To the Editor—A new emm-cluster typing system has been recently proposed for group A Streptococcus (GAS) [1]. This system classifies most of the 223 emm types [2] into 48 functional emm clusters containing closely related M proteins that share structural properties. emm clusters help to predict the virulence potential of any GAS isolate by ascribing M protein binding attributes to emm types belonging to the same emm cluster [1, 3]. This system correlates with M protein vaccine antigen content and serves as a framework to investigate immunologic cross-protection between emm types [1, 4, 5]. emm clusters have been used to analyze the epidemiology of GAS in the Pacific region, which is characterized by high GAS disease burden and a great variety of circulating emm types [6, 7]. The emm-cluster system identified epidemiologic similarities across the Pacific region and highlighted vaccine target priorities [8].
We applied the emm-cluster system to GAS epidemiology in a high-income setting by analyzing prospective surveillance data for GAS pharyngitis in North America, 2000–2007 [9]. A total of 56 and 33 different emm types were recovered from 7040 US and 1434 Canadian GAS isolates, respectively. In contrast with the Pacific region, the 15 most prevalent emm types accounted for 97.1% and 96.9% of GAS pharyngeal isolates, respectively, indicating that only a relative minority of emm types are responsible for most pharyngitis in North America.
By deducing the emm-cluster allocation from the emm-typing results [1], we observed that the 56 US emm types belonged to 18 emm clusters (Table 1), whereas the 33 Canadian emm types belonged to 14 emm clusters (data not shown). Eleven emm clusters were responsible for the majority of cases in both countries (99.6% and 98.7%, respectively) (Table 1). emm types 1 and 12 were the 2 most common emm types in the United States (17.8% and 17.6%, respectively) [9], but did not belong to the most common emm cluster; rather, emm cluster E4 (notably including the frequent emm types 2, 22, 28, 77, and 89) was more common (27.2%). Furthermore, we observed that 8 of the 56 emm types belonged to emm cluster D4, although representing only a small number of isolates (17 of 7040), a surprising result given that emm cluster D4 is associated with skin rather than pharyngeal infections [1]. Finally, emm cluster E2, which includes 15 emm types, was nearly completely absent from North America (0.2%–0.5% of isolates), whereas it was the most frequent emm cluster in New Caledonia (21% of isolates), suggesting that some emm clusters are restricted to defined geographical areas.
Table 1.
Frequencies of emm Types and emm Clusters Among 7040 Group A Streptococcus Isolates Recovered From Pharyngitis in the United States
| emm Type | emm Cluster | No. | % of Isolates |
|
|---|---|---|---|---|
| All Isolates | 15 Most Frequent emm Types | |||
| 2, 8, 22, 28, 73, 77, 89, 102, 114 | E4a | 1912 | 27.16 | 26.68 |
| 1, 163 | A-C3a | 1252 | 17.78 | 17.76 |
| 12 | A-C4a | 1236 | 17.56 | 17.56 |
| 4, 60, 78 | E1a | 696 | 9.89 | 9.62 |
| 3 | A-C5a | 614 | 8.72 | 8.72 |
| 11, 48, 63, 75, 94, 177 | E6a | 429 | 6.09 | 5.87 |
| 6 | M6a | 393 | 5.58 | 5.58 |
| 9, 44, 49, 58, 82, 87, 103, 118, 219 | E3a | 350 | 4.97 | 3.85 |
| 5 | M5a | 106 | 1.51 | 1.51 |
| 33, 41, 43, 53, 70, 83, 101, 119 | D4 | 17 | 0.24 | |
| 18 | M18a | 14 | 0.20 | |
| 62, 68, 76, 92, 96, 110, 117 | E2a | 12 | 0.17 | |
| 170, 205 | E5 | 4 | 0.06 | |
| 14 | M14 | 1 | 0.01 | |
| 57 | M57 | 1 | 0.01 | |
| 74 | M74 | 1 | 0.01 | |
| 234 | M234 | 1 | 0.01 | |
| 236 | M236 | 1 | 0.01 | |
| 7040 | 100.00 | 97.15 | ||
The emm-type data originate from a previous study [9]. The 15 most frequent emm types are underlined.
a Stands for the emm cluster in common with the Canadian collection (1434 isolates).
As shown here, and in the study in New Caledonia, application of the emm-cluster system to both tropical and nontropical settings improves our understanding of complex GAS epidemiology. This new system helps to refine clinically meaningful questions such as tissue tropism and the immune response to GAS infections in all settings worldwide.
Note
Potential conflicts of interest. All authors: No potential conflicts of interest.
All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
References
- 1.Sanderson-Smith M, De Oliveira DM, Guglielmini J, et al. A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development. J Infect Dis. 2014 doi: 10.1093/infdis/jiu260. doi:10.1093/infdis/jiu260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.McMillan DJ, Dreze PA, Vu T, et al. Updated model of group A Streptococcus M proteins based on a comprehensive worldwide study. Clin Microbiol Infect. 2013;19:E222–9. doi: 10.1111/1469-0691.12134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Smeesters PR, McMillan DJ, Sriprakash KS. The streptococcal M protein: a highly versatile molecule. Trends Microbiol. 2010;18:275–82. doi: 10.1016/j.tim.2010.02.007. [DOI] [PubMed] [Google Scholar]
- 4.Smeesters PR, Mardulyn P, Vergison A, Leplae R, Van Melderen L. Genetic diversity of group A Streptococcus M protein: implications for typing and vaccine development. Vaccine. 2008;26:5835–42. doi: 10.1016/j.vaccine.2008.08.037. [DOI] [PubMed] [Google Scholar]
- 5.Smeesters PR, Dramaix M, Van Melderen L. The emm-type diversity does not always reflect the M protein genetic diversity—is there a case for designer vaccine against GAS. Vaccine. 2010;28:883–5. doi: 10.1016/j.vaccine.2009.10.137. [DOI] [PubMed] [Google Scholar]
- 6.Steer AC, Law I, Matatolu L, Beall BW, Carapetis JR. Global emm type distribution of group A streptococci: systematic review and implications for vaccine development. Lancet Infect Dis. 2009;9:611–6. doi: 10.1016/S1473-3099(09)70178-1. [DOI] [PubMed] [Google Scholar]
- 7.Smeesters PR, McMillan DJ, Sriprakash KS, Georgousakis MM. Differences among group A streptococcus epidemiological landscapes: consequences for M protein-based vaccines? Expert Rev Vaccines. 2009;8:1705–20. doi: 10.1586/erv.09.133. [DOI] [PubMed] [Google Scholar]
- 8.Baroux N, D'Ortenzio E, Amedeo N, et al. The emm-cluster typing system for group A Streptococcus identifies epidemiologic similarities across the Pacific region. Clin Infect Dis. 2014;59:e84–92. doi: 10.1093/cid/ciu490. [DOI] [PubMed] [Google Scholar]
- 9.Shulman ST, Tanz RR, Dale JB, et al. Seven-year surveillance of North American pediatric group A streptococcal pharyngitis isolates. Clin Infect Dis. 2009;49:78–84. doi: 10.1086/599344. [DOI] [PubMed] [Google Scholar]