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Severe Hand, Foot, and Mouth Disease (HFMD) is now vaccine-preventable (at least in China)!

January 08, 2016

We’ve heard about dengue fever now being a vaccine-preventable disease after the approval of the dengue vaccine in Mexico, the Philippines, and Brazil. Severe hand foot, and mouth disease (HFMD) is also vaccine-preventable now, at least in China after the China Food and Drug Administration approved the world’s first (and second) vaccine against Enterovirus 71 (EV71).

Hand, foot, and mouth disease (HFMD) is a common viral illness that usually affects infants and children, but can sometimes occur in adults. Coxsackievirus A16 is the most common cause of HFMD, but other viruses, such as Entervoirus 71 (EV71) has also been associated with such cases. Of these two viruses, EV71 infection is associated with a higher death rate and is primarily responsible for fatalities and outbreaks in Southeast Asia. HFMD is typically a benign and self-limiting disease but a minority of individuals with HFMD may require hospital admission due to uncommon complications such as inflammation of the brain and the meninges (protective membrane of the brain and spinal cord) or acute flaccid paralysis (weakness or paralysis of the muscle without other obvious cause).

HFMD has recently emerged in the Asia-Pacific region as the most severe epidemic disease affecting children. A number of outbreaks of EV71 HFMD in the Asia-Pacific region have been reported since 1997. Over the years, outbreaks have been reported in Malaysia, Taiwan, mainland China, Australia, and Singapore among other areas in the region, making EV71 a public health threat to children in Asia. According to the statistics from National Health and Family Planning Commission of China from 2008 to 2013, more than 9 million cases of HFMD were reported, resulting in around 2,700 reported deaths. For the period 2008 to 2012, around 80% of the severe cases and over 90% of fatal cases were caused by EV71.

In December 2015, the China Food and Drug Administration (CFDA) approved the 1st vaccine against EV71, an inactivated (killed) vaccine made by the Institute of Medical Biology at the Chinese Academy of Medical Sciences. The vaccine developed by the institute showed vaccine efficacy of 97.4% (95% confidence interval, 92.9% - 99.0%). Overall, the team identified 155 confirmed cases of EV71-associated HFMD with 4 occurring in the vaccine group and 151 in the placebo group. This vaccine targets children aged 6-71 months, with each child requiring a total of two doses one month apart.

2nd vaccine, also an inactivated vaccine, developed by Sinovac Biotech Ltd was approved January 2016. The vaccine developed by Sinovac showed a 97.5% vaccine efficacy (6 month) and a 94.8% vaccine efficacy (12 month) against EV71-associated HFMD cases and 89.3% (6 month) and 88.0% (12 month) for EV71-associated cases. This vaccine targets children aged 6-35 months, with each child requiring a total of two doses one month apart. Despite differences in the seed strains used, manufacture processes and dosages, the Phase III trials conducted in various regions of mainland China, have indicated satisfactory safety and efficacies against EV71-related diseases and EV71-associated HFM cases. 

These new vaccines have the potential to significantly reduce suffering and death from EV71 disease in China and in the future, the rest of the world. Nevertheless, manufacturing capacity and policy challenges remain for market entry and regulatory applications in other countries in the region with large populations of infants and children. Some questions remain: Will Chinese manufacturers make the vaccine available to other countries with EV71 outbreaks? Cross-protection of the vaccines against pandemic virus strains? How will they incorporate EV71 vaccine into the EPI? Can the vaccine be co-administered with other vaccines? How do you standardize the vaccine quality control and evaluation of EV71 vaccines? Having 2 vaccines against HFMD made in China is not only a milestone in the global vaccine field, but a testament to the hard work and innovation of the country’s scientific community and a boost to the local manufacturing sector.

References:

  •  Ang LW, Koh BK, Chan KP, Chua LT, James L, Goh KT. Epidemiology and control of hand, foot and mouth disease in Singapore, 2001–2007. Ann Acad Med Singapore. 2009; 38:106–12.
  • China FDA http://app1.sfda.gov.cn
  • Hand-foot-and-mount disease. Mayo clinic. Available at http://www.mayoclinic.org/diseases-conditions/hand-foot-and-mouth-disease/basics/causes/con-20032747 [Accessed 06 January 2016].
  • Ho M, Chen ER, Hsu KH, Twu SJ, Chen KT, Tsai SF, et al. An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group. N Engl J Med. 1999; 341:929–35.
  • Li R, Liu L, Mo Z, et al. An inactivated enterovirus 71 vaccine in healthy children. N Engl J Med.2014; 370:829–837.
  • Li, Y; Zhu, R; Qian, Y; Deng, J (2012). "The characteristics of blood glucose and WBC counts in peripheral blood of cases of hand foot and mouth disease in China: a systematic review". PLOS ONE 7 (1): e29003.
  • Liu L, Mo Z, Liang Z. Immunity and clinical efficacy of an inactivated enterovirus 71 vaccine in healthy Chinese children: a report of further observations. BMC Med 2015 Sep 17; 13:226.
  • Tan X, Huang X, Zhu S, Chen H, Yu Q, Wang H, et al. The persistent circulation of enterovirus 71 in People’s Republic of China: causing emerging nationwide epidemics since 2008. PLoS One. 2011; 6:e25662.
  • Wang Y, Feng Z, Yang Y, Self S, Gao Y, Longini IM, et al. Hand, foot, and mouth disease in China: patterns of spread and transmissibility. Epidemiology. 2011; 22:781–92.
  • Xu W, Liu CF, Yan L, Li JJ, Wang LJ, Qi Y, et al. Distribution of enteroviruses in hospitalized children with hand, foot and mouth disease and relationship between pathogens and nervous system complications. Virol J. 2012; 9:8.
  • Zhu F, Xu W, Xia J, et al. Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China.N Engl J Med. 2014;370:818–828.
  • Zhu FC, Meng FY, Li JX, 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; 381:2024–2032.
 
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