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Preplanned Studies: Increased Incidence of Scarlet Fever — China, 1999−2018

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  • Summary

    What is already known about this topic?

    Scarlet fever had high incidence between the 1950s and 1980s, but during the 1980s and 1990s, the incidence of scarlet fever dropped to a relatively low and stable levels in China.

    What is added by this report?

    Starting in 2011, scarlet fever incidence significantly increased in China. In the eight years between 2011 and 2018, 479,555 cases were reported, which exceeded the total number of 241,365 cases reported in the previous twelve years 1999–2010.

    What are the implications for public health practice?

    Both patient and pathogen epidemiological surveillance need to be heightened to monitor serious cases of scarlet fever and to implement timely control measures.

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  • [1] Walker MJ, Barnett TC, McArthur JD, Cole JN, Gillen CM, Henningham A, et al. Disease manifestations and pathogenic mechanisms of group A Streptococcus. Clin Microbiol Rev 2014;27(2):264 − 301. http://dx.doi.org/10.1128/CMR.00101-13CrossRef
    [2] You Y, Davies MR, Protani M, McIntyre L, Walker MJ, Zhang J. Scarlet fever epidemic in China caused by Streptococcus pyogenes serotype M12: epidemiologic and molecular analysis. E Bio Medicine 2018;28:128 − 35. http://dx.doi.org/10.1016/j.ebiom.2018.01.010CrossRef
    [3] Kim JH, Cheong HK. Increasing number of scarlet fever cases, South Korea, 2011-2016. Emerging Infectious Diseases 2018;24(1):172 − 3. http://dx.doi.org/10.3201/eid2401.171027CrossRef
    [4] Yung CF, Thoon KC. A 12 year outbreak of scarlet fever in Singapore. Lancet Infect Dis 2018;18(9): 942. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30464-X/fulltext.https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30464-X/fulltext
    [5] Lamagni T, Guy R, Chand M, Henderson KL, Chalker V, Lewis J, et al. Resurgence of scarlet fever in England, 2014-16: a population-based surveillance study. Lancet Infect Dis 2018;18(2):180 − 7. http://dx.doi.org/10.1016/S1473-3099(17)30693-XCrossRef
    [6] Brockmann SO, Eichner L, Eichner M. Constantly high incidence of scarlet fever in Germany. Lancet Infect Dis 2018;18(2018):499 − 500. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30210-X/fulltext.https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30210-X/fulltext
    [7] Walker MJ, Brouwer S, Forde BM, Worthing KA, McIntyre L, Sundac L, et al. Detection of epidemic scarlet fever group A Streptococcus in Australia. Clin Infect Dis 2019;69(7):1232 − 4. http://dx.doi.org/10.1093/cid/ciz099CrossRef
    [8] You Y, Davies MR, Walker MJ, Zhang J. Hypotheses for the resurgence of scarlet fever in China. Lancet Infect Dis 2018;18(9): 942 − 3. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30470-5/fulltext.https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30470-5/fulltext
    [9] Davies MR, Holden MT, Coupland P, Chen JH, Venturini C, Barnett TC, et al. Emergence of scarlet fever Streptococcus pyogenes emm12 clones in Hong Kong is associated with toxin acquisition and multidrug resistance. Nat. Genet 2015;47(1):84 − 7. http://dx.doi.org/10.1038/ng.3147CrossRef
    [10] Lynskey NN, Jauneikaite E, Li HK, Zhi X, Turner CE, Mosavie M, et al. Emergence of dominant toxigenic M1T1 Streptococcus 1 pyogenes clone during increased scarlet fever activity in England: a population-based molecular epidemiological study. Lancet Infect Dis 2019;19(11):1209 − 18. http://dx.doi.org/10.1016/S1473-3099(19)30446-3CrossRef
  • FIGURE 1.  Total reported scarlet fever cases and incidence between 1999 and 2018 in China.

    FIGURE 2.  Reported scarlet fever incidence according to geographic region in China in 2010 and 2018. (A) Reported incidence in 2010. (B) Reported incidence in 2018.

    TABLE 1.  Reported number of cases, incidence rates, and number of deaths caused by scarlet fever per year, 1999−2018 in China.

    YearReported casesReported incidence (1/100,000 persons)Reported deaths from scarlet fever
    199915,2461.235
    200013,7201.083
    200111,2610.942
    200215,2341.142
    200310,0630.751
    200418,9391.461
    200525,0681.932
    200627,6202.110
    200733,4882.551
    200827,7822.100
    200922,0681.660
    201020,8761.560
    201163,8784.761
    201246,4593.452
    201334,2072.532
    201454,2474.000
    201568,2495.001
    201659,2824.320
    201774,3695.390
    201878,8645.680
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Increased Incidence of Scarlet Fever — China, 1999−2018

View author affiliations

Summary

What is already known about this topic?

Scarlet fever had high incidence between the 1950s and 1980s, but during the 1980s and 1990s, the incidence of scarlet fever dropped to a relatively low and stable levels in China.

What is added by this report?

Starting in 2011, scarlet fever incidence significantly increased in China. In the eight years between 2011 and 2018, 479,555 cases were reported, which exceeded the total number of 241,365 cases reported in the previous twelve years 1999–2010.

What are the implications for public health practice?

Both patient and pathogen epidemiological surveillance need to be heightened to monitor serious cases of scarlet fever and to implement timely control measures.

  • 1. State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
  • 2. Division of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing, China
  • 3. School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia
  • Corresponding author:

    Jianzhong Zhang, zhangjianzhong@icdc.cn

    doi: 10.46234/ccdcw2019.019
  • Scarlet fever is a common pediatric respiratory disease caused by Streptococcus pyogenes (Group A Streptococcus; GAS), which can also cause other mild infections such as pharyngitis and impetigo and serious invasive infections including necrotizing fasciitis. The major clinical manifestations of scarlet fever include sore throat, fever, diffuse red rash, and a “strawberry tongue” (1). China CDC affiliated researchers analyzed reported scarlet fever cases from 1999 to 2018 from the National Notifiable Diseases Reporting System (NNDRS) of Mainland China to determine incidence trends. In this period, 720,920 cases were reported with a sudden increase in 2011 and a peak incidence in 2018 of 5.68 cases per 100,000 population, which represents a 2018 total of 78,864 reported cases.

    Scarlet fever was considered a fatal disease during 19th and early 20th centuries. The morbidity and mortality of scarlet fever dramatically dropped worldwide when antimicrobial drugs became widely used. Most scarlet fever cases are now diagnosed as mild infections, and fatal infections are now rare. However, a small proportion of cases still may develop serious sequelae.

    Since 1950 in China, scarlet fever has been listed as a Type B notifiable disease, which is required to be reported within 24 hours. According to previous analysis (2), the incidence of scarlet fever in China was high between the 1950s and 1980s and then dropped to a low level during the 1990s. In 2011, compared to the baseline level prior to the epidemic, a sudden 2.6-fold increase in the incidence of reported scarlet fever cases was recorded (2). Meanwhile, many other countries also reported significant increases of scarlet fever epidemics worldwide (3-6). The resurgence of scarlet fever has been a concerning public health problem globally.

    In early 2019, an emm12 genotype scarlet fever isolate related to UK scarlet fever outbreak strains was detected in Australia through sentinel hospital surveillance (7). The surveillance in China indicates that emm12-type GAS has been predominantly responsible for the scarlet fever resurgence since 2011. All isolates in China are susceptible to β-lactams but are mostly resistant to macrolide antibiotics (2).

    Scarlet fever cases reported through the NNDRS of China from 1999 to 2018 were retrieved for analysis (2). Only verified clinic-diagnosed and laboratory-confirmed cases from Mainland China were included in the analysis, excluding Hong Kong, Macao, Taiwan, and foreign residents. Population size data from the China National Bureau of Statistics for denominators were used to calculate incidence rates of scarlet fever. Annual case number and incidence of reported scarlet fever from 1999 to 2018 were analyzed to investigate long term temporal trends. The geographic incidence data and case number were extracted from 1999 to 2018. After a comparison between each year, the incidence data for the year 2010 and 2018 were shown to reflect the variation of geographic incidence before and after the year 2011 when the outbreak started. The age data for scarlet fever incidence were also extracted and shown for the years 2010 and 2018 as representatives before and after the year 2011.

    Between 1999 and 2018, there have been three peaks at four-year intervals including 2007, 2011, and 2015. A fourth peak has now been observed in 2018 with 78,864 reported cases and an incidence rate 5.68 per 100,000, which is the highest total over the last 20 years. The incidence increased 5.34% compared to that of 2017 (Table 1, Figure 1). Rare cases of death were reported during 1999 and 2018 (Table 1). The highest number occurred in 1999 with five reported deaths. There was one death in the 2011 epidemic, and in the following years, a total of five deaths were reported. Both 2010 and 2018 data show incidences of northern regions are higher than southern regions. The incidence rate of 2018 significantly increased compared to that of 2010 (t of 2010 (Figure 2). The age group from 5 to 6 years old had the highest incidence for both 2010 and 2018 (Supplementary Figure S1 ).

    Figure 1.  Total reported scarlet fever cases and incidence between 1999 and 2018 in China.

    YearReported casesReported incidence (1/100,000 persons)Reported deaths from scarlet fever
    199915,2461.235
    200013,7201.083
    200111,2610.942
    200215,2341.142
    200310,0630.751
    200418,9391.461
    200525,0681.932
    200627,6202.110
    200733,4882.551
    200827,7822.100
    200922,0681.660
    201020,8761.560
    201163,8784.761
    201246,4593.452
    201334,2072.532
    201454,2474.000
    201568,2495.001
    201659,2824.320
    201774,3695.390
    201878,8645.680

    Table 1.  Reported number of cases, incidence rates, and number of deaths caused by scarlet fever per year, 1999−2018 in China.

    Figure 2.  Reported scarlet fever incidence according to geographic region in China in 2010 and 2018. (A) Reported incidence in 2010. (B) Reported incidence in 2018.

    • The data reported in this and a previous study (2) indicate the incidence of scarlet fever in China is still increasing, which emphasizes the importance of national scarlet fever alerts. Before 2011 when the epidemic began, the highest number of scarlet fevers occurred in 2007 during the period of 1999 and 2018 (Table 1, Figure 1). Similar epidemic patterns were observed in other East Asian countries including Singapore, and European countries (Germany), where an incidence peak was observed in 2008, prior to the 2011 epidemic surge (4,6). These clues may reflect a similar mechanism attributed to the resurgence of scarlet fever across different parts of the world. The higher incidence of northern regions suggests that more attention should be given to strengthen surveillance in these areas. Active bacterial surveillance on the susceptible populations of age group with highest incidence is necessary.

      The reasons underlying the scarlet fever resurgence in China and other countries are still unclear. Several studies have suggested possible reasons for this scarlet fever incidence increase (2,8-9), such as weakened herd immunity, environmental factors, and genetic mutations in the pathogen. Because there is no commercial vaccine for scarlet fever (GAS) prevention (1), natural population immunity may play an important role in the disease epidemic cycle. Further investigations are needed to learn more about the changing immunity patterns in susceptible and resistant populations.

      For the current epidemic in Western and Asian countries including China, multiple scarlet fever-causing serotypes and clones have been identified, many of which contain genetic elements carrying streptococcal exotoxins and antimicrobial resistance genes that are widely detected among Asian and European predominant clones. These virulence determinants are thought to play an important role in triggering the epidemic, though further investigations are required (2,10).

      The findings in this report are subject to one limitation. The most accurate diagnosis of scarlet fever should be based on pathogen isolation. The majority of reported cases are clinically diagnosed and the proportion of confirmed cases based on pathogen isolation is less than 5%. Thus, the accuracy of surveillance data could be affected by introducing false negative or false positive clinically diagnostic cases.

      In summary, China is in a new period of high incidence of scarlet fever. A vaccine is not available for prevention of scarlet fever currently, although advances are being made in GAS vaccine research. Nonetheless, antibiotic treatment is effective. Prevention and cont