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Keywords:

  • Group C streptococcus;
  • group G streptococcus;
  • pharyngitis;
  • streptococcal infections;
  • paediatrics

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Group C streptococci (GCS) and group G β-haemolytic streptococci (GGS) have caused well-documented epidemics of acute pharyngitis in children, but the importance of these organisms in causing endemic or sporadic pharyngitis is uncertain. The heterogeneity of GCS and GGS may obscure the role of certain subtypes, such as the large-colony-forming strains of group C (Streptococcus dysgalactiae subsp. equisimilis) or group G, in endemic pharyngitis. For a 1-year period, children (aged 6 months to 18 years) (n = 2085) who presented with pharyngitis to the children's hospital emergency department and two outpatient offices were enrolled in a cross-sectional study to ascertain the role of large-colony-forming GCS and GGS in acute pharyngitis. Control patients (n = 194) were children who presented to the same locations during the same time period with non-respiratory tract symptoms or to the orthopaedic cast clinic. Throat cultures were obtained by a standard reference method, and swabs were plated on Strep-Selective Agar. Lancefield grouping and species identification was performed on all β-haemolytic isolates. In total, 65 (3%) large-colony-forming GCS and GGS strains were obtained from pharyngitis patients, and three (1.5%) were obtained from the control group (odds ratio 2.0; 95% confidence interval 0.6–6.1). The low isolation rate of large-colony-forming strains of GCS and GGS indicates that even if these organisms are associated with acute, sporadic pharyngitis in paediatric patients, they represent an unusual pathogen.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Non-group A β-haemolytic streptococci, particularly Lancefield groups C (GCS) and G (GGS), have been implicated as causes of acute pharyngitis in children [1–7] and adults [8–11]. These organisms have caused well-documented epidemic, often food-borne, outbreaks of pharyngitis [2–7]. The importance of these organisms in causing acute, sporadic pharyngitis is uncertain.

In addition to being classified by Lancefield group carbohydrate, the β-haemolytic streptococci are distinguished morphologically as being large-colony or small-colony formers on sheep blood agar [8,12,13]. The large-colony-forming phenotypes of group A and group B β-haemolytic streptococci are the pathogenic species Streptococcus pyogenes and Streptococcus agalactiae. Large-colony-forming phenotypes of GCS (Streptococcus dysgalactiae subsp. equisimilis) and GGS are closely related and are often termed ‘pyogenes-like’, because they share virulence factors, including haemolysins, extracellular enzymes, and M-proteins, with group A streptococci (S. pyogenes) [12,14–16]. Small-colony-forming phenotypes, regardless of Lancefield group carbohydrate, are placed in the Streptococcus anginosus group (formerly known as Streptococcus milleri), and are not believed to be significant causes of pharyngitis, but are infrequent causes of abscess formation and bacteraemia [6,8,17,18].

A limited number of studies in children have suggested that large-colony-forming species of GCS and GGS may have a role in acute, sporadic pharyngitis in children [17]. A cross-sectional study was therefore performed to further investigate this possible role.

Materials and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

A prospective study of children (6 months to 18 years of age) who presented with pharyngitis, based on symptoms and clinical findings, was conducted. Patients from the emergency department of the Alfred I. duPont Hospital for Children and two outpatient paediatric offices in Delaware, affiliated with the hospital, were surveyed for a 1-year period from 1 April 1999. Control patients were children who presented during the same time period with non-respiratory tract symptoms (e.g., lacerations and musculoskeletal injuries) at the same locations, in addition to the orthopaedic cast clinic at the Alfred I. duPont Hospital for Children. Children with a history of recent antibiotic use within 5 days of presentation were excluded. Subjects were only enrolled in the study once.

Emergency department physicians were instructed to swab the posterior oropharyngeal wall and the tonsils bilaterally with a sterile rayon-tipped cotton swab. This technique was standardised by the use of an illustration of the anatomical area on the data-collection form provided for each patient at the time of enrolment. After collection, the transport medium of the culturette was activated, and the specimen was transported to the hospital laboratory, where each swab was plated on two Strep-Selective Agar media plates (Remel Inc., Lenexa, KS, USA). Plates were incubated anaerobically at 35 °C to optimise recovery of β-haemolytic colonies, and examined after 24 and 48 h. β-Haemolytic isolates were subcultured on fresh sheep blood agar plates. Lancefield grouping was performed with the PathoDx agglutination kit (Remel Inc.). Streptococcal isolates were identified with the API 20S Strep Strip (bioMerieux Vitek, Hazelwood, MO, USA).

Informed consent was obtained before enrolment of all control patients. Consent was not obtained for case patients, because throat swabs formed part of standard care and the results of this study would not affect treatment. Approval of the study was obtained prior to initiation from the Committee on Human Subjects of the Alfred I. duPont Hospital for Children.

Rates of isolation of β-haemolytic streptococci were calculated for both the pharyngitis patients and the controls. The odds ratio and 95% confidence interval of the association between pharyngitis and isolation of large-colony-forming group C and G streptococci were calculated. Data were analysed using the SAS statistical system (SAS Institute, Cary, NC, USA) and STATA 6.0 (StataCorp College Station, TX, USA).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Patients with pharyngitis (n = 2085) and 194 controls were enrolled. The median age of patients was 6.0 years (interquartile range: 3–9 years), and that of controls was 10.0 years (interquartile range: 6–13 years). The patients were younger than the controls (p < 0.001). Among the patients, there were 991 (48%) males, while 102 (53%) of the controls were males (p > 0.5). The controls were more likely to be enrolled from a hospital site than were the patients (90% vs. 49%, p < 0.001).

Overall, the isolation rates of all non-group A β-haemolytic streptococci were 17.7% (370/2085) from study patients and 9.8% (19/194) from controls. Table 1 shows that large-colony-forming GCS and GGS phenotypes were detected at a low rate (3%) in pharyngitis patients, but this was twice the rate seen in the controls (Table 1). However, this difference was not statistically significant. Group A β-haemolytic streptococci were isolated from 455 (21.8%) of the study patients and from 29 (14.9%) of the controls (p = 0.03).

Table 1.  Association between isolation of group C and group G streptococci and pharyngitis
Identification Patients (n=2085) Controls (n=194)Odds ratio (95% confidence interval)
  • a

    p = 0.03.

  • GCS, group C streptococci; GGS, group G streptococci.

Large-colony GCS (S. dysgalactiae subsp. equisimilis) and GGS 65 (3.1%) 3 (1.5%)2.0 (0.6–6.1)
 Group C 33 (1.6%) 1 (0.5%)3.1 (0.5–126)
 Group G 32 (1.5%) 2 (1.0%)1.5 (0.4–13.0)
Small-colony GCS and GGS101 (4.8%) 9 (4.6%)1.0 (0.5–2.1)
Group A β-haemolytic streptococci455 (21.8%)29 (14.9%)1.6 (1.1–2.5)a

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

A low prevalence of large-colony-forming GCS and GGS was demonstrated in a large cohort of children who presented with acute pharyngitis. The study was performed over the course of 1 year to reduce the possible effects of seasonal variation in the prevalence of GCS and GGS, and patients from different ambulatory settings were evaluated. The observed odds ratio of 2.0 suggests that these organisms may be causative of this disease; however, the 95% confidence interval crosses unity, and therefore definite conclusions cannot be drawn. Nevertheless, the rate of isolation of these organisms in this setting is low (3%), and therefore, even if they cause sporadic pharyngitis, GCS and GGS would represent an uncommon cause in the population of children studied.

The importance of GCS and GGS as causes of sporadic pharyngitis in children is controversial. Turner et al.[13] reported that patients from whom large-colony-forming (S. equisimilis) group C organisms were isolated had more clinical features of group A streptococcal infection than did patients from whom small-colony-forming (S. anginosus) organisms were isolated. Cimolai et al.[17] showed a non-statistically significant association between large-colony-forming GCS and GGS in children with pharyngitis when compared to controls, consistent with the findings of the present study. The difference became significant when the comparison was limited to moderate or heavy growth of these streptococci as determined by semiquantitative culture methods. This distinction was not made in the present assessment of the cultures. Several other studies that did not distinguish between large-colony-forming and small-colony-forming species found no increased association between GCS and GGS and pharyngitis [17,19,20]. These studies may have missed the association by including both small-colony-forming (non-pathogenic) and large-colony-forming (pathogenic) GCS and GGS in the analysis.

Even if this association is true, its clinical significance is unclear, since cases of rheumatic fever after pharyngitis with GCS and GGS have not been reported. Interestingly, however, investigators in Australia recently reported a high carriage rate of GCS and GGS in an Aboriginal population that had a high rate of rheumatic fever but a low incidence of group A streptococcal disease. It was demonstrated in vitro that GCS and GGS have the potential to elicit an autoimmune response that may trigger acute rheumatic fever. This relationship needs to be further explored in Aboriginal and other populations, since rigorous studies on preceding GCS and GGS infections in patients with rheumatic fever have not been performed [21]. If such an association were found, the clinical significance of the low rate of large-colony-forming GCS and GGS that was observed in the current study would need to be re-evaluated.

The prevalence of group A disease in the patients in the present study was similar to that reported in previous studies of children with pharyngitis [3,15,16]. This suggests that the results may be extrapolated to similar paediatric patients at other institutions or paediatric practices.

There are several limitations of the present study. First, although the survey involved the largest series of pharyngitis cases cultured for large-colony-forming GCS and GGS to date, the wide odds ratio confidence intervals suggest that this study had limited power to find an association. Furthermore, the low rate of colonisation did not control for potential confounding factors in the analysis, such as age and location, both of which were different between cases and controls. It is plausible that age was a potential confounder, because there are suggestions in the literature that the isolation rates of GCS and GGS may be even higher in older children and adolescents [11]. With respect to location, the outpatient offices used in the study are hospital-affiliated practices and serve the same population as the emergency department, and therefore any differences between cases and controls are unlikely to alter the study findings.

Second, since the disease was already present at the time of culture, it cannot be determined if the GCS and GGS presence in the pharynx even preceded the pharyngitis. However, there is no reason to believe that subjects with pharyngitis would be at increased risk of colonisation with streptococci, and therefore the limitations of the cross-sectional study design are minimised in this setting.

Third, patient outcomes were not followed to determine if controls with large-colony-forming GCS and GGS developed pharyngitis. Prospective studies of this sort would provide stronger evidence of association and would provide attack rates when these organisms are present. However, the low rate of colonisation and the low point estimate of the association (i.e., an odds ratio of 2.0) suggest that a very large cohort study design would be required to confirm an association.

In summary, in this largest series to date, there was a low rate of isolation of large-colony-forming species of GCS and GGS from paediatric patients with acute, sporadic pharyngitis.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

This study was funded by grant number W20-8625 from the Nemours Research Programs of The Nemours Foundation, Wilmington, DE and performed at the Alfred I. duPont Hospital for Children, PO Box 269, Wilmington, DE, USA. We thank Paige Walsh and the Clinical Laboratory Microbiology Section for their assistance, Michelle Stofa for her editorial assistance, and the residents and staff members of the Division of Emergency Services of the Alfred I. duPont Hospital for Children for their support. We thank Dr Louis M. Bell and Dr Samir Shah for their critical reviews of the manuscript.

This work was presented in part at the 39th Annual Meeting of the Infectious Diseases Society of America, September 2000, New Orleans, LA.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References
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