979
0.007
0.207
0.306
1.6
1.1
0.932
0.997
1.4
1.6
1.1
Egypt
Signs
No Cough *
Hoarseness
Fever
Pharyngeal Erythema
Tonsillar Erythema
Erythema posterior *
Faucial Erythema *
+ 1 Tonsillar enlargement
+ 2 Tonsillar enlargement
+ 3 Tonsillar enlargement
Tonsillar exudates *
Tender Cervical lymph node *
Enlarged lymph node
Nares exoriations
Pharyngeal exudates
Palatal petecliac sign
Strawberry tongue
Diarrhea
Demographic characteristics
Male
Above 3 years *
% with
symptom
GABHS
– ve
(n = 1205)
GABHS
+ ve
(n = 432)
Pvalue
OR
71.0
7.3
48.5
95.1
89.1
82.3
81.6
68.9
6.9
48.2
94.6
88.3
81.1
79.5
76.6
8.6
51.0
96.5
91.2
85.6
87.3
0.003
0.251
0.306
0.112
0.097
0.033
0.000
1.5
1.3
1.1
1.6
1.4
1.4
1.8
22.1
44.8
26.0
14.3
18.1
20.3
12.3
11.5
0.6
1.5
4.2
23.2
46.2
23.7
12.3
16.5
19.3
12.6
11.0
0.5
1.3
4.2
19.0
40.7
32.4
19.9
22.5
23.4
11.6
13.2
0.9
2.1
3.9
0.07
0.05
0.000
0.000
0.006
0.068
0.573
0.211
0.327
0.270
0.791
0.8
0.8
1.5
1.8
1.5
1.4
0.907
1.2
1.9
1.6
0.9
57.7
65.4
57.9
62.4
57.0
73.5
0750
0.000
1.0
1.7
Table (5): The performance of Individual Predictors for
a Positive Diagnosis of GABHS Pharyngitis in Egypt
EGYPT
Sensitivity Specificity PPR NPR LR+ LRNo Runny Nose
56.3
56.4
31.6 78.3 1.3 0.7
Activity below normal
53.7
53.9
29.4 76.4 1.2 0.9
Faucial erythema
87.3
20.5
28.2 81.8 1.1 0.6
+ 3 & more tonsillar
32.4
76.3
32.9 75.9 1.4 0.9
enlargement
Age above 3y.
73.7
79.9
29.8 37.6 3.7 0.3
Table (6): Clinical Prediction Model Egypt
OR
(95 % C.I)
1.7
No runny Nose
(1.3-2.1)
1.4
Activity below normal
(1.1-1.7)
1.8
Faucial erythema
(1.3-2.4)
1.5
+ 3 & more tonsillar enlargement
(1.2-2.0)
1.7
Age above 3y.
(1.3-2.2)
Clinical feature
B
0.43
0.33
0.55
0.36
0.44
Exp. (B)
(95% C.I)
1.49
(1.16-9.90)
0.72
(0.58-0.91)
0.58
(0.42-0.80)
0.70
(0.55-0.90)
0.6
(0.50-0.82
Table (7): Predictive Value of clinical prediction Rules
at Varying Treatment Cut off Score
Egypt
& No Runny Nose, Activity Below Normal, Faucial Erythema, +3(
and More Tonsillar Enlargement, Age Above 3)
Cut off score
1
2
3
4
5
Sensitivity
92.8
82.2
47.6
26.3
9.2
Specificity
11.6
25.7
60.1
81.5
93.4
PPR
27.4
28.5
30.0
33.8
33.6
NPR
81.9
80.1
76.1
75.5
74.1
LR+
1.1
1.1
1.2
1.4
1.4
LR0.6
0.7
0.9
0.9
0.9
List of Participants in the Study
Cairo University
- Dr. Hadeer Mahmoud
- Dr. Naglaa Abdel Rahman
- Dr. Nivin El Menawy
- Dr. Hussam Galal
- Dr. Soha Emam
- Dr Sanaa Youssef
- Dr. Inas El Eleimy
- Dr. Aya Ahmed
- Dr. Hala Hamza
- Dr.Sanaa El Awady
- Dr.Hend EL Sherbiny
- Dr.Mona El Lawendy
Johns Hopkins University
- Dr. Mark Steinhoff
- Mrs. Ann Rimoin
WHO
-Dr.Shamim Qazi
Center for Social and Preventive
Medicine , Cairo University
Thank you