- Email: [email protected]
Hand, foot, and mouth disease in mainland China before it was listed as category C disease in May, 2008
Comment
Hand, foot, and mouth disease in mainland China before it was listed as category C disease in May, 2008
www.thelancet.com/infection Vol 17 October 2017
before 2008 but the research was certainly active (figure). Publications before 1983 were mainly introductions to the disease—some were excerpted from foreign literature, presenting medical history, epidemiology, pathogenic viruses, clinical symptoms, and treatment of HFMD.11 From then on, studies on clinical observations, treatments, epidemiology, and pathogenic viruses isolated from previous outbreaks have been reported routinely. In 2004, phylogenetic analysis of EV71 was done.9 By 2005, the complete nucleotide sequence of CA16 was identified.12 One of the important reasons that the EV71 virus reached such a stage of evolution in Fuyang4 was genetic recombinations in the 3D region (non-structural protein and RNA-dependent polymerase that is a major component of the viral replication complex) between EV71 strain and CA16. Besides host and environmental factors, genetic recombination of EV71 has a crucial role in the recurrent outbreaks of HFMD in mainland China and worldwide, but the exact time of the recombinations are still unclear and the role of genetic changes in HFMD outbreaks remains open to debate.13–15 In the Lancet Infectious Diseases, Shimizu Hiroyuki and Nakashima Kazutoshi16 stated that “Until early
2052 2155 2023 1930 1855 1715
2500
1417
1710
2000
1500
1082
Number of publications
1000
500
0
1 1 0 0 1 0 3 2 1 5 3 20 12 13 13 14 15 9 6 13 14 14 17 13 21 18 41 36 38 50 61 63 64 126
Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by a group of enteroviruses, including coxsackievirus A16 (CA16) and enterovirus 71 (EV71).1 Mainland China experienced several large outbreaks of HFMD in 2007 and early 2008 and established a national enhanced surveillance system partly in response to these outbreaks.2 On May 2, 2008, HFMD was listed as a category C infectious disease and made statutorily notifiable.3 Publications on HFMD flourished after May, 2008, but are limited before this time. We searched PubMed with the keywords “HFMD” and “China”, which returned 701 articles, of which only 13 articles were dated before May, 2008. By contrast, when we searched the China National Knowledge Infrastructure (CNKI) for Chinese entries of “HFMD” 16 951 articles were returned, of which 922 articles were published before May, 2008 (accessed April 27, 2017). With the large amount of publications that exist exclusively in Chinese, there has been some misunderstanding about research and surveillance on HFMD in mainland China, as manifested in the two papers we discuss here. Jane Qiu reported in The Lancet Neurology in October, 2008, that “The first sign of an outbreak of EV71 was from Fuyang…It is a mystery to many clinicians why the virus has reached such a stage of evolution…”.4 Actually, highly suspicious cases of HFMD appeared in Shanghai and Guangzhou around 1980; they were mainly diagnosed by clinical symptoms although not confirmed by virology analysis.5,6 The first confirmed outbreak of HFMD was from Tianjin in April, 1983, when CA16 was isolated from throat swabs, faeces, and skin lesions of suspected patients.7 In November, 1983, suspected cases in Beijing and Jilin were also confirmed by virology and serology analysis.8 The first sign of an EV71 outbreak was in south China in 1985, before which CA16 was the only pathogenic virus identified.9 By the end of April, 2008, all provinces, municipalities, and autonomous regions except Tibet in mainland China had HFMD incidences reported. HFMD is no mystery, either. Chinese scholars were aware of HFMD in 1974.10 The total number of publications on HFMD that we identified in the CNKI database was low
1974
1979
1984
1989
1994
Year
1999
2004
2009
2014
2015
Figure: Number of publications on hand, foot, and mouth disease from China National Knowledge Infrastructure (accessed April 27, 2017)
1017
Comment
2008, hand, foot, and mouth disease outbreaks passed unnoticed in China partly because of the insufficient national surveillance and reporting systems for the disease and EV71 infections”. In fact, although HFMD had not been made statutorily notifiable until May, 2008, it had been reported on a voluntary basis, including via the internet using the China Information System for Disease Control and Prevention.17 Furthermore, local governments such as Shandong and Shanghai have required HFMD to be monitored and reported compulsorily since 2003 and 2005, respectively.18,19 Medical practitioners in mainland China have been treating the symptoms of HFMD actively since 1975 despite the fact that no effective therapy was available until an inactivated EV71 vaccine was developed by Chinese scholars in 2014.11,20 Over the years, various methods employing western and traditional Chinese medicine have been applied. In summary, scholars and medical workers in mainland China were aware of HFMD no later than 1974. A unified, comprehensive, and rapid surveillance systems for HFMD and other infectious diseases had already been in operation before May, 2008. The underlying cause and potential mechanism of genetic recombination of pathogenic viruses of HFMD still need to be studied further to fully understand the pattern of HFMD distribution and devise preventive measures. Jie Li, *Jinfeng Wang, Chengdong Xu, Qian Yin, Maogui Hu, Zhaojun Sun, Dewang Shao School of Resources and Environment, Ningxia University, Yinchuan, Ningxia, China (JL, ZS); State Key Laboratory of Resources and Environmental Information System, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing 100101, China (JW, CX, QY, MH); Key Laboratory of Surveillance and Early Warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China (JW); Department of Geography and Regional Research, University of Vienna, Vienna, Austria (JL); Ningxia (China-Arab) Key Laboratory of Resource Assessment and Environmental Regulation in Arid Region, Ningxia University, Yinchuan, Ningxia, China (JL, ZS); and Medical Department, Air Force Aviation Medicine Research Institute Affiliation Hospital, Beijing, China (DS) [email protected]
1018
We declare no competing interests. This work was supported by the national Natural Science Foundation of China (NSFC; grant numbers NSFC 41531179 and NSFC 41421001). We would like to thank Yang Wang, Bing Xu, Zhoupeng Ren, Dacang Huang, Jiehao Zhang, and Junming Li (State Key Laboratory of Resources and Environmental Information System, Chinese Academy of Sciences, Beijing, China) for their valuable opinion on the drafts of the comment. 1 2 3
4 5 6 7 8 9
10 11 12 13 14 15 16 17 18 19 20
Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH. Virology, epidemiology, pathogenesis, and control of enterovirus 71. Lancet Infect Dis 2010; 10: 778–90. Xing W, Liao Q, Viboud C, et al. Hand, foot, and mouth disease in China, 2008–12: an epidemiological study. Lancet Infect Dis 2014; 14: 308–18. Ministry of Health of the People’s Republic of China. Notice on listing and managing hand, foot, and mouth disease as statutory infectious disease. http://www.moh.gov.cn/jkj/s3577/200805/1a8bb3668b7d4540afb0531d fcef978d.shtml (accessed Jun 27, 2017). Qiu J. Enterovirus 71 infection: a new threat to global public health? Lancet Neurol 2008; 7: 868–69. Ye YC, Men GS. Clinical analysis of 26 cases of hand, foot, and mouth disease. Zhong Ji Yi Kan 1984; 5: 10–12 (in Chinese). Wang ZF, Liu ZQ. Report on one case of hand, foot, and mouth disease. Nan Fang Yi Ke Da Xue Xue Bao 1983; 3: 147 (In Chinese). Xiao MH, Ye ZZ, Zhang ZL, Tian XQ, Zheng JM, Liu ZY. Coxsackie A16 entervirus isolated from patients with hand-foot-mouth disease in Tianjin. Tianjin Yi Yao 1985; 6: 355–72 (in Chinese). Cao YY, Yang XX, Li J, et al. Study on the etiology of hand, foot and mouth disease (HFMD) in China. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 1985; 7: 333–36 (in Chinese). Lin SE, Zhang Q, Xie HP, et al. Phylogenetic analysis of enterovirus 71 isolated from patients with hand, foot and mouth disease in Guangdong and Fujian provinces, 2000–2001. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2004; 18: 227 (in Chinese). Yu WX. Clinical observations of hand, foot, and mouth disease. Guo Wai Yi Xue Er Ke Xue Fen Ce 1974; 4: 205 (in Chinese). Zhou DC. Hand, foot, and mouth disease (review). Guo Wai Yi Xue Kou Qiang Yi Xue Fen Ce 1975; 3: 98–102 (in Chinese). Li LL, He YQ, Zhu JP, et al. Complete genome analysis of coxsackievirus A16 SHZH00–1 strain isolated from the mainland of China. Bing Du Xue Bao 2005; 21: 217–22 (in Chinese). Palmenberg AC. Proteolytic processing of picornaviral polyprotein. Annu Rev Microbiol 1990; 44: 603–23. Zhang Y, Zhu Z, Yang WZ, et al. An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of hand foot and mouth disease in Fuyang City of China. Virol J 2010; 7: 1–9. Bible JM, Pantelidis P, Chan PKS, Tong CYW. Genetic evolution of enterovirus 71: epidemiological and pathological implications. Rev Med Virol 2007; 17: 371–79. Shimizu H, Nakashima K. Surveillance of hand, foot, and mouth disease for a vaccine. Lancet Infect Dis 2014; 14: 262. Wang LP, Jin LM, Xiong WY, Tu WX, Ye CC. Infectious disease surveillance in China. In: Yang WZ, ed. Early warning for infectious disease outbreak theory and practice. Cambridge, MA: Academic Press, 2017: 388. Chen DY, Lin XL, Yang ZH. Surveillance in the hand-foot-mouth disease based on National Disease Supervision Information Management System. Ji Bing Jian Ce 2006; 21: 435–38 (in Chinese). Zhu WP, Chu Q, Wang Y, Shen YF. Surveillance and analysis of hand-foot-mouth disease in Pudong New Area 2005–2007. Shanghai J Prev Med 2008; 20: 372–75. Li RC, Liu LD, Mo ZJ, et al. An inactivated enterovirus 71 vaccine in healthy children. N Engl J Med 2014; 370: 829–37.
www.thelancet.com/infection Vol 17 October 2017
Hand, foot, and mouth disease in mainland China before it was listed as category C disease in May, 2008
www.thelancet.com/infection Vol 17 October 2017
before 2008 but the research was certainly active (figure). Publications before 1983 were mainly introductions to the disease—some were excerpted from foreign literature, presenting medical history, epidemiology, pathogenic viruses, clinical symptoms, and treatment of HFMD.11 From then on, studies on clinical observations, treatments, epidemiology, and pathogenic viruses isolated from previous outbreaks have been reported routinely. In 2004, phylogenetic analysis of EV71 was done.9 By 2005, the complete nucleotide sequence of CA16 was identified.12 One of the important reasons that the EV71 virus reached such a stage of evolution in Fuyang4 was genetic recombinations in the 3D region (non-structural protein and RNA-dependent polymerase that is a major component of the viral replication complex) between EV71 strain and CA16. Besides host and environmental factors, genetic recombination of EV71 has a crucial role in the recurrent outbreaks of HFMD in mainland China and worldwide, but the exact time of the recombinations are still unclear and the role of genetic changes in HFMD outbreaks remains open to debate.13–15 In the Lancet Infectious Diseases, Shimizu Hiroyuki and Nakashima Kazutoshi16 stated that “Until early
2052 2155 2023 1930 1855 1715
2500
1417
1710
2000
1500
1082
Number of publications
1000
500
0
1 1 0 0 1 0 3 2 1 5 3 20 12 13 13 14 15 9 6 13 14 14 17 13 21 18 41 36 38 50 61 63 64 126
Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by a group of enteroviruses, including coxsackievirus A16 (CA16) and enterovirus 71 (EV71).1 Mainland China experienced several large outbreaks of HFMD in 2007 and early 2008 and established a national enhanced surveillance system partly in response to these outbreaks.2 On May 2, 2008, HFMD was listed as a category C infectious disease and made statutorily notifiable.3 Publications on HFMD flourished after May, 2008, but are limited before this time. We searched PubMed with the keywords “HFMD” and “China”, which returned 701 articles, of which only 13 articles were dated before May, 2008. By contrast, when we searched the China National Knowledge Infrastructure (CNKI) for Chinese entries of “HFMD” 16 951 articles were returned, of which 922 articles were published before May, 2008 (accessed April 27, 2017). With the large amount of publications that exist exclusively in Chinese, there has been some misunderstanding about research and surveillance on HFMD in mainland China, as manifested in the two papers we discuss here. Jane Qiu reported in The Lancet Neurology in October, 2008, that “The first sign of an outbreak of EV71 was from Fuyang…It is a mystery to many clinicians why the virus has reached such a stage of evolution…”.4 Actually, highly suspicious cases of HFMD appeared in Shanghai and Guangzhou around 1980; they were mainly diagnosed by clinical symptoms although not confirmed by virology analysis.5,6 The first confirmed outbreak of HFMD was from Tianjin in April, 1983, when CA16 was isolated from throat swabs, faeces, and skin lesions of suspected patients.7 In November, 1983, suspected cases in Beijing and Jilin were also confirmed by virology and serology analysis.8 The first sign of an EV71 outbreak was in south China in 1985, before which CA16 was the only pathogenic virus identified.9 By the end of April, 2008, all provinces, municipalities, and autonomous regions except Tibet in mainland China had HFMD incidences reported. HFMD is no mystery, either. Chinese scholars were aware of HFMD in 1974.10 The total number of publications on HFMD that we identified in the CNKI database was low
1974
1979
1984
1989
1994
Year
1999
2004
2009
2014
2015
Figure: Number of publications on hand, foot, and mouth disease from China National Knowledge Infrastructure (accessed April 27, 2017)
1017
Comment
2008, hand, foot, and mouth disease outbreaks passed unnoticed in China partly because of the insufficient national surveillance and reporting systems for the disease and EV71 infections”. In fact, although HFMD had not been made statutorily notifiable until May, 2008, it had been reported on a voluntary basis, including via the internet using the China Information System for Disease Control and Prevention.17 Furthermore, local governments such as Shandong and Shanghai have required HFMD to be monitored and reported compulsorily since 2003 and 2005, respectively.18,19 Medical practitioners in mainland China have been treating the symptoms of HFMD actively since 1975 despite the fact that no effective therapy was available until an inactivated EV71 vaccine was developed by Chinese scholars in 2014.11,20 Over the years, various methods employing western and traditional Chinese medicine have been applied. In summary, scholars and medical workers in mainland China were aware of HFMD no later than 1974. A unified, comprehensive, and rapid surveillance systems for HFMD and other infectious diseases had already been in operation before May, 2008. The underlying cause and potential mechanism of genetic recombination of pathogenic viruses of HFMD still need to be studied further to fully understand the pattern of HFMD distribution and devise preventive measures. Jie Li, *Jinfeng Wang, Chengdong Xu, Qian Yin, Maogui Hu, Zhaojun Sun, Dewang Shao School of Resources and Environment, Ningxia University, Yinchuan, Ningxia, China (JL, ZS); State Key Laboratory of Resources and Environmental Information System, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing 100101, China (JW, CX, QY, MH); Key Laboratory of Surveillance and Early Warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China (JW); Department of Geography and Regional Research, University of Vienna, Vienna, Austria (JL); Ningxia (China-Arab) Key Laboratory of Resource Assessment and Environmental Regulation in Arid Region, Ningxia University, Yinchuan, Ningxia, China (JL, ZS); and Medical Department, Air Force Aviation Medicine Research Institute Affiliation Hospital, Beijing, China (DS) [email protected]
1018
We declare no competing interests. This work was supported by the national Natural Science Foundation of China (NSFC; grant numbers NSFC 41531179 and NSFC 41421001). We would like to thank Yang Wang, Bing Xu, Zhoupeng Ren, Dacang Huang, Jiehao Zhang, and Junming Li (State Key Laboratory of Resources and Environmental Information System, Chinese Academy of Sciences, Beijing, China) for their valuable opinion on the drafts of the comment. 1 2 3
4 5 6 7 8 9
10 11 12 13 14 15 16 17 18 19 20
Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, Ooi MH. Virology, epidemiology, pathogenesis, and control of enterovirus 71. Lancet Infect Dis 2010; 10: 778–90. Xing W, Liao Q, Viboud C, et al. Hand, foot, and mouth disease in China, 2008–12: an epidemiological study. Lancet Infect Dis 2014; 14: 308–18. Ministry of Health of the People’s Republic of China. Notice on listing and managing hand, foot, and mouth disease as statutory infectious disease. http://www.moh.gov.cn/jkj/s3577/200805/1a8bb3668b7d4540afb0531d fcef978d.shtml (accessed Jun 27, 2017). Qiu J. Enterovirus 71 infection: a new threat to global public health? Lancet Neurol 2008; 7: 868–69. Ye YC, Men GS. Clinical analysis of 26 cases of hand, foot, and mouth disease. Zhong Ji Yi Kan 1984; 5: 10–12 (in Chinese). Wang ZF, Liu ZQ. Report on one case of hand, foot, and mouth disease. Nan Fang Yi Ke Da Xue Xue Bao 1983; 3: 147 (In Chinese). Xiao MH, Ye ZZ, Zhang ZL, Tian XQ, Zheng JM, Liu ZY. Coxsackie A16 entervirus isolated from patients with hand-foot-mouth disease in Tianjin. Tianjin Yi Yao 1985; 6: 355–72 (in Chinese). Cao YY, Yang XX, Li J, et al. Study on the etiology of hand, foot and mouth disease (HFMD) in China. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 1985; 7: 333–36 (in Chinese). Lin SE, Zhang Q, Xie HP, et al. Phylogenetic analysis of enterovirus 71 isolated from patients with hand, foot and mouth disease in Guangdong and Fujian provinces, 2000–2001. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2004; 18: 227 (in Chinese). Yu WX. Clinical observations of hand, foot, and mouth disease. Guo Wai Yi Xue Er Ke Xue Fen Ce 1974; 4: 205 (in Chinese). Zhou DC. Hand, foot, and mouth disease (review). Guo Wai Yi Xue Kou Qiang Yi Xue Fen Ce 1975; 3: 98–102 (in Chinese). Li LL, He YQ, Zhu JP, et al. Complete genome analysis of coxsackievirus A16 SHZH00–1 strain isolated from the mainland of China. Bing Du Xue Bao 2005; 21: 217–22 (in Chinese). Palmenberg AC. Proteolytic processing of picornaviral polyprotein. Annu Rev Microbiol 1990; 44: 603–23. Zhang Y, Zhu Z, Yang WZ, et al. An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of hand foot and mouth disease in Fuyang City of China. Virol J 2010; 7: 1–9. Bible JM, Pantelidis P, Chan PKS, Tong CYW. Genetic evolution of enterovirus 71: epidemiological and pathological implications. Rev Med Virol 2007; 17: 371–79. Shimizu H, Nakashima K. Surveillance of hand, foot, and mouth disease for a vaccine. Lancet Infect Dis 2014; 14: 262. Wang LP, Jin LM, Xiong WY, Tu WX, Ye CC. Infectious disease surveillance in China. In: Yang WZ, ed. Early warning for infectious disease outbreak theory and practice. Cambridge, MA: Academic Press, 2017: 388. Chen DY, Lin XL, Yang ZH. Surveillance in the hand-foot-mouth disease based on National Disease Supervision Information Management System. Ji Bing Jian Ce 2006; 21: 435–38 (in Chinese). Zhu WP, Chu Q, Wang Y, Shen YF. Surveillance and analysis of hand-foot-mouth disease in Pudong New Area 2005–2007. Shanghai J Prev Med 2008; 20: 372–75. Li RC, Liu LD, Mo ZJ, et al. An inactivated enterovirus 71 vaccine in healthy children. N Engl J Med 2014; 370: 829–37.
www.thelancet.com/infection Vol 17 October 2017