Figure 1

Figure 1. Incidence of scarlet fever in Gwangju, South Korea, 2008–2015. A) The number of cases per 100,000 persons in Gwangju and South Korea. B) Distribution of cases by month of each year....

The incidence of scarlet fever in the Gwangju metropolitan area is the highest among all South Korea cities (61.5 cases/100,000 persons); according to the Korean Disease Web Statistics System, the national incidence from 2008 through 2015 was 36.9 cases/100,000 persons (https://is.cdc.go.kr/dstat/index.jsp). Incidence of scarlet fever in South Korea began to increase in 2011 (Figure 1, panel A), coinciding with an outbreak of scarlet fever in China and Hong Kong. Scarlet fever mainly occurs during the late fall, winter, and early spring. Our study results indicate that the incidence of scarlet fever in South Korea peaks in the winter; however, it also peaked in the summers of 2011 and 2015 (Figure 1, panel B).

During 2008­–2015, we collected 1,460 pharyngeal swab samples from patients suspected of having scarlet fever from 8 major hospitals in the Gwangju metropolitan area. We tested the β-hemolytic isolates for susceptibility to bacitracin (0.04 U) and for streptococcal grouping; a total of 705 samples were positive for GAS.

Figure 2

Figure 2. emm type characterization of group A Streptococcus isolates from patients with scarlet fever, Gwangju, South Korea, 2008–2015. A) Annual fluctuations of emm types. Number of isolates by year: 7 in 2008,...

Because variation in the circulating emm types could contribute to the incidence of disease and changes in the epidemiology of scarlet fever, we determined the emm sequence type for the 705 samples by using a standard protocol (https://www.cdc.gov/streplab/protocol-emm-type.html) (2). A total of 11 different emm sequence types were identified (Figure 2, panels A and B). emm4 (35.6%, 251/705) was the most predominant. The other 3 predominant emm types were emm28 (14.8%, 104/705), emm1 (14.5%, 102/705), and emm3 (11.6%, 82/705), and these 4 emm types accounted for ≈76.5% (539/705) of all isolates. These results differed from those of previous studies in mainland China and Hong Kong, where the outbreaks of scarlet fever were caused mainly by emm12 (2,3). Our results showed that emm3 in 2011 (the year incidence began increasing in South Korea) and emm1 and emm28 in 2015 (the year of a sharp increase in incidence) played major roles in the epidemics in the Gwangju metropolitan area (Figure 2, panel A). To our knowledge, emm3 has not been reported to be prevalent in other Asian countries but has been associated with scarlet fever in the United Kingdom (9).

Scarlet fever is a toxin-mediated disease (10). Therefore, we tested all isolates for the presence of the speA and speC genes by using PCR and previously reported primer pairs and reaction conditions (8). We found isolates that harbored speA (57/705, 8.1%), speC (249/705, 35.3%), and both (3/705, 0.4%). The exotoxin gene detection rate differed by emm gene type. The isolates positive for speA were predominantly emm1 (56.1%, 32/57) and emm28 (28.1%, 16/57); the other emm types made up only 15.8% (9/57). When we examined the reverse association, 31.4% (32/102) of emm1 isolates and 15.4% (16/104) of emm28 isolates were positive for speA; in contrast, only 1.8% (9/499) of the other emm types were positive for speA. The main emm types identified in the speC-positive isolates were emm4 (68.7%, 171/249), emm75 (10.8%, 27/249), and emm28 (6.4%, 16/249); 68.1% (171/251) of emm4, 67.5% (27/40) of emm75, and 15.4% (16/104) of emm28 isolates were positive for speC. Only 11.3% (35/310) of the other emm types were positive for speC. Therefore, speA and speC exotoxin genes were more prevalent in bacteria of certain emm types (p<0.01).

GAS remains universally susceptible to β-lactams and glycopeptides. However, the rates of resistance against the macrolides and lincosamides used in penicillin-allergic patients have increased (11). We performed susceptibility tests by using the disk-diffusion method as recommended by the Clinical and Laboratory Standards Institute (12). For all samples collected 2008–2015, the antimicrobial agents chloramphenicol, tetracycline, erythromycin, and clindamycin were tested. Resistance to antimicrobial drugs was detected in 9.1% (64/705) of isolates: 0.3% of the isolates (2/705) showed resistance to chloramphenicol, 7.0% (49/705) to tetracycline, 3.0% (21/705) to erythromycin, and 2.8% (20/705) to clindamycin (Table).

In some isolates, antimicrobial drug resistance is tightly correlated with specific emm types (13). Resistance to erythromycin, clindamycin, and tetracycline is common in bacteria with the emm28 gene. In our study, 18/104 (17.3%) isolates that harbored emm28 were resistant to erythromycin, clindamycin, or tetracycline (p<0.01). Of all emm types, emm28 accounted for 71.0% (44/62) of all cases of resistance to these 3 antimicrobial drugs. In our study, 16/44 isolates harboring emm28 showed resistance to >2 antimicrobials. emm28 isolates in France were also found to be associated with multidrug resistance (13,14). Furthermore, in 2015, we found sharp increases in intermediate tetracycline resistance mainly in isolates harboring emm1 (57.9%, 22/38). Tetracycline resistance associated with emm12 and emm1 isolates was also found in scarlet fever patients in Hong Kong and China (3,15).

This study has a limitation. We collected samples from only 1 city in South Korea, the Gwangju metropolitan area. Because of the genetic diversity of GAS, our results should not be applied to other countries, even those nearby. However, we do believe that our data are representative of South Korea.

In 2011, rapid increases in the incidence of scarlet fever in South Korea, as well as China and Hong Kong, reflected the beginning of a pandemic in Asia. However, the emm types contributing to disease differed from country to country. emm4, emm28, emm1, and emm3 were the most common emm types associated with scarlet fever in South Korea. Antimicrobial drug resistance in GAS in South Korea is closely associated with emm28, and resistance to tetracycline (observed emerging in 2015) is associated with type emm1. However, further studies are necessary to characterize the circulating strains and to control and prevent the further spread of scarlet fever.