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Comparison of Clinical Symptoms in Children Later Determined to be Group A Streptococcal Carriers or Acutely InfectedAnne-Marie Rick, MD, MPH; Haniah A. Zaheer and Judith M. Martin, MD

UPMC Children’s Hospital of Pittsburgh and the University of Pittsburgh School of Medicine

Background

References

• 11 million throat infections are attributed to Group A Streptococcus (GAS) annually1,2

• Antibiotics for GAS reduce symptom duration and rheumatic fever risk1

• ~20-25% of symptomatic children are GAS carriers for whom antibiotics may not be necessary1,2

• Rapid streptococcal antigen test (RST) and culture cannot distinguish GAS acute infection from carrier state1,3

Objective

Conclusions

To determine if presence of upper respiratory symptoms and absence of other symptoms at time of throat culture can distinguish acute infection from carrier state.

• We examined findings from two longitudinal studies of children 5 to 15 years of age with throat cultures for the detection of GAS and symptom data. • Cohort 1: surveillance study3

• Non-selective testing at regular intervals and with respiratory illness as identified or requested by parent/child

• Cohort 2: acute illness study• Selective testing as determined by clinician based on

clinical symptoms and signs with longitudinal follow-up

• Illness throat culture inclusion criteria: • GAS positive AND:

• ≥ 1 symptom endorsed• 2 follow-up cultures performed between 7-21 and 22-35

days after 1st culture

• Illness throat culture exclusion criteria:• GAS negative• GAS positive but:

• no symptoms• culture already included as follow-up• < 2 follow-up cultures within time window• 2 follow-up cultures with discordant results (+/- or -/+)

• Symptoms at time of 1st culture were compared using 2-sided Fisher’s exact statistics.

Results

Methods

• Selective testing (Cohort 2) for GAS based on illness symptoms and clinical judgement yielded identification of fewer carriers than non-selective testing (Cohort 1).

• Selective testing (Cohort 2) also identified associations between carriers and reported clinical symptoms including more abdominal pain and nasal congestion/rhinorrhea and less vomiting and lower severity score.

• Non-selective testing (Cohort 1) did not identify any symptoms associated with the carrier state compared to acute infection.

• Clinicians who follow IDSA guidelines for GAS pharyngitis testing may be able to use additional clinical symptoms to help interpret a positive result to distinguish acute infection from carrier status.4

Discussion

Limitations• Missing symptom data may reduce ability to see

associations between symptoms and acute versus carrier state.

• Differences in study design and data collection for Cohort 1 & 2 limit ability to combine datasets, thus reducing ability to see significant associations.

• As there is no "gold standard" definition for acute infection versus carrier status, our definition could lead to some misclassification or exclusion of positive cultures which may limit our ability to identify significant symptoms.

Table 2: Cohort 1 demographic characteristics of included participants.

Table 5. Cohort 2 symptom characteristics for included participants compared by acute infection versus carrier status using Fisher’s exact tests

Table 3. Cohort 1 symptom characteristics for included participants compared by acute infection versus carrier status using Fisher’s exact tests.

Symptomatic patients who were GAS positive on selective testing and later identified as carriers were more likely to present with symptoms of nasal congestion/rhinorrhea and abdominal pain than patients identified as acutely infected.

Case Definition: 1st Culture 2nd Culture 3rd CultureAcute Infection Positive &

³ 1 SymptomNegative Negative

Carrier State Positive Positive

Table 1: Case definition of acute infection and carrier state for both cohorts.

Figure 1. Schematic of culture accrual and study inclusion for Cohorts 1 & 2.

Characteristics Acute Infection Carrier StateN (%) N=96 N (%) N=26

Age (yrs) mean [range] 9.2 [5.2-15.4] 8.9 [5.9-13.8] Gender:

MaleFemale

51 (53.1)

45 (46.9)

12 (46.2)

14 (53.9)Race:

CaucasianAfrican AmericanOther

71 (74.0)7 (7.3)

18 (18.7)

19 (73.1)3 (11.5)4 (15.4)

Figure 3: Cohort 2 flow diagram throat cultures.

Table 4: Cohort 2 demographic characteristics of included participants.

Characteristics Acute Infection Carrier StateN (%) N=94 N (%) N=12

Age (yrs) mean [range] 8.5 [5-15] 8.5 [5-15] Gender:

Male

Female

42 (44.5)52 (55.3)

6 (50.0)6 (50.0)

Race:

Caucasian

African American

Other

84 (89.4)

6 (6.4)

4 (4.3)

9 (75.0)

1 (8.3)

2 (16.7)

Figure 2: Cohort 1 flow diagram of throat cultures.

Symptom Characteristics Acute Infectionn/N (%)

Carriern/N (%)

1-sidedFisher’s Exact

Sore Throat: YesNo

79/94 (84.0)15/94 (16.0)

10/12 (83.3)2/12 (16.7)

0.610

Evidence of Pharyngitis: YesNo

82/94 (87.2)12/94 (12.8)

11/11 (100.0)0/11 (0.0)

0.245

Fever: YesNo

40/92 (43.5)52/92 (56.5)

7/11 (63.6)4/11 (36.4)

0.172

Headache: YesNo

40/90 (44.4)50/90 (55.6)

8/11 (72.7)3/11 (27.3)

0.072

Abdominal Pain: YesNo

27/94 (28.7)67/94 (71.3)

7/11 (63.6)4/11 (36.4)

0.026*

Vomiting: YesNo

79/94 (84.0)15/94 (16.0)

5/11 (45.5)6/11 (54.5)

0.033*

Activity Decreased: YesNo

59/94 (62.8)35/94 (37.2)

8/10 (80.0)2/10 (20.0)

0.237

Cough: YesNo

19/78 (24.4)59/78 (75.6)

4/9 (44.4)5/9 (55.6)

0.183

Congestion/Rhinorrhea: YesNo

11/77 (14.3)66/77 (85.7)

4/9 (44.4)5/9 (55.6)

0.046*

Any URI Symptom: None≥1

23/94 (24.5)71/94 (75.5)

5/12 (41.7)7/12 (58.3)

0.176

Symptom Duration: £72 hours>72 hours

81/92 (88.0)11/92 (12.0)

11/11 (100.0)0/11 (0.0)

0.269

Severity Score: £ 5> 5

62/94 (66.0)32/94 (34.0)

3/11 (27.3)8/11 (72.7)

0.016*

*Indicates significance with alpha <0.05

Symptom Characteristics Acute Infectionn/N (%)

Carriern/N (%)

1-sided Fisher’s

ExactSore Throat: Yes

No57/73 (78.1)16/73 (21.9)

14/20 (70.0)6/20 (30.0)

0.316

Evidence of Pharyngitis: YesNo

14/73 (19.2)59/73 (80.8)

16/20 (80.0)4/20 (20.0)

0.579

Fever: YesNo

27/69 (39.1)42/69 (60.9)

3/17 (17.7)14/17 (82.3)

0.080

Headache: YesNo

21/68 (30.9)47/68 (69.1)

3/17 (17.7)14/17 (82.4)

0.221

Abdominal Pain: YesNo

18/68 (26.5)50/68 (73.5)

3/17 (17.7)14/17 (82.4)

0.341

Vomiting: YesNo

5/64 (7.8)59/64 (92.2)

2/13 (15.4)11/13 (15.4)

0.336

Activity Decreased: YesNo

31/60 (51.7)29/60 (48.3)

4/13 (30.8)9/13 (69.2)

0.144

Cough: YesNo

20/63 (31.8)43/63 (68.2)

9/20 (45.0)11/20 (55.0)

0.207

Congestion/Rhinorrhea: YesNo

39/65 (60.0)26/65 (40.0)

12/21 (57.1)9/21 (42.9)

0.506

Any URI Symptom: None≥1

23/87 (35.4)42/87 (64.6)

7/21 (33.3)14/21 (66.7)

0.542

Symptom Duration: £72 hours>72 hours

27/53(50.9)26/53 (49.1)

6/10 (60.0)4/10 (40.0)

0.430

Severity Score: £ 5> 5

43/54 (79.6)11/54 (20.4)

9/11 (81.8)2/11 (18.2)

0.618

1. Martin JM. Pharyngitis and streptococcal throat infections. Pediatr Ann. 2010;39:22-27.2. Pichichero ME, Green JL, Francis AB, et al. Recurrent group A streptococcal tonsillopharyngitis. The Pediatric infectious disease journal. 1998;17:809-815.3. Martin JM, Green M, Barbadora KA, Wald ER. Group A streptococci among school-aged children: clinical characteristics and the carrier state. Pediatrics. 2004;114:1212-1219.4. Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis. 2012;55:1279-1282.

ContactEmail: Annemarie.rick@chp.edu; Judith.martin@chp.edu