- Email: [email protected]
Hand, foot, and mouth disease in mainland China
Correspondence
Hand, foot, and mouth disease in mainland China Weijia Xing and colleagues reported the epidemiological profile of hand, foot, and mouth disease in mainland China between 2008 and 2012, according to variations in climate, population, and geographical region, 1 and their findings support the introduction of enterovirus 71 (EV71) vaccines in China and other countries. Their Article is interesting and important, but the incidences and aetiological profiles of hand, foot, and mouth disease were underestimated because of the limitations of passive surveillance in the national infectious disease information management system. Usually, patients who are not admitted to hospital are not included in the national disease information management reporting system. In a retrospective study, Feng-Cai Zhu and colleagues2 reported that cases of hand, foot, and mouth disease reported to this system were far fewer than the actual number of cases (only 16 [11%] of 143 cases). Additionally, the incidence of hand, foot, and mouth disease obtained by active surveillance in three phase 3 clinical trials of EV71 inactivated vaccine was between two-times and six-times greater than that reported by Xing and colleagues.3–5 Xing and colleagues also pointed out that most cases went undetected. Therefore, we want to emphasise that the actual prevalence of hand, foot, and mouth disease is far more serious in mainland China than has been reported, and we speculate that a similar situation might exist in other countries. Furthermore, in addition to EV71 and Coxsackievirus A16, other enteroviruses that can cause severe hand, foot, and mouth disease also deserve our attention. Recently published studies propose that Coxsackievirus A6, A10, B3, B5, and E30 (CA6, CA10, CB3, CB5, and E30) account for a large proportion of the disease’s pathogenic range. CB3
can cause viral myocarditis, whereas E30 and CB5 are associated with encephalitis and aseptic encephalitis. The alternation or co-circulation of different enteroviruses in infants and young children can cause serious complications in the CNS and increase the chances of genetic recombination. Therefore, although the results of phase 3 clinical trials of inactivated enterovirus 71 vaccine are promising, when these vaccines become available in the market, the epidemiological characteristics and pathogenic range of hand, foot, and mouth disease should be actively monitored in highly epidemic areas. Future research should focus on the development of bivalent and multivalent vaccines of enteroviruses to reduce the harm caused by hand, foot, and mouth disease and other related nervous system disorders in infants and children. We declare no competing interests.
Qunying Mao, Yiping Wang, *Zhenglun Liang [email protected] National Institutes for Food and Drug Control, No.2, Tiantan Xili, Beijing 100050, China 1
2
3
4
5
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. Zhu F, Liang Z, Meng F, et al. Retrospective study of the incidence of HFMD and seroepidemiology of antibodies against EV71 and CoxA16 in prenatal women and their infants. PLoS One 2012; 7: e37206. Zhu F, Xu W, Xia J, et al. Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China. N Engl J Med 2014; 370: 818–28. Li R, Liu L, Mo Z, et al. An inactivated enterovirus 71 vaccine in healthy children. N Engl J Med 2014; 370: 829–37. Zhu F, Meng F, Li J, et al. Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2013; 381: 2024–32.
Large outbreaks of hand, foot, and mouth disease were reported in China in both 2008 and 2009.1 The cumulative reported number of cases in the country reached 489 540 in 2008 and 1 155 575 in 2009, marking an era of unprecedented large-scale outbreaks in the Asia-Pacific region.1
www.thelancet.com/infection Vol 14 November 2014
The outbreaks of hand, foot, and mouth disease triggered some panic in the Chinese population, particularly with regard to children with skin lesions on their hands or feet. In clinics, doctors saw many children with such lesions. In May 2008, the health ministry of China added hand, foot, and mouth disease to category C of notifiable diseases, which means that all diagnosed cases must be reported through a national webbased system for disease surveillance, and took measures to streamline reporting requirements.2 Doctors were concerned about missing cases of hand, foot, and mouth disease. Many probable cases of the disease were submitted to the provincial Centre for Disease Control and Prevention (CDC), but some of these were misdiagnosed, especially in rural hospitals. In our clinics, we met some of these patients who had been misdiagnosed and reported to the CDC. Weijia Xing and colleagues3 extracted epidemiological, clinical, and laboratory data from cases of hand, foot, and mouth disease reported to the Chinese CDC. Both probable cases and definite cases were included in their study, but whether or not the probable cases were misdiagnosed as hand, foot, and mouth disease was not mentioned. The fact that misdiagnosed cases of the disease were included in the study casts doubt on any results. We declare no competing interests.
Bin Lu, Huan Guo, *Hongguang Lu [email protected] Dermatology Department, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou, China (BL, HL); Dermatology Department (BL) and Medical Laboratories (HG), Affiliated Hospital of Jining Medical College, Jining, Shandong, China; and Dermatology Department, the First Hospital of China Medical University, Shenyang, Liaoning, China (BL, HL) 1
2 3
Wang Y, Feng Z, Yang Y, et al. Hand, foot, and mouth disease in China: patterns of spread and transmissibility. Epidemiology 2011; 22: 781–92. Qiu J. Viral outbreak in China tests government efforts. Nature 2009; 458: 554–55. 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.
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Hand, foot, and mouth disease in mainland China Weijia Xing and colleagues reported the epidemiological profile of hand, foot, and mouth disease in mainland China between 2008 and 2012, according to variations in climate, population, and geographical region, 1 and their findings support the introduction of enterovirus 71 (EV71) vaccines in China and other countries. Their Article is interesting and important, but the incidences and aetiological profiles of hand, foot, and mouth disease were underestimated because of the limitations of passive surveillance in the national infectious disease information management system. Usually, patients who are not admitted to hospital are not included in the national disease information management reporting system. In a retrospective study, Feng-Cai Zhu and colleagues2 reported that cases of hand, foot, and mouth disease reported to this system were far fewer than the actual number of cases (only 16 [11%] of 143 cases). Additionally, the incidence of hand, foot, and mouth disease obtained by active surveillance in three phase 3 clinical trials of EV71 inactivated vaccine was between two-times and six-times greater than that reported by Xing and colleagues.3–5 Xing and colleagues also pointed out that most cases went undetected. Therefore, we want to emphasise that the actual prevalence of hand, foot, and mouth disease is far more serious in mainland China than has been reported, and we speculate that a similar situation might exist in other countries. Furthermore, in addition to EV71 and Coxsackievirus A16, other enteroviruses that can cause severe hand, foot, and mouth disease also deserve our attention. Recently published studies propose that Coxsackievirus A6, A10, B3, B5, and E30 (CA6, CA10, CB3, CB5, and E30) account for a large proportion of the disease’s pathogenic range. CB3
can cause viral myocarditis, whereas E30 and CB5 are associated with encephalitis and aseptic encephalitis. The alternation or co-circulation of different enteroviruses in infants and young children can cause serious complications in the CNS and increase the chances of genetic recombination. Therefore, although the results of phase 3 clinical trials of inactivated enterovirus 71 vaccine are promising, when these vaccines become available in the market, the epidemiological characteristics and pathogenic range of hand, foot, and mouth disease should be actively monitored in highly epidemic areas. Future research should focus on the development of bivalent and multivalent vaccines of enteroviruses to reduce the harm caused by hand, foot, and mouth disease and other related nervous system disorders in infants and children. We declare no competing interests.
Qunying Mao, Yiping Wang, *Zhenglun Liang [email protected] National Institutes for Food and Drug Control, No.2, Tiantan Xili, Beijing 100050, China 1
2
3
4
5
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. Zhu F, Liang Z, Meng F, et al. Retrospective study of the incidence of HFMD and seroepidemiology of antibodies against EV71 and CoxA16 in prenatal women and their infants. PLoS One 2012; 7: e37206. Zhu F, Xu W, Xia J, et al. Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China. N Engl J Med 2014; 370: 818–28. Li R, Liu L, Mo Z, et al. An inactivated enterovirus 71 vaccine in healthy children. N Engl J Med 2014; 370: 829–37. Zhu F, Meng F, Li J, et al. Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2013; 381: 2024–32.
Large outbreaks of hand, foot, and mouth disease were reported in China in both 2008 and 2009.1 The cumulative reported number of cases in the country reached 489 540 in 2008 and 1 155 575 in 2009, marking an era of unprecedented large-scale outbreaks in the Asia-Pacific region.1
www.thelancet.com/infection Vol 14 November 2014
The outbreaks of hand, foot, and mouth disease triggered some panic in the Chinese population, particularly with regard to children with skin lesions on their hands or feet. In clinics, doctors saw many children with such lesions. In May 2008, the health ministry of China added hand, foot, and mouth disease to category C of notifiable diseases, which means that all diagnosed cases must be reported through a national webbased system for disease surveillance, and took measures to streamline reporting requirements.2 Doctors were concerned about missing cases of hand, foot, and mouth disease. Many probable cases of the disease were submitted to the provincial Centre for Disease Control and Prevention (CDC), but some of these were misdiagnosed, especially in rural hospitals. In our clinics, we met some of these patients who had been misdiagnosed and reported to the CDC. Weijia Xing and colleagues3 extracted epidemiological, clinical, and laboratory data from cases of hand, foot, and mouth disease reported to the Chinese CDC. Both probable cases and definite cases were included in their study, but whether or not the probable cases were misdiagnosed as hand, foot, and mouth disease was not mentioned. The fact that misdiagnosed cases of the disease were included in the study casts doubt on any results. We declare no competing interests.
Bin Lu, Huan Guo, *Hongguang Lu [email protected] Dermatology Department, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou, China (BL, HL); Dermatology Department (BL) and Medical Laboratories (HG), Affiliated Hospital of Jining Medical College, Jining, Shandong, China; and Dermatology Department, the First Hospital of China Medical University, Shenyang, Liaoning, China (BL, HL) 1
2 3
Wang Y, Feng Z, Yang Y, et al. Hand, foot, and mouth disease in China: patterns of spread and transmissibility. Epidemiology 2011; 22: 781–92. Qiu J. Viral outbreak in China tests government efforts. Nature 2009; 458: 554–55. 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.
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